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"Not a guideline but a guidance" is the motto of this document of guidance by the European Society of Cardiology, which is designed as an orientation aid to learning for physicians in the coronavirus disease 2019 (COVID-19) pandemic. A total of 62 European cardiologists as authors and 29 further experts as reviewers have contributed to this 119-page document. The emphasis of the guidelines is on a cautious strategy in dealing with a pandemic, which is still characterized by many unknown factors. It is consciously limited to cardiovascular diseases. In the last update from 10 June 2020 many practical instructions for cardiovascular diagnostics and treatment under the conditions of a pandemic are given. These recommendations largely depend on the already well-known guidelines of the ESC. To recapitulate them might be helpful but much is redundant. The sections on the pathophysiology and pathomechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could specifically affect the cardiovascular system, are informative but sometimes in need of supplementation. It is counterproductive to recommend that pathohistological and molecular investigations of tissues from affected and deceased patients should be avoided. This document of guidance is an ambitious attempt of a learning recommendation that needs some further improvement. It needs an early update if it intends to do justice to the ambitions.„No guideline but guidance“ ist das Motto dieses Leitfadens der European Society of Cardiology (ESC), der als lernende Orientierungshilfe für Ärzte in der Coronapandemie konzipiert ist. 62 europäische Kardiologen haben als Autoren und 29 weitere Experten als Reviewer zu dem 119 Seiten starken Dokument beigetragen. Der Leitfaden ist geprägt von einer vorsichtigen Strategie im Umgang mit einer Pandemie, von der vieles noch nicht bekannt ist. Er beschränkt sich bewusst auf kardiovaskuläre Erkrankungen. In seiner letzten Fassung vom 10. Juni 2020 gibt er zahlreiche praktische Anleitungen zur kardiovaskulären Diagnostik und Therapie unter Pandemiebedingungen. Die Empfehlungen sind oft redundante Rückgriffe auf die bekannten Leitlinien der ESC. Informativ, aber in Teilen ergänzungsbedürftig sind die Abschnitte zur Pathophysiologie und zu den Pathomechanismen, über die SARS-CoV‑2 („severe acute respiratory syndrome coronavirus 2“) spezifisch auf das Herz-Kreislauf-System wirken dürfte. Kontraproduktiv ist die Empfehlung, auf pathohistologische und molekulare Untersuchungen von Gewebe betroffener oder verstorbener Patienten zu verzichten. Den hohen Ansprüchen an einen sich immer wieder ergänzenden Leitfaden genügt die letzte verfügbare Fassung dennoch in weiten Teilen. Sie benötigt aber eine baldige Aktualisierung, wenn sie ihren Ambitionen gerecht werden will.

Background The clinical phenotype dilated cardiomyopathy is assumed to be the endstage of a multifactorial aetiopathogenetic pathophysiology which includes a not satisfactorily defined group of patients with inflammatory cardiomyopathy. Methods Within the German Competence Network Heart Failure patients with heart failure due to dilated cardiomyopathy of viral/inflammatory (DCMi/v) and nonviral/noninflammatory (DCM) aetiology were enrolled. After 1 year 237 patients (180 male/57 female) were re-examined including complete clinical work-up. The association of different clinical courses with the time from initial diagnosis of heart failure (newly: ≤ 1 year; late: > 1 year) was investigated. Results After 1-year-follow-up New York Heart Association (NYHA) class (by −0·48 in newly diagnosed DCM and −0·82 in newly diagnosed DCMi/v in addition to −0·24 in late diagnosed DCM and −0·17 in late diagnosed DCMi/v) as well as left ventricular ejection fraction (+14% in newly diagnosed DCM and DCMi/v and +6% in later diagnosed DCM and DCMi/v) were significantly improved in all patients. In patients with early diagnosed dilated cardiomyopathy a strong improvement of NYHA class could be demonstrated. Conclusions This study demonstrates for the first time a significant interaction between duration of disease, NYHA class and left ventricular ejection fraction in patients with DCM. Our results clearly demonstrate that in patients with DCM an early diagnosis within 1 year after occurrence of clinical signs is associated with a strong improvement in the clinical course, whereas late diagnosis results in a loss of change in clinical course and outcome.

