Background: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19–associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. Methods: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19–associated AM. Results: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19–associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia ( P =0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P <0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). Conclusions: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

While clinical gene therapy celebrates its first successes, with several products already approved for clinical use and several hundreds in the final stages of the clinical approval pipeline, there is not a single gene therapy approach that has worked for the heart. Here, we review the past experience gained in the several cardiac gene therapy clinical trials that had the goal of inducing therapeutic angiogenesis in the ischemic heart and in the attempts at modulating cardiac function in heart failure. Critical assessment of the results so far achieved indicates that the efficiency of cardiac gene delivery remains a major hurdle preventing success but also that improvements need to be sought in establishing more reliable large animal models, choosing more effective therapeutic genes, better designing clinical trials, and more deeply understanding cardiac biology. We also emphasize a few areas of cardiac gene therapy development that hold great promise for the future. In particular, the transition from gene addition studies using protein-coding cDNAs to the modulation of gene expression using small RNA therapeutics and the improvement of precise gene editing now pave the way to applications such as cardiac regeneration after myocardial infarction and gene correction for inherited cardiomyopathies that were unapproachable until a decade ago.

Aims Admission rates for acute decompensated heart failure declined during COVID‐19. However, the impact of this reduction on hospital mortality is unknown. We describe temporal trends in the presentation of patients with acute heart failure (HF) and their in‐hospital outcomes from two referral centres in London during the COVID‐19 pandemic. Methods and results A total of 1372 patients hospitalized for HF in two referral centres in South London between 7^th January and 14^th June 2020, were included in the study and compared to the same time period in 2019. The primary outcome was all‐cause in‐hospital mortality. HF hospitalizations were significantly reduced during the COVID‐19 pandemic, compared to 2019 (p<0.001). Specifically, we observed a temporary reduction in hospitalizations during the COVID‐19 peak, followed by a return to 2019 levels. Patients admitted during the COVID‐19 pandemic had similar demographic characteristics compared to the same period in 2019. However, in‐hospital mortality was significantly higher in 2020 compared to 2019 (p=0.015). Hospitalization in 2020 was independently associated with worse in‐hospital mortality (hazard ratio [HR] 2.23, 95% Confidence Interval [CI] 1.34 – 3.72; p=0.002). Conclusion During the COVID‐19 pandemic there was a reduction in HF hospitalizations and higher in‐hospital mortality. Hospitalisation for HF in 2020 is independently associated with more adverse outcomes. Further studies are required to investigate the predictors of these adverse outcomes to help inform potential changes to the management of HF patients while some constraints to usual care remain.

The aging myopathy manifests itself with diastolic dysfunction and preserved ejection fraction. We raised the possibility that, in a mouse model of physiological aging, defects in electromechanical properties of cardiomyocytes are important determinants of the diastolic characteristics of the myocardium, independently from changes in structural composition of the muscle and collagen framework. Here we show that an increase in the late Na⁺ current (I_NaL) in aging cardiomyocytes prolongs the action potential (AP) and influences temporal kinetics of Ca²⁺ cycling and contractility. These alterations increase force development and passive tension. Inhibition of I_NaL shortens the AP and corrects dynamics of Ca²⁺ transient, cell contraction and relaxation. Similarly, repolarization and diastolic tension of the senescent myocardium are partly restored. Thus, I_NaL offers inotropic support, but negatively interferes with cellular and ventricular compliance, providing a new perspective of the biology of myocardial aging and the aetiology of the defective cardiac performance in the elderly.