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Fulminant myocarditis (FM) is a form of acute myocardial inflammation leading to rapid-onset hemodynamic instability due to cardiogenic shock or life-threatening arrhythmias. As highlighted by recent registries, FM is associated with high rates of death and heart transplantation, regardless of the underlying histology. Because of a paucity of evidence-based management strategies exists for this disease, an International workshop on FM was held in Wuhan, China, in October 2019, in order to share knowledge on the disease and identify areas of consensus. The present report highlights both agreements and controversies in FM management across the world, focusing the attention on areas of opportunity, FM definition, the use of endomyocardial biopsy and viral identification on heart specimens, treatment algorithms including immunosuppression and the timing of circulatory support escalation. This report incorporates the most recent recommendations from national and international professional societies. Main areas of interest and aims of future prospective observational registries and randomized controlled trials were finally identified and suggested.

"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.

Inflammatory dilated cardiomyopathy (DCMi) is a syndrome, not an etiological disease entity. The infective etiology and the immunopathology can be best determined through endomyocardial biopsy with a complete work-up by light microscopy, immunohistology, and polymerase chain reaction for microbial agents. This review focuses on the methodological advances in diagnosis in the past few years and exemplifies the importance of an etiology-orientated treatment in different case scenarios. In fulminant nonviral myocarditis, immunosuppressive treatment together with hemodynamic stabilization of the patient via mechanical circulatory support (e.g., microaxial pumps, extracorporeal membrane oxygenation, left ventricular assist device) can be life-saving. For viral inflammatory cardiomyopathy, intravenous immunoglobulin treatment can resolve inflammation and often eradicate the virus.

For myocarditis and inflammatory cardiomyopathy, an etiologically driven treatment is today the best option beyond heart failure therapy. Prerequisites for this are noninvasive and invasive biomarkers including endomyocardial biopsy and polymerase chain reaction on cardiotropic agents. Imaging by Doppler echocardiography and cardiac magnetic resonance imaging as well as cardiac biomarkers such as C‑reactive protein, N‑terminal pro-B-type natriuretic peptide , and troponins can contribute to the clinical work-up of the syndrome but not toward elucidating the underlying cause or pathogenetic process. This review summarizes the phases and clinical features of myocarditis and gives an up-to-date short overview of the current treatment options starting with heart failure and antiarrhythmic therapy. Although inflammation in myocardial disease can resolve spontaneously, often specific treatment directed against the causative agent is required. For fulminant, acute, and chronic autoreactive myocarditis, immunosuppressive treatment has proven to be beneficial in the TIMIC and ESETCID trials; for viral cardiomyopathy and myocarditis, intravenous immunoglobulin IgG subtype and polyvalent intravenous immunoglobulins IgG, IgA, and IgM can frequently resolve inflammation. However, despite the elimination of inflammation, the eradication of parvovirus B19 and human herpesvirus-6 is still a challenge, for which ivIg treatment can become a future key player.

Interventional procedures for pericardial diseases include pericardiocentesis, drainage of pericardial effusion, intrapericardial therapy, and percutaneous balloon pericardiotomy or percutaneous pericardiostomy. Echocardiographic and fluoroscopic guidance have greatly increased safety and feasibility. Several devices for pericardiocentesis have been tested (PerDucer, PeriAttacher, visual puncture systems, Grasper, Scissors, and Reverse slitter), mainly to facilitate access to the pericardium in the absence of effusion for epicardial ablations or left atrial appendage ligation. In selected patients with pericardial effusions that cannot be managed medically or with prolonged drainage, various medications can be applied intrapericardially to prevent further recurrences or induce sclerosis of the pericardial space.

Myocarditis and inflammatory cardiomyopathy are syndromes, not aetiological disease entities. From animal models of cardiac inflammation we have detailed insight of the strain specific immune reactions based on the genetic background of the animal and the infectiosity of the virus. Innate and adaptive immunity also react in man. An aetiological diagnosis of a viral vs. a non-viral cause is possible by endomyocardial biopsy with histology, immunohistology and PCR for microbial agents. This review deals with the different etiologies of myocarditis and inflammatory cardiomyopathy on the basis of the genetic background and the predisposition for inflammation. It analyses the epidemiologic shift in cardiotropic viral agents in the last 30 years. Based on the understanding of the interaction between infection and the players of the innate and adaptive immune system it summarizes pathogenetic phases and clinical faces of myocarditis. It gives an up-to-date information on specific treatment options beyond symptomatic heart failure and antiarrhythmic therapy. Although inflammation can resolve spontaneously, specific treatment directed to the causative etiology is often required. For fulminant, acute, and chronic autoreactive myocarditis without viral persistence immunosuppressive treatment can be life-saving, for viral inflammatory cardiomyopathy ivIg treatment can resolve inflammation and often eradicate the virus.

