1. Clin Chem Lab Med. 2010 Feb 12. [Epub ahead of print]
Association of hyperhomocysteinemia with left ventricular dilatation and mass in
human heart.
Alter P, Rupp H, Rominger MB, Figiel JH, Renz H, Klose KJ, Maisch B.
Internal Medicine - Cardiology, Philipps University, Marburg, Germany.
Abstract Background: Hyperhomocysteinemia is a risk factor for ischemic heart
disease. Several other mechanisms apply also to dilative types of heart failure
of various, non-ischemic etiologies. We hypothesized that hyperhomocysteinemia is
associated with left ventricular (LV) dilatation and hypertrophy in dilative
cardiomyopathy. Methods: Homocysteine was measured in 66 individuals with
suspected cardiomyopathy. Cardiac magnetic resonance imaging was used to assess
LV volume, mass, and wall stress. Results: Hyperhomocysteinemia (>12 mumol/L) was
found in 45 patients (68%). LV mass was greater in these patients compared with
individuals with normal homocysteine (83+/-27 vs. 67+/-19 g/m(2); p<0.02).
Homocysteine was increased in patients with increased brain natriuretic peptide
>/=100 pg/mL (18.3+/-5.9 vs. 14.9+/-5.1 mumol/L; p=0.018). LV mass, LV
end-diastolic and end-systolic volume (LVEDV, LVESV) were significantly increased
in individuals in the upper quartile compared with the lower quartile (90+/-25
vs. 65+/-18 g/m(2), p=0.021; 114+/-50 vs. 71+/-23 mL/m(2), p=0.042; 76+/-51 vs.
36+/-22 mL/m(2), p=0.045). LV dilatation (LVEDV>/=90 mL/m(2)) was more common in
hyperhomocysteinemia (>12 mumol/L, p=0.0166). Normalized LV mass was correlated
with homocysteine (r=0.346, p=0.065). Homocysteine was not significantly
correlated with LVEDV (r=0.229, p=0.065), LV end-diastolic wall stress (r=0.226,
p=0.069) and LV ejection fraction. Conclusions: Hyperhomocysteinemia appears to
be, at least in part, involved in a disproportional LV dilatation, where the
ensuing hypertrophy is not sufficient to compensate for the increased wall
stress. A potential mechanism is the hyper-homocysteinemia associated increase in
oxidative stress that favors muscle fiber slippage. Clin Chem Lab Med 2010;48.
PMID: 20148720 [PubMed - as supplied by publisher]
2. Eur J Hum Genet. 2010 Feb 10. [Epub ahead of print]
Evidence for CTLA4 as a susceptibility gene for dilated cardiomyopathy.
Ruppert V, Meyer T, Struwe C, Petersen J, Perrot A, Posch MG, Ozcelik C, Richter
A, Maisch B, Pankuweit S.
Department of Cardiology, University of Marburg, Germany.
The cytotoxic T-lymphocyte antigen 4 (CTLA4) is an inhibitory receptor expressed
on activated T cells with downregulatory properties. The aim of this study was to
analyse whether single-nucleotide polymorphisms (SNPs) within the CTLA4 gene are
associated with the diagnosis and disease course of dilated cardiomyopathy (DCM).
In two independent cohorts of DCM patients (n=251 and 223) and healthy controls
(n=591), the promoter and all four exons of the CTLA4 gene, including their
flanking regions, were genotyped, and the resulting allele and genotype
distributions of the identified SNPs were compared between the groups. We
confirmed two known SNPs in the promoter region (-318C>T) and in exon 1
(+49A>G;Thr17Ala). The allelic frequencies and genotypic distribution of the
promoter SNP were similar for DCM patients compared with controls. However, the
G/G genotype of the Thr17Ala variant was significantly more frequent in DCM
patients compared with controls (37 out of 251 patients (14.7%) versus 44 out of
591 controls (7.4%), P=0.005). The higher frequency of the G/G genotype was
confirmed in an additional DCM cohort (29 out of 223 patients (13.0%), P=0.039),
indicating that this SNP functions as a risk factor for DCM. At follow-up after 1
year, the ejection fraction and the end-diastolic diameter of the left ventricle
did not differ significantly between DCM patients carrying the G/G genotype
versus other genotypes (n=199). Our data indicate that the common CTLA4 variant,
Thr17Ala, confers susceptibility for DCM, but does not seem to influence the
course of the disease 1 year after diagnosis.European Journal of Human Genetics
advance online publication, 10 February 2010; doi:10.1038/ejhg.2010.3.
PMID: 20145677 [PubMed - as supplied by publisher]
3. Herz. 2009 Dec;34(8):624-33.
[Differentiation of malignant from nonmalignant, inflammatory pericardial
effusions with biomarkers]
[Article in German]
Karatolios K, Alter P, Maisch B.
Klinik für Innere Medizin, Schwerpunkte Kardiologie, Angiologie, Internistische
Intensivmedizin und Prävention, Universitätsklinikum Giessen und Marburg GmbH,
Standort Marburg, und Philipps-Universität Marburg, Marburg, Germany.
karatoli@med.uni-marburg.de
Disorders of the pericardium are commonly associated with pericardial effusion.
Its etiology comprises a broad spectrum of diseases including also malignancies.
Pericardiocentesis, pericardioscopy and targeted epicardial biopsy with
consecutive pericardial fluid and epicardial biopsy analysis by cytology,
molecular biology and immunology establish the underlying etiology in the
majority of cases. Of particular therapeutic and prognostic importance is the
definite differentiation of malignant pericardial effusion from benign
pericardial effusion. Biomarkers for cardiovascular diseases can be divided into
biochemical, histological, immunologic, serologic and molecular markers as well
as imaging biomarkers. Biomarkers have proven to be useful in the diagnosis,
differential diagnosis and prognosis of ischemic heart disease and heart failure.
With respect to pericardial disorders, a comprehensive approach combining
clinical information, imaging biomarkers, biomarkers of pericardial effusion and
analysis of epicardial biopsies often leads to the definite etiologic diagnosis
of pericardial effusion. Computed tomography and magnetic resonance imaging allow
further characterization of the effusion and, of note, also of the surrounding
tissue, which is of particular interest in case of malignancies. Biomarkers of
pericardial effusion include biochemical markers, autoantibodies, tumor markers,
and cytokines. Analysis of pericardial fluid specific gravity, protein level and
lactate dehydrogenase (LDH) separates transudates from exsudates. High adenosine
deaminase levels (ADA) and low levels of carcinoembryonic antigen (CEA) in the
pericardial effusion are observed in tuberculous pericarditis allowing the
differentiation from malignant pericardial effusion. Additional markers, such as
interferon and lysozyme, have also been suggested for the diagnosis of
tuberculous pericarditis. Tumor markers in pericardial fluid have been used to
diagnose malignant pericarditis. CEA levels are significantly higher in malignant
than benign effusion. By a cutoff level of CEA > 5 ng/ml the diagnostic
sensitivity and specificity are 75% and 100%, respectively, in the diagnosis of
malignant pericardial effusion. Further analysis of cytokines and mediators,
serologic, immunologic and inflammatory markers may help to understand the
pathophysiology of the pericardial disease and provide useful diagnostic
information.
PMID: 20024642 [PubMed - indexed for MEDLINE]
4. Herz. 2009 Dec;34(8):614-23.
Biomarkers in inflammatory and noninflammatory cardiomyopathy.
Noutsias M, Pankuweit S, Maisch B.
Department of Internal Medicine - Cardiology, University Hospital of Marburg and
Giessen/UKGM GmbH, Faculty of Medicine, Philipps University of Marburg, Marburg,
Germany. michel.noutsias@staff.uni-marburg.de
Acute myocarditis (AMC) and its sequela, dilated cardiomyopathy (DCM), are most
often caused by cardiotropic viral infections in the Western world. Inflammatory
cardiomyopathy (DCMi) is a specific cardiomyopathy entity of DCM, being defined
by the proof of intramyocardial inflammation and/or viral infection in
endomyocardial biopsies (EMBs). Diagnostic procedures of EMBs are indispensable
for the etiopathogenic differentiation of the disease. Experienced cardiology
centers have reported low complication rates of EMB obtainment. The histological
Dallas criteria are prone to substantial sampling error and interobserver
variability, have no prognostic impact and, moreover, are not suitable to select
AMC/DCMi patients who favorably respond to immunosuppression. Immunohistological
detection of myocarditis and viral persistence have proven adverse prognostic
impact in AMC and DCM patients, respectively. This contemporary diagnostic
repertoire on EMBs is essential for the selection of DCMi patients who will
likely benefit from immunomodulatory treatment, which has been addressed in
randomized trials. During the past decade, cardiac magnetic resonance (CMR) has
developed as a valuable noninvasive diagnostic approach for the detection and
localization of intramyocardial inflammation, and CMR guidelines for AMC have
been elaborated. Late gadolinium enhancement (LGE) has been associated with
adverse prognostic outcome in DCM patients. CMR techniques, however, are not
suitable to specifically detect myocardial viral infections. To date, no classic
biomarker has been shown to differentiate between DCMi and noninflammatory
cardiomyopathies.
PMID: 20024641 [PubMed - indexed for MEDLINE]
5. Herz. 2009 Dec;34(8):579-80.
Biomarker and no end to it?
Maisch B.
Department of Internal Medicine - Cardiology, Angiology and Cardioprevention,
University Hospital of Marburg and Giessen/ UKGM GmbH, Faculty of Medicine,
Philipps University of Marburg, Marburg, Germany. maisch@staff.uni-marburg.de
PMID: 20024635 [PubMed - indexed for MEDLINE]
6. Herz. 2009 Mar;34(2):161-2.
Image of the month. Behind the curtain of pericardial tamponade: cardiac
hemangioendotheliosarcoma.
Maisch B, Bechtold H, Moll R, Moosdorf R.
Department of Internal Medicine and Cardiology, University Hospital of Internal
Medicine Giessen and Marburg GmbH, Marburg, Germany. maisch@med.uni-marburg.de
PMID: 19370334 [PubMed - indexed for MEDLINE]
7. Herz. 2009 Mar;34(2):110-6.
[Familial predisposition and microbial etiology in dilated cardiomyopathy]
[Article in German]
Pankuweit S, Richter A, Ruppert V, Maisch B.
Klinik für Innere Medizin - Kardiologie, Philipps-Universität Marburg,
Baldingerstrasse, 35043 Marburg, Germany. pankuwei@staff.uni-marburg.de
Cardiomyopathies are an important and diverse group of heart muscle diseases in
which the heart muscle itself is structurally or functionally abnormal and in
which coronary artery disease, hypertension, valvular and congenital heart
disease are absent or do not sufficiently explain the observed myocardial
abnormality. This often results in severe heart failure accompanied by
arrhythmias and/or sudden death. Clinical and morphological diversity of
cardiomyopathies can reflect the broad spectrum of distinct underlying molecular
causes or genetic heterogeneity. In many cases the disease is inherited and is
termed familial dilated cardiomyopathy (FDC), which may account for up to 30% of
dilated cardiomyopathies (DCM). FDC is principally caused by genetic mutations in
FDC genes that encode for cytoskeletal, nuclear and sarcomeric proteins in the
cardiac myocyte. In addition, modifying genes, lifestyle and additional factors
were reported to influence onset of disease, disease progression, and prognosis.
The individual patient's phenotype may reflect a summation and/or interaction of
the underlying mutation(s) with other genetic or environmental factors. During
the last years major advances have been made in the understanding of the
molecular and genetic basis of this type of disease. Nevertheless, much more
progress in the identification of underlying mutations, susceptibility genes and
modifier genes is important and indispensable for the development of new
etiology-orientated forms of therapy. A pivotal role for autoimmunity in a
substantial proportion of patients with DCM is supported by the presence of
organ-specific autoantibodies, inflammatory infiltrates and pro-inflammatory
cytotoxic cytokines. Furthermore, familial occurrence of DCM goes ahead with the
presence of autoantibodies and abnormal cytokine profiles in first-degree
relatives with asymptomatic left ventricular enlargement. These relatives suffer
from a higher risk for the development of DCM after years. This suggests the
involvement of a disrupted humoral and cellular immunity early in the development
of the disease. There is reasonable clinical and experimental evidence, that DCM
in addition may occur as late stage of cardiac infection and inflammation. The
large spectrum of clinical forms depends on several factors such as genetic
determinants of the infective agent, the genetics, age and gender of the host,
and the host immunocompetence. In general, infectious agents, including viruses
such as entero-, cytomegalo-, and adenoviruses, bacteria such as Borrelia
burgdorferi or Chlamydia pneumoniae, protozoa and even fungi can cause
inflammatory heart disease leading to DCM. The infectious agents most often
identified in DCM nowadays are parvovirus B19, human herpesvirus 3, and
Epstein-Barr virus. Persistence of these viruses within the myocardium is
associated with reduction of ejection fraction after 6 months. For patients with
suspected inflammatory heart disease the immunohistochemical detection of
inflammatory infiltrates is related to poor outcome. Many faces of inflammatory
heart disease coexist where different phases of the disease progress
simultaneously: phase 1 is dominated by viral infection itself, phase 2 by the
onset of (probably) multiple autoimmune reactions, and phase 3 by the progression
to cardiac dilatation. Further investigations with regard to the etiology of
structural heart diseases should include an intensive clinical investigation of
the given patient. A possible family history including a pedigree should be
ascertained and with regard to a possible inflammatory or viral heart disease,
endomyocardial biopsies should be investigated by polymerase chain reaction and
immunohistochemistry.
PMID: 19370326 [PubMed - indexed for MEDLINE]
8. Pacing Clin Electrophysiol. 2009 Mar;32 Suppl 1:S8-11.
Sleep-disordered breathing in recipients of implantable defibrillators.
Grimm W, Sharkova J, Heitmann J, Jerrentrup A, Koehler U, Maisch B.
Department of Cardiology, University of Marburg and Giessen, Marburg, Germany.
grimmw@med.uni-marburg.de
STUDY OBJECTIVES: To examine the prevalence and clinical significance of
sleep-disordered breathing in patients with implantable cardioverter
defibrillators (ICD). METHODS AND RESULTS: Overnight sleep studies were performed
in 129 ICD recipients who had no history of sleep apnea. The mean left
ventricular ejection fraction (LVEF) was 29 +/- 11%. Mild, moderate, and severe
sleep apnea was diagnosed in the presence of an apnea/hypopnea index (AHI) of
5-15/h, 15.1-30/h, and >30/h, respectively. No sleep apnea was present in 49
patients (38%), 57 (44%) had central sleep apnea (CSA), and 23 patients (18%) had
obstructive sleep apnea (OSA). Mild, moderate, and severe sleep apnea were
present in 25%, 31%, and 44% of patients with CSA, compared with 52%, 22%, and
26% of patients with OSA (P < 0.05). LVEF was similar in patients with versus
without OSA or CSA. Patients with CSA were significantly older and had a higher
prevalence of ischemic cardiomyopathy than patients without sleep apnea.
CONCLUSIONS: Previously undiagnosed CSA is common in ICD recipients. Severely
disordered breathing during sleep was more prevalent among patients with CSA than
patients with OSA. This prospective, observational study will examine the
long-term clinical significance of sleep-disordered breathing in ICD recipients.
PMID: 19250118 [PubMed - indexed for MEDLINE]
9. Pacing Clin Electrophysiol. 2009 Mar;32 Suppl 1:S26-31.
Depression of heart rate variability in patients with increased ventricular wall
stress.
Alter P, Rupp H, Rominger MB, Czerny F, Vollrath A, Klose KJ, Maisch B.
Department of Internal Medicine - Cardiology, Philipps University, Marburg,
Gremany. alter@staff.uni-marburg.de
BACKGROUND: Heart failure is characterized by neurohumoral dysfunction that can
be assessed by measurement of heart rate variability (HRV). Depression of HRV is
related to several hemodynamic parameters. We hypothesized that an increased left
ventricular (LV) wall stress is related to a depressed HRV in patients with LV
dilatation or dysfunction. METHODS: Cardiac function and mass were measured in 31
patients with LV dilatation or dysfunction and 21 controls using cardiac magnetic
resonance (CMR) imaging. LV wall stress was calculated using a CMR-based
thick-walled sphere model. Standard deviation of normal-to-normal (NN) intervals
(SDNN) and average NN intervals over 5 minutes (SDANN-i) were calculated.
RESULTS: LV end-diastolic (ED) and end-systolic (ES) wall stress were
significantly increased in patients with SDNN < 75 ms (P < 0.05). SDNN and
SDANN-i were decreased (P = 0.001, P < 0.001) in patients with LVED wall stress
>8 kPa and LVES wall stress >30 kPa (P < 0.05). To examine potential effects of
LVEF, LVED and LVES volume, and wall stress on HRV, a multiple linear regression
analysis was performed, which revealed LVED wall stress as the only independent
parameter influencing SDNN (P = 0.039). LV ejection fraction, LV mass, and
volumes were not significantly related to HRV. CONCLUSIONS: LV wall stress was
independently related with depression of HRV. Therefore, LV wall stress might be
prognostically important and a therapeutic target in heart failure.
PMID: 19250107 [PubMed - indexed for MEDLINE]
10. Herz. 2009 Feb;34(1):55-62.
[Classification of cardiomyopathies and indication for endomyocardial biopsy
revisited]
[Article in German]
Pankuweit S, Richter A, Ruppert V, Maisch B.
Klinik für Innere Medizin - Kardiologie, Philipps-Universität Marburg,
Baldingerstrasse, 35043, Marburg. pankuwei@staff.uni-marburg.de
The first classifications of cardiomyopathies from 1980 and 1996 described them
as heart muscle diseases, with dilated (DCM), hypertrophic (HCM), restrictive
(RCM), arrhythmogenic right ventricular (ARVC), and nonclassifiable
cardiomyopathies. Furthermore, the World Health Organization/International
Society and Federation of Cardiology (WHO/ISFC) classification from 1996 listed
among the specific cardiomyopathies inflammatory cardiomyopathy as a new and
distinct entity, which was defined histologically as myocarditis in association
with cardiac dysfunction. Infectious and autoimmune forms of inflammatory
cardiomyopathy were recognized. Viral cardiomyopathy was defined as viral
persistence in a dilated heart without ongoing inflammation. If it was
accompanied by myocardial inflammation, it was termed inflammatory viral
cardiomyopathy (or viral myocarditis with cardiomegaly). This entity was further
elucidated in a World Heart Federation consensus meeting in 1999 by quantitative
immunohistological criteria (< 14 infiltrating cells/mm(2)) and the etiology by
molecular biological methods, e.g., polymerase chain reaction, as viral,
bacterial, or autoimmune (= nonmicrobial). The development of molecular genetics,
with the discovery of a genetic background in several forms of cardiomyopathies
previously alluded to as "of unknown origin", was the origin of a debate on a new
classification based on genomics. A genomic/postgenomic classification was
postulated taking the underlying gene mutations and the cellular level of
expression of encoded proteins into account, thus distinguishing cytoskeleton
(cytoskeletalopathies, e.g., DCM or ARVC), sarcomeric (sarcomyopathies as in HCM
and RCM) and ion channel (channelopathies, e.g., long or short QT syndrome and
Brugada's syndrome) cardiomyopathies. Such a classification of cardiomyopathies
was proposed in 2006 by the American Heart Association (AHA), which took the
rapid evolution of molecular genetics in cardiology into account. It also
introduced several recently described diseases, and is unique in that it
incorporated ion channelopathies even without hemodynamic dysfunction as a
"primary" cardiomyopathy. The ESC (European Society of Cardiology) Working Group
on Myocardial and Pericardial Diseases has deliberately taken a different
approach based on a clinically oriented classification in which heart muscle
disorders were grouped according to morphology and function. This obviously
remains the clinically most useful approach for the diagnosis and management of
patients and families with heart muscle disease. In the ESC position statement
published in 2008, cardiomyopathies were defined as myocardial disorders in which
the heart muscle is structurally and functionally abnormal, and in which coronary
artery disease, hypertension, valvular and congenital heart disease are absent or
do not sufficiently explain the observed myocardial abnormality. The aim was to
help clinicians look beyond generic diagnostic labels in order to reach more
specific diagnoses. In parallel, a scientific statement on the role of
endomyocardial biopsy in the management of cardiovascular disease was published
at the end of 2007 making useful recommendations for clinical practice and
providing an understanding for the use of endomyocardial biopsy in an individual
patient. Taking the classification of cardiomyopathies and the statement on the
role of endomyocardial biopsies in different clinical scenarios together, the
clinician is now able to identify genetic, autoimmune and viral causative factors
by using a thorough and logical approach to reach a diagnosis in patients with
familial and nonfamilial forms of the underlying structural heart muscle
diseases.
PMID: 19214409 [PubMed - indexed for MEDLINE]
11. Autoimmunity. 2009 Jan;42(1):33-40.
HLA-DQB1* polymorphism and associations with dilated cardiomyopathy, inflammatory
dilated cardiomyopathy and myocarditis.
Portig I, Sandmoeller A, Kreilinger S, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University Marburg, Marburg,
Germany. portig@med.uni-marburg.de
To date, only weak associations have been reported between idiopathic dilated
cardiomyopathy (DCM) and certain HLA class II alleles. Associations between HLA
class II alleles and specific causes of DCM, especially myocarditis, have as yet
not been systematically investigated. Typing of HLA DQB1* allele was performed
using a sequence-specific primer-polymerase chain reaction technique in 22
unrelated patients with idiopathic DCM, 19 patients with myocarditis and normal
left ventricular function, and 16 patients with myocarditis and impaired left
ventricular function (i.e. inflammatory DCM). Controls comprised 44 patients
without (inflammatory) cardiac disease and a population control. A significant
association was found for presence of HLA DQB1*0303 with myocarditis without
cardiac dysfunction. Weaker associations were seen for presence of HLA DQB1*0301
and absence of HLA DQB1*06 with inflammatory DCM. Additionally, allelic
combination DQB1*02-DQB1*03 may be able to distinguish idiopathic from
inflammatory DCM, and HLA DQB1*02 myocarditis with cardiac dysfunction from
myocarditis without, if results are confirmed by larger prospective studies.
PMID: 19127454 [PubMed - indexed for MEDLINE]
12. Clin Res Cardiol. 2009 Feb;98(2):80-8. Epub 2008 Oct 13.
Athlete's heart or hypertrophic cardiomyopathy?
Lauschke J, Maisch B.
Department of Internal Medicine and Cardiology, Philipps-Universität Marburg,
Marburg, Germany. lauschke@med.uni-marburg.de
Comment in:
Clin Res Cardiol. 2009 Jul;98(7):465-6; author reply 467-8.
Clin Res Cardiol. 2009 Jul;98(7):463-4; author reply 467-8.
Intensive endurance training is able to cause a distinct pattern of functional
and structural changes of the cardiovascular system. In an unknown proportion of
athletes a so called "athlete's heart" develops. There is an overlap between this
type of physiologic cardiac hypertrophy and mild forms of hypertrophic
cardiomyopathy (HCM), the most common genetic disorder of the cardiovascular
system with a prevalence of 0.2%. HCM is caused by mutations in 14 genes coding
for sarcomere proteins. In the literature up to 50% of cases of sudden cardiac
death (SCD) in younger sportsmen were connected to hypertrophic cardiomyopathy.
It is therefore the most common cause of SCD in highly trained young athletes.
Because of this data a great interest in distinguishing these two diagnoses
exists. Apart from clinical examination and some non-specific ECG-changes,
Echocardiography is the method of choice. The athlete's heart shows an eccentric
biventricular hypertrophy with wall thicknesses under 15 mm and a moderately
dilated left ventricle (LVEDD up to 58 mm). HCM is commonly characterized by
asymmetric left ventricular hypertrophy with a reduced LV-diameter. In up to 70%
of cases left ventricular outflow tract obstruction is evident during stress
echocardiography. Systolic function is normal in highly trained athletes and the
majority of HCM patients as well. There are important differences regarding
diastolic filling patterns. Physiological hypertrophy is consistent with a normal
diastolic function with even increased early diastolic filling. In case of HCM
diastolic dysfunction (mostly relaxation disturbances) occurs in the majority of
patients and is therefore inconsistent with an athlete's heart. If the diagnosis
could not be stated using echocardiography, methods like cardiac-MRI, metabolic
exercise testing, histological studies of endomyocardial biopsies and genetic
testing can provide further information. A correct diagnosis may on the one hand
prevent some athletes from sudden cardiac death. On the other hand sportsmen with
an athlete's heart are reassured and able to continue as competitors. New
insights into electrophysiological changes during physiological hypertrophy could
probably change this view.
PMID: 18853091 [PubMed - indexed for MEDLINE]
13. Hum Genet. 2008 Oct;124(3):314.
Gene symbol: MYBPC3. Disease: Cardiomyopathy, hypertrophic.
Ruppert V, Meyer T, Pankuweit S, Maisch B, Funck RC.
Philipps-Universität Marburg, Innere Medizin, Kardiologie, Hans-Meerwein-Strasse,
1, 35043 Marburg, Germany. ruppert@med.uni-marburg.de
PMID: 18846659 [PubMed - indexed for MEDLINE]
14. J Thorac Cardiovasc Surg. 2008 Aug;136(2):360-369.e1. Epub 2008 May 12.
Gene expression profiling from endomyocardial biopsy tissue allows distinction
between subentities of dilated cardiomyopathy.
Ruppert V, Meyer T, Pankuweit S, Möller E, Funck RC, Grimm W, Maisch B; German
Heart Failure Network.
Department of Cardiology, University of Marburg, Baldingerstrasse, Marburg,
Germany.
OBJECTIVE: Expression profile analysis using endomyocardial biopsy specimens from
patients with cardiomyopathies promises to improve the differential diagnosis of
heart failure. METHODS: In this study, left ventricular endomyocardial biopsy
specimens were obtained from 50 patients and histopathologically classified
according to the World Heart Federation Task Force criteria as having dilated
cardiomyopathy (n = 17), inflammatory cardiomyopathy (n = 11), myocarditis (n =
15), or pericarditis (n = 7). Microarrays were performed by hybridization of
synthesized complementary DNA against a Lab-Arraytor60-combi microarray
(SIRS-Lab, Jena, Switzerland). Differentially expressed genes were clustered
hierarchically according to their variation in hybridization signals. RESULTS: In
samples from patients with dilated cardiomyopathy, two different types of gene
expression profiles were distinguishable. One pattern was unique for dilated
cardiomyopathy and inflammatory cardiomyopathy, respectively, and the other more
closely resembled that seen in samples from inflammatory heart disease.
Additionally, we confirmed the microarray data by showing that dilated
cardiomyopathy is associated with a reduced myocardial toll-like receptor 9
expression that resulted from progressive loss of functional cardiomyocytes.
Taken together, our data demonstrate the utility and validity of microarrays from
endomyocardial biopsy specimens in detecting subentities of dilated
cardiomyopathy that do not differ histopathologically, but transcriptionally,
from each other. The gene expression profile observed in one subgroup of patients
with dilated cardiomyopathy is indicative of ongoing immune activation, albeit
infiltrating immunocompetent cells were not detected histopathologically.
CONCLUSION: Thus, our transcriptional data indicate that dilated cardiomyopathy
constitutes a heterogeneous disease with an broad overlap to inflammatory heart
disease.
PMID: 18692642 [PubMed - indexed for MEDLINE]
15. Apoptosis. 2008 Jul;13(7):857-66.
Glycosylphosphatidylinositol-induced cardiac myocyte death might contribute to
the fatal outcome of Plasmodium falciparum malaria.
Wennicke K, Debierre-Grockiego F, Wichmann D, Brattig NW, Pankuweit S, Maisch B,
Schwarz RT, Ruppert V.
Department of Internal Medicine - Cardiology, Philipps-University of Marburg,
University Hospital, Baldingerstrasse 1, 35043 Marburg/Lahn, Germany.
BACKGROUND: Glycosylphosphatidylinositol (GPI) purified from Plasmodium
falciparum has been shown to play an important role as a toxin in the pathology
of malaria. Previous studies demonstrated cardiac involvement in patients
suffering from severe malaria due to P. falciparum. Therefore, we tested the
hypothesis that GPI induces apoptosis in cardiomyocytes. METHODS AND RESULTS: By
using TUNEL and caspase activity assays, we provided evidence for apoptosis
induction in cardiomyocytes by P. falciparum GPI after 48 h of incubation. A
similar result was obtained in heart cells of mice 48 h after in vivo injection
of GPI. Gene expression analyses in GPI-treated cardiomyocytes showed an
up-regulation of apoptotic genes (apaf-1, bax) and of a myocardial damage marker
bnp (brain natriuretic peptide), while a down-regulation was observed for the
anti-apoptotic gene bcl-2 and for the heat shock protein hsp70. In spite of
inflammatory cytokine gene up-regulation by GPI, co-culture with peripheral
mononuclear cells (PMNCs) did not change the results obtained with cardiomyocytes
alone, indicating a direct effect of GPI on cardiac myocytes. Co-culture with
non-myocytic cardiac cells (NMCCs) resulted in up-regulation of Hsp70 and Bcl-2
genes in GPI-treated cardiomyocytes but without repercussion on the apoptosis
level. A malaria-infected patient, presenting fulminant heart failure showed
typical signs of cardiac myocyte apoptosis demonstrating the clinical relevance
of toxin induced heart damage for the lethality of malaria. Our studies performed
in vitro and in mice suggest that the GPI could be responsible for cardiomyocyte
apoptosis that occurred in this patient. CONCLUSION: Plasmodium falciparum
GPI-induced apoptosis might participate in the lethality of malaria.
PMID: 18470700 [PubMed - indexed for MEDLINE]
16. Mol Cell Biochem. 2008 Jul;314(1-2):179-91. Epub 2008 May 7.
B-type natriuretic peptide and wall stress in dilated human heart.
Alter P, Rupp H, Rominger MB, Vollrath A, Czerny F, Figiel JH, Adams P, Stoll F,
Klose KJ, Maisch B.
Internal Medicine, Cardiology, Philipps University, Baldingerstrasse, Marburg,
Germany. alter@staff.uni-marburg.de
Background Although B-type natriuretic peptide (BNP) is used as complimentary
diagnostic tool in patients with unknown thoracic disorders, many other factors
appear to trigger its release. In particular, it remains unresolved to what
extent cellular stretch or wall stress of the whole heart contributes to enhanced
serum BNP concentration. Wall stress cannot be determined directly, but has to be
calculated from wall volume, cavity volume and intraventricular pressure of the
heart. The hypothesis was, therefore, addressed that wall stress as determined by
cardiac magnetic resonance imaging (CMR) is the major determinant of serum BNP in
patients with a varying degree of left ventricular dilatation or dysfunction
(LVD). Methods A thick-walled sphere model based on volumetric analysis of the LV
using CMR was compared with an echocardiography-based approach to calculate LV
wall stress in 39 patients with LVD and 21 controls. Serum BNP was used as in
vivo marker of a putatively raised wall stress. Nomograms of isostress lines were
established to assess the extent of load reduction that is necessary to restore
normal wall stress and related biochemical events. Results Both enddiastolic and
endsystolic LV wall stress were correlated with the enddiastolic LV volume (r =
0.54, P < 0.001; r = 0.81, P < 0.001). LV enddiastolic wall stress was related to
pulmonary pressure (capillary: r = 0.69, P < 0.001; artery: r = 0.67, P < 0.001).
Although LV growth was correlated with the enddiastolic and endsystolic volume (r
= 0.73, P < 0.001; r = 0.70, P < 0.001), patients with LVD exhibited increased LV
wall stress indicating an inadequately enhanced LV growth. Both enddiastolic (P <
0.05) and endsystolic (P < 0.01) wall stress were increased in patients with
increased BNP. In turn, BNP concentration was elevated in individuals with
increased enddiastolic wall stress (>8 kPa: 587 +/- 648 pg/ml, P < 0.05; >12 kPa:
715 +/- 661 pg/ml, P < 0.001; normal < or =4 kPa: 124 +/- 203 pg/ml). Analysis of
variance revealed LV enddiastolic wall stress as the only independent hemodynamic
parameter influencing BNP (P < 0.01). Using nomograms with "isostress" curves,
the extent of load reduction required for restoring normal LV wall stress was
assessed. Compared with the CMR-based volumetric analysis for wall stress
calculation, the echocardiography based approach underestimated LV wall stress
particularly of dilated hearts. Conclusions In patients with LVD, serum BNP was
increased over the whole range of stress values which were the only hemodynamic
predictors. Cellular stretch appears to be a major trigger for BNP release.
Biochemical mechanisms need to be explored which appear to operate over this wide
range of wall stress values. It is concluded that the diagnostic use of BNP
should primarily be directed to assess ventricular wall stress rather than the
extent of functional ventricular impairment in LVD.
PMID: 18461428 [PubMed - indexed for MEDLINE]
17. Herzschrittmacherther Elektrophysiol. 2008 Mar;19(1):41-7.
[Biventricular stimulation for AV block]
[Article in German]
Funck RC, Kölsch S, Maisch B.
Universitätsklinikum Giessen und Marburg, Standort Marburg Klinik für Innere
Medizin - Kardiologie, Angiologie und Kardioprävention, Marburg.
funck@mailer.uni-marburg.de
Since the establishment of cardiac resynchronization therapy in left bundle
branch block and mechanical asynchrony, the adverse effects of right ventricular
apical pacing have gained increasing scientific interest. The sequelae of
"iatrogenic desynchronization" on cardiac structure and function as well as on
patients' prognosis could be well documented. "Minimally desynchronizing"
stimulation strategies could be an alternative for patients needing ventricular
pacing. The search for hemodynamically more advantageous alternative right
ventricular pacing sites has failed so far to deliver well validated results, and
due to the somewhat higher lead dislodgment rates pure left ventricular pacing
cannot be recommended, at least not in pacemaker-dependent patients. Hence there
is the question for primary biventricular stimulation in patients with AV block.
The results of several biventricular studies with limited numbers of patients
have been promising with respect to structural and functional surrogate
endpoints. Two major controlled prospective and prognostically orientated
studies, the BIOPACE study and the BLOCK-HF study, are currently underway and
will report results in the next few years. According to the actual guidelines of
the European Society of Cardiology (ESC) the implantation of a biventricular
system is recommended in patients with AV block even without left bundle branch
block (Class IIa, evidence level C) if they fulfill the remaining criteria that
justify the implantation of a biventricular system. According to the guidelines
for pacemaker therapy of the German Cardiac Society (GCS) biventricular pacing
can be considered in these patients. Both societies do expressly permit the
implantation of biventricular systems with ICD backup if indicated.
PMID: 18330674 [PubMed - indexed for MEDLINE]
18. Cardiovasc Pathol. 2008 Mar-Apr;17(2):81-92. Epub 2007 Sep 14.
Activation of STAT1 transcription factor precedes up-regulation of
coxsackievirus-adenovirus receptor during viral myocarditis.
Ruppert V, Meyer T, Pankuweit S, Jonsdottir T, Maisch B.
Department of Cardiology, University of Marburg, Marburg, Germany.
ruooert@med.uni-marburg.de
The coxsackievirus-adenovirus receptor (CAR) was originally described as a
transmembrane protein involved in viral infection and was later found to be
required for normal heart development. However, the role of CAR in virus-induced
myocarditis has not been investigated so far. The purpose of this study was to
assess myocardial CAR expression in response to cytokine-induced inflammatory
reactions during the course of coxsackievirus-induced myocarditis. In Balb/c mice
intraperitoneally infected with either 2x10(4) plaque-forming units (PFUs) of
coxsackie B3 virus (CVB3) or 10(2) PFUs CVB3, CAR expression and tyrosine
phosphorylation of signal transducer and activator of transcription 1 (STAT1), a
known cytokine-inducible transcription factor involved in viral defense, were
determined. Our results demonstrated that within the first 7 days after virus
inoculation, when the viral replication and STAT1 activation in the heart tissue
was most prominent, the expression of CAR did not surpass that of uninfected
controls. However, the up-regulation of CAR was observed 9 weeks later, when
enteroviral RNA was no longer detectable and activation of STAT1 had already
ceased. In contrast to the STAT1 target genes Mig and Irf1, interferon gamma
stimulation failed to up-regulate Car expression in isolated cardiomyocytes. In
human endomyocardial biopsies, Car expression was found to be elevated in
approximately one third of patients with dilated cardiomyopathy (9 of 30
patients) as compared with controls. Thus, activation of STAT1 clearly precedes
the enhanced CAR expression observed during tissue reorganization, suggesting an
essential role of STAT1 transcription factors in orchestrating the sequential
actions involved in adaptive immune response.
PMID: 18329552 [PubMed - indexed for MEDLINE]
19. Internist (Berl). 2008 Apr;49(4):441-2, 444-7.
[Classification, genetic predisposition and risk factors for the development of
cardiomyopathies]
[Article in German]
Pankuweit S, Richter A, Ruppert V, Funck R, Maisch B.
Klinik für Innere Medizin-Kardiologie, Universitätsklinikum Giessen und Marburg,
Standort Marburg, Baldingerstrasse, 35043, Marburg, Germany.
pankuwei@staff.uni-marburg.de
Cardiomyopathies are an important and diverse group of heart muscle diseases in
which the heart muscle itself is structural or functional abnormal. This often
results in severe heart failure accompanied by arrhythmias and/or sudden death.
Clinical and morphological diversity of cardiomyopathies can reflect the broad
spectrum of distinct underlying molecular causes or genetic heterogeneity. In
addition, modifying genes, life style and additional factors were reported to
influence onset of disease, disease progression and prognosis. The individual
patient's phenotype may reflect a summation and/or interaction of the underlying
mutation with other genetic or environmental factors. During the last years major
advances have been made in the understanding of the molecular and genetic basis
of this type of disease. Nevertheless, much more progress in the identification
of underlying mutations, susceptibility genes and modifier genes is important and
indispensable for the development of new etiology orientated forms of therapy.
PMID: 18274717 [PubMed - indexed for MEDLINE]
20. Curr Treat Options Cardiovasc Med. 2007 Dec;9(6):473-81.
Diagnosis and treatment of myocarditis: the role of endomyocardial biopsy.
Karatolios K, Pankuweit S, Maisch B.
Bernhard Maisch, MD Department of Internal Medicine-Cardiology, University
Hospital of Giessen and Marburg GmbH, Baldingerstrasse 1, D-35033 Marburg,
Germany. maisch@med.uni-marburg.de.
Viral infections often affect the heart. In the majority of cases, the course of
the disease is benign and patients recover spontaneously. However, viral
infection may persist and lead to acute cardiac failure or progress to dilated
cardiomyopathy. Viral infections are considered to be the most common causes of
myocarditis. There is evidence that intramyocardial viral persistence is
associated with progressive ventricular dysfunction, even when the infiltrate is
sparse or missing. The diagnosis of viral myocarditis necessitates the detection
of viral genome by molecular biology techniques and the evaluation of myocardial
inflammation by the immunohistochemistry on endomyocardial biopsy samples.
Autoreactive myocarditis can also only be diagnosed by endomyocardial biopsy.
Infiltration of leukocytes and a negative polymerase chain reaction on microbial
agents are their hallmarks. Apart from symptomatic or supportive therapy,
etiologic treatment strategies have to address the underlying causative virus or
the autoimmune process. In symptomatic or deteriorating patients, targeted
antiviral therapy is a reasonable algorithm to eradicate the virus, which will
contribute to resolving inflammation or apoptosis, thus confining myocardial
damage. The Marburg registry favors intravenous immunoglobulin treatment in
biopsy-proven adenovirus and parvovirus B19 myocarditis combined with optimal
conventional therapy to achieve virus clearance. In fulminant myocarditis, biopsy
is mandatory to identify giant cell myocarditis and cardiac sarcoidosis to be
treated by immunosuppression. In cardiogenic shock, the use of mechanical
circulatory support by means of a ventricular assist device as a bridge to
recovery may be a lifesaving approach. In perimyocarditis with dominant
pericardial affection, colchicine over a period of 1 to 6 months can dissolve the
pericardial effusion effectively in more than 80% of cases.
PMID: 18221599 [PubMed - in process]
21. Internist (Berl). 2008 Jan;49(1):17-26.
[New possibilities of diagnostics and therapy of pericarditis]
[Article in German]
Maisch B, Karatolios K.
Klinik für Innere Medizin, Schwerpunkt Kardiologie, Universitätsklinikum Giessen
und Marburg, Baldingerstrasse 1, 35033, Marburg, Deutschland.
Bernhard.Maisch@med.uni-marburg.de
Pericarditis is an inflammatory disorder of the pericardium with or without an
associated pericardial effusion. The diagnosis is based on the clinical
manifestations and typical ECG changes. Echocardiography is essential to reveal
the size of the pericardial effusion and to determine its hemodynamic
significance. The precise etiology of pericarditis may be established by
pericardiocentesis, pericardioscopy and targeted biopsy and consecutive
pericardial fluid and biopsy analysis by molecular biology, cytology,
microbiology and immunological techniques. Non steroidal anti-inflammatory drugs
and/or colchicine are the mainstay of anti-inflammatory treatment of
pericarditis. Systemic corticoid treatment should be restricted to patients with
associated autoimmune disorder, relapsing pericarditis and as a complementary
therapy in tuberculous pericarditis. In autoreactive pericarditis
intrapericardial instillation of triamcinolone is effective with few side
effects. In malignant pericarditis the intrapericardial administration of
cisplatin prevents early recurrences.
PMID: 18210029 [PubMed - indexed for MEDLINE]
22. Clin Appl Thromb Hemost. 2009 May-Jun;15(3):297-308. Epub 2007 Dec 26.
Monitoring of functional plasminogen in the blood of patients on fibrinolytics.
Stief TW, Richter A, Maisch B, Renz H.
Department of Laboratory Medicine, Hospital of Philipps-University, Marburg,
Germany. thstief@med.uni-marburg.de
There are no reliable data on functional plasminogen in the blood of patients
receiving fibrinolytic treatment. Here, artifactual in vitro changes of
functional plasminogen were prevented by arginine stabilization blood samples of
myocardial infarction patients: 12 received 36.4 mg reteplase in bolus, and 1
patient received 100 mg tissue plasminogen activator in continuous infusion.
Arginine (1.5 M, 1.3 mL, pH 8.7) was used to stabilize 2.6 mL
ethylenediaminetetraacetic acid-blood. The arginine-stabilized plasma was
analyzed with a functional oxidative assay for plasminogen. Functional
plasminogen decreased within 2 minutes of reteplase treatment by about 40% and by
about 80% after 60 minutes. Lowest plasminogen concentrations were found in
plasmas with highest plasmin activities. Chloramine oxidation of purified
Glu-plasminogen increased its activation by urokinase up to 3-fold. Arginine
stabilization allows reliable determinations of functional plasminogen in the
blood of patients receiving fibrinolytics, enabling the rapid diagnosis of
prothrombotic plasminogen consumption. The present findings support the
profibrinolytic action of chloramines.
