Background 

The theoretical basis for BiV pacing is relatively simple. Up to 40% of patients with CHF have significant intraventricular conduction abnormalities. These conduction delays can result in abnormal activation of ventricular myocardium and, perhaps more importantly, in asynchronous activation of the atrial and ventricular chambers. BiV pacing simultaneously activates the right and left ventricles using a combination of conventional pacing of the right ventricle and specialized pacing of the left ventricle through leads positioned via the coronary sinus. Early reports suggest that BiV pacing improves cardiac function and alleviates symptoms; however, most these studies are small, poorly controlled and unblinded. BiV pacing has been extensively discussed in previous issues of the Arrhythmia News (July 2000 and January 2001).

MIRACLE Design

The MIRACLE trial was designed to evaluate the safety and efficacy of BiV pacing in-patients with CHF and significant conduction abnormalities. Only patients with NYHA Class III or IV heart failure symptoms, LVEF £35% and LV end-diastolic dimension of >55 mm were included in the study. Patients were required to have QRS duration >130 ms on surface ECG. In addition, all patients were required to be on a stable regimen that included ACE inhibition and beta-blocker therapy.

All patients received devices capable of BiV pacing. After implantation, patients were randomized to either BiV pacing or control (with backup pacing only) for their first 6 months of participation in the trial. Exercise capacity was determined by a 6-minute walk test and metabolic testing; functional classification and quality-of-life were determined by investigator evaluation. To maintain the double-blind nature of heart failure evaluations, each site had two investigators: a heart failure specialist who remained blinded and an electrophysiologist who was unblinded. The trial was specifically designed with significant statistical power to analyze differences in quality-of-life data.

MIRACLE Results

A total of 266 patients from 44 centers in North America were enrolled in the MIRACLE trial between November, 1998 and June, 2000. Of these, 134 received BiV pacing during the first 6 months and 132 acted as controls. The average age was 64±11 years; 70% were male and 90% were Caucasian. The average QRS duration was 165±19 ms; the average LVEF was 21± 6%. Differences between the groups were not significant. Implantation was successful in 93% of attempts; system safety criteria exceeded all requirements.

Over the 6 month period of the study, NYHA class improved significantly in the majority of patients treated with BiV pacing. Upon entrance into the trial, 90% were classified as Class III and 10% as Class IV; at 6 months, 52% had improved to Class II and 13% to Class I. This compared to only 27% of controls that were evaluated as improving to Class II with 64% remaining at Class III (p<0.001). Evaluation of heart failure by 6-minute hall walk demonstrated dramatic improvement at 1, 3 and 6 months in patients receiving BiV pacing; the average improvement was 39 meters as compared to no significant change in controls. Quality-of-life scores were also significantly improved in patients receiving BiV pacing.

Objective evaluation of left ventricular function demonstrated significant improvement with BiV pacing. LV end-diastolic dimension decreased from 73 to 68 mm with BiV pacing as compared no change in controls (p<0.001). LVEF also improved from 24% to 31% with BiV pacing as compared no change in controls (p<0.001). The study was not powered to evaluate mortality differences between the groups. Of note, however, there were similar numbers of deaths in the BiV pacing group (8) and the control group (10).

Future Directions 

The MIRACLE trial is the largest, randomized double-blind trial of BiV pacing to date. This trial demonstrates that BiV pacing is safe and well tolerated; it improves quality-of-life, functional class and exercise capacity; and it improves cardiac structure and function. Trials currently underway evaluate the value of additional defibrillator function for these patients, and are large enough to evaluate mortality outcomes. If you have patients who may qualify please contact the Arrhythmia Service at our offices in your area. Stay tuned!

Reproduced with permission. Published by the Arrhythmia Service of St. Luke's-Roosevelt Hospital Center, New York, New York.