Congenital Long QT syndrome and torsade de pointes

Abstract

Since its initial description by Jervell and Lange-Nielsen in 1957, the congenital long QT syndrome (LQTS) has been the most investigated cardiac ion channelopathy. A prolonged QT interval in the surface electrocardiogram is the sine qua non of the LQTS and is a surrogate measure of the ventricular action potential duration (APD). Congenital as well as acquired alterations in certain cardiac ion channels can affect their currents in such a way as to increase the APD and hence the QT interval. The inhomogeneous lengthening of the APD across the ventricular wall results in dispersion of APD. This together with the tendency of prolonged APD to be associated with oscillations at the plateau level, termed early afterdepolarizations (EADs), provides the substrate of ventricular tachyarrhythmia associated with LQTS, usually referred to as torsade de pointes (TdP) VT. This review will discuss the genetic, molecular, and phenotype characteristics of congenital LQTS as well as current management strategies and future directions in the field.

Drug‐induced Proarrhythmia and Torsade de Pointes: A Primer for Students and Practitioners of Medicine and Pharmacy

“…In clinical medicine, QT interval prolongation is of concern because it is the defining phenotypic characteristic of a group of inherited long QT syndromes that have been associated with TdP and sudden death . One long QT syndrome, LQT2, is seen when an individual's genetic inheritance includes an abnormal variant of the human ether‐a‐go‐go–related gene ( hERG , or KCNH2 ) that encodes the α‐helix subunit of the cardiac potassium ion channel through which I Kr flows .…”

Sudden Unexplained Nocturnal Death Syndrome: The Hundred Years' Enigma

“…Mutations in 2 different potassium channels, namely, Kv7.1 encoded by KCNQ1 and Kv11.1 encoded by KCNH2 , caused >60% Long QT Syndrome (LQTS). To form functional Kv11.1 and Kv7.1 channels, 1 accessory subunit called MinK encoded by KCNE1 and another called MiRP1 encoded by KCNE2 are necessary . Since LQTS can cause SCD, mutations in KCNQ1 , KCNH2 , and their accessory KCNE1 , KCNE2 may explain some SUNDS.…”

Quantitative T‐wave morphology assessment from surface ECG is linked with cardiac events risk in genotype‐positive KCNH2 mutation carriers with normal QTc values

“…LQTS affects 1 in 2000 people . There are three main subtypes of LQTS defined by mutations in KCNQ1, KCNH2, and SCN5A with different T‐wave patterns and arrhythmogenic triggers as well as specific treatment based strategies . For instance, patients with LQT1 typically have broad‐based T‐waves, while LQT2 patients typically have biphasic or flattened T‐waves .…”

“…Assessment of the shape of the T‐wave can be a way to identify patients with LQT2 without QTc prolongation at risk for cardiac events; however, qualitative methods may be operator‐dependent and subject to interindividual variability. The T‐wave vector magnitude (TwVM) defined as the maximum distance from the origin of the 3‐dimensional T‐wave loop and calculated from the amplitudes of the T‐wave in the orthogonal leads offers and attractive quantitative measure of T‐wave polarity, amplitude and shape and has demonstrated diagnostic utility in other populations but not in LQTS patients …”

“…4 For instance, patients with LQT1 typically have broad-based T-waves, while LQT2 patients typically have biphasic or flattened T-waves. 4 Although in patients with LQT1, the arrhythmogenic risk is associated with prolongation of the heart rate corrected QT intervals, the second most common type of LQTS, LQT2, does not necessarily have arrhythmogenic risk associated with the degree of QTc prolongation. 5 About 20% to 50% of patients with LQTS do not have prolonged QTc.…”