Temporal Repolarization Lability in Hypertrophic Cardiomyopathy Caused by β-Myosin Heavy-Chain Gene Mutations

Background —Certain genetic mutations associated with hypertrophic cardiomyopathy (HCM) carry an increased risk of sudden death. QT variability identifies patients at a high risk for sudden death from ventricular arrhythmias. We tested whether patients with HCM caused by β-myosin heavy-chain (β-MHC) gene mutations exhibit labile ventricular repolarization using beat-to-beat QT variability analysis.Methods and Results —We measured the QT variability index and heart rate–QT interval coherence from Holter monitor recordings in 36 patients with HCM caused by known β-MHC gene mutations and in 26 age- and sex-matched controls. There were 7 distinct β-MHC gene mutations in these 36 patients; 9 patients had HCM caused by the malignant Arg403 Gln mutation and 8 patients had HCM caused by the more benign Leu908 Val mutation. The QT variability index was higher in HCM patients than in controls (−1.24±0.17 versus −1.58±0.38,P <0.01), and the greatest abnormality was detected in patients with the Arg403 Gln mutation (−0.99±0.49 versus −1.46±0.43 in controls,P <0.05). In keeping with this finding, coherence was lower for the entire HCM group than for controls (P <0.001). Coherence was also significantly lower in patients with the Arg403 Gln mutation compared with controls (P <0.05).Conclusions —These findings suggest that (1) patients with HCM caused by β-MHC gene mutations exhibit labile repolarization quantified by QT variability analysis and, hence, may be more at risk for sudden death from ventricular arrhythmias, and (2) indices of QT variability may be particularly abnormal in patients with β-MHC gene mutations that are associated with a poor prognosis.