Trial Description
Implantation of the biventricular pacing ICD (InSync ICD, Medtronic Model 7272) with right ventricular sensing only, biventricular pacing, antitachycardia pacing, and dual chamber pacing.

Hypothesis
Biventricular pacing improves Quality of Life, NYHA Classification, and 6 minute walk compared to no pacing.

Protocol
Implantation of the biventricular pacing ICD (InSync ICD, Medtronic Model 7272) with right ventricular sensing only, biventricular pacing, antitachycardia pacing, and dual chamber pacing was performed. Patients were randomized to biventricular pacing program on or off for 6 months. At 6 months, all patients had biventricular pacing programmed on.

Endpoints
The primary endpoint was based upon Quality of Life (Minnesota Living With Heart Failure Questionnaire); NYHA Class, and 6 minute walk. The primary endpoint was defined as being met if all three parameters achieved a significance at a P value of < 0.05, if two parameters had a P value of <0.025, or if one parameter had a P value of < 0.0167.

Secondary endpoints included exercise performance, a clinical composite, a health score, QRS duration, echocardiographic parameters, and neurohormone levels.

Inclusion Criteria
18 years of age or greater; Class II, III, IV Heart Failure; QRS > 130 ms; Left ventricular ejection fraction < 35%; LVEDD >55 mm; Stable heart failure > 1 month ACE inhibitor or equivalent and beta-blocker > 3months; ICD indication

Principal Findings
A total of 636 patients underwent attempted implant. Of these 215 patients were Class II and 421 patients were Class III/IV. Of the Class II patients, 192 patients were randomized. Of the Class III/IV patients, 362 patients were randomized. The Class III/IV patients were reported separately as planned before start of the trial.The study was stopped when paired 6 month data became available for 112 patients in each group without crossovers or withdrawal.

The study was closed for analysis on October 5, 2001. There were 176 patients in the control arm and 186 patients in the resynchronization arm, resulting in 124 patients and 133 patients with 6 month data, respectively. There were 15 deaths in the control arm and 12 deaths in the resynchronization arm.

All pre-selected safety endpoints were achieved. The Quality of Life measurements revealed a decrease of 10 points in the Control Arm compared to a decrease of 19 points in the Resynchronization Arm at 6 months, consistent with an improvement in quality of life (p=0.0098). Patients in the Resynchronization Arm demonstrated greater improved in terms of NYHA Class compared to the Control Arm.

There was no difference in the 6 minute walk duration in the two groups (p=NS).

There was no change in peak VO2 in the Control Arm compared to an increase of 1.1 in peak VO2 in the Resynchronization Arm (p=0.05). Exercise time decreased by 26 seconds in the Control Arm compared to an increase in exercise time of 58 seconds in the Resynchronization Arm (p<0.001).

Some echocardiographic parameters were different in the two groups. The LVEDV decreased by 5 mm in the Control Arm and by 25 mm in the Resynchronization Arm (p=0.046). The LV ejection fraction increased by 1.6% in the Control Arm and increased by 3.0% in the Resynchronization Arm (p=0.06).

There was a trend in decreased mortality in the Resynchronization Arm with a hazard ratio of 0.69 (95 CI 0.46,1.04) (p=0.07).

Interpretation/Conclusions
Resynchronization therapy with biventricular pacing results in improved Quality of Life and NYHA classification in this patient population.

Report submitted by Paul Wang, M.D.
Presented at the American College of Cardiology Annual Scientific Sessions, March 20, 2002 Late-Breaking Clinical Trials III