[Canada's guidance on alcohol and health : A paradigm shift]. / Kanadas Leitlinienempfehlung zu Alkohol und Gesundheit : Ein Paradigmenwechsel.

Alcohol is a socially accepted food and beverage and as a cultural asset is also part of religious rituals. It can be an intoxicant and an addictive substance. It is also a noxious substance as around 3 million people worldwide die every year as a result of alcohol consumption. With the publication by Zhao et al. 2023 the relationship between the quantity of alcohol consumption and mortality reached a new level and changed the recommendations of Canada's Guidance on Alcohol and Health. The J­curve of the French paradox became a linear relationship between alcohol consumption and mortality because the review of several control groups in previous studies revealed a recruitment error from abstinent ex-drinkers. In their systematic analysis, taking this bias into account the assessment of small amounts of alcohol as a cardioprotective stimulant had to be revised. This is a paradigm shift.

SARS-CoV-2, vaccination or autoimmunity as causes of cardiac inflammation. Which form prevails?

The causes of cardiac inflammation during the COVID-19 pandemic are manifold and complex, and may have changed with different virus variants and vaccinations. The underlying viral etiology is self-evident, but its role in the pathogenic process is diverse. The view of many pathologists that myocyte necrosis and cellular infiltrates are indispensable for myocarditis does not suffice and contradicts the clinical criteria of myocarditis, i.e., a combination of serological evidence of necrosis based on troponins or MRI features of necrosis, edema, and inflammation based on prolonged T1 and T2 times and late gadolinium enhancement. The definition of myocarditis is still debated by pathologists and clinicians. We have learned that myocarditis and pericarditis can be induced by the virus via different pathways of action such as direct viral damage to the myocardium through the ACE2 receptor. Indirect damage occurs via immunological effector organs such as the innate immune system by macrophages and cytokines, and then later the acquired immune system via T cells, overactive proinflammatory cytokines, and cardiac autoantibodies. Cardiovascular diseases lead to more severe courses of SARS-CoV­2 disease. Thus, heart failure patients have a double risk for complicated courses and lethal outcome. So do patients with diabetes, hypertension, and renal insufficiency. Independent of the definition, myocarditis patients benefitted from intensive hospital care, ventilation, if needed, and cortisone treatment. Postvaccination myocarditis and pericarditis affect primarily young male patients after the second RNA vaccine. Both are rare events but severe enough to deserve our full attention, because treatment according to current guidelines is available and necessary.

[The AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guidelines 2021 on thoracic pain]. / AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR-Leitlinie 2021 zum Thoraxschmerz.

The AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guidelines 2021 on thoracic pain focusses on chest pain as a single but important symptom. The guidelines fall back on many guidelines on cardiac disease entities, such as myocardial infarction with (STEMI) or without ST segment elevation (NSTEMI), chronic coronary artery disease (CAD), pericarditis and aortic dissection. They also refer to guidelines on cardiac syndromes, such as acute coronary syndrome (ACS) or ACS without persisting ST segment elevation (NSTE-ACS), in which angina pectoris is an integral component. The guideline separates acute from stable angina pectoris. It gives a comprehensive overview on risk stratification and clinical work-up of chest pain. It stretches the main theme to angina equivalents, such as dyspnoe. They meticulously weigh up the noninvasive against the invasive diagnostic methods under the aspects of a cost-benefit analysis. In this context, a clear trend towards evidence-based, cost-effective noninvasive methods in recent years is unmistakable.

[2 years COVID-19 pandemic-What have we learned?] / 2 Jahre COVID-19-Pandemie ­ was haben wir gelernt?

After 2 years and 5 waves of the coronavirus disease 2019 (COVID-19) pandemic in Germany and experience with superspreader events worldwide, we know that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly mutating virus with changing clinical phenotypes. Besides infections of the respiratory tract, which in severe cases are accompanied by pneumonia requiring mechanical ventilation, the involvement of the heart with myocarditis and pericarditis as well as the kidneys have short-term and also long-term consequences. We have learnt to deal with myocarditis and pericarditis in acute infections and after vaccinations, which in rare cases can also lead to myocarditis and pericarditis. Myocarditis with myocytolysis in autopsy specimens or endomyocardial biopsy specimens is rare. In contrast, elevated troponin levels and suspicious cardiac magnetic resonance imaging (MRI) findings are much more frequent. The best preventive measure is a complete double basic vaccination and booster vaccination with an mRNA vaccine. For patients and medical personnel precise information is given with respect to personal protective equipment and behavior (distancing-hygiene-mask-airing rule).

[The ESC recommendations for COVID-19-no guideline, but a learning guidance]. / Die ESC zu COVID-19 ­ keine Leitlinie, aber ein lernender Leitfaden.

"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 : Etiology and clinical management.

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.

[ESC and AHA guidelines 2015 on endocarditis : In competition or synchrony?] / ESC/AHA-Endokarditisleitlinien 2015 : Wettstreit oder Gleichklang?

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

Influence of different aetiologies on clinical course and outcome in patients with dilated cardiomyopathy.

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.

A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy.

AIMS: Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM. METHODS AND RESULTS: Applying a three-staged study design, we analysed more than 4100 DCM cases and 7600 controls. We identified and successfully replicated multiple single nucleotide polymorphism on chromosome 6p21. In the combined analysis, the most significant association signal was obtained for rs9262636 (P = 4.90 × 10(-9)) located in HCG22, which could again be replicated in an independent cohort. Taking advantage of expression quantitative trait loci (eQTL) as molecular phenotypes, we identified rs9262636 as an eQTL for several closely located genes encoding class I and class II major histocompatibility complex heavy chain receptors. CONCLUSION: The present study reveals a novel genetic susceptibility locus that clearly underlines the role of genetically driven, inflammatory processes in the pathogenesis of idiopathic DCM.

Management of fulminant myocarditis: a diagnosis in search of its etiology but with therapeutic options.

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.

Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases.

In this position statement of the ESC Working Group on Myocardial and Pericardial Diseases an expert consensus group reviews the current knowledge on clinical presentation, diagnosis and treatment of myocarditis, and proposes new diagnostic criteria for clinically suspected myocarditis and its distinct biopsy-proven pathogenetic forms. The aims are to bridge the gap between clinical and tissue-based diagnosis, to improve management and provide a common reference point for future registries and multicentre randomised controlled trials of aetiology-driven treatment in inflammatory heart muscle disease.

Trypomastigotes and amastigotes of Trypanosoma cruzi induce apoptosis and STAT3 activation in cardiomyocytes in vitro.

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.