Background In heart failure (HF), traditional cardiovascular risk factors (RF) as body mass index (BMI), total cholesterol (TC) and systolic blood pressure (SBP) are associated with better survival. It is unknown at which time point along the disease continuum the adverse impact of these RF ceases and may ‘start to reverse'. We analyzed the distribution of RF and their association with survival across HF stages. Methods We pooled data from four cohort studies from the German Competence Network HF. Employing ACC/AHA-criteria, patients were allocated to stage A (n=218), B (n=1324), C1 (i.e., New York Heart Association [NYHA] classes I & II; n=1134), and C2+D (NYHA III & IV; n=639). Results With increasing HF severity median age increased (63/67/67/70years), whereas the proportion of females (56/52/37/35%), median BMI (26.1/28.8/27.7/26.6kg/m 2 ), TC (212/204/191/172mg/dl), and SBP (140/148/130/120mmHg) decreased (P 2 BMI 0.91 (95% confidence interval 0.88; 0.95); per +10mg/dl TC 0.93 (0.92; 0.95); per +5mmHg SBP 0.94 (0.92; 0.95). Conclusion In this well-characterized sample of patients representing the entire HF continuum, reverse associations were only consistently observed in symptomatic HF stages. Our data indicate that the phenomenon of a "reverse epidemiology" in HF is subject to significant selection bias in less advanced disease.

Fulminant myocarditis is a clinical syndrome with signs of acute heart failure, cardiogenic shock, or life-threating rhythm disturbances in the context of suspected myocarditis. It is not an etiological diagnosis, but may have different underlying causes and pathogenetic processes - viral, bacterial, toxic, and autoreactive. Clinical management of the disease entity at the acute stage involves hemodynamic monitoring in an intensive care unit or similar setting. Rapid routine work-up is mandatory with serial EKGs, echocardiography, cardiac MRI, heart catheterization with endomyocardial biopsy for histology, immunohistology, and molecular analysis for the underlying infection and pathogenesis. Heart failure therapy is warranted in all cases according to current guidelines. For fulminant autoreactive myocarditis, immunosuppressive treatment is beneficial; for viral myocarditis, IVIg can resolve the inflammation, reduce the viral load, and even eradicate the microbial agent. ECMO, IABP, ventricular assist devices, LifeVest, or ICD implantation can bridge to recovery or to heart transplantation.

