Paradoxical Prolongation of QT Interval During Exercise in Patients with Hypertrophic Cardiomyopathy

Abstract

Background In patients with long QT 1 syndrome, prolongation of action potential duration (APD) due to reduced I Ks is associated with QTc prolongation in response to both epinephrine and exercise. We recently showed that ventricular myocytes from patients with hypertrophic cardiomyopathy (HCM) have markedly prolonged APD associated with downregulation of I Ks . Thus, we determined the effects of isoproterenol (ISO) on APD in ventricular myocytes of patients with HCM and the changes in QTc and TQ interval during exercise. Methods Ventricular myocytes were isolated from myocardial samples of 8 HCM patients who underwent septal myectomy and 4 nonhypertrophic surgical patients (controls). Fifty HCM patients underwent standard exercise ECG test (Bruce treadmill protocol). All clinical procedures were performed at the Referral Center for Cardiomyopathies of Careggi University Hospital in Florence, Italy. Results In myocytes (paced at 0.2 Hz) from HCM patients, ISO (10 7– mol/L) prolonged APD at 90% repolarization (APD 90 ) by +26% ± 8%, whereas ISO shortened APD 90 in control myocytes (–20% ± 4%, P Conclusions In HCM patients, exercise led to QTc prolongation accompanied by shortening in TQ interval, which may reduce diastolic filling time, impair ventricular relaxation, and reduce myocardial perfusion. This abnormal response is likely to contribute to the reduced exercise tolerance and stress-induced angina in patients with HCM.