Die 2015 von der ESC und der AHA veroffentlichten Leitlinien zur infektiosen Endokarditis stutzen sich in der Diagnostik auf die modifizierten Duke-Kriterien. Diese beruhen auf dem Nachweis endokarditistypischer Erreger und dem Nachweis der endokarditischen Lasion in der Bildgebung, die sich neben der transthorakalen und transosophagealen Echokardiographie auch PET/CT, Kardio-CT und nuklearmedizinischer Methoden bedienen kann. Das Management soll durch ein interdisziplinares Endokarditisteam im dafur ausgewiesenen Referenzzentrum weiter verbessert werden. Die medikamentose Behandlung stutzt sich weitgehend unverandert auf bewahrte Antibiotika in Mono- oder Kombinationstherapie. Lediglich bei Staphylokokkenendokarditis kann auf Gentamycin verzichtet werden. Bis zu 50 % der Falle mussen fruher oder spater einer herzchirurgischen Masnahme zugefuhrt werden. Die Dringlichkeit dieses Eingriffs hangt ab vom Ausmas der Herzinsuffizienz, der Erregerpersistenz trotz Antibiose und den neurologischen Komplikationen.

The individual amount of alcohol consumed acutely or chronically decides on harm or benefit to a person’s health. Available data suggest that one to two drinks in men and one drink in women will benefit the cardiovascular system over time, one drink being 17.6 ml 100 % alcohol. Moderate drinking can reduce the incidence and mortality of coronary artery disease, heart failure, diabetes, ischemic and hemorrhagic stroke. More than this amount can lead to alcoholic cardiomyopathy, which is defined as alcohol toxicity to the heart muscle itself by ethanol and its metabolites. Historical examples of interest are the Munich beer heart and the Tübingen wine heart. Associated with chronic alcohol abuse but having different etiologies are beriberi heart disease (vitamin B1 deficiency) and cardiac cirrhosis as hyperdynamic cardiomyopathies, arsenic poising in the Manchester beer epidemic, and cobalt intoxication in Quebec beer drinker’s disease. Chronic heavy alcohol abuse will also increase blood pressure and cause a downregulation of the immune system that could lead to increased susceptibility to infections, which in turn could add to the development of heart failure. Myocardial tissue analysis resembles idiopathic cardiomyopathy or chronic myocarditis. In the diagnostic work-up of alcoholic cardiomyopathy, the confirmation of alcohol abuse by carbohydrate deficient transferrin (CDT) and increased liver enzymes, and the involvement of the heart by markers of heart failure (e.g., NT-proBNP) and of necrosis (e.g., troponins or CKMb) is mandatory. Treatment of alcoholic cardiomyopathy consists of alcohol abstinence and heart failure medication.

Cardiac tamponade is a pericardial syndrome characterized by compression of the heart by the exudate accumulating within the pericardial space and impairing diastolic filling and cardiac output. Pericardial diseases of any aetiology but also haemorrhage during interventional procedures may cause tamponade. If pericardial effusion accumulates slowly, 2000 mL or more could be tolerated (unless precipitated by dehydration, loop diuretics, vasodilators, anticoagulants, or thrombolytics), but acute accumulation of more than 250 mL is fatal.

In developed countries, more than 80% of cases of acute pericarditis remain without an established diagnosis after a conventional and standard diagnostic approach. These cases are generally labelled as 'idiopathic', i.e. without a known cause. This lack of information is a matter of concern for both patients and clinicians. Some years ago, this term reflected the state of the art of scientific knowledge on the topic. Advances have changed this point of view, in light of available molecular techniques like polymerase chain reaction able to identify viral cardiotropic agents in pericardial fluid and biopsies. Furthermore, the remarkable efficacy of interleukin-1 antagonists, a therapy targeting the innate immune response, suggests clinical and pathogenic similarity between a proportion of patients with idiopathic recurrent pericarditis and classical autoinflammatory diseases. So, it seems useful to discuss the pros and cons of using the term "idiopathic" in light of the new knowledge.

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.

