Response to cardiac resynchronisation therapy in men and women: a secondary analysis of the SMART-AV randomised controlled trial.

There is a controversy about whether both sexes' response to cardiac resynchronisation therapy (CRT) is similar. We aimed to assess a causal effect of sex on CRT response. Secondary analysis of a randomised controlled trial (RCT) data. Doubly robust augmented-inverse-probability-weighted (AIPW) estimation of sex effect on CRT response. The SmartDelay Determined Atrioventricular (AV) Optimisation (SMART-AV) RCT. The SMART-AV RCT enrolled New York Heart Association class III-IV patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≤35% despite optimal medical therapy and QRS duration ≥120 ms, in sinus rhythm. After exclusion of those with missing outcome or covariates, 741 participants (age 66±11 years; 33% female; 78% white; LVEF 28%±9%; 58% ischaemic cardiomyopathy; 75% left bundle branch block; left ventricular end-systolic volume index (LVESVI) 65±30 mL/m Implanted CRT defibrillator with randomly assigned AV delay as either (1) fixed at 120 ms, or (2) echocardiography-determined, or (3) SmartDelay algorithm-programmed. A composite of freedom from death and HF hospitalisation and a >15% reduction in LVESVI at 6 month post-CRT was the endpoint. The primary endpoint was met by 337 patients (45.5%); 134 were women (55.6% response) and 203 were men (40.6% response); p<0.0001. After conditioning for 33 covariates that included baseline demographic, clinical, ECG, echocardiographic and biomarker characteristics, known predictors of CRT response, logistic regression showed a higher probability for composite CRT response for women versus men (OR 1.79; 95% CI 1.08 to 2.98; p<0.0001), whereas AIPW estimation showed no difference in CRT response (average treatment effect 0.88; 95% CI 0.41 to 1.89; p=0.739). After removing colliders from the model, both logistic regression (OR 1.00; 95% CI 0.69 to 1.44) and AIPW (ATE 1.06; 95% CI 0.96 to 1.16) reported similar results. Both sexes' response to CRT is similar. Sex differences in HF substrate, treatment and comorbidities explain sex disparities in CRT outcomes. ClinicalTrials.gov Identifier; NCT00677014.

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Déclaration de conflit d'intérêts

Competing interests: The SMART-AV trial was sponsored by Boston Scientific Corporation. Two co-authors are the Boston Scientific Corporation employees. Boston Scientific had role in the design of this study and had no any role during its execution, analyses, interpretation of the data, or decision to submit results.