PMID: 18160581 [PubMed - indexed for MEDLINE]
23. Can J Physiol Pharmacol. 2007 Aug;85(8):790-9.
Relation of B-type natriuretic peptide to left ventricular wall stress as
assessed by cardiac magnetic resonance imaging in patients with dilated
cardiomyopathy.
Alter P, Rupp H, Rominger MB, Vollrath A, Czerny F, Klose KJ, Maisch B.
Philipps University, Internal Medicine - Cardiology, Baldingerstrasse, D-35033
Marburg, Germany. alter@staff.uni-marburg.de
Ventricular loading conditions are crucial determinants of cardiac function and
prognosis in heart failure. B-type natriuretic peptide (BNP) is mainly stored in
the ventricular myocardium and is released in response to an increased
ventricular filling pressure. We examined, therefore, the hypothesis that BNP
serum concentrations are related to ventricular wall stress. Cardiac magnetic
resonance imaging (MRI) was used to assess left ventricular (LV) mass and cardiac
function of 29 patients with dilated cardiomyopathy and 5 controls. Left
ventricular wall stress was calculated by using a thick-walled sphere model, and
BNP was assessed by immunoassay. LV mass (r = 0.73, p < 0.001) and both LV
end-diastolic (r = 0.54, p = 0.001) and end-systolic wall stress (r = 0.66, p <
0.001) were positively correlated with end-diastolic volume. LV end-systolic wall
stress was negatively related to LV ejection fraction (EF), whereas end-diastolic
wall stress was not related to LVEF. BNP concentration correlated positively with
LV end-diastolic wall stress (r = 0.50, p = 0.002). Analysis of variance revealed
LV end-diastolic wall stress as the only independent hemodynamic parameter
influencing BNP (p < 0.001). The present approach using a thick-walled sphere
model permits determination of mechanical wall stress in a clinical routine
setting using standard cardiac MRI protocols. A correlation of BNP concentration
with calculated LV stress was observed in vivo. Measurement of BNP seems to be
sufficient to assess cardiac loading conditions. Other relations of BNP with
various hemodynamic parameters (e.g., EF) appear to be secondary. Since an
increased wall stress is associated with cardiac dilatation, early diagnosis and
treatment could potentially prevent worsening of the outcome.
PMID: 17901889 [PubMed - indexed for MEDLINE]
24. Herz. 2007 Sep;32(6):458-72.
Integrated biomarkers in cardiomyopathies: cardiovascular magnetic resonance
imaging combined with molecular and immunologic markers--a stepwise approach for
diagnosis and treatment.
Schulz-Menger J, Maisch B, Abdel-Aty H, Pankuweit S.
Cardiology, Franz Volhard Clinic, Charité Campus Buch, Helios Klinikum Berlin,
University Medicine, Berlin, and Department of Internal Medicine-Cardiology,
University Hospital Giessen, Marburg, Germany. jeanette.schulz-menger@charite.de
In an integrated approach, the authors examine the most efficient combination of
noninvasive and invasive biochemical, immunologic, functional, molecular, imaging
and biopsy-derived biomarkers for their applicability in the diagnosis of
cardiomyopathies in general and dilated cardiomyopathy (DCM) in particular. A
careful selection out of the cascade of available biomarkers will allow, in
individual patients, to diagnose certain conditions of cardiomyopathies without
endomyocardial biopsy, e.g., borreliosis, rickettsiosis, HIV cardiomyopathy.
Viral persistence in DCM associated with inflammation will need both noninvasive
(echocardiography, cardiovascular magnetic resonance) and invasive biomarkers
(polymerase chain reaction for viral persistence or their exclusion in case of
autoreactive myocarditis and quantitative immunohistology, both from
endomyocardial biopsy).
PMID: 17882371 [PubMed - indexed for MEDLINE]
25. J Periodontol. 2007 Sep;78(9):1724-30.
Periodontal microbiota in patients with coronary artery disease measured by
real-time polymerase chain reaction: a case-control study.
Nonnenmacher C, Stelzel M, Susin C, Sattler AM, Schaefer JR, Maisch B, Mutters R,
Flores-de-Jacoby L.
Institute of Medical Microbiology and Hygiene, Philipps University Marburg,
Marburg, Germany.
BACKGROUND: Recent data have shown that periodontal disease may increase the risk
of occurrence of coronary heart disease in which inflammation initiated by
bacteria and their compounds might be a common causal factor. This case-control
study aimed at studying the relationship between periodontal disease and coronary
artery disease (CAD) based on clinical and periodontal microbiologic parameters.
METHODS: A total of 90 male subjects, 48 to 80 years of age, were included in
this study. Forty-five men had CAD (CAD+), which was confirmed by coronary
angiography. Forty-five age-matched controls showed no history or symptoms of CAD
(CAD-). All subjects underwent a clinical periodontal examination including
assessment of tooth loss, probing depth, clinical attachment level, and bleeding
on probing. In the CAD+ group, this examination took place 1 day before coronary
angiography. Subgingival microbial samples were taken and evaluated by means of
real-time polymerase chain reaction (RT-PCR) for the total amount of bacteria and
the following periodontopathogens: Actinobacillus actinomycetemcomitans,
Porphyromonas gingivalis, Prevotella intermedia, Parvimonas micra (formerly
Micromonas micros), Dialister pneumosintes, and Campylobacter rectus. RESULTS:
Compared to control subjects, CAD+ subjects had significantly deeper pockets
(2.28 mm versus 2.96 mm; P <0.001) and greater attachment loss (2.85 mm versus
3.65 mm; P <0.001), and this difference remained statistically significant after
adjusting for smoking. No significant differences were observed between cases and
controls with regard to the number of teeth present. P. intermedia was the only
periodontal pathogen that showed significantly higher mean counts in CAD+
subjects compared to CAD- subjects. Higher counts of total bacteria, P. micra, D.
pneumosintes, and C. rectus were found in the CAD- group. CONCLUSION: The results
suggest that a relationship between periodontal disease and coronary heart
disease exists, although P. intermedia was the only periodontopathogen related to
CAD.
PMID: 17760542 [PubMed - indexed for MEDLINE]
26. Pflugers Arch. 2008 Jan;455(4):627-36. Epub 2007 Aug 25.
A new methodological approach to assess cardiac work by pressure-volume and
stress-length relations in patients with aortic valve stenosis and dilated
cardiomyopathy.
Alter P, Rupp H, Rominger MB, Klose KJ, Maisch B.
Internal Medicine--Cardiology, Philipps University, Baldingerstrasse, 35033
Marburg, Germany. alter@staff.uni-marburg.de
In experimental animals, cardiac work is derived from pressure-volume area and
analyzed further using stress-length relations. Lack of methods for determining
accurately myocardial mass has until now prevented the use of stress-length
relations in patients. We hypothesized, therefore, that not only pressure-volume
loops but also stress-length diagrams can be derived from cardiac volume and
cardiac mass as assessed by cardiac magnetic resonance imaging (CMR) and
invasively measured pressure. Left ventricular (LV) volume and myocardial mass
were assessed in seven patients with aortic valve stenosis (AS), eight with
dilated cardiomyopathy (DCM), and eight controls using electrocardiogram
(ECG)-gated CMR. LV pressure was measured invasively. Pressure-volume curves were
calculated based on ECG triggering. Stroke work was assessed as area within the
pressure-volume loop. LV wall stress was calculated using a thick-wall sphere
model. Similarly, stress-length loops were calculated to quantify
stress-length-based work. Taking the LV geometry into account, the normalization
with regard to ventricular circumference resulted in "myocardial work." Patients
with AS (valve area 0.73+/-0.18 cm(2)) exhibited an increased LV myocardial mass
when compared with controls (P<0.05). LV wall stress was increased in DCM but not
in AS. Stroke work of AS was unchanged when compared with controls (0.539+/-0.272
vs 0.621+/-0.138 Nm, not significant), whereas DCM exhibited a significant
depression (0.367+/-0.157 Nm, P<0.05). Myocardial work was significantly reduced
in both AS and DCM when compared with controls (129.8+/-69.6, 200.6+/-80.1,
332.2+/-89.6 Nm/m(2), P<0.05), also after normalization (7.40+/-5.07,
6.27+/-3.20, 14.6+/-4.07 Nm/m(2), P<0.001). It is feasible to obtain LV
pressure-volume and stress-length diagrams in patients based on the present novel
methodological approach of using CMR and invasive pressure measurement.
Myocardial work was reduced in patients with DCM and noteworthy also in AS, while
stroke work was reduced in DCM only. Most likely, deterioration of myocardial
work is crucial for the prognosis. It is suggested to include these basic
physiological procedures in the clinical assessment of the pump function of the
heart.
PMID: 17721708 [PubMed - indexed for MEDLINE]
27. Dtsch Med Wochenschr. 2007 Aug;132(33):1707-10.
[Pericardiocentesis]
[Article in German]
Karatolios K, Maisch B.
Klinik für Innere Medizin-SP, Kardiologie der Universitätsklinikums GmbH Giessen
und Marburg, Standort Marburg, Germany.
PMID: 17713869 [PubMed - indexed for MEDLINE]
28. Cardiology. 2008;109(2):117-21. Epub 2007 Aug 17.
Isolated cardiac sarcoidosis associated with the expression of a splice variant
coding for a truncated BTNL2 protein.
Meyer T, Lauschke J, Ruppert V, Richter A, Pankuweit S, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University of Marburg,
Marburg, Germany. meyert@med.uni-marburg.de
Comment in:
Cardiology. 2009;112(1):76-7; author reply 78-9.
A 33-year-old woman presented with clinical signs of heart failure and previously
diagnosed complete atrioventricular block. DNA sequencing revealed a homozygous
point mutation in exon 5 of the btnl2 gene coding for a truncated protein which
lacks the membrane-anchoring motif. This single nucleotide polymorphism is known
to be a risk factor for sarcoidosis. Indeed, endomyocardial biopsy demonstrated
multiple nonnecrotizing granulomas composed of epitheloid cells and moderate
numbers of multinucleated giant cells. Because no other organs were affected,
isolated cardiac sarcoidosis was diagnosed and treated with corticosteroids.
Thus, detection of the disease-associated btln2 allele may help to identify
patients with sarcoidosis as the underlying cause of heart failure.
PMID: 17703092 [PubMed - indexed for MEDLINE]
29. Interact Cardiovasc Thorac Surg. 2004 Mar;3(1):171-3.
Development of a saphenous vein coronary artery bypass graft pseudoaneurysm.
Alter P, Herzum M, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University of Marburg/Lahn,
Baldingerstrasse, D-35033 Marburg, Germany. alter@mailer.uni-marburg.de
This report shows the long-term development of a saphenous vein bypass
pseudoaneurysm that is a rare complication after bypass surgery. The patient
underwent CABG procedure in 1986 because of three vessel coronary artery disease.
Initial signs of venous wall disturbances were observed first time in 1996. At
the present admission the patient complained of angina pectoris probably
resulting from progression of coronary artery disease. Angiography revealed an
approximately 15x8 mm enlarged venous graft pseudoaneurysm. Subsequently, the
entrance was successfully occluded by a covered stent graft. Six month follow-up
was uneventful; angiography showed a still sufficiently occluded pseudoaneurysm.
PMID: 17670207 [PubMed]
30. Can J Physiol Pharmacol. 2007 Mar-Apr;85(3-4):326-31.
Separation of large mammalian ventricular myosin differing in ATPase activity.
Rupp H, Maisch B.
Molecular Cardiology Laboratory, Department of Internal Medicine and Cardiology,
Philipps University of Marburg, Karl-von-Frisch-Strasse 1, 35033 Marburg,
Germany. rupp@staff.uni-marburg.de
To investigate a possible heterogeneity of human ventricular myosin, papillary
muscles of patients with valvular dysfunction were examined using a modified
native gel electrophoresis. Myosin was separated into 2 components termed VA and
VB, whereby the VA to VB proportion appeared to depend on the ventricular load.
The proportion of the faster migrating band VA was correlated (P<0.05) with
end-diastolic pressure and the aortic pressure-cardiac index product. The
regression based on these variables accounted for 67% of the variation in VA
(R2=0.67). The VA proportion was, however, not significantly correlated with
cardiac norepinephrine concentration. The ATPase activity of the 2 components of
myosin was assessed from the Ca3(PO4)2 precipitation by incubating the gel in the
presence of ATP and CaCl2. The ATPase activity of VA was 60% of that of VB. The
VA and VB forms were observed also in the cat (31.4% VA), dog (32.1% VA), pig
(28.5% VA), wild pig (33.7% VA), and roe deer (30.5% VA). VA and VB were not
detected in the rat exhibiting the 3 isoforms V1, V2, and V3, rabbit (100% V3),
and hare (86% V1). The data demonstrate a heterogeneity of large mammalian
ventricular myosin, whereby an increased cardiac load appeared to be associated
with a higher myosin VA proportion that exhibited a reduced ATPase activity.
PMID: 17612641 [PubMed - indexed for MEDLINE]
31. Herz. 2006 Dec;31 Suppl 3:30-49.
Microdetermination of fatty acids by gas chromatography and cardiovascular risk
stratification by the "EPA+DHA level".
Rupp H, Rupp TP, Wagner D, Alter P, Maisch B.
Molecular Cardiology Laboratory, Department of Internal Medicine and Cardiology,
Philipps University of Marburg, Germany.
The therapeutic options for interfering with the electrical instability of a
pathologically remodeled or ischaemic heart remain limited. Of increasing
importance become interventions which target the fatty acid composition of blood
and membrane lipids. In particular, the long-chain omega-3 fatty acids
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provide parameters for
stratification of risks associated with severe arrhythmia disorders and sudden
cardiac death. Since EPA and DHA appear to have their anti-arrhythmogenic actions
when present as free fatty acids, the parameters which determine a critical free
fatty acid concentration are of great interest. In the present study, conclusions
on EPA and DHA incorporation in blood lipids are derived from the administration
of Omacor which contains highly purified (84%) EPA and DHA ethyl esters and
reduced the risk of sudden cardiac death by 45% in post-myocardial infarction
patients (GISSI-Prevention study). The "EPA+DHA level" is described as risk
identifying parameter for severe arrhythmia disorders, particularly if they are
associated with myocardial ischaemia. It appears essential not only to build up
body stores for release of EPA and DHA but to provide also a sustained uptake of
EPA and DHA in the form of ethyl esters. In contrast to more rapidly absorbed
triacylglycerols from fish, ethyl esters are taken up slowly within 24 h. For the
administration of 1 g/day Omacor to healthy volunteers, it is shown that in whole
blood EPA is increased from 0.6% to 1.4% within 10 days while DHA is increased
from 2.9% to 4.3%. After withdrawal, the EPA and DHA levels approach baseline
values within 10 days. A gas chromatographic procedure was established which
requires only 10 microl of whole blood for the identification of more than 30
fatty acids. Evidence is summarized strengthening the concept that a low "EPA+DHA
level" presents a risk for severe arrhythmia disorders and sudden cardiac death.
The administration of 840 mg/day of EPA and DHA ethyl esters raises the "EPA+DHA
level" to approximately 6% that is associated with protection from sudden cardiac
death. The pharmacological effects of ethyl esters are compared with the
naturally occurring EPA and DHA triacylglycerols present in fish or fish oils
which are of interest in primary prevention of cardiovascular disorders.
PMID: 17575804 [PubMed - indexed for MEDLINE]
32. Herz. 2006 May;31(3):270-2.
[Heart insufficiency--what is it?]
[Article in German]
Maisch B, Maisch I, Richter A, Pankuweit S.
Klinik für Innere Medizin-Kardiologie, Philipps-Universität, Marburg, Germany.
Bernard.Maisch@med.uni-marburg.de
PMID: 17431947 [PubMed - indexed for MEDLINE]
33. Internist (Berl). 2007 Mar;48(3):255-67.
[The heart in cases of viral, bacterial and parasitic infections]
[Article in German]
Maisch B, Alter P, Karatolius K, Ruppert V, Pankuweit S.
Klinik für Innere Medizin, Schwerpunkt Kardiologie, Universitätsklinikum Giessen
und Marburg, Baldingerstr. 1, 35033 Marburg, Deutschland.
Bernhard.Maisch@med.uni-marburg.de
The heart can be the primary target for a viral, bacterial or parasitic infection
(primary myocarditis/inflammatory cardiomyopathy). It can also participate in the
"collateral damage" due to toxins, chemo- and cytokines, autoreactive antibodies
or the native and acquired immune response through T- and B-cells, monocytes and
macrophages (secondary myocarditis/inflammatory cardiomyopathy), when it is not
the dominant organ of the disease. Infective agents show remarkable organ
specificity: viral infections, toxic and autoreactive processes affect primarily
the myocardium and the pericardium, whereas bacterial infections prefer
endothelial surfaces and cause endocarditis and, less frequently, pericarditis.
They are even discussed as part of the inflammatory process involved in coronary
artery disease. Infective agents and their adequate diagnosis and treatment are
discussed for these clinical entities according to current guidelines and
clinical pathways.
PMID: 17333055 [PubMed - indexed for MEDLINE]
34. Pacing Clin Electrophysiol. 2007 Jan;30 Suppl 1:S134-8.
Outcomes of elderly recipients of implantable cardioverter defibrillators.
Grimm W, Stula A, Sharkova J, Alter P, Maisch B.
Department of Cardiology, Hospital of the Philipps-University of Marburg,
Philipps-University of Marburg, Germany. grimmw@med.uni-marburg.de
Erratum in:
Pacing Clin Electrophysiol. 2007 Nov;30(11):1424.
AIMS OF THE STUDY: To examine the patterns of use, complication rates, and
survival in elderly recipients of implantable cardioverter defibrillators (ICD).
METHODS AND RESULTS: We followed 500 consecutive patients included in the Marburg
Defibrillator database for 48+/-39 months. There were 40 patients (8%) >/= 75 and
460 (92%) < 75 years of age at the time of implant. The 5-year Kaplan-Meier
estimate for appropriate treatment of VT or VF by ICD was 49% among patients <
75- versus 57% among patients >/= 75-years-old (P = 0.17). The 5-year sudden
death rate was similarly low in both groups of patients (2% versus 3%). The
5-year overall mortality rate was significantly higher in patients >/= 75 than in
patients < 75 years of age (55% versus 21%, P = 0.001), due to a higher mortality
from heart failure (HF). All procedure-related, lead-related, and pulse
generator-related complications were similar in both patient groups (23% versus
25%). CONCLUSIONS: ICD therapy was equally effective in patients >/= 75 and
patients < 75 years of age in the prevention of sudden cardiac death. While the
complication rates were similar in both age groups, the long-term mortality was
considerably higher in elderly patients, due to a higher mortality from HF. The
current ICD therapy guidelines appear applicable to elderly patients who are
otherwise medically stable and without advanced HF.
PMID: 17302690 [PubMed - indexed for MEDLINE]
35. J Surg Res. 2007 May 1;139(1):136-42. Epub 2007 Feb 7.
Different profile of antioxidative capacity results in pulmonary dysfunction and
amplified inflammatory response After CABG surgery.
Vogt S, Sattler A, Sirat AS, Müller B, Seifart C, Maisch B, Moosdorf RG.
Heart Surgery, Internal Medicine, Philipps University, Marburg, Germany.
vogts@med.uni-marburg.de
BACKGROUND: Respiratory complications after cardiosurgical interventions are
frequent and cause severe problems, postoperatively. The present study addresses
the question for group-specific release of radical oxygen species (ROS) by
extracorporeal circulation (ECC) with emphasis on pulmonary function. MATERIALS
AND METHODS: Fifty-one patients who had undergone bypass surgery were evaluated
for serum antioxidative capacity (AOC). Blood gas analysis, leukocyte counts,
C-reactive protein (CRP), and hemodynamic data cardiac output (CO), pulmonary
capillary wedge pressure (PCWP) arterial-alveolar gradient (AaDO(2)), and Murray
scores were measured after ECC up to 48 h. According to AOC levels at baseline
before ECC, patients were divided into two groups (group A: "high" AOC equal to
or above median of the whole sample; n=26; versus group B: "low" AOC below
median; n=25). RESULTS: A different time course in AOC could be detected between
both groups. Both groups had an improvement in postoperative cardiac output
evaluation, but in group A (high AOC) the PCWP was reduced (P=0.015). In this
group, an increased AaDO(2) and elevated Murray score were seen 12 h
postoperatively (P<0.001), suggesting reduced oxygen uptake. Moreover, increased
CRP values and a trend to reduced leukocyte counts indicate differences in
amplified inflammatory response to ECC. CONCLUSIONS: Free radical production
after ECC is not a uniform process. Preoperative differences in AOC indicate
interindividual variations. The surgical trauma results in a clear decrease of
AOC in group A, while in group B AOC showed no major changes. As shown for
reduced PCWP, release of ROS can affect pulmonary function. Therefore, AOC may be
a useful parameter for prediction of postoperative complications.
PMID: 17291533 [PubMed - indexed for MEDLINE]
36. J Electrocardiol. 2007 Nov-Dec;40(6):504-9. Epub 2007 Feb 6.
Hereditary long QT syndrome due to autoimmune hypoparathyroidism in autoimmune
polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.
Meyer T, Ruppert V, Karatolios K, Maisch B.
Abteilung Innere Medizin-Kardiologie, Philipps-Universität Marburg,
Baldingerstrasse, 35033 Marburg, Germany. meyert@med.uni-marburg.de
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also
known as autoimmune polyglandular syndrome type I, is a rare autosomal
recessively inherited disorder characterized by variable combinations of
endocrine and nonendocrine symptoms. In this report, we describe two 20- and
17-year-old Turkish siblings presenting with typical symptoms of APECED,
including Addison disease, alopecia, vitiligo, and hypopituitarism, in whom
electrocardiographic examinations demonstrated an abnormal prolongation of the QT
interval. In both cases, excessive hypocalcemia due to primary hypoparathyroidism
was identified as the underlying cause of the long QT syndrome. Sequencing the
gene coding for the autoimmune regulator revealed a homozygous missense mutation
in exon 14 with a C-to-T transition that resulted in the substitution of proline
539 for leucine in the carboxy-terminal protein molecule. Our data show that a
single point mutation in the transcriptional active autoimmune regulator protein
is associated with inherited alterations in calcium metabolism resulting from
autoimmune reactions against the parathyroid glands. This finding defines a
congenital autoimmune disease as a hereditary long QT syndrome.
PMID: 17289071 [PubMed - indexed for MEDLINE]
37. Herz. 2006 Dec;31(9):881-90.
Management of patients with suspected (peri-)myocarditis and inflammatory dilated
cardiomyopathy.
Maisch B, Richter A, Koelsch S, Alter P, Funck R, Pankuweit S.
Department of Internal Medicine - Cardiology, UKGM GmbH and Philipps University
Marburg, Baldingerstrasse, 35043, Marburg, Germany. Bermaisch@aol.com
Inflammatory cardiomyopathy and myocarditis are considered acquired forms of
dilated cardiomyopathy. Whereas consensus documents on the diagnosis of
myocarditis and perimyocarditis do exist, guidelines on the specific treatment
have been established only for the management of pericardial diseases, which at
least partly can be applied in analogy to myocarditis. Presently, feasible
clinical pathways are available, which can lead to a correct diagnosis and
specific treatment. This is illustrated with two cases of fulminant myocarditis,
in one with successful diagnosis and treatment of a cardiac sarcoid and another
one in which diagnostic nihilism led to a lethal outcome in giant cell
myocarditis at necropsy. A case of active parvo B19-positive myocarditis
demonstrates the role of immunoglobulin treatment under these conditions.
PMID: 17180652 [PubMed - indexed for MEDLINE]
38. J Cell Biochem. 2007 Apr 15;100(6):1430-9.
Osteoprotegerin expression in dendritic cells increases with maturation and is
NF-kappaB-dependent.
Schoppet M, Henser S, Ruppert V, Stübig T, Al-Fakhri N, Maisch B, Hofbauer LC.
Department of Internal Medicine and Cardiology, Philipps-University, Marburg,
Germany. schoppet@mailer.uni-marburg.de
Dendritic cells (DC) comprise a unique leukocyte population which controls
primary immune responses. Recent studies indicate that DC express osteoprotegerin
(OPG), a secreted tumor necrosis factor receptor homolog, which regulates DC
survival, monocyte chemotaxis, and B cell development and function by ligating
TNF family member receptor activator of NF-kappaB ligand (RANKL). The precise
regulators of OPG expression in DC have not been investigated. In this study, we
assessed OPG mRNA steady state levels by Northern blot analysis and OPG protein
secretion by an immunoassay in monocyte-derived DC of different maturation, and
the effect of different cytokines and hormones on OPG expression. OPG was
upregulated with maturation of DC, whereas pretreatment of DC with
1alpha,25(OH)(2) vitamin D(3), tamoxifen, or dexamethasone, agents that inhibit
differentiation of DC, decreased OPG expression. In vivo, OPG was found to be
colocalized with mature CD83(+) DC in human tonsils by immunofluorescence
confocal microscopy analysis. Furthermore, OPG was upregulated by TNF superfamily
members TNF-alpha, anti-CD40, and RANKL, and by ligands of the Toll-like/IL-1
receptor family including IL-1beta, double-stranded RNA (poly I:C), or
lipopolysaccharide (LPS), all of which induce maturation of DC. Gene silencing by
small interfering RNA (siRNA) directed against transcription factor NF-kappaB
abrogated the expression of OPG as demonstrated by real-time PCR. In summary, we
describe that the expression of OPG by DC increases with maturation and is
NF-kappaB-dependent, possibly regulating immune responses in lymphoid tissues.
PMID: 17171649 [PubMed - indexed for MEDLINE]
39. Herz. 2006 Nov;31(8):801-4.
[For patients. Acute heart failure syndrome]
[Article in German]
Karatolios K, Richter A, Maisch I, Maisch B.
Klinik für Innere Medizin-Kardiologie, Universitätsklinikum Giessen und Marburg
und Philipps-Universität Marburg, Marburg.
PMID: 17149683 [PubMed - indexed for MEDLINE]
40. Herz. 2006 Nov;31(8):727-35.
Acute heart failure--basic pathomechanism and new drug targets.
Rupp H, Rupp TP, Alter P, Maisch B.
Molecular Cardiology Laboratory, Department of Internal Medicine and Cardiology,
Philipps University of Marburg, 35043, Marburg, Germany.
Rupp@staff.uni-marburg.de
In view of the high incidence of heart failure and sudden cardiac death, efforts
in the development of compounds which target-specific mechanisms such as a
reduced expression of SERCA2, the Ca2+ pump of sarcoplasmic reticulum, of
hypertrophied cardiomyocytes of pressure-overloaded or infarcted hearts should be
strengthened. Lead compounds for correcting a dysregulated gene expression are
the carnitine palmitoyltransferase-1 (CPT-1) inhibitors etomoxir and oxfenicine.
Since bypassing the CPT-1 inhibition by a medium-chain fatty acid diet had a
lesser effect on myosin V1 proportion than on lipid droplet number, one has to
infer also other mechanisms such as PPARalpha activation (FOXIB/PPARalpha). In
view of the intricate interrelationship between depressed pump function and
malignant arrhythmias, stimulation of endogenous antiarrhythmogenic mechanisms
linked to an enhanced production of eicosapentaenoic acid (EPA) and
docosahexaenoic acid (DHA) could potentially provide alternatives to the
administration of 1 g EPA and DHA ethyl esters (minimum 84% EPA + DHA) for
secondary prevention of myocardial infarction. The apparently greater efficacy of
omega-3 fatty acids in post-myocardial infarction patients (GISSI-Prevention
study) compared with ICD patients (SOFA study) can be attributed to the greater
ischemia-induced release of membrane-bound EPA and DHA and a better compliance
(one vs. four capsules daily).
PMID: 17149674 [PubMed - indexed for MEDLINE]
41. Dtsch Med Wochenschr. 2006 Sep 29;131(39):2143-6.
[Recurrent autoreactive pericardial effusion. Impact of an aetiological
classification of pericarditis]
[Article in German]
Maisch B, Karatolios K, Pankuweit S.
Klinik für Innere Medizin-Schwerpunkt Kardiologie der Universitätsklinikums GmbH
Gissen und Marburg, Standort Marburg. Maisch@med.uni-marburg.de
HISTORY: A 36 year-old man suffered from fever, fatigue, pleurodynia and
precordial discomfort. His family physician suspected febrile tracheobronchitis
and treated it with ampicillin for 5 days. Because symptoms persisted an ECG was
done which suggested acute myocardial infarction. The patient underwent an
emergency coronary angiography which excluded coronary artery disease and aortic
dissection. Pericarditis was suspected and the patient put on aspirin, 500 mg/d.
Because of persisting cardiac symptoms an echocardiography was performed which
revealed systolic separation between epi- and pericardium, characteristic of a
small pericardial effusion after acute pericarditis. The symptoms improved after
one week of treatment with diclofenac and the ECG had become normal. Two months
later the patient was seen at our cardiac outpatient clinic. He had night sweats,
sporadic precordial pain and severe dyspnoe. INVESTIGATIONS: Further
investigations revealed tachycardia (120/min), hypotension (95/70 mm Hg), pulsus
paradoxus and jugular vein sustension. Echocardiography revealed a large
pericardial effusion ("swinging heart"), which explained the low voltage and the
electrical alternans in the ECG. TREATMENT AND COURSE: Pericardiocentesis was
carried out the same day to relieve the tamponade. It was followed by
pericardioscopy and epi- as well as pericardial biopsy. 485 ml of a serous
effusion were drained. Cytology and histology demonstrated a lymphocytic
fibrinous pericarditis. Polymerase chain reaction (PCR) on viral and bacterial
RNA and DNA of potentially cardiotropic agents remained negative. The pigtail
catheter was left in place and 80 mg of gentamycin were given intrapericardially
on day 1 and 2, followed by 500 mg of crystalloid triamcinolone acetate after the
PCR was found to be negative. Oral treatment with 0.5 mg colchicine three times a
day (off-label use) was started and maintained for 6 months. After 9 months no
effusion was detected and the patient was free of symptoms. CONCLUSIONS: After
exclusion of bacterial and viral pericardial infection, a high single dose of
intrapericardial triamcinolone combined with long-term oral colchicine has proven
to be a highly efficacious treatment of autoreactive pericarditis which will
avoid relapses in most cases.
PMID: 16991029 [PubMed - indexed for MEDLINE]
42. Rheumatology (Oxford). 2006 Oct;45 Suppl 4:iv32-8.
Invasive techniques--from diagnosis to treatment.
Maisch B, Pankuweit S, Karatolios K, Ristić AD.
Department of Internal Medicine and Cardiology, University Hospital of Giessen
and Marburg, Baldingerstr, 35043 Marburg, Germany.
Bernhard.Maisch@med.uni-marburg.de
Invasive diagnostic and therapeutic techniques are indispensable for the
diagnosis and interventional treatment of coronary artery disease, valvular
involvement and, in particular, if the specific components of the inflammatory or
degenerative processes in rheumatic disease are to be identified in the different
components of the heart. Although impairment of cardiac function and ischaemia
can be suspected also by non-invasive techniques, coronary involvement needs the
final proof by angiography. Endomyocardial or epicardial biopsy identifies the
key players of autoreactivity: the infiltrating cells and the bound and
circulating antibodies. Before corticoid treatment is started, a viral or
microbial aetiology has to be excluded at the site of cardiac inflammation. This
again can only be done by the analysis of cardiac tissue samples.
PMID: 16980721 [PubMed - indexed for MEDLINE]
43. Int J Cardiol. 2007 May 16;118(1):14-20. Epub 2006 Aug 10.
Clinical and immunologic characteristics in peripartum cardiomyopathy.
Lamparter S, Pankuweit S, Maisch B.
Diakonie Krankenhaus Wehrda, Internal Medicine, Hebronberg 5, D-35041
Marburg-Wehrda, Germany. CS.Lamparter@t-online.de
Peripartum cardiomyopathy (PPCM) is a rare disorder of dilated cardiomyopathy and
left ventricular dysfunction occurring in the last month of pregnancy or within 5
months postpartum. Outcome of PPCM is highly variable, comprising clinical
improvement and rapid deterioration unresponsive to medical treatment requiring
heart transplantation or even death. In this study, we report the
clinicopathologic findings of 10 patients with PPCM who were retrospectively
identified in our cardiomyopathy registry. During a follow-up of 69+/-27 months,
no patient died or required orthotopic heart transplantation. Left ventricular
ejection fraction was 38+/-7% at the time of diagnosis and 53+/-7% during
follow-up. While all patients had sinus rhythm at the time of diagnosis, three
patients presented with left bundle branch block. We found no evidence of viral
infection in endomyocardial biopsy samples of seven patients by PCR.
Histopathologic findings revealed the presence borderline myocarditis in two of
seven patients (29%). Circulating autoantibodies to cardiac tissue of any kind
were observed in all patients. In conclusion, in our retrospective observational
study, no patient diagnosed with PPCM died or received orthotopic heart
transplantation. Improvement of left ventricular ejection fraction was present in
eight patients (80%), while LV dysfunction persisted in four patients. Our
findings support the hypothesis of an underlying autoimmune pathomechanism in
this rare disease.
PMID: 16904777 [PubMed - indexed for MEDLINE]
44. Pacing Clin Electrophysiol. 2006 Jul;29(7):759-64.
Antitachycardia pacing for spontaneous rapid ventricular tachycardia in patients
with prophylactic cardioverter-defibrillator therapy.
Grimm W, Plachta E, Maisch B.
Department of Cardiology, Hospital of the Philipps-University of Marburg,
Marburg, Germany. grimmw@med.uni-marburg.de
AIMS: Antitachycardia pacing (ATP) has not routinely been used in patients who
received implantable cardioverter defibrillators (ICDs) for primary prevention of
sudden death. This study investigated the efficacy of empirical ATP to terminate
rapid ventricular tachycardia (VT) in heart failure patients with prophylactic
ICD therapy. METHODS AND RESULTS: Ninety-three patients with a mean left
ventricular ejection fraction of 22 +/- 7% (range: 9-35%) due to nonischemic or
ischemic cardiomyopathy received prophylactic ICDs with empiric ATP. At least 2
ATP sequences with 6-pulse burst pacing trains at 81% of VT cycle length (CL)
were programmed in one or two VT zones for CL below 335 +/- 23 ms and above 253
+/- 18 ms. Ventricular flutter and fibrillation (VF) with CL below 253 +/- 18 ms
were treated in a separate VF zone with ICD shocks without preceding ATP
attempts. During 38 +/- 27 months follow-up, 339 spontaneous ventricular
tachyarrhythmias occurred in 36 of 93 study patients (39%). A total of 232 VT
episodes, mean CL 293 +/- 22 ms, triggered ATP in 25 of 36 patients with ICD
interventions (69%). ATP terminated 199 of 232 VT episodes (86%) with a mean CL
of 294 +/- 23 ms in 23 of 25 patients (88%) who received ATP therapy. ATP failed
to terminate or accelerated 33 of 232 VT episodes (14%) with a mean CL of 287 +/-
19 ms in 12 of 25 patients (48%) who received ATP therapy. CONCLUSIONS: Painfree
termination of rapid VT with empirical ATP is common in heart failure patients
with prophylactic ICD therapy. The occasional inability of empiric ATP to
terminate rapid VT in almost 50% of patients who receive ATP for rapid VT
warrants restrictive ICD programming with regard to the number of ATP attempts in
order to avoid syncope before VT termination occurs.
PMID: 16884513 [PubMed - indexed for MEDLINE]
45. Europace. 2006 Aug;8(8):629-35.
Biventricular stimulation to prevent cardiac desynchronization: rationale,
design, and endpoints of the 'Biventricular Pacing for Atrioventricular Block to
Prevent Cardiac Desynchronization (BioPace)' study.
Funck RC, Blanc JJ, Mueller HH, Schade-Brittinger C, Bailleul C, Maisch B;
BioPace Study Group.
Department of Cardiology and Angiology, Clinic of Internal Medicine and
Cardiology, University Hospital Philipps-University Marburg, Baldingerstr 1,
D-35033 Marburg, Germany. funck@mailer.uni-marburg.de
Despite the deleterious effects of cardiac dyssynchrony and the positive effects
of cardiac resynchronization therapy, patients with high-degree atrioventricular
block continue to receive desynchronizing right ventricular (RV) pacing systems.
Although it is unclear whether the negative effects of RV pacing and left bundle
branch block (LBBB) are comparable, and whether they depend on the presence and
the degree of structural heart disease, one may hypothesize that RV pacing may
have similar effects to LBBB. In the BioPace trial, the long-term effects of RV
pacing vs. biventricular pacing will be prospectively compared in 1200 pacemaker
patients with high likelihood of mostly paced ventricular events, regardless of
whether in sinus rhythm or in atrial fibrillation (AF). After echocardiographic
examination of left ventricular (LV) function, patients will be randomly assigned
to the implantation of an RV vs. a biventricular pacing system and followed for
up to 5 years. Primary study endpoints are survival, quality of life (QoL), and
the distance covered in a 6-min hall walk (6-MHW) at 24 months after
implantation. Secondary endpoints are QoL and the 6-MHW result at 12 months after
implantation, hospitalization rate, LV dimensions, LV ejection fraction, and the
development of chronic AF and other adverse events.
PMID: 16864616 [PubMed - indexed for MEDLINE]
46. Herz. 2006 Jun;31(4):361-5.
[Diagnosis and treatment of inflammatory heart diseases: role of endomyocardial
biopsy]
[Article in German]
Pankuweit S, Funck R, Grimm W, Maisch B.
Klinik für Kardiologie, Universitätsklinikum GmbH Giessen und Marburg, Standort
Marburg, Marburg. pankuwei@staff.uni-marburg.de
PMID: 16810476 [PubMed - indexed for MEDLINE]
47. Herz. 2006 May;31(3):260-8.
[Myocardial fibrosis: a cardiopathophysiologic Janus head]
[Article in German]
Maisch B, Rupp H.
Direktor der Klinik für Innere Medizin-Kardiologie, Angiologie, Intensivmedizin
und Kardioprävention, Philipps-Universität, Baldingerstrasse, 35043, Marburg,
Germany. bernhard.maisch@med.uni-marburg.de
PMID: 16770563 [PubMed - indexed for MEDLINE]
48. Herz. 2006 May;31(3):200-6.
Molecular basis of obesity and the risk for cardiovascular disease.
Soufi M, Sattler AM, Herzum M, Maisch B, Schaefer JR.
Department of Internal Medicine, Cardiology, Angiology and CAD Prevention,
University Hospital Giessen and Marburg, Philipps University, Marburg, Germany.
Atherosclerosis and cardiovascular disease (CVD) are the main causes of death in
the Western world, for both men and women. The onset and development of diseases
of the cardiovascular and cerebrovascular system are strongly dependent on
multiple risk factors that promote pathologic conditions like atherosclerosis,
hypertension and thrombosis. Besides genetic factors also environmental
influences such as diet composition are known to be closely related to CVD. In
this context obesity has been postulated as an independent cardiovascular risk
factor. Data from the Framingham Heart Study have consistently shown that
increasing degrees of obesity are accompanied by greater rates of CVD. At
present, obesity affects 10-35% of the European and US population and increases
steadily. As obesity is a serious health problem which promotes metabolic
abnormalities (insulin resistance, hyperinsulinemia and dyslipidemia) and
dramatically increases the risk for CVD, this review will focus on the
epidemiologic and genetic background of obesity. Furthermore, the molecular
mechanisms involved in obesity development and their contribution to CVD will be
discussed.
PMID: 16770555 [PubMed - indexed for MEDLINE]
49. Internist (Berl). 2006 Jul;47(7):699-700, 702-6.
[Clinical pathway "Acute Coronary Syndrome"]
[Article in German]
Grimm W, Maisch B.
Klinik für Innere Medizin, Schwerpunkt Kardiologie, Angiologie und
Intensivmedizin, Philipps-Universität Marburg.
The clinical pathway "acute coronary syndrome" of the university hospital Marburg
describes the guideline-conform and consented management of patients with
ST-segment elevation infarct (STEMI), non-ST-segment elevation infarct (NSTEMI)
and Troponin negative unstable angina. A 12-lead ECG recording is made and read
in all patients within 10 minutes. All patients with STEMI undergo immediate
revascularisation using primary percutanuous catheter intervention (PCI) after
administration of basic medical therapy. Primary PCI is also used in all patients
with NSTEMI, persistent chest pain, rhythm or hemodynamic instability. Patients
with unstable angina, who became free of symptoms after application of basic
medication, but who have additional risk factors undergo cardiac catheterisation
within 48 hours. Acute myocardial infarction can be ruled out in patients with
twofold negative cardiac troponin levels during 6-12 hours. In the absence of
further symptoms, these patiens undergo differential diagnostic evaluation of
cardiac and extracardiac causes of chest pain. The introduction of this clinical
pathway 2 years ago, which was consented before by the hospital board and the
clinical directors, has lead to a remarkable improvement in the clinical
decision-making at the emergency room of the hospital and reduced the door to
intervention time considerably.
PMID: 16763796 [PubMed - indexed for MEDLINE]
50. Hellenic J Cardiol. 2006 Mar-Apr;47(2):54-65.
Inflammatory cardiomyopathy.
Karatolios K, Pankuweit S, Kisselbach C, Maisch B.
Department of Internal Medicine and Cardiology, University Hospital of Giessen
and Marburg, Philipps University Marburg, Germany.
PMID: 16752524 [PubMed - indexed for MEDLINE]
51. Herz. 2006 Apr;31(2):153-5.
Echocardiographic findings mimicking type A aortic dissection.
Alter P, Herzum M, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University of Marburg/Lahn,
Baldingerstrasse, 35033 Marburg, Germany. alter@mailer.uni-marburg.de
BACKGROUND: Type A aortic dissection is a rare, but life-threatening disease. The
prognosis is determined by an accurate and immediate diagnosis. CASE STUDY: A
patient with suspected type A dissection based on outward transesophageal
echocardiography (TEE) findings is reported. Renewed TEE showed dilation of the
ascending aorta with pronounced wall thickness. A membrane-like structure was
found in the ascending aorta. M-mode technique revealed movement of the suspected
membrane that was partially in parallel to the aortic wall. Thus, there were
severe doubts on the presence of type A dissection. By contrast, typical intimal
rupture was found in the descending aorta. Computed tomography (CT) and
angiography showed aortic dilation and an extended wall hematoma deriving from
the entry at the descending part. There was no evidence of type A dissection.