Pericardial diseases only affect a small proportion of patients with heart disease. But their diagnosis and differential diagnosis is, though too often neglected by cardiologists and internists, extremely important for the individual patient and of therapeutic and prognostic relevance in the differential diagnosis of cardiac symptoms [1, 2]: An excellent example for precordial pain is acute pericarditis, which should be differentiated from aortic dissection, myocardial infarction, pneumonia or pleuritis, pulmonary embolism, pneumothorax, costochondritis (Da Costa syndrome), gastroesophageal reflux or neoplasm and herpes zoster. In the spectrum of heart failure syndromes, it is pericardial constriction that causes dyspnoea and peripheral edema. Seferovic et al. particularly address these issues in their contribution, which was designed to update the 2004 guidelines of the European Society of Cardiology [3]. These guidelines are still the only guidelines worldwide on the management of pericardial diseases. Interventional pericardiologists nowadays use intrapericardial endoscopy and biopsy together with classic cytology to establish an etiologically based diagnosis [4, 5] by making use of techniques that have been accepted and applied to diagnose inflammatory cardiomyopathies [6] or tumors or rheumatic diseases since several decades. Pericardial access has become a vital interest for electrophysiologists, who now also ablate epicardial foci and reentry sites to treat malignant ventricular tachycardia [7, 8]. Pericardial access is also discussed for localized pharmacological treatment [9], even for stem cells or cocktails with growth factors [10]. Devices for locomotion on the epicardial surface have been designed and applied in preclinical settings [10, 11]. Apart from the patient’s symptoms, echocardiography remains the mainstay of imaging of acute pericardial syndromes but also of constrictive pericarditis, effusive–constrictive pericarditis, pericardial effusion, tamponade, absence of the pericardium and cysts or tumors. The remarkable progress, which has been made in echocardiography in the last years, is very well described by Veress, Feng and Oh from the Mayo-Clinic. Progress in cardiac tissue Doppler analysis, strain and strain rate imaging by speckle tracking imaging and three-dimensional echocardiography, the assessment of early diastolic annulus velocity and annulus reversus by TDI improves the differentiation of constriction from restrictive myocardial disease and is in the focus of their contribution. Threedimensional echocardiography may come up as a useful method for the precise assessment pericardial masses as it provides incremental value to 2D echocardiography by detecting anatomical and pathological structures with higher accuracy. Of particular interest are their contributions and that of others on effusive–constrictive pericarditis [12–14] and on the differential diagnosis of constrictive pericarditis to restrictive cardiomyopathy [15]. Syed and coworkers in this issue point out that effusive– constrictive pericarditis is best characterized in patients with tamponade who continue to have elevated intracardiac pressure after removal of pericardial fluid. The underlying causes are pericardial inflammation in conjunction with the presence of pericardial fluid under pressure, whereby the etiology is diverse. Alter et al. add valuable information on imaging by reviewing MRI and CT [16, 17] as well as scintigraphic Bernhard Maisch: Former Director of the University Hospital of Internal Medicine and Cardiology.

Diabetic cardiomyopathy is a controversial clinical entity that in its initial state is usually characterized by left ventricular diastolic dysfunction in patients with diabetes mellitus that cannot be explained by coronary artery disease, hypertension, or any other known cardiac disease. It was reported in up to 52-60% of well-controlled type-II diabetic subjects, but more recent studies, using standardized tissue Doppler criteria and more strict patient selection, revealed a much lower prevalence. The pathological substrate is myocardial damage, left ventricular hypertrophy, interstitial fibrosis, structural and functional changes of the small coronary vessels, metabolic disturbance, and autonomic cardiac neuropathy. Hyperglycemia causes myocardial necrosis and fibrosis, as well as the increase of myocardial free radicals and oxidants, which decrease nitric oxide levels, worsen the endothelial function, and induce myocardial inflammation. Insulin resistance with hyperinsulinemia and decreased insulin sensitivity may also contribute to the left ventricular hypertrophy. Clinical manifestations of diabetic cardiomyopathy may include dyspnea, arrhythmias, atypical chest pain, and dizziness. Currently, there is no specific treatment of diabetic cardiomyopathy that targets its pathophysiological substrate, but various therapeutic options are discussed that include improving diabetic control with both diet and drugs (metformin and thiazolidinediones), the use of ACE inhibitors, beta blockers, and calcium channel blockers. Daily physical activity and a reduction in body mass index may improve glucose homeostasis by reducing the glucose/insulin ratio and the increase of both insulin sensitivity and glucose oxidation by the skeletal and cardiac muscles.

In the 2015 guidelines of the European Society of Cardiology (ESC) and the American Heart Association (AHA) on infective endocarditis, the diagnostics are based on the modified Duke criteria. The diagnosis can be confirmed by a combination of micro-organisms demonstrated in culture or in situ, with the detection of valvular lesions or abscess formation by an imaging modality using echocardiography, positron emission tomography computed tomography (PET/CT), cardio-CT or nuclear medical methods. The management should be further improved by an interdisciplinary endocarditis team in a specifically designated reference center. Pharmaceutical treatment is largely unchanged and based on classical antibiotics in monotherapy or as combination therapy but for staphylococcal endocarditis, gentamycin is no longer required. As cardiac surgery is needed in 50 % of the cases during the course of the disease, the urgency for surgery depends on the extent of cardiac insufficiency, the persistence of the pathogen despite antibiotic treatment and on neurological complications.

