Women with mild heart failure and left bundle branch block benefit from cardiac resynchronization therapy at a shorter QRS duration – less than 150 milliseconds – than do men, according to a report published online June 23 in JAMA Internal Medicine.
Current guidelines limit the class I indication for CRT to patients with mild heart failure, LBBB, and a QRS interval of 150 msec or longer. They are based on clinical trials in which women were underrepresented, comprising only about 20% of participants. Noting that QRS duration is generally shorter in women than in men, Food and Drug Administration researchers examined whether women might benefit from CRT at a shorter QRS duration than men do, said Dr. Robbert Zusterzeel and his associates at the FDA’s Center for Devices and Radiological Health.
They performed a pooled analysis of patient-level data from three large, randomized clinical trials submitted to the FDA as part of an application for premarketing approval of the CRT devices: 1,820 participants in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy), 1,663 from the RAFT (Resynchronization-Defibrillation for Ambulatory Heart Failure Trial) study, and 593 from the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial.
In women overall, CRT produced a 60% relative reduction in the combined end point of heart failure event or death and a 55% relative reduction in death alone, compared with relative reductions of only 26% and 15% in men. In the subgroup of women who had QRS durations of 130-139 msec, CRT resulted in an 85% relative reduction in heart failure event or death; and in women with QRS durations of 140-149 msec, CRT resulted in a 69% relative reduction. In contrast, men with QRS durations in this low range did not benefit from CRT, Dr. Zusterzeel and his associates said (JAMA Intern. Med. 2014 June 23 [doi:10.1001/jamainternmed.2014.2717]).
"Considering that women receive CRT less often than men, we believe that the current findings are important to communicate" to clinicians and patients, they said.
Their study also "highlights the importance of sex-specific analysis in medical device clinical studies and the public health value of combining individual-patient data from clinical trials submitted to the FDA," the investigators added.
This study was supported in part by the FDA Office of Women’s Health, the Oak Ridge Institute for Science and Education, and the U.S. Department of Energy. No financial conflicts of interest were reported.