• Heart Failure
• Cardiology Clinical Trials
• Interventional Techniques & Devices

• Cardiology & Cardiovascular Medicine
• Heart Failure
• Cardiology Clinical Trials
• Interventional Techniques & Devices

The Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy [MADIT-CRT; Moss AJ et al. N Engl J Med 2009] trial evaluated the effect of CRT with biventricular pacing on the combined endpoint of death from any cause and nonfatal heart failure (HF) events in 1820 patients with mild HF. Eligible patients had ischemic or nonischemic cardiomyopathy with NYHA Class I or II symptoms, an ejection fraction of ≤30%, and a QRS duration of ≥130 msec. At a median follow-up of 2.4 years, the primary endpoint occurred in 17.2% of patients who received a CRT plus an implantable cardioverter defibrillator (ICD) compared with 25.3% of patients who received an ICD alone (HR, 0.66; 95% CI, 0.52 to 0.84; p=0.001). The benefit of a CRT plus ICD (CRT-D) was driven by a 41% reduction in the risk of nonfatal HF events and was observed only in patients with left bundle-branch block (LBBB) [Zareba W et al. Circulation 2011].

Because a survival benefit was not demonstrated for CRT-D during the MADIT-CRT trial, the aim of the long-term follow-up analysis [Goldenberg I et al. N Engl J Med 2014], presented by Ilan Goldenberg, MD, University of Rochester Medical Center, Rochester, New York, USA, was to prospectively assess the effect of CRT-D on long-term survival.

All of the surviving MADIT-CRT trial patients (n=1691) participated in Phase 1 of the long-term follow-up until September 10, 2010. Of these, 854 were included in the Phase 2 registry and followed until September 30, 2013. The primary endpoint was all-cause mortality from MADIT-CRT enrollment until post-trial follow-up. Secondary endpoints included nonfatal HF events and a combined endpoint of a nonfatal HF event or death. The analyses were performed on an intention-to-treat basis and by LBBB status at enrollment.

Overall after 7 years of follow-up, 292 patients (16%) had died and 442 patients (24%) had experienced a nonfatal HF event. Among patients with LBBB, the all-cause mortality rate among was 18% in the CRT-D group compared with 29% in the ICD-only group (adjusted HR, 0.59; 95% CI, 0.43 to 0.80; p<0.001; Table 1). Patients in the CRT-D group also had a significantly lower probability of nonfatal HF events than the ICD-only group (adjusted HR, 0.38; 95% CI, 0.30 to 0.48; p<0.001) and the composite endpoint of HF or death (adjusted HR, 0.45; 95% CI, 0.37 to 0.56; p<0.001).

Among patients without LBBB, CRT-D provided no benefit (possibly harm) over ICD-only for all-cause mortality (adjusted HR, 1.57; 95% CI, 1.03 to 2.39; p=0.04), nonfatal HF events (adjusted HR, 1.13; 95% CI, 0.80 to 1.60; p=0.48), and the combined endpoint of HF or death (adjusted HR, 1.27; 95% CI, 0.94 to 1.73; p<0.001).

No subgroup with LBBB demonstrated worse survival when treated with CRT-D versus CRT alone. Patients with LBBB benefited from CRT-D regardless of QRS duration (QRS 130 to <150 msec or ≥150 msec), while those without LBBB did not benefit from CRT-D regardless of QRS duration.

Dr. Goldenberg concluded that early intervention with CRT-D compared with ICD-only is associated with a significant long-term survival benefit in patients with mild HF symptoms, left ventricular dysfunction, and LBBB. However, early CRT-D intervention does not benefit patients without LBBB and may be harmful.

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