Authors
Cleland J, Daubert J-C, Erdmann E, et al.
Title
The Effect of Cardiac Resynchronization on Morbidity and Mortality in Heart Failure
References
N Engl J Med 2005;352:1539-49
Background
In short term studies, cardiac resynchronization therapy (CRT) has been shown to improve symptoms, cardiac function and quality of life in heart failure patients. The COMPANION trial demonstrated that CRT with or without a defibrillator significantly reduced the composite outcome of death from any cause or hospitalization, but CRT alone did not reduce the risk of death.
Purpose
To determine if CRT, when added to standard pharmacotherapy positively affects survival and clinical outcomes in patients with moderate or severe heart failure and cardiac dyssynchrony as compared to standard pharmacotherapy alone.
Design
  • Multicenter, randomized, open-label, controlled trial
  • 813 patients with ≥6 weeks of HF, NYHA class III or IV symptoms, on standard pharmacotherapy, age ≥18 yrs, LVEF ≤35%, LVEDD ≥30 mm, and QRS ≥120 ms.
  • if QRS 120-149 ms, then must meet two of the following criteria for dyssynchrony: aortic preejection delay >140 ms, interventricular mechanical delay >40 ms or delayed activation of the posterolateral left ventricular wall
  • Standard pharmacotherapy may include ACE inhibitor or ARB, β-blocker, high dose diuretic, spironolactone, digoxin
Exclusion Criteria
  • Major CV event within past 6 weeks, clinical indication for pacemaker or implantable defibrillator, atrial arrhythmia, heart failure requiring continuous IV therapy
Follow-Up
Mean 29.4 months (ranged from 18 - 44.7 months)
Treatment Regimen
  • CRT and standard pharmacotherapy (CRT+MED) vs. standard pharmacotherapy (MED)
  • patient evaluated and medications adjusted if appropriate at month 1, 3, 3, 9, 12,18 and then every 6 months; at month 3 and 18, measurement of LVEF, LVESV, N-terminal pro-BNP, mitral regurgitation area, interventricular mechanical delay
  • hospitalization endpoint adjudicated by blinded committee
Results

Primary Endpoints

Composite of death from any cause or CV hospitalization: 39% (CRT+MED) vs. 55% (MED); HR 0.63 (0.51-0.77), p < 0.001

Secondary Endpoints (see study for complete list)

CRT+MED
n=409		MED
n=404		HRp
All cause death (primary)
20%30%0.64 (0.48-0.85)< 0.002
Composite of all cause death or HF hospitalization
29%47%0.54 (0.43-0.68)< 0.001
HF hospitalization
18%33%0.48 (0.36-0.64)< 0.001

  • CRT+MED group had a better quality of life (< 0.001; measured by EuroQoL ED-5D score and Minnesota Living with Heart Failure score) & less severe NYHA class symptoms (< 0.001)
  • CRT+MED also increased LVEF, lowered LVESV, and reduced mitral regurgitation and shorter interventricular mechanical delay
Summary
When combined with standard pharmacotherapy, cardiac resynchronization therapy reduces the rate of death from any cause and hospitalization, as well as improves the symptoms and quality of life in patients with cardiac dyssynchrony and moderate-severe heart failure.