Aims Hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be due to mutations in the genes encoding β-myosin heavy chain (MYH7) or cardiac myosin-binding protein C (MYBPC3). The aim of the present study was to determine the prevalence and spectrum of mutations in both genes in German HCM and DCM patients and to establish novel genotype-to-phenotype correlations. Methods and results Coding exons and intron flanks of the two genes MYH7 and MYBPC3 of 236 patients with HCM and 652 patients with DCM were sequenced by conventional and array-based means. Clinical records were established following standard protocols. Mutations were detected in 41 and 11% of the patients with HCM and DCM, respectively. Differences were observed in the frequency of splice site and frame-shift mutations in the gene MYBPC3, which occurred more frequently (P< 0.02, P< 0.001, respectively) in HCM than in DCM, suggesting that cardiac myosin-binding protein C haploinsufficiency predisposes to hypertrophy rather than to dilation. Additional novel genotype-to-phenotype correlations were found in HCM, among these a link between MYBPC3 mutations and a particularly large thickness of the interventricular septum (P= 0.04 vs. carriers of a mutation in MYH7). Interestingly, this correlation and a link between MYH7 mutations and a higher degree of mitral valve regurgitation held true for both HCM and DCM, indicating that the gene affected by a mutation may determine the magnitude of structural and functional alterations in both HCM and DCM. Conclusion A large clinical-genetic study has unravelled novel genotype-to-phenotype correlations in HCM and DCM which warrant future investigation of both the underlying mechanisms and the prognostic use.

Aims Occurrence of late gadolinium enhancement (LGE) as assessed by cardiac magnetic resonance (CMR) imaging has been attributed to various myocardial injuries. We hypothesized that LGE is associated with left ventricular (LV) wall stress. Methods and results We examined 300 patients with suspected non-ischaemic dilated cardiomyopathy. Cardiac magnetic resonance was used to assess LV volume, mass, wall stress, and LGE. Increased LV end-diastolic wall stress (> 4 kPa) was found in 112 patients (37 %), and increased end-systolic wall stress (>18 kPa) in 121 patients (40%). Presence of LGE was observed in 93 patients (31%). End-diastolic (94 ± 43 vs. 79 ± 42 ml/m², P = 0.006) and end-systolic LV volumes (62 ± 44 vs. 44 ± 37 ml/m², P < 0.001) and LV mass (95 ± 34 vs. 78 ± 31 g/m², P < 0.001) were increased in patients exhibiting LGE. In particular, LV end-diastolic and end-systolic wall stress were increased (4.5 ± 2.8 vs. 3.6 ± 3.0 kPa, P = 0.025; 19.6 ± 9.1 vs. 17.5 ± 8.2 kPa, P = 0.045). Late gadolinium enhancement was observed more frequently than would be expected from random occurrence in patients with increased end-diastolic (39 vs. 26%, P = 0.020) and end-systolic wall stress (41 vs. 24%, P = 0.002). Both normal end-diastolic and end-systolic wall stress had a high negative predictive value for LGE (75 and 76%). Conclusions The present study shows that occurrence of LGE in cardiomyopathy is associated with increased LV wall stress and mass. Suspected causes are an increased capillary leakage by stretch, impaired contrast agent redistribution, or increased diffusion distances. It is proposed that LGE should be considered as a potential prognostic determinant of heart failure and severe arrhythmias.

Cardiovascular diseases and cancer are the leading causes of death in the Western world. Cancer treatment has been associated with cardiovascular complications, among others cardiotoxicity of mediastinal radiation and certain chemotherapeutics. Identification of patients at high risk, prevention, early diagnosis, and treatment of cardiovascular diseases are emerging fields in cancer patients. Close interdisciplinary work between oncologists and cardiologists is pertinent for the treatment of cardiovascular diseases and complications in cancer patients. Diagnostics and treatment applied to the individual case should be based on the available evidence in terms of patient-centered management. Further clinical research focused on the pathogenesis and treatment of cardiovascular diseases in cancer patients is warranted to pave the way to guidelines for this nonhomogeneous patient group.