Physical training has a well-established role in the primary and secondary prevention of coronary artery disease. Moderate exercise has been shown to be beneficial in chronic stable heart failure. Competitive sports, however, is contraindicated in most forms of hypertrophic cardiomyopathy (HCM), in myocarditis, in pericarditis, and in right ventricular cardiomyopathy/dysplasia. In most European countries, the recommendations of medical societies or public bodies state that these diseases have to be ruled out by prescreening before an individual can take up competitive sports. But the intensity and quality of this health check vary considerably from country to country, from the type of sports activity, and from the individuals who want to participate in sports. Prescreening on an individual basis should also be considered for leisure sports, particularly in people who decide to start training in middle age after years of physical inactivity to regain physical fitness. In leisure sports the initiative for a medical check-up lies primarily in the hands of the "healthy" individual. If she or he plans to participate in extreme forms of endurance sports with excessive training periods such as a marathon or ultramarathon and competitive cycling or rowing, they should be aware that high-intensity endurance sports can lead to structural alterations of the heart muscle even in healthy individuals. Physical exercise in patients with heart disease should be accompanied by regular medical check-ups. Most rehabilitation programs in Europe perform physical activity and training schedules according to current guidelines. Little is known about athletes who are physically handicapped and participate in competitive sports or the Paralympics, and even less is known about individuals with intellectual disabilities (ID) who participate in local, regional, international competitions or the Special Olympics or just in leisure sport activities.

Die ESC Leitlinie 2014 zur hypertrophischen Kardiomyopathie (HCM) fasst mit 133 ausformulierten und abgestimmten Empfehlungen, fur die 506 Literaturstellen hinterlegt sind, den aktuellen Erkenntnisstand zu Diagnostik, Management und Therapie des Phanotyps HCM zusammen. Neu im Vergleich zur letzten, 10 Jahre alten ACC/ESC-Leitlinie sind die Einarbeitung aktueller Erkenntnisse zur Genetik, konkrete Empfehlungen zum genetischen Screening von betroffenen Familien, die Betonung klinischer Leitsymptome (Signale) zur Zuordnung zu selteneren nichtobstruktiven HCM-Varianten, die Betonung der nicht-invasiven Bildgebung mit Echokardiographie und Kardio-MRT sowie eine Formel zur Abschatzung des Risikos fur einen plotzlichen Herztod. Dabei sollte nicht vergessen werden, dass die meisten Patienten mit einer HCM ein weitgehend normales Leben fuhren. Der hohe Detaillierungsgrad der Leitlinie erweist sich sowohl fur den Kardiomyopathieexperten als auch fur den Internisten und Allgemeinmediziner als eine ausgezeichnete, strukturierte Zusammenfassung des gegenwartigen Wissenstands.

In diesem Beitrag werden Diagnostik, Differenzialdiagnostik, multimodale Bildgebung sowie medikamentose und invasiv diagnostische Therapie der akuten und chronischen Perikarditis, der konstriktiven Perikarditis, des Perikardergusses und der Herztamponade unter atiologischen Gesichtspunkten und in Anlehnung an die Leitlinie der European Society of Cardiology (ESC) beschrieben. Ausgangspunkt des klinischen Entscheidungsbaums ist der symptomatische Patient mit echokardiographisch nachweisbarem Perikarderguss. Im Vordergrund der Diagnostik steht die atiopathogenetische Einordnung der Perikarderkrankung, die klinisches Bild, Verlauf, Therapie und Prognose pragen. Die infektiose Perikarditis (viral, bakteriell oder tuberkulos) wird von der sterilen autoreaktiven Perikarditis und vom neoplastischen Perikarderguss durch Ergusszytologie sowie (immun-)histologische und molekulare Untersuchungen der Perikard- und Epikardbiopsie abgegrenzt. Hierzu leistet die Perikardioskopie zur Erkennung suspekter Areale einen wichtigen Beitrag. Intraperikardiale Cisplatingabe bei neoplastischem Perikarderguss und Instillation von Triamcinolon bei autoreaktiver Perikarditis verhindern ebenso wie eine mehrmonatige Behandlung mit Colchicin in vielen Fallen Rezidive.

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.

Background Aortic wall strains are indicators of biomechanical changes of the aorta due to aging or progressing pathologies such as aortic aneurysm. We investigated the potential of time-resolved three-dimensional ultrasonography coupled with speckle-tracking algorithms and finite element analysis as a novel method for noninvasive in vivo assessment of aortic wall strain. Methods Three-dimensional volume datasets of 6 subjects without cardiovascular risk factors and 2 abdominal aortic aneurysms were acquired with a commercial real time three-dimensional echocardiography system. Longitudinal and circumferential strains were computed offline with high spatial resolution using a customized commercial speckle-tracking software and finite element analysis. Indices for spatial heterogeneity and systolic dyssynchrony were determined for healthy abdominal aortas and abdominal aneurysms. Results All examined aortic wall segments exhibited considerable heterogenous in-plane strain distributions. Higher spatial resolution of strain imaging resulted in the detection of significantly higher local peak strains ( p ≤ 0.01). In comparison with healthy abdominal aortas, aneurysms showed reduced mean strains and increased spatial heterogeneity and more pronounced temporal dyssynchrony as well as delayed systole. Conclusions Three-dimensional ultrasound speckle tracking enables the analysis of spatially highly resolved strain fields of the aortic wall and offers the potential to detect local aortic wall motion deformations and abnormalities. These data allow the definition of new indices by which the different biomechanical properties of healthy aortas and aortic aneurysms can be characterized.

