ObjectiveOwing to the paucity of data, this study aimed to investigate sex differences in clinical features and prognosis of patients with cardiac sarcoidosis (CS). MethodsThis study was a... Show moreObjectiveOwing to the paucity of data, this study aimed to investigate sex differences in clinical features and prognosis of patients with cardiac sarcoidosis (CS). MethodsThis study was a secondary analysis of the ILLUstration of the Management and prognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis registry-a retrospective multicentre registry that enrolled patients with CS between 2001 and 2017. The primary outcome was potentially fatal ventricular arrhythmia events (pFVAEs)-a composite of sudden cardiac death, sustained ventricular tachycardia lasting >30 s, ventricular fibrillation or the requirement for implantable cardioverter defibrillator therapy. ResultsOf the 512 participants (mean age +/- SD 61.6 +/- 11.4 years), 329 (64.2%) were females. Both sexes had peak ages of 60-64 years at diagnosis. Male patients were younger and had a higher prevalence of coronary artery disease and lower left ventricular ejection fraction than female patients. During a median follow-up of 3 years (IQR 1.6-5.6), pFVAEs were observed in 99 patients, with males having a significantly higher risk than females (p=0.002). This association was retained even after adjustment for other risk factors for pFVAEs, including left ventricular ejection fraction (adjusted HR 1.80; 95% CI 1.08 to 3.01, p=0.025). ConclusionApproximately two-thirds of patients with CS were females, with a peak age of approximately 60 years at clinical diagnosis in both sexes; male patients were younger than female patients. Male patients had a significantly higher risk of pFVAEs than female patients. Show less
Background:Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely... Show moreBackground:Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. Methods:Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. Results:There were 98 probands and 72 family members (mean age at diagnosis 43 +/- 8 years, 59% women) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 genome aggregation database control variants (148 [83.6%] versus 29 [16.4%]; P<0.0001). Conclusions:In the largest series of individuals with DSPtv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management. Show less
