Arrhythmia/Electrophysiology Transmural Differences in Myocardial Contraction in Long-QT Syndrome Mechanical Consequences of Ion Channel Dysfunction
نویسندگان
چکیده
Background—Long-QT syndrome (LQTS) is characterized by prolonged myocardial action potential duration. The longest action potential duration is reported in the endomyocardium and midmyocardium. Prolonged action potential duration in LQTS may cause prolonged cardiac contraction, which can be assessed by strain echocardiography. We hypothesized that myocardial contraction is most prolonged in subendocardial myofibers in LQTS patients and that inhomogeneous transmural contraction is related to the risk of spontaneous arrhythmia. Methods and Results—We included 101 genotyped LQTS mutation carriers and 35 healthy individuals. A history of cardiac arrhythmias was present in 48 mutations carriers, and 53 were asymptomatic. Myocardial contraction duration was assessed by strain echocardiography as time from the ECG Q wave to peak strain in 16 LV segments. Strain was assessed along the longitudinal axis, predominantly representing subendocardial fibers, and along the circumferential axis, representing midmyocardial fibers. Mean contraction duration was longer in LQTS mutation carriers compared with healthy individuals (445 45 versus 390 40 milliseconds; P 0.001) and longer in symptomatic compared with asymptomatic LQTS mutation carriers (460 40 versus 425 45 milliseconds; P 0.001). Contraction duration by longitudinal strain was longer than by circumferential strain in symptomatic LQTS patients (460 45 versus 445 45 milliseconds; P 0.008) but not in asymptomatic patients and healthy individuals, indicating transmural mechanical dispersion. This time difference was present in a majority of LV segments and was most evident in patients with LQT2 and the Jervell and Lange-Nielsen syndrome. Conclusion—Contraction duration in symptomatic LQTS mutation carriers was longer in the subendocardium than in the midmyocardium, indicating transmural mechanical dispersion, which was not present in asymptomatic and healthy individuals. (Circulation. 2010;122:1355-1363.)
منابع مشابه
Transmural differences in myocardial contraction in long-QT syndrome: mechanical consequences of ion channel dysfunction.
BACKGROUND Long-QT syndrome (LQTS) is characterized by prolonged myocardial action potential duration. The longest action potential duration is reported in the endomyocardium and midmyocardium. Prolonged action potential duration in LQTS may cause prolonged cardiac contraction, which can be assessed by strain echocardiography. We hypothesized that myocardial contraction is most prolonged in sub...
متن کاملProarrhythmic consequences of a KCNQ1 AKAP-binding domain mutation: computational models of whole cells and heterogeneous tissue.
The KCNQ1-G589D gene mutation, associated with a long-QT syndrome, has been shown to disrupt yotiao-mediated targeting of protein kinase A and protein phosphatase-1 to the I(Ks) channel. To investigate how this defect may lead to ventricular arrhythmia during sympathetic stimulation, we use integrative computational models of beta-adrenergic signaling, myocyte excitation-contraction coupling, a...
متن کاملDilated cardiomyopathy due to sodium channel dysfunction: what is the connection?
The cardiac sodium channel mediates the rapid upstroke of the cardiac action potential and thereby constitutes a critical determinant of cardiac excitability and conduction. Mutations in the SCN5A gene encoding the -subunit of this channel have been linked to a broad clinical spectrum of arrhythmia disorders, including long QT syndrome, Brugada syndrome, sick sinus syndrome, conduction disease,...
متن کاملSearching for mechanical abnormalities in subjects with early repolarization pattern: another Holy Grail of cardiac imaging?
Early repolarization pattern (ERP) may not be the entirely benign condition it was initially thought to be. In a recent metaanalysis, it was associated with increased risk and low to intermediate absolute incidence rate of arrhythmia death (1). However, the vast majority of subjects with ERP will never experience any malignant arrhythmia during their lifetime, and therefore, ability to identify...
متن کاملIntracellular calcium attenuates late current conducted by mutant human cardiac sodium channels.
BACKGROUND Mutations of the cardiac voltage-gated sodium channel (SCN5A gene encoding voltage-gated sodium channel [NaV1.5]) cause congenital long-QT syndrome type 3 (LQT3). Most NaV1.5 mutations associated with LQT3 promote a mode of sodium channel gating in which some channels fail to inactivate, contributing to increased late sodium current (INaL), which is directly responsible for delayed r...
متن کامل