[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.

[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.

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.

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.

[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.

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.

Differential diagnosis of pericardial effusion after stem cell transplantation in acute myeloic leukemia.

The pathology underlying a pericardial effusion in a 24-year-old patient, who had suffered from acute myeloic leukemia 5 years previously and undergone chemotherapy followed by whole body radiation prior to allogeneic stem cell transplantation, could be identified by the careful analysis of pericardial cytology and epicardial biopsy guided by flexible pericardioscopy. Molecular, histological, cytochemical and immunological examination of the effusion and the epicardial biopsy for a viral or bacterial infection despite known CMV reactivation, or an effusion induced by radiation or graft-versus-host reaction, could be ruled out as possible causes of pericardial tamponade. The infiltration of CD 117-positive cells in the biopsied cardiac tissue revealed recurrent acute myeloic leukemia now also affecting the heart and the pericardium. An intrapericardial instillation of 1000 mg triamcinolone acetate at day 1 and 50 mg/m(2) cisplatin at day 3 effectively prevented the recurrence of tamponade, but could not prevent a lethal outcome 3 weeks later.

Treatment of cardiovascular diseases in cancer patients.

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.

[Tumor markers in the assessment of malignant and benign pericardial effusion]. / Tumormarker im Perikarderguss bei malignen und nichtmalignen Perikardergüssen.

BACKGROUND: The differential diagnosis of pericardial effusion is often challenging because different etiologies can be discussed. Of particular therapeutic and prognostic importance is the definitive differentiation of malignant pericardial effusion from benign effusions. The definitive diagnosis of malignant pericardial effusion is established by a positive cytological examination of the pericardial fluid. However, pericardial fluid cytology, although specific has variable sensitivity. Tumor markers are often investigated after pericardiocentesis but their utility as an aid for the diagnosis of malignant pericardial effusion is not well established. The aim of this study was to measure the concentrations of the tumor markers CEA, CA 19-9, CA 72-4, SCC and NSE in malignant and non-malignant pericardial effusions and to assess their diagnostic utility in differentiating malignant from benign pericardial effusion. METHODS: We investigated the pericardial fluid of 29 patients with proven malignant pericardial effusion and 25 patients with non-malignant pericardial effusion. The etiology of the pericardial effusion was defined by pericardial cytology, epicardial histology and PCR for cardiotropic viruses from pericardial and epicardial tissue acquired by pericardioscopy. The group with non-malignant pericardial effusion comprised 15 patients with autoreactive effusion and 10 patients with viral pericardial effusion. We analyzed the following tumor markers in the pericardial fluid: carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, carbohydrate antigen (CA) 72-4, squamous cell carcinoma (SCC) antigen and neuron-specific enolase (NSE). RESULTS: Of the tumor markers tested the mean concentrations of the CEA, CA 72-4 and CA 19-9 were significantly higher in malignant pericardial effusions than in non-malignant effusions (CEA 450.66 ±1620.58 µg/l vs. 0.72 ±1.49 µg/l, p<0.001; CA 19-9 1331.31 ±3420.87 kU/l vs. 58.85 ±17.53 kU/l, p=0.04; CA 72-4 707.90 ±2397.55 kU/l vs. 0.48 ±2.40 kU/l, p<0.001). ROC curve analysis showed that pericardial fluid CA 72-4 yielded an area under the curve (AUC) of 0.85 (95% confidence interval 0.74-0.95), followed by CEA with 0.80 (95% confidence interval 0.68-0.92). Pericardial fluid CA 72-4 levels >1.0 kU/l had 72% sensitivity (95% confidence interval 53%-87%) and 96% specificity (95% confidence interval 80%-99.9%) and CA 72-4 levels >2.5 kU/l had 69% sensitivity (95% confidence interval 49%-85%) and 96% specificity (95% confidence interval 80%-99.9%) in differentiating malignant pericardial effusions from effusions due to benign conditions. CONCLUSION: Malignant pericardial effusions are associated with significantly higher pericardial concentrations of the tumor markers CEA, CA 72-4 and CA 19-9. Of the tested tumor markers, measurement of CA 72-4 levels in pericardial fluid offered the best diagnostic accuracy. Based on our data evaluation of every patient with unexplained pericardial effusion and negative pericardial fluid cytology should include the measurement of pericardial fluid CA 72-4 levels. Under these circumstances the elevation of pericardial fluid CA 72-4 levels should include malignancy as a probable diagnosis.

Diabetic cardiomyopathy--fact or fiction?

