[Management of pericarditis and pericardial effusion, constrictive and effusive-constrictive pericarditis]. / Management von Perikarditis und Perikarderguss, konstriktiver und effusiv-konstriktiver Perikarditis.

This CME review takes stock of the progress in the etiology, pathophysiology, diagnostics and treatment of pericarditis and pericardial effusion brought about by the publication of the 2nd European Society of Cardiology (ESC) guidelines on the management of pericardial diseases in 2015. It also emphasizes special forms, which have received less attention in the past, such as therapy-refractory (incessant), effusive-constrictive and constrictive pericarditis and the treatment of acute and recurrent pericarditis with colchicine. After the diagnosis of pericarditis with or without effusion has been made, the first step is to clarify its etiology, which affects the clinical symptoms, course, treatment and the prognosis. In this aspect the requirements of the guidelines and the reality of an etiological classification of pericardial diseases diverge in many cases. The diagnosis of "idiopathic" acute or recurrent pericarditis is still much too often the result of insufficient efforts to find the cause. Too often only malignant and bacterial forms are excluded. If the etiology is known local intrapericardial treatment with the already inserted pigtail catheter from the diagnostic pericardial puncture can be carried out with few systemic side effects. The 2015 ESC guidelines recommend colchicine as first line treatment in all forms of pericarditis except for neoplastic pericardial effusion. It accelerates healing and reduces the frequency of recurrence of pericarditis but cannot eliminate recurrence completely. The best treatment and prevention of recurrence is the eradication of the underlying etiological cause.

Treatment options in myocarditis and inflammatory cardiomyopathy : Focus on i. v. immunoglobulins.

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 C­reactive protein, N­terminal 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.

[Inflammatory cardiomyopathy and myocarditis]. / Inflammatorische Kardiomyopathie und Myokarditis.

We describe diagnosis, differential diagnosis, multimodality imaging and medical and invasive diagnostic treatment in patients with inflammatory cardiomyopathy and myocarditis under etiological considerations in reference to a landmark position paper of the Working Group Myocardial and Pericardial Diseases of the European Society of Cardiology together with recent developments in diagnosis and treatment. Diagnosis of the symptomatic patient is the assessment of etiology of inflammatory cardiomyopathy, followed by the clinical presentation, course, treatment option and prognosis. Viral myocarditis in its different facets can clearly be separated from autoreactive forms by histological and molecular methods in the endomyocardial biopsy, thus leading to an individualized targeted therapy beyond heart failure treatment.

Alcoholic cardiomyopathy : The result of dosage and individual predisposition.

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.

Exercise and sports in cardiac patients and athletes at risk: Balance between benefit and harm.

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.

[Vasculitis : EULAR/ACR guidelines with respect to the clinical cardiological routine]. / Vaskulitiden : EULAR-/ACR-Leitlinien im Spiegel des klinisch-kardiologischen Alltags.

In this article the diagnostics, differential diagnosis, laboratory findings, multimodal imaging and treatment of vasculitis of small, medium and large vessels as well as granulomatous and eosinophilic vascular diseases are described in the context of previous and current European League against Rheumatism (EULAR) and American College of Rheumatology (ACR) recommendations. Vasculitis is a syndrome which is part of various clinical disease entities, such as Wegener's granulomatosis, polyangiitis, Churg-Strauss syndrome, polyarteritis nodosa, cryoglobulinemia and other forms of vasculitis.

[Progress or regress or both? ESC guidelines on pericardial diseases 2015]. / Fortschritt oder Rückschritt oder beides zugleich? ESC-Leitlinien zu Perikarderkrankungen 2015.