Hemodynamic instability is the major concern in surgical patients with pericardial diseases, since general anesthesia and positive pressure ventilation may precipitate cardiac tamponade. In advanced constriction diastolic impairment and myocardial fibrosis/atrophy may cause low cardiac output during and after surgery. Elective surgery should be postponed in unstable patients with pericardial comorbidities. Pericardial effusion should be drained percutaneously (in local anesthesia) and pericardiectomy performed for constrictive pericarditis before any major surgical procedure. In emergencies, volume expansion, catecholamines, and anesthetics keeping cardiac output and systemic resistance should be applied. Etiology of pericardial diseases is an important issue is the preoperative management. Patients with neoplastic pericardial involvement have generally poor prognosis and any elective surgical procedure should be avoided. For patients with acute viral or bacterial infection or exacerbated metabolic, uremic, or autoimmune diseases causing significant pericardial effusion, surgery should be postponed until the causative disorder is stabilized and signs of pericarditis have resolved.

NT-proBNP is an important prognostic predictor in patients with heart failure. However, it is unknown whether a change of NT-proBNP plasma levels in the early phase of decompensation might be of additional prognostic value in patients with acute decompensation of heart failure.NT-proBNP plasma levels of 116 patients with decompensated heart failure from ischemic/non-ischemic origin were measured at baseline and at 12, 24 and 48 h after hospital admission. Baseline levels and changes of plasma levels within the first 48 h were correlated with 30-day mortality. In all patients, NT-proBNP 12 h after admission was highest and superior with respect to the prediction of 30-day mortality compared to plasma levels on admission. In total, 38 patients died within the first 30 days. In these patients absolute NT-proBNP plasma levels were significantly higher and the increase within 12 h after admission was more pronounced compared to survivors (p0.001). NT-proBNP at 12 h after admission also had the highest predictive value for the 30-day mortality rate in patients with acute myocardial infarction. The increase of NT-proBNP plasma levels within 12 h after admission had the highest predictive value in patients suffering from decompensated heart failure.NT-proBNP is a powerful marker of 30-day mortality in patients with decompensated heart failure of ischemic and non-ischemic origin. Compared with single baseline measurements, serial measurements of NT-proBNP plasma levels within 12 h after hospital admission may be used to increase the predictive value of NT-proBNP with regard to the early identification of patients who are at high risk of mortality.

There is no question that cholesterol, especially low-density lipoprotein (LDL) cholesterol, represent a major cardiovascular risk factor. The so-called lipid hypothesis has been proven by almost all epidemiologic studies, animal studies and, most importantly, by interventional studies with lipid-lowering drugs, especially statins. However, despite our better understanding of atherogenesis we cannot explain why atherosclerosis occurs most frequently and severely on coronary arteries rather than on other arteries such as those of the hands or feet. In addition, the "lipid hypothesis" is unable to explain the dramatic change in severity of a far more generalized atherosclerosis in patients suffering from diabetes mellitus.Recently, we studied the effects of fatty acids on endothelial integrity and found a dramatic increase in apoptosis under fatty acid exposition. Since it is well known that the heart depends highly on fatty acid delivery to cover its energy demand, we hypothesize that the heart becomes the victim of its energy demand. With the so-called Marburg hypothesis of atherogenesis we can explain the fact why especially the arteries of the heart show early atherosclerotic lesions, but also the fact why patients with diabetes develop more generalized atherosclerosis. Finding mechanisms to reduce the presence of fatty acids within the arterial wall might prevent plaque destabilization and could be a potential target in our fight against atherosclerosis.

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 μmol/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/m2; p2, p=0.021; 114±50 vs. 71±23 mL/m2, p=0.042; 76±51 vs. 36±22 mL/m2, p=0.045). LV dilatation (LVEDV≥90 mL/m2) was more common in hyperhomocysteinemia (>12 μmol/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 hyperhomocysteinemia associated increase in oxidative stress that favors muscle fiber slippage. Clin Chem Lab Med 2010;48:555–60.