CONCLUSION: TEE is a noninvasive diagnostic tool to assess aortic dissection of
type A with a sensitivity of 90-98% that is equal to CT or magnetic resonance
imaging (MRI) solely. Complementary use of CT or MRI could improve the diagnostic
accuracy. False-positive findings could result from echocardiographic artifacts
concealing an intimal flap in the ascending aorta. Echo reverberations in dilated
or calcified aortas had been judged to account for this phenomenon. In the
present case, it could be assumed that the extended wall hematoma in accordance
with vessel dilation mimicked the membrane-like structure. Oscillation or flutter
of the suspicious intimal flap independently of aortal wall movement seem to be
mandatory to avoid false-positive diagnoses. Ancillary findings such as flow
signals, intimal fenestration or thrombosis are helpful to enhance the diagnostic
specificity of TEE.
PMID: 16738839 [PubMed - indexed for MEDLINE]
52. Eur J Heart Fail. 2007 Jan;9(1):98-9. Epub 2006 May 30.
Non-compaction cardiomyopathy in an adult with hereditary spherocytosis.
Alter P, Maisch B.
Philipps University of Marburg, Department of Internal Medicine - Cardiology,
Baldingerstrasse, D-35033 Marburg, Germany. alter@mailer.uni-marburg.de
Comment in:
Eur J Heart Fail. 2007 Jan;9(1):100; author reply 101.
A 23-year old male (199 cm, 88 kg) presented muscular weakness due to skeletal
myopathy and symptoms of heart failure NYHA functional class II. Total creatine
kinase was increased up to 830 U/l, but troponin was negative. Prior episodes of
intermittent atrial fibrillation were reported and 6 years ago splenectomy was
performed due to hereditary spherocytosis. Cardiac magnetic resonance imaging
revealed the spongy appearance of non-compacted left ventricular myocardium. This
impaired fetal morphogenesis occurred predominantly in the apical to
midventricular anterior, lateral and inferior segments. Non-compaction
cardiomyopathy was initially described in paediatric patients. Occasional
associations with other congenital disorders are known, e.g., Barth syndrome,
which is an X-linked disease characterized by cardio-skeletal myopathy of
variable severity and neutropenia. To our knowledge, combined occurrence of
non-compaction cardiomyopathy, skeletal myopathy and hereditary spherocytosis has
not previously been reported.
PMID: 16731037 [PubMed - indexed for MEDLINE]
53. Eur J Heart Fail. 2006 Dec;8(8):816-25. Epub 2006 Mar 6.
Familial inflammatory dilated cardiomyopathy.
Portig I, Wilke A, Freyland M, Wolf MJ, Richter A, Ruppert V, Pankuweit S, Maisch
B.
Philipps-University Hospital, Department of Internal Medicine and Cardiology,
Baldingerstrasse, 35033 Marburg, Germany. portig@med.uni-marburg.de
BACKGROUND: Systematic family screening has recently identified dilated
cardiomyopathy as an inherited disorder in up to 30% of cases. Mutations in genes
encoding proteins responsible for myocardial architecture have been identified,
but additional pathophysiological mechanisms including inflammatory reactions
have been proposed. AIMS: Identification and characterization of familial DCM,
where at least one affected family member fulfils the criteria for inflammatory
DCM may lead to a better understanding of the aetiology and pathogenesis of
(inflammatory) DCM. METHODS AND RESULTS: Ten families were examined. In six
families, clinical characteristics and mode of inheritance were compatible with
pure fDCM, fDCM with conduction defect and autosomal recessive fDCM. In four
families, (auto-)immune features were diagnosed in affected and non-affected
family members. CONCLUSIONS: Familial DCM with an inflammatory component was
identified as a specific subgroup of familial DCM. In most cases, the
inflammatory process seems to modify, i.e. aggravate, the "classic,
cytoskeletopathic" familial DCM, but in some, especially when taking clinical and
genetic aspects into account, inflammatory (auto-)immune features can be
addressed as the leading pathogenetic principle. Further elucidation of these
families may provide a better insight into pathophysiologic processes and may aid
in the development of specific therapeutic strategies.
PMID: 16713338 [PubMed - indexed for MEDLINE]
54. Clin Appl Thromb Hemost. 2006 Apr;12(2):213-8.
Monitoring of plasmin and plasminogen activator activity in blood of patients
under fibrinolytic treatment by reteplase.
Stief TW, Richter A, Bünder R, Maisch B, Renz H.
Department of Laboratory Medicine, Hospital of Philipps-University Marburg,
Germany. thstief@med.uni-marburg.de
There are no reliable data on plasmin or plasminogen activator (PA) activities in
blood of patients receiving fibrinolytic treatment. This is due to continuing in
vitro action of PA after blood withdrawal. These artefactual changes of PA or
plasmin activities have been prevented by arginine stabilization of blood samples
of myocardial infarction patients treated with plasminogen activators. Twelve
patients with myocardial infarction were treated with reteplase 2 x 10,000,000
units in bolus application; one patient was treated with 100 mg t-PA in
continuous infusion. Blood was immediately stabilized with EDTA and arginine. The
plasma was analyzed with newly developed assays for plasmin and PA. Maximal
plasmin activities in blood were obtained at 40 to 60 minutes reteplase treatment
time (0.1-0.6 U/mL = approximately 0.05-0.3 micromol/L plasmin). The 50%
clearance rate for plasmatic Pli was greater than 30 minutes. The plasmatic
reteplase concentration peaked at approximately 2,000 U/mL after the first bolus
infusion and at approximately 1,500-3,500 U/mL after the second bolus infusion.
Reteplase was cleared to 50% within less than 30 minutes, also with great
inter-individual variation. Arginine stabilization of blood allows reliable
determinations of activities of plasmin and PA in blood of patients under
fibrinolytic treatment: substantial plasmin activities occur in patients treated
by reteplase. Therapeutic thrombolysis might be improved, imitating the
physiologic cellular thrombolysis; i.e., polymorphonuclear phagocytes (PMN) that
can be activated by singlet oxygen ((1)O(2)). PMN might be superior to PA in
selective lysis of pathologic thrombi.
PMID: 16708124 [PubMed - indexed for MEDLINE]
55. Am Heart J. 2006 Apr;151(4):829-36.
Heart rate variability in patients with cardiac hypertrophy--relation to left
ventricular mass and etiology.
Alter P, Grimm W, Vollrath A, Czerny F, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University of Marburg,
D-35033 Marburg, Germany. palter@med.uni-marburg.de
Comment in:
Am Heart J. 2006 Jul;152(1):e13; author reply e15.
BACKGROUND: Decreased heart rate variability (HRV) has been shown to reflect
disturbances of the autonomic nervous system that is related to increased
cardiovascular mortality. Most studies investigated HRV in patients with systolic
left ventricular dysfunction due to remote myocardial infarction or dilated
cardiomyopathy. To date, only few data are available on HRV in patients with
predominant diastolic dysfunction in the presence of cardiac hypertrophy of
different etiologies. METHODS: Time domain analysis of HRV was performed from
digital 24-hour Holter electrocardiogram recordings in 86 patients with sinus
rhythm and cardiac hypertrophy, which was due to aortic valve stenosis in 33
patients, hypertrophic cardiomyopathy in 29 patients, and hypertensive heart
disease in 24 patients. Heart rate variability analysis was compared with 91
healthy controls. RESULTS: The SD of all normal-to-normal R-R intervals (SDNN)
was reduced in patients with aortic valve stenosis, hypertrophic cardiomyopathy,
and hypertensive heart disease when compared with controls (SDNN 119 +/- 42 vs
154 +/- 36 milliseconds, P < .001). The extent of cardiac hypertrophy indexed by
echocardiography based left ventricular mass calculation and increased patient
age were independent predictors for depression of SDNN. CONCLUSIONS: Cardiac
hypertrophy of various etiologies is related to decreased HRV on 24-hour Holter
electrocardiogram. Both the patient age and the extent of left ventricular
hypertrophy are independently associated with depression of HRV. These findings
are independent of the cause of cardiac hypertrophy. The significance of these
findings remains to be determined by future studies.
PMID: 16569542 [PubMed - indexed for MEDLINE]
56. Cardiovasc Hematol Agents Med Chem. 2006 Jan;4(1):1-5.
Cardiotoxicity of 5-fluorouracil.
Alter P, Herzum M, Soufi M, Schaefer JR, Maisch B.
Philipps University of Marburg/Lahn, Department of Internal Medicine -
Cardiology, Baldingerstrasse, 35033 Marburg, Germany. palter@med.uni-marburg.de
Cardiac side effects of the cytostatic agent 5-fluorouracil (5-FU) have an
incidence of 1.2-7.6%. Potentially, arrhythmias, myocardial infarction and sudden
cardiac death could occur. Life-threatening cardiotoxicity is rarely observed
with a frequency <1%. Cardiotoxicity of 5-FU seems to differ from well known
effects of other cytostatics, e.g., anthracyclines. Myocardial ischemia was
suggested as potential mechanism due to occasionally observed ECG alterations
during 5-FU administration. Experimental studies revealed potential mechanisms of
cardiotoxicity ranging from direct toxic effects on vascular endothelium
involving endothelial NO synthase leading to coronary spasms and endothelium
independent vasoconstriction via protein kinase C. In addition, rheological side
effects have to be considered. Coronary artery disease is judged to increase the
risk of cardiac side effects. Despite lack of prospective trials, verapamil type
calcium antagonists as well as nitrates seem to be useful for treatment of 5-FU
induced coronary spasms. In addition, modification of the cytostatic regimen has
to be considered in patients who had been symptomatic. It could be assumed that
5-FU toxicity is reversible in the majority of cases when acute complications,
e.g., arrhythmias, are resolved.
PMID: 16529545 [PubMed - indexed for MEDLINE]
57. Herz. 2005 Nov;30(7):663-7.
Right ventricular cardiac myxoma. Diagnostic usefulness of cardiac magnetic
resonance imaging.
Alter P, Grimm W, Rominger MB, Ritter M, Klose KJ, Moosdorf R, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University of Marburg,
Germany.
BACKGROUND: Cardiac myxomas are the most common type of cardiac tumors. About
75-85% of cardiac myxomas originate in the left atrium, 15-20% in the right
atrium. Most myxomas arise from the interatrial septum adjacent to the fossa
ovalis. Only 3-4% are found in the left and right ventricle each. Although
myxomas are histologically benign, they may be fatal because of their strategic
position. CASE STUDY: The authors report on a 24-year-old patient with stabbing
thoracic pain and dyspnea due to pulmonary thromboembolism that was caused by an
atypically localized myxoma at the right ventricular apex originating from the
interventricular septum. The diagnosis was based on cardiac magnetic resonance
(CMR) imaging. Superior to echocardiography, CMR could strengthen the diagnostic
accuracy by additional information on tissue characterization using different
imaging sequences. Typically for cardiac myxomas, contrast enhancement was
moderate and delayed enhancement was found in the outer circumferential tumor
margins only. CONCLUSION: High spatial resolution and multiplane imaging combined
with different acquisition patterns of CMR achieve a global view of the heart
that seems to be useful for diagnosing cardiac tumorous masses.
PMID: 16333594 [PubMed - indexed for MEDLINE]
58. J Vet Med B Infect Dis Vet Public Health. 2005 Sep-Oct;52(7-8):344-7.
Pathophysiology and aetiological diagnosis of inflammatory myocardial diseases
with a special focus on parvovirus B19.
Pankuweit S, Ruppert V, Eckhardt H, Strache D, Maisch B.
Department of Internal Medicine-Cardiology of the Philipps-University Marburg,
Marburg, Germany. pankuwei@staff.uni-marburg.de
Inflammatory processes induced by viral or bacterial infections are believed to
be one of the major pathogenetic mechanisms in myocardial diseases. Although the
reason for progression to myocardial failure is not fully understood, postulated
mechanisms include persistent viral infection alone or in combination with
autoimmune processes. A variety of cardiotropic viruses have been identified to
elicit myocarditis, with enteroviruses and adenoviruses as the most frequent
causative agents in children and adolescents. However, parvovirus B19 (PVB19) has
recently emerged as another potential pathogen in adult patients associated with
inflammatory heart disease. Many dimensions of inflammatory heart disease coexist
while different phases of the disease progress simultaneously: phase 1 is
dominated by viral infection, phase 2 by the onset of (probably) multiple
autoimmune reactions, and phase 3 by the progression to cardiac dilatation
without the role of an infectious agent and cardiac inflammation. Taking these
mechanisms into account, screening for viral and bacterial genome by polymerase
chain reaction (PCR) and detection of inflammatory infiltrates by
immunohistochemistry are considered crucial for establishing an aetiological
diagnosis, thereby allowing initiation of specific therapeutic strategies. In a
large cohort of 3345 consecutive patients with left ventricular dysfunction
evaluated over a period of 10 years, prevalence of PVB19, coxsackievirus (CVB),
human cytomegalovirus (HCMV), influenza A virus and adenovirus (ADV) genome was
assessed by PCR. Inflammatory infiltrates within the myocardium were detected by
immunohistochemistry according to the WHF criteria and by histopathology
according to the Dallas criteria of myocarditis. For control, endomyocardial
samples of patients with arterial hypertension were studied. Parvovirus B19 was
the most often detected virus in all patient subgroups, with positivity ranging
from 17% to 33%. Except for PVB19, CVB RNA (3%), ADV (2%) and CMV (3.9%) were the
most frequently detected viral genomes. Interestingly, detection of PVB19 genome
was significantly correlated with inflammatory heart disease and reduced ejection
fraction. Importantly, an aetiological diagnosis requires the immunohistochemical
and molecular biological investigation of endomyocardial biopsies. Such an
approach may change the management of these diseases in the future. One of the
aims of the study was to reveal the underlying dominant pathophysiological
mechanisms in a for deciding on the most approriate therapy.
PMID: 16316398 [PubMed - indexed for MEDLINE]
59. Biochem Biophys Res Commun. 2006 Jan 6;339(1):180-7. Epub 2005 Nov 10.
Activated nuclear transcription factor kappaB in patients with myocarditis and
dilated cardiomyopathy--relation to inflammation and cardiac function.
Alter P, Rupp H, Maisch B.
Philipps University of Marburg, Department of Internal Medicine-Cardiology,
Germany. palter@med.uni-marburg.de
OBJECTIVES AND BACKGROUND: Myocarditis is caused by various agents and autoimmune
processes. It is unknown whether viral genome persistence represents inactive
remnants of previous infections or whether it is attributed to ongoing adverse
processes. The latter also applies to the course of autoimmune myocarditis. One
principal candidate for an adverse remodeling is nuclear factor-kappaB
(NFkappaB). METHODS: A total of 93 patients with suspected
myocarditis/cardiomyopathy was examined. Hemodynamics were assessed by
echocardiography as well as right and left heart catheterization. Endomyocardial
biopsies were taken from the left ventricle. Biopsies were examined by
immunohistochemistry and PCR for viral genomes. Selective immunostaining of
activated NFkappaB was performed. RESULTS: NFkappaB was increased in patients
with myocarditis when compared with controls (11.1+/-7.1% vs. 5.0+/-5.3%,
P<0.005) whereas dilated cardiomyopathy showed no significant increase. Patients
with myocarditis and preserved left ventricular function exhibited increased
activated NFkappaB when compared with reduced function (r2=0.72, P<0.001). In
parallel, inverse correlation of NFkappaB and left ventricular enddiasstolic
volume was found (r2=0.43, P<0.02). Increased activated NFkappaB was found in
adenovirus persistence when compared with controls (P=0.001). Only a trend of
increased NFkappaB activation was seen in cytomegalovirus persistence. Parvovirus
B19 persistence did not affect NFkappaB activation. CONCLUSIONS: Increased
activation of NFkappaB is related to inflammatory processes in myocarditis. Since
activated NFkappaB correlates with left ventricular function, it could be assumed
that NFkappaB activation occurs at early stages of inflammation. Potentially,
NFkappaB could inhibit loss of cardiomyocytes by apoptosis and protect from
cardiac dilation. Since NFkappaB is a crucial key transcription factor of
inflammation, its prognostic and future therapeutic relevance should be
addressed.
PMID: 16297880 [PubMed - indexed for MEDLINE]
60. Biochem Biophys Res Commun. 2005 Dec 30;338(4):1745-50. Epub 2005 Nov 2.
TNF-related apoptosis-inducing ligand and its decoy receptor osteoprotegerin in
nonischemic dilated cardiomyopathy.
Schoppet M, Ruppert V, Hofbauer LC, Henser S, Al-Fakhri N, Christ M, Pankuweit S,
Maisch B.
Department of Internal Medicine and Cardiology, Philipps-University, D-35033
Marburg, Germany. schoppet@mailer.uni-marburg.de
Apoptosis has been attributed an essential role in dilated cardiomyopathy (DCM)
recently. We assessed expression of TNF-related apoptosis-inducing ligand (TRAIL)
and its decoy receptor osteoprotegerin (OPG) in men with nonischemic DCM, who
underwent coronary angiography and endomyocardial biopsy (EMB) after exclusion of
coronary artery disease compared to control patients. TRAIL plasma concentrations
were elevated in DCM (p=0.02 vs. controls), and were positively correlated with
left ventricular enddiastolic diameter (r=0.15, p=0.04), whereas OPG plasma
levels did not differ between both groups (p=0.96). In EMB of DCM patients, TRAIL
and OPG protein were detected by immunohistochemistry but not in controls.
Furthermore, gene expression in EMB or peripheral blood leukocytes (PBL) of DCM
patients assessed by real-time PCR showed an increase of TRAIL mRNA in PBL
(p=0.01 vs. controls), whereas OPG mRNA was upregulated in endomyocardial
specimens (p<0.001 vs. controls). In conclusion, myocardial overexpression of
antiapoptotic OPG in DCM patients may represent a compensatory mechanism to limit
systemic activation of TRAIL in patients with congestive heart disease.
PMID: 16288714 [PubMed - indexed for MEDLINE]
61. Chest. 2005 Oct;128(4):2944-53.
Preoperative and perioperative care for patients with suspected or established
aortic stenosis facing noncardiac surgery.
Christ M, Sharkova Y, Geldner G, Maisch B.
Department of Internal Medicine and Cardiology, Philipps University Marburg,
Germany. christ_michael@yahoo.de
Current medicine has displayed a trend toward less interfering techniques but
more invasive surgical approaches in older patients with more comorbidities. In
this population, the prevalence of symptomatic cardiac disease including aortic
stenosis is increased. More than 25 years have elapsed since severe aortic
stenosis was identified as an independent, important risk factor for patients
undergoing general anesthesia for noncardiac surgery. Despite impressive advances
in anesthesiologic and surgical techniques, morbidity and mortality in patients
with severe aortic stenosis remains high. Published study results clearly show
that adverse perioperative risk in patients with aortic stenosis depends on the
interaction of factors such as the severity of valve disease, concomitant
coronary artery disease, and the severity and/or urgency of the surgical
procedures. The mainstay of preoperative evaluation remains the obtaining of a
comprehensive preoperative medical history and a physical examination, while
transthoracic echocardiography is necessary to establish or exclude
hemodynamically relevant aortic stenosis in selected patients. Perioperative care
is established in patients with asymptomatic aortic stenosis and/or those
undergoing low-risk surgery. However, further preoperative testing or aortic
valve replacement prior to noncardiac surgery should be discussed individually
with the patients awaiting urgent surgical procedures who are at medium or high
risk. At this point, decisions should be made in an interdisciplinary manner,
including the opinions/wishes of the patient and the patient's family.
PMID: 16236971 [PubMed - indexed for MEDLINE]
62. Herz. 2005 Sep;30(6):535-44.
Inflammatory dilated cardiomyopathy (DCMI).
Maisch B, Richter A, Sandmöller A, Portig I, Pankuweit S; BMBF-Heart Failure
Network.
Department of Internal Medicine-Cardiology, Philipps University Marburg,
Baldingerstrasse, 35043, Marburg, Germany. maisch@med.uni-marburg.de
Cardiomyopathies are heart muscle diseases, which have been defined by their
central hemodynamics and macropathology and divided in five major forms: dilated
(DCM), hypertrophic (HCM), restrictive (RCM), right ventricular (RVCM), and
nonclassifiable cardiomyopathies (NCCM). Furthermore, the most recent WHO/WHF
definition also comprises, among the specific cardiomyopathies, inflammatory
cardiomyopathy as a distinct entity, defined as myocarditis in association with
cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory
cardiomyopathy were recognized. Viral cardiomyopathy has been defined as viral
persistence in a dilated heart. It may be accompanied by myocardial inflammation
and then termed inflammatory viral cardiomyopathy (or viral myocarditis with
cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (<
14 lymphocytes and macrophages/mm(2)), the term viral cardiomyopathy or viral
persistence in DCM should be applied according to the WHF Task Force
recommendations. Within the German heart failure net it is the authors' working
hypothesis, that DCM shares genetic risk factors with other diseases of presumed
autoimmune etiology and, therefore, the same multiple genes in combination with
environmental factors lead to numerous different autoimmune diseases including
DCM. Therefore, the authors' primary goal is to acquire epidemiologic data of
patients with DCM regarding an infectious and inflammatory etiology of the
disease. Circumstantial evidence points to a major role of viral myocarditis in
the etiology of DCM. The common presence of viral genetic material in the
myocardium of patients with DCM provides the most compelling evidence, but proof
of causality is still lacking. In addition, autoimmune reactions have been
described in many studies, indicating them as an important etiologic factor.
Nevertheless, data on the proportion of patients, in whom both mechanisms play a
role are still missing.A pivotal role for autoimmunity in a substantial
proportion of patients with DCM is supported by the presence of organ-specific
autoantibodies, inflammatory infiltrates and pro-inflammatory cytotoxic
cytokines. Furthermore, familial occurrence of DCM has been described in about
20-30% of cases, with the presence of autoantibodies and abnormal cytokine
profiles in first-degree relatives with asymptomatic left ventricular
enlargement. This suggests the involvement of a disrupted humoral and cellular
immunity early in the development of the disease. A similar pattern of humoral
and cellular immune dysregulation has been described in other autoimmune
diseases. There is considerable evidence that genetic factors play an important
role in the pathogenesis of DCM, either as contributors to the susceptibility to
environmental factors or as determinants of functional and structural changes
that characterize the phenotypic expression of the disease.Yet, it is not known
whether the susceptibility to immunologically mediated myocardial damage reflects
the presence of genetic risk factors shared by other autoimmune diseases.
Preliminary investigations suggest, that this is the case, because the frequency
of autoimmune disorders other than DCM was higher in first-degree relatives of
the subjects with DCM including juvenile diabetes, rheumatoid arthritis,
thyroiditis, psoriasis, and asthma. The nature of the genetic risk is
undetermined and probably involves genes in the major histocompatibility (MHC)
locus as well as other susceptibility loci. Therefore, the authors started their
investigation with the search for MHC class 2 DQ polymorphisms in the peripheral
blood of patients with DCM in parallel to the search for new interesting
susceptibility loci by the use of the microarray analysis regarding genes
responsible for inflammatory and autoimmune diseases. By this approach a new
insight in the familial clustering of other autoimmune diseases in patients with
DCM and in genetic predisposition can be expected.
PMID: 16170686 [PubMed - indexed for MEDLINE]
63. Herz. 2005 Sep;30(6):522-6.
[Women and autoimmune diseases with cardiovascular manifestations]
[Article in German]
Portig I, Sandmöller A, Pankuweit S, Maisch B.
Klinik für Innere Medizin-Kardiologie, Angiologie und Prävention,
Philipps-Universität Marburg, Baldingerstrasse, 35033, Marburg.
Women's greater susceptibility to autoimmune diseases has been recognized for
more than 100 years. And although the basic immune response (including a more
vigorous immune response and increased antibody production) has been known to
differ between men and women, conclusive pathophysiological explanations for this
phenomenon are still lacking. Experimental work done in animal models have
revealed a profound influence of sex hormones on the susceptibility to autoimmune
diseases and on clinical disease via direct and indirect signaling pathways.
Apart from sex hormones additional factors seem to participate in the
pathogenesis of autoimmune diseases, which remain to be elucidated ("so far, you
cannot explain autoimmunity [only] with estrogen" [lockshin]).
PMID: 16170683 [PubMed - indexed for MEDLINE]
64. Herz. 2005 Aug;30(5):409-15; quiz 429-30.
[Women and pericardial neoplastic manifestations of the heart and pericardium]
[Article in German]
Kisselbach C, Ristic AD, Pankuweit S, Karatolius K, Maisch B.
Klinik für Innere Medizin -- Kardiologie, Philipps- Universität Marburg, Marburg.
BACKGROUND: In every year since 1984, cardiovascular disease has claimed the
lives of more females than males. In the Western world more than 450,000 women
succumb to heart disease annually. Despite the proportions, most women believe
that heart disease is a man's disease and that they will die of breast cancer.
Data on epidemiology and incidence are rare: there is only an estimated incidence
of cardiac neoplasm at necropsy ranging from 0,001% to 0,3%. The majority of the
primary tumors are benign. Females are affected more often than males. The most
common tumor entity is benign cardiac myxoma. Malignant heart tumors are less
common. Most often they are different types of sarcomas, which have a poor
outcome and affect more males than females. Metastatic tumors of the heart are
100 times more common than the primary ones. They originate mainly from
melanomas, leukemias, lymphomas, and cancer, especially of the lung or breast.
Indeed in women breast cancer is the most common metastatic tumor associated with
pericardial effusion. To prevent death from tamponade, pericardiocentesis, in
addition to the systemic chemotherapy, is mandatory, best when instillation of
chemotherapeutics (cisplatin or thiotepa) or radioisotopes is given into the
pericardial sac to prevent recurrence of the effusion. However, more of the
malignant tumors may be curable if exactly diagnosed at an earlier stage.
METHODS: A retrospective study was conducted of all patients with cardiac and
pericardial neoplasm exactly diagnosed by endomyocardial or epicardial biopsy and
pericardiocentesis, using hospital medical records and a biopsy and
pericardiocentesis registry from 2000-2005 with 297 patients. Pericardial
effusion and biopsy analyses included biochemistry, cytology, serology,
microbiology, histology, immunohistology, and polymerase chain reaction (PCR).
All patients were investigated in relation to Herzmetasgender differences to
histopathologic findings, clinical presentation and outcome. RESULTS: In 76 cases
(25.6%) a neoplasm was the reason for a pericardial effusion. 36 women suffered
from the breast carcinoma (47%) and 40 males lung cancer (42%) as the firstly
metastatic tumor. There was no recurrence of a relevant pericardial effusion in
patients who were treated by intrapericardial instillation of cisplatin (30 mg/m2
body surface in 100 ml 0.9% NaCl). CONCLUSION: Females are more often affected by
primary cardiac tumors than males with an excellent outcome. By contrast, the
preventive checkup and aftercare will gain more prognostic importance, especially
in case of breast cancer, to earlier recognize a secondary cardiac neoplasm by
biopsy and pericardiocentesis with intrapericardial treatment of neoplastic
pericarditis.
PMID: 16132244 [PubMed - indexed for MEDLINE]
65. Herz. 2005 Aug;30(5):368-74; quiz 429-30.
Lipids and lipoproteins in women.
[Article in English, German]
Sattler AM, Soufi M, Maisch B, Schaefer JR.
Center of Internal Medicine, Cardiology, Angiology and Prevention, Philipps,
University Marburg, Marburg, Germany.
Atherosclerosis and coronary artery disease (CAD) are the main causes of death in
the Western world, for both men and women. However, in premenopausal women CAD is
less frequent than in men, but in elderly women (e.g., > 75 years) myocardial
infarction (MI) occurs even more often than in men. In summary, women suffer from
CAD and MI but at a later age than men. Therefore it is important to observe and
compare the cardiovascular risk factors in women and men. The typical CAD risk
factors such as hyperlipidemia, smoking, arterial hypertension, diabetes
mellitus, obesity, physical inactivity, and unhealthy nutrition are increasingly
important for both genders. Many of these factors are comparable between men and
women, but due to hormonal influences especially the lipoprotein metabolism shows
some striking differences between men and women, but interestingly enough also
between pre- and postmenopausal women. Therefore this paper will focus especially
on the gender-specific differences in lipid metabolism as a potential target
which might explain both the gender-specific and also pre- and postmenopausal
differences in the occurrence of CAD.
PMID: 16132239 [PubMed - indexed for MEDLINE]
66. Clin Appl Thromb Hemost. 2005 Jul;11(3):311-23.
Functional determination of plasminogen activator in arginine-stabilized plasma.
Stief TW, Richter A, Bünder R, Maisch B, Renz H.
Department of Clinical Chemistry, Hospital of Philipps-University, Marburg,
Germany. thstief@med.uni-marburg.de
Reliable data on plasminogen activator (PA) activities in blood of patients
receiving fibrinolytic treatment are lacking. This is due to the continuing in
vitro action of PA after blood withdrawal. We have elaborated a new simple
stabilization technique for plasma involving the addition of arginine in final
concentrations greater than 500 mM. In this study, new assays for PA in
stabilized plasma are developed. The assay was performed with substrate plasma,
that is, pooled normal plasma, preoxidized with chloramine-T; oxidant amount and
oxidation time were optimized. The chloramine consumption by plasma was assayed
with a KJ-assay (absorbance increase at 405 nm by addition of 200 microL 4 M KJ
to 25 microL oxidized plasma). The substrate plasma concentration in the PA assay
and the PA acting time was optimized. The inhibition of PA by the cations Na(+),
K(+), Mg(2+), and Ca(2+) was evaluated. The optimized PA assay consists of
incubation of 10 microL arginine-stabilized plasma with 10 microL 1.5 M arginine,
pH 8.7 and 10 microL 100 mM CT in PBS. After 30 minutes (37 degrees C), 175
microL 15 mM CT oxidized EDTA plasma are added. After 40 minutes (37 degrees C),
75 microL Stop-CS Reagent is added and DeltaA at 405 nm was determined, giving PA
+ plasmin activity in plasma. A control value (basal plasmin activity) consists
of the addition of Stop-CS Reagent before 175 microL oxidized EDTA plasma. To
obtain plasmatic PA activity, the control value has to be subtracted from the PA
main value. The assay is matrix-independent and linear up to 1250 IU/mL t-PA, 790
U/mL reteplase, or 199 IU/mL u-PA (37 nM). With arginine stabilization of plasma
and the described determination of plasminogen activator activity in
arginine-stabilized plasma, it is feasible to determine the activity of
plasminogen activators in blood of patients receiving fibrinolytic treatment
without artefactual in vitro changes of the samples.
PMID: 16015417 [PubMed - indexed for MEDLINE]
67. Clin Appl Thromb Hemost. 2005 Jul;11(3):303-9.
Functional determination of plasmin in arginine-stabilized plasma.
Stief TW, Richter A, Bünder R, Maisch B, Renz H.
Department of Clinical Chemistry, Hospital of Philipps-University Marburg,
Germany. thstief@med.uni-marburg.de
Reliable data on plasmin activities in blood of patients during fibrinolytic
treatment are lacking. This is due to continuing plasminogen activation by
plasminogen activators after blood withdrawal. The purpose of this study was to
establish a new method for stabilization of blood and to detect plasmin activity
in stabilized plasma. For optimization of plasma stabilization by arginine, 50
microL pooled normal citrated plasma was incubated with 50 microL of 0 to 1500 mM
arginine, pH 8.7, and 25 microL 100 IU/mL u-PA, 1250 IU/mL t-PA, 10000 U/mL
reteplase, 400 U/mL plasminogen-streptokinase-activator complex, 10 microg/mL
tenecteplase in 6% BSA-PBS or 25 microL 25 microg/mL plasmin in 20% glycerol.
Twenty-five microliters 3 mM HD-Val-Leu-Lys-pNA were added immediately (1 step)
or after 90 minutes (room temperature [RT]). The same experiment was performed
with pooled normal citrated plasma supplemented with 3.2 mg/mL EDTA, preoxidized
with 0 mM or 20 mM chloramine-T for 10 minutes (37 degrees C). For optimization
of plasmin activity, the oxidation time of the arginine-stabilized plasma sample
containing 0.5 U/mL active plasmin and the chloramine-T amount was varied.
Citrated plasma is stabilized against the in vitro action of all six plasminogen
activators tested if the final arginine concentration is greater than 500 mM.
Neither the addition of EDTA nor the addition of chloramine-T changes this
plasma-stabilizing power of arginine. The optimized functional plasmin assay
consists of incubation of 10 microL arginine-stabilized plasma with 10 microL 1.5
M arginine, pH 8.7, and 10 microL 100 mM CT in PBS. After 30 minutes (37 degrees
C), 75 microL 1.2 M KCl, 1.6 M Arg, 0.75 mM Val-Leu-Lys-pNA (Stop-CS Reagent),
and 175 microL 6% BSA-PBS are added and the absorbance increase (DeltaA) at 405
nm is determined. With the present arginine stabilization procedure of plasma and
the determination of plasmin activity in arginine-stabilized plasma as described,
it is feasible to determine the activity of plasmin in blood of patients
receiving fibrinolytic treatment without artefactual in vitro changes in the
samples.
PMID: 16015416 [PubMed - indexed for MEDLINE]
68. Z Kardiol. 2005 Jul;94(7):429-30.
Lipomatous hypertrophy of the interatrial septum. Diagnosis by cardiac magnetic
resonance imaging.
Alter P, Grimm W, Maisch B.
Philipps University of Marburg/Lahn, Department of Internal Medicine--Cardiology,
Baldingerstrasse, 35033 Marburg, Germany. alter@mailer.uni-marburg.de
PMID: 15997341 [PubMed - indexed for MEDLINE]
69. Am Heart J. 2005 Jun;149(6):1082-90.
Indications for angiography subsequent to coronary artery bypass grafting.
Alter P, Vogt S, Herzum M, Irqsusi M, Rupp H, Maisch B, Moosdorf R.
Department of Internal Medicine-Cardiology, Philipps University of Marburg/Lahn,
Marburg, Germany. palter@mailer.uni-marburg.de <palter@mailer.uni-marburg.de>
BACKGROUND: Postoperative myocardial infarction is a rare, but potentially severe
complication after coronary artery bypass grafting (CABG). Early markers for
coronary bypass graft failure or native vessel occlusion are required, because
immediate intervention could prevent major myocardial damage. METHODS: One
thousand patients with coronary artery disease consecutively underwent CABG.
Postoperative coronary angiography was performed in 40 patients with suspected
myocardial ischemia. Creatine kinase (CK), CK-MB, leukocyte count, C-reactive
protein (CRP), lactate dehydrogenase (LDH), and glutamate-oxalacetate
transaminase (GOT) were assessed at 0, 6, 12, 24, 48, and 72 hours after CABG as
well as 12-lead standard electrocardiography (ECG). RESULTS: Postoperative
angiography of 40 patients with suspected myocardial infarction revealed graft
failure or occluded native vessels in 13 (32.5%) individuals. Patients with graft
or vessel occlusion presented elevated (P < .005) leukocyte counts (17,215 +/-
6632 vs 10,773 +/- 3902 G/L) immediately after CABG. CK-MB concentrations
differed ( P < .05) at 6 hours after CABG (54 +/- 48 vs 30 +/- 18 U/L). CK, CRP,
LDH, and GOT did not show any differences between both groups. Frequency of ECG
ST-segment elevation was increased (P < .05) in ischemic patients (69.2% vs
29.6%). CONCLUSIONS: Common signs of myocardial ischemia usually allow to
diagnose unstable angina or myocardial infarction under native conditions. In
contrast, these criteria frequently fail after CABG. Combined diagnostic criteria
of elevated leukocytes (>14,000 G/L, at hour 0) and either ST elevation or CK-MB
concentrations >35 U/L (at hour 6) at least seem to be very useful in detecting
myocardial infarction after bypass grafting. In parallel, CK-MB elevation (>70
U/L, at hour 6) alone seems to predict ischemia. Both criteria should indicate
angiography and potential revascularization. If these conditions were not
fulfilled, the risk of perioperative myocardial infarction appears to be
moderate.
PMID: 15976792 [PubMed - indexed for MEDLINE]
70. Herz. 2004 Sep;29(6):638.
Asymptomatic thrombus formation on patent foramen ovale occluder 3.5 months after
implantation.
Richter A, Funck RC, Maisch B.
Deptartment of Internal Medicine and Cardiology, Philipps-University Marburg,
Germany. richter@med.uni-marburg.de
PMID: 15912439 [PubMed - indexed for MEDLINE]
71. Herz. 2004 Sep;29(6):624-36.
Treatment of inflammatory dilated cardiomyopathy and (peri)myocarditis with
immunosuppression and i.v. immunoglobulins.
Maisch B, Hufnagel G, Kölsch S, Funck R, Richter A, Rupp H, Herzum M, Pankuweit
S.
Department of Internal Medicine and Cardiology, Philipps-University Marburg,
Germany. BerMaisch@AOL.COM
OBJECTIVES: Treatment objectives in inflammatory dilated cardiomyopathy (DCMi),
myocarditis (M) and peri(myo)carditis are 1) the elimination of inflammatory
cells from the myocardium and pericardium, 2) the elimination or (second best)
mitigation of B-cell products such as antibodies and immuncomplexes directed
against cardiac epitopes such as sarcolemmal, fibrillary and mitochondrial
epitopes, and 3) the eradication of the causative viral or microbial agent, if
present. ANTIPHLOGISTIC TREATMENT: A "non-specific" anti-inflammatory treatment
in peri(myo)carditis can be carried out with antiphlogistics (NSAIDs preferably
colchicine 1-3 mg/d) independent from the presence of the infective agent. In
larger virus and bacteria negative effusions we recommend intrapericardial
instillation of cristalloid triamcinolon (Volon A) at a dose of 500 mg/m(2),
which should be left in place to have a sustained effect over at least 4 weeks.
This will effectively prevent recurrences particularly when colchicine is added
over a period of at least 3-6 months. Taking into account the 2004 ESC task force
recommendations on the management of pericardial diseases the treatment
recommendation for NSAIDs and colchicine can be classified as level of evidence
A, indication class I, for intrapericardial triamcinolon instillation as level of
evidence B, indication class IIa. IMMUNOSUPPRESSION: In (immuno)histologically
validated autoreactive (virus negative) myocarditis and DCMi double-blind
randomized trials are lacking to demonstrate the superiority of immunosuppression
over conventional heart failure management. The only published randomized and
double-blind immunosuppression treatment trial (American Myocarditis Treatment
Trial) was underpowered and did not distinguish viral from non-viral disease. It
showed neither benefit nor harm of a combination of cyclosporin and prednisone. A
number of retrospective analyses of immunosuppression in myocarditis showed some
benefit of surrogate parameters (ejection fraction, exercise tolerance) but
improvement under conventional heart failure treatment cannot be ruled out
completely as the main cause for amelioration. ESETCID (European Study on the
Epidemiology and Treatment of Cardiac Inflammatory Disease) is a double-blind,
randomized, placebo-controled three-armed trial with prednisolone and
azathioprine for autoreactive (virus negative) DCMi, interferon alpha for
enterovirus positive DCMi, high-dose immunoglobulin for cytomegalovirus and
intermediate dose for adeno- and Parvo B19 DCMi. It has now randomized more than
120 patients to the different treatment arms. Its final result has still to be
awaited.-Patients not willing to randomize in the trial were included in a
registry follow-up, which shows improvement of hemodynamic parameters and
elimination of the inflammation in the majority of patients. This is in
concordance with several non-randomized trials. Since evidence is conflicting
(level of evidence C, indication class IIb; if negative viral etiology is taken
into consideration class IIa) treatment with immunosuppression cannot be
generally recommended but should be further evaluated in doubleblind randomized
clinical trials or at least in controlled trials and registries. This also
applies to treatment with interferon for enteroviral or other viral infections in
the heart. IMMUNOADSORPTION: : The elimination of anticardiac antibodies, which
have been associated with DCMi, is a currently discussed concept, which is
supported by published registry data and a few very small controlled
investigations but not by a randomized double-blind trial with clinical endpoints
of relevance. In some studies immunoglobulins have been substituted, so that an
additional immunomodulatory effect has to be taken into account. The current
proof of concept can be ranked level of evidence C, indication class IIa only. An
even more challenging and still more attractive hypothesis is that cardiac
inflammation caused by specific circulating beta-adrenoceptor antibodies can be
eradicated with the elimination of the beta-receptor antibody thus healing
dilated cardiomyopathy. Application of this approach can be ranked level of
evidence C, indication class IIb at present only. Therefore these two
pathophysiologically attractive concepts have to await further validation by a
double-blind, randomized clinical endpoint trial. IMMUNOGLOBULIN TREATMENT: It
has been shown that immunoglobulins have both an antiviral and an
anti-inflammatory effect. They may suppress proinflammatory cytokines and reduce
oxidative stress. HIGH-DOSE I.V. IMMUNOGLOBULINS (IVIG): In biopsy proven
CMVmyocarditis a controlled trial demonstrated eradication of inflammation and of
the virus (level of evidence B, indication class IIa), which is in accordance
with registry data and case reports. In suspected myocarditis (not biopsy proven,
no viral etiology established or excluded) conflicting data exist with respect to
the improvement of surrogate markers such as the ejection fraction under
high-dose immunoglobulins. More evidence can be weighted in favour of a positive
treatment effect (level of evidence B, indication class IIb). Importantly there
were no detrimental effects of the ivIG reported in these trials. One has to
consider the high costs of this treatment, however. A trial taking into account
the different etiologies (different viruses assessed separately vs.
non-viral/autoreactive vs. placebo) is still lacking. MODERATE-DOSE I.V.
IMMUNOGLOBULINS: Registry data support a positive effect of 20 g i.v. pentaglobin
(IgG and IgM) in adenovirus positive myocarditis for clinical improvement,
eradication of both the inflammation and the virus. In Parvo B19 myocarditis our
own registry data indicate that clinical improvement can be noted, but only
inflammation is successfully eliminated, whereas Parvo B19 persistence remains a
problem in the majority of patients. In Parvo B19 associated DCMi therefore dose
finding studies and randomized trials are needed.
PMID: 15912438 [PubMed - indexed for MEDLINE]
72. Heart. 2005 Jun;91(6):e46.
Managing a complication after direct stenting: removal of a maldeployed stent
with rotational atherectomy.
Herzum M, Cosmeleata R, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University of Marburg,
Marburg, Germany. mhherzum@yahoo.com
A 40 year old patient presented with acute anterior wall infarction. A
non-calcified lesion was stented directly without significant expansion of the
stent. Rotational atherectomy successfully removed parts of the maldeployed stent
and resistant arterial wall substance allowing full dilatation of the lesion.
