Bifid T waves on the ECG and genetic variation in calcium channel voltage‐dependent beta 2 subunit gene ( CACNB2 ) in acute Kawasaki disease

Abstract

Background:We previously described the association of genetic variants in calcium channel genes and susceptibility to Kawasaki disease (KD), an acute, self-limited vasculitis, and the most common cause of acquired cardiac disease in children. Abnormal repolarization of cardiomyocytes and changes in T wave morphology have been reported in KD but have not been studied systematically. Methods:We analyzed acute and convalescent ECG T wave morphology in two independent cohorts of KD subjects and studied the association between bifid T waves and genetic variants in previously reported genes with SNVs associated with cardiac repolarization.Results: Bifid T waves in limb leads were identified in 24% and 27% of two independent cohorts of acute KD subjects. Calcium channel voltage-dependent beta 2 subunit gene (CACNB2) (rs1409207) showed association with bifid T waves in both cohorts (nominal P = .04 and P = .0003, respectively). This CACNB2 polymorphism also showed association with KD susceptibility in a previously published KD genome wide association study data (nominal P = .009). Conclusion: This genotype/phenotype association study uncovered a variant inCACNB2 that may be associated with both KD susceptibility and bifid T waves, a novel signature of altered myocardial repolarization. The present study combined with published reports suggests that genetic variants in calcium channels and intracellular calcium signaling play a prominent role in shaping susceptibility to KD.

Dome-and-dart T Waves and Hyperthyroidism – A Case Report

“…3,5,13 Bifid (or dome-and-dart or notched) T waves are defined as an indented T wave with two distinguished peaks. 14 The pathophysiological mechanism of bifid T wave is still controversial. These alterations have been related to various conditions, either electrophysiological or anatomical, and could lead to inhomogeneous and local delayed ventricular repolarisation, generating a second component of T wave on the surface ECG.…”

Cardiovascular Involvement in Kawasaki Disease Is Much More Than Mere Coronary Arteritis

“…In presence of severe myocarditis/pericarditis, low voltage complexes, and symptomatic arrhythmias may be seen (56)(57)(58). Bifid T-wave in limb leads have also been noted during the acute phase of KD (59). QT dispersion abnormalities may persist for several months (56,57).…”

Current State of Precision Medicine in Primary Systemic Vasculitides

“…Susceptibility genes for KD (5-16) HLA, HCP5, FCGR2A, BLK, SLC8A1, CD40, NMNAT2, DAB1, COPB2, NAALADL2, IGHV, ZFHX3, NFKBIL1, ERAP1, EBF2, CACNB2, LTA, and LEF1 SNP in SLC8A1 (calcium signaling pathway) can be proof for using calcineurin inhibitors in KD and LEF1) (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) to the risk of cardiovascular disease in KD (TIAM1, NEBL, PLCB4/PLCB1, TUBA3C, SLC8A1, PELI1, KCNN2, TIFAB, and AGT) (8,12,(17)(18)(19)(20)(21)(22) and to the risk of intravenous immunoglobulin (IVIG) resistance (BCL2L11 and SAMD9L) (23,24). Involvement of the HLA region in susceptibility to KD has been controversial and has not been replicated across different ancestral groups.…”