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Background Sarcoidosis is an inflammatory, granulomatous disease of unknown cause affecting multiple organs, including the heart. Untreated, unresolved granulomatous inflammation can lead to cardiac fibrosis, arrhythmias, and eventually heart failure. Here we characterize the cardiac phenotype of mice with chronic activation of mammalian target of rapamycin (mTOR) complex 1 signaling in myeloid cells known to cause spontaneous pulmonary sarcoid‐like granulomas. Methods and Results The cardiac phenotype of mice with conditional deletion of the tuberous sclerosis 2 (TSC2) gene in CD11c+ cells (TSC2fl/flCD11c‐Cre; termed TSC2KO) and controls (TSC2fl/fl) was determined by histological and immunological stains. Transthoracic echocardiography and invasive hemodynamic measurements were performed to assess myocardial function. TSC2KO animals were treated with either everolimus, an mTOR inhibitor, or Bay11‐7082, a nuclear factor‐kB inhibitor. Activation of mTOR signaling was evaluated on myocardial samples from sudden cardiac death victims with a postmortem diagnosis of cardiac sarcoidosis. Chronic activation of mTORC1 signaling in CD11c+ cells was sufficient to initiate progressive accumulation of granulomatous infiltrates in the heart, which was associated with increased fibrosis, impaired cardiac function, decreased plakoglobin expression, and abnormal connexin 43 distribution, a substrate for life‐threatening arrhythmias. Mice treated with the mTOR inhibitor everolimus resolved granulomatous infiltrates, prevented fibrosis, and improved cardiac dysfunction. In line, activation of mTOR signaling in CD68+ macrophages was detected in the hearts of sudden cardiac death victims who suffered from cardiac sarcoidosis. Conclusions To our best knowledge this is the first animal model of cardiac sarcoidosis that recapitulates major pathological hallmarks of human disease. mTOR inhibition may be a therapeutic option for patients with cardiac sarcoidosis.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterised by adenergically mediated bidirectional and/or polymorphic ventricular tachycardia. CPVT is a significant cause of autopsy-negative sudden death in children and adolescents, although it can also affect adults. It is often caused by pathogenic variants in the cardiac ryanodine receptor gene as well as other rarer genes. Early identification and risk stratification is of major importance. β-blockers are the cornerstone of therapy. Sodium channel blockers, specifically flecainide, have an additive role. Left cardiac sympathetic denervation is playing an increasing role in suppression of arrhythmia and symptoms. Concerns have been raised, however, about the efficacy of implantable cardioverter defibrillator therapy and the risk of catecholamine driven proarrhythmic storms. In this review, we summarise the clinical characteristics, genetics, and diagnostic and therapeutic strategies for CPVT and describe recent advances and challenges.

The burden of AF is increasing in prevalence and healthcare resource usage in the UK and worldwide. It can result in impaired quality of life for affected patients, as well as increased risk of stroke, heart failure and mortality. A holistic, integrated approach to AF management is recommended, which may include a focus on reducing risk factors and on medical management with anticoagulation and anti-arrhythmic drugs. There are also various ablation strategies that may be considered when anti-arrhythmic drugs fail to alleviate symptoms and reduce AF burden. These ablation techniques range from standalone percutaneous endocardial catheter ablation to open surgical ablation procedures concomitant with cardiac surgery. More recently, hybrid ablation that combines aspects of both surgical and electrophysiologically targeted ablation has been described. This article reviews the evolution of ablation strategies, beginning with the origin of the Cox maze IV procedure and continuing to the recent hybrid convergent approach, and provides a summary of the associated outcomes.

We present a case of a 25-year-old woman with multiple blackouts and no structural heart disease, with abnormal T-U waves and borderline QT interval on her resting electrocardiogram. During emotional stress she developed frequent monomorphic ventricular premature beats, with characteristic changes of the sinus complexes immediately following the premature beats, namely augmentation and greater degree of merging of the T and U waves and QTc interval prolongation. The changes alert about the possibility of congenital long QT syndrome, specifically genotype 2 or 1.