Despite great advances in the pathophysiology and etiology of myocarditis, the clinical diagnosis of myocarditis in daily clinical practise remains challenging. Often the diagnosis was not clear because of the heterogeneity of clinical symptoms and the lack of guidelines for adequate diagnostic requirements and consecutive treatment options. The European Society of Cardiology (ESC) Working Group on Myocardial and Pericardial Diseases established a working group of experts to improve the diagnosis and management of myocarditis and to provide a common consensus statement as a reference for future registries and controlled trials. The goal was to bridge the gap between clinical- and tissue-based diagnosis by formulating a concept concerning essential diagnostics and treatment of these patients that would be accepted across Europe. Only in this manner is it possible to establish a basis for national and international registries and double-blind randomized treatment trials for the etiologically differentiated treatment of myocarditis, which appear promising due to numerous studies in recent years. In this paper, two members from the expert working group summarize the most important aspects of this position paper on the etiology, diagnosis, management, and treatment of myocarditis, which were published in the July 2013 issue of European Heart Joumal.

Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with autosomal dominant inheritance caused by mutations in genes coding for sarcomeric and/or regulatory proteins expressed in cardiomyocytes. In a small cohort of HCM patients (n = 8), we searched for mutations in the two most common genes responsible for HCM and found four missense mutations in the MYH7 gene encoding cardiac β-myosin heavy chain (R204H, M493V, R719W, and R870H) and three mutations in the myosin-binding protein C3 gene ( MYBPC3 ) including one missense (A848V) and two frameshift mutations (c.3713delTG and c.702ins26bp). The c.702ins26bp insertion resulted from the duplication of a 26-bp fragment in a 54-year-old female HCM patient presenting with clinical signs of heart failure due to diastolic dysfunction. Although such large duplications (> 10 bp) in the MYBPC3 gene are very rare and have been identified only in 4 families reported so far, the identical duplication mutation was found earlier in a Dutch patient, demonstrating that it may constitute a hitherto unknown founder mutation in central European populations. This observation underscores the significance of insertions into the coding sequence of the MYBPC3 gene for the development and pathogenesis of HCM.

Depression is common in heart failure (HF) and associated with adverse outcomes. This study aimed to investigate incidence rates and predictors of depression in patients sampled from four subprojects of the German Competence Network Heart Failure.Eight hundred thirty nine symptomatic HF patients free of depression at baseline underwent repeat depression screening (Patient Health Questionnaire, PHQ-9) after 12 months. Ordered logistic regression analysis was employed to search for predictors of incident depression.Incident minor (major) depression was observed in 61 (7.3%) and 47 (5.6%) of the population. Depression was recurrent in 15 (25%) and 16 (34%), respectively. Multiple regression analysis revealed seven variables predicting minor or major depression: Previous depressive episode (odds ratio [OR] 4.04, 95% confidence interval [CI] 2.37-6.89, p ≤ 0.001), previous resuscitation (OR 2.44, CI 1.23-4.81, p=0.010), current smoking (OR 2.06, CI 1.08-3.50, p=0.008),4 visits/year to general practitioner (OR 1.67, CI 1.06-2.63, p=0.026), New York Heart Association class (OR 1.54/class, 95% CI 1.05-2.25, p=0.027), PHQ-9 baseline sum-score (OR 1.18/point, CI 1.11-1.27, p0.001), and SF-36 physical functioning (OR 1.08/-5 points, CI 1.03-1.13, p=0.002).In these HF patients initially free of depression annual incidence rates were high. Several independent predictors allowed identification of patients at particular risk. Although obtained in a selected cohort these findings call, in view of the grave prognosis of HF patients with comorbid depression, for regular depression screening and development of specific supportive strategies to improve patient care and outcomes in HF.

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.

