Exercise-induced regional heterogeneity of myocardial left ventricular contraction in hereditary long QT syndrome

Abstract

Abstract Background Hereditary long QT syndrome (LQTS) is characterized by prolonged ventricular repolarization and an increased risk for ventricular arrhythmias (VA) and sudden cardiac death. Dispersion of ventricular repolarization in LQTS may be more pronounced during exercise and not only impacts the heart’s electrical functions but also the pattern of mechanical contraction. Little is known about the intraventricular heterogeneity of wall motion abnormalities in LQTS patients. Methods In this cross-sectional study we quantify regional, transmural, and longitudinal alterations in left ventricular (LV) contraction at rest, during exercise, and recovery in genetically confirmed LQTS patients and healthy controls to evaluate their value in differentiating high risk patients as defined by a history of VA. ECG and echocardiographic assessments were conducted during rest, peak ergometer activity (105 to 125 bpm), and four minutes into recovery phases. Longitudinal strain (LStr) parameters were measured for each LV segment separately. We differentiated LStr variations as heterogeneity of LStr amplitude (hetLStr; standard deviation [SD] or mean range) and dispersion of time-to-peak LStr (disLStr; SD or mean range). Here, we present the analyses of disLStr. Results At present, 15 patients with genetically confirmed LQTS (LQT1: 8, LQTS 2: 7; mean QTc 475 ± 46 ms) have been included of which 9 had a history of VA. In addition, we collected data from 8 age- and gender-matched control patients (mean QTc 401 ± 18 ms). LV ejection fraction and LStr were not significantly different between the LQTS and control groups. However, LQTS patients exhibited a significantly lower mean LStr in both the endocardial and epicardial layers across all phases compared to control. We observed a significantly more pronounced disLStr across all segments in the LQTS group during the rest and recovery phases in the endocardial layer and during all phases in the epicardial layer. Regional differences (apical vs. basal) were found in all LQTS patients only endocardially at rest. Globally, disLStr showed transmural differences (epicardial vs. endocardial) in both asymptomatic and symptomatic LQTS patients during peak exercise and recovery. Upon segmental analysis, it was observed that symptomatic patients exhibited these transmural differences apically already at rest (p=.004), as well as in the basal region during peak exercise (p=.01), and in the apical region during recovery (p=.02). Conclusion LQTS patients show regional (base to apex) and transmural (endocardial to epicardial) heterogeneities in myocardial contraction at rest, during exercise, and recovery as compared to healthy patients. These regional variations in myocardial contraction patterns may be more pronounced in high risk LQTS patients. Ongoing analyses of hetLStr are in progress to corroborate our findings.