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Multicenter InSync Implantable Cardioversion Defibrillation Randomized Clinical Evaluation - MIRACLE ICD
Description:
The goal of the MIRACLE ICD trial was to compare the effect of cardiac resynchronization therapy (CRT) plus implantable cardioverter defibrillator (ICD) versus ICD alone on the quality of life, functional capacity, and safety in patients with chronic heart failure (CHF) and ventricular dysynchrony.
Hypothesis:
Patients with moderate to severe HF symptoms, a wide QRS interval, left ventricular (LV) systolic dysfunction, and an established indication for an ICD would benefit from CRT, and that CRT would not be proarrhythmic or compromise ICD therapy.
Study Design
Study Design:
Patients Screened: 639
Patients Enrolled: 369
NYHA Class: Class III 89%; class IV 11%
Mean Follow Up: 6 month
Mean Patient Age: Mean age 67 years
Female: 23
Mean Ejection Fraction: Mean EF 24%
Patient Populations:
Age ≥18 years; cardiac arrest due to ventricular fibrillation or ventricular tachyarrhythmia, or spontaneously sustained ventricular tachyarrhythmia, or inducible ventricular fibrillation or sustained ventricular tachyarrhythmia; NYHA functional class III or IV CHF; LVEF ≤35%; QRS duration ≥130 ms; LV end-diastolic diameter ≥55 mm; and stable drug regimen for ≥1 month
Exclusions:
Estimated survival <6 months; baseline six-minute walk test >450 m; bradycardia requiring pacemaker; unstable angina, myocardial ischemia, coronary artery bypass graft, percutaneous coronary transluminal angioplasty, cerebral vascular accident, or transient ischemic attack within previous three months; >2 infusions of inotropic drug per week; systolic blood pressure <80 mm Hg or >170 mm Hg; resting heart rate >140/min; 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 one month; heart transplant recipient; or severe valvular heart disease
Primary Endpoints:
NYHA functional class, quality of life score, and distance covered during the six-minute walking test
Secondary Endpoints:
Peak oxygen consumption, treadmill exercise duration, LVEF, LV end-systolic and end-diastolic volumes, LV end-diastolic dimension, severity of mitral regurgitation, QRS duration, neurohormone concentrations, and a clinical composite response (worsened, improved, or unchanged)
Drug/Procedures Used:
Following baseline assessment, patients underwent implant attempt within one week. Following successful lead placement, patients underwent a predischarge randomization to the control group (ICD on but CRT not on, n=182) or experimental group (both ICD and CRT on, n=187), then underwent a six-month period of double-blinded study with follow-up at one, three, and six months.
For patients in the CRT arm, the device was programmed to pace both ventricles simultaneously following atrial-sensed events at rates of ≤130/min, while atrial pacing occurred only for sinus rates <35/min. In the control arm, the device did not provide atrial or ventricular pacing unless the intrinsic rate was <35/min.
The electrophysiologist served as an unblinded third party, and the heart failure specialist, the managing physician, and the patient were kept blinded to study assignment during the six-month period of the study.
Concomitant Medications:
Patients in both arms were to receive optimal medical treatment in addition to the randomized treatment.
Principal Findings:
Device implantation was unsuccessful in 50 patients who were subsequently not randomized. Compared with placebo, CRT was associated with a significantly improved New York Heart Association (NYHA) class by at least one class (median class change -1 vs. 0, p=0.007) and quality of life (-17.5 vs. -11 points, p=0.02), but no difference in six-minute walk distance (+55 vs. +53 m, p=0.36).
Many of the secondary endpoints were improved in the CRT arm, including time on the treadmill during exercise testing (+55.5 vs. -11 second, p<0.001) and peak oxygen consumption (+1.1 vs. +0.1 ml/kg/min, p=0.04), and trend towards improved end-diastolic volume (-19.9 vs. -5.7 ml, p=0.06), end-systolic volume (-22.2 vs. -8.2 ml, p=0.06), and ejection fraction (+2.1% vs. +1.7%, p=0.12). The QRS duration was significantly lower in CRT patients compared with control (-20 vs. 0 ms, p<0.001).
Using the change in overall clinical status, there was a trend for a higher percentage of CRT patients to be classified as improved (52% vs. 43%, p=0.07). There was no difference in mortality (7.6% vs. 7.8%, p=0.96) or the composite of death or repeat hospitalization for worsening HF (25.7% vs. 25.9%, p=0.69).
Interpretation:
Among patients with CHF, a wide QRS interval, and arrhythmias, cardiac resynchronization with ICD was associated with improved functional class and improved quality of life, but no difference in six-minute walk distance over ICD alone.
While two of the three primary endpoints of the MIRACLE ICD trial were positive for CRT therapy, the data were not as consistent as the benefit seen in the MIRACLE trial, which had a similar design, but enrolled patients without an indication for ICD therapy. In the MIRACLE trial, CRT was associated with improvements in all three of the primary endpoints as well as all of the prespecified secondary endpoints, including clinical status, LV volume, and ejection fraction (EF).
The authors hypothesize that the difference in outcomes between the two similarly designed trials may be due to the fact the patients in the MIRACLE ICD trial were sicker, with less opportunity for morphometric remodeling from the CRT. Nonetheless, CRT was associated with improvement in two of the three primary endpoints in the MIRACLE ICD trial as well as many of the prespecified secondary endpoints (treadmill exercise duration, peak oxygen consumption, QRS duration).
References:
Young JB, Abraham WT, Smith AL, et al. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure: the MIRACLE ICD Trial. JAMA 2003;289:2685–94.
Keywords: Tachycardia, Ventricular, Follow-Up Studies, Oxygen Consumption, Quality of Life, Ventricular Fibrillation, Heart Failure, Heart Arrest, Defibrillators, Implantable, Cardiac Resynchronization Therapy
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