The etiology of pericardial effusions remains unresolved in many cases because not the full spectrum of diagnostic methods including cytology, histology, immunohistology and PCR on cardiotropic agents, which are currently available, used in many institutions. After comprehensive clinical workup and use of imaging methods, such as echocardiography and cardiac MRI, pericardiocentesis and epicardial and pericardial biopsy were carried out under pericardioscopical control of the biopsy site. Biopsies and fluid were evaluated by cytological, histological, immunological and molecular (PCR) methods in 259 patients of our tertiary referral center following an identical clinical pathway, diagnostic and therapeutic algorithm in all cases. A standard clinical pathway and the same diagnostic and therapeutic algorithms were used in all cases. When all methods are applied to patients with pericardial effusions, "idiopathic" pericardial effusion is no longer a relevant diagnosis. Autoreactive and lymphocytic pericardial effusions are the leading diagnosis in 35 % of patients in the prospective Marburg registry, followed by malignant effusions in 28 % of cases. Viral genome was assessed in fluid and epi- as well as pericardial biopsies in 12 %, followed by post-traumatic/iatrogenic effusions in 15 % and purulent/bacterial effusions in only 2 %. Pericardioscopy permits the macroscopic inspection of the pulsating heart and its disease-associated macroscopic alterations. It also permits safe and targeted biopsy for further investigations of the tissue. Therapy, tailored to the individual etiology, can be selected such as intrapericardial instillation in autoreactive effusions with triamcinolone and with cisplatin or thiotepa in neoplastic effusions. With this approach the recurrence of pericardial effusion can be avoided effectively. A comprehensive approach to the diagnosis of pericardial effusions in conjunction with pericardioscopy for targeted tissue sampling is the prerequisite for an etiologically based intrapericardial and systemic treatment, which improves outcome and prognosis.

International audience; The haemoflagellate Trypanosoma cruzi is the causative agent of Chagas' disease that occurs in approximately 8 million people in Latin America. Patients infected with T. cruzi frequently suffer of cardiomegaly and may die of myocardial failure. Here we show that T. cruzi trypomastigotes (extracellular form) increased in vitro apoptosis of rat cardiomyocytes. Additionally, we demonstrated that amastigotes (intracellular form), for which a method for purification was established, were also able to induce cardiomyocyte apoptosis. Increase of apoptosis was associated with up-regulation of the apoptotic gene bax by trypomastigotes, while expression of the anti-apoptotic gene bcl-2 was down-regulated by amastigotes. The transcription factor STAT3 but not STAT1 was activated in cardiomyocytes by trypomastigotes. In addition, tlr7 gene expression was up-regulated in cardiomyocytes incubated with trypomastigotes, suggesting that this Toll-like receptor is involved in the intracellular recognition after host cell invasion by T. cruzi. Glycosylphosphatidylinositols purified from trypomastigotes did not induce cardiomyocyte apoptosis and STAT activation but down-regulated tlr7 gene expression. In conclusion, cardiomyopathy observed in Chagas' disease might be in part due to apoptosis of cardiomyocytes induced directly by the parasite.

Pericardial cysts are rare. They are often asymptomatic mediastinal abnormalities, which are usually congenital. If symptomatic differential diagnosis can pose a diagnostic challenge since it has to consider the different causes of pericardial effusion including malignant forms. In 2 symptomatic female patients (aged 51 and 58 years) pericardiocentesis, pericardioscopy and pericardial fluid analysis confirmed the diagnosis of "spring water cysts." Pericardioscopy excluded protrusions, petechial bleeding, neovascularization or inflammation. Application of contrast media into the cyst confirmed by radiological control that no communication to the true pericardial sac was present. So after aspiration of the entire fluid, subsequent instillation of 10 ml ethanol for a few minutes was carried out to prevent recurrence of the cystic formation. The aspiration of the residual fluid under moderate suction demonstrated and 24-h clinical observation at the ICU completed the short intervention. All symptoms were relieved immediately in both patients. Recurrence was not observed in the follow-up.

The aetiology of pericardial effusion has been generally assessed by clinical work-up only, which leaves a large cohort of patients with "idiopathic" effusions virtually undiagnosed. In accordance with the ESC guidelines, this contribution intends to change this attitude. After therapeutic or diagnostic pericardiocentesis of 259 patients with large to moderate pericardial effusions, pericardial fluid, epicardial and pericardial biopsies, and blood samples were analysed by PCR for cardiotropic microbial agents. Cytology, histology, immunohistology of tissue and fluids and laboratory tests were performed. Of the 259 patients, 35 % suffered from an autoreactive aetiology, 28 % suffered from a malignant and 14 % from an infectious cause. Investigating all samples by PCR, we identified viral genomes in 51 (19.7 %) patients, parvovirus B19 (B19 V) being identified in 25 and Epstein-Barr virus (EBV) in 19 cases. In patients with a sole infectious aetiology (n = 36), B19 V was detected in 21 and EBV in 10 cases. When differentiating with regard to the material investigated for the presence of cardiotropic viruses, parvovirus B19 was most often detected in the epicardium and EBV was most frequently detected in the pericardial fluid independent from the final diagnostic categorisation. Bacterial cultures including tests for tuberculosis were all negative. Molecular techniques improve sensitivity, specificity and diagnostic accuracy for the underlying aetiology in pericarditis patients with effusion. The identification of specific viral signatures will help to understand pathogenetic mechanisms in pericarditis and allow to tailor an adequate therapy beyond antiphlogistic treatment.

