TY - JOUR
T1 - Response to cardiac resynchronisation therapy in men and women
T2 - a secondary analysis of the SMART-AV randomised controlled trial
AU - Howell, Stacey
AU - Stivland, Timothy M.
AU - Stein, Kenneth
AU - Ellenbogen, Kenneth
AU - Tereshchenko, Larisa G.
N1 - Funding Information:
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.
Funding Information:
Funding This work was supported in part by the National Heart, Lung, and Blood Institute (HL118277 to Tereshchenko). Boston Scientific Corporation funded the SMART-AV trial.
Publisher Copyright:
© Author(s) (or their employer(s)) 2021.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Objectives 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. Design Secondary analysis of a randomised controlled trial (RCT) data. Doubly robust augmented-inverse-probability-weighted (AIPW) estimation of sex effect on CRT response. Setting The SmartDelay Determined Atrioventricular (AV) Optimisation (SMART-AV) RCT. Participants 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 2) were included. Interventions Implanted CRT defibrillator with randomly assigned AV delay as either (1) fixed at 120 ms, or (2) echocardiography-determined, or (3) SmartDelay algorithm-programmed. Outcome A composite of freedom from death and HF hospitalisation and a >15% reduction in LVESVI at 6 month post-CRT was the endpoint. Results 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. Conclusions Both sexes' response to CRT is similar. Sex differences in HF substrate, treatment and comorbidities explain sex disparities in CRT outcomes. Trial registration number ClinicalTrials.gov Identifier; NCT00677014.
AB - Objectives 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. Design Secondary analysis of a randomised controlled trial (RCT) data. Doubly robust augmented-inverse-probability-weighted (AIPW) estimation of sex effect on CRT response. Setting The SmartDelay Determined Atrioventricular (AV) Optimisation (SMART-AV) RCT. Participants 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 2) were included. Interventions Implanted CRT defibrillator with randomly assigned AV delay as either (1) fixed at 120 ms, or (2) echocardiography-determined, or (3) SmartDelay algorithm-programmed. Outcome A composite of freedom from death and HF hospitalisation and a >15% reduction in LVESVI at 6 month post-CRT was the endpoint. Results 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. Conclusions Both sexes' response to CRT is similar. Sex differences in HF substrate, treatment and comorbidities explain sex disparities in CRT outcomes. Trial registration number ClinicalTrials.gov Identifier; NCT00677014.
KW - adult cardiology
KW - cardiomyopathy
KW - heart failure
KW - pacing & electrophysiology
KW - statistics & research methods
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U2 - 10.1136/bmjopen-2021-049017
DO - 10.1136/bmjopen-2021-049017
M3 - Article
C2 - 34706949
AN - SCOPUS:85118800614
VL - 55
SP - 3245
EP - 3279
JO - RAIRO - Operations Research
JF - RAIRO - Operations Research
SN - 0399-0559
IS - 5
ER -