PMCID: PMC1768921
PMID: 15894747 [PubMed - indexed for MEDLINE]
73. Herz. 2005 Mar;30(2):153-8.
[A paradigm change in German academic medicine. Merger and privatization as
exemplified with the university hospitals in Marburg and Giessen]
[Article in German]
Maisch B.
Abteilung Innere Medizin-Kardiologie, Universitätsklinik, Marburg.
maisch@med.uni-marburg.de
1. The intended fusion of the university hospitals Marburg and Giessen in the
state of Hessia is "a marriage under pressure with uncalculated risk" (Spiegel
2005). In the present political and financial situation it hardly appears to be
avoidable. From the point of the view of the faculty of medicine in Marburg it is
difficult to understand, that the profits of this well guided university hospital
with a positive yearly budget should go to the neighboring university hospital
which still had a fair amount of deficit spending in the last years.2. Both
medical faculties suffer from a very low budget from the state of Hessia for
research and teaching. Giessen much more than Marburg, have a substantial need
for investments in buildings and infrastructure. Both institutions have a similar
need for investments in costly medical apparatuses. This is a problem, which many
university hospitals face nowadays.3. The intended privatisation of one or both
university hospitals will need sound answers to several fundamental questions and
problems:a) A privatisation potentially endangers the freedom of research and
teaching garanteed by the German constitution. A private company will undoubtedly
influence by active or missing additional support the direction of research in
the respective academic institution. An example is the priorisation of clinical
in contrast to basic research.b) With the privatisation practical absurdities in
the separation of research and teaching on one side and hospital care on the
other will become obvious with respect to the status of the academic employees,
the obligatory taxation (16%) when a transfer of labor from one institution to
the other is taken into account. The use of rooms for seminars, lectures and
bedside with a double function for both teaching, research and hospital care has
to be clarified with a convincing solution in everyday practice.c) The potential
additional acquisition of patients, which has been advocated by the Hessian state
government, may be unrealistic, when the 4th biggest university hospital in
Germany will be created by the merger. University hospitals recrute the patients
for high end medicine beyond their region because of the specialized academic
competence and advanced technical possibilities. Additional recruitment of
patients for routine hospital can hardly be expected.d) A private management will
have to consider primarily the "shareholder value", even when investing in
infrastructure and buildings, as it can be expected for one partner. On the
longterm this will not be possible without a substantial reduction of employees
in both institutions. There are, however, also substantial efforts of some
private hospital chains in clinical research, e. g. by Helios in Berlin and Rhön
Gmbh at the Leipzig Heart Center.e) There is a yet underestimated but very
substantial risk because of the taxation for the private owner when academic
staff is transferred from the university to hospital care in their dual function
as academic teachers and doctors. This risk also applies for the university if
the transfer should come from hospital to the university. These costs would add
to the financial burden, which has to be carried in addition to the DRGs.
PMID: 15875106 [PubMed - indexed for MEDLINE]
74. Herz. 2005 Mar;30(2):144-50.
Management of pericardial effusion the role of echocardiography in establishing
the indications and the selection of the approach for drainage.
Ristic AD, Seferovic PM, Maisch B.
University Institute for Cardiovascular Diseases, Clinical Center of Serbia,
Belgrade, Serbia and Montenegro. ristic@mailer.uni-marburg.de
PMID: 15875103 [PubMed - indexed for MEDLINE]
75. Cytokine. 2005 May 21;30(4):177-81.
Caffeine inhibits cytokine expression in lymphocytes.
Ritter M, Hohenberger K, Alter P, Herzum M, Tebbe J, Maisch M.
Department of Internal Medicine & Cardiology, Philipps-University of Marburg,
Germany. ritter4@mailer.uni-marburg.de
Caffeine alters intracellular calcium signalling patterns in lymphocytes which
are important for the specific regulation of activation and effector function in
lymphocytes. The effect of caffeine on calcium signalling is probably mediated
via a ryanodine receptor type 3 dependent intracellular calcium store which
releases calcium after exposure to caffeine. Also, caffeine decreases lymphocyte
cytotoxicity against allogenic myocyte. Which cytotoxic mechanisms are actually
altered by caffeine is unknown. In mouse splenocyte cultures containing about 87%
lymphocytes we show that concanavalin A (ConA, 5 microg/ml) stimulated cells
increase the expression of TNF-alpha, IL-2 and IFN-gamma (ELISA) significantly.
Caffeine (3.75 mM) inhibits cytokine expression of ConA stimulated cells almost
completely. Ryanodine (1 microM) specifically blocks ryanodine receptors and
thereby prevents caffeine induced calcium release. In our experiments, however,
ryanodine has no effect on ConA stimulated IL-2 and IFN-gamma expression and only
suppresses TNF-alpha expression by 20%. Furthermore, ryanodine does not prevent
the inhibitory effect of caffeine on TNF-alpha, IL-2 and IFN-gamma expression in
stimulated effector cells. We postulate that caffeine suppresses cytokine
expression and thereby contributes to decreased cytotoxicity of lymphocytes
against allogenic myocytes. The ryanodine receptor dependent intracellular
calcium store does not seem to play a significant role in this process. Possibly,
the blockade of IP3 receptors by caffeine is more important for cytokine
suppression.
PMID: 15863391 [PubMed - indexed for MEDLINE]
76. Am J Cardiol. 2005 May 1;95(9):1065-9.
Matrix metalloproteinases and their inhibitors in malignant and autoreactive
pericardial effusion.
Lamparter S, Schoppet M, Christ M, Pankuweit S, Maisch B.
Diakonie Krankenhaus Wehrda, Department of Internal Medicine, Marburg, Germany.
cs.lamparter@t-online.de
Matrix metalloproteinases (MMPs) are proteolytic enzymes essentially involved in
tissue remodeling and tumor invasion, and their activity is counterbalanced by
endogenous antagonists, the tissue inhibitors of matrix proteinases (TIMPs).
Recent reports have suggested a potential role of MMPs in the evolution of
pericardial effusion (PE). In this study, we determined the levels of MMP-2 and
MMP-9 and their inhibitors TIMP-1 and TIMP-2 in 19 patients who had malignant PE
that was confirmed by histology or cytology and 30 patients who had nonmalignant,
autoreactive PE compared with pericardial fluid of 19 patients who had preserved
left ventricular function and who underwent aortocoronary bypass surgery for
control. Samples were assayed by zymography, immunoblotting, and quantitative
enzyme-linked immunosorbent assay. We found significantly higher MMP-2 levels in
malignant PE than in pericardial fluid (2,906 +/- 348 vs 1,493 +/- 114 ng/ml, p =
0.0005) or autoreactive PE (2,079 +/- 269 ng/ml, p = 0.01). No significant
differences in MMP-9 levels were found between malignant PE and autoreactive PE
(83 +/- 28.6 vs 106 +/- 30.4 ng/ml, p = 0.22), whereas MMP-9 was below the
detection limit in pericardial fluid. No differences in TIMP-1 levels were found
across the different study groups, whereas compared with pericardial fluid,
TIMP-2 levels were significantly lower in autoreactive PE (113 +/- 18.9 vs 187
+/- 12.2 ng/ml, p = 0.002). In addition, there was a trend to lower TIMP-2 levels
in malignant PE (137 +/- 27.1 ng/ml, p = 0.07). The present findings indicate
that proteolytic enzymes and their inhibitors are involved in the pathogenesis of
PE, with an expression pattern that depends on etiology. The involvement of MMP-2
in the pathogenesis of malignant PE may indicate a potential role of MMP
inhibitors in the control of malignant PE.
PMID: 15842972 [PubMed - indexed for MEDLINE]
77. Eur Heart J. 2006 Mar;27(6):691-9. Epub 2005 Apr 8.
Prognostic significance of serum cholesterol levels in patients with idiopathic
dilated cardiomyopathy.
Christ M, Klima T, Grimm W, Mueller HH, Maisch B.
Klinik für Innere Medizin, Kardiologie und Intensivmedizin, Philipps University
Marburg, Baldingerstrasse, D-35033 Marburg, Germany. christ_michael@yahoo.de
Comment in:
Eur Heart J. 2005 Sep;26(18):1931; author reply 1931-2.
Eur Heart J. 2006 Mar;27(6):641-3.
AIMS: Previous studies indicate that low cholesterol levels are associated with
adverse prognosis in heart failure patients, because elevated lipoprotein levels
may negate bacterial endotoxin load induced by gastrointestinal congestion.
METHODS AND RESULTS: We examined the prognostic significance of lipid levels in a
cohort of 422 patients with idiopathic dilated cardiomyopathy (iDCM) [50+/-12
years, 342 males, 80 females, left ventricular ejection fraction (LV-EF):
31.6+/-10.6%]. During 42 months of follow-up, 86 patients (20.3%) died or
received a heart transplant. In univariate Cox regression analysis, reduced
LV-EF, high New York Heart Association (NYHA) class, and increased LV
end-diastolic diameter (LVEDD) were strong risk factors associated with that
endpoint, whereas decreased total cholesterol, HDL-cholesterol, and apoprotein I
levels were identified as weak risk predictors. After step-wise multivariable
analysis, only LVEDD, NYHA class, and LV-EF emerged as parameters independently
contributing to the model predicting risk for death or heart transplantation
(P<0.05). Cholesterol levels were positively associated with LV-EF and negatively
associated with LVEDD (P<0.05). Circulating sCD14 levels, a marker of endotoxin
exposure, were related to cholesterol levels (P<0.05) and LV-EF (P<0.05).
CONCLUSION: Decreased cholesterol levels do not independently predict adverse
prognosis in patients with iDCM. Our findings indicate that low cholesterol
levels are dependent on the severity of cardiac disease.
PMID: 15821011 [PubMed - indexed for MEDLINE]
78. Dtsch Med Wochenschr. 2005 Mar 24;130(12):726-30.
[Metabolism and the hypertrophied heart of the elderly]
[Article in German]
Rupp H, Rupp TP, Maisch B.
Molekular-kardiologisches Labor, Klinik für Innere Medizin und Kardiologie,
Philipps-Universität Marburg, Marburg. Rupp@staff.uni-marburg.de
In elderly patients, an inadequately treated high blood pressure often leads to
hypertrophied cardiomyocytes with various defects in gene expression. Due to a
decreased expression of the transcription factor PPARalpha, fatty acid oxidation
is reduced. If it can be compensated by an increased glucose oxidation, it has
been considered as a favorable process. Nonetheless, reduced PPARalpha influences
ensue involving e. g. anti-inflammatory mechanisms. The question arises thus
whether drugs can normalize reduced PPARalpha effects without increasing fatty
acid oxidation. As lead compound of these "fatty acid oxidation inhibitors with
PPARalpha activation", the carnitine palmitoyltransferase-1 inhibitor etomoxir
was characterized. An increased expression and activity of the Ca (2+) pump of
sarcoplasmic reticulum, a faster relaxation and a slowed progression of heart
failure was observed in animal experiments. It should, therefore, be examined
whether the impaired function of pressure overloaded hypertrophied cardiomyocytes
of particularly elderly patients should be a therapeutic target before
progression of heart failure, neuroendocrine activation and symptoms such as
shortness of breath occur.
PMID: 15776359 [PubMed - indexed for MEDLINE]
79. Am J Cardiovasc Drugs. 2005;5(2):103-12.
Bacterial pericarditis: diagnosis and management.
Pankuweit S, Ristić AD, Seferović PM, Maisch B.
Department of Internal Medicine - Cardiology, Philipps University, Marburg,
Germany.
Bacterial pericarditis occurs by direct infection during trauma, thoracic
surgery, or catheter drainage, by spread from an intrathoracic, myocardial, or
subdiaphragmatic focus, and by hematogenous dissemination. The frequent causes
are Staphylococcus and Streptococcus (rheumatic pancarditis), Haemophilus, and M.
tuberculosis. In AIDS pericarditis, the incidence of bacterial infection is much
higher than in the general population, with a high proportion of Mycobacterium
avium-intracellulare infection. Purulent pericarditis is the most serious
manifestation of bacterial pericarditis, characterized by gross pus in the
pericardium or microscopically purulent effusion. It is an acute, fulminant
illness with fever in virtually all patients. Chest pain is uncommon. Purulent
pericarditis is always fatal if untreated. The mortality rate in treated patients
is 40%, and death is mostly due to cardiac tamponade, systemic toxicity, cardiac
decompensation, and constriction. Tuberculous infection may present as acute
pericarditis, cardiac tamponade, silent (often large) relapsing pericardial
effusion, effusive-constrictive pericarditis, toxic symptoms with persistent
fever, and acute, subacute, or chronic constriction. The mortality in untreated
patients approaches 85%. Urgent pericardial drainage, combined with intravenous
antibacterial therapy (e.g. vancomycin 1g twice daily, ceftriaxone 1-2g twice
daily, and ciprofloxacin 400 mg/day) is mandatory in purulent pericarditis.
Irrigation with urokinase or streptokinase, using large catheters, may liquify
the purulent exudate, but open surgical drainage is preferable. The initial
treatment of tuberculous pericarditis should include isoniazid 300 mg/day,
rifampin 600 mg/day, pyrazinamide 15-30 mg/kg/day, and ethambutol 15-25
mg/kg/day. Prednisone 1-2 mg/kg/day is given for 5-7 days and progressively
reduced to discontinuation in 6-8 weeks. Drug sensitivity testing is essential.
Pericardiectomy is reserved for recurrent effusions or continued elevation of
central venous pressure after 4-6 weeks of antituberculous and corticosteroid
therapy.
PMID: 15725041 [PubMed - indexed for MEDLINE]
80. Pacing Clin Electrophysiol. 2005 Jan;28 Suppl 1:S5-7.
Marked improvement in left ventricular function and significant reverse left
ventricular remodeling within 3 months of cardiac resynchronization therapy in
patients with dilated cardiomyopathy.
Funck RC, Koelsch S, Waldhans S, Prinz H, Grimm W, Moosdorf R, Maisch B.
Clinic for Cardiology, Philipps University Marburg, Marburg, Germany.
funck@mailer.uni-marburg.de
We monitored reverse left ventricular (LV) remodeling and LV function during the
first 6 months of cardiac resynchronization therapy (CRT) in 34 patients (mean
age = 55.3 +/- 13.6 years, 28 men) with dilated cardiomyopathy (DCM), left bundle
branch block, in stable New York Heart Association class III, and on fixed drug
regimen who underwent implantation of CRT systems with or without cardioverter
defibrillator back-up. QRS-complex duration was reduced from 169.69 +/- 19.6 ms
(SD) to 144.1 +/- 23.4 ms during CRT. Parasternal M-mode and apical
2D-echocardiography was performed before and 3 and 6 months after device
implantation. LV enddiastolic (EDD) and endsystolic (ESD) diameters were
measured, and biplane LV enddiastolic (EDV), and endsystolic (ESV) volumes and
ejection fractions (EF) were calculated using a modified Simpson formula.
Significant decreases in LVEDD (P = 0.0064 at 3 months and P = 0.021 at 6
months), LVESD (P = 0.023 at 3 months, and P = 0.003 at 6 months), and LVESV (P =
0.006 resp. P = 0.007), and increases in LVEF (P = 0.003 at 3 months and P <
0.001 at 6 months) were observed. Mean LVEF increased from 23% at baseline to 39%
at 6 months. CRT induced prominent reverse LV remodeling and significantly
increased LVEF within a few months in patients with DCM.
PMID: 15683524 [PubMed - indexed for MEDLINE]
81. Pacing Clin Electrophysiol. 2005 Jan;28 Suppl 1:S207-10.
Long runs of non-sustained ventricular tachycardia on 24-hour ambulatory
electrocardiogram predict major arrhythmic events in patients with idiopathic
dilated cardiomyopathy.
Grimm W, Christ M, Maisch B.
Department of Cardiology, Hospital of the Philipps-University of Marburg,
Germany. grimmw@med.uni-marburg.de
This study examined the prognostic significance of the rate and length of
non-sustained (NS) ventricular tachycardia (VT) on 24-hour ambulatory
electrocardiograms (ECG) recorded in 343 patients with idiopathic dilated
cardiomyopathy (IDC) in the prospective Marburg Cardiomyopathy study. NSVT was
defined as >/=3 consecutive ventricular premature beats at >120 bpm. During 52
+/- 21 months of follow-up, major arrhythmic events defined as sustained VT, VF,
or sudden cardiac death occurred in 46 of 343 patients (13%). Patients with 3-4
beat runs of NSVT had a similar arrhythmia-free survival as patients without NSVT
on baseline 24-hour ambulatory ECG. The incidence of major arrhythmic events
during follow-up increased significantly from 2% per year in patients without
NSVT, to 5% per year in patients with 5-9 beat runs of NSVT, to 10% per year in
patients with >/=10 beat runs of NSVT (P < 0.05). Unlike the length, the rate of
NSVT was similar in patients with versus without subsequent major arrhythmic
events (163 +/- 23 vs 160 +/- 24 bpm). Thus, the length but not the rate of NSVT
on 24-hour ambulatory ECG was a predictor of major arrhythmic events in patients
with IDC. The presence of NSVT with >/=10 beat runs on ambulatory ECG was
associated with a particularly high risk of major arrhythmic events.
PMID: 15683498 [PubMed - indexed for MEDLINE]
82. Pacing Clin Electrophysiol. 2005 Jan;28 Suppl 1:S202-6.
Arrhythmia risk prediction in idiopathic dilated cardiomyopathy based on heart
rate variability and baroreflex sensitivity.
Grimm W, Christ M, Sharkova J, Maisch B.
Department of Cardiology, Hospital of the Philipps-University of Marburg,
Germany. grimmw@med.uni-marburg.de
This study examined the relation between heart rate variability (HRV) and
baroreflex sensitivity (BRS) and subsequent major arrhythmic events (MAE),
defined as sustained VT, VF or sudden death, in 263 patients with idiopathic
dilated cardiomyopathy (IDC) in sinus rhythm. The predefined measure of HRV was
the standard deviation of all normal-to-normal RR intervals (SDNN) on baseline
24-hour ambulatory ECG. BRS was determined by the phenylephrine method. Over 52
+/- 21 months of follow-up, MAE occurred in 38 patients (14%). SDNN at baseline
24-hour ambulatory ECG (106 +/- 46 vs 109 +/- 45, ns) and BRS (7.9 +/- 5.5 vs 7.7
+/- 5.3 ms/mmHg, ns) were both similar in patients with versus without MAE during
follow-up. In contrast, left ventricular ejection fraction was significantly
lower in patients with versus without MAE (24%+/- 7% vs 31%+/- 10%, P < 0.019.
CONCLUSIONS: Neither HRV nor BRS predicted MAE in patients with IDC.
PMID: 15683497 [PubMed - indexed for MEDLINE]
83. Z Kardiol. 2005 Feb;94(2):79-80.
Bidirectional ventricular tachycardia due to digitalis intoxication.
Grimm W, Ritter M, Alter P, Funck R, Maisch B.
Department of Cardiology, Hospital of the Phillips-University Marburg,
Baldingerstrasse, 35033 Marburg, Germany. grimmw@med.uni-marburg.de
PMID: 15674736 [PubMed - indexed for MEDLINE]
84. Z Kardiol. 2005 Jan;94(1):33-7.
Coronary artery spasm induced by 5-fluorouracil.
Alter P, Herzum M, Schaefer JR, Maisch B.
Philipps University of Marburg/Lahn, Department of Internal Medicine-Cardiology,
Baldingerstrasse, 35033 Marburg, Germany. palter@med.uni-marburg.de
The frequently used chemotherapeutic drug 5-fluorouracil (5-FU) is known to cause
angina pectoris and arrhythmias; myocardial infarction and sudden cardiac death
could occur. Potential reasons for these phenomena range from toxic/metabolic
disturbances to coronary artery spasms. This report shows angiographically proven
spasmophilia of the coronary arteries and contributes to the understanding of
angina pectoris occurring during treatment with 5-FU. Thus, verapamil type
calcium antagonists as well as nitrates should be administered primarily in
patients with coronary artery disease and in all patients who had been
symptomatic during 5-FU administration in order to prevent further episodes.
PMID: 15668828 [PubMed - indexed for MEDLINE]
85. Herz. 2004 Dec;29(8):788-93.
Inflammation in dilated cardiomyopathy.
Pankuweit S, Ruppert V, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University Marburg,
Baldingerstrasse, 35043, Marburg, Germany. pankuwei@staff.uni-marburg.de
Inflammation is an important component in the pathogenesis of many common
cardiovascular diseases. In most cases, the role of inflammation is a natural
response to injury, and an important mechanism for healing and tissue repair.
However, the inflammatory response can be either inadequate or overwhelming,
leading to direct injury or severe host disease. Accumulating data has revealed
an important inflammatory component in the pathogenesis of dilated cardiomyopathy
(DCM), and there is growing evidence, that myocarditis and DCM are closely
related. Many faces of DCM coexist, while different phases of the disease
progress simultaneously: phase 1 is dominated by viral infection itself, phase 2
by the onset of (probably) multiple autoimmune reactions, and phase 3 by the
progression to cardiac dilatation without an infectious agent and cardiac
inflammation. Separation between the phases is not always distinct, they may
overlap one another and phase 1 and 2 may recur after progression of DCM.
Appropriate treatment during phase 1 includes eradication of virus and
amelioration of injury caused by the virus. During phase 2, which is
characterized by autoimmune processes, immunosuppression is the most appropriate
therapy and warrants sophisticated diagnostic strategies including molecular
biological and immunohistochemical techniques. Phase 3, DCM, although a result of
viral and autoimmune injury, may then progress independently. The more attention
given to serologic, molecular and immunologic factors to characterize and
diagnose DCM lead to several changes in the terminology. The term cardiomyopathy
is no longer reserved for the idiopathic forms but can be used interchangeably
with the term heart muscle diseases including specific, secondary forms. Right
ventricular cardiomyopathy (RVCM), valvular, hypertensive, ischemic, and
inflammatory cardiomyopathy have been introduced. Idiopathic, autoimmune, and
infectious forms of inflammatory cardiomyopathy were recognized. Viral
cardiomyopathy is defined as viral persistence in a dilated heart. It may be
accompanied by myocardial inflammation and is then termed inflammatory viral
cardiomyopathy. Because of the overlap of pathophysiological stages in DCM,
design of the appropriate therapy is important. It requires the
immunohistochemical and molecular biological investigation of endomyocardial
biopsies in parallel. In the modern molecular era the infective agent-immune
system-host interaction has to be clarified leading to a better knowledge of the
etiology of DCM. This may change the management of the disease in the future. One
of the hopes is to discern the underlying dominant mechanism in a given patient
to make a decision for the most promising therapy.
PMID: 15599676 [PubMed - indexed for MEDLINE]
86. Herz. 2004 Nov;29(7):673-85.
Risk stratification by the "EPA+DHA level" and the "EPA/AA ratio" focus on
anti-inflammatory and antiarrhythmogenic effects of long-chain omega-3 fatty
acids.
Rupp H, Wagner D, Rupp T, Schulte LM, Maisch B.
Molecular Cardiology Laboratory, Department of Internal Medicine and Cardiology,
Philipps University of Marburg, Marburg, Germany. Rupp@staff.uni-marburg.de
Erratum in:
Herz. 2004 Dec;29(8):805.
The identification of risks associated with sudden cardiac death requires further
investigations. The question was addressed whether parameters can be established
which not only describe an increased risk for an enhanced electrical instability
of the heart but also of inflammatory events underlying plaque rupture. Emphasis
is placed on dose-dependent effects of the long-chain omega-(omega-)3 fatty acids
eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Since free acids of
EPA and DHA are required for most of their biological effects, it appears
essential not only to build up stores in the body for release of these fatty
acids, but also to provide a sustained uptake of EPA and DHA in the form of ethyl
esters. In contrast to rapidly absorbed triacylglycerols from fish, ethyl esters
are taken up more slowly within 24 h. For the administration of 1 g/day highly
purified EPA+DHA ethyl esters (Omacor) to healthy volunteers, it is shown that
EPA is increased from 0.6% to 1.4% within 10 days, while DHA is increased from
2.9% to 4.3%. After withdrawal, EPA and DHA approach baseline values within 10
days. A gas chromatographic procedure was established which requires only 10
microl of whole blood for the identification of more than 35 fatty acids.
Evidence is summarized strengthening the concept that a low "EPA+DHA level"
presents a risk for sudden cardiac death and that the administration of 840
mg/day of EPA+DHA ethyl esters raises the "EPA+DHA level" to approximately 6%
that is associated with a marked protection from sudden cardiac death. For
reducing pro-inflammatory eicosanoids and cytokines, a higher "EPA+DHA level" is
required which can be achieved with an intake of 2-4 g/day of 84% EPA+DHA ethyl
esters. For assessing influences from pro-inflammatory eicosanoids and cytokines,
the EPA/arachidonic acid ratio ("EPA/AA ratio") was identified as diagnostic
parameter. To assess the dietary EPA+DHA intake, fatty acids were determined in
fish dishes of the cafeteria of the Philipps University Hospital Marburg,
Germany. The EPA+DHA content of the popular Alaska Pollock was 125 +/- 70 mg/100
g. A once daily fish dish can thus not provide the 840 mg/day EPA+DHA
administered in the GISSI Prevention Study in the form of ethyl ester which
markedly reduced the risk of sudden cardiac death in postmyocardial infarction
patients. Nonetheless, at least two preferably oily fish meals per week should be
consumed as preventive measure by persons without coronary artery disease. With
documented coronary heart disease, it was advised to consume approximately 1
g/day of EPA+DHA.
PMID: 15580322 [PubMed - indexed for MEDLINE]
87. Ann Thorac Surg. 2004 Dec;78(6):2178-80.
Long-term survival with acquired ventricular septal defect after myocardial
infarction.
Alter P, Maisch B, Moosdorf R.
Department of Internal Medicine-Cardiology, Philipps University of Marburg/Lahn,
Marburg, Germany. alter@mailer.uni-marburg.de
Acquired ventricular septal defects (VSD) are rare and devastating complications
after myocardial infarction. The long-term prognosis with medical therapy is
extremely poor. We report on a patient who developed progressive heart failure
within 3 months after myocardial infarction due to an unknown VSD. The left
ventricular function was severely impaired. After diagnosing VSD by
echocardiography, surgical occlusion was performed. In addition, a biventricular
pacemaker was applied using epicardial leads. The patient recovered almost
completely 6 weeks postoperative. Beside hemodynamic changes, biventricular
pacing is potentially sufficient to improve the postoperative outcome of patients
with severe heart failure in these conditions.
PMID: 15561069 [PubMed - indexed for MEDLINE]
88. Dtsch Med Wochenschr. 2004 Oct 8;129(41):2173-6.
[Complicated course of Churg-Strauss syndrome with eosinophilic perimyocarditis
and pericardial tamponade]
[Article in German]
Lamparter S, Pankuweit S, Kölsch S, Maisch B.
Abteilung für Innere Medizin, Diakonie-Krankenhaus Wehrda, Marburg.
CS.Lamparter@t-online.de
Comment in:
Dtsch Med Wochenschr. 2005 Jan 28;130(4):176; author reply 176.
HISTORY: A 30-year-old patient suffered from a dry cough and increasing dyspnea
since two years; he further complained about non radiating chest pain and weight
loss of 15 kg in the past 8 weeks. EXAMINATIONS: Physical examination revealed
pulsus paradoxus and distended neck veins. On chest x-ray, signs of cardiomegaly
without infiltrations were found. Echocardiographic studies demonstrated a large
pericardial effusion with signs of pericardial tamponade. Pericardiocentesis and
pericardioscopy was performed and pericardial as well as epimyocardial biopsy
samples were taken. Serum studies revealed increased markers of myocardial
infarction and hypereosinophilia without clinical evidence of parasitic,
myeloproliferative, or neoplastic diseases. Diagnosis of acute eosinophilic
myocarditis was established in the epimyocardial biopsy samples. DIAGNOSIS,
TREATMENT AND COURSE: Based on the clinicopathologic findings, we diagnosed Churg
Strauss syndrome with cardiac involvement. We instilled 500 mg triamcinolone
intrapericardially and initiated systemic treatment with corticosteroids which
resulted in normalization of the blood eosinophil count. During a follow up of 18
months, no recurrence of pericardial effusion was detected. However, while trying
to reduce the steroids below 15 mg prednisolone equivalent per day, eosinophil
numbers raised and wheezing increased. We suggested an immunosuppressive therapy
including cyclophosphamide according to the Fauci protocol, which was denied by
the patient due to potential adverse side effects. CONCLUSION: We suggest a
detailed invasive strategy including endomyocardial biopsy to rule out viral
myocarditis before immunosuppressive therapy with steroids is initiated in
patients with suspected cardiac involvement in Churg Strauss syndrome.
PMID: 15457397 [PubMed - indexed for MEDLINE]
89. Dtsch Med Wochenschr. 2004 Oct 8;129(41):2169-72.
[Endomyocardial biopsy-guided diagnosis and treatment of inflammatory
cardiomyopathies]
[Article in German]
Pankuweit S, Lamparter S, Funck R, Maisch B.
Klinik für Innere Medizin -- Kardiologie, Philipps-Universität Marburg.
pankuwei@mailer.uni-marburg.de
BACKGROUND: Over 50 % of cases of inflammatory cardiomyopathy are caused by
bacterial or viral infection, the latter frequently Parvovirus B19, enterovirus
(Coxsackie B virus) or adenovirus. Regarding the pathogenesis of the disease, its
early phase is dominated by the infectious pathogen, which directly damages the
myocardium, while in the second phase an important role is played by activation
of the immune system and the antiviral immune response with immunological
processes. HISTORY AND CLINICAL FINDINGS: A 24-year-old woman (height 175 cm,
weight 88 kg) was admitted because of recurrent exertional dyspnea. She also
reported increased feeling of weakness, fainting and vertigo for the preceding
six months. She reported an influenza-like infection just before the onset of
these symptoms. EXAMINATIONS: No abnormalities were found on physical
examination. But echocardiography revealed markedly reduced ventricular
contractility with an ejection fraction (EF) of 30 %. A cardiac catheterization
was performed, as part of which a myocardial biopsy was obtained. DIAGNOSIS,
TREATMENT AND COURSE: The biopsies showed an inflammatory cardiomyopathy and
Parvovirus B19 was demonstrated. The patient received the accepted management of
heart failure plus hyper-immunoglobins, 2 x 10 g i. v. on days 1 and 3. This
treatment resulted in marked and lasting improvement of the clinical symptoms.
After 36 months the clinical status was only slightly reduced, the EF being 40 %
and the LV end-diastolic dimension 56 mm. CONCLUSION: Without an endomyocardial
biopsy it would have been impossible to establish the diagnosis of inflammatory
cardiomyopathy due to Parvovirus B19. It was only through the demonstration of
the causative pathogen in myocardium that it was possible to provide
aetiologically targeted treatment.
PMID: 15457396 [PubMed - indexed for MEDLINE]
90. Dtsch Med Wochenschr. 2004 Oct 8;129(41):2161.
[Management of cardiovascular diseases]
[Article in German]
Maisch B, Erdmann E.
Klinik für Innere Medizin -- Kardiologie, Angiologie, Intensivmedizin und
Kardioprävention, Marburg. BerMaisch@aol.com
PMID: 15457394 [PubMed - indexed for MEDLINE]
91. Internist (Berl). 2004 Oct;45(10):1136-46.
[Extracardiac causes of right ventricular insufficiency]
[Article in German]
Maisch B, Christ M.
Klinik für Innere Medizin, Philipps-Universität Marburg. BerMaisch@aol.com
Evidence for manifest right ventricular dysfunction is considered a critical
threshold in the development of a fatal event after acute pulmonary embolism.
While the acute event impressively reflects the clinical significance of right
ventricular function, various disorders such as idiopathic pulmonary arterial
hypertension, secondary pulmonary hypertension in lung diseases, carcinoid heart
disease, and portopulmonary hypertension can lead to chronic right ventricular
failure. Adapted treatment makes it possible to alleviate the patients' distress
and presumably also improve the prognosis. The clinical picture of right
ventricular insufficiency can also be imitated in constrictive or adhesive
pericarditis and pericardial tamponade. Pericardiocentesis of the tamponade
provides initial hemodynamic improvement. Causal treatment is based on
cytological findings and/or results of epicardial or pericardial biopsy to
classify malignant and nonmalignant effusions. Cardiac surgery with
pericardiolysis and (partial) pericardial resection remains the method of choice
for symptomatic constrictive pericarditis.
PMID: 15365640 [PubMed - indexed for MEDLINE]
92. Ann Thorac Surg. 2004 Sep;78(3):883-9; discussion 889.
Detection of anti-hsp70 immunoglobulin G antibodies indicates better outcome in
coronary artery bypass grafting patients suffering from severe preoperative
angina.
Vogt S, Portig I, Kusch B, Pankuweit S, Sirat AS, Troitzsch D, Maisch B, Moosdorf
R.
Department of Cardiovascular Surgery, Philipps-University Hospital, Marburg,
Germany. vogts@med.uni-marburg.de
BACKGROUND: Recent findings indicate that molecular chaperones actively
participate in myocardial cytoprotection. Moreover, ischemic tolerance can be
induced in humans by brief ischemic events. Therefore, we investigated patients
with severe angina attacks before coronary artery bypass grafting. We focused on
appearance of anti-hsp70 antibodies as an immunologic response to heat shock
protein induction by ischemia followed up by hemodynamic measurements
perioperatively. We correlated these clinical findings with the presence of
antibodies against hsp70 and the antioxidative capacity of patients' sera.
METHODS: Thirty-five consecutive patients with coronary artery disease scheduled
for coronary artery bypass grafting were included. Seventeen patients had severe
angina, and 18 patients suffered from chronic stable angina preoperatively. In
the patients' sera, antibodies against hsp70 were detected by enzyme-linked
immunosorbent assay, and antioxidative capacity was detected using the chromogen
assay. Cardiac output and pulmonary capillary wedge pressure were measured using
a thermodilution catheter. We also evaluated C-reactive protein and creatine
kinase MB isoenzyme, and performed a conventional leukocyte count. RESULTS: The
sera of the 17 patients with severe angina attacks before surgery contained
antibodies against hsp70 and a low antioxidative capacity. The interval between a
severe angina attack and anti-hsp70 antibody titer are inversely correlated.
These patients had better cardiac output and lower pulmonary capillary wedge
pressure values after surgery. CONCLUSIONS: Severe angina before cardiac surgery
coincided with an improved outcome as measured by hemodynamic variables as
compared with chronic stable angina. This finding correlated significantly with a
low antioxidative capacity and the presence of antibodies against hsp70. These
pathophysiologic mechanisms might therefore play a role in myocardial protection.
PMID: 15337014 [PubMed - indexed for MEDLINE]
93. J Clin Endocrinol Metab. 2004 Aug;89(8):4104-12.
Localization of osteoprotegerin, tumor necrosis factor-related apoptosis-inducing
ligand, and receptor activator of nuclear factor-kappaB ligand in Mönckeberg's
sclerosis and atherosclerosis.
Schoppet M, Al-Fakhri N, Franke FE, Katz N, Barth PJ, Maisch B, Preissner KT,
Hofbauer LC.
Department of Internal Medicine, Philipps University, Baldingerstrasse, D-35033
Marburg, Germany. schoppet@mailer.uni-marburg.de
Vascular calcification may occur at different areas of the vessel wall, including
the intima in atherosclerosis and the media in Mönckeberg's sclerosis. Medial
calcification of arteries is common in patients with diabetes mellitus or chronic
renal failure. Osteoprotegerin (OPG) and receptor activator of nuclear
factor-kappaB ligand are essential modulators of bone homeostasis and may be
involved in the process of vascular calcification. In this study we investigated
arteries from patients with Mönckeberg's sclerosis and atherosclerosis.
Apoptosis, which precedes vascular calcification in vitro, was assessed by an in
situ ligation assay and was localized to the medial layer of arteries
(Mönckeberg's sclerosis) and the neointima (atherosclerosis).
Immunohistochemistry and in situ hybridization revealed OPG immunoreactivity and
mRNA expression surrounding calcified areas in the medial layer (Mönckeberg's
sclerosis), whereas OPG was mainly expressed adjacent to calcified neointimal
lesions (atherosclerosis). Receptor activator of nuclear factor-kappaB ligand
protein and mRNA were barely or not detectable. Of note, TNF-related
apoptosis-inducing ligand, an inducer of apoptosis that is also blocked by OPG,
displayed a similar spatial distribution as OPG. In summary, we demonstrate
enhanced apoptosis adjacent to vascular calcification, and the concurrent
expression of regulators of apoptosis and osteoclastic differentiation,
TNF-related apoptosis-inducing ligand and OPG, suggesting their involvement in
the pathogenesis of vascular calcification.
PMID: 15292354 [PubMed - indexed for MEDLINE]
94. J Clin Endocrinol Metab. 2004 Aug;89(8):3764-8.
Osteoprotegerin gene polymorphisms in men with coronary artery disease.
Soufi M, Schoppet M, Sattler AM, Herzum M, Maisch B, Hofbauer LC, Schaefer JR.
Department of Internal Medicine and Cardiology, Philipps University, Marburg,
Germany.
Osteoprotegerin (OPG) antagonizes receptor activator of nuclear factor-kappaB
ligand (RANKL), the principal regulator of osteoclasts. Of note, OPG-deficient
mice display osteoporosis and arterial calcification. Recently, OPG gene
polymorphisms have been associated with osteoporosis and early predictors of
cardiovascular disease. In this study, we examined OPG gene polymorphisms in 468
men who had absence of coronary artery disease (CAD) or single-, double-, or
triple-vessel disease on coronary angiography. Denaturing gradient gel
electrophoresis followed by DNA sequencing revealed nucleotide substitutions 149
T-->C, 163 A-->G, 209 G-->A, 245 T-->G, 950 T-->C (all promoter), 1181 G-->C
(exon 1), and 6890 A-->C (intron 4), respectively. Although single polymorphisms
were not associated with CAD, linkage of polymorphisms 950 and 1181 revealed that
haplotypes were overrepresented in men with CAD (chi(2) = 17.05; P = 0.03) with
an increased risk of CAD in carriers of genotypes 950 TC/1181 GC and 950 CC/1181
CC (odds ratio, 1.67; 95% confidence interval, 1.02-2.72; P = 0.04). Furthermore,
serum OPG levels were correlated with the presence of a C allele at position 950
(P = 0.02). In summary, linkage of genetic variations of the OPG gene at
positions 950 and 1181 may confer an increased risk of CAD in Caucasian men.
PMID: 15292302 [PubMed - indexed for MEDLINE]
95. Z Kardiol. 2004 Jul;93(7):524-32.
Escape from cardiomyocyte apoptosis by enterovirus persistence due to elevated
soluble Fas-receptors.
Alter P, Maisch B.
University of Marburg/Lahn, Department of Internal Medicine Cardiology,
Baldingerstrasse, 35033 Marburg, Germany. alter@mailer.uni-marburg.de
BACKGROUND: Apoptosis causes loss of contractile cardiomyocytes in inflammatory
heart disease. Despite recent examinations, the influence of virus infection on
apoptosis remained ill-defined. METHODS: Apoptosis was assessed in left
ventricular endomyocardial biopsies by the TUNEL method frompatients with chronic
myocarditis and adeno-, cytomegalo- and enterovirus persistence. Soluble
Fas-ligands, sFas-receptors, TNF-alpha, IL-6, IL-10 and IFN-gamma were measured
using ELISA technique. RESULTS: Elevated (P < 0.05) rates of apoptosis were found
in patients with autoimmune myocarditis. Apoptosis was increased (P < 0.05) in
the case of cytomegalovirus persistence, but not significantly increased in the
presence of adenoviral genome. No evidence for apoptosis, but elevated
concentrations of soluble Fas-receptors were found only in the case of
enterovirus persistence. In turn, elevated percentages of apoptosis and normal
soluble Fas-receptor concentrations were found in patients with chronic
myocarditis. Serum levels of soluble Fas-ligands, TNF-alpha, IL-6, IL-10 and
IFN-gamma did not predict changes in TUNEL-positivity. CONCLUSIONS: Escape
mechanisms to protect cardiomyocytes from apoptosis are yet not known for
enterovirus infections. Soluble Fas-receptors have to be considered to counteract
binding of soluble Fas-ligands that results in the blockade of apoptosis
induction. It is a new finding that soluble Fasreceptors were elevated in the
presence of enterovirus genome in the heart. Inhibition of apoptosis can impair
virus clearing and prolong its replication with a potential worse outcome. In
turn, sufficient protection from apoptosis in autoimmune myocarditis should
reduce loss of cardiomyocytes. Therefore, the interaction of the Fas components
could provide a new therapeutic target in myocarditis.
PMID: 15243763 [PubMed - indexed for MEDLINE]
96. Herz. 2004 Jun;29(4):391-400.
[Physical activity and sports in heart failure due to myocarditis and dilated
cardiomyopathy]
[Article in German]
Alter P, Grimm W, Herzum M, Ritter M, Rupp H, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University of Marburg,
Germany. alter@mailer.uni-marburg.de
BACKGROUND: Sudden cardiac death of suspected healthy young athletes is a rare,
but deeply moving event. Usually, the affected person has been completely free of
symptoms. Commonly, unrecognized inflammatory, hypertrophic or dilated
cardiomyopathies are the most frequent causes. All therapeutic principles of
angiotensin-converting-enzyme (ACE) inhibition, beta-blockade, and diuretics in
heart failure aim to unload the heart. During physical activity increased
sympathetic tonus and loading conditions for the heart point into the opposite
direction. This raises the question to what extent physical activity in patients
with myocarditis, dilated cardiomyopathy or heart failure in general is
tolerable. SYNOPSIS: Several experimental studies revealed disadvantages of
physical exercise during acute myocarditis leading to an increase in mortality.
On the other hand, several small trials in men demonstrate an improvement of
physical fitness and quality of life attributed to controlled supervised exercise
training in patients with heart failure without assessment of mortality. Dilated
cardiomyopathy was diagnosed in one third of these patients. There was no biopsy
confirmation of these conditions. The other two thirds of patients suffered from
ischemic heart diseases. CONCLUSION: Since the borderline between inflammatory
heart disease and noninflammatory or postinflammatory dilated cardiomyopathy is
difficult to determine, abstention from physical training during and shortly
after inflammatory heart disease is recommended, because it is known that viral
persistence or autoimmune processes could last for several months.
PMID: 15241538 [PubMed - indexed for MEDLINE]
97. Anaesthesist. 2004 Sep;53(9):862-70.
[Premedication visits. Economizing at the cost of the patient?]
[Article in German]
Kratz CD, Christ M, Maisch B, Kerwat KM, Olt C, Zielke A, Hellinger A, Wulf H,
Geldner G.