In inflammatory dilated cardiomyopathy and myocarditis, there is apart from heart failure and antiarrhythmic therapies no alternative to an etiologically driven specific treatment. Their prerequisites are noninvasive and invasive biomarkers including endomyocardial biopsy and PCR on cardiotropic agents. This review deals with the different etiologies of myocarditis and inflammatory cardiomyopathy including the genetic background, the predisposition for heart failure and inflammation. It analyses the epidemiologic shift in pathogenetic agents in the last 20 years, the role of innate and acquired immunity including the T cell and B cell driven immune responses. On this basis, it summarizes phases and clinical faces of myocarditis. It gives an up-to-date information on current treatment options starting with heart failure and antiarrhythmic therapy. Although inflammation can resolve spontaneously, often specific treatment directed to the causative etiology is required. For fulminant, acute and chronic autoreactive myocarditis immunosuppressive treatment is beneficial; for viral cardiomyopathy and myocarditis, IVIG can resolve inflammation and is as successful as interferon therapy in enteroviral and adenoviral myocarditis. Eradication of parvovirus B19 and HHV6 myocarditis is still a problem by anyone of these treatment options. The potential of stem cell therapy has to be tested in future trials. In perimyocardial disease, a locoregional approach with high local doses and low systemic side effects have been shown highly efficient by intrapericardial treatment of triamcinolonacetate facilitated by pericardioscopy for adequate etiopathogenetic diagnosis.

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.

Myocarditis, a common heart disease pathologically defined as an inflammatory reaction of the myocardium, is most frequently caused by infectious agents, including viruses and bacteria, and may develop in later stages into dilated cardiomyopathy (DCM). Several studies have identified inflammatory components engaged in the transition from acute myocarditis to chronic DCM, and there is growing evidence that myocarditis and DCM are closely related. Novel technological advances in genomic screening have gained insight into molecular and cellular mechanisms involved the pathogenesis of inflammatory heart disease and, in particular, in the development of systolic dysfunction resulting from DCM. Detection of differential gene expression profiles have become valid tools in the study of inflammatory heart disease. Molecular signatures are defined as individual sets of genes, mRNA transcripts, proteins, genetic variations or other variables, which can be used as markers for a particular phenotype. These signatures may be useful for clinical diagnosis or risk assessment and, in addition, may help to identify molecules not previously known to be involved in the pathogenesis of these disease conditions. Microarray analyses have dramatically refined our knowledge about tissue-specific gene expression patterns, simply by being able to study thousands of genes simultaneously in a single experiment. In the field of cardiovascular research, microarrays are increasingly used in the study of end-stage cardiomyopathies, such as DCM, that ultimately lead to symptoms of heart failure. By means of microarray analysis, a set of differentially expressed genes can be detected, among them are transcripts coding for sarcomeric and extracellular matrix proteins, stress response and inflammatory proteins as well as transcription factors and translational regulators. Expression profiling may be particularly helpful to improve the differential diagnosis of heart failure and enable novel insight into selected molecular pathways.

Pericardial cytokine patterns in various diseases are not well established. We have analyzed pericardial proinflammatory (interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha) and immunoregulatory cytokines (transforming growth factor (TGF)-beta1 and interferon (IFN)-gamma) in patients with pericarditis, myocarditis, and ischemic heart disease. Pericardial fluid was obtained in 30 subsequent patients undergoing pericardiocentesis (Group 1: 60 % males, 52.4 ± 14.2 years) and in 21 patients during aortocoronary bypass surgery (Group 2: 42.9 % males, age 67.2 ± 7.4 years). After clinical, laboratory, echocardiography examination, fiberoptic pericardioscopy (Storz-AF1101Bl, Germany) and pericardial/epicardial biopsy Group 1 was subdivided to 40 % neoplastic, 36.6 % autoreactive, 10 % iatrogenic, and 13.3 % viral pericarditis. Samples were promptly aliquoted, frozen, and stored at −70 °C. The cytokines were estimated using quantikine enzyme amplified-sensitivity immuno-assays (R&D Systems, USA) and the results compared between neoplastic, viral, iatrogenic, and autoreactive pericarditis and surgical groups. IL-6 was significantly increased in PE versus serum in all forms of pericarditis (except in autoreactive) and increased in comparison with pericardial fluid of surgical patients. TNF-alpha was increased only in PE of patients with viral pericarditis in comparison with Group 2. TGF-beta1 was strikingly lower in the PE than in the serum of all pericarditis patients. However, TGF-beta1 levels in PE were significantly higher in Group 1 than in Group 2, except in viral pericarditis. IFN-gamma levels did not significantly differ between PE and serum or in comparison with Group 2. The cytokine pattern “high TNF-alpha/low TGF-beta1” was found in viral pericarditis and low IL-6 in autoreactive PE. Different etiologies of pericardial inflammation did not influence the IFN-gamma levels. IL-6 pericardial to serum ratio was significantly higher in autoreactive PE than in viral and neoplastic forms. However, TNF-alpha and IFN-gamma pericardial to serum ratios were significantly higher in viral than in autoreactive and neoplastic PE.

