Exercise-QTc is associated with diffuse interstitial fibrosis reflected by lower approximated T1 relaxation time in hypertrophic cardiomyopathy patients

Hypertrophic cardiomyopathy (HCM) is frequently associated with exercise-related sudden death. One possible contributor to arrhythmias is pathologic hypertrophy, which can lead to QTc prolongation. Since beta-adrenergic stimulation increases inward ionic currents and can increase spatial repolarization heterogeneity, we hypothesized that exercise would prolong QTc and predispose to arrhythmias in HCM patients. We tested this hypothesis by measuring QTc at rest and peak exercise, and examining ECGs for arrhythmias during exercise/recovery in 163 patients with a clinical diagnosis of HCM. Since hypertrophy and fibrosis are risk factors for arrhythmias in HCM, left ventricular (LV) mass and cardiac fibrosis were quantified using cardiac magnetic resonance imaging. Exercise led to an increase in QTc interval (436 +/- 37 to 482 +/- 45, p < 0.001), QRS duration (100 +/- 9 to 109 +/- 12, p < 0.001) and ST-T abnormalities. The proportion of patients with QTc prolongation (>470 ms) increased from 28% at rest, to 58% at peak exercise. An inverse correlation was detected between the approximated T1 relaxation time (using the Look Locker sequence) and rest-QTc (r = -0.68, p < 0.001); this association was increased during exercise (r = -0.81, p < 0.001). Late gadolinium enhancement (LGE) and LV mass were weakly associated with exercise-QTc. A weak inverse correlation was also observed between approximated T1 relaxation time and rest/exercise-QRS duration. A trend for association with arrhythmia (non-sustained ventricular tachycardia on Holler) was observed for rest-QTc >470 ms (OR = 3.0;p = 0.06). We conclude that exercise leads to QTc prolongation in a subset of HCM patients. The association between the approximated T1 relaxation time and QTc interval may reflect concomitant electrical and structural remodeling in HCM.