The congenital long QT syndrome Type 3: An update

Abstract

Congenital long QT syndrome type 3 (LQT3) is the third in frequency compared to the 15 forms known currently of congenital long QT syndrome (LQTS). Cardiac events are less frequent in LQT3 when compared with LQT1 and LQT2, but more likely to be lethal; the likelihood of dying during a cardiac event is 20% in families with an LQT3 mutation and 4% with either an LQT1 or an LQT2 mutation. LQT3 is consequence of mutation of gene SCN5A which codes for the Nav1.5 Na+ channel α-subunit and electrocardiographically characterized by a tendency to bradycardia related to age, prolonged QT/QTc interval (mean QTc value 478 ± 52 ms), accentuated QT dispersion consequence of prolonged ST segment, late onset of T wave and frequent prominent U wave because of longer repolarization of the M cell across left ventricular wall.

Update on long QT syndrome

“…A, T‐Wave alternans in a 6‐year‐old caucasian female diagnosed with congenital LQT3, QTc interval of 670 milliseconds. Reproduced with permission from Pérez‐Riera et al B, Torsades de Pointes due to prolonged QT interval in the context of acquired third‐degree AV block. LQTS, long QT syndrome…”

The Multifaced Perspectives of Genetic Testing in Pediatric Cardiomyopathies and Channelopathies

“…Arrhythmic episodes (which are bradycardia-dependent and appear at rest) in LQTS-3 have higher lethality than in LQTS-1/2 (roughly 20%), even if events are rarer and happen most frequently before 40 years old [ 82 ]. However, in genetically tested individuals, the LQTS-3 genotype is the most powerful predictor of fatal or near-fatal cardiac events after 40 years, warranting the importance of long-term follow-up [ 84 ].…”

The Citrus Flavonoid Hesperetin Has an Inadequate Anti-Arrhythmic Profile in the ΔKPQ NaV1.5 Mutant of the Long QT Type 3 Syndrome

“…The fatal arrhythmic events in LQT3 occur at a much higher percentage at low heart rates (during sleep or rest) and antiarrhythmic drugs are currently prescribed together with β-blockers [ 8 , 14 , 17 ]. However, the use of antiarrhythmic drugs might increase the risk of SCD [ 18 , 19 ], particularly in certain patients (e.g., with a particular LQT3 genotype) [ 20 , 21 , 22 ].…”

“…Channel mutants, such as the R1623Q, show a reduced rate of Na + current inactivation and a small late Na + current (I Na-Late ) [ 28 , 29 ], while mutants such as the ΔKPQ are characterized by a marked I Na-Late [ 30 ]. This raises the possibility that LQT3 patients with different genetic backgrounds (i.e., different mutations) might react differently to the same drug [ 20 , 21 , 22 ].…”