Eleven years after the publication of the first guidelines worldwide on pericardial diseases by the European Society of Cardiology (ESC), the international expert group of the ESC has updated the original document of 28 pages with 275 references. The final version of the new guidelines is more voluminous with 44 pages of recommendations but only 233 references. A continuing medical education (CME) certified update of the 2004 guidelines was published in the journal Herz volume 7/2014. In comparison to 2004 the 2015 guidelines have remained virtually unchanged in the sections detailing diagnostics, differential diagnosis, pathology and pathophysiology. Substantial progress has been made in magnetic resonance imaging (MRI) of pericarditis and epicarditis and in the practically universal recommendation of colchicine for all forms of pericarditis and pericardial effusion, whether acute, chronic or recurrent. This can truly be called progress; however, little has changed since 2004 even in tertiary referral centers or universities with respect to the etiological classification of acute or recurrent forms of pericarditis or pericardial effusion. By classifying pericardial syndromes much too often as idiopathic when a malignant or bacterial cause has been excluded, the underlying cause is often overlooked. Standstill in diagnosis is in the end regress because we too often lag behind our actual diagnostic and interventional possibilities.

Suspected inflammatory cardiomyopathy. Prevalence of Borrelia burgdorferi in endomyocardial biopsies with positive serological evidence.

BACKGROUND: Cardiac involvement in Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi, has been reported to occur in 0.3-4 % of infected patients in Europe. Cardiac manifestations may include conduction disturbances, and also myocarditis, pericarditis, and left ventricular dysfunction. We investigated the prevalence of B. burgdorferi DNA in endomyocardial biopsies from patients with suspected inflammatory heart disease and positive serology for B. burgdorferi. METHODS AND RESULTS: In 64 patients, endomyocardial biopsies were taken after exclusion of coronary heart disease by coronary angiography, and investigated with polymerase chain reaction (PCR) for the presence of B. burgdorferi and cardiotropic viruses. B. burgdorferi DNA was not detected in any of the endomyocardial biopsies. Viruses, particularly parvovirus B19, were detected as infectious agents in 19 (30 %) patients. CONCLUSION: The results of our study demonstrate that PCR analysis of endomyocardial biopsies from patients with suspected inflammatory heart disease, including individuals with dilated cardiomyopathy (DCM) and positive serology for B. burgdorferi, did not reveal the B. burgdorferi genome in any biopsy sample.

[The 2014 ESC guidelines on the diagnosis and management of hypertrophic cardiomyopathy : what is new?]. / ESC-Leitlinie 2014 zur Diagnose und zum Management der hypertrophischen Kardiomyopathie : Was ist neu?

The 2014 European Society of Cardiology (ESC) guidelines on the diagnosis and management of hypertrophic cardiomyopathy (HCM) comprise 133 recommendations with 506 references. In comparison to the last 10-year-old American College of Cardiology Foundation (ACCF)/ESC guidelines new data have been added, such as recent studies on genetics, updated recommendations for family and genetic screening, a special emphasis on red flags in clinical symptomatology and diagnostic features for the identification of non-obstructive variants of HCM, on multimodality non-invasive imaging by echocardiography and cardiac magnetic resonance imaging (MRI) and a HCM risk formula for the assessment of sudden cardiac death within 5 years. Nevertheless, it should not be forgotten that the majority of patients with HCM lead a normal life. This detailed update and the structured recommendations are an excellent summary of the current knowledge on HCM for the cardiomyopathy specialist and also for internists and general physicians.

[Diagnostics and therapy of pericarditis and pericardial effusion]. / Diagnostik und Therapie der Perikarditis und des Perikardergusses.

This article describes the diagnostics, differential diagnostics, multimodal imaging, medicinal and invasive diagnostic therapy of acute and chronic pericarditis, constrictive pericarditis, pericardial effusion and cardiac tamponade under etiological aspects and on the basis of the guidelines of the European Society of Cardiology (ESC). The starting point of the decision tree is the symptomatic patient with echocardiographic evidence of pericardial effusion. The principle feature of the diagnostics is the etiopathogenetic allocation of the pericardial disease which influences the clinical picture, course therapy and prognosis. Infectious pericarditis (e.g. viral, bacterial and tuberculous) is differentiated from sterile autoreactive pericarditis and from neoplastic pericardial effusion by the cytology of the effusion and immunohistological and molecular investigations of the pericardial and epicardial biopsies. Pericardioscopy plays an important role in the recognition of suspicious areas. In many cases intrapericardial administration of cisplatin for neoplastic pericardial effusion and instillation of triamcinolone for autoreactive pericarditis prevent recurrence just as a treatment of several months with colchicine.

