Her ECG revealed QT-prolongation associated with LQT2-specific T-U wave patterns, T wave alternans, long QT-dependent torsade de pointes (TdP) and ventricular fibrillation (VF).
In long QT syndrome type 2 (I<sub>Kr</sub> blockade or bradycardia), the higher Ca<sup>2+</sup> influx via I<sub>Ca,L</sub> causes Ca<sup>2+</sup> overload, spontaneous sarcoplasmic reticulum Ca<sup>2+</sup> release, and reactivation of I<sub>Ca,L</sub> that triggers early afterdepolarizations and torsades de pointes.
A systematic review was performed to categorize the hERG (human ether-a-go-go-related gene) liability of antihistamines, antipsychotics, and anti-infectives and to compare it with current clinical risk of torsade de pointes (TdP).
A greater instability of most aspects of VR already at rest seems to be a salient feature in both LQT1 and LQT2, which might pave the way for early afterdepolarizations and torsades de pointes ventricular tachycardia.
Four fetuses (2 KCNH2 and 2 SCN5A), all with corrected QT ≥ 620 ms, had frequent episodes of Torsade de Pointes, which were present 22-79% of the time.
Thus, patients with an acute MI carrying the KCNH2-K897T polymorphism had an 8-fold greater risk of experiencing TdP compared with controls (95% confidence interval = 2-40).
The level of inhibition of the human Ether-à-go-go-related gene (hERG) channel is one of the earliest preclinical markers used to predict the risk of a compound causing Torsade-de-Pointes (TdP) arrhythmias.
Block of the human Ether-a-go go Related Gene (hERG) ion channel in particular is associated with life-threatening arrhythmias, such as Torsade de Pointes (TdP).
The main mechanism of QT prolongation and TdP is block of the rapid component of the cardiac delayed rectifier K(+) current (I(Kr)), which is encoded by hERG (human ether-à-go-go-related gene).
The main mechanism underlying an acquired QT syndrome and a potentially fatal arrhythmia called torsades de pointes is the inhibition of potassium channel encoded by hERG (the human ether-a-go-go-related gene).
KCNQ1 and KCNH2 are the two most common potassium channel genes causing long QT syndrome (LQTS), an inherited cardiac arrhythmia featured by QT prolongation and increased risks of developing torsade de pointes and sudden death.
A likely mechanism for QT interval prolongation and TdP arrhythmias is blockade of the rapid component of the cardiac delayed rectifier K+ current (IKr), which is encoded by human ether-a-go-go-related gene (HERG).
The most common problem is acquired long QT syndrome caused by drugs that block human ether-a-go-go-related-gene (hERG) K(+) channels, delay cardiac repolarization and increase the risk of torsades de pointes arrhythmia (TdP).
High concentrations of intravenous nicorandil, a potassium channel opener, have been shown to be capable of decreasing QT and TDR, and preventing TdP in LQT1 and LQT2 but not in LQT3.
KCNH2 codes for the HERG ion channel and mutations in the gene are associated with congenital long-QT syndrome (LQTS), and in the family of this case of SIDS, the mutation was associated with Torsades de pointes tachycardia, making SIDS the most likely outcome of congenital LQTS.
Rare mutations in KCNH2 provide the pathogenic substrate for type 2 congenital long QT syndrome (LQTS), thus placing this cardiac potassium channel squarely in the intersection between congenital LQTS (the "Rosetta stone" of the heritable channelopathies) and acquired LQTS (drug-induced TdP).
Putative interactions between the Human Ether-a-go-go Related Gene (HERG), QT interval prolongation and Torsades de Pointes (TdP) are now integral components of any discussion on drug safety.
To determine what role genetic variation in the hERG gene plays in drug-induced arrhythmias, we screened DNA samples collected from 105 atrial-fibrillation patients treated with dofetilide for polymorphisms, seven of whom developed TdP.
A decrease of IKr or IKs by mutations in either HERG, KvLQT1, or KCNE family results in inherited long QT syndrome (LQTS) with high risk for Torsades de pointes (TdP)-type polymorphic ventricular tachycardia and ventricular fibrillation.