Is There a Benefit to Cardiac Resynchronization Therapy in Patients with a Narrow QRS and Echocardiographic Dyssychrony?
Abstract & Commentary
Edward P. Gerstenfeld, MD Professor of Medicine, Chief, Cardiac Electrophysiology, University of California, San Francisco
Dr. Gerstenfeld does research for Biosense Webster, Medtronic, and Rhythmia Medical.
Source: Ruschitzka F, et al and the EchoCRT Study Group. Cardiac-resynchronization therapy in heart failure with a narrow QRS complex. N Engl J Med 2013;369:1395-1405.
Cardiac resynchronization therapy (CRT) has been shown to reduce mortality and improve symptoms in patients with reduced ejection fraction and a wide QRS complex. However, QRS width is only an indirect measure of mechanical dyssynchrony. It has been hypothesized that patients with congestive heart failure and mechanical measures of dyssynchrony without a wide QRS would also benefit from resynchronization.
The EchoCRT study was a prospective, randomized, multicenter, clinical trial. The study enrolled patients ≥ 18 years of age with New York Heart Association (NYHA) Class III or IV heart failure, a left ventricular ejection fraction of ≤ 35%, QRS duration of < 130 msec, echocardiographic evidence of dyssynchrony, and a standard indication for a cardiac resynchronization implantable defibrillator (CRT-D). Dyssynchrony was measured by Doppler echocardiography and speckle tracking software. All enrolled patients underwent implantation of a CRT-D device with atrial, and right and left ventricular (LV) leads; those who had unsuccessful LV lead placement exited the study. Patients were then randomized to CRT-D pacing on or off (control) with customized programming in the CRT-on patients to maximize biventricular pacing. The primary endpoint was mortality or first heart failure hospitalization; a safety endpoint of freedom from complications at 6 months was also included. After enrolling 809 patients (405 to CRT-on and 404 to CRT-off), the study was terminated by the data and safety monitoring board for futility and possible harm. The mean follow-up time was 19.4 months. The mean QRS duration of randomized patients was 105 msec. The primary endpoint, death or worsening heart failure, was not significantly different between the CRT and control groups (28.7% vs 25.2%; hazard ratio [HR], 1.2; 95% confidence interval [CI], 0.92-1.47; P = 0.15). Mortality was actually higher in the CRT group compared to the control group (11.1% vs 6.4%; HR 1.81; 95% CI, 1.11-2.93; P = 0.02) with an excess of cardiovascular deaths (37 vs 17; P = 0.004). The hospitalization rate for worsening heart failure and change in NYHA class did not differ between groups. Freedom from complications overall was 89% at 6 months, with no significant difference between the CRT and control groups (12.5% vs 8.9%; P = 0.11). Inappropriate ICD shocks were more common in the CRT group compared to the control group (5% vs 1.7%; P = 0.01). The authors concluded that in patients with systolic heart failure and a QRS duration < 130 msec, CRT implantation did not reduce the primary endpoint of death or worsening heart failure, and may increase the mortality rate.
The improvements in heart failure symptoms and mortality in trials of patients with reduced ejection and wide QRS complexes undergoing CRT-D have made CRT-D an important part of the heart failure treatment armamentarium.1 There are few options available for those patients who remain symptomatic after optimization of medical therapy, other than cardiac transplantation. This has led to the hope that other patients, namely those with narrow QRS but echocardiographic evidence of dyssynchrony, would benefit from CRT-D. The first randomized study of CRT-D in patients with heart failure and a narrow QRS2 was negative and terminated early due to futility. A second study showed possible harm.3 Now, EchoCRT shows not only lack of benefit, but actually an increase in mortality in patients with narrow QRS complexes undergoing CRT-D implantation. This should put to rest the question of whether resynchronization has a role in patients with narrow QRS complexes. Clearly biventricular pacing cannot improve upon the native conduction system, and may actually cause harm through worsening interventricular dyssynchrony. In fact, one should consider that even those patients with only mild QRS widening of 120-130 msec may not benefit, particularly if an ideal pacing location is not present. In the recent MADI-CRT trial,4 those who benefitted most had a classic LBBB and QRS duration ≥ 150 msec. While there is always a temptation to consider CRT-D in patients with QRS of 120-130 msec because there are few options available, the additional implant time and complication rate of adding two additional leads should not be underestimated. Simpler is often better. However, in patients with LBBB and QRS > 150 msec, CRT-D remains an important therapeutic option.
- Cleland JG, et al and the Cardiac Resynchronization-Heart Failure (CARE-HF) study investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med 2005;352:1539-1549.
- Beshai JF, et al. RethinQ study investigators. Cardiac-resynchronization therapy in heart failure with narrow QRS complexes. N Engl J Med 2007;357:2461-2471.
- Thibault B, et al and the LESSER-EARTH investigators. Cardiac resynchronization therapy in patients with heart failure and a QRS complex <120 milliseconds: The Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) trial. Circulation 2013; 127:873-881.
- Moss AJ, et al and the MADIT-CRT trial investigators. Cardiac-resynchronization therapy for the prevention of heart-failure events. N Engl J Med 2009;361:1329-1338.