Title of Trial
Multicenter InSynch ICD Randomized Clinical Evaluation (MIRACLE-ICD)

Initial Presentation
American College of Cardiology 2002

Date and Citation of Primary Publication(s) or References
Young JB, Abraham WT, Smith AL et al for the MIRACLE ICD investigators study group. Combined cardiac resynchronization and implantable cardioversion defibrillation in advanced chronic heart failure. JAMA 2003; 289: 2685-94.

Purpose of the Trial
Evaluate the effects of cardiac resynchronization therapy (CRT) on quality of life and symptoms with patients in chronic heart failure who have an indication for defibrillator implantation.

Study Categories
Pacemakers and ICD

Patient Population

Inclusion Criteria
Class III or IV heart failure, left ventricular ejection fraction < 0.35, left ventricular end diatolic volume > 55 mm, QRS interval > 130 ms, and a 6 minute walking distance < 450 m) and an indication for defibrillator implantation.

Exclusion Criteria
Pacemaker or defibrillator, cardiac or cerebral ischemic event within the last 3 months, atrial arrhythmia in the last month, systolic blood pressure > 170 mm Hg or < 80 mm Hg, heart rate > 140 beats per minute, serum creatinine > 3.0 mg/dl serum aminotransferase level more than three times the upper limit of normal.

Study Design
Randomized double blind parallel controlled trial

Primary Endpoints
NYHA class, quality of life, six minute walk distance.

Secondary Endpoints
Peak oxygen consumption, exercise time

Baseline Characteristics

Patient number: 369 patients

Mean Age: 67 ± 11 years

Gender: 23% female

Other characteristics: Clinical characteristics: 90% Class III, QRS duration 163 ± 20 ms, ejection fraction 24 ± 6%, isolated right bundle branch block: 13%. Heart failure etiology: 70% ischemic and 30% nonischemic. Indication for ICD: cardiac arrest: 10%; sustained ventricular tachycardia: 40%; Inducible ventricular arrhythmias: 50%.

Follow-up
639 enrolled and consented. 210 patients were Class II (placed in a separate study) and 60 were not randomized (see below). Of the 369 patients, 182 were randomized to ICD only and 187 were randomized to ICD and CRT. At six month follow-up 162 patients in the control group and 165 patients in the CRT group completed the six month follow-up period.

Results
Of the 429 patients undergoing an implant attempt, 60 patients were not randomized. Fifty of those patients did not have placement of a left ventricular lead and therefore received a standard ICD system, and 120 patients (28%) had complications. Thirty seven complications were related to the left ventricular lead including 15 coronary sinus dissections and 4 cardiac perforations. Of the 369 patients randomized there were 29 deaths (Control: 15 and CRT: 14) and 24 crossovers (Control to CRT: 14 (11 worsening heart failure, 2 bradycardia, 1 programming error) and CRT to control: 10 (2 LV lead dislodgement, 2 diaphragmatic stimulation, 6 programming errors). CRT was associated with an improved functional class and quality of life (-17.5 vs. -11 points, p = 0.02) when compared to the control group (Table 1). No significant difference in the six minute walk distance was detected. For secondary endpoints, CRT was associated with improved peak oxygen consumption (+1.1 vs. +0.1 ml/kg/min; p = 0.04), and increased exercise time (+56 sec vs. -11 sec; p< 0.001). No significant differences in echocardiographic parameters were identified (Table 2). No significant differences in hospital care use were identified (Table 3).

Table 1: Primary and secondary endpoints

Endpoint	Control Median change (95%)	CRT Median Change (95% CI)	P
Change in quality-of-life score (lower score better)	-11 (-16 to -7)	-17.5 (-21 to -14)	0.02
Change in NYHA functional class	0 (-1 to 0)	-1 (-1 to -1)	0.007
Change in 6 minute walk distance (m)	53 (43 to 75)	55 (44 to 79)	0.36
Change in peak VO2 (mL/kg/min)	0.1 (-0.1 to 0.8)	1.1 (0.7 to 1.6)	0.04
Change in exercise duration (s)	-11 (-55 to 12)	55.5 (30 to 79)	< 0.001

Table 2: Echocardiographic parameters

Endpoint	Control Median change (95%)	CRT Median change (95% CI)	P
Change in diastolic volume (mL)	-5.7 (-16.2 to 1.8)	-19.9 (-39.7 to -6.3)	0.06
Change in ejection fraction (%)	1.7 (0.7 to 2.4)	2.1 (1.2 to 4.1)	0.12
Change in mitral regurgitation jet area (mm2)	-0.33 (-0.85 to 0)	-0.55 (-2.00 to 0)	0.58

Table 3: Change in hospital use

Endpoint	Control	CRT	P
Hospitalizations	78	85	NS
Mean hospital stay (days)	5.4 ± 4.7	4.8 ± 4.9	0.06
Probability of hospitalization for worsening heart failure (%)	25.9	25.7	0.69

Sponsor:  Medtronic

Trial Status:  Completed