Rethinking Resynchronization: Why Women Fare Better Than Men



MIAMI BEACH – When it comes to heart failure, women tend to respond better to cardiac resynchronization therapy than do men, but for a long time no one knew why.

Turns out women have some distinct physiologic advantages, specifically more left bundle branch block and more nonischemic cardiomyopathy. Each drives a better response to cardiac resynchronization therapy (CRT), said Dr. David G. Strauss, a medical officer at the Food and Drug Administration’s Center for Devices and Radiologic Health in Silver Spring, Md.

Dr. David G. Strauss

In addition, timing of a specific electrical component within the heart triggers a third important distinction. Women benefit significantly from CRT even when their QRS duration is shorter than 150 msec. This supports the need for new gender-specific criteria for left bundle branch block and, ultimately, better identification of patients most likely to benefit from CRT device placement, Dr. Strauss said at the annual meeting of the International Society on Hypertension in Blacks.

"This is important because different professional societies recently have recommended that CRT be given to patients with QRS duration of 150 msec or more, and primarily in class II heart failure," he said. However, this cutoff "would exclude women with left bundle branch block and QRS duration 130-149 msec that derived significant benefit in MADIT-CRT" (Circulation 2011;123:1061-72).

In MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy), 1,820 patients were randomly assigned to receive CRT with an implantable cardioverter-defibrillator (ICD) or an ICD alone. In men with QRS duration of 130-140 msec in the study, there was no benefit from CRT and a trend toward harm associated with the device (hazard ratio, 1.69), Dr. Strauss said.

In contrast, women with QRS durations of 130-140 msec "had very significant benefit from CRT with a hazard ratio of 0.20, indicating 80% decrease in heart failure hospitalization or death," Dr. Strauss said.

More nonischemic cardiomyopathy among women translates to less myocardial scar and, ultimately, to a better CRT response. Scar tissue, no matter how it is electrically activated, does not contract, Dr. Strauss said.

Presence of left bundle branch block conferred a significant benefit in terms of reduced heart failure hospitalizations and deaths with use of CRT in the MADIT-CRT research. Conversely, participants without left bundle branch block realized no clinical advantage with CRT.

Be careful, however, to correctly identify left bundle branch block, Dr. Strauss said. Research suggests that one third of patients diagnosed with left bundle branch block by conventional electrocardiographic criteria are misdiagnosed (Am. J. Cardiol. 2011;107:927-34). Patients with intraventricular conduction delays, such as those caused by left ventricular hypertrophy and left ventricular dilation who do not have a blocked left bundle branch, can still display a prolonged QRS duration. This duration can be in the range generally considered diagnostic of left bundle branch block.

New criteria could parlay into better patient selection in the future, Dr. Strauss said. "CRT has been shown to improve heart failure symptoms, reduce heart failure hospitalization, and reduce mortality. However, not all patients benefit and significant risks exist." For example, addition of a CRT device with a left ventricular lead is associated with more complications, compared with ICD alone. "Thus there is a need for better patient risk stratification and patient identification criteria."

Based on results of electrical activation mapping and simulation studies, "My colleagues and I proposed stricter left bundle branch block criteria," he said. For example, they propose QRS duration of 130 msec or greater in women and 140 msec greater in men to replace the conventional 120 msec definition of left bundle branch block in either gender.

Another proposed new requirement is mid-QRS notching in at least two of the electrocardiographic leads of I, aVL, V1, V2, V5, or V6. This is important for diagnosing left bundle branch block because it reflects two events, Dr. Strauss said. There is an initial notch when electrical activation reaches the endocardium of the left ventricle and a second notch when activation reaches the lateral wall opposite the septum.

Other researchers support changing the current criteria for left bundle branch block. In a study of 111 patients, researchers found meeting what they termed "false" criteria was associated with a fourfold higher rate of heart failure hospitalization or death, compared with those meeting strict criteria (Pacing Clin. Electrophysiol. 2012;35:927-34).

CRT is FDA approved for class 3 or 4 heart failure, both of ischemic and nonischemic etiology, with a left ventricular ejection fraction less than 35% and a QRS duration over 120 msec. The FDA also approved CRT for class I ischemic or class II (ischemic or nonischemic) heart failure with an ejection fraction less than 30%, a QRS duration over 130 msec, and left bundle branch block.


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