BACKGROUND The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age-and sex-matched patients who had an acute coronary syndrome. RESULTS Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

n patients with coronavirus disease 2019 (COVID-19), cardiovascular involvement occurs frequently. Myocardial injury with elevated troponin levels is described in patients hospitalized with COVID-19 1 and seems to be associated with outcome. 2 The origin of myocardial injury can result from ischemia due to thrombotic coronary obstruction but can also include other causes such as heart failure, pulmonary embolism, tachycardia, and sepsis. 3 Obviously, an infection of the myocardium with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is another alternative for elevated troponin. Next to elevated biomarkers for cardiac injury, myocardial dysfunction determined by echocardiography is also reported in up to 70% of hospitalized patients. 4 This makes cardiac involvement during COVID-19, which manifests primarily as a pulmonary disease, likely.Myocarditislike clinical presentations have been described in only a few patients with COVID-19 to date, 5 suggesting that fulminant myocarditis is rare. 6 In the very few cases with clinically suspected myocarditis, SARS-CoV-2 infection was associated with cardiac inflammation. 7 Whether SARS-CoV-2 can be documented and replicates within the heart and whether this is associated with mononuclear cell infiltration or induces cytokine expression remains elusive in deceased patients without clinically overt myocarditis. Therefore, we investigated whether myocardial infection occurred in autopsy cases of patients with COVID-19. IMPORTANCE Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be documented in various tissues, but the frequency of cardiac involvement as well as possible consequences are unknown.OBJECTIVE To evaluate the presence of SARS-CoV-2 in the myocardial tissue from autopsy cases and to document a possible cardiac response to that infection. DESIGN, SETTING, AND PARTICIPANTSThis cohort study used data from consecutive autopsy cases from Germany between April 8 and April 18, 2020. All patients had tested positive for SARS-CoV-2 in pharyngeal swab tests.EXPOSURES Patients who died of coronavirus disease 2019. MAIN OUTCOMES AND MEASURESIncidence of SARS-CoV-2 positivity in cardiac tissue as well as CD3 + , CD45 + , and CD68 + cells in the myocardium and gene expression of tumor necrosis growth factor α, interferon γ, chemokine ligand 5, as well as interleukin-6, -8, and -18.RESULTS Cardiac tissue from 39 consecutive autopsy cases were included. The median (interquartile range) age of patients was 85 (78-89) years, and 23 (59.0%) were women. SARS-CoV-2 could be documented in 24 of 39 patients (61.5%). Viral load above 1000 copies per μg RNA could be documented in 16 of 39 patients (41.0%). A cytokine response panel consisting of 6 proinflammatory genes was increased in those 16 patients compared with 15 patients without any SARS-CoV-2 in the heart. Comparison of 15 patients without cardiac infection with 16 patients with more than 1000 copies revealed no inflammatory cell infiltrates or differences in leukocyte numbers per high power field. CO...

Muscle cells respond to mechanical stretch stimuli by triggering downstream signals for myocyte growth and survival. The molecular components of the muscle stretch sensor are unknown, and their role in muscle disease is unclear. Here, we present biophysical/biochemical studies in muscle LIM protein (MLP) deficient cardiac muscle that support a selective role for this Z disc protein in mechanical stretch sensing. MLP interacts with and colocalizes with telethonin (T-cap), a titin interacting protein. Further, a human MLP mutation (W4R) associated with dilated cardiomyopathy (DCM) results in a marked defect in T-cap interaction/localization. We propose that a Z disc MLP/T-cap complex is a key component of the in vivo cardiomyocyte stretch sensor machinery, and that defects in the complex can lead to human DCM and associated heart failure.

Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally <1 month). In contrast, chronic inflammatory cardiomyopathy indicates myocardial inflammation with established dilated cardiomyopathy or hypokinetic nondilated phenotype, which in the advanced stages evolves into fibrosis without detectable inflammation. Suggested diagnostic and treatment recommendations for AM and chronic inflammatory cardiomyopathy are mainly based on expert opinion given the lack of well-designed contemporary clinical studies in the field. We will provide a shared and practical approach to patient diagnosis and management, underlying differences between the European and US scientific statements on this topic. We explain the role of histology that defines subtypes of myocarditis and its prognostic and therapeutic implications.

The increasing prevalence of heart failure poses enormous challenges for health care systems worldwide. Despite effective medical interventions that target neurohumoral activation, mortality and morbidity remain substantial. Evidence for inflammatory activation as an important pathway in disease progression in chronic heart failure has emerged in the last two decades. However, clinical trials of ‘anti‐inflammatory’ therapies (such as anti‐tumor necrosis factor‐α approaches) have to date failed to show benefit in heart failure patients. The Heart Failure Association of the European Society of Cardiology recently organized an expert workshop to address the issue of inflammation in heart failure from a basic science, translational and clinical perspective, and to assess whether specific inflammatory pathways may yet serve as novel therapeutic targets for this condition. This consensus document represents the outcome of the workshop and defines key research questions that still need to be addressed as well as considering the requirements for future clinical trials in this area.