[Etiology, diagnosis, management, and treatment of myocarditis. Position paper from the ESC Working Group on Myocardial and Pericardial Diseases]. / Ätiologie, Diagnose, Management und Therapie der Myokarditis. Positionspapier der ESC Working Group on Myocardial and Pericardial Diseases.

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.

Molecular signatures and the study of gene expression profiles in inflammatory heart diseases.

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.

Current treatment options in (peri)myocarditis and inflammatory cardiomyopathy.

In inflammatory dilated cardiomyopathy and myocarditis there is--apart from heart failure and antiarrhythmic therapies--no alternative to an aetiologically driven specific treatment. Prerequisite 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 aquired immunity including the T- and B-cell driven immune responses. The phases and clinical faces of myocarditis are summarized. Up-to-date information on current treatment options starting with heart failure and antiarrhythmic therapy are provided. Although inflammation can resolve spontaneously, specific treatment directed to the causative aetiology is often required. For fulminant, acute and chronic autoreactive myocarditis immunosuppressive treatment is beneficial, while for viral cardiomyopathy and myocarditis ivIg can resolve inflammation and is as successful as interferon therapy in enteroviral and adenoviral myocarditis. For Parvo B19 and HHV6 myocarditis eradication of the virus is still a problem by any of these treatment options. Finally, the potential of stem cell therapy has to be tested in future trials. In virus-negative, autoreactive perimyocardial disease a locoregional approach with intrapericardial instillation of high local doses of triamcinolone acetate has been shown to be highly efficient and with few systemic side-effects.

Cellular immune mechanisms in myocarditis.

The introduction of immunohistological techniques enabled a substantially more reliable diagnosis of inflammatory cardiomyopathy (DCMi) in endomyocardial biopsies (EMB) compared to the histological Dallas criteria. Decisive progress has been made in the understanding of cellular immune mechanisms in DCMi using immunohistological techniques, which apart from the field of diagnosis refinement have had prognostic implications and an influence on the selection criteria of DCMi patients who will likely benefit from immunosuppressive treatment. Digital image analysis systems have been employed to standardize quantification of immunohistological EMB stainings. Quantification of T cell-related genes by a methodologically validated preamplified real-time RT-PCR revealed that the T cells are characterized by differential expression of Th1-, Treg-, and CTL-related markers, while no major role could be confirmed for Th17 cells. The reported virus-associated differential T cell receptor Vbeta dominance suggests an antiviral specificity of virus-induced T cell responses in human DCMi.

Diabetic cardiomyopathy: ongoing controversies in 2012.

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.

Pericardial effusion of HIV-infected patients ? Results of a prospective multicenter cohort study in the era of antiretroviral therapy.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection have an increased risk of cardiovascular diseases. Previous publications described pericardial effusion as one of the most common HIV-associated cardiac affiliations. The aim of the current study was to investigate if pericardial effusion still has a relevant meaning of HIV-infected patients in the era of antiretroviral therapy. METHODS: The HIV-HEART (HIV-infection and HEART disease) study is a cardiology driven, prospective and multicenter cohort study. Outpatients with a known HIV-infection were recruited during a 20-month period in a consecutive manner from September 2004 to May 2006. The study comprehend classic parameters of HIV-infection, comprising CD4-cell count (cluster of differentiation) and virus load, as well as non-invasive tests of cardiac diseases, including a thorough transthoracic echocardiography. RESULTS: 802 HIV-infected patients (female: 16.6%) with a mean age of 44.2 ± 10.3 years, were included. Duration of HIV-infection since initial diagnosis was 7.6 ± 5.8 years. Of all participants, 85.2% received antiretroviral therapy. Virus load was detectable in 34.4% and CD4 - cell count was in 12.4% less than 200 cells/µl. Pericardial effusions were present in only two patients of the analysed population. None of the participants had signs of a relevant cardiovascular impairment by pericardial effusion. CONCLUSIONS: Our results demonstrate that the era of antiretroviral therapy goes along with low rates of pericardial effusions in HIV-infected outpatients. Our findings are in contrast to the results of publications, performed before the common use of antiretroviral therapy.