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Sex Differences in CRT-D for Class I-II Heart Failure
Abstract & Commentary
By John P. DiMarco, MD, PhD
Source: Arshad A, on behalf of the MADIT-CRT Executive Committee. The MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) trial. Cardiac resynchronization therapy is more effective in women than in men. J Am Coll Cardiol. 2011;57:813-820.
The madit-crt trial compared the effects of implanting defibrillators with and without resynchronization therapy in patients with New York Heart Association (NYHA) functional class I and II heart failure symptoms, indications for an ICD and a QRS duration > 130 m/sec. This report compares results in men versus women in MADIT-CRT.
MADIT-CRT enrolled a total of 1,820 patients randomly assigned in the 3:2 ratio to receive an ICD either with (CRT-D) or without resynchronization. Patients were followed longitudinally with death and heart failure hospitalization as the primary endpoints. Secondary endpoints included ventricular function, reverse cardiac remodeling, and adverse events.
There were 1,367 men and 453 women in MADIT-CRT. Female patients were more likely to have nonischemic cardiomyopathy and left bundle branch block conduction patterns than male patients. Men were more likely to have ischemic heart disease, prior coronary revascularization procedures, and renal dysfunction. The average follow-up duration was 2.4 years. The primary endpoint of heart failure or death occurred in 376 patients. Among women, 29 of 275 (11%) with CRT-D and 51 of 178 (29%) with an ICD reached a primary endpoint. In contrast, among men, the event rate was 159 of 814 (20%) with CRT-D compared to 137 of 553 (25%) with an ICD. The hazard ratios for death or heart failure, heart failure only, or death at any time in women were 0.31, 0.30, and 0.28. In contrast, the hazard ratios for the same endpoints in men were 0.72, 0.65, and 1.05. Other factors associated with increased likelihood of benefit were the diagnosis of nonischemic cardiomyopathy, QRS durations of greater than 150 msec in men but not women, and the presence of left bundle branch block conduction patterns. Echocardiographic findings confirm this pattern with women showing consistently greater improvements in cardiac reverse remodeling with CRT-D therapy than did men. Once again, the most significant differences were seen in patients with QRS durations greater than 150 m/sec or left bundle branch block. Device-related adverse events were seen in 10.5% of women vs 7.9% of men. Women were more likely to have pneumothorax (3% in women vs 0.7% in men), but men more commonly had lead dislodgments (1.7% in women vs 3.2% in men).
The authors conclude that women with class I or II heart failure are more likely to respond favorably than men if they receive CRT-D therapy as opposed to a standard ICD.
In MADIT-CRT, there was clearly an enhanced benefit of early CRT in women compared to men. Although benefit was seen in both genders, the hazard ratios are strikingly lower in women than in men. As discussed by the authors, the reasons for this are not clear and a similar increased benefit among women has not been seen in all studies on CRT. They propose that since women have a baseline QRS duration that is about 10 msec shorter than men, for any given QRS duration women are more likely to have dysynchrony. This hypothesis, in combination with the higher proportion of women with nonischemic cardiomyopathy and left bundle branch block, may well explain the observation. For clinicians the message is that they should not hesitate to recommend CRT therapy in women even though the complication rate may be slightly higher.