Examining electrical dyssynchrony in the left ventricle using GEH: the atherosclerosis risk in communities (ARIC) study

Introduction Cardiac resynchronization therapy (CRT) candidates are selected based on wide QRS and left bundle branch block (LBBB) morphology as proxies of electrical dyssynchrony. Yet, 30% of CRT patients show no clinical improvement, suggesting that conventional criteria inadequately capture electrical discoordination. We propose that global electrical heterogeneity (GEH) more accurately reflects electrical dyssynchrony in the left ventricle. Methods We analyzed data of 3330 participants of the ARIC cohort (33% male, 22% black, mean age 75+/-4.9, without coronary heart disease) who underwent 12-lead ECG and echocardiography on the same date. Mechanical dyssynchrony was measured by the standard deviation of time to peak longitudinal strain (Yu index) in 12 left ventricle segments in the apical 4- and 2-chamber views using speckle-tracking. ECGs were transformed to vectorcardiograms. GEH was measured by QRS-T angle, magnitude and direction (azimuth/elevation) of the spatial ventricular gradient (SVG) and sum absolute integral (SAI) QRST.1 Regression was adjusted for age, sex, race [model 1], BMI, hypertension, diabetes, smoking [model 2], and eGFRCKD-EPI and left ventricular mass by echocardiogram [model 3]. Analyses were stratified by ventricular conduction type: normal (NC), incomplete RBBB, LBBB, RBBB, LAFB, RBBB+LAFB, and nonspecific intraventricular conduction delay (IVCD). Results In the fully adjusted model of patients with NC, 1mVms increase in SAI QRST and 1ms increase in QTc were associated with Yu index (+0.031ms [CI: 0.57–5.52], +0.096ms [CI: 0.04–0.14]). In LAFB, 1 degree increase in SVG elevation was associated with Yu index (+0.50ms [CI: -0.02–1.03]). In patients with RBBB, 1mVms increase in SVG magnitude and 1mVms of increase in SAI QRST were associated with Yu index (+17.90ms [4.60–31.10], +0.16ms [CI: 0.03–0.29]). In patients with LBBB, an association of SVG azimuth and QRS duration with mechanical dyssynchrony was fully explained by LV mass measured by echocardiogram (Table). Conclusion After adjustment for LV mass and CV risk factors, GEH is associated with mechanical dyssynchrony in normal conduction, LAFB, and RBBB. In LBBB, left ventricular mass and cardiovascular-kidney-metabolic syndrome fully explain associations between mechanical and electrical dyssynchrony. Further research is needed to quantify electrical dyssynchrony and assess whether GEH can improve CRT candidate selection.