Klinik für Anästhesie und Intensivmedizin, Klinikum der Philipps-Universität
Marburg.
The older the patient, the higher the risk of perioperative cardiac
complications. Therefore, patients at risk have to be identified and the
appropriate diagnostic or therapeutic measures initiated. The most important
factor in this context is whether a planned surgery can be postponed. Several
strategies have been developed (e.g. Goldman index, Eagle criteria) and the
American Heart Association (AHA/ACC) has produced guidelines concerning
perioperative diagnosis and therapy of cardiac risk patients. The common goal of
these strategies is always the risk classification of the patient by combining
the operative risk and the risk factors of the patient. The further procedure
(diagnostic or therapeutic measures) is based on the risk classification. If
further invasive therapy proves to be necessary, the determining factor is the
period of time for which the operation can be delayed. This appears to be about 3
months but if this is not possible the outcome could be improved with a
beta-blocker therapy in advance. A working group from the university hospital in
Marburg has developed a strategy for risk classification and further diagnostic
and therapeutic measures as outlined in this article.
PMID: 15221120 [PubMed - indexed for MEDLINE]
98. Herz. 2004 May;29(3):353.
Image of the month. Cardiac arrest due to severe hyperkalemia.
Grimm W, Alter P, Maisch B.
Department of Cardiology, Philipps University Marburg, Baldingerstrasse, 35033
Marburg, Germany. grimmw@med.uni-marburg.de
PMID: 15167964 [PubMed - indexed for MEDLINE]
99. Herz. 2004 May;29(3):348-52.
Arrhythmia risk stratification with regard to prophylactic implantable
defibrillator therapy in patients with dilated cardiomyopathy. Results of MACAS,
DEFINITE, and SCD-HeFT.
Grimm W, Alter P, Maisch B.
Department of Internal Medicine and Cardiology, Hospital of the Philipps
University, Marburg, Germany. grimmw@med.uni-marburg.de
To date, generally accepted indications for prophylactic defibrillator
implantation in patients with dilated cardiomyopathy do not exist. Recently, the
Marburg Cardiomyopathy Study (MACAS) revealed left ventricular ejection fraction
to be the only significant arrhythmia risk predictor in a relatively large
patient population with dilated cardiomyopathy. Meanwhile, the preliminary
results of two prospective randomized trials evaluating prophylactic
defibrillator therapy in dilated cardiomyopathy have been reported. The
Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation study
(DEFINITE) randomized 458 patients with a history of symptomatic heart failure, a
left ventricular ejection fraction < or = 35% and arrhythmias on Holter to an ICD
versus no ICD. As a result, ICD therapy was associated with a significant
reduction of arrhythmic deaths, which failed to result in a significant decrease
in total mortality due to an insufficient number of patients in DEFINITE. The
Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) was a three-arm study
comparing placebo to amiodarone to prophylactic ICD therapy in a total of 2,521
patients with ischemic cardiomyopathy (51%) or nonischemic dilated cardiomyopathy
(49%). All patients in SCD-HeFT had a left ventricular ejection fraction inverted
exclamation mark U 35% despite optimized medical heart failure therapy. SCD-HeFT
showed a significant reduction of total mortality in the ICD group, whereas
amiodarone did not improve survival.
PMID: 15167963 [PubMed - indexed for MEDLINE]
100. Atherosclerosis. 2004 May;174(1):11-6.
A new but frequent mutation of apoB-100-apoB His3543Tyr.
Soufi M, Sattler AM, Maerz W, Starke A, Herzum M, Maisch B, Schaefer JR.
Department of Internal Medicine-Cardiology, Philipps-University, Marburg,
Germany.
ApolipoproteinB 100 (apoB-100) is an important component of atherogenic
lipoproteins such as LDL and serves as a ligand for the LDL-receptor. Familial
defective apolipoproteinB 100 (FDB) is caused by a R3500Q mutation of the apoB
gene and results in decreased binding of LDL to the LDL-receptor. So far FDB is
the most frequent and best studied alteration of apoB-100. Apart from this, three
other apoB mutations, R3500W, R3531C and R3480W, affecting binding to the
LDL-receptor are known to date. We screened the apoB gene segment of codons
3448-3561 by denaturing gradient gel electrophoresis (DGGE) analysis in a total
of 853 consecutively sampled German patients undergoing diagnostic coronary
angiography for suspected CAD. By this, a new single base mutation was detected
and confirmed by DNA sequencing. The mutation, CAC(3543)TAC results in a
His3543Tyr substitution in apoB-100 (H3543Y). The prevalence of heterozygotes for
H3543Y in the study population was 0.47% compared to 0.12% for the known Arg 3500
Gln (R3500Q) mutation. In conclusion, the new mutation is four times more
frequent than "classical" FDB and thus appears to be the most common apoB
mutation in Germany.
PMID: 15135245 [PubMed - indexed for MEDLINE]
101. Biochem Biophys Res Commun. 2004 May 28;318(2):535-43.
Novel point mutations in the mitochondrial DNA detected in patients with dilated
cardiomyopathy by screening the whole mitochondrial genome.
Ruppert V, Nolte D, Aschenbrenner T, Pankuweit S, Funck R, Maisch B.
Department of Internal Medicine and Cardiology, Philipps University Marburg,
Marburg, Germany. ruppert@med.uni-marburg.de
Dilated cardiomyopathy (DCM) is widely accepted as a pluricausal or
multifactorial disease. Because of the linkage between energy metabolism in the
mitochondria and cardiac muscle contraction, it is reasonable to assume that
mitochondrial abnormalities may be responsible for some forms of DCM. We analysed
the whole mitochondrial genome in a series of 45 patients with DCM for
alterations and compared the findings with those of 62 control subjects. A total
of 458 sequence changes could be identified. These sequence changes were
distributed among the whole mitochondrial DNA (mtDNA). An increased number of
novel missense mutations could be detected nearly in all genes encoding for
protein subunits in DCM patients. In genes coding for NADH dehydrogenase subunits
the number of mtDNA mutations detected in patients with DCM was significantly
increased (p < 0.05) compared with control subjects. Eight mutations were found
to occur in conserved amino acids in the above species. The c.5973G > A (Ala-Trp)
and the c.7042T > G (Val-Asp) mutations were located in highly conserved domains
of the gene coding for cytochrome c oxidase subunit. Two tRNA mutations could be
detected in the mtDNA of DCM patients alone. The T-C transition at nt 15,924 is
connected with respiratory enzyme deficiency, mitochondrial myopathy, and
cardiomyopathy. The c.16189T > C mutation in the D-loop region that is associated
with susceptibility to DCM could be detected in 15.6% of patients as well as in
9.7% of controls. Thus, mutations altering the function of the enzyme subunits of
the respiratory chain can be relevant for the pathogenesis of dilated
cardiomyopathy.
PMID: 15120634 [PubMed - indexed for MEDLINE]
102. Eur Heart J. 2004 Apr;25(7):587-610.
Guidelines on the diagnosis and management of pericardial diseases executive
summary; The Task force on the diagnosis and management of pericardial diseases
of the European society of cardiology.
Maisch B, Seferović PM, Ristić AD, Erbel R, Rienmüller R, Adler Y, Tomkowski WZ,
Thiene G, Yacoub MH; Task Force on the Diagnosis and Management of Pricardial
Diseases of the European Society of Cardiology.
Department of Internal Medicine-Cardiology, Philipps University, Marburg,
Germany. bermaisch@aol.com
Comment in:
Eur Heart J. 2005 May;26(10):1046-7.
PMID: 15120056 [PubMed - indexed for MEDLINE]
103. Heart. 2004 May;90(5):e24.
Giant left atrial mass in an asymptomatic patient.
Lamparter S, Moosdorf R, Maisch B.
Department of Internal Medicine and Cardiology, Heart Centre, Philipps University
of Marburg, Marburg, Germany. lamparte@mailer.uni-marburg.de
A large atrial myxoma, attached in an atypical location, was identified in the
left atrium of a 70 year old patient. Although the tumour occupied a large part
of the left atrium the patient remained in sinus rhythm and displayed no
symptoms.
PMCID: PMC1768196
PMID: 15084572 [PubMed - indexed for MEDLINE]
104. Internist (Berl). 2004 Mar;45(3):347-54.
[Significance of aldosterone antagonist therapy]
[Article in German]
Christ M, Grimm W, Maisch B.
Klinik für Innere Medizin, Kardiologie, Philipps-Universität Marburg,
christ_michael@yahoo.de
Since the introduction of ACE-inhibitors into clinical practice, the diuretic
treatment with the classical aldosterone antagonist spironolactone has
disappeared. It was generally believed that chronic treatment with ACE-inhibitors
significantly reduces aldosterone secretion via reduction of angiotensin
II-dependent aldosterone formation. However, aldosterone "escape" occurs: Even
during chronic treatment with ACE-inhibitors, plasma levels of aldosterone rise
again, which is associated with increased cardiovascular risk. Furthermore,
extrarenal actions of aldosterone have been demonstrated, which detrimentally
affect coagulation, autonomic activity, inflammatory signalling, hemodynamics,
and fibrosis, subsequently leading to cardiovascular damage. Recently published
studies (RALES, EPHESUS) convincingly support the concept of detrimental
cardiovascular aldosterone actions even during chronic ACE-inhibition. In
addition to those cardiovascular effects, aldosterone antagonism has beneficial
impacts on ascites, chronic renal disease, renal volume regulation, and
hypokalemia induced by diuretics. Of note, aldosterone dependent mechanisms are
believed to be even involved in essential hypertension, and the value of
aldosterone antagonism is currently tested in those patients. In conclusion, an
old-fashioned, previously abandoned treatment strategy is currently celebrating
its revival.
PMID: 14997312 [PubMed - indexed for MEDLINE]
105. Herz. 2004 Feb;29(1):130.
Echocardiographic diagnosis of ischemic ventricular septal defect in a patient
with acute myocardial infarction.
Kölsch S, Funck RC, Maisch B.
Department of Internal Medicine and Cardiology, Philipps-University Marburg,
Germany. koelsch@mailer.uni-marburg.de
PMID: 14968349 [PubMed - indexed for MEDLINE]
106. Herz. 2004 Feb;29(1):17-25.
[Noninvasive methods in the diagnosis of macro- and microangiopathy of
peripherial and carotid arteries]
[Article in German]
Portig I, Maisch B.
Klinik für Innere Medizin, SP Kardiologie, Angiologie und Intensivmedizin,
Philipps-Universität Marburg, Marburg, Germany.
PURPOSE: Indications and diagnostic value of the most important noninvasive
procedures for the diagnosis of peripheral arterial disease and diseases of the
supraaortic arteries are reviewed in this article with particular emphasis on
cardiologic questions. PERIPHERAL ARTERIAL DISEASE: As compared to coronary
artery disease, peripheral arterial disease has long been addressed as being
negligible in number and importance, a view that had to be reassessed in recent
years. The prevalence of claudication and critical leg ischemia has increased.
Earlier diagnosis and specific therapeutic regimens will be able to prevent or at
least slow progression of the disease and, thereby, major amputation. The
patient's history and physical examination in addition to measurement of the
ankle-brachial index (ABI; determined by dividing the systolic pressure measured
by Doppler ultrasonography of the A. dorsalis pedis or A. tibialis posterior by
that of the A. brachialis) usually allows for the diagnosis of peripheral
arterial disease (ABI < 0.9). If in doubt (ABI > 0.9, but presence of typical
claudication), a treadmill test or additional tests such as pressure-pulse
recording (mechanical oscillography), toe pressure measurements, or duplex
ultrasonography should be performed. When peripheral arterial disease has been
diagnosed, duplex ultrasonography or treadmill testing aids in planning
additional diagnostic procedures and the adequate therapeutic regimen.
Transcutaneous oxymetry is of prognostic value in assessing the tendency of wound
healing in distal limb ulceration and can distinguish between critical limb
ischemia and complicated claudication. Thermography is used to document
functional and organic peripheral arterial occlusions and capillaroscopy to
directly view nail fold capillaries in order to distinguish between primary and
secondary Raynaud's phenomenon. Noninvasive radiologic techniques in the
diagnosis of peripheral arterial disease are also discussed in this journal.
SUPRAAORTIC ARTERIES: Noninvasive diagnostic procedures in assessing disease of
the supraaortic arteries include history-taking, physical examination,
continuous-wave-(cw-)Doppler and color-coded ultrasonography. Cw-Doppler
ultrasonography is still widely used and sufficient in diagnosing moderate to
severe stenosis or occlusion of the carotid artery. B-mode and color-coded
ultrasonography has several advantages over cw-Doppler ultrasonography through
direct visualization of the vascular membrane, perivascular structures, and
intravascular blood flow. Carotid stenosis < 50% and plaque morphology can be
assessed, inflammatory processes, aneurysms, and dissections diagnosed. Increase
in intima-media thickness and echolucent plaques are associated with cerebral
ischemic events and can be diagnosed via duplex sonography. These findings have
great implications in the consultation of patients with atherogenic risk factors.
PMID: 14968338 [PubMed - indexed for MEDLINE]
107. Herz. 2003 Dec;28(8):744-53.
Effects of ACE inhibition versus non-ACE inhibitor antihypertensive treatment on
myocardial fibrosis in patients with arterial hypertension. Retrospective
analysis of 120 patients with left ventricular endomyocardial biopsies.
Brilla CG, Rupp H, Maisch B.
Division of Cardiology, Center of Internal Medicine, Philipps University of
Marburg, Germany. brilla@t-online.de
BACKGROUND AND PURPOSE: In experimental arterial hypertension, left ventricular
hypertrophy (LVH) becomes pathologic with impaired myocardial function if
myocardial fibrosis occurs. Myocardial fibrosis is associated with activated
circulating or local renin-angiotensin-aldosterone systems. The primary objective
of this retrospective study was to determine whether patients with arterial
hypertension treated with angiotensin-converting enzyme inhibitors (ACEI) have
less myocardial fibrosis than patients on non-ACEI treatment. MATERIAL AND
METHODS: We examined left ventricular (LV) endomyocardial biopsies of 97
consecutive patients with hypertensive heart disease due to primary hypertension
treated with either any ACEI for at least 6 months (n = 34; HTN + ACEI) or
non-ACEI antihypertensive drugs (n = 63; HTN). Normal hearts designated for heart
transplantation served as controls (n = 23; CTR). Myocyte diameter (MyoD) and
collagen volume fraction (CVF) were measured by morphometry, and pro-matrix
metalloproteinases (proMMPs) 2 and 9 by zymography. In a subset of 35 patients,
LV myocardial stiffness was determined by left heart catheterization with
calculation of stiffness constant k. RESULTS: In HTN + ACEI or HTN, MyoD (21.8
+/- 0.3 micro m and 22.4 +/- 0.3 micro m, respectively) and CVF (5.3 +/- 0.6% and
7.6 +/- 0.7%, respectively) were increased (p < 0.01) compared with CTR (16.0 +/-
0.4 micro m and 0.5 +/- 0.2%, respectively). In HTN + ACEI, CVF was significantly
lower (p < 0.02) and proMMP 2 was higher (0.063 +/- 0.013 OD/mg) compared with
HTN (0.037 +/- 0.006 OD/mg; p < 0.05) while no significant difference of MyoD was
evident. We found no correlation between CVF and MyoD (r = 0.13; p = 0.47), a
positive correlation between k and CVF (r = 0.71; p < 0.00001), and no
correlation between k and MyoD (r = 0.22; p = 0.24). CONCLUSION: In patients with
hypertensive heart disease, myocyte hypertrophy and myocardial fibrosis are
present. Myocardial fibrosis and not myocyte hypertrophy determines myocardial
stiffness. ACEI appear to diminish myocardial fibrosis associated with enhanced
collagen degradation irrespective of LVH regression.
PMID: 14689110 [PubMed - indexed for MEDLINE]
108. Herz. 2003 Dec;28(8):674-85.
[Arterial hypertension and metabolic syndrome]
[Article in German]
Christ M, Klima T, Maisch B.
Klinik für Innere Medizin, Kardiologie, Angiologie, Intensivmedizin und
Prävention, Philipps-Universität, Marburg, Germany. christ_michael@yahoo.de
BACKGROUND AND THERAPY: The metabolic syndrome comprises a virulent and lethal
group of atherosclerotic risk factors, including dyslipidemia, obesity, systemic
hypertension and insulin resistance. The prevalence of the metabolic syndrome has
continuously grown in industrialized and developing countries during the last
decades, and affects tens of millions of people in Germany and Europe.
Particularly prominent as a risk factor for the development of insulin resistance
is central obesity, which is causally involved in the pathogenesis of insulin
resistance in addition to genetic predisposition. The metabolic syndrome can
easily be diagnosed in clinical practice (guidelines of the WHO and ATP III
panel), and immediate treatment of the metabolic syndrome is mandatory because
those patients are at increased risk to develop overt diabetes mellitus, coronary
artery disease and stroke. The high risk for cardiovascular diseases is supported
by findings that the risk for myocardial infarction in patients with insulin
resistance is as high as the risk of patients after their first myocardial
infarction. Intentional weight reduction reduces abdominal obesity and
beneficially modulates all features of the metabolic syndrome, while the benefits
of aerobic exercise training are discussed controversially. Thus, weight
reduction causally undoes essential features of the metabolic syndrome, but
effects are often not enduring. Therefore, the treatment of cardiovascular risk
factors such as hypertension and dislipidemia is essential. Of note,
antihypertensive treatment is more effective than tight glucose control to reduce
cardiovascular events. Diuretics, ACE-inhibitors and angiotensin II type 1
receptor antagonists are suggested as first line therapeutics. However, at least
two antihypertensives are usually necessary to achieve the suggested goals of
blood pressure reduction. In conclusion, the prevalence of the metabolic syndrome
is continuously growing. Due to its adverse impact on cardiovascular disease,
early detection and aggressive treatment is mandatory to ensure longlasting
benefits for affected patients.
PMID: 14689101 [PubMed - indexed for MEDLINE]
109. Herz. 2003 Dec;28(8):668-73.
Abdominal fat and sympathetic overactivity. From calorie intake to postmenopausal
hypertension.
Rupp H, Maisch B.
Molecular Cardiology Laboratory, Department of Internal Medicine and Cardiology,
Philipps University Marburg, Germany. Rupp@staff.uni-marburg.de
BACKGROUND: Epidemiologic studies have found an association between overweight
and increased mortality arising primarily from cardiovascular disorders. A major
determinant is a chronically raised sympathetic nervous system activity which can
arise from calorie intake-dependent and -independent mechanisms.
Calorie-dependent parameters reflecting sympathetic overactivity are an increased
body fat mass and body mass index. VISCERAL FAT: Although influenced by calorie
intake to a certain extent, visceral fat accumulation is a mechanism which is
determined also by estrogen deficiency (postmenopausal hypertension) or enhanced
corticoid influences. It is hypothesized that excess catecholamines trigger
various adverse processes which, if they persist, can lead or aggravate
hypertension and insulin resistance. Visceral but not peripheral fat mass was
correlated with atherogenic metabolites. EXCESS CATECHOLAMINE SYNDROME: The
present focus on visceral fat accumulation strengthens the concept of an "excess
catecholamine syndrome" of which the "metabolic syndrome" appears as one
consequence. It is proposed to further assess the potential of transthoracic
echocardiography as routine imaging method for the prediction of visceral fat
accumulation and its adverse health consequences.
PMID: 14689100 [PubMed - indexed for MEDLINE]
110. Herz. 2003 Dec;28(8):655-62.
Genetics of human hypertension.
Ruppert V, Maisch B.
Department of Internal Medicine and Cardiology, Philipps University Marburg,
Germany. ruppert@med.uni-marburg.de
BACKGROUND: Hypertension is a multifactorial disease involving interactions among
genetic, environmental, demographic, vascular and neuroendocrine factors.
Essential hypertension is the most frequent diagnosis in this syndrome,
indicating that a monocausal etiology has not been identified. However, a number
of risk factors underlying essential hypertension have also been identified
including age, sex, genetics, demographic factors, and others. Remarkable
progress in molecular biological research has been achieved in clarifying the
molecular basis of Mendelian hypertensive disorders. Causative genes and
chromosomal fragments harboring disease susceptibility genes have been
identified, e. g., for glucocorticoid-remediable aldosteronism, Liddle's
syndrome, mineralocorticoid excess. MOLECULAR GENETIC STUDIES: Molecular genetic
studies have now identified mutations in eight genes that cause Mendelian forms
of hypertension and nine genes that cause Mendelian forms of hypotension in
humans. No single genetic variant has emerged from linkage or association
analyses as consistently related to blood pressure level in every sample and in
all populations. However, a number of polymorphisms in candidate genes have been
associated with differences in blood pressure. Most prominent have been the
polymorphisms in the renin-angiotensin-aldosterone system. CONCLUSION: Essential
hypertension is likely to be a polygenic disorder that results from the
inheritance of a number of susceptibility genes and involves multiple
environmental determinants. These determinants complicate the study of blood
pressure variations in the general population. The complex nature of the
hypertension phenotype makes large-scale studies indispensable, when screening of
familial and genetic factors is intended.
PMID: 14689098 [PubMed - indexed for MEDLINE]
111. Z Kardiol. 2003;92(Suppl 3):III64-7.
[LDL-Apheresis for the treatment of hyperchylomicronemia-induced pancreatitis]
[Article in German]
Sattler AM, Bock K, Schmidt S, Maisch B, Schaefer JR.
Klinik für Innere Medizin-Kardiologie Klinikum der Philipps-Universität, 35033
Marburg, Germany.
Severe hyperchylomicronemia due to defects of lipoprotein lipase or apoC-II is a
rare cause for acute pancreatitis. Food with a high content of fat, as well as
alcoholic or hormonal influences, can lead to excessive hypertriglyceridemia.
Especially hyperchylomicronemia due to hormonal influences during pregnancy are
troublesome. Here, we are confronted with both the risk to the mother as well as
the vital risk to the unborn. Conventional plasma apheresis has been used to
successfully eliminate chylomicrons and, thus, the primary cause of
chylomicron-induced pancreatitis. Most recently, we reported the use of selective
LDL-apheresis in a 24-year-old pregnant woman (thirteenth week of pregnancy), who
was admitted with the signs of acute pancreatitis to our hospital. The patient
was known to have a history of severe hyperchylomicronemia and she had also been
treated several years before for acute pancreatitis by LDL-apheresis. Her
triglycerides were severely elevated (11500 mg/dl) and, in order to achieve a
rapid decrease of chylomicrons, we decided to treat her by selective
LDL-apheresis utilizing HELP-apheresis. The treatment was well tolerated and
within half an hour the patient was free of any abdominal pain. However, due to
the enormous triglyceride load, we needed to change the precipitate filters
several times and at the end of the treatment triglyceride levels were 6600
mg/dl. Under a low-fat diet (<30 gram fat per day), the follow-up was uneventful
and the patient delivered a healthy baby at the end of week 39. We conclude that
LDL-apheresis is a safe and rapid procedure to eliminate chylomicrons in
chylomicron-induced pancreatitis.
PMID: 14663605 [PubMed - indexed for MEDLINE]
112. Circulation. 2003 Dec 9;108(23):2883-91. Epub 2003 Nov 17.
Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy:
results of the Marburg Cardiomyopathy Study.
Grimm W, Christ M, Bach J, Müller HH, Maisch B.
Department of Cardiology, Philipps-University Marburg, Baldingerstrasse, 35033
Marburg, Germany. wolfram.grimm@med.uni-marburg.de
BACKGROUND: Arrhythmia risk stratification with regard to prophylactic
implantable cardioverter-defibrillator therapy is a completely unsolved issue in
idiopathic dilated cardiomyopathy (IDC). METHODS AND RESULTS: Arrhythmia risk
stratification was performed prospectively in 343 patients with IDC, including
analysis of left ventricular (LV) ejection fraction and size by echocardiography,
signal-averaged ECG, arrhythmias on Holter ECG, QTc dispersion, heart rate
variability, baroreflex sensitivity, and microvolt T-wave alternans. During
52+/-21 months of follow-up, major arrhythmic events, defined as sustained
ventricular tachycardia, ventricular fibrillation, or sudden death, occurred in
46 patients (13%). On multivariate analysis, LV ejection fraction was the only
significant arrhythmia risk predictor in patients with sinus rhythm, with a
relative risk of 2.3 per 10% decrease of ejection fraction (95% CI, 1.5 to 3.3;
P=0.0001). Nonsustained ventricular tachycardia on Holter was associated with a
trend toward higher arrhythmia risk (RR, 1.7; 95% CI, 0.9 to 3.3; P=0.11),
whereas beta-blocker therapy was associated with a trend toward lower arrhythmia
risk (RR, 0.6; 95% CI, 0.3 to 1.2; P=0.13). In patients with atrial fibrillation,
multivariate Cox analysis also identified LV ejection fraction and absence of
beta-blocker therapy as the only significant arrhythmia risk predictors.
CONCLUSIONS: Reduced LV ejection fraction and lack of beta-blocker use are
important arrhythmia risk predictors in IDC, whereas signal-averaged ECG,
baroreflex sensitivity, heart rate variability, and T-wave alternans do not seem
to be helpful for arrhythmia risk stratification. These findings have important
implications for the design of future studies evaluating prophylactic implantable
cardioverter-defibrillator therapy in IDC.
PMID: 14623812 [PubMed - indexed for MEDLINE]
113. Clin Appl Thromb Hemost. 2003 Jul;9(3):211-20.
In vitro simulation of therapeutic plasmatic fibrinolysis.
Stief TW, Bünder R, Richter A, Maisch B, Renz H, Fareed J.
Department of Clinical Chemistry, Hospital of Philipps-University Marburg,
Germany. thstief@med.uni-marburg.de
One type of therapy for thromboembolism is plasmatic thrombolysis. Several
plasminogen activators (PA) are clinically available, including urokinase (u-PA),
tissue plasminogen activator (t-PA), streptokinase (SK),
plasminogen-streptokinase-activator-complex (PSAC), or mutants of t-PA such as
reteplase (RP) or tenecteplase (TP). Therapeutic plasmatic fibrinolysis was
simulated, using the PA at relevant plasma concentrations, and plasmin (Pli) and
PA activities were determined. Normal citrated plasma was supplemented with 31 to
1,000 IU/mL u-PA, 0.31 to 20 microg/mL t-PA, 125 to 4,000 IU/mL SK, 12.5 to 400
U/mL PSAC, 125 to 4,000 U/mL RP, or 0.31 to 10 microg/mL TP. Ten IU/mL urokinase
was also incubated with pooled plasma of stroke patients, that was previously
oxidized with the singlet oxygen (1O2) donor chloramine T (CT), to destroy
plasmatic PAI-1 and alpha2-antiplasmin. After 0 to 80 minutes (37 degrees C),
50-microL samples were withdrawn and added to 100 microL 1.5 M arginine, pH 8.7,
and oxidized with 50 microL of 20 mM CT. For determination of plasmin activity,
10 microL thereof was incubated with 150 microL 1.5 M arginine, pH 8.7, and 100
microL 20 mM CT preoxidized (15 minutes 37 degrees C) pooled normal citrate
buffered EDTA-plasma for 30 minutes (37 degrees C). For determination of
[PA+Pli]-activity, arginine was added after this incubation. 25-microL 6 mM
Val-Leu-Lys-pNA were added and deltaA/h at room temperature (RT) was monitored,
using a microtiterplate reader. [PA+Pli]-Pli = PA. The PA concentration required
to induce 25% [ED25] of the maximally inducible Pli-activity in plasma (= 1 U/mL
= 45 mg/L = 0.53 micromol/L active Pli; deltaA = 363 +/- 8 mA/h RT) after 10
minutes (37 degrees C) were 320 IU/mL u-PA, 8 microg/mL t-PA, 140 U/mL PSAC,
6,000 IU/mL SK, 720 U/mL RP, and approximately 150 microg/mL TP. The approximate
activity half-lives of the PA in plasma were 30 minutes for u-PA, 30 minutes for
t-PA, greater than 80 minutes for SK, greater than 80 minutes for PSAC, 50
minutes for RP, and 80 minutes for TP. The present study shows--for the first
time--a combined kinetic in vitro simulation of the plasmatic activity of six
different PAs. At clinically used concentrations, RP induces the highest
plasmatic Pli activity. Due to unselective generation of plasmin in plasma, all
PA are of some danger in inducing severe hemorrhagias. Clinical thrombolysis
might be improved by usage of more physiologic activators of thrombolysis, such
as activators of polymorphonuclear neutrophils.
PMID: 14507109 [PubMed - indexed for MEDLINE]
114. Arch Pathol Lab Med. 2003 Sep;127(9):1207-10.
Cardiac sarcoidosis: cytokine patterns in the course of the disease.
Schoppet M, Pankuweit S, Maisch B.
Department of Internal Medicine and Cardiology, Philipps-University,
Baldingerstrasse, D-35033 Marburg, Germany.
Sarcoidosis is a chronic systemic disease of unknown etiology, which is
characterized by noncaseating epitheloid granulomas usually in multiple organs.
Here we describe changes in cytokine mRNA expression by peripheral blood
mononuclear cells (PBMCs) and changes of cytokine protein levels in plasma over a
time course of 12 months in a patient with sarcoidosis confined to the heart as
diagnosed by endomyocardial biopsy. Mitogen-stimulated PBMCs exhibited a more
T(H)1 cytokine profile at onset of symptoms before immunosuppressive therapy was
initiated, with a change to a T(H)0 response in the course of the disease as
evidenced by multiplex-polymerase chain reaction. In plasma, high levels of
interleukin-6 could be detected by an enzyme-linked immunosorbent assay system,
with rapid decline correlating with immunosuppression and improving clinical
course. These changes may point to a role of T(H)1 and T(H)2 cytokines in the
pathogenesis and the healing process of cardiac sarcoidosis.
PMID: 12946220 [PubMed - indexed for MEDLINE]
115. Heart. 2003 Sep;89(9):1096-103.
Practical aspects of the management of pericardial disease.
Maisch B, Ristić AD.
Department of Internal Medicine-Cardiology, Faculty of Medicine, Philipps
University, Marburg, Germany. BerMaisch@aol.com
PMCID: PMC1767862
PMID: 12923044 [PubMed - indexed for MEDLINE]
116. Am Heart J. 2003 Aug;146(2):372-6.
Prognostic significance of morphometric endomyocardial biopsy analysis in
patients with idiopathic dilated cardiomyopathy.
Grimm W, Rudolph S, Christ M, Pankuweit S, Maisch B.
Department of Cardiology, Hospital of the Philipps-University of Marburg,
Marburg, Germany. Wolfram.Grimm@med.uni-marburg.de
BACKGROUND: To date, considerable controversy exists on the prognostic
significance of morphometric endomyocardial biopsy findings in patients with
idiopathic dilated cardiomyopathy (IDC). METHODS: Quantitative analyses of
interstitial structured tissue, myofibril volume fraction, and myocytic fiber
diameters of left ventricular endomyocardial biopsy specimens were performed in
124 patients with IDC. RESULTS: During 51 +/- 22 months follow-up after left
ventricular endomyocardial biopsy, major arrhythmic events, defined as sustained
ventricular tachycardia (VT), ventricular fibrillation (VF), or sudden cardiac
death, were observed in 24 patients (19%). Death from any cause or heart
transplant was observed in 39 patients (31%). The amount of interstitial
structured tissue, myofibril volume fraction, and myocytic fiber diameters
determined from left ventricular endomyocardial biopsy specimens did not differ
significantly between patients with and patients without major arrhythmic events
or between patients with and patients without transplant-free survival during
follow-up. CONCLUSIONS: Quantitative analysis of the amount of interstitial
structured tissue, myofibril volume fraction, and myocytic fiber diameters in
left ventricular endomyocardial biopsy specimens does not appear to be useful for
predicting arrhythmic events and transplant-free survival in IDC.
PMID: 12891210 [PubMed - indexed for MEDLINE]
117. J Cardiovasc Electrophysiol. 2003 Aug;14(8):819-24.
Prognostic significance of heart rate turbulence following ventricular premature
beats in patients with idiopathic dilated cardiomyopathy.
Grimm W, Schmidt G, Maisch B, Sharkova J, Müller HH, Christ M.
Department of Cardiology, Hospital of the Philipps-University of Marburg,
Marburg, Germany. Wolfram.Grimm@med.uni-marburg.de
Heart Rate Turbulence in Dilated Cardiomyopathy. INTRODUCTION: The aim of this
study was to investigate the prognostic significance of heart rate turbulence
(HRT) characterized by HRT onset and slope after ventricular premature beats in
patients with idiopathic dilated cardiomyopathy (IDC). METHODS AND RESULTS:
Blinded HRT analysis was performed in 242 patients with IDC who were enrolled in
the Marburg Cardiomyopathy database between 1992 and 2000. During 41 +/- 23
months of follow-up, 54 patients (22%) died or underwent heart transplant. On Cox
univariate regression analysis, abnormal HRT onset, HRT slope, HRT onset combined
with HRT slope, left ventricular (LV) ejection fraction, LV size, and New York
Heart Association (NYHA) functional class III showed a significant association
with total mortality or the need for heart transplant. On multivariate analysis,
abnormal HRT onset identified patients without transplant-free survival, as did
LV size and NYHA class III heart failure. Major arrhythmic events were observed
in 42 patients (17%) during follow-up. On univariate analysis, abnormal HRT
onset, HRT onset combined with HRT slope, male sex, NYHA class III, LV ejection
fraction, and LV size were associated with a higher incidence of major arrhythmic
events. On multivariate analysis, only LV ejection fraction remained as a
significant arrhythmia risk predictor, with a relative risk of 2.2 per 10%
decrease in ejection fraction (95% confidence interval 1.5-3.2). CONCLUSION: In
this selected patient population with IDC, HRT onset is a significant predictor
of transplant-free survival, as are LV size and NYHA class. For arrhythmia risk
stratification, however, only LV ejection fraction remained a significant risk
predictor on multivariate analysis.
PMID: 12890042 [PubMed - indexed for MEDLINE]
118. Hum Pathol. 2003 Jul;34(7):725-8.
Acute parvovirus B19 infection associated with myocarditis in an immunocompetent
adult.
Lamparter S, Schoppet M, Pankuweit S, Maisch B.
Department of Internal Medicine and Cardiology, Philipps-University, Marburg,
Germany.
Inflammatory heart disease is causally linked with progressive left ventricular
dysfunction and congestive heart failure. In childhood, infection with parvovirus
B19 (PVB19) is usually benign, causing erythema infectiosum. However, severe
fetal PVB19 infection may be associated with hydrops fetalis and fetal death
caused by myocarditis. Here we report a PVB19-induced myocarditis in a previously
healthy 37-year-old patient admitted to the hospital because of chest pain and
dyspnea due to left ventricular dysfunction. Four weeks after the onset of
symptoms, we found lymphocytic infiltrates and PVB19 genome in left ventricular
endomyocardial biopsy specimens. Consistently, acute PVB19 infection was
indicated serologically by elevated IgM titers and the presence of PVB19 genome
in peripheral blood lymphocytes. In conclusion, PVB19 infection may be
complicated by acute myocarditis in immunocompetent adults. Because PVB19
myocarditis may progress to chronic dilated cardiomyopathy, early diagnosis by
endomyocardial biopsy is important to initiate anti-inflammatory treatment.
PMID: 12874772 [PubMed - indexed for MEDLINE]
119. Ann Noninvasive Electrocardiol. 2003 Apr;8(2):127-31.
Heart rate turbulence following ventricular premature beats in healthy controls.
Grimm W, Sharkova J, Christ M, Schneider R, Schmidt G, Maisch B.
Department of Cardiology, Munich University of Technology, Germany.
Wolfram.Grimm@med.uni-marburg.de
BACKGROUND: Heart rate turbulence (HRT) has recently been described as a strong,
independent risk stratifier in postinfarct patients. To date, however, the
incidence of false positive HRT findings in adults is unknown. Therefore, we
performed a blinded, retrospective analysis of HRT in a prospectively collected
database of 110 apparently healthy persons to determine the prevalence and
clinical significance of abnormal HRT findings in healthy controls using
previously published cut-off values. METHODS AND RESULTS: The study included 43
out of 110 apparently healthy adults, in whom a sufficient number of ventricular
premature beats were available for HRT analysis on 24-hour Holter recordings. The
HRT slope was dichotomized at 2.5 ms per R-R interval and HRT onset was
dichotomized at 0% using previously established criteria to define an abnormal
HRT analysis in postinfarct patients. Using these definitions, abnormal HRT
results were found in 2 out of 43 controls (5%) for HRT slope and in 8 out of 43
controls (19%) for HRT onset without any cardiac deaths during 32 +/- 15 months
follow-up. CONCLUSIONS: The incidence of false positive HRT results in healthy
middle-aged volunteers is low for HRT slope (5%), but not for HRT onset (19%)
when previously published cut-off values are used to define abnormal HRT results.
Thus, HRT slope dichotomized at 2.5 ms per R-R interval, but not HRT onset
dichotomized at 0%, may be used as a relatively specific tool for risk
stratification in middle-aged persons.
PMID: 12848793 [PubMed - indexed for MEDLINE]
120. Hum Pathol. 2003 May;34(5):497-503.
Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens.
Pankuweit S, Moll R, Baandrup U, Portig I, Hufnagel G, Maisch B.
Department of Internal Medicine'Cardiology and Patholody, Philipps'University
Marburg, Marburg, Germany.
Although enteroviruses have long been considered the most common cause of
inflammatory heart muscle diseases, parvovirus B19 (PVB19) is emerging as a new
and important candidate for myocarditis and dilated cardiomyopathy with
inflammation (DCMi) and without inflammation (DCM). We investigated left
ventricular endomyocardial biopsy specimens from 110 patients with suspected
inflammatory heart disease for the presence of PVB19, Coxsackie virus (CVB), and
adenovirus (Ad2) genome by polymerase chain reaction. Diagnosis of myocarditis
(36 patients), DCM (18 patients), DCMi (13 patients), and perimyocarditis (12
patients) was made by immunohistochemical and histopathological investigation of
endomyocardial biopsy specimens. A control group consisting of patients with
arterial hypertension was also investigated. Prevalence of the PVB19 genome in
endomyocardial biopsy specimens was highest in patients with DCMi (3 of 13) and
patients with myocarditis (7 of 36); in patients with DCM and perimyocarditis,
prevalence was 3 of 13 and 2 of 12, respectively. In patients with resolved
myocarditis, no PVB19 DNA was detected; in patients with no inflammation and
controls, prevalence was only 4% and 7%, respectively. CVB-RNA was detected in
endomyocardial biopsy specimens from 3 of 37 patients with myocarditis; Ad2-DNA
was found in 1 patient with DCM and 1 patient with perimyocarditis. These
findings suggest an association of the PVB19 genome in endomyocardial biopsy
specimens of adults with the development of DCM, DCMi, and chronic myocarditis
more frequently than previously expected. PVB19 should therefore be recognized as
a potential cardiotropic pathogen in patients of all ages.
PMID: 12792925 [PubMed - indexed for MEDLINE]
121. Herz. 2003 May;28(3):257-61.
[Excessive hyperchylomicronemia--a rare cause of acute retrosternal and
epigastric pain in pregnancy]
[Article in German]
Sattler AM, Bock K, Schmidt S, Maisch B, Schaefer JR.
Klinik für Innere Medizin - Kardiologie, Klinikum der Philipps-Universität,
Marburg. alexander.sattler@mailer.uni-marburg.de
CASE REPORT: A 24-year-old woman in her 13th gestational was admitted to our
department with acute retrosternal and epigastric pain. She had been transferred
from the gynecologic department where she was treated for vaginal bleeding
because of abortus imminens. A cardiac cause was excluded by ECG and echo.
Clinical chemistry and abdominal ultrasound confirmed the diagnosis of acute
pancreatitis. The woman was known in our outpatient department for
hyperchylomicronemia and had already had an earlier episode of acute pancreatitis
under oral contraception years ago. At current admission, triglycerides were
11,500 mg/dl. To reduce plasma triglycerides, selective lipid apheresis was
performed. Apheresis was well tolerated, and the patient became free of pain
within the first 30 min of treatment. Triglycerides decreased to 6,600 mg/dl at
this session. Keeping to a low-fat diet (< 30 g fat per day), the patient
remained healthy and completed pregnancy with the delivery of a healthy girl in
her 39th week of pregnancy. CONCLUSION: Selective lipid apheresis is a safe and
effective option in the treatment of hyperlipidemic pancreatitis, even in
pregnant patients.
PMID: 12759743 [PubMed - indexed for MEDLINE]
122. Herz. 2003 May;28(3):196-208.
[Pregnancy and cardiomyopathies]
[Article in German]
Maisch B, Lamparter S, Ristić A, Pankuweit S.
Klinik für Innere Medizin-Kardiologie, Philipps-Universität, Marburg, Germany.
BerMaisch@aol.com
This overview on the topic of cardiomyopathy and gestation comprises the
diagnostic and therapeutic options of patients with preexistent cardiomyopathies
(dilated, hypertrophic, inflammatory, and others) and with cardiomyopathies which
have been discovered during or in the 6 months following delivery.
CARDIOMYOPATHIES PREEXISTENT BEFORE GESTATION: If cardiomyopathy is present
before an intended gestation, the couple should be advised against pregnancy
because of the high risk of deterioration both during gestation and peripartum.
If pregnancy occurs, according to ESC (European Society of Cardiology)
recommendations termination should be advised if the ejection fraction is < 50%
and/or the LV dimensions are definitely above normal. If termination is refused,
the patient must be checked regularly by both gynecologist and cardiologist, by
the latter to perform regular echocardiograms. Termination is not recommended for
the hypertrophic (nonobstructive) cardiomyopathies. If atrial fibrillation
occurs, anticoagulation with low molecular weight heparin and digoxin and/or
Betablockers are recommended for rhythm and rate control. PERIPARTUM
CARDIOMYOPATHIES: In peripartum cardiomyopathies, which are discovered clinically
postpartum, inflammation of the myocardium sometimes associated with pericarditis
is frequently found. For those patients, we recommend heart catheterization with
endomyocardial biopsy to allow for the exact diagnosis of the underlying cardiac
process (inflammatory and/or viral vs autoreactive myocarditis or noninflammatory
or nonviral [= idiopathic] forms). This diagnostic algorithm, which we recommend
for any form of dilated cardiomyopathy, bears impact on treatment options beyond
the mere heart failure therapy that should be instigated anyhow.
PMID: 12756477 [PubMed - indexed for MEDLINE]
123. J Sleep Res. 2003 Jun;12(2):161-7.
Association of right ventricular dysfunction and Cheyne-Stokes respiration in
patients with chronic heart failure.
