April 26th, 2013

Conflicting Results from Two Trials of Cardiac Resynchronization Therapy

Two new trials have ended up reporting conflicting results regarding the expansion of the indication for cardiac resynchronization therapy (CRT) for patients without a wide QRS interval.  The positive results of the smaller trial seem likely to be undermined by the early stopping of the much larger trial.

The first trial, NARROW-CRT, published in Circulation: Arrhythmia and Electrophysiology, concluded that CRT “improved clinical status in some patients with ischemic cardiomyopathy, mild-to-moderate symptoms, narrow QRS duration, and mechanical dyssynchrony on echocardiography.” The second trial, EchoCRT, which was testing CRT in heart failure (HF) patients with narrow QRS, was terminated early due to futility.

In NARROW-CRT, Carmine Muto and colleagues randomized 120 ischemic HF patients with echo evidence of dyssynchrony and a QRS < 120 ms to either a CRT device or a dual chamber ICD. At one year improvement in the clinical composite score — the primary endpoint — had occurred in 41% of the CRT patients versus 16% of the ICD patients (p=0.004). The investigators reported a trend in favor of CRT for the secondary endpoint of HF hospitalization and HF death (p=0.077) and a significant benefit for another secondary endpoint — HF hospitalization, HF death, and spontaneous ventricular fibrillation.

The positive finding of NARROW-CRT appears not to have been supported by the early termination of the much larger EchoCRT. The trial, sponsored by Biotronik, was recently halted due to futility. (Although patients and investigators have been informed of the early stopping, no public announcement by the company or the sponsor has been made to date.) The trial had been designed to evaluate the effect of CRT on morbidity and mortality in HF patients with a narrow QRS (< 130 ms) and with echo evidence of dyssynchrony. Results of the trial are expected to be presented at a medical meeting in the near future.

Although the full results of the trial are not yet known, it appears unlikely that they will support an expanded FDA indication for CRT or that another large trial will be performed in this population. However, several trials are now exploring expanded use of CRTs in other areas. The publication in the New England Journal of Medicine earlier this week of the BLOCK HF trial may lead to an indication for CRT in patients with heart block and LV dysfunction. Other trials include the recently initiated MIRACLE EF trial, which is looking at CRT as a primary treatment in HF patients with LBBB and mild LV dysfunction, and the ongoing PROMPT trial, which is evaluating LV or biventricular pacing as a treatment to prevent adverse myocardial remodeling early after myocardial infarction.









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