The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal Mendelian Long QT Syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals we identified 35 common variant QT interval loci, that collectively explain ∼8-10% of QT variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 novel QT loci in 298 unrelated LQTS probands identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode for proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies novel candidate genes for ventricular arrhythmias, LQTS,and SCD.

Purpose of review Cardiomyopathies are rare in the pediatric population, but significantly impact on morbidity and mortality. The present review aims to provide an overview of cardiomyopathies in children and some practical guidelines for their prognostic stratification and management. Recent findings Pediatric cardiomyopathies may present as isolated cardiac muscle disease or in the context of complex clinical syndromes. The etiologic characterization represents an important step in the diagnosis and treatment of cardiomyopathies because of its impact on prognosis and on therapeutic measures. Indeed, replacement therapy is nowadays widely available and changes the natural history of the disease. More complex is the management of isolated cardiomyopathies, which lack specific therapies, mainly aimed at symptomatic relief. In this context, heart transplantation shows excellent outcomes in children, but wait-list mortality is still very high. Device therapy for sudden cardiac death prevention and the use of mechanical assist devices are becoming more common in the clinical practice and may help to reduce mortality. Summary Providing insight into pediatric cardiomyopathies classification helps in the prognostication and management of such diseases. Recent years witnessed a significant improvement in mortality, but future research is still needed to improve quality of life and life expectations in the pediatric population.

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Background Pulmonary arterial hypertension consists in an increase of mean pulmonary arterial pressure (PAPm ≥ 25 mmHg), and may lead to right ventricular failure. Pulmonary arterial hypertension can arise in several disorders, encompassing inflammatory conditions and connective tissue diseases. The occurrence of pulmonary arterial hypertension has recently been reported in monogenic interferonopathies and in systemic lupus erythematosus, highlighting the pathogenic role of type I interferons and paving the way to therapies aimed at inhibiting interferon signaling. Case We describe a 17-year-old boy with DNase II deficiency, presenting a clinical picture with significant overlap with systemic lupus erythematosus. During treatment with the Janus kinase inhibitor ruxolitinib, he developed pulmonary arterial hypertension, raising the question whether it could represent a sign of insufficient disease control or a drug-related adverse event. The disease even worsened after drug withdrawal, but rapidly improved after starting the drug again at higher dosage. Summary and conclusion Pulmonary arterial hypertension can complicate type I interferonopathies. We propose that ruxolitinib was beneficial in this case, but the wider role of Janus kinase inhibitors for the treatment of pulmonary arterial hypertension is not clear. For this reason, a strict cardiologic evaluation must be part of the standard care of subjects with interferonopathies, especially when Janus kinase inhibitors are prescribed.

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