Epidemiologic as well as clinical studies confirm the close link between diabetes mellitus and heart failure. Diabetic cardiomyopathy (DCM) is still a poorly understood "entity", however, with several contributing pathogenetic factors which lead in different stages of diabetes to characteristic clinical phenotypes. Hyperglycemia with a shift from glucose metabolism to increased beta-oxidation and consecutive free fatty acid damage (lipotoxicity) to the myocardium, insulin resistance, renin-angiotensin-aldosterone system (RAAS) activation, altered calcium homeostasis and structural changes from the natural collagen network to a stiffer matrix due to advanced glycation endproduct (AGE) formation, hypertrophy and fibrosis contribute to the respective clinical phenotypes of DCM. We propose the following classification of cardiomyopathy in diabetic patients: a) Diastolic heart failure with normal ejection fraction (HFNEF) in diabetic patients often associated with hypertrophy without relevant hypertension. Relevant coronary artery disease (CAD), valvular disease and uncontrolled hypertension are not present. This is referred to as stage 1 DCM. b) Systolic and diastolic heart failure with dilatation and reduced ejection (HFREF) in diabetic patients excluding relevant CAD, valvular disease and uncontrolled hypertension as stage 2 DCM. c) Systolic and/or diastolic heart failure in diabetic patients with small vessel disease (microvascular disease) and/or microbial infection and/or inflammation and/or hypertension but without CAD as stage 3 DCM. d) If heart failure may also be attributed to infarction or ischemia and remodeling in addition to stage 3 DCM the term should be heart failure in diabetes or stage 4 DCM. These clinical phenotypes of diabetic cardiomyopathy can be separated by biomarkers, non-invasive (echocardiography, cardiac magnetic resonance imaging) and invasive imaging methods (levocardiography, coronary angiography) and further analysed by endomyocardial biopsy for concomitant viral infection. The role of specific diabetic drivers to the clinical phenotypes, to macro- and microangiopathy as well as accompanying risk factors or confounders, e.g. hypertension, autoimmune factors or inflammation with or without viral persistence, need to be identified in each individual patient separately. Thus hyperglycemia, hyperinsulinemia and insulin resistance as well as lipotoxicity by free fatty acids (FFAs) are the factors responsible for diabetic cardiomyopathy. In stage 1 and 2 DCM diabetic cardiomyopathy is clearly a fact. However, precise determination of to what degree the various underlying pathogenetic processes are responsible for the overall heart failure phenotype remains a fiction.

[Preoperative cardiac risk assessment and perioperative cardiac management in non-cardiac surgery. The 2009 ESC guidelines]. / Präoperatives kardiales Risiko und perioperatives kardiales Management bei nichtkardialer Chirurgie. Die ESC-Leitlinie 2009.

In November 2009 the first European guidelines were presented regarding preoperative risk assessment and perioperative management in non-cardiac surgery. They were designed by the European Society of Cardiology (ESC) and endorsed by the European Society of Anesthesiology.In a standardized manner, patient-specific clinical variables, their exercise capacity and surgery-specific risk factors are summarized to a recommendation concerning medication and preoperative cardiac evaluation. These guidelines are straightforward and feasible for cardiologists as well as specialists in internal medicine and general practicioners. Nevertheless, some points still lack evidence.

Intrapericardial procedures for cardiac regeneration by stem cells: need for minimal invasive access (AttachLifter) to the normal pericardial cavity.

In view of the only modest functional and anatomical improvements achieved by bone marrow-derived cell transplantation in patients with heart disease, the question was addressed whether the intracoronary, transcoronary-venous, and intramyocardial delivery routes are adequate. It is hypothesized that an intrapericardial delivery of stem cells or activators of resident cardiac stem cells increases therapeutic benefits. From such an intrapericardial depot, cells or modulating factors, such as thymosin ß4 or Ac-SDKP, are expected to reach the myocardium with sustained kinetics. Novel tools which provide access to the pericardial space even in the absence of pericardial effusion are, therefore, described. When the pericardium becomes attached to the suction head (monitored by an increase in negative pressure), the pericardium is lifted from the epicardium ("AttachLifter"). The opening of the suction head ("Attacher") is narrowed by flexible clamps which grab the tissue and improve the vacuum seal in the case of uneven tissue. A ridge, i.e.,"needle guidance", on the suction head excludes injury to the epicardium, whereby the pericardium is punctured by a needle which resides outside the suction head. A fiberscope can be used to inspect the pericardium prior to puncture. Based on these procedures, the role of the pericardial space and the presence of pericardial effusion in cardiac regeneration can be assessed.

[The heart in viral infections]. / Das Herz bei viralen Infektionen.

Between 10 and 20% of patients with histologically proven inflammatory disease of the heart muscle develop a chronic disorder after acute myocarditis which results in dilated cardiomyopathy with increasing cardiac insufficiency. Viral infections are a frequent cause of inflammatory heart muscle diseases and thus also responsible for myocardial damage in the initial phase. In the past, evidence for enterovirus, adenovirus, and cytomegalovirus was in the focus of attention. In the meantime, "new" cardiotropic pathogens such as parvovirus B19, Epstein-Barr virus, and human herpesvirus 6 have been detected in patients with dilated cardiomyopathy with and without inflammation. Their persistence in the myocardium correlates with a decline in pumping capability within 6 months. While the virus is still being eliminated, the second phase of the disease begins, which is characterized by autoimmune phenomena and often a cardiac inflammatory response which likewise correlates with a worsening prognosis. The transition to the third and final phase with development of dilated cardiomyopathy occurs gradually and can take years. The goal of every diagnostic and therapeutic intervention must be to eradicate the virus and eliminate the inflammatory response to prevent the disease from progressing to terminal cardiac insufficiency.

[New possibilities of diagnostics and therapy of pericarditis]. / Neue Möglichkeiten der Diagnostik und Therapie der Perikarditis.

Pericarditis is an inflammatory disorder of the pericardium with or without an associated pericardial effusion. The diagnosis is based on the clinical manifestations and typical ECG changes. Echocardiography is essential to reveal the size of the pericardial effusion and to determine its hemodynamic significance. The precise etiology of pericarditis may be established by pericardiocentesis, pericardioscopy and targeted biopsy and consecutive pericardial fluid and biopsy analysis by molecular biology, cytology, microbiology and immunological techniques. Non steroidal anti-inflammatory drugs and/or colchicine are the mainstay of anti-inflammatory treatment of pericarditis. Systemic corticoid treatment should be restricted to patients with associated autoimmune disorder, relapsing pericarditis and as a complementary therapy in tuberculous pericarditis. In autoreactive pericarditis intrapericardial instillation of triamcinolone is effective with few side effects. In malignant pericarditis the intrapericardial administration of cisplatin prevents early recurrences.