Cardiac dilatation is associated with impaired pump function, progression of heart failure and electrical instability. Risk of sudden death is associated with a low blood level of n-3 polyunsaturated fatty acids.The hypothesis was, therefore, addressed that left ventricular dilatation as assessed by echocardiography is associated with a reduced serum polyunsaturated fatty acid level.Fatty acids were determined with gas chromatography/mass spectrometry in serum of 308 patients with dilative heart failure unrelated to myocardial infarction (age 48 (SD12) years, NYHA class 2.2 (0.6), ejection fraction 31% (10%)).The extent of left ventricular dilatation as assessed by left ventricular end-diastolic diameter was associated with a reduction of both n-3 and n-6 polyunsaturated fatty acids. The n-3 docosahexaenoic acid (1.0% (0.5%) vs 1.3% (0.6%), p0.001) and the n-6 arachidonic acid (4.6% (1.8%) vs 5.2% (1.9%), p0.01) were reduced in patients with left ventricular dilatation (end-diastolic diameter, 68-90 mm, upper tertile vs 48-61 mm, lower tertile). By contrast, monounsaturated fatty acids were increased (the n-9 oleic acid 26.1% (4.8%) vs 23.9% (4.8%), p0.01). A low docosahexaenoic acid (0.01-0.9%, lower tertile vs 1.4-3.1%, upper tertile) was associated with greater left ventricular dilatation (end-diastolic diameter, 67 (8) vs 63 (7) mm, p0.001). The cut-off for the absence of severe dilatation (end-diastolic diameter70 mm) was set at1.24% docosahexaenoic acid. In our sample, the negative-predictive value for severe dilatation was 91% and sensitivity was 84%.Docosahexaenoic acid provides a new sensitive biomarker for monitoring and detecting severe left ventricular dilatation in heart failure patients.

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.

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.

The most frequent pericardial emergency is cardiac tamponade, but complications of an acute coronary syndrome and aortic dissection may also involve the pericardium. Acute pericarditis can also represent a medical emergency due to chest pain of upsetting intensity. Decompensations in chronic advanced constriction and in the clinical course of purulent pericarditis necessitate critical care as well. The diagnosis of cardiac tamponade is based on clinical presentation and physical findings, confirmed by echocardiography and cardiac catheterization. Tamponade is an absolute indication for urgent drainage, either by pericardiocentesis or surgical pericardiotomy. The approach for pericardiocentesis can be subxiphoid or intercostal using echocardiographic or fluoroscopic guidance. Urgent drainage, combined with intravenous antibiotics, is also mandatory in suspected purulent pericarditis. If confirmed, it should be combined with intrapericardial rinsing (best by a surgical drainage). Pericardiocentesis is contraindicated in cardiac tamponade complicating aortic dissection. This condition should immediately lead to cardiac surgery. Although pericardiectomy is the only treatment for permanent constriction, this procedure is contraindicated when extensive myocardial fibrosis and/or atrophy are demonstrated. Iatrogenic tamponade may occur during percutaneous mitral valvuloplasty, implantation of pacemakers, electrophysiology and radiofrequency ablation procedures, right ventricular endomyocardial biopsy, percutaneous coronary interventions, and rarely during Swan-Ganz catheterization. The authors report on a 79-year-old who suffered coronary perforation and cardiac tamponade during elective stent implantation. Tamponade was successfully treated with pericardiocentesis and implantation of a membrane-covered graft stent. Subsequent recurrent pericarditis/postpericardial injury syndrome with moderate pericardial effusion was initially treated with aspirin and then with aspirin and colchicine. At 6 months, the patient is in stable remission even after withdrawal of colchicine. Natural history of pericardial diseases can be complicated with pericardial emergencies requiring prompt diagnosis, intensive care with hemodynamic monitoring, and early aggressive management. Medical supportive measures, drainage of pericardial effusion, surgical pericardiotomy, and pericardiectomy should be applied when needed with no delay. This procedural approach also applies to iatrogenic interventions leading to tamponade.

