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Background: Adaptive cardiac resynchronization therapy (aCRT) is known to have clinical benefits over conventional CRT, but the mechanisms are unclear., Objective: Compare effects of aCRT and conventional CRT on electrical dyssynchrony., Methods: A prospective, double-blind, 1:1 parallel-group assignment randomized controlled trial in patients receiving CRT for routine clinical indications. Participants underwent cardiac computed tomography and 128-electrode body surface mapping. The primary outcome was change in electrical dyssynchrony measured on the epicardial surface using noninvasive electrocardiographic imaging before and 6 months post-CRT. Ventricular electrical uncoupling (VEU) was calculated as the difference between the mean left ventricular (LV) and right ventricular (RV) activation times. An electrical dyssynchrony index (EDI) was computed as the standard deviation of local epicardial activation times., Results: We randomized 27 participants (aged 64 ± 12 years; 34% female; 53% ischemic cardiomyopathy; LV ejection fraction 28% ± 8%; QRS duration 155 ± 21 ms; typical left bundle branch block [LBBB] in 13%) to conventional CRT (n = 15) vs aCRT (n = 12). In atypical LBBB (n = 11; 41%) with S waves in V 5 -V 6 , conduction block occurred in the anterior RV, as opposed to the interventricular groove in strict LBBB. As compared to baseline, VEU reduced post-CRT in the aCRT (median reduction 18.9 [interquartile range 4.3-29.2 ms; P = .034]), but not in the conventional CRT (21.4 [-30.0 to 49.9 ms; P = .525]) group. There were no differences in the degree of change in VEU and EDI indices between treatment groups., Conclusion: The effect of aCRT and conventional CRT on electrical dyssynchrony is largely similar, but only aCRT harmoniously reduced interventricular dyssynchrony by reducing RV uncoupling., (© 2021 Heart Rhythm Society. Published by Elsevier Inc.)

Background—: Sex is a well-recognized risk factor for sudden cardiac death (SCD). We hypothesized that sex modifies the association of electrophysiological (EP) substrate with SCD., Methods—: Participants from the Atherosclerosis Risk in Communities study with analyzable ECGs (n=14,725; age, 54.2±5.8 yrs; 55% female, 74% white) were included. EP substrate was characterized by heart rate, QRS, QTc, Cornell voltage, spatial ventricular gradient (SVG), and sum absolute QRST integral (SAI QRST) ECG metrics. Two competing outcomes were adjudicated SCD and nonSCD. Interaction of ECG metrics with sex was studied in Cox proportional hazards and Fine-Gray competing risk models. Model 1 was adjusted for prevalent cardiovascular disease (CVD) and risk factors. Time-updated model 2 was additionally adjusted for incident non-fatal CVD. Relative hazard ratio (RHR) and relative sub-hazard ratio (RSHR) with a 95% confidence interval for SCD and nonSCD risk for women relative to men was calculated. Model 1 was adjusted for prevalent CVD and risk factors. Time-updated model 2 was additionally adjusted for incident non-fatal CVD., Results—: Over a median follow-up of 24.4 years, there were 530 SCDs (incidence 1.72 (1.58-1.88)/1000 person-years). Women as compared to men experienced a greater risk of SCD associated with Cornell voltage (RHR 1.18(1.06-1.32); P=0.003), SAI QRST (RHR 1.16(1.04-1.30); P=0.007), and SVG magnitude (RHR 1.24(1.05-1.45); P=0.009), independently from incident CVD., Conclusion—: In women, the global EP substrate is associated with up to 24% greater risk of SCD than in men, suggesting differences in underlying mechanisms and the need for sex-specific SCD risk stratification., Competing Interests: Conflict of interest: None.