Abstract 13995: Proarrhythmic Electromechanical Heterogeneities in Patients With KCNJ2 Mutations

Introduction: Loss-of-function mutations of the KCNJ2 gene encoding the inward-rectifier potassium channel, I K1 , are associated with QT prolongation, prominent U waves, abnormal impulse formation and ventricular tachycardia (VT), besides non-cardiac manifestations. The electromechanical consequences of genetic I K1 dysfunction are unknown. Hypothesis: We hypothesize that I K1 dysfunction leads to increased electrical and mechanical dispersion and electromechanical (EMW) negativity. Dynamic heterogeneity of these functional parameters may conspire to arrhythmia. Methods: High-resolution mapping using ECG imaging, speckle-tracking echocardiography and/or tissue-phase mapping CMR were performed in genotyped KCNJ2 -mutation carriers, besides standard 12-lead and ambulatory recording. Results: Five patients (44±13 years; 2 females) were included; KCNJ2 p.(Val93Ile), p.(Arg218Gln), p.(Thr75Arg), p.(Lys49Arg), p.(Gly144Ala). Three had experienced polymorphic VT/VF. Multifocal ventricular ectopic burden averaged 13%. Mean QTc/QTUc were 446±42/610±78 ms, with U-waves of 149±18 ms and 0.087±0.045 mV. ECG-imaging revealed increased epicardial recovery time gradients (168±58 ms/cm), with LV- and RV-contractile heterogeneities by strain: Delta contraction duration (CD) LV 213±77 ms, standard deviation (SD) 58±14 ms; RV Delta CD 30±22 ms, SD 13±9 ms. Abnormal postsystolic shortenings (Fig.), prolonged isovolumic relaxation times (103±25 ms) and reduced diastolic peak velocities (-7.2±1.7 cm/s) indicated impaired early relaxation. The EMW was -51±35 ms with more pronounced negativity in symptomatic patients (-74 vs. -17 ms). Conclusions: Genetic I K1 dysfunction underlies nonuniform mechanical heterogeneities in contraction and relaxation, besides repolarization and resting membrane-potential instability. Significant EMW negativity further promotes ventricular ectopy, potentially precipitating VT.