Christ M, Grimm W, Rostig S, Klima T, Fenske H, Becker HF, Vogelmeier C, Maisch
B.
Klinik für Innere Medizin, Kardiologie, Philipps Universität Marburg, Marburg,
Germany. christ_michael@yahoo.de
Cheyne-Stokes respiration (CSR) is present in up to 40% of patients with
congestive heart failure (CHF) and is an independent risk factor for increased
overall mortality. We examined whether CSR is associated with right ventricular
(RV) dysfunction in CHF patients. Parameters of RV function were assessed by
two-dimensional echocardiography and tissue velocity imaging in 42 patients (aged
23-75 years) with a left ventricular (LV) ejection fraction below 40%.
Respiratory polygraphy revealed CSR with an central apnea-hypopnea index (CAHI)
>10 h-1 in 13 of the 42 patients (31%). Demographic characteristics did not
differ among the patient groups. The velocity of the tricuspid annular systolic
motion (TASM), a parameter reflecting systolic RV function, was significantly
reduced in CHF patients with CSR (10.5 +/- 2.3 cm s-1) compared with those
without CSR (15.0 +/- 5.1 cm s-1, P = 0.004), and was inversely associated with
the CAHI (y = 15.2-0.2x; r = 0.46, P = 0.003). The RV dimensions were
significantly increased and the fractional RV area changes significantly reduced
in CHF patients with CSR (33 +/- 17 versus 48 +/- 20%; P = 0.04). Doppler
parameters of pulmonary artery flow indicate higher pulmonary artery pressures in
CSR patients compared with patients without CSR, which is also reflected by an
increased RV free-wall thickness in CSR patients (6.5 +/- 1.1 vs. 5.3 +/- 1.3 mm;
P = 0.05). Parameters of systolic LV function, forced expiratory volume in 1 s
(FEV1), and PaO2 and PaCO2 were not different among patients with or without CSR.
In conclusion, CSR is associated with depressed systolic RV function and
increased RV dimensions in CHF patients. Future studies will show whether
optimized treatment of CSR will improve RV function.
PMID: 12753354 [PubMed - indexed for MEDLINE]
124. Pacing Clin Electrophysiol. 2003 Jan;26(1 Pt 2):155-7.
How many patients with dilated cardiomyopathy may potentially benefit from
cardiac resynchronization therapy?
Grimm W, Sharkova J, Funck R, Maisch B.
Department of Cardiology, Hospital of the Philipps-University of Marburg,
Baldingerstrasse, 35033 Marburg, Germany. Wolfram.Grimm@med.uni-marburg.de
The clinical and electrocardiographic Marburg Cardiomyopathy database was
analyzed to identify potential candidates for cardiac resynchronization therapy
(CRT) with biventricular or left ventricular pacing among 566 patients with
dilated cardiomyopathy (DCM). All of the following restrictive selection criteria
were fulfilled by 38 patients (7%): NYHA functional class > or = 3 (n = 193,
34%), left ventricular ejection fraction (LVEF) < 30% (n = 238, 42%), sinus
rhythm (n = 437, 77%), left bundle branch block (LBBB, n = 142, 25%), and QRS
duration > or = 150 ms (n = 136, 24%). In 78 of the 566 patients (14%) all of the
following less restrictive selection criteria were fulfilled: NYHA functional
class > or = 3 (n = 193, 34%), LVEF < 35% in presence of any underlying rhythm (n
= 326, 58%), QRS duration > or = 120 ms with right or left bundle branch block (n
= 223, 39%). Thus, between 7% and 14% of patients with DCM were candidates for
CRT depending on the application of strict versus less restrictive selection
criteria.
PMID: 12687803 [PubMed - indexed for MEDLINE]
125. J Clin Endocrinol Metab. 2003 Mar;88(3):1024-8.
Increased osteoprotegerin serum levels in men with coronary artery disease.
Schoppet M, Sattler AM, Schaefer JR, Herzum M, Maisch B, Hofbauer LC.
Department of Internal Medicine, Philipps University, Baldingerstrasse, D-35033
Marburg, Germany.
Osteoprotegerin (OPG) regulates osteoclast and immune functions and appears to
represent a protective factor for the vascular system. However, the role of OPG
in human atherosclerosis has not been evaluated. In this study, we assessed OPG
serum levels in 522 age-matched men who, on the basis of coronary angiography,
had either absence of coronary artery disease (CAD) or presence of single-vessel
disease, double-vessel disease, or severe triple-vessel disease. OPG serum levels
were positively correlated with age (r = 0.28; P < 0.001) and were higher in men
with diabetes mellitus (P < 0.01). OPG serum levels in men without CAD were 5.4
+/- 2.0 pmol/liter, compared with 6.1 +/- 2.1 pmol/liter in single-vessel disease
(P < 0.005), 5.9 +/- 2.4 in double-vessel disease (P < 0.05), and 6.3 +/- 2.3
pmol/liter in triple-vessel disease (P < 0.001). Moreover, OPG serum levels were
positively correlated with the severity of CAD as determined by a CAD scoring
system (r = 0.17; P < 0.01). In conclusion, our data underline that OPG serum
levels are associated with the severity of CAD and are increased in elderly men
and patients with diabetes mellitus. We conclude that increased OPG serum levels
may reflect advanced cardiovascular disease in men.
PMID: 12629080 [PubMed - indexed for MEDLINE]
126. Herz. 2002 Dec;27(8):750-9.
Sudden cardiac death in dilated cardiomyopathy -- therapeutic options.
Grimm W, Maisch B.
Department of Cardiology, Hospital of the Philipps University Marburg, Germany.
Wolfram.Grimm@med.uni-marburg.de
BACKGROUND: Despite routine use of angiotensin-converting enzyme (ACE)
inhibitors, beta-blockers and spironolactone in patients with heart failure due
to dilated cardiomyopathy (DCM), these patients still have a considerable annual
mortality rate of 5-10%. Sudden unexpected death accounts for up to 50% of all
deaths and is most often due to rapid ventricular tachycardia or ventricular
fibrillation and less often due to bradyarrhythmias or asystole. THERAPEUTIC
OPTIONS: The use of beta-blockers in patients with heart failure has been shown
to improve overall mortality considerably. This survival benefit has been
demonstrated for bisoprolol, metoprolol and carvedilol. Therefore, one of these
three beta-blocking agents should be administered routinely starting with low
doses in all patients with New York Heart Association (NYHA) class II or III
heart failure in addition to ACE inhibitors, unless there is a contraindication
to beta-blocker use. In addition, NYHA class IV heart failure patients have been
shown to benefit from carvedilol therapy, if tolerated. The conflicting results
of GESICA and CHF-STAT studies do not support a strategy of "prophylactic"
amiodarone therapy in patients with DCM in order to prevent sudden cardiac death.
Despite growing evidence that implantable cardioverter defibrillator (ICD)
therapy results in improved overall survival py preventing sudden cardiac death
in patients at high risk for serious arrhythmic events, arrhythmia risk
stratification with regard to prophylactic ICD implantation remains highly
controversial in patients with DCM. CONCLUSION: This review describes potential
arrhythmia mechanisms in DCM and summarizes the results of antiarrhythmic drug
trials and of prophylactic ICD trials in patients with heart failure as well as
our knowledge concerning arrhythmia risk stratification in patients with DCM.
PMID: 12574892 [PubMed - indexed for MEDLINE]
127. Arch Pathol Lab Med. 2003 Jan;127(1):98-101.
CD83+ dendritic cells in inflammatory infiltrates of Churg-Strauss myocarditis.
Schoppet M, Pankuweit S, Maisch B.
Department of Internal Medicine and Cardiology, Philipps-University,
Baldingerstrasse, D-35033 Marburg, Germany. schoppet@mailer.uni-marburg.de
Churg-Strauss syndrome (CSS) is characterized by a granulomatous vasculitis of
multiple organs with the cardiovascular system being commonly affected. The
initiation of the disease is not well understood, but immunologic phenomena are
thought to contribute at least partially to the syndrome. We have studied
endomyocardial biopsy specimens from a patient with CSS and eosinophilic
myocarditis for characterization of infiltrating immune cells by
immunofluorescence staining techniques and found a major population to be
composed of CD83+CD14-CD19-CD56-HLA-DR+ dendritic cells (DCs). Further phenotypic
characterization of infiltrating CD83+ cells in CSS myocarditis showed a surface
profile reminiscent of immature DCs. In the same patient, the cytokine expression
pattern of mitogen-stimulated peripheral blood mononuclear cells revealed a TH0
response as evidenced by multiplex polymerase chain reaction, and interleukin-5
levels were elevated in plasma analyzed by enzyme-linked immunosorbent assay.
Thus, in this case of CSS myocarditis, we found DC-like cells in myocardial
lesions, which may suggest that DCs are involved in the inflammatory process
possibly triggered or sustained by an imbalance of DCs and their failure to
confer tolerance to self-antigens.
PMID: 12521377 [PubMed - indexed for MEDLINE]
128. Int J Cardiovasc Intervent. 2000 Sep;3(3):185-188.
Acute severe thrombocytopenia after c7E3 Fab (abciximab) therapy in a patient
with unstable angina and stenting of the right coronary artery. Occurrence of
subacute stent thrombosis and safe readministration of the GPIIb/IIIa inhibitor
tirofiban.
Simon BC, Herzum M, Klisch A, Schürmann M, Zeiler T, Kretschmer V, Maisch B.
Department of Cardiology, University Hospital, Philipps-University of Marburg,
Marburg, Germany.
This paper reports a case of acute severe thrombocytopenia (platelet count: 1 x
10(9)/liter) occurring within minutes of an initial abciximab bolus during
coronary angioplasty and stenting in a patient with unstable angina. After six
days with platelets again in the normal range the patient developed stent
thrombosis. The stent was reopened and the glycoprotein receptor inhibitor
tirofiban (Aggrastat) was administered without any adverse effects on platelet
count. Antibodies against heparin-platelet factor 4 complexes could be excluded.
Allo- and autoantibodies (IgG, IgA, IgM) directed against platelets with and
without binding of abciximab could not be detected by indirect and direct
platelet fluorescence antiglobulintest. A possible activation or lysis of the
platelets by abciximab could also be excluded by an in vitro bleeding test
investigating the effect of abciximab on heparin and citrate blood of the patient
and two healthy donors. The mechanisms of abciximab-induced thrombocytopenia in
this case remain unclear. The possible mechanisms are discussed.
PMID: 12470370 [PubMed - as supplied by publisher]
129. Front Biosci. 2003 Jan 1;8:s39-67.
Human viral cardiomyopathy.
Maisch B, Ristic AD, Portig I, Pankuweit S.
Department of Internal Medicine-Cardiology, Philipps-University Marburg, Germany.
maisch@Mailer.Uni-Marburg.DE
Viral infection of the heart is relatively common, usually asymptomatic and has a
spontaneous and complete resolution. It can, however, in rare cases, lead to
substantial cardiac damage, development of viral cardiomyopathy and congestive
heart failure. Viral cardiomyopathy is defined as viral persistence in a dilated
heart. It may be accompanied by myocardial inflammation and then termed
inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no
inflammation is observed in the biopsy of a dilated heart (<14 lymphocytes and
macrophages/mm ) the term viral cardiomyopathy or viral persistence in dilated
cardiomyopathy should be applied. The diagnosis of myocarditis and viral
cardiomyopathy can be made only by endomyocardial biopsy, implementing the
WHO/WHF criteria, and PCR techniques for identification of viral genome. The most
frequent cardiotropic viruses detected by endomyocardial biopsy are Parvo B19,
enteroviruses, adenoviruses, cytomegalovirus, and less frequently Epstein-Barr
virus, and influenza virus.
PMID: 12456345 [PubMed - indexed for MEDLINE]
130. Herz. 2002 Nov;27(7):669-76.
Pathophysiology of cardiac inflammation: molecular mechanisms.
Pankuweit S, Portig I, Maisch B.
Department of Internal Medicine, University of Marburg, Germany.
pankuweit@mailer.uni-marburg.de
BACKGROUND: Inflammatory processes induced by rival infection are believed to be
one of the major pathogenetic mechanisms in inflammatory dilated cardiomyopathy.
Although the reason for progression to myocardial failure is not fully
understood, postulated mechanisms include persistent viral infection alone or in
combination with autoimmune processes. PATHOPHYSIOLOGY: Murine models of
myocarditis have provided insight into the mechanisms by which autoimmune
responses to cardiac antigens, probably in response to viral infection of the
myocardium, arise and cause tissue pathology. Organ-specificity, cross-reactivity
between microbial agents and cardiac tissue, and induction of tolerance to
self-antigen are issues still at stake. In addition, cytokines mediate activation
and effector phase of innate and specific immunity, which are both important in
controlling viral infection. The innate immune response not only has an important
protective function but also serves to initiate and regulate subsequent specific
immune responses. In man, on the one hand specific T cells and antibodies against
different cardiac tissue components have been demonstrated in myocardium and sera
of patients with inflammatory cardiomyopathy, and on the other hand viral genome
has been identified in endomyocardial biopsies due to the rapid development of
new molecular biological techniques such as polymerase chain reaction (PCR),
southern blot analysis and in-situ hybridization. But it is still a mater of
debate whether virus infection itself, the ensuing immune response, or both,
contribute to the deterioration of left ventricular function. CONCLUSION: Taking
these mechanisms into account, screening for viral genome by PCR and detection of
inflammatory infiltrates by immunohistochemistry are considered crucial for the
establishment of a definite diagnosis thereby allowing for the initiation of
specific therapeutic strategies.
PMID: 12439638 [PubMed - indexed for MEDLINE]
131. Herz. 2002 Nov;27(7):637-48.
Molecular mechanisms involved in atherosclerosis.
Soufi M, Sattler AM, Maisch B, Schaefer JR.
Department of Internal Medicine, Philipps-University Marburg, Germany.
BACKGROUND: Research in atherosclerosis is a good example how helpful different
disciplines such as clinicians, epidemiologists and basic science can
collaborate. In recent years our knowledge on cellular and subcellular mechanisms
involved in initiation and progress of atherosclerosis has expanded due to the
shared knowledge of different disciplines and thanks to new technologies in
molecular biology. PATHOPHYSIOLOGY OF LDL AND HDL METABOLISM: The understanding
of the molecular basis of inborn errors of LDL metabolism - such as familial
hypercholesterolemia due to a defect of the LDL receptor - provided us new
insights in physiology and pathophysiology of LDL metabolism. Most recently we
have learned much about the vasoprotective HDL cholesterol. HDL is the major
player in reverse cholesterol transport and some of its receptors such as ABCA1
and SR-BI were identified. This knowledge gives us a deeper understanding of the
complex system which performs reverse cholesterol transport from peripheral
tissue and the vessel wall back to the liver. PLAQUE FORMATION: Furthermore the
process of formation and progression of the atherosclerotic plaque has been the
focus of recent research. The stability or instability of plaques is depending on
the complex interaction of adhesion molecules, monocytes, macrophages,
endothelial cells, cytokines, transmitters and proteinases. Since we are unable
to prevent plaque formation completely, the stabilization of plaques is a major
goal for the coming years. Despite some success (such as the use of statines and
ACE inhibitors) there is still a long way to go.
PMID: 12439635 [PubMed - indexed for MEDLINE]
132. Herz. 2002 Nov;27(7):621-36.
The use of partial fatty acid oxidation inhibitors for metabolic therapy of
angina pectoris and heart failure.
Rupp H, Zarain-Herzberg A, Maisch B.
Molecular Cardiology Laboratory, Department of Internal Medicine and Cardiology,
University of Marburg, Germany. Rupp@mailer.uni-marburg.de
BACKGROUND: Partial fatty acid oxidation inhibitors have raised great interest
since they are expected to counteract a dysregulated gene expression of
hypertrophied cardiocytes. Some of these compounds have been developed for
treating non-insulin-dependent diabetes mellitus and stable angina pectoris. A
shift from fatty acid oxidation to glucose oxidation leads to a reduced
gluconeogenesis and improved economy of cardiac work. An increased glucose
oxidation can be achieved with the following enzyme inhibitors: etomoxir,
oxfenicine, methyl palmoxirate, S-15176, metoprolol, amiodarone, perhexiline
(carnitine palmitoyltransferase-1); aminocarnitine, perhexiline (carnitine
palmitoyltransferase-2); hydrazonopropionic acid (carnitine-acylcarnitine
translocase); MET-88 (gamma-butyrobetaine hydroxylase); 4-bromocrotonic acid,
trimetazidine, possibly ranolazine (thiolases); hypoglycin (butyryl-CoA
dehydrogenase); dichloroacetate (pyruvate dehydrogenase kinase). CLINICAL TRIALS
with trimetazidine and ranolazine showed that this shift in substrate oxidation
has an antianginal action. Etomoxir and MET-88 improved the function of
overloaded hearts by increasing the density of the Ca(2+) pump of sarcoplasmic
reticulum (SERCA2). The promoters of SERCA2 and alpha-myosin heavy-chain exhibit
sequences which are expected to respond to transcription factors responsive to
glucose metabolites and/or peroxisome proliferator-responsive element (PPAR)
agonists. Further progress in elucidating novel compounds which upregulate SERCA2
expression is closely linked to the characterization of regulatory sequences of
the SERCA2 promoter.
PMID: 12439634 [PubMed - indexed for MEDLINE]
133. Pflugers Arch. 2002 Oct;445(1):32-9. Epub 2002 Aug 1.
Characterization of sucrose-induced changes in cardiac phenotype.
Rupp H, Wahl R, Maisch B, Hansen M.
Department of Internal Medicine and Cardiology, Karl-von-Frisch-Strasse 1, 35033
Marburg, Germany. Rupp@mailer.uni-marburg.de
The neuroendocrine factors responsible for long-term regulation of cardiac
contractile performance remain ill defined. We examined influences of diet on the
expression of myosin isozymes, sarcoplasmic reticulum (SR) Ca(2+) uptake and
serum parameters. Dietary regimens (ad libitum feeding, intermittent fasting and
32% sucrose feeding) were used to alter the neurohumoral status of rats.
Intermittent fasting decreased serum insulin levels ( P<0.05) and was associated
with decreased SR Ca(2+) uptake and myosin V1 proportion ( P<0.05). Sucrose (32%)
feeding increased myosin V1 of fasted and ad libitum fed rats ( P<0.05) but had
no effect on insulin or SR Ca(2+) uptake. Expression of the alpha-myosin heavy
chain correlated with serum insulin. Treatment of sucrose-fed rats with the
sympatholytic compound moxonidine and the hypoglycaemic compounds BM13.907 and
ciglitazone partially prevented the increase in myosin V1 ( P<0.05) but had no
effect on SR Ca(2+) uptake and insulin. The data show that adrenergic activity
and metabolic signals are important for an increase in myosin V1 in sucrose-fed
rats, which can be associated with an unaltered SR Ca(2+) uptake rate.
PMID: 12397384 [PubMed - indexed for MEDLINE]
134. Eur Heart J. 2002 Oct;23(20):1625-31.
Neoplastic pericardial effusion. Efficacy and safety of intrapericardial
treatment with cisplatin.
Maisch B, Ristić AD, Pankuweit S, Neubauer A, Moll R.
Department of Internal Medicine-Cardiology, Philipps University, Marburg,
Germany.
AIMS: To evaluate the clinical efficacy, safety, and long-term effect of
intrapericardial treatment with cisplatin in large neoplastic pericardial
effusions. METHODS AND RESULTS: Out of the registry of 260 patients undergoing
pericardiocentesis, 42 patients with neoplastic pericardial effusion (69% males,
mean age 58.8+/-13.2 years) were selected for treatment with cisplatin (single
instillation of 30 mg.m(-2) x 24h(-1)) in addition to the tumour-specific
systemic chemotherapy. All patients underwent clinical examination,
echocardiography, pericardiocentesis, pericardioscopy, and epicardial biopsy.
Pericardial effusion and biopsy analyses included biochemistry, cytology,
serology, microbiology, histology, immunohistology, and PCR. The following
malignancies were established: lung cancer, 52.4%; breast cancer, 19.0%;
Hodgkin's disease, 4.8%; oesophageal cancer, 2.4%; mesothelioma, 2.4%; colon
cancer, 4.8%; and undifferentiated cancer of unknown origin, 14.2%. Cisplatin
appeared to prevent recurrence of pericardial effusion during the first 3 months
of the follow-up in 92.8%, and after 6 months in 83.3% of the patients. Lung
cancer patients had fewer effusion relapses at the 6 months follow-up (4.5%) than
breast cancer patients (37.5%)(P<0.05). Myocardial ischemia occurred after 1/42
cisplatin instillations, but there were no other complications. CONCLUSION:
Intrapericardial treatment with cisplatin appeared to successfully prevent
recurrences of neoplastic pericardial effusion. The treatment was more successful
in lung than in breast cancer patients.
PMID: 12323163 [PubMed - indexed for MEDLINE]
135. Eur Heart J. 2002 Oct;23(19):1503-8.
Intrapericardial treatment of autoreactive pericardial effusion with
triamcinolone; the way to avoid side effects of systemic corticosteroid therapy.
Maisch B, Ristić AD, Pankuweit S.
Department of Internal Medicine-Cardiology, Philipps University, Marburg,
Germany.
Comment in:
Eur Heart J. 2002 Oct;23(19):1481-2.
AIMS: To evaluate efficacy and safety of intrapericardial treatment with the
crystalloid corticosteroid triamcinolone in autoreactive pericardial effusion.
METHODS AND RESULTS: Two hundred and sixty consecutive patients with
pericarditis/myopericarditis underwent pericardiocentesis, pericardioscopy
(Storz-AF1101B1), and epicardial biopsy with pericardial fluid and tissue
analyses. By polymerase chain reaction for cardiotropic viruses/bacteria in
pericardial effusion and epicardial biopsies as well as by immunohistochemistry
and immunocytochemistry of epicardial and endomyocardial biopsies, 84/260
patients were classified as autoreactive pericarditis and underwent
intrapericardial instillation of triamcinolone (group 1: 54 patients, 50% males,
mean age 48.9 +/- 14.3 years, triamcinolone 600 mg x m(-2) x 24 h(-1); group 2:
30 patients, 46.7% males, mean age 52.5 +/- 12.7 years, triamcinolone 300 mg x
m(-2) x 24 h(-1)). Intrapericardial administration of triamcinolone resulted in
symptomatic improvement and prevented effusion recurrence in 92.6% vs 86.7% of
the patients after 3 months and in 86.0% vs 82.1% after 1 year in groups 1 and 2,
respectively (P>0.05). There were no treatment-related acute complications.
During the follow-up, 29.6% of the patients developed transitory iatrogenic
Cushing syndrome in group 1 in contrast to 13.3% in group 2 (P<0.05). Conclusion
Intrapericardial treatment of autoreactive pericarditis with 300 mg x m(-2) x 24
h(-1) of triamcinolone prevented recurrence of symptoms and relapse of effusion
as effectively as the 600 mg x m(-2) x 24 h(-1) regimen, but with significantly
fewer side effects. Copyright 2002 The European Society of Cardiology
PMID: 12242070 [PubMed - indexed for MEDLINE]
136. J Periodontol. 2002 Aug;73(8):868-70.
Detection of Porphyromonas gingivalis DNA in aortic tissue by PCR.
Stelzel M, Conrads G, Pankuweit S, Maisch B, Vogt S, Moosdorf R, Flores-de-Jacoby
L.
Department of Periodontology, University of Marburg, Germany.
stelzel@med.uni-marburg.de
BACKGROUND: Periodontopathogens may play a role in the etiology of cardiovascular
disease. The aim of the present study was to investigate biopsies of aortic
tissue for the presence of periodontopathogens. METHODS: Samples taken from the
aortas of 26 patients connected to a heart-lung machine during open-heart surgery
were analyzed in a gene-diagnostics laboratory by polymerase chain reaction.
Immediately after biopsy, the samples were transferred into liquid nitrogen and
stored at -80 degrees C. 16S rRNA gene-directed primers were used for general
detection of bacterial cells, and specific primers for detection of Porphyromonas
gingivalis and Actinobacillus actinomycetemcomitans. Questionable amplificons
were verified by Southern hybridization using DNA probes. RESULTS: Bacterial DNA
was found in 23 of 26 (88.5%) samples, in most cases only in concentrations
around the detection limit. Four samples were clearly positive for P. gingivalis;
A. actinomycetemcomitans was not detected. CONCLUSION: These results might
indicate a link between periodontopathogens entering the cardiovascular system
and cardiovascular disease.
PMID: 12211495 [PubMed - indexed for MEDLINE]
137. Am J Cardiol. 2002 Jun 15;89(12):1400-4.
Usefulness of cytokines interleukin-6 and interleukin-2R concentrations in
diagnosing active infective endocarditis involving native valves.
Alter P, Hoeschen J, Ritter M, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University of Marburg,
Marburg, Germany. alter@mailer.uni-marburg.de
The most important diagnostic value in infective endocarditis (IE) is isolation
of the causative microorganism. Because premature antibiotic treatment is
commonly administered before the assessment of blood cultures, the percentages of
isolated microorganisms has decreased significantly within the last decades.
Therefore, additional criteria for the diagnosis of IE may be helpful. It was
hypothesized that assessment of interleukin-6 (IL-6) and interleukin-2R (IL-2R)
may provide new diagnostic criteria for inflammation in IE. IL-6 and IL-2R serum
concentrations, white blood cell count (WBC), and C-reactive protein (CRP) were
measured in the blood of 47 patients with IE at the time of diagnosis and during
treatment. WBC and CRP were elevated in patients with IE at the time of
diagnosis. Both parameters were higher (p <0.05) in patients with positive blood
cultures when compared with negative cultures. The differences persisted during
the first week of treatment (p <0.01). In contrast, IL-6 and IL-2R concentrations
were elevated (p <0.001) independently of the status of blood cultures. Serum
concentrations of IL-6 and IL-2R decreased continuously during antibiotic
treatment. Assessment of IL-6 and IL-2R could thus provide new diagnostic
criteria for inflammation in IE, and these interleukins could also be suitable
for monitoring the course of inflammation during treatment.
PMID: 12062735 [PubMed - indexed for MEDLINE]
138. Herz. 2002 Mar;27(2):166-73.
[Functional genomics of pressure-loaded cardiomyocytes: etomoxir in heart
failure?]
[Article in German]
Rupp H, Maisch B.
Klinik für Innere Medizin-Kardiologie, Philipps-Universität Marburg.
Rupp@mailer.uni-marburg.de
BACKGROUND: Drugs for counteracting the neuroendocrine activation in heart
failure can reduce the adverse remodelling of the extracellular matrix of the
heart. Progression of heart failure can, however, often not be prevented and the
question arises whether important pharmacological targets remain unidentified.
Promising are drugs targeted at ventricular diastolic dysfunction which is a
marker of early progression of heart failure. PATHOPHYSIOLOGY: Left ventricular
dysfunction is characteristic of overloaded hypertrophied hearts with molecular
structures that are not adapted to the increased Ca2+ diffusion distances. Thus,
the Ca(2+)-pump (SERCA2) of sarcoplasmic reticulum is inadequately expressed
leading to a reduced force development and relaxation of hypertrophied
cardiomyocytes. ETOMOXIR: Drugs in development (CPT-1 inhibitor/PPARalpha
activator) that increase glucose oxidation can enhance SERCA2 expression. The
lead compound etomoxir had a selective influence on the contraction and
relaxation rate of pressure-overloaded hearts. The functional parameters were
correlated with the proportion of alpha-myosin heavy chains. Since viral or
inflammatory injury of the heart can also induce a fetal phenotype, metabolic
modulators such as etomoxir represent a promising therapeutic approach also for
cardiomyopathies with inadequate SERCA2 expression.
PMID: 12025461 [PubMed - indexed for MEDLINE]
139. Herz. 2002 Mar;27(2):150-65.
[Beta blockers in therapy of chronic heart failure]
[Article in German]
Hoffman J, Grimm W, Maisch B.
Klinik für Innere Medizin-Kardiologie, Philipps-Universität Marburg.
HoMarburg@Aol.com
BACKGROUND: Once contraindicated, beta-blockers have become an established,
evidence-based, recommended treatment concept in chronic heart failure during the
last years. PATHOPHYSIOLOGY: The increased activation of the adrenergic system in
heart failure syndrome, which leads to transmission of several adverse biological
signals to myocytes through adrenergic receptors, provides the rationale for the
use of beta-blockers in patients with chronic heart failure. Long-term treatment
with different types of beta-blockers addictive to an ACE-inhibitor and diuretics
results in normalization of left ventricular shape, an improvement of left
ventricular function, and a reduction of hospitalization rate for heart failure.
Hemodynamic and clinical improvement is independent of etiology and severity of
left ventricular dysfunction. THERAPEUTICAL RECOMMENDATIONS ACCORDINGS TO
STUDIES: Adequately powered clinical trials (CIBIS II, MERIT-HF, COPERNICUS)
testing different types of beta-blockers (bisoprolol, metoprolol, carvedilol)
clearly demonstrated that total mortality and the incidence of sudden cardiac
death were significantly reduced in heart failure patients by each of these
agents. On the basis of all available evidence, all patients with chronic, stable
heart failure (NYHA class II-IV) and with impaired left ventricular function
(LVEF < 45%) should receive one of the three above mentioned beta-blockers.
Protective effects of beta-blockers in heart failure comprise decrease in heart
rate, a decrease of energy consumption, antifibrillatory effects, protection
against adrenergic overactivation, and hence, inhibition of myocardial cell
necrosis. Moreover, several beta-blockers induce an up-regulation of
beta-receptors leading to an improvement of contractility during long-term
treatment. It should be mentioned that even a low dosage of beta-blockers exert
negative inotropic effects and may lead to a deterioration of hemodynamics and
heart failure symptoms in patients with heart failure. The patients treated
should be informed that the success of the "paradoxical intervention" will be
obvious until 2-3 months after initiation of additional beta-blocker therapy.
Beta-blocker treatment for heart failure should be started in stable patients
with a very low initial dosage and then up-titrated to the maximal tolerated
dosage and should be continued indefinitely. Mortality reduction by beta-blockade
in heart failure is no class effect. So far, beneficial effects could only be
demonstrated for lipophilic agents. Whether the non-selective beta-blocker
carvedilol with additional properties has advantages over the beta-1-selective
metoprolol is currently investigated in the COMET (Carvedilol or Metoprolol
European Trial) study. Despite the impressive effects in terms of morbidity and
mortality reduction, the transfer of these benefits to the clinical practice
setting is difficult, with international data showing only 10% of patients with
heart failure being treated.
PMID: 12025460 [PubMed - indexed for MEDLINE]
140. Herz. 2002 Mar;27(2):135-49.
[Value of aldosterone receptor blockade in diuretic therapy of patients with
chronic heart failure]
[Article in German]
Christ M, Ludwig N, Maisch B.
Klinik für Innere Medizin-Kardiologie, Philipps-Universität Marburg.
christ_michael@yahoo.de
PATHOGENESIS: All forms of chronic heart failure (high-output and low-output
failure) are accompanied by an "arterial underfilling" inducing the activation of
various neurohumoral systems (renin-angiotensin-aldosterone system, sympathic
nervous system, non-osmotic stimulation of vasopressin). Elevated levels of those
neurohormones detrimentally modulate renal function. Subsequently, renal salt and
volume retention occurs leading to the main symptoms of heart failure, edema
formation and dyspnea. DIURETIC THERAPY: Diuretics, which have been discovered
more than 40 years ago, beneficially influence renal salt- and volume retention
by their effects on tubular sodium reabsorption. While thiazides are recommended
in mild forms, loop diuretics are used in severe stages of congestive heart
failure. The clinician has to consider the changed pharmacokinetic and -dynamic
properties during the application of diuretics in patients with chronic heart
failure. In addition, increased sodium reabsorption occurs immediately after
cessation of diuretic action often nullifying the preceding diuresis. Thus, salt-
and volume restriction should be guaranteed, and a regular application of loop
diuretics during the day should be preferred due to the short-acting nature of
currently available loop diuretics. Sometimes, diuresis does not longer occur
during the treatment with one substance (diuretic resistance), although the
therapeutic goals of water excretion have not been achieved. After ruling out
factors reducing the actions of diuretics (non-compliance, hyponatremia, etc.), a
sequential nephron blockade should be initiated (combination of loop diuretics
and a thiazide or an aldosterone-receptor antagonist) to increase diuresis and to
elevate symptoms of volume overload. SIDE EFFECTS: Loop diuretics and thiazides
often induce mild hypokalemia, which has been demonstrated to be not as benign as
thought before. Chronic treatment with oral potassium supplements has several
drawbacks, as urine excretion of potassium is subsequently increased and
supplementation is not as effective as believed. Diuretic-induced hypokalemia
seems to be aldosterone dependent. As aldosterone levels increase during diuretic
therapy even during chronic treatment with an angiotensin-converting enzyme
(aldosterone-escape) a combined treatment including an aldosterone-receptor
antagonist has been suggested. Beneficial effects of aldosterone-receptor
blockade on mortality (RALES trial) appear to be mediated be extrarenal and renal
mechanisms. The suggested beneficial renal mechanisms of aldosterone receptor
blockade are discussed in detail in the review. CONCLUSION: In conclusion,
diuretic therapy of patients with congestive heart failure is effective to
relieve symptoms and, presumably, to prolong life. As renal function and
pharmacokinetics and -dynamics of diuretics are changed in heart failure,
diuretic treatment has to be adapted to provide optimal treatment. Increased
levels of aldosterone appear to play an important role in diuretic-induced
hypokalemia, and in the progression of heart and renal failure. Thus, aldosterone
receptor antagonists should be used in the treatment of heart failure more
frequently.
PMID: 12025459 [PubMed - indexed for MEDLINE]
141. Herz. 2002 Mar;27(2):113-34.
Dilated cardiomyopathies as a cause of congestive heart failure.
Maisch B, Ristić AD, Hufnagel G, Funck R, Alter P, Tontsch D, Pankuweit S.
Department of Internal Medicine-Cardiology, Angiology, Intensive Care Medicine,
and Preventive Cardiology, Philipps University, Marburg, Germany.
maisch@mailer.uni-marburg.de
DEFINITION AND CLASSIFICATION: Cardiomyopathies are disorders affecting the heart
muscle that frequently result in congestive heart failure. Five major forms are
recognized: dilated, hypertrophic, restrictive, right ventricular, and
nonclassifiable cardiomyopathies with distinct hemodynamic properties.
Furthermore, the new WHO/WHF definition also comprises inflammatory
cardiomyopathy, defined as myocarditis in association with cardiac dysfunction.
Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were
recognized. Viral cardiomyopathy is defined as viral persistence in a dilated
heart. It may be accompanied by myocardial inflammation and then termed
inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no
inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and
macrophages/mm2), the term viral cardiomyopathy or viral persistence in dilated
cardiomyopathy should be applied. DIAGNOSIS AND TREATMENT: In recent years, there
have been breakthroughs in understanding the molecular and genetic mechanisms
involved in this group of conditions, enabling improvement of diagnostic
strategies and introduction of new therapies. Ongoing evaluation of antiviral,
immunoglobulin, and immunosuppressive therapies including the European Study of
Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID), removal of
antibodies by immunoadsorption, anticytokine and gene therapy, as well as the
mechanical support devices may provide new treatment options.
PMID: 12025458 [PubMed - indexed for MEDLINE]
142. Internist (Berl). 2002 Apr;43 Suppl 1:S45-6, S49-65.
[Dilated cardiomyopathy and myocarditis. Current diagnostic requirements and
therapeutic possibilities]
[Article in German]
Maisch B, Funcker R, Alter P, Portig I, Pankuweit S.
Klinik für Innere Medizin-Kardiologie, Angiologie, Intensivmedizin und Präventive
Kardiologie der Philipps-Universität Marburg, Baldinger Strasse 1, Postfach 23
60, 35033 Marburg. maisch@mailer.uni-marburg.de
PMID: 11993000 [PubMed - indexed for MEDLINE]
143. Cardiovasc Pathol. 2002 Mar-Apr;11(2):112-22.
Pathophysiology of viral myocarditis: the role of humoral immune response.
Maisch B, Ristić AD, Hufnagel G, Pankuweit S.
Department of Internal Medicine-Cardiology, Philipps-University Marburg,
Baldingerstrasse 1, D-35033 Marburg, Germany. bermaisch@aol.com
The pathophysiology of viral myocarditis is still a matter of debate. Humoral
autoimmunity in postviral heart disease remains an attractive but complex
hypothesis. Antigenic mimicry with or without cytolytic antibody properties has
been shown to play a role in the immunopathogenesis of myocarditis with respect
to sarcolemmal/myolemmal epitopes (including the beta-receptor), myosin and some
mitochondrial proteins including the antinucleotide translocator (ANT)-carrier
and dihydrolipoamid dehydrogenase. Today, refined two-dimensional Western blots
are able to identify receptors and enzymes that are target of a humoral immune
response or the consequence of an "immunization process." A humoral immune
response to an invading agent will most likely lead to immunodestruction first.
After conversion to IgG, the continuing antibody response may indicate the
healing or healed process and last for many years or life-long. This paper
reviews our present knowledge on the humoral immune response in myocarditis and
its interplay with the viral agents and the other components of the immune
system.
PMID: 11934603 [PubMed - indexed for MEDLINE]
144. Circulation. 2002 Mar 26;105(12):e67-8.
Images in cardiovascular medicine. Phenotype of infiltrating T lymphocytes in
cardiac sarcoidosis.
Schoppet M, Pankuweit S, Moll R, Baandrup U, Maisch B.
Department of Internal Medicine and Cardiology, Philipps-University,
Baldingerstrasse, Marburg, Germany. schoppet@mailer.uni-marburg.de
PMID: 11914265 [PubMed - indexed for MEDLINE]
145. J Am Coll Cardiol. 2002 Mar 6;39(5):780-7.
Implantable defibrillator event rates in patients with idiopathic dilated
cardiomyopathy, nonsustained ventricular tachycardia on Holter and a left
ventricular ejection fraction below 30%.
Grimm W, Hoffmann J J, Müller HH, Maisch B.
Department of Cardiology, Hospital of the Philipps-University of Marburg,
Marburg, Germany. wolfram.grimm@med.uni-marburg.de
Comment in:
J Am Coll Cardiol. 2002 Mar 6;39(5):788-9.
OBJECTIVES: This study investigated the incidence of appropriate implantable
cardioverter defibrillator (ICD) interventions for ventricular tachycardia (VT)
or ventricular fibrillation (VF) in patients with idiopathic dilated
cardiomyopathy (IDC) and nonsustained VT in the presence of a left ventricular
ejection fraction below 30%, versus in patients with syncope and patients with a
history of VT or VF. BACKGROUND: To date, only limited information is available
about the prophylactic use of ICDs in patients with IDC. METHODS: From January
1993 to July 2000, 101 patients with IDC underwent implantation of ICDs with
electrogram storage capability at our institution. Patients were placed into one
of three groups according to their clinical presentation: asymptomatic or mildly
symptomatic nonsustained VT in the presence of a left ventricular ejection
fraction < or = 30% (49 patients, prophylactic group), unexplained syncope or
near syncope (26 patients, syncope group) and a history of sustained VT or VF (26
patients, VT/VF group). RESULTS: During 36 +/- 22 months follow-up, 18 of 49
patients (37%) in the prophylactic group received appropriate shocks for VT or
VF, compared with 8 of 26 patients (31%) in the syncope group and with 9 of 26
patients (35%) of the VT/VF group. Multivariate Cox analysis of baseline clinical
variables identified left ventricular ejection fraction, atrial fibrillation and
a history of sustained VT or VF as predictors for appropriate ICD interventions
during follow-up. CONCLUSIONS: Patients with IDC and prophylactic ICD
implantation for nonsustained VT in the presence of a left ventricular ejection
fraction < or = 30% had an incidence of appropriate ICD interventions similar to
that of patients with a history of syncope or sustained VT or VF. These findings
indicate that ICDs may have a role in not only secondary but also primary
prevention of sudden death in IDC.
PMID: 11869841 [PubMed - indexed for MEDLINE]
146. Pneumologie. 2002 Jan;56(1):31-5.
[Amiodarone induced pulmonary toxicity]
[Article in German]
Alter P, Grimm W, Maisch B.
Zentrum für Innere Medizin - Kardiologie, Philipps-Universität Marburg/Lahn,
Germany. alter@mailer.uni-marburg.de
Abstract. BACKGROUND: Antiarrhythmic therapy with class III drug amiodarone
(Cordarex(R)) for supraventricular and ventricular tachycardia is commonly used
because of its high efficacy and absent negative inotropy. Pulmonary toxicity of
amiodarone possibly leading to lung fibrosis is a rare, but severe side effect of
chronic therapy. In contrast to patients with coronary artery disease, there are
only a few data about pulmonary toxicity in patients with dilated cardiomyopathy.
CASE REPORT: We report on two patients with dilated cardiomyopathy who received
amiodarone because of symptomatic non-sustained or sustained ventricular
tachycardia. After 6 weeks resp. 8 months of treatment with amiodarone both
patients developed pulmonary toxicity. Other causes of pulmonary toxicity were
ruled out by bronchoscopy, bronchoalveolar lavage and biopsy. Pulmonary function
improved in both patients within some weeks after discontinuation of amiodarone.
CONCLUSIONS: This report deals with two cases of amiodarone induced pulmonary
toxicity in dilated cardiomyopathy leading to respiratory insufficiency.
Pulmonary toxicity is a rare, but potentially lethal side effect of amiodarone.
Reversibility of pulmonary changes in case of an early drug discontinuation is
shown. Because of severe reduced left ventricular function in dilated
cardiomyopathy, heart failure symptoms could conceal clinical signs of pulmonary
amiodarone toxicity. Therefore, pulmonary function should be controlled
periodically during amiodarone therapy including bronchoscopy, bronchoalveolar
lavage, biopsy and measurement of diffusion capacity.
PMID: 11797156 [PubMed - indexed for MEDLINE]
147. Vasa. 2001 Nov;30(4):299-302.
Angiography, CT and MR imaging of a high vena cava inferior interruption in a
patient with Hirschsprung disease.
Alter P, Walthers EM, Schaefer JR, Maisch B.
Department of Internal Medicine, Cardiology, Philipps-University Marburg/Lahn,
Germany. alter@mailer.uni-marburg.de
We report on a high vena cava inferior interruption immediately at the insertion
to the right atrium in a patient with Hirschsprung disease assessed by
angiography, CT, and MRI. Hirschsprung disease is frequently associated with
Down, Undine, Waardenburg, Bardet-Biedl, Smith-Lemli-Opitz and
Goldberg-Sphrintzen syndromes. We suggest that the association of these two
malformations are most likely interrelated and should be considered as a new
syndrome.