The aim of this study was to examine the biochemical composition of pericardial effusions of different etiology and to evaluate the diagnostic utility of biochemical parameters and tumor markers to discriminate malignant from benign effusion. Pericardial and serum levels of biochemical parameters and tumor markers were compared in 105 patients who underwent pericardiocentesis and pericardioscopy with targeted epicardial biopsy. Etiologic diagnosis was based on pericardial fluid and epicardial biopsy analysis by cytology, histology, immunohistochemistry, microbiology and polymerase chain reaction. The total of 105 patients comprised 29 patients with malignant and 76 patients with non-malignant pericardial effusions (40 autoreactive, 28 viral, 5 postcardiotomy syndromes and 3 associated with systemic diseases). Malignant pericardial effusions had significantly higher pericardial fluid levels of the tumor markers CEA, CA 19-9, CA 72-4, SCC and NSE (p < 0.001, p = 0.002, p < 0.001, p = 0.004 and p < 0.001, respectively) as well as higher pericardial fluid hemoglobin (p < 0.001), pericardial fluid white blood cells (p = 0.003), pericardial fluid LDH (p < 0.001) and ratio of pericardial to serum LDH levels compared to benign effusions. None of the biochemical or cell-count parameters tested proved to be accurate enough for distinguishing malignant from benign effusions. However, measurement of pericardial CA 72-4 levels offered a high diagnostic accuracy for malignancy, particularly in bloody pericardial effusions. None of the biochemical parameters tested was useful for the discrimination of malignant from benign effusions. However, measurement of pericardial CA 72-4 levels in bloody pericardial effusions yielded a high diagnostic accuracy and thus offers the potential as a diagnostic tool to distinguish between malignant and benign effusions.

Although echocardiography remains the standard diagnostic tool for identifying pericardial diseases, procedures with better delineation of morphology and heart function are often required. The pericardium consists of an inner visceral (epicardium) and outer parietal layer (pericardium), which constitute for the pericardial cavity. Pericardial effusion can occur as transudate, exudate, pyopneumopericardium, or hemopericardium. Potential causes are inflammatory processes, that is, pericarditis due to autoimmune or infective reasons, neoplasms, irradiation, or systemic disorders, chronic renal failure, endocrine, or metabolic diseases. Pericardial fat can mimic pericardial effusion. Using various image-acquisition sequences, MRI allows identifying and separating fluid and solid structures. Fast spin-echo T1-weighted sequences with black-blood preparation are favourably used for morphological evaluation. Fast spin-echo T2-weighted sequences, particularly with fat saturation, and short-tau inversion-recovery sequences are useful to visualize oedema and inflammation. For further tissue characterization, delayed inversion-recovery imaging is used. Therefore, image acquisition is performed at 5-20 min subsequent to contrast agent administration, the so-called technique of late gadolinium enhancement. Ventricular volumes and myocardial mass can be assessed accurately by steady-state free-precession sequences, which is required to measure cardiac function and ventricular wall stress. Constrictive pericarditis usually results from chronic inflammatory processes leading to increased stiffness, which impedes the slippage of both pericardial layers and thereby the normal cardiac filling. CT imaging can favourably assess pericardial calcification. Thus, MR and CT imaging allow a comprehensive delineation of the pericardium. Superior to echocardiography, both methods provide a larger field of view and depiction of the complete chest including abnormalities of the surrounding mediastinum and lungs. PET provides unique information on the in vivo metabolism of 18-fluorodeoxyglucose that can be superimposed on CT findings and is useful for identifying inflammatory processes or masses, for example neoplasms. These imaging techniques provide advanced information of anatomy and cardiac function to optimize the pericardial access, for example by the AttachLifter system, for diagnosis and treatment.