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.

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

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.

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.

UNLABELLED 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.

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 ≤ 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 iU 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.

Guidelines and Expert Consensus documents aim to present all the relevant evidence on a particular issue in order to help physicians to weigh the benefits and risks of a particular diagnostic or therapeutic procedure. They should be helpful in everyday clinical decision-making. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by different organisations, the European Society of Cardiology (ESC) and by other related societies. By means of links to web sites of National Societies several hundred guidelines are available. This profusion can put at stake the authority and validity of guidelines, which can only be guaranteed if they have been developed by an unquestionable decision-making process. This is one of the reasons why the ESC and others have issued recommendations for formulating and issuing Guidelines and Expert Consensus Documents. In spite of the fact that standards for issuing good quality Guidelines and Expert Consensus Documents are well defined, recent surveys of Guidelines and Expert Consensus Documents published in peer-reviewed journals between 1985 and 1998 have shown that methodological standards were not complied within the vast majority of cases. It is therefore of great importance that guidelines and recommendations are presented in formats that are easily interpreted. Subsequently, their implementation programmes must also be well conducted. Attempts have been made to determine whether guidelines improve the quality of clinical practice and the utilisation of health resources. The ESC Committee for Practice Guidelines ( CPG ) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups or consensus panels. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements. The strength of evidence related to a particular diagnostic or treatment option depends on the available data: (1) level of evidence A: multiple …

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. 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. In HTN + ACEI or HTN, MyoD (21.8 ± 0.3 µm and 22.4 ± 0.3 µm, 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 µm 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). 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.

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.

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. (J Cardiovasc Electrophysiol, Vol. 14, pp. 819-824, August 2003)

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.

Prompt recognition of cardiac tamponade is critical since the underlying haemodynamic disorder can lead to death if not resolved by percutaneous or surgical drainage of the pericardium. Cardiac tamponade is a condition caused by the compression of the heart due to slow or rapid accumulation of fluid (exudate), pus, blood, clots, or gas within the pericardial space resulting in impaired diastolic filling and cardiac output due to increased intrapericardial pressure.1–3 Pericardial diseases of any aetiology may cause cardiac tamponade, but with highly variable incidence reflecting the local epidemiological background ( Table 1 ).3–6 However, all interventional procedures (i.e. percutaneous coronary intervention, transcatheter aortic valve implantation, pacemaker/implantable cardioverter defibrillator implantation, arrhythmias ablation, endomyocardial biopsy) are emerging causes of cardiac tamponade.7 Although rare, cardiac tamponade may also occur in pregnancy and in post-partum.8,9 Thus cardiologists should be aware of this possibility including specific contraindications for pregnancy (i.e. avoid the use of colchicine and X-ray exposure using echo-guided procedure).13,14 View this table: Table 1 Causes of pericardial disease and precipitating factors causing cardiac tamponade Management of cardiac tamponade can be challenging because of the lack of the validated criteria for the risk stratification that should guide clinicians in the decision-making process: (i) which patients need immediate drainage of the pericardial effusion? (ii) Is echocardiography sufficient for guidance of pericardiocentesis or should patient be taken to the cardiac catheterization laboratory? (iii) Who should be transferred to specialized/tertiary institution or surgical service? (iv) What type of medical support is necessary during transportation? Current European guidelines published in 2004 by the European Society of Cardiology3 do not cover these issues and no additional guidelines are available from major medical and Cardiology societies. Therefore, the aim of this position statement is to provide updated, evidence-based recommendations, when available, for …

GRIMM, W., et al.: Reversal of Tachycardia Induced Cardiomyopathy Following Ablation of Repetitive Monomorphic Right Ventricular Outflow Tract Tachycardia. 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.

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 for 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° 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.

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.

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.

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. (Am Heart J 2000;140:43-51.)

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.

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.

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.

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

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.

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.