PMID: 11771218 [PubMed - indexed for MEDLINE]
148. Curr Cardiol Rep. 2002 Jan;4(1):13-21.
The classification of pericardial disease in the age of modern medicine.
Maisch B, Ristić AD.
Department of Internal Medicine-Cardiology, Philipps University, Marburg,
Baldingerstrasse 1, 35033 Marburg, Germany. BerMaisch@aol.com
The spectrum of pericardial diseases comprises pericarditis, pericardial
neoplasms, cysts, and congenital defects. Due to the insufficient diagnostic
value of standard, noninvasive diagnostic techniques, many cases remained
etiologically unclear, and were therefore classified as idiopathic. A major
improvement in the classification of pericardial disease is its clear distinction
between the two most frequent forms of idiopathic pericarditis: viral infection
and autoreactive pericarditis. This classification has major therapeutic
consequences. In autoreactive forms, systemic and intrapericardial corticosteroid
treatment has a favorable effect; its application in viral forms is
contraindicated. The new classification of pericardial diseases synthesizes the
achievements of modern imaging with molecular biology and immunology. Systematic
implementation of new techniques of pericardial fluid analyses, pericardioscopy
and pericardial biopsy, and the application of molecular biology and immunology
techniques have opened new windows to the pericardial diseases, permitting early
specific diagnosis, and creating foundations for etiologic treatment in many
cases.
PMID: 11743917 [PubMed - indexed for MEDLINE]
149. Am J Cardiol. 2001 Dec 1;88(11):1323-6.
Pericardial access using the PerDUCER and flexible percutaneous pericardioscopy.
Maisch B, Ristić AD, Rupp H, Spodick DH.
Department of Internal Medicine-Cardiology, Philipps University, Marburg,
Germany. BerMaisch@aol.com
PMID: 11728368 [PubMed - indexed for MEDLINE]
150. Herz. 2001 Sep;26(6):418-23.
[Possibilities and limits of outpatient antibiotic therapy of infective
endocarditis]
[Article in German]
Ritter M, Alter P, Maisch B.
Klinik für Innere Medizin-Kardiologie, Herzzentrum der Philipps-Universität
Marburg.
BACKGROUND: Infective endocarditis has a high morbidity and lethality. Therefore
antibiotic treatment has to be intravenous to achieve high blood levels and has
to last several weeks without an interruption of treatment at the weekends.
PATIENT SELECTION FOR OUTPATIENT THERAPY: It is therefore crucial to select the
patient group that is suited for an outpatient, antibiotic therapy very
carefully. In general only hemodynamically stable patients without complications
in whom the responsible organism has been identified should be considered.
TREATMENT: From a pharmacological point of view intravenous or intramuscular
application for the complete duration of therapy is obligatory. Endocarditis
caused by penicillin-susceptible streptococci, the biggest group of organisms
responsible for endocarditis, can be treated with Ceftriaxon once daily for 4
weeks. For other organisms there are at present no data available which support
the feasibility of an outpatient therapy. In particular antibiotic therapy with a
complex regimen for those organisms is not practicable for outpatient usage.
Possibly, in the near future computer controlled pumps might overcome this
disadvantage. LIMITS: Every outpatient therapy should be initiated under
inpatient conditions and only after an initial response to the antibiotic therapy
continued in an outpatient setting. Today reliable outpatient therapy and
follow-up 7 days a week under the given outpatient infrastructure is problematic
and remains an exception. However, considering cost-effectiveness outpatient as
compared to inpatient antibiotic therapy could be an interesting economically
advantageous alternative.
PMID: 11683072 [PubMed - indexed for MEDLINE]
151. Cardiovasc Pathol. 2001 Sep-Oct;10(5):229-34.
Apoptosis in myocarditis and dilated cardiomyopathy: does enterovirus genome
persistence protect from apoptosis? An endomyocardial biopsy study.
Alter P, Jobmann M, Meyer E, Pankuweit S, Maisch B.
Department of Internal Medicine and Cardiology, Philipps-University Marburg/Lahn,
Baldingerstrasse, D-35033, Marburg, Germany. alter@mailer.uni-marburg.de
The purpose of this study was to examine the role of apoptosis in myocarditis and
dilated cardiomyopathy. Apoptosis is an active energy-consuming mechanism of cell
death in several cardiac diseases in different quality and quantity. METHODS:
Endomyocardial biopsies from 81 patients with active (1) and chronic myocarditis
(10), dilated cardiomyopathy with inflammation (DCMi; 10) and without
inflammation (DCM; 20), with borderline myocarditis and positive PCR for
cytomegalovirus-DNA (6), adenovirus-DNA, or enterovirus-RNA (7), and controls
(17) were analysed. Apoptosis was detected by using the TUNEL method. The highest
rate of apoptotic cardiocytes was found in active and chronic myocarditis. One
patient with severe active myocarditis demonstrated 6.15% of apoptotic
cardiocytes. Mean percentage of apoptotic cardiocytes in chronic myocarditis was
significantly increased (0.61+/-1.25%) when compared to controls (0.01+/-0.04%,
P<.05). Particularly, patients with cytomegalovirus-DNA persistence in borderline
myocarditis had an elevated rate of apoptosis (0.34+/-0.68%, P<.05). Increased
rates of apoptosis were found in borderline myocarditis with adenovirus-DNA
persistence (0.20+/-0.57%) and in DCM (0.06+/-0.15%). Only a nonsignificant
increase of apoptotic cardiocytes was found in DCMi (0.03+/-0.08%). No apoptosis
was found in patients with enteroviral genome persistence in borderline
myocarditis. CONCLUSIONS: Apoptosis of cardiac cells is increased in myocarditis
and dilated cardiomyopathy, being highest in severe active myocarditis. Apoptosis
thus contributes to cell death in active myocarditis and may play a role not to
be neglected in dilated cardiomyopathy. Enteroviruses seem to have anti-apoptotic
effects, because no apoptosis at all was found in the myocardium.
PMID: 11673061 [PubMed - indexed for MEDLINE]
152. Herz. 2001 Aug;26(5):345-52.
Alcohol and the heart.
Schoppet M, Maisch B.
Department of Internal Medicine, Cardiology and Angiology, Philipps University
Marburg, Germany. schoppet@mailer.uni-marburg.de
ALCOHOLISM IN GENERAL: Alcoholism is one of the major health problems in the
world. Alcohol consumption has an impact on different body systems like the
central nervous system, the gastrointestinal tract, the hematopoetic organs, and
the cardiovascular system. Alcohol interferes with other medications, and
drinking can exacerbate a variety of medical illnesses. IMPACT ON THE HEART: In
the heart, alcohol and its metabolite acetaldehyde confer a toxic effect on
mitochondria as well as on the sarcoplasmatic reticulum, which is dependent on
both the mean daily consumption and the duration of alcohol intake. A wide range
of toxic effects of alcohol in distinct individuals can be observed and modest
doses of alcohol can exert beneficial effects on the cardiovascular system
probably by an increase in high density lipoprotein cholesterol (HDL) or changes
in blood clotting mechanisms. Detrimental effects of alcohol on the heart
comprise a decrease in myocardial contractility, hypertension, atrial and
ventricular arrhythmias, and secondary non-ischemic dilated cardiomyopathy. After
consuming large quantities of alcohol over years, alcoholic cardiomyopathy may
develop, which presents with dilation and impaired contractility of the left or
both ventricles. Endomyocardial biopsies of patients with alcoholic
cardiomyopathy reveal in up to 30% of all cases myocarditis with lymphocytic
infiltrates. TREATMENT: Abstinence after development of milder heart failure can
stop progression or even reverse symptoms in some cases, otherwise severe heart
failure ensues leading to a poor prognosis. Except abstinence, treatment of
alcoholic cardiomyopathy is based on the regimen of therapy for heart failure to
reduce the size of the dilated heart and to mitigate the symptoms of heart
failure.
PMID: 11556162 [PubMed - indexed for MEDLINE]
153. Internist (Berl). 2001 Jun;42(6):901-4.
[Reversible grade III atrioventricular block in a 35-year-old patient]
[Article in German]
Alter P, Grimm W, Maisch B.
Philipps-Universität Marburg, Klinik für Innere Medizin-Kardiologie,
Baldingerstrasse, 35033 Marburg. alter@mailer.uni-marburg.de
PMID: 11449636 [PubMed - indexed for MEDLINE]
154. Eur Heart J. 2001 May;22(10):813-24.
Immunological basis of the cardiac conduction and rhythm disorders.
Maisch B, Ristić AD.
Department of Internal Medicine-Cardiology, Philipps University, Marburg,
Germany.
PMID: 11350091 [PubMed - indexed for MEDLINE]
155. Pacing Clin Electrophysiol. 2001 Feb;24(2):166-71.
Reversal of tachycardia induced cardiomyopathy following ablation of repetitive
monomorphic right ventricular outflow tract tachycardia.
Grimm W, Menz V, Hoffmann J, Maisch B.
Clinical Electrophysiology Laboratory, Department of Cardiology, Hospital of the
Philipps-University of Marburg, Germany.
Radiofrequency catheter ablation was performed in four adults with myocardial
dysfunction related to repetitive monomorphic ventricular tachycardia (RMVT)
originating in the right ventricular outflow tract. Serial echocardiographic
assessment of left ventricular function before and after radiofrequency catheter
ablation of RMVT showed complete reversal of left ventricular dysfunction without
arrhythmia recurrence during 31+/-28 months follow-up.
PMID: 11270695 [PubMed - indexed for MEDLINE]
156. Herz. 2001 Feb;26(1):18-29.
[Prevention of atrial arrhythmias by pacing]
[Article in German]
Funck RC, Pomsel K, Grimm W, Hufnagel G, Maisch B.
Klinik für Innere Medizin-Kardiologie, Philipps-Universität Marburg.
funck@mailer.uni-marburg.de
BACKGROUND: Atrial fibrillation is the most frequent arrhythmia. It can impair
quality of life considerably. Due to thromboembolic complications it contributes
to the patients' morbidity and mortality and to the costs for their medical
treatment. PREVENTION: In chronic atrial fibrillation there is a need for
adequate anticoagulation and heart rate control. In paroxysmal and intermittent
atrial fibrillation it should be sought to prevent its progression to chronic
atrial fibrillation. Since atrial fibrillation initiates negative processes of
remodeling within the atrial myocardium, it has the tendency to perpetuate
itself. From a theoretical point of view, it can be expected that all means which
prevent episodes of atrial fibrillation or which terminate it immediately after
its onset, are able to prevent or at least to delay the progression to chronic
atrial fibrillation. Pharmacologic treatment is usually used to prevent
recurrences of atrial fibrillation. Based on the actual data it can also be
expected that pacemakers with special preventive pacing algorithms are able to
reduce the atrial arrhythmic burden. Besides consequent overdrive pacing, more
sophisticated algorithms like "suppression of premature atrial contractions",
"post exercise response", "automatic rest rate" or "post mode-switch pacing" have
been developed. They can be applied either alone or in combination with special
lead positions (interatrial septal pacing or pacing of the triangle of Koch) or
special stimulation configurations like dual site right atrial pacing or biatrial
pacing. These pacing strategies cover the most relevant onset mechanisms of
atrial fibrillation. Furthermore, there are algorithms to treat atrial
tachyarrhythmias actively by antitachycardia pacing (ATP). First clinical results
have shown that about 2/3 of the diagnosed atrial tachyarrhythmias could be
terminated by these means immediately after their onset. ONGOING TRIALS: This
article gives an overview over the principles of pacing in the management of
atrial arrhythmias and ongoing clinical trials in this field. Before a definite
judgement on the clinical relevance of these new preventive and therapeutic
pacing strategies can be given, the results of these ongoing controlled clinical
studies have to be analyzed.
PMID: 11258105 [PubMed - indexed for MEDLINE]
157. Dtsch Med Wochenschr. 2001 Jan 26;126(4):76-8.
[Fulminant course of falciparum malaria]
[Article in German]
Lamparter S, Schoner K, Moll R, Mennel HD, Maisch B.
Klinik für Innere Medizin-SP Kardiologie, Philipps-Universität Marburg.
lamparte@mailer.uni-marburg.de
HISTORY AND ADMISSION FINDINGS: A 57-year-old white man had been travelling in
Kenya for vacation until 14 days before admission. Due to apprehension about side
effects, the patient had refused any malaria prophylaxis. Ten days before
admission he developed low grade temperatures and suffered from pain in the
limbs, from nausea and vomiting. A new episode of tachyarrhythmia was diagnosed
two days before admission and was treated by his general practitioner. Finally he
was admitted to our hospital because of high temperatures, chills and progressive
clinical deterioration. Autopsy revealed prominent congestion of liver, spleen
and cerebral vessels as well as subdural and subarachnoidal hemorrhage.
INVESTIGATIONS: In both thin and thick peripheral blood smears Plasmodium
parasites were demonstrated in approximately 30% of the eryhthrocytes and the
diagnosis of Plasmodium falciparum was immediately confirmed by an immunological
test. TREATMENT AND COURSE: Due to the fulminant clinical and neurological
deterioration with progressive hypoxaemia, the patient required ventilator
therapy already one hour after admission. Therapy with chinine and doxycycline
was initiated and exchange transfusion was considered. However, due to
hyperkalaemia and cardiac arrest, the patient died 4 hours after admission due to
parasitic hemolysis. CONCLUSIONS: Severe Plasmodium falciparum infection in
non-immunized patients is a medical emergency and requires immediate diagnosis
and treatment. Malaria should always be considered in the differential diagnosis
in persons who have travelled to endemic areas and presenting not only with
temperatures, but also with non-specific clinical signs, like cardiac
arrhythmias. Although never entirely effective, chemoprophylaxis is highly
recommended.
PMID: 11218564 [PubMed - indexed for MEDLINE]
158. Basic Res Cardiol. 2001 Feb;96(1):75-81.
Antiendothelial antibodies in sera of patients with infective endocarditis.
Portig I, Beck V, Pankuweit S, Maisch B.
Klinikum der Philipps--Universität SP Kardiologie, Marburg, Germany.
wolf@mailer.uni-marburg.de
Infective endocarditis is characterized by the colonization of endocardium by
microorganisms. Except for Staphylococcus aureus, microorganisms are not able to
adhere to and grow on endocardial cells; prior damage, e.g., by shear stress or
other mechanical factors, is necessary. But other causes may well have a share.
This study was, therefore, designed to identify immunological factors, especially
antibodies against endothelial cells, which could contribute to the initiation of
endocardial injury. Sera of patients with infective endocarditis and healthy
controls were investigated for the presence of antibodies against endothelial
antigen. As the antigen source human umbilical vein endothelial cells were used.
Antibodies against endothelial cells were detected by indirect
immunofluorescence, ELISA, immunoblotting, antibody dependent cellular
cytotoxicity, and antibody mediated cytotoxicity. Antibodies against endothelial
cells were found in seven out of fifteen patients. These antibodies were directed
against cytoplasmic structures and only appeared in the course of the disease. A
correlation between the presence of these antibodies and disease activity or the
outcome of disease was not observed. These antibodies may develop as a
consequence of damage to endocardial cells (thereby exposing intracellular
antigen to the immune system) and do not seem to play a role in the pathogenesis
of infective endocarditis.
PMID: 11215535 [PubMed - indexed for MEDLINE]
159. Herz. 2000 Dec;25(8):781-6.
Intrapericardial treatment of autoreactive myocarditis with triamcinolon.
Successful administration in patients with minimal pericardial effusion.
Maisch B, Ristić AD, Seferovic PM, Spodick DH.
Department of Internal Medicine-Cardiology, Philipps University, Marburg,
Germany. BerMaisch@aol.com
A major clinical drawback in the treatment of autoreactive pericarditis is its
inherent feature to relapse. Intrapericardial treatment with triamcinolone was
reported to be efficient in patients with large, symptomatic autoreactive
pericardial effusions, avoiding side effects of systemic treatment as well as
compliance problems. Intrapericardial treatment with 300 mg/m2 triamcinolone was
for the first time performed in patients with autoreactive myopericarditis and
minimal pericardial effusions (75 to 110 ml). After 12 months of follow-up both
patients are asymptomatic and there were no further recurrences of pericardial
effusion. Pericardiocentesis in these patients was performed with the application
of the PerDUCER device, guided by pericardioscopy. This device has a
hemispherical cavity at the top of the instrument connected with a
vacuum-producing syringe. In this cavity the pericardium is captured by vacuum
and tangentially punctured by the introducer needle. Pericardium that can be
captured, must be up to 2 mm thin to fit into the hemispherical cavity.
Pericardioscopy performed from the anterior mediastinum significantly contributed
to the success of the procedures enabling visualization of the portions of the
pericardium free of adipose tissue or adhesions, suitable for puncture with the
PerDUCER. In conclusion, intrapericardial treatment of symptomatic autoreactive
myopericarditis with minimal pericardial effusion was safely and efficiently
performed in 2 patients. Pericardiocentesis was enabled by means of the PerDUCER
device, facilitated by pericardioscopy.
PMID: 11200127 [PubMed - indexed for MEDLINE]
160. Herz. 2000 Dec;25(8):769-80.
New directions in diagnosis and treatment of pericardial disease. A project of
the Taskforce on Pericardial Disease of the World Heart Federation.
Maisch B, Ristić AD, Seferovic PM.
Department of Internal Medicine-Cardiology, Philipps-University Marburg, Germany.
BerMaisch@aol.com
New directions in the diagnosis and treatment of pericardial diseases synthesize
the achievements of modern imaging with molecular biology and immunology
techniques. Comprehensive and systematic implementation of new techniques of
pericardiocentesis, pericardial fluid analysis, pericardioscopy, epicardial and
pericardial biopsy, as well the application of comprehensive molecular biology
and immunology techniques for pericardial fluid and biopsy analyses have opened
new windows to the pericardial diseases, permitting early specific diagnosis and
creating foundations for etiologic treatment in many cases. In patients with
recurrent pericarditis, resistant to conventional treatments, as well as in
patients with neoplastic pericarditis an alternative intrapericardial treatment
regimen was suggested by the Taskforce on Pericardial Diseases of the World Heart
Federation. Intrapericardial application of medication avoids systemic side
effects with increased local efficacy. The following protocols are proposed: CIRP
(colchicine in recurrent pericarditis)--colchicine vs placebo in
chronic/recurring pericarditis without pericardiocentesis; TRIPE (triamcinolone
in pericardial effusion)--intrapericardial instillation of triamcinolone + 6
months colchicine vs pericardial puncture without instillation + 6 months
colchicine; NEPIN (neoplastic effusion and pericardial
instillation)--pericardiocentesis and drainage + intrapericardial instillation of
cisplatin or thiotepa.
PMID: 11200126 [PubMed - indexed for MEDLINE]
161. Herz. 2000 Dec;25(8):748-54.
Cytokine activation in pericardial fluids in different forms of pericarditis.
Pankuweit S, Wädlich A, Meyer E, Portig I, Hufnagel G, Maisch B.
Department of Internal Medicine-Cardiology, Philipps-University Marburg, Germany.
pankuwei@mailer.uni-marburg.de
There are many causes of pericardial effusion and it is useful to classify them
etiologically, since this disorder is the most common pathologic process
involving the pericardium. This report details our experience with
pericardioscopy and epicardial biopsy in 101 patients with pericardial effusions
in whom pericardioscopy was performed. By means of clinical data and polymerase
chain reaction we tried to elucidate the etiology of the pericardial effusion
which were classified as follows: we found 41 effusions to be induced by primary
malignant tumors or tumors metastatic to the pericardium. Specific diagnosis of
viral and bacterial pericarditis was established in 17 patients by examination of
the pericardial effusion with PCR, where we found 3 patients positive for
adenovirus, 5 patients positive for cytomegalovirus, 2 patients positive for
enterovirus-RNA and 5 patients positive for borrelia Burgdorferi-DNA.
Additionally, idiopathic effusions (lymphocytic and autoreactive) were seen in 35
patients. In summary immunological and molecular biology investigations seem to
provide an additional tool in the diagnostic of pericardial effusion with unknown
etiology. If we focus on the ELISA results, there is some evidence, that the
demonstration [table: see text] of activation markers and soluble mediators of
inflammation such as Il-6, Il-8 and IFN-gamma in pericardial effusion and the
simultaneously lack of these mediators in sera of the patients first may be
helpful in the discrimination of autoreactive and lymphocytic effusion. Second,
this cytokine pattern or distribution indicates a possible local inflammatory
process, where these cytokines were all released from activated T lymphocytes
present in lymphocytic effusion. In the future, this may have therapeutic
implications.
PMID: 11200123 [PubMed - indexed for MEDLINE]
162. Herz. 2000 Dec;25(8):729-33.
Arrhythmias in acute pericarditis. An endomyocardial biopsy study.
Ristić AD, Maisch B, Hufnagel G, Seferovic PM, Pankuweit S, Ostojic M, Moll R,
Olsen E.
University Institute for Cardiovascular Diseases, Medical Centre of Serbia,
Belgrade, Yugoslavia. ristic@mailer.uni-marburg.de
It is still controversial whether the arrhythmias in acute pericarditis are of
myocardial or pericardial origin. The aim of the present study was to investigate
the occurrence of arrhythmias and conduction disorders in patients with acute
pericarditis with no endomyocardial biopsy evidence of myocarditis (group 1: 40
patients, 65% males, mean age 45.6 +/- 15.7 years, mean heart rate [HR] 98.7 +/-
22.2 beats per minute) in comparison to endomyocardial biopsy proven acute
myocarditis/perimyocarditis (group 2: 10 patients, 3/10 with perimyocarditis, 70%
males, mean age 46.1 +/- 15.8 years, mean heart rate 76.7 +/- 33.1 beats per
minute). At the initial assessment all patients underwent comprehensive clinical
work-up including echocardiography, cardiac catheterization, and endomyocardial
biopsy. In all patients biventricular endomyocardial biopsy was performed using
standard femoral approach and Schikumed 7 F or 8 F bioptomes. Tissue samples were
stained by H & E, v. Gieson and independently reviewed by two cardiac
pathologists. In addition immunohistochemistry and immunocytochemistry were
performed, and only patients fulfilling Dallas and World Heart Federation
criteria were selected for group 2. Comparative analysis of electrocardiograms
and 24-hour Holter recordings at initial presentation revealed in group 1 vs
group 2 significantly less frequent paroxysmal supraventricular tachyarrhythmias
(5% vs 40%), and ventricular fibrillation (0 vs 20%), in contrast to atrial
fibrillation that occurred more often (20% vs 0) (all p < 0.05). Furthermore, in
the group 2 one patient died due to VF and two patients underwent ICD
implantation. Low voltage (40% vs 30%) and ST/T wave changes (47.5% vs 30%), as
well as the incidence of the II degree AV block (5% vs 0) and complete AV block
(2.5% vs 10%) were not significantly different between the groups. In conclusion,
patients with pericarditis and no endomyocardial biopsy indications of
myocarditis had significantly less often life threatening rhythm disorders in
contrast to patients with endomyocardial biopsy proven acute
myocarditis/perimyocarditis. On the contrary, incidence of transitory atrial
fibrillation was higher in acute pericarditis, than in myocarditis.
PMID: 11200120 [PubMed - indexed for MEDLINE]
163. Europace. 2000 Oct;2(4):346-9.
Prevention of recurrent ventricular fibrillation by ventricular rate
stabilization.
Grimm W, Hoffmann J, Menz V, Maisch B.
Clinical Electrophysiology Laboratory, Cardiology Division, Department of
Medicine, Hospital of Philipps-University of Marburg, Marburg, Germany.
This report describes a post-infarct patient with recurrent ventricular
fibrillation in the absence of acute ischaemia, in whom arrhythmia recurrences
could be prevented by ventricular rate stabilization of a third-generation
cardioverter defibrillator. Review of the literature and clinical implications
are discussed.
PMID: 11194604 [PubMed - indexed for MEDLINE]
164. Digestion. 2001;63(1):35-42.
Prognostic value of heart rate variability analysis in patients with carcinoid
syndrome.
Hoffmann J, Grimm W, Menz V, Wied M, Sprenger A, Arnold R, Maisch B.
Cardiovascular Section, Department of Internal Medicine, Philipps University of
Marburg, Baldingerstrasse, D-35033 Marburg, Germany. HoMarburg@aol.com
BACKGROUND/AIMS: Recently, a decrease in heart rate variability measures was
found in patients with carcinoid syndrome suffering from carcinoid heart disease
compared to those without cardiac involvement of carcinoid syndrome. The
prognostic relevance of this finding, however, was not clear. PATIENTS AND
METHODS: Therefore, 35 patients with carcinoid syndrome (21 men, age 56 +/- 11
years), all of them suffering from metastatic carcinoid tumors, were followed
prospectively at our institution. Digital 24-hour Holter monitoring,
echocardiography, and serum serotonin and urine 5-hydroxyindole acetic acid
(5-HIAA) samplings were performed in all study patients at baseline. Indices of
time domain heart rate variability obtained from Holter recordings included the
standard deviation of all normal RR intervals (SDNN) representing overall
variability, the square root of the mean of the squared differences between
adjacent normal RR intervals (rMSSD), and the percentage of the number of pairs
of adjacent normal RR intervals differing by >50 ms (pNN50), both indices
reflecting predominantly vagal influences on heart rate. RESULTS: During a mean
follow-up of 18 +/- 7 months, 15 of 35 patients with carcinoid syndrome (43%)
died. Patients with cardiac manifestation of the carcinoid syndrome showed a
tendency towards an increased mortality in comparison to patients without cardiac
involvement (p = 0.09). Patients with the combination of decreased heart rate
variability (SDNN <100 ms) and presence of carcinoid heart disease had a
significant worse prognosis (p = 0.04) compared to patients without carcinoid
heart disease and preserved heart rate variability (SDNN > or =100 ms).
CONCLUSIONS: The presence of carcinoid heart disease in combination with
decreased heart rate variability is associated with the most adverse prognosis in
the setting of carcinoid syndrome. Copyright 2001 S. Karger AG, Basel
PMID: 11173898 [PubMed - indexed for MEDLINE]
165. Pacing Clin Electrophysiol. 2000 Nov;23(11 Pt 2):1960-4.
Relation between microvolt level T wave alternans and other potential noninvasive
predictors of arrhythmic risk in the Marburg Cardiomyopathy Study.
Grimm W, Hoffmann J, Menz V, Maisch B.
Hospital of the Philipps-University Marburg, Department of Cardiology
Baldingerstrasse, 35033 Marburg, Germany.
The relation between microvolt level T wave alternans (TWA) and other noninvasive
arrhythmia risk predictors was analyzed in 221 consecutive patients with
idiopathic dilated cardiomyopathy (IDC) and sinus rhythm enrolled in the Marburg
Cardiomyopathy Study between March 1996 and May 2000. TWA analysis was also
performed in 110 healthy controls of similar age and sex. TWA during
symptom-limited exercise was positive, negative and indeterminate in,
respectively, 108 (49%), 65 (29%) and 48 (22%) patients with IDC versus,
respectively, 5 (5%), 98 (89%) and 7 (6%) healthy controls (P < 0.05). Patients
with IDC and positive TWA had a lower left ventricular (LV) ejection fraction (29
+/- 9% vs 34 +/- 10%, P < 0.05) and greater LV end-diastolic diameter (69 +/- 8
mm versus 64 +/- 6 mm, P < 0.05) than patients with negative TWA. Other
variables, including age, gender, New York Heart Association functional class,
presence of bundle branch block, arrhythmias on 24-hour ambulatory
electrocardiogram, heart rate variability and baroreflex sensitivity, were not
significantly different between patients with positive vs negative TWA. The
prognostic significance of TWA in IDC with regard to arrhythmic events and total
mortality will be determined by multivariate Cox analysis at the end of a 5-year
follow-up in this ongoing study.
PMID: 11139967 [PubMed - indexed for MEDLINE]
166. Pacing Clin Electrophysiol. 2000 Nov;23(11 Pt 2):1939-43.
Circadian variation and onset mechanisms of ventricular tachyarrhythmias in
patients with coronary disease versus idiopathic dilated cardiomyopathy.
Grimm W, Walter M, Menz V, Hoffmann J, Maisch B.
Hospital of the Philipps-University Marburg, Department of Cardiology,
Baldingerstrasse, 35033 Marburg, Germany.
To determine the circadian variations and the onset mechanisms of ventricular
tachyarrhythmias (VT) in patients with implantable cardioverter defibrillators,
stored electrograms of 364 VT episodes occurring in 40 patients with coronary
artery disease (CAD) and in 29 patients with idiopathic dilated cardiomyopathy
(DCM) were analyzed. A similar circadian distribution of VT episodes was observed
in both groups, with a morning peak and less pronounced evening peak. After
exclusion of patients with atrial fibrillation, VT onset was classified as (1)
sudden if preceded by > or = 8 regular cycles without ventricular premature
beats, (2) onset with a short-long-short interval, and (3) a more complex onset
with variable patterns of ventricular premature beats before initiation of VT.
Sudden onset was found in 26% and 21% of VTs in CAD and DCM respectively. A
short-long-short interval preceded 29% of VTs in CAD compared to 14% of VTs in
DCM (P < 0.05). A more complex onset was observed in the remaining 45% of VTs in
CAD and 65% of VTs in DCM (P < 0.05). In conclusion, patients with DCM and CAD
had similar circadian distributions of VT episodes. The majority of episodes were
preceded by complex occurrence of ventricular premature beats rather than by the
classic short-long-short sequence. These findings have important implications for
the development of preventive pacing methods.
PMID: 11139962 [PubMed - indexed for MEDLINE]
167. Pacing Clin Electrophysiol. 2000 Nov;23(11 Pt 2):1848-51.
Linear lesion formation by ND:YAG laser versus radiofrequency energy in porcine
atria.
Menz V, Scholz S, Baumgärtel D, Hoffmann J, Grimm W, Moosdorf R, Maisch B.
Department of Cardiology, Philipps-University of Marburg, Marburg, Germany.
Pruente@mailer.uni-marburg.de
The efficacy of RF energy versus the neodymium:yittrium aluminum-garnet laser to
create linear lesions was compared in fresh ex vivo swine hearts. A total of 598
lesions were created in four locations: ostium of the pulmonary veins,
trabeculated lateral left atrium, smooth posterior part of the right atrium, and
the isthmus between the inferior vena cava and tricuspid valve. A 400-micron bare
quartz fiber with CO2 cooling (distance to the tissue 5, 10, and 15 mm) and an RF
ablation catheter (4-mm tip) were mechanically dragged over the tissue at speeds
0.5, 1.0, and 1.5 mm/s. A continuous and transmural ablation line was recorded as
successful. A 100% success rate was achieved at the pulmonary veins and the
isthmus at some settings of energy delivery by the laser and RF. In the thick
posterior right atrium, RF resulted in transmural lesions only when associated
with carbonization, while the laser produced successful ablation lines in 100% of
the attempts. In the left atrium, because of the presence of prominent
trabeculations, RF was unsuccessful at all settings of energy delivery. In
contrast, deep photocoagulation by laser resulted in successful ablations in the
left atrium in 100% of attempts. Lesion formation was faster by laser ablation
and mean lesion width was at least 25% smaller with the laser than with RF. In
conclusion, the formation of linear lesions at the isthmus and at the pulmonary
veins was successful with the laser and RF. In the trabeculated left atrium and
the thick posterior right atrium, only laser ablation was successful.
PMID: 11139940 [PubMed - indexed for MEDLINE]
168. Heart. 2001 Jan;85(1):E2.
Varicella myocarditis in an adult.
Alter P, Grimm W, Maisch B.
Department of Internal Medicine-Cardiology, Philipps-University of Marburg,
Baldingerstrabetae, D-35033 Marburg/Lahn, Germany. alter@mailer.uni-marburg.de
A 24 year old male with varicella myocarditis was admitted with chest pain and
fever up to 39 degrees C. The ECG showed J point and ST elevation in leads V2-V4,
and inverted T waves in leads V5 and V6. Creatine kinase (CK) was raised to 435
U/l (CK-MB 36 U/l), troponin I was 63.4 microgram/l, and lactate dehydrogenase
was 359 U/l, suggesting cardiac involvement of varicella infection. The left
ventricle was dilated (58 mm) and left ventricular ejection fraction was globally
reduced (ejection fraction 45%). Myocarditis was confirmed by endomyocardial
biopsy. The patient was treated with specific varicella hyperimmunoglobulins,
aciclovir, and a non-steroidal anti-inflammatory drug. During two months follow
up the patient recovered completely. This case report is a reminder that a
varicella infection can cause myocarditis in adults. Early diagnosis and
appropriate treatment of this rare form of myocarditis may lead to complete
recovery.
PMCID: PMC1729589
PMID: 11119480 [PubMed - indexed for MEDLINE]
169. Angiology. 2000 Oct;51(10):831-6.
Hyperinsulinemia, lipoprotein (a), and Chlamydia pneumoniae antibodies--are they
risk factors or serologic predictors for progression of coronary artery disease?
Tontsch D, Noll B, Schaefer JR, Herzum M, Maisch B, Goeke B.
Department of Internal Medicine, Philipps-University, Marburg, Germany.
The authors studied 134 patients with unstable angina pectoris symptoms and 32
subjects without coronary artery disease (CAD) for the presence of classical risk
factors such as hypercholesterolemia, smoking, and family history of CAD. In
addition they analyzed plasma insulin levels, lipoprotein (a) (Lp [a]) levels,
and antibody titers against Chlamydia pneumoniae. All patients had a heart
catheterization. Patients with diabetes mellitus were excluded from the study.
Fasting insulin, low-density lipoprotein (LDL) cholesterol and Chlamydia
pneumoniae immunoglobulin G (IgG) and IgA antibody titers did not show any
difference in CAD from healthy control subjects, whereas Lp(a) was increased and
high-density lipoprotein (HDL) decreased in CAD patients. These data indicate
that lipoprotein (a), low HDL cholesterol, and smoking, but neither
hyperinsulinemia nor elevated Chlamydia pneumoniae titers, are risk factors or
predictors for CAD.
PMID: 11108327 [PubMed - indexed for MEDLINE]
170. Mol Cell Biochem. 2000 Sep;212(1-2):135-42.
Control of cardiomyocyte gene expression as drug target.
Rupp H, Benkel M, Maisch B.
Department of Internal Medicine and Cardiology, Philipps University of Marburg,
Germany.
Pressure overload of the heart is associated with a perturbed gene expression of
the cardiomyocyte leading to an impaired pump function. The ensuing
neuro-endocrine activation results in disordered influences of angiotensin II and
catecholamines on gene expression. To assess whether angiotensin II type 1
receptor inhibition can also counteract a raised sympathetic nervous system
activity, spontaneously hypertensive rats fed a hypercaloric diet were treated
with eprosartan (daily 90 mg/kg body wt) and cardiovascular parameters were
monitored with implanted radiotelemetry pressure transducers. Both, blood
pressure and heart rate were increased (p < 0.05) by the hypercaloric diet.
Although eprosartan reduced (p < 0.05) the raised systolic and diastolic blood
pressure, the diet-induced rise in heart rate was blunted only partially. In
addition to drugs interfering with the enhanced catecholamine influence,
compounds should be considered that selectively affect cardiomyocyte gene
expression via 'metabolic' signals.
PMID: 11108145 [PubMed - indexed for MEDLINE]
171. Z Kardiol. 2000 Oct;89(10):949-57.
[Significance of matrix metalloproteinases in cardiovascular diseases]
[Article in German]
Lamparter S, Maisch B.
Klinik für Innere Medizin Schwerpunkt Kardiologie, Marburg.
lamparte@mailer.uni-marburg.de
The cardiovascular interstitial space is largely composed of type I and III
fibrillar collagens. Tissue structure, form and function are determined not only
by the collagen content but also by the ratio of different collagens to each
other. Matrix metalloproteinases are members of a family of secreted and
membrane-bound enzymes that are capable of degrading highly proteolytic resistant
fibrillar type I and III collagens. Collagen tissue content is determined by
balanced collagen synthesis and degradation. MMP activity and adverse tissue
remodeling have been identified in coronary plaques in unstable angina. It has
also been linked with the progression of aortic aneurysms and with left
ventricular dilatation in congestive heart failure in patients with ischemic and
non-ischemic cardiomyopathy. The role of MMPs in these cardiovascular diseases
and possible therapeutic options are the focus of this review.
PMID: 11098546 [PubMed - indexed for MEDLINE]
172. Med Klin (Munich). 2000 Sep 15;95(9):523-6.
[Recurrent ventricular fibrillation after defibrillation in a patient with
pacemaker]
[Article in German]
Wilke A, Noll B, Maisch B.
Abteilung Innere Medizin-Schwerpunkt Kardiologie, Klinikum der
Philipps-Universität Marburg. wilke3@mailer,uni-marburg.de
HISTORY: A 62-year-old patient was admitted for an operation of a hernia of the
right groin in the surgical department. He had a dual chamber pacemaker because
of a binodal disease. Pre-operatively the patient was reanimated because of
ventricular fibrillation in dilated cardiomyopathy and was defibrillated 12
times, unexpectedly often. DIAGNOSIS: The reason of the repeated ventricular
fibrillation was a spike-on-T-phenomenon due to loss of the sensing function of
the pacemaker (entrance bloc). TREATMENT: Therefore, the pacemaker was explanted,
and the ventricular fibrillation came to an end. The patient recovered.
CONCLUSIONS: The repeated defibrillations with the electrodes over the basis and
the apex of the heart damaged the pacemaker. The following fibrillation episodes
were founded on a spike-on-T-phenomenon. In order to prevent such damage of
pacemakers, pacemaker patients should be defibrillated and cardioverted in
anterior-posterior position of the electrodes.
PMID: 11028169 [PubMed - indexed for MEDLINE]
173. Z Kardiol. 2000 Aug;89(8):691-7.
[Impediment of cellular immune response under treatment with ticlopidine in a
patient with Staphylococcus aureus endocarditis]
[Article in German]
Alter P, Schaefer JR, Maisch B.
Abteilung für Innere Medizin-Kardiologie Philipps-Universität Marburg.
A 52-year-old male with coronary artery disease was admitted with acute aortic
valve endocarditis and a temperature up to 39.5 degrees C caused by
Staphylococcus aureus. The patient was treated with ticlopidine (Tiklyd) after
percutaneous transluminal coronary angioplasties to reduce restenosis by
inhibiting thrombocyte aggregation. Upon admission c-reactive protein (CRP) was
389 mg/l. Interleukin-6 (IL-6) and Interleukin-2-receptor (IL-2-rec) were
distinctly increased. Monoclonal antimyocardial antibodies were found. Leukocyte
count never exceeded 9.8 G/l; however, transesophageal echocardiography validated
a soft vegetation of the aortic valve. Antibiotic therapy was initiated with
imipenem, gentamicin and vancomycin; clarithromycin was added after five days.
Temperature normalized after 24 days. The c-reactive protein decreased from 389
mg/l to 6 mg/l, and the elevated cytokine levels decreased accordingly.
Agranulocytosis or pancytopenia by ticlopidine through a toxic mechanism have
been described, which are normally reversible within three weeks; there has not
yet been a description of a missing leukocyte response in endocarditis as in this
case report. This is a special situation with lack of or impeded immunological
response, which limits the use of ticlopidine, especially since a therapeutic
alternative with clopidogrel is available.
PMID: 11013974 [PubMed - indexed for MEDLINE]
174. Am J Cardiol. 2000 Sep 15;86(6):688-92, A9.
Outcome of patients with sleep apnea-associated severe bradyarrhythmias after
continuous positive airway pressure therapy.
Grimm W, Koehler U, Fus E, Hoffmann J, Menz V, Funck R, Peter JH, Maisch B.
Department of Cardiology, Philipps-University Marburg, Germany.
Twenty-nine patients in whom severe bradyarrhythmias occurred exclusively during
obstructive sleep apnea and in whom advanced sinus node disease or
atrioventricular conduction system dysfunction had been excluded by invasive
electrophysiologic evaluation were prospectively followed on nasal continuous
positive airway pressure. During 54 +/- 10 months follow-up, no syncope and no
sudden deaths were observed, suggesting that patients with sleep apnea-associated
bradyarrhythmias and a normal electrophysiologic study appear to have a favorable
prognosis with continuous positive airway pressure.
PMID: 10980227 [PubMed - indexed for MEDLINE]
175. Clin Exp Immunol. 2000 Aug;121(2):270-4.
Autoantibodies in the sera of patients with rheumatic heart disease:
characterization of myocardial antigens by two-dimensional immunoblotting and
N-terminal sequence analysis.
Tontsch D, Pankuweit S, Maisch B.
Department of Internal Medicine-Cardiology, Philipps-University of Marburg,
Marburg, Germany. Tontsch@mailer.Uni-Marburg.de
The concept of antigenic mimicry in autoimmune diseases such as rheumatic fever
has been under investigation for decades and the range of cross-reactive tissue
antigens for streptococcal-induced antibodies identified in rheumatic heart
disease is still expanding. To identify heart tissue-reactive antigens which may
be implicated in the secondary immunopathogenesis of rheumatic fever, sera from
56 patients with acute rheumatic heart disease were probed in two-dimensional
Western blots for reactivity against heart tissue antigens. After two-dimensional
immunoblot analysis, proteins were submitted to N-terminal amino acid sequence
analysis. This analysis identified creatine kinase, two mitochondrial proteins
and, at a low level, various stress proteins as cross-reactive myocardial
antigens. Therefore, in addition to myosin, creatine kinase may represent another
major antigen for autoreactive antibodies in rheumatic heart disease.
Mitochondrial proteins have been implicated in the pathogenesis of inflammatory
heart disease for some years, and in this study we have identified two
mitochondrial proteins as relevant antigens in rheumatic heart disease.
PMCID: PMC1905712
PMID: 10931141 [PubMed - indexed for MEDLINE]
176. Herz. 2000 May;25(3):279-85.
The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases
(ESETCID). First epidemiological results.
Hufnagel G, Pankuweit S, Richter A, Schönian U, Maisch B.
Department of Internal Medicine and Cardiology, Philipps-University of Marburg,
Germany. hufnagel@mailer.uni-marburg.de
By including immunohistochemical parameters the WHF Task Force for the Definition
of Acute and Chronic Myocarditis expanded the light microscopical Dallas criteria
of myocarditis. The rapid development of new molecular biological techniques such
as polymerase chain reaction (PCR) and in-situ hybridization has improved our
understanding of the underlying etiological and pathophysiological mechanisms in
inflammatory heart disease. Treatment of dilated cardiomyopathy with inflammation
is still controversial, however. The American Myocarditis Treatment Trial could
not demonstrate a significant difference in the improvement of ejection fraction
between patients with active myocarditis in the cyclosporine/prednisolone treated
group when compared to placebo. In the European Study of Epidemiology and
Treatment of Inflammatory Heart Disease (ESETCID) patients with acute or chronic
myocarditis are treated specifically according to the etiology of the disease.