Background: The pathogenetic role of vascular endothelial growth factor (VEGF) in malignant pericardial effusion and diagnostic value of pericardial VEGF levels to discriminate malignant from benign pericardial effusions are uncertain. Hypothesis: We hypothesized that pericardial VEGF levels would be higher in malignant than benign pericardial effusion and that VEGF would be a useful marker for the diagnosis of malignant pericardial effusion. Methods: Using an enzyme-linked immunosorbent assay, we assessed pericardial and serum VEGF levels in patients with malignant pericardial effusion (n = 19), in patients with nonmalignant pericardial effusion (n = 30), and for control, in patients without pericardial disease (n = 26). Results: Vascular endothelial growth factor pericardial levels in malignant pericardial effusion (13 593.8 ± 22 410.24 pg/mL) were significantly higher compared with VEGF in nonmalignant effusion (610.63 ± 1289.08 pg/mL; P = 0.001) and pericardial fluid (5.5 ± 15.97 pg/mL; P < 0.001). In serum, VEGF was significantly higher in patients with nonmalignant pericardial effusion (188.3 ± 240.35 pg/mL) compared with patients with malignant pericardial effusion (67.52 ± 125.77 pg/mL; P = 0.024) and coronary artery disease patients (29.13 ± 76.26 pg/mL; P < 0.001). Pericardial VEGF levels were significantly higher than matched serum levels only in patients with malignant pericardial effusion (P = 0.023). Pericardial VEGF levels ≥2385 pg/mL had 75% sensitivity and 90% specificity for the recognition of malignant pericardial effusion in patients with breast or lung cancer. Conclusions: Vascular endothelial growth factor levels in pericardial effusion are markedly elevated in patients with malignant pericardial effusion, indicating abundant local release within the pericardial cavity. It is thus possible that VEGF participates in the pathogenesis of malignant pericardial effusion. Measurement of VEGF in pericardial effusion offers potential as a diagnostic tool to discriminate malignant from benign effusions in patients with breast or lung cancer. The authors have no funding, financial relationships, or conflicts of interest to disclose.

Osteoprotegerin (OPG) is a regulator of bone and vascular homeostasis and acts as a decoy receptor for proapoptotic TNF-related apoptosis-inducing ligand (TRAIL).We assessed pericardial and serum levels of OPG and TRAIL in pericardial effusions (PE) of malignant (mPE, n=24) or non-malignant (nPE, n=34) origin, and in pericardial fluid (PF, n=25) of coronary artery disease (CAD) patients by ELISA.OPG was at least 5 fold higher in PE or PF compared to serum, with a significantly higher ratio of pericardial to serum OPG in patients with mPE or nPE compared to PF (mPE vs. PF, p=0.011; nPE vs. PF, p0.001). TRAIL was only detectable in mPE and PF. Logistic regression analysis revealed that a high ratio of pericardial to serum OPG and high TRAIL in PE were the best variable combination to predict malignancy of PE.Pericardial and systemic OPG or TRAIL are potential diagnostic tools to discriminate between malignant or benign PE.

Background. The role of inflammatory and angiogenic cytokines in patients with inflammatory pericardial effusion still remains uncertain.Methods. We assessed pericardial and serum levels of VEGF, bFGF, IL-1βand TNF-αby ELISA in patients with inflammatory pericardial effusion (PE) of autoreactive () and viral () origin, and for control in pericardial fluid (PF) and serum () of patients with coronary artery disease (CAD) undergoing coronary artery bypass graft surgery.Results. VEGF levels were significantly higher in patients with autoreactive and viral PE than in patients with CAD in both PE ( for autoreactive and for viral PE) and serum ( for autoreactive and for viral PE). Pericardial bFGF levels were higher compared to serum levels in patients with inflammatory PE and patients with CAD ( for CAD; for autoreactive PE; for viral PE). Pericardial VEGF levels correlated positively with markers of pericardial inflammation, whereas pericardial bFGF levels showed a negative correlation. IL-1βand TNF-αwere detectable only in few PE and serum samples.Conclusions. VEGF and bFGF levels in pericardial effusion are elevated in patients with inflammatory PE. It is thus possible that VEGF and bFGF participate in the pathogenesis of inflammatory pericardial disease.

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.

Systolic chronic heart failure (CHF) is currently one of the most prevalent cardiac diseases. The present analysis sought to estimate the 1-year disease-related resource use and associated management costs of patients with CHF. A total of 2,710 individuals with systolic CHF [mean age 62.9 years ± 13.6, 25.2% female, New York Heart Association (NYHA) I–IV] were included from the German Competence Network Heart Failure. Disease-related resource use was assessed with regard to outpatient contacts with physicians, hospitalizations including rehabilitation stays and drug utilization. During 1 year, patients had on average 6.1 contacts with their general practitioner, 1.7 contacts with cardiologists and 0.8 hospital stays per year. Overall disease-related health care costs per patient were calculated at 3,150 € per year. The largest component related to hospitalizations (2,328 €, 74%), while costs of rehabilitation (294 €, 9%), medication (290 €, 9%) and outpatient contacts (238 €, 8%) were considerably lower. Compared with 2,474 € in NYHA class I, there was a cost increase in NYHA II, III and IV of 14, 48 and 71%, respectively. About 76% of this cost increase resulted from augmented hospital (inpatient) resource use. The present analysis demonstrates a high disease-related resource consumption of heart failure care. In particular, patients in higher NYHA classes require increased inpatient resources. Hence, improved treatment strategies need to be developed to optimize care thus reducing hospitalization rates.