Authors
Abraham WT, Fisher WG, Smith AL, et al.
Title
Cardiac Resynchronization in Chronic Heart Failure
References
New Engl J Med 2002; 346: 1845-53
Background
Intraventricular conduction delay and dyssynchrony have been associated with clinical instability and an increased risk of death in patients with heart failure. Previous literature has suggested that atrial-synchronized biventricular pacing can improve cardiac function and enhance functional capacity and quality of life.
Purpose
To determine the clinical efficacy of biventricular pacing in patients with moderate to severe heart failure and intraventricular conduction delay.
Design
  • Double-blind, randomized, controlled study
  • 453 patients with moderate to severe (NYHA III or IV) chronic heart failure (ischemic or non-ischemic), LVEF ≤ 35%, LV end-diastolic dimension ≥ 55 mm, QRS ≥ 130 msec, and six-minute walk distance ≤ 450 m
  • All patients on appropriate medical therapy for heart failure: diuretic, ACE inhibitor or ARB, digitalis, and beta-blocker (doses of medications stable for at least one month with beta-blocker dose stable for at least three months)
Exclusion Criteria
  • Pacemaker of ICD already implanted
  • Indication for or contraindication to cardiac pacing
  • Cardiac or cerebral ischemic event within previous three months
  • Systolic blood pressure ≥ 170 mmHg or ≤ 80 mmHg
  • Heart rate > 140 bpm
  • Serum creatinine > 3.0 mg/dl (265 µmol/L)
  • Serum aminotransferase levels more than three times the upper limit of normal
Follow-Up
6 months
Treatment Regimen
  • Implantation of cardiac-resynchronization device with right atrial lead, RV lead, and LV lead
  • Randomized to atrial-synchronized biventricular pacing (resynchronization group) or control group (no pacing)
  • Medical therapy to be kept constant during study period
Results
Primary End Points:
  • Change in NYHA Class: CRT group vs control group – improvement (p < 0.001)
  • Change in Quality of Life Score (Minnesota questionnaire – higher score, worse QOL): CRT group (-18.0) vs control group (-9.0) (p = 0.001)
  • Change in distance walked in six minutes: CRT group (+ 39) vs control group (+ 10) (p = 0.005)
Secondary End Points:
  • Change in peak oxygen consumption: CRT group (+ 1.1 ml/kg/min) vs control group (+ 0.2 ml/kg/min) (p = 0.009)
  • Change in time on a treadmill: CRT group (+ 81 seconds) vs control group (+ 19 seconds) (p = 0.001)
  • Change in LVEF: CRT group (+ 4.6%) vs control group (- 0.2%) (p < 0.001)
  • Change in end-diastolic dimension: CRT group (- 3.5 mm) vs control group (0.0 mm) ( p < 0.001)
  • Change in area of mitral regurgitant jet: CRT group (- 2.7 cm2) vs control group (0.5 cm2) (p < 0.001)
  • QRS duration: CRT group (- 20 ms) vs control group (0 ms) (p < 0.001)
  • Clinical composite response: CRT group vs control group – improvement (p < 0.001)
  • All-cause death: CRT group (5.2%) vs control group (7.0%) (HR 0.73, 95% CI 0.34 – 1.54, p = 0.40)
  • Death or worsening heart failure requiring hospitalization: CRT group (12.3%) vs control group (19.6%) (HR 0.60, 95% CI 0.37 – 0.96, p = 0.03)
  • Death or worsening heart failure requiring hospitalization or intravenous treatment: CRT group (15.8%) vs control group (24.4%) (HR 0.61, CI 0.40 – 0.93, p = 0.02)
  • Hospitalization for worsening heart failure: CRT group (7.9%) vs control group (15.1%) (HR 0.50, 95% CI 0.28 – 0.88, p = 0.02)
  • Worsening heart failure leading to the use of intravenous diuretic agents: CRT group (5.7%) vs control group (10.7%) (HR 0.51, 95% CI 0.26 – 1.00, p = 0.05)
  • Worsening heart failure leading to the use of intravenous vasodilators or positive inotropic agents: CRT group (2.6%) vs control group (6.2%) (HR 0.41, 95% CI 0.16 – 1.08, p = 0.06)
  • Worsening heart failure leading to the use of intravenous medication for heart failure: CRT group (7.0%) vs control group (15.6%) (HR 0.43, 95% CI 0.24 – 0.77, p = 0.004)
Summary
In a patient population with moderate to severe heart failure (NYHA III or IV and LVEF ≤ 35%) and intraventricular conduction delay (QRS ≥ 130 ms), cardiac resynchronization therapy improves functional class, quality of life, and cardiac function. This study also demonstrates a reduction in worsening heart failure requiring hospitalization or the use of intravenous medications.