Patients are screened not only for infiltrating cells, but also for the presence
of persisting viral genome (enterovirus, cytomegalovirus and adenovirus). By
investigating endomyocardial biopsies of 3,055 patients ongoing inflammatory
processes in the heart could be found in 17.2%. Only 182 showed a reduced
ejection fraction below 45% fulfilling the entrance criteria for the ESETCID
trial. These data imply that in symptomatic patients inflammatory heart muscle
disease has to be considered regardless of left ventricular function and that
endomyocardial biopsy can be an important tool for diagnosis. Virus could be
detected in 11.8% (enterovirus 2.2%, cytomegalovirus 5.4%, adenovirus 4.2%).
These first epidemiological results of this prospective randomized study
demonstrate that viral persistence may contribute to the pathogenesis of
inflammatory heart muscle disease, and that in chronic myocarditis viral
persistence occurs in a smaller percentage of patients compared to previously
published studies which were performed on highly selected patients.
PMID: 10904853 [PubMed - indexed for MEDLINE]
177. Herz. 2000 May;25(3):221-6.
Prevalence of viral genome in endomyocardial biopsies from patients with
inflammatory heart muscle disease.
Pankuweit S, Portig I, Eckhardt H, Crombach M, Hufnagel G, Maisch B.
Department of Internal Medicine-Cardiology, Philipps-University Marburg, Germany.
pankuwei@mailer.uni-marburg.de
In the report of the 1995 World Health Federation/International Society and
Federation of Cardiology (WHF/ISFC) Task Force on the Definition and
Classification of Cardiomyopathies, the definition of heart muscle diseases was
updated. Idiopathic, autoimmune, and infectious forms of inflammatory
cardiomyopathy are now recognized in this definition. Enteroviruses, adenoviruses
and cytomegaloviruses are considered as main etiopathological factors in the
pathogenesis of inflammatory heart disease. A wide range of different assays have
been and are currently being used, either alone or in combination, to assay for
the presence of enteroviral RNA and/or DNA of cytomegalo- and adenoviruses in
endomyocardial biopsy and explanted heart samples. The prevalence of cardiotropic
viruses in endomyocardial biopsies of patients with clinically suspected
inflammatory cardiomyopathy varies widely: enteroviral genome was detected in
endomyocardial biopsies of 3 to 53% of patients, cytomegaloviral DNA was detected
in 3 to 40% of patients with inflammatory heart disease and adenoviruses in 3 to
23% of the patients. This report summarizes the methods that have been used and
the results of molecular biological investigation with polymerase chain reaction,
which were reported by several groups over the last years. Taking this together
it seems to be clear that the improvement of molecular biological techniques and
the experience of people working with these methods will lead to more reliable
results on prevalence, persistence and the diagnostic value of these
investigations. These findings have to be taken into account in future diagnostic
and therapeutic studies in the field of cardiomyopathies.
PMID: 10904842 [PubMed - indexed for MEDLINE]
178. Herz. 2000 May;25(3):200-9.
Definition of inflammatory cardiomyopathy (myocarditis): on the way to consensus.
A status report.
Maisch B, Portig I, Ristic A, Hufnagel G, Pankuweit S.
Department of Internal Medicine-Cardiology, Philipps-University Marburg, Germany.
maisch@mailer.uni-marburg.de
This article reviews the current state of consensus reached for the diagnosis of
myocarditis and dilated cardiomyopathy on the basis of conventional
histopathological and immunohistochemical methods for inflammatory infiltrates in
addition to molecular biological methods for persistence of viral genome in
endomyocardial biopsies. Additionally, a brief overview is presented stating the
current knowledge on effector mechanisms of the immune system in myocarditis and
dilated cardiomyopathy.
PMID: 10904839 [PubMed - indexed for MEDLINE]
179. Herz. 2000 May;25(3):189-99.
Prediction of major arrhythmic events and sudden cardiac death in dilated
cardiomyopathy. The Marburg Cardiomyopathy Study design and description of
baseline clinical characteristics.
Grimm W, Hoffmann J, Menz V, Müller HH, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University, Marburg,
Germany.
The Marburg Cardiomyopathy Study (MACAS) is a prospective observational study
designed to determine the value of the following potential non-invasive
arrhythmia risk predictors in more than 200 patients with idiopathic dilated
cardiomyopathy (IDC) over a 5-year follow-up period: New York Heart Association
functional class, left ventricular end-diastolic diameter and ejection fraction,
left bundle branch block and atrial fibrillation on ECG, QTc and JTc-dispersion
on 12-lead ECG, abnormal time-domain analysis and spectral turbulence analysis of
the signal-averaged ECG, ventricular arrhythmias and heart-rate variability on
24-hour Holter ECG, baroreflex sensitivity, and microvolt T wave alternans during
exercise. This report describes the rationale of MACAS as well as the clinical
characteristics of the first 236 patients enrolled between March 1996 and October
1999. The prognostic significance of the potential arrhythmia risk predictors in
MACAS will be determined by multivariate Cox analysis at the end of 5-year
follow-up. Primary endpoints are total mortality and major arrhythmic events
defined as sustained ventricular tachycardia, ventricular fibrillation or sudden
cardiac death. The results of MACAS will have important implications for the
design of future studies evaluating the role of prophylactic defibrillator
therapy in idiopathic dilated cardiomyopathy.
PMID: 10904838 [PubMed - indexed for MEDLINE]
180. Herz. 2000 May;25(3):181-8.
Cardiac rhythm and conduction disturbances: what is the role of autoimmune
mechanisms?
Ristic AD, Maisch B.
Department of Internal Medicine-Cardiology, Philipps University, Marburg,
Germany.
The immunopathogenesis of cardiac rhythm and conduction disorders has been
underestimated. Therefore, the aim of this review is to analyze the current data
and controversial issues in this area. The incidence of autoantibodies to human
conducting tissue has been analyzed in sick sinus syndrome, bradyarrhythmia, and
hypersensitive carotid sinus syndrome. Patients with anti-sinus node antibodies
(ASNab) have a 10-fold higher risk of developing sick sinus syndrome, compared to
age-matched controls. The risk of acquiring an atrioventricular block was up to
3-fold in patients with anti-atrioventricular node antibodies (AAVNab) in
comparison to controls. The incidence of anti His antibodies (AHISab) was low
both in patients and controls. Anti-cardiac Purkinje cell antibodies (ACPCab)
seemed to be an epiphenomenon and not a pathogenetic marker of conduction
disorders. In congenital heart block association with HLA-B27 and HLA-DR3 is a
possible prerequisite in the pathophysiology of the disease, although
transplacental passage of various antibodies and immune complexes is widely
recognized. The main autoantibodies detected both in children with congenital
heart block and their mothers are anti-Ro/SS-A and anti-La/SS-B antibodies. The
cross-reactivity of laminin with anti-La antibodies could be important in the
initiation of the autoimmune process. Autoantibodies against adrenoceptors and
muscarinic cholinergic receptors of neonatal heart and human endogenous
retrovirus-3 expressed in fetal cardiac tissue could also play a role in the
pathogenesis of the congenital heart block. Of note, apoptosis could be one of
the possible mechanisms of the progression of the congenital conduction
disturbances to the complete heart block. In addition, evidence is compiling that
cellular activation and cellular cytotoxicity specific for a given target tissue
appears to be at least equally important in the pathogenesis of the disease as
the humoral response. In conclusion, the immunopathogenesis of certain cardiac
rhythm and conduction disorders is well established in sick sinus syndrome,
congenital heart block, and connective tissue diseases. ASNab, AAVNab,
anti-Ro/SS-A, and anti-La/SS-B antibodies can be regarded as diagnostic and
prognostic markers.
PMID: 10904837 [PubMed - indexed for MEDLINE]
181. Herz. 2000 May;25(3):161-7.
Mitochondrial DNA deletions in cardiomyopathies.
Ruppert V, Maisch B.
Department of Internal Medicine and Cardiology, Philipps University Marburg,
Germany. ruppertv@aol.com
Structural changes in the mitochondrial DNA (mtDNA) have been implicated in the
pathogenesis of a number of diseases. In this study we report on deletions in the
mtDNA of patients with dilated cardiomyopathy (DCM) and post mortem control
samples. Total DNA was extracted from left ventricular tissue and nearly the
whole mtDNA was amplified using the long PCR technique. For quantitative analysis
of the PCR-products with mtDNA deletions the fragments were scanned by a laser
densitometer. With the method of long PCR we could detect wild-type and deleted
mtDNA in 1 reaction. A total of 14 different deletions ranging from 3.3 to 12.6
kb could be detected. The highest rate of deleted as compared to wild-type mtDNA
was 12% in 1 control and 9% in a patient with dilated cardiomyopathy. The number
of mitochondrial deletions increase with age in the control group. Additional
deletions appear sooner in cardiomyopathic hearts than in control hearts. With
regard to the low quantity of the deleted mtDNA and the cumulative nature of
these deletions by ageing, we conclude that they may be relevant in individual
cases only. A general pathogenic effect on the development of dilated
cardiomyopathy is less likely. The mutations may be a sign of increasing stress
to the heart, however, thus promoting consecutive damage of mtDNA by initiating a
vicious circle.
PMID: 10904834 [PubMed - indexed for MEDLINE]
182. Arterioscler Thromb Vasc Biol. 2000 Jul;20(7):1796-9.
Increased production of HDL ApoA-I in homozygous familial defective ApoB-100.
Schaefer JR, Winkler K, Schweer H, Hoffmann MM, Soufi M, Scharnagl H, Maisch B,
Wieland H, Steinmetz A, März W.
Department of Internal Medicine, Division of Cardiology, University of Marburg,
Germany.
Familial defective apolipoprotein (apo) B-100 (FDB) is a frequent cause of
hypercholesterolemia. Hypercholesterolemia in homozygous FDB is less severe than
in homozygotes for familial hypercholesterolemia. Recently, we showed decreased
low density lipoprotein (LDL) apoB-100 fractional catabolism and decreased
production of LDL due to an enhanced removal of apoE-containing precursors in a
patient with homozygous FDB. The effects of defective apoB-100 on high density
lipoprotein (HDL) metabolism are unknown. We studied HDL apoA-I metabolism in
this FDB patient and in 6 control subjects by using (2)H(3)-L-leucine as a
tracer. ApoA-I levels were normal in all study subjects. However, the fractional
catabolic rate and the production rate of apoA-I were increased, by 79% and 70%,
respectively, in FDB; the fractional catabolic rate of apoA-I in FDB was 0.34
day(-1) compared with 0.19+/-0.03 day(-1) in normal controls. The production rate
of apoA-I in FDB was 18.4 mg. kg(-1). d(-1) compared with 10.8+/-2.3 mg. kg(-1).
d(-1) in controls. Thus, we have shown for the first time that defective apoB-100
may influence HDL kinetics. The increase in total HDL turnover might enhance
reverse cholesterol transport and could contribute to the seemingly benign
clinical course of FDB compared with that of familial hypercholesterolemia.
PMID: 10894819 [PubMed - indexed for MEDLINE]
183. Am Heart J. 2000 Jul;140(1):43-51.
Arrhythmia risk stratification in idiopathic dilated cardiomyopathy based on
echocardiography and 12-lead, signal-averaged, and 24-hour holter
electrocardiography.
Grimm W, Glaveris C, Hoffmann J, Menz V, Müller HH, Hufnagel G, Maisch B.
Department of Cardiology, Hospital of the Philipps-University of Marburg,
Germany.
BACKGROUND: To date, considerable controversy exists regarding noninvasive
arrhythmia risk stratification in idiopathic dilated cardiomyopathy (IDC).
Methods and Results Between 1992 and 1997, 202 patients with IDC without a
history of sustained ventricular tachycardia (VT) underwent echocardiography,
signal-averaged electrocardiogram (ECG), and 24-hour Holter ECG in the absence of
antiarrhythmic drugs. During 32 +/- 15 months of prospective follow-up, major
arrhythmic events, including sustained VT, ventricular fibrillation, or sudden
death, occurred in 32 (16%) of 202 patients. After adjusting for baseline medical
therapy and antiarrhythmic therapy during follow-up, multivariate Cox regression
analysis identified a left ventricular (LV) end-diastolic diameter >/=70 mm and
nonsustained VT on Holter as the only independent arrhythmia risk predictors. The
combination of an LV end-diastolic diameter >/=70 mm and nonsustained VT was
associated with a 14. 3-fold risk for future arrhythmic events (95% confidence
interval 2. 3-90). To further elucidate the prognostic value of LV ejection
fraction, multivariate Cox analysis was repeated with ejection fraction forced to
remain in the model. In the latter model, an ejection fraction </=30% combined
with nonsustained VT on Holter was found to be a significant arrhythmia risk
predictor with a relative risk of 14.6 (95% confidence interval 2.2-97).
CONCLUSIONS: The combination of an LV end-diastolic diameter >/=70 mm and
nonsustained VT on Holter, and the combination of LV ejection fraction </=30% and
nonsustained VT on Holter, identify a subgroup of patients with IDC with a
14-fold risk for subsequent arrhythmic events. These findings have important
implications for the design of future studies evaluating the role of prophylactic
defibrillator therapy in patients with IDC.
PMID: 10874262 [PubMed - indexed for MEDLINE]
184. Herz. 2000 Mar;25(2):113-6.
Strategies to optimize CAD prevention in modern cardiology. The "Marburg CAD
Prevention Project".
Schaefer JR, Simon B, Soufi M, Sattler A, Noll B, Herzum M, Maisch B.
Department of Internal Medicine & Cardiology, University Hospital Marburg,
Germany. schaefer@mailer.uni-marburg.de
In recent years we identified numerous cardiovascular risk factors and had been
able to reduce cardiovascular events by a variety of different interventions.
There is no question that we can improve the course of coronary artery disease
(CAD) in patients with a high-risk profile by modifying these factors. Despite
this knowledge, many patients with known CAD or myocardial infarction are not
treated for secondary prevention as recommended by well established guidelines
(http:¿www.chd-taskforce.com). In order to improve secondary prevention in our
patients we started a project, the so called "Marburg CAD Prevention Project". By
this we combine our computer data base of the CAD preventional routine laboratory
with the computer program CARDDAS. Individual risk factors and the angiographic
findings were analyzed. Patients as well as local physicians were informed on the
need to treat the important risk factors. This approach ensures that at least all
of our patients with documented CAD receive the appropriate preventional
recommendations and treatment.
PMID: 10829250 [PubMed - indexed for MEDLINE]
185. Herz. 2000 Mar;25(2):91-4.
Restenosis after percutaneous coronary interventions and infection.
Herzum M, Schaefer JR, Simon B, Menz V, Noll B, Maisch B.
Department of Internal Medicine, Philipps University of Marburg.
herzum@mailer.uni-marburg.de
Infectious agents may directly or indirectly (through the response of the host's
immune system) modulate the growth of vascular cells. Local and/or systemic
increase of cytokines could influence the extent of (re-)stenosis in the vascular
tree. Further studies in this field may identify patients at a high risk for
atherogenesis and restenosis. Their results should be helpful in treating
restenosis after percutaneous coronary interventions.
PMID: 10829246 [PubMed - indexed for MEDLINE]
186. Dtsch Med Wochenschr. 2000 Apr 20;125 Suppl 1:S15.
[Endomyocardial biopsy in myocarditis]
[Article in German]
Maisch B.
Klinik für Innere Medizin Schwerpunkt Kardiologie Klinikum der
Philipps-Universität, Marburg.
PMID: 10819001 [PubMed - indexed for MEDLINE]
187. Z Kardiol. 2000 Feb;89(2):84-92.
[Correlation between cardiac autonomic activity and compromise of left
ventricular function in dilated cardiomyopathy]
[Article in German]
Hoffmann J, Grimm W, Menz V, Maisch B.
Philipps-Universität Marburg, Klinik für Innere Medizin und Kardiologie, Marburg.
HoMarburg@AOL.com
In recent years, evaluation of cardiac autonomic activity by means of heart rate
variability (HRV) determination and baroreflex sensitivity (BRS) testing has
become readily available. The results of the ATRAMI (Autonomic Tone and Reflexes
After Myocardial Infarction) study showed that both diminished HRV and
baro-reflex sensitivity are associated with poor outcome in patients after
myocardial infarction. In contrast to patients with coronary disease little
information is available concerning cardiac autonomic activity in idiopathic
dilated cardiomyopathy (IDC). Therefore, HRV and BRS were assessed in 160
patients with IDC and preserved sinus rhythm in order to investigate the
relationship between HRV, BRS, and left ventricular ejection fraction. Time
domain indices of HRV were computed from 24-hour digital Holter recordings. BRS
testing was performed using the noninvasive phenylephrine method. Mean standard
deviation of all normal RR intervals (SDNN) of the whole study population was 112
+/- 46 ms. A well preserved HRV (SDNN > 105 ms) was found in 74 patients (46%), a
moderately decreased HRV (SDNN 70-105 ms) in 59 patients (37%), and a severely
decreased HRV (SDNN < 70 ms) in 27 patients (17%). Mean BRS was 7.5 +/- 5.0 ms/mm
Hg. A well preserved BRS (> 6 ms/mm Hg) was present in 78 patients (57%), a
moderately decreased BRS (3-6 ms/mm Hg) was present in 38 patients (28%), and a
severely decreased BRS (< 3 ms/mm Hg) in 21 patients (15%). There was only a weak
correlation between SDNN and BRS (r = 0.19; p < 0.05). A weak correlation was
found for SDNN and left ventricular ejection fraction (r = 0.29; p < 0.05). There
was no significant correlation between BRS and left ventricular ejection fraction
(r = 0.14). In summary, there was only a weak correlation between the HRV, BRS,
and left ventricular ejection fraction in patients with IDC suggesting that these
3 variables may be independent predictors of sudden death in IDC. The relative
prognostic value of these variables and other potential risk predictors including
the presence of arrhythmias on Holter, microvolt T wave alternans, QTc
dispersion, and signal-averaged ECG is currently under investigation in a large
prospective observational study (Marburg Cardiomyopathy Study (MACAS)) during
5-year follow-up at our institution.
PMID: 10768276 [PubMed - indexed for MEDLINE]
188. Heart. 2000 May;83(5):531-8.
Heart rate variability and baroreflex sensitivity in idiopathic dilated
cardiomyopathy.
Hoffmann J, Grimm W, Menz V, Müller HH, Maisch B.
Department of Internal Medicine and Cardiology, Hospital of the Philipps-
University of Marburg, Baldingerstrasse, 35033 Marburg, Germany.
HoMarburg@aol.com
OBJECTIVE: To examine the relation between cardiac autonomic tone, assessed by
baroreflex sensitivity and heart rate variability, and left ventricular function,
arrhythmias on Holter monitoring, and clinical variables in patients with
idiopathic dilated cardiomyopathy. DESIGN: A prospective observational study.
PATIENTS: 160 patients with idiopathic dilated cardiomyopathy and preserved sinus
rhythm in the absence of antiarrhythmic drug treatment. Measures of heart rate
variability obtained by digital 24 hour Holter recordings included the mean of
all coupling intervals between normal beats (RRm), the standard deviation of the
mean of normal RR intervals (SDNN), and the square root of the mean of the
squared differences between adjacent normal RR intervals (rMSSD). Baroreflex
sensitivity testing was performed using the phenylephrine method. RESULTS: Mean
SDNN (SEM) was 112 (46) ms, and baroreflex sensitivity was 7.5 (5.0) ms/mm Hg.
SDNN showed a weak correlation with baroreflex sensitivity (r = 0.19, p < 0.05)
and with left ventricular ejection fraction (r = 0.29, p < 0.05). SDNN showed no
significant correlation with age (r = -0.07), the presence of non-sustained
ventricular tachycardia (r = -0.13), or left ventricular end diastolic diameter
(r = -0.07). In addition, baroreflex sensitivity showed no significant
correlation with age (r = -0.13), non-sustained ventricular tachycardia (r =
-0.08), left ventricular end diastolic diameter (r = 0.09), or ejection fraction
(r = 0.14). CONCLUSIONS: The weak correlation between baroreflex sensitivity and
heart rate variability suggests that these two indices explore different aspects
of cardiac autonomic control in patients with idiopathic dilated cardiomyopathy.
The weak or absent correlation between baroreflex sensitivity, heart rate
variability, and other potential non-invasive risk predictors, including left
ventricular ejection fraction, left ventricular end diastolic diameter, and
non-sustained ventricular tachycardia on Holter monitoring, indicate that these
variables may have independent prognostic value in idiopathic dilated
cardiomyopathy.
PMCID: PMC1760828
PMID: 10768902 [PubMed - indexed for MEDLINE]
189. Am J Cardiol. 2000 Apr 1;85(7):899-904, A10.
Significance of accelerated idioventricular rhythm in idiopathic dilated
cardiomyopathy.
Grimm W, Hoffmann J, Menz V, Schmidt C, Müller HH, Maisch B.
Department of Cardiology, Hospital of the Philipps-University of Marburg,
Germany.
Holter monitoring was performed in 202 patients with idiopathic dilated
cardiomyopathy, which revealed accelerated idioventricular rhythm in 16 patients
(8%) and nonsustained ventricular tachycardia in 70 patients (35%). During 32 +/-
15-month prospective follow-up, no significant difference was observed for major
arrhythmic events and transplant-free survival between patients with and without
accelerated idioventricular rhythm, whereas patients with nonsustained
ventricular tachycardia had a significantly higher incidence of major arrhythmic
events and a lower transplant-free survival rate.
PMID: 10758938 [PubMed - indexed for MEDLINE]
190. Internist (Berl). 2000 Jan;41(1):68-9.
[Endocarditis prophylaxis]
[Article in German]
Alter P, Maisch B.
Klinik für Innere Medizin-Kardiologie, Philipps-Universität, Marburg.
PMID: 10712094 [PubMed - indexed for MEDLINE]
191. Clin Cardiol. 2000 Feb;23(2):103-8.
Cardiac autonomic tone and its relation to nonsustained ventricular
tachyarrhythmias in idiopathic dilated cardiomyopathy.
Hoffmann J, Grimm W, Menz V, Maisch B.
Department of Cardiology, Hospital of the Philipps-University of Marburg,
Germany.
BACKGROUND: In contrast to postinfarct patients, little is known about cardiac
autonomic tone and its relation to spontaneous ventricular tachyarrhythmias in
idiopathic dilated cardiomyopathy (IDC). Both heart rate variability (HRV) and
baroreflex sensitivity (BRS) are indices of autonomic innervation of the heart.
HYPOTHESIS: The aim of the present study was to determine the relation between
cardiac autonomic tone assessed by HRV and BRS and spontaneous nonsustained
ventricular tachycardia (NSVT) on Holter in a large patient population with IDC.
METHODS: 24-h digital Holter recordings including HRV analysis and BRS testing
were prospectively performed in 137 patients with IDC and preserved sinus rhythm.
Mean age was 48 +/- 12 years, and mean left ventricular (LV) ejection fraction
was 32 +/- 9%. The HRV analysis on Holter included the mean RR interval (RRm),
the standard deviation of all normal RR intervals (SDNN), the square root of the
mean of the squared differences between adjacent normal RR intervals (rMSSD), and
the proportion of adjacent normal RR intervals differing more than 50 ms (pNN50).
Testing for BRS was performed noninvasively using the phenylephrine method.
RESULTS: Of 137 study patients, 42 (31%) had spontaneous NSVT on 24-h Holter.
Compared with patients without NSVT, patients with NSVT on Holter had a higher
New York Heart Association (NYHA) functional class (NYHA III: 40 vs. 18%, p <
0.01), a lower ejection fraction (29 +/- 9 vs. 34 +/- 9%, p = 0.01), and an
increased LV end-diastolic diameter (69 +/- 8 mm vs. 66 +/- 7 mm, p = 0.03). The
HRV variables rMSSD, pNN50, RRm, and BRS did not differ significantly between
patients with and without spontaneous NSVT. Only SDNN on Holter was slightly
lower in patients with versus without NSVT (106 +/- 45 vs. 121 +/- 46 ms, p =
0.08). CONCLUSIONS: Patients with IDC and spontaneous NSVT on Holter are
characterized by a higher NYHA functional class, a lower LV ejection fraction, an
increased LV end-diastolic diameter, and a tendency toward a lower SDNN value
compared with patients without NSVT. The remaining measures of HRV including
rMSSD and pNN50 reflecting primarily tonic vagal activity, as well as BRS
reflecting predominantly reflex vagal activity, were similar in patients with and
without NSVT. The prognostic significance of these findings in patients with IDC
is currently under investigation in the Marburg Cardiomyopathy Study (MACAS) at
our institution.
PMID: 10676601 [PubMed - indexed for MEDLINE]
192. J Cardiovasc Electrophysiol. 1999 Dec;10(12):1631-5.
Transient QT prolongation with torsades de pointes tachycardia after ablation of
permanent junctional reciprocating tachycardia.
Grimm W, Hoffmann J, Menz V, Maisch B.
Department of Medicine, Hospital of the Philipps-University of Marburg, Germany.
INTRODUCTION: Catheter ablation with radiofrequency energy is a curative therapy
in patients with permanent junctional reciprocating tachycardia (PJRT). METHODS
AND RESULTS: For the first time, we report a case of transient QT prolongation
with torsades de pointes tachycardia 18 hours after successful radiofrequency
energy ablation of PJRT in a 25-year-old woman with tachycardia-induced
cardiomyopathy. Of note, the torsades de pointes occurred in the absence of
bradycardia, electrolyte disturbances, or QT-prolonging drugs. This patient
initially was thought to have a hereditary long QT syndrome that was unmasked by
PJRT ablation. Therefore, the patient received an implantable defibrillator in
addition to beta-blocker therapy, which was discontinued 6 months later.
Surprisingly, the QT interval completely normalized within 1 week after PJRT
ablation, and the patient remained free of arrhythmias during a follow-up period
of 4.5 years. CONCLUSION: Patients with incessant tachyarrhythmias should undergo
ECG monitoring for at least 24 hours following successful radiofrequency catheter
ablation because transient QT prolongation with torsades de pointes may occur
even in the absence of bradycardia, QT-prolonging drugs, or electrolyte
disturbances.
PMID: 10636193 [PubMed - indexed for MEDLINE]
193. Herzschrittmacherther Elektrophysiol. 2000 Jan;11 Suppl 1:89-90.
[In Process Citation]
[Article in German]
Funck RC, Kriebel B, Himmrich E, Hartung W, Dänschel W, Saborowski F, Kühnert H,
Maisch B; PROVE-Studiengruppe.
Philipps-Universität Marburg, Marburg.
PMID: 19495658 [PubMed - in process]
194. Z Kardiol. 1999 Sep;88(9):653-60.
[Prospective evaluation of effect of carvedilol therapy on heart rate variability
in patients with dilated cardiomyopathy]
[Article in German]
Hoffmann J, Grimm W, Menz V, Hufnagel G, Maisch B.
Philipps-Universität Marburg, Abteilung für Innere Medizin und Kardiologie,
Baldingerstrasse, 35033 Marburg. HoMarburg@aol.com
The aim of the present study was to assess the effects of carvedilol therapy in
addition to conventional heart failure therapy on heart rate variability (HRV)
and on left ventricular function in 14 patients with mild to moderate heart
failure due to idiopathic dilated cardiomyopathy (IDC). After a 3- to 4-week
titration period, carvedilol was titrated up to 50mg daily, or the highest dose
tolerated (at least 25mg daily). Maintenance treatment was then continued for 8
weeks. Digital 24-hour Holter recordings were obtained at baseline and after 8
weeks of carvedilol therapy. HRV for the entire 24-hour period was computed in
the time domain using the Oxford Medilog Excel 2 analysis system. Measures of HRV
included the mean of all coupling intervals between normal beats (RRm), the
standard deviation of all normal RR intervals (SDNN), the square root of the mean
of the squared differences between adjacent normal RR intervals (rMSSD), and the
proportion of adjacent normal RR intervals differing >50 ms (pNN50). Additional
treatment with carvedilol induced a significant increase in HRV: SDNN increased
from 77+/-21 ms to 110+/-22 ms (p=0.001), rMSSD from 19+/-7 ms to 26+/-7 ms
(p=0.02), and mean pNN50-value increased from 1.7+/-1.3% to 5.5+/-4.5% (p<0.01)
under therapy with carvedilol. Mean heart rate on carvedilol calculated over 24
hours was 13 beats less than at baseline (75 bpm versus 88 bpm, p<0.01). After 2
months of additional treatment with carvedilol, both hemodynamic and clinical
parameters improved: left ventricular ejection fraction increased from 24+/-7% to
30+/-10% (p<0.05), and New York Heart Association class decreased from 2.5+/-0.8
to 1.8+/-0.7 (p<0.05). In summary, eight weeks of additional carvedilol therapy
induced a significant increase in HRV parameters related to parasympathetic
activity in patients with IDC. Whether increased vagal tone may contribute to the
protective effect of carvedilol has to be evaluated by further studies.
PMID: 10525927 [PubMed - indexed for MEDLINE]
195. Am J Physiol. 1999 Oct;277(4 Pt 2):H1540-5.
Radiotelemetric characterization of overweight-associated rises in blood pressure
and heart rate.
Rupp H, Maisch B.
Molecular Cardiology Laboratory, Department of Internal Medicine, Philipps
University of Marburg, 35033 Marburg, Germany. Rupp@mailer.uni-marburg.de
We addressed the hypothesis that hypercaloric diets induce hyperkinetic
hypertension irrespective of day-night cycle and locomotor activity that is
associated with altered cardiac myosin isozymes. Normotensive rats with implanted
radiotelemetry pressure transducers were fed increasing amounts of coconut fat
(8, 16, and 24%, each for 2 wk) corresponding to 20-47% of total calories from
fat. Thereafter, increasing amounts of sucrose (16, 32, and 50%) and fructose
(50%) were added to the 24% fat diet corresponding to 13-40% of total calories
from sugar. In contrast to the fat diets, the 32% and 50% sucrose diets as well
as the 50% fructose diets increased (P < 0.05) blood pressure (systolic maximum
+13 mmHg, diastolic maximum +4 mmHg, mean maximum +7 mmHg) and heart rate
(maximum +50 beats/min) irrespective of the day-night cycle and the unaltered
locomotor activity. Furthermore, body weight increased (P < 0.05) during the 32%
and 50% sucrose feedings. The increased blood pressure and heart rate normalized
after rats were fed a regular chow. We concluded that an excessive caloric intake
results in hyperkinetic hypertension that increases the myosin V(1) proportion.
PMID: 10516193 [PubMed - indexed for MEDLINE]
196. Clin Chem Lab Med. 1999 Jun;37(6):643-8.
Semi-automated rapid isoelectric focusing of apolipoproteins C from human plasma
using Phastsystem and immunofixation.
Noll B, Hackler R, Pelzer M, Pelzer S, Nusser P, Maisch B, Schaefer JR, Steinmetz
A.
Zentrum Innere Medizin, Abteilung Kardiologie, Klinikum der Philipps Universität
Marburg, Germany.
Apolipoproteins (apo) C-I, C-II, and C-III play crucial roles in intravascular
lipid metabolism. Whereas apo C-II is an obligate cofactor for lipoprotein
lipase, apo C-III was shown to inhibit its action. Apo C-I can be a potent
cofactor of human lecithin:cholesterol acyltransferase. Structural mutants and
deficiencies of apo C-II lead to hypertriglyceridemia. A similar phenotype is
associated with apo C-III mutants and is inducible by overexpression of human apo
C-III in transgenic animals. No structural variant has so far been reported for
apo C-I. The present paper describes a rapid semi-automated procedure for
isoelectric focusing analysis of these C-apolipoproteins from whole plasma or
serum and their visualization by immunofixation and silver staining. The
procedure allows detection of charged variants of C-apolipoproteins. As applied
to 295 patients with coronary heart disease and 85 controls, it also serves to
detect deficiency syndromes of these apolipoproteins. The procedure provides
reliable, easy and quick analysis of C-apolipoproteins applicable as a routine or
screening procedure not restricted to specialized laboratories.
PMID: 10475072 [PubMed - indexed for MEDLINE]
197. Herz. 1999 May;24(3):225-31.
Control of apoptosis of cardiovascular fibroblasts: a novel drug target.
Rupp H, Maisch B.
Department of Internal Medicine and Cardiology, Philipps-University of Marburg,
Germany. Rupp@mailer.uni-marburg.de
Adequate control of survival or programmed cell death (apoptosis) of
cardiovascular cells appears as an important drug target. While prevention of
apoptotic death of cardiomyocytes has been assessed in detail, selective
induction of apoptosis of vascular smooth muscle cells or fibroblasts could also
be of relevance. Thus, induction of apoptosis of vascular smooth muscle cells by
p65 NF-kappa B and Bcl-xL antisense oligonucleotides or p53 overexpression could
be useful for limiting vascular lesions associated with restenosis. Although
fibroblasts represent the majority of cardiac cells, few attempts were made to
induce fibroblast apoptosis in disorders associated with excessive collagen
deposition and fibrosis. It is hypothesized that early interference with
fibroblast proliferation after myocardial infarction or inflammatory heart
disease limits fibrosis which further impairs cardiac performance. A candidate
approach could involve growth factor analogues which are known to induce
fibroblast apoptosis when an incomplete growth stimulus persists.
PMID: 10412646 [PubMed - indexed for MEDLINE]
198. Herz. 1999 May;24(3):211-8.
[Cell death in inflammatory heart muscle diseases--apoptosis or necrosis?]
[Article in German]
Pankuweit S, Jobmann M, Crombach M, Portig I, Alter P, Kruse T, Hufnagel G,
Maisch B.
Klinik für Innere Medizin und Kardiologie, Philipps-Universität Marburg.
pankuwei@mailer.uni-marburg.de
Cell death can be induced by 2 different mechanisms: necrosis and apoptosis.
Necrosis, on the one hand, is usually caused by unphysiological stress factors
such as hyperthermia or hypoxia, apoptosis, on the other hand, is part of the
normal organ development and controls for example immune responses.
Morphologically, necrosis is characterized by swelling of cells and their
organelles leading to the disruption of the cell membrane, which in turn causes
an inflammatory reaction in the surrounding tissue. Morphological and biochemical
criteria (Figure 1, Table 1) of apoptosis are the condensation of chromatin
leading to the development of apoptotic bodies or membrane-enclosed vesicles
containing oligonucleosomal DNA fragments. Important diagnostic tools of cell
death (Table 2), such as the TUNEL test (Figure 2) or gel electrophoresis of
extracted DNA (Figure 3) are based on the above mentioned biochemical
characteristics, but a reliable differentiation of apoptotic versus necrotic
processes is not always possible. Experimental studies in animals and studies in
various diseases of the cardiovascular system were able to show that apoptosis in
myocytes can be induced, an issue that has long been discussed controversially.
Ischemia, reperfusion, and myocardial infarction were also shown to lead to
apoptosis in cardiomyocytes, whereas cell destruction was caused mainly by
necrosis. Several authors (Table 3) demonstrated apoptotic indices in
cardiomyocytes of patients with dilatated cardiomyopathy, arrhythmogenic right
ventricular cardiomyopathy and patients with acute infarction from 0.25 to 35% by
the use of the TUNEL test. Others were able to demonstrate an elevated expression
of Fas-receptor in cells of atheroslerotic plaques in patients with
atherosclerosis and high indices of apoptotic cardiomyocytes in patients with
chronic heart failure. We investigated endomyocardial biopsies of patients with
inflammatory cardiomyopathy, DCM without inflammatory reaction but the presence
of adenoviral or cytomegaloviral genome and idiopathic DCM using the TUNEL test.
The percentage of apoptotic cardiomyocytes in biopsies of patients with DCMi was
1.03 and in biopsies of patients with adenoviral genome 0.25, whereas in all
other groups no apoptosis was found. If apoptosis plays a major role in
myocardial diseases such as heart failure, arrhythmia and others, blocking this
mechanism will have to be considered as a therapeutical strategy. Therefore,
studies on the extent of apoptotic processes in diseased versus healthy cardiac
tissue are of great importance.
PMID: 10412644 [PubMed - indexed for MEDLINE]
199. Atherosclerosis. 1999 May;144(1):177-84.
Metabolic basis of high density lipoproteins and apolipoprotein A-I increase by
HMG-CoA reductase inhibition in healthy subjects and a patient with coronary
artery disease.
Schaefer JR, Schweer H, Ikewaki K, Stracke H, Seyberth HJ, Kaffarnik H, Maisch B,
Steinmetz A.
Philipps-University, Internal Medicine, Division of Cardiology, Marburg, Germany.
HMG-CoA reductase inhibitors, such as pravastatin, are widely used as lipid
lowering drugs in hypercholesterolemia. Pravastatin does not only reduce the
atherogenic low density lipoprotein (LDL)-cholesterol, but is also increasing
high density lipoprotein (HDL)-cholesterol. However, the mechanism leading to an
increase of HDL are unclear. Therefore, the effects of pravastatin on the in vivo
kinetics of apolipoprotein (apo) A-I were studied in six normolipidemic subjects
and in a patient with coronary artery disease (CAD) utilizing stable isotope
tracer techniques. Two turnover studies were performed. The first turnover study
was carried out before any drug treatment, the second study after 6 weeks of 40
mg pravastatin/day. Three times deuterium labeled L-leucine (3D-leucine) was
given as a primed bolus constant infusion (bolus: 1340 microg/kg; infusion: 22
microg/kg per h), and tracer uptake into HDL apoA-I was determined by gas
chromatography (GC)-mass-spectrometry (MS). In the healthy subjects
HDL-cholesterol increased by 13% and apoA-I increased by 12% under pravastatin
treatment. The HDL in the CAD patient decreased by 3% and apoA-I increased by 2%.
Prior to drug treatment the mean apoA-I fractional synthetic rate (FSR) was 0.194
per day (S.D. +/- 0.02) and apoA-I production rate (PR) was 10.8 mg/kg per day
(S.D. +/- 2.1). The CAD patient had a FSR of 0.219 per day and a PR of 10.6 mg/kg
per day. After treatment with pravastatin the mean apoA-I FSR was 0.204 per day
(S.D. +/- 0.02) and apoA-I PR was 12.5 mg/kg per day (S.D. +/- 1.5) in the
healthy subjects. Despite only minor changes of HDL and apoA-I in the CAD
patient, there were significant changes of FSR (0.267 per day) and PR (13.1 mg/kg
per day) with pravastatin treatment. The in vivo kinetic data demonstrate an
increased FSR of apoA-I. The increase in apoA-I is due to an increased PR of
apoA-I. This study demonstrates increased production of HDL apoA-I as the
metabolic cause of the increase in HDL and apoA-I levels under inhibition of
HMG-CoA reductase in man.
PMID: 10381291 [PubMed - indexed for MEDLINE]
200. Herz. 1999 Apr;24(2):132-9.
[Angina pectoris in extracoronary diseases]
[Article in German]
Wilke A, Noll B, Maisch B.
Klinik für Innere Medizin-Kardiologie, Philipps-Universität Marburg.
wilke3@mailer.uni-marburg.de
Chest pain can arise from cardiovascular or noncardiovascular causes. Among the
latter are the skin, the chest wall, intrathoracic structures, or
subdiaphragmatic organs. The problem to attribute the chest discomfort to either
the heart or extracardiac organs arises because the heart, pleura, aorta, and
esophagus are all supplied by sensory fibers from the same spinal segments. In
contrast to the diseases mentioned above, angina pectoris in sensu strictu is
defined as chest pain or discomfort of cardiac origin that arises because of
temporary imbalance between myocardial oxygen supply and demand. The metabolic
oxygen requirements of the myocardium are essentially dictated by myocardial
contraction since only a fraction of the consumed oxygen is needed by the
quiescent heart. Therefore, the factors that primarily influence myocardial
oxygen consumption include heart rate, the force of cardiac contraction, and
myocardial wall tension, as determined by pressure (afterload), volume (preload),
and wall thickness. Extracoronary diseases, e.g. hypertensive heart disease,
aortic stenosis or cardiomyopathies, can influence these factors and induce
angina pectoris (Figure 1). On the other hand, different diseases influencing the
oxygen supply, e.g. anemia, can cause angina pectoris, too. In addition, the
modulation of the coronary tone by mediators and cytokines can cause angina,
coronary spasm being one example. The neurophysiological substrate of angina
pectoris are ganglia which are present within the heart, particularly in
epicardial fat. The sympathetic nervous system is the main conveyer of afferent
pain fibers from the heart and pericardium, but many fibers may travel by the
vagus and the phrenic nerves. Therefore, multiple thoracic structures may cause
similar pain syndromes in the distressed patient. The blood supply of intrinsic
cardiac ganglia arises primarily from branches of the proximal coronary arteries.
Adenosine, among a number of substances, can modulate the activity generated by
cardiac afferent nerve endings and intrinsic cardiac neurones. During myocardial
ischemia adenosine is released in large quantities into the interstitial space.
Given as an intravenous bolus to healthy volunteers or to patients with ischemic
heart disease and angina pectoris, adenosine provokes angina pectoris-like pain,
which is similar to habitual angina pectoris with regard to quality and location.
But other mediators (e.g. bradykinin, histamine, prostaglandins, potassium,
lactate) can be involved in the development of angina pectoris, too. As most
emphasis should be given to the most serious causes first, the cardiologist has
to consider ischemic cardiac disease in the differential diagnosis of nearly
every case of acute chest pain. The differential diagnosis contains several
causes of nonischemic cardiac chest pain. Dissecting aortic aneurysm may cause
severe anterior chest pain that can be mistaken for myocardial infarction.
Patients frequently will note the sudden onset of the pain rather than the
relatively slower onset of ischemic pain. Furthermore, they feel as a tear and
describe it as the most severe pain they have ever had. Pericarditis can be
characterized as a sharp precordial knife-like pain that is often increased by
lying down, breathing, swallowing, or any other thoracic motion. Radiation of
pericardial pain is often relieved by sitting up or leaning forward. It may
involve the shoulders, upper back, and neck because of the irritation of the
diaphragmatic pleura. Acute pulmonary embolism is associated with severe chest
pain. It may mimic acute myocardial infarction. Pulmonary embolism should be
suspected when dyspnea or tachypnea seems to be disproportionate to the severity
of the chest pain. Diffuse esophageal spasm is the extracardiac condition that is
confused most often with ischemic cardiac chest pain. This pain presents as a
deep thoracic pain that may be present over most of the thorax. It may extend
down the anterome
PMID: 10372299 [PubMed - indexed for MEDLINE]