Authors
Young JB, Abraham WT, Smith AL, et al.
Title
Combined Cardiac Resynchronization and Implantable Cardioversion Defibrillation in Advanced Chronic Heart Failure
References
JAMA 2003; 289: 2685-94
Background
Previous literature on CRT had demonstrated improvements in functional class and quality of life in patients with moderate to severe heart failure and evidence of intraventricular conduction delay. However, these studies had excluded patients with standard indications for an ICD.
Purpose
To determine the impact of the addition of CRT in a patient population with moderate to severe heart failure symptoms, wide QRS interval, and LV systolic dysfunction with an established indication for an ICD.
Design
Randomized, double-blind, parallel-controlled trial 369 patients age ≥ 18 years, cardiac arrest due to VF or ventricular tachyarrhythmia or spontaneously sustained ventricular tachyarrhythmia or inducible VF or sustained ventricular tachyarrhythmia, NYHA III or IV, LVEF ≤ 35%, QRS ≥ 130 ms, left ventricular end diastolic diameter ≥ 55 mm, and a stable drug regimen for ≥ 1 month
Exclusion Criteria
Estimated survival < 6 months Baseline 6-minute walk test > 450 m Bradycardia requiring pacemaker Unstable angina, myocardial infarction, CABG, PTCA, cerebral vascular accident, or TIA within prior 3 months > 2 infusions of inotropic drug per week Systolic blood pressure <80 mmHg or > 170 mmHg Resting heart rate > 140 bpm Serum creatinine > 3 mg/dL (> 265 µmol/L) Hepatic enzymes > 3-fold upper normal values Severe lung disease Chronic atrial arrhythmias, or cardioversion or paroxysmal atrial fibrillation within previous 1 month Heart transplant recipient Severe valvular heart disease
Follow-Up
6 months
Treatment Regimen
Implantation of ICD/CRT device, right atrial pacing lead, RV pacing/defibrillator lead, and LV lead Random assignment to active CRT and active ICD therapy (CRT group) or active ICD therapy alone (control group) Optimal medical therapy continued as background in both groups Evaluation at baseline, 1 month, 3 months, and 6 months after implantation
Results
Primary End Points: Change in NYHA class: CRT group (-1) vs control group (0) (p = 0.007) Change in Quality of Life Score (Minnesota questionnaire – higher score, worse QOL): CRT group (-17.5) vs control group (-11) (p = 0.02) Change in distance walked in six minutes: CRT group (+ 55 m) vs control group (+ 53 m) (p = 0.36) Secondary End Points: Change in peak oxygen consumption: CRT group (+ 1.1 mL/kg/min) vs control group (+ 0.1 mL/kg/min) (p = 0.04) Change in treadmill exercise duration: CRT group (+ 55.5 seconds) vs control group (- 11 seconds) (p < 0.001) Change in LVEF: CRT group(+ 2.1%) vs control group (+ 1.7%) (p = 0.12) Change in LV end-diastolic volume: CRT group (- 19.9 mL) vs control group (- 5.7 mL) (p = 0.06) Change in LV end-systolic volume: CRT group (- 22.2 mL) vs control group (- 8.2 mL) (p = 0.06) Change in LV end-diastolic dimension: CRT group (- 0.1 mm) vs control group (- 0.2 mm) (p = 0.81) Change in LV end-systolic diameter: CRT group (- 0.1 mm) vs control group (- 0.3 mm) (p = 0.53) Change in mitral regurgitant jet area: CRT group (- 0.55 mm) vs control group (- 0.33 mm) (p = 0.58) Change in QRS duration: CRT group (- 20 ms) vs control group (0 ms) (p < 0.001) Clinical composite response – improvement (p = 0.07) Change in BNP: CRT group (- 50 pg/mL) vs control group (- 68 pg/mL) (p = 0.77) Change in Dopamine: CRT group (0 pg/mL) vs control group (0 pg/mL0 (p = 0.37) Change in Norepinephrine: CRT group (+ 4 ng/dL) vs control group (- 17 ng/dL) (p = 0.58) Change in Epinephrine: CRT group (0 pg/mL) vs control group (- 3 pg/mL) (p = 0.05) Change in Big endothelin: CRT group (- 2.5 pg/mL) vs control group (- 1.8 pg/mL) (p = 0.98) Occurrence of VF/VT: CRT group (22%) vs control group (26%) (p = 0.47) Cumulative survival: CRT group (92.4%) vs control group (92.2%) (p = 0.96) Hospitalization for worsening heart failure or all-cause death: CRT group (25.7%) vs control group (25.9%) (p = 0.69) Death or all-cause hospitalization: CRT group (47.4%) vs control group (48.3%) (p = 0.88)
Summary
Cardiac resynchronization therapy improved quality of life, functional status, and exercise capacity in patients with moderate to severe heart failure (NYHA III or IV and LVEF ≤ 35%), evidence of intraventricular dyssynchrony (QRS ≥ 130 ms), and life-threatening arrhythmias.