Application of Multigene Panel Sequencing in Patients with Prolonged Rate-corrected QT Interval and No Pathogenic Variants Detected in KCNQ1, KCNH2, and SCN5A

Long QT syndrome (LQTS) is an inherited cardiac disease characterized by a prolonged heart rate-corrected QT (QTc) interval. We investigated the genetic causes in patients with prolonged QTc intervals who were negative for pathogenic variants in three major LQTS-related genes (KCNQ1, KCNH2, and SCN5A). Molecular genetic testing was performed using a panel including 13 LQTS-related genes and 67 additional genes implicated in other cardiac diseases. Overall, putative genetic causes of prolonged QTc interval were identified in three of the 30 patients (10%). Among the LQTS-related genes, we detected a previously reported pathogenic variant, CACNA1C c.1552C>T, responsible for cardiac-only Timothy syndrome. Among the genes related to other cardiac diseases, a likely pathogenic variant, RYR2 c.11995A>G, was identified in a patient with catecholaminergic polymorphic ventricular tachycardia. Another patient who developed dilated cardiomyopathy with prolonged QTc interval was found to carry a likely pathogenic variant, TAZ c.718G>A, associated with infantile dilated cardiomyopathy. Comprehensive screening of genetic variants using multigene panel sequencing enables detection of genetic variants with a possible involvement in QTc interval prolongation, thus uncovering unknown molecular mechanisms underlying LQTS.

Association between physical performance and electrocardiographic heart rate corrected-QT interval in elderly subjects / 体力科学

It is well known that decreased physical performance induces the decreased activity of daily living and increment of mortality rate in elderly subjects. On the other hand, a prolonged heart rate corrected-QT (QTc) interval is associated with an increased risk of cardiac sudden death and cardiac autonomic dysfunction. We investigated the associations between physical performance and QTc interval in elderly subjects. The subjects included 605 elderly persons (274 men and 331 women, age; 71.2±4.7 years) without a history of cardiovascular disease and taking cardioactive drugs. Resting 12-leads electrocardiography was measured after more than 5 minutes of rest. The QTc interval was calculated according to Bazett’s formula. The physical fitness test was performed to determine the physical performance (muscle strength, balance and walking abilities). The subjects were divided into four categories, which were defined as equally quantile distributions of QTc interval. The physical performance levels were significantly lower in the longest QTc interval group compared to the shortest QTc interval group in both men and women (p<0.05, respectively). Moreover, after adjusting for the age, the physical performance levels were significantly lower in the longest QTc interval group compared to the shortest QTc interval group, especially, this relationship was observed in late-stage elderly group (p<0.05, respectively). These results suggest that decreased physical performance levels were also associated with prolonged QTc interval in elderly subjects.