Background-Small selected cohort studies suggest that mutations in the cardiac myosin binding protein-C (MYBPC3) gene cause late-onset, clinically benign hypertrophic cardiomyopathy (HCM). Pϭ0.03). In 9 families (25 individuals) with the R502W mutation, there was marked heterogeneity in age at diagnosis (5 to 80 years), pattern of hypertrophy (11 none, 9 asymmetrical, 3 concentric, 1 apical, 1 eccentric), and prognosis (premature sudden death in 2 individuals compared with survival to advanced age in 6 individuals). During follow up of 7.9ϩ/Ϫ4.5 years, in 82 clinically affected individuals the annual risk of sudden death and all cause mortality was 0.46% and 0.93% per year, respectively. Conclusions-Disease expression in families with HCM related to MYBPC3 mutations shows marked heterogeneity with incomplete, age-related, and gender specific penetrance. Importantly, complex genetic status is observed and should be considered when mutation analysis and cascade screening is used in the evaluation of at risk family members. (Circ Cardiovasc Genet. 2012;5:156-166.)

The present study aimed to investigate the causative medications and underlying risk factors that predispose to drug-induced QT interval prolongation. Twenty-one patients with drug-induced long QT (90% females, mean age 64.3 +/- 14.1 years) were included in the study. Transthoracic echocardiography as well as continuous or ambulatory 48-h electrocardiographic monitoring was carried out in all patients during their hospitalization. The mean corrected QT (QTc) interval was 542 +/- 56.8 ms. Known cardiac agents (mainly class III antiarrhythmics) were implicated in 13/21 (62%), antipsychotics in 8/21 (38%), and antibiotics in 5/21 patients (24%). Potential drug-interactions through inhibition of cytochrome P450 isoenzymes were considered responsible in 5/21 cases (24%). The underlying cardiovascular diseases included hypertension (57%) with left ventricular hypertrophy (29%), paroxysmal atrial tachyarrhytmias (48%), heart failure (14%), valvular heart disease (10%), and coronary artery disease (5%). Torsade de pointes (TdP) was recorded in 6/21 of patients, and cardiac arrest necessitating resuscitation occurred in five of them. A significant correlation was observed between administration of cardiac agents and TdP events (P < 0.05). TdP and cardiac arrest events were both associated with a QTc interval >510 ms (P < 0.05). Advanced age (>60 years), female gender, hypertension and paroxysmal atrial tachyarrhytmias were the most common identifiable pre-existing factors for drug-induced long QT in our patient cohort. Marked QTc interval prolongation should be considered of prognostic significance for TdP and cardiac arrest events.

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