Sex Differences in Device Therapies in MADIT-CRT
Sex Differences in Device Therapies in MADIT-CRT
The design and primary results of MADIT-CRT were previously published. Briefly, the MADIT-CRT trial was a multicenter, prospective randomized trial designed to assess whether cardiac resynchronization therapy with defibrillator (CRT-D) would reduce the risk of death or heart failure admissions in patients with mild heart failure symptoms (NYHA class I–II heart failure) due to either ischemic or nonischemic cardiomyopathy (EF ≤ 30%), and a QRS duration ≥130 milliseconds. Subjects were randomized in a 3:2 ratio to receive either cardiac resynchronization therapy with an implantable cardioverter defibrillator (CRT-D) or an implantable cardioverter defibrillator (ICD) alone. Subjects enrolled in MADIT-CRT underwent detailed clinical and echocardiographic evaluation just prior to recruitment and were seen in follow-up 1 month after cardiac device implantation, then every 3 months until termination of the trial.
The primary endpoint for this post hoc analysis was appropriate device (ICD or CRT-D) therapies for VT/VF or death from any cause, whichever occurred first. Secondary endpoints included subsequent heart failure events and death as separate endpoints following the first appropriate therapy or shock.
Device programming was left to the discretion of the implanting physician. However, initial programming consisting of a VT zone at 180 bpm and VF zone of 210 bpm was recommended. The electrograms for each ICD or CRT-D therapy (i.e., antitachycardia pacing or shock) were reviewed by an adjudication committee. ICD therapy was considered appropriate if it was delivered for VT/VF.
Continuous variables are expressed as mean ± standard deviation and compared using Wilcoxon's rank sum test. Proportional variables are expressed as frequency counts or percentages, and differences were determined using Chi-square or Fisher's exact test as appropriate. Kaplan–Meier life-table method was used to calculate the probability of appropriate ICD therapies based on sex and type of device implanted. Cox proportional regression models were used to evaluate the risk (hazard ratio) of developing death or heart failure following the first appropriate device therapy in men versus women. The covariates adjusted for included age ≥65, EF ≤25%, ischemic cardiomyopathy, QRS ≥150 milliseconds and BUN >25. A P value <0.05 was considered statistically significant. All statistical tests were 2-sided. Statistical analyses were performed using the SAS software (SAS version 9.3, Cary, NC, USA).
Methods
Study Population
The design and primary results of MADIT-CRT were previously published. Briefly, the MADIT-CRT trial was a multicenter, prospective randomized trial designed to assess whether cardiac resynchronization therapy with defibrillator (CRT-D) would reduce the risk of death or heart failure admissions in patients with mild heart failure symptoms (NYHA class I–II heart failure) due to either ischemic or nonischemic cardiomyopathy (EF ≤ 30%), and a QRS duration ≥130 milliseconds. Subjects were randomized in a 3:2 ratio to receive either cardiac resynchronization therapy with an implantable cardioverter defibrillator (CRT-D) or an implantable cardioverter defibrillator (ICD) alone. Subjects enrolled in MADIT-CRT underwent detailed clinical and echocardiographic evaluation just prior to recruitment and were seen in follow-up 1 month after cardiac device implantation, then every 3 months until termination of the trial.
Cardiac Events
The primary endpoint for this post hoc analysis was appropriate device (ICD or CRT-D) therapies for VT/VF or death from any cause, whichever occurred first. Secondary endpoints included subsequent heart failure events and death as separate endpoints following the first appropriate therapy or shock.
Device Programming
Device programming was left to the discretion of the implanting physician. However, initial programming consisting of a VT zone at 180 bpm and VF zone of 210 bpm was recommended. The electrograms for each ICD or CRT-D therapy (i.e., antitachycardia pacing or shock) were reviewed by an adjudication committee. ICD therapy was considered appropriate if it was delivered for VT/VF.
Statistical Analysis
Continuous variables are expressed as mean ± standard deviation and compared using Wilcoxon's rank sum test. Proportional variables are expressed as frequency counts or percentages, and differences were determined using Chi-square or Fisher's exact test as appropriate. Kaplan–Meier life-table method was used to calculate the probability of appropriate ICD therapies based on sex and type of device implanted. Cox proportional regression models were used to evaluate the risk (hazard ratio) of developing death or heart failure following the first appropriate device therapy in men versus women. The covariates adjusted for included age ≥65, EF ≤25%, ischemic cardiomyopathy, QRS ≥150 milliseconds and BUN >25. A P value <0.05 was considered statistically significant. All statistical tests were 2-sided. Statistical analyses were performed using the SAS software (SAS version 9.3, Cary, NC, USA).