Title of Trial
Pacing Therapies for Congestive Heart Failure (Path-CHF) Trial

Date and Citation of Primary Publication(s) or References
Auricchio A, Stellbrink C, Block M, et al. The effect of pacing chamber and atrioventricular delay on acute systolic function of paced patients with congestive heart failure. Circulation 1999; 99: 1567-73.

Stellbrink C, Breithardt OA, Franke A, et al. Impact of resynchronization therapy using hemodynamically optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances. J Am Coll Card 2001; 38: 1957-65.

Auricchio A, Stellbrink C, Sack S, et al. Long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Card 2002; 39: 2026-33.

Purpose of the Trial
Evaluate the effects of cardiac resynchronization therapy in chronic heart failure on quality of life and symptoms. Evaluate the best method for cardiac resynchronization (left ventricular vs. biventricular).

Study Categories
Pacemakers

Patient Population
Inclusion Criteria
Class III or IV heart failure for six months before enrollment despite optimal medical therapy, sinus rhythm, a QRS interval > 150 ms and a PR interval > 120 ms.

Exclusion Criteria
Correctable valvular heart disease, limited life expectancy or limited exercise capacity due to noncardiac conditions, indication for a pacemaker or defibrillator.

Study Design
Single blind randomized crossover trial. Patients underwent implantation of two separate pacemakers; one connected to right atrial and right ventricular leads and the other to an epicardial left ventricular and a second right atrial lead. The epicardial lead was positioned to obtain the best hemodynamic effect (Auricchio 1999). Patients were randomized to one month of cardiac resynchronization using optimized univentricular or biventricular pacing. For optimal unviventricular pacing, the left ventricular site was selected in 36 patients and right ventricular pacing was selected in 4 patients. After a one-month period of no pacing therapy, the patient was crossed over to the other pacing mode for one month. After the crossover portion of the study, patients were programmed to the pacing mode (univentricular or biventricular) judged best by the attending physician and followed-up at twelve months.

Primary Endpoints
Oxygen uptake at peak exercise, oxygen uptake at anaerobic threshold, and six-minute walk distance.

Secondary Endpoints
Quality-of-life and NYHA functional class.

Baseline Characteristics

Patient number: 41 patients

Mean Age: 60 ± 7 years

Gender: 50% female

Other characteristics: Etiology: 29% ischemic and 71% nonischemic. Functional class: 86% class III and 14% class IV. Electrocardiographic parameters: Resting heart rate: 78 ± 15 bpm, QRS duration 175 ± 32 ms (93% of patients with LBBB), PR interval 196 ± 33 ms. Echocardiographic measurements: LV EF 21 ± 7%, LVEDD: 73 ± 11 mm.

Follow-up
42 patients initially enrolled and one patient was disqualified due to aortic stenosis. 35 patients completed all three study periods (2 patients died of sudden cardiac death; 1 patient presented with ventricular tachycardia and was excluded from the analysis; 1 patient underwent heart transplant; and 2 patients refused crossover), and 29 patients were followed to 12 months. For these 29 patients 12 patients were programmed to biventricular pacing, 13 patients were programmed to univentricular pacing using the left ventricle, and 4 patients were programmed to univentricular pacing using the right ventricle.

Results
Clinical effects of optimal univentricular pacing and biventricular pacing were similar (Table 1). As shown in Table 2, at twelve-month follow-up, cardiac resynchronization using either optimal univentricular pacing or biventricular pacing was associated with significant improvements in oxygen uptake, 6-minute walk distance, quality-of-life, and NYHA functional class compared to baseline

Table 1: Biventricular pacing vs. optimal univentricular pacing: Clinical effects.

Endpoint	Biventricular	Univentricular LV: 36 patients RV: 4 patients	P
Oxygen uptake at peak exercise (ml/kg/min)	14.91 ± 0.66	14.58 ± 0.77	0.324
Oxygen uptake at anaerobic threshold (ml/kg/min)	10.70 ± 0.47	10.39 ± 0.51	0.290
6-min walk distance (m)	402 ± 16	401 ± 16	0.345
Quality-of-life score (Minnesota Living with Heart Failure)	25.2 ± 3.3	28.1 ± 3.5	0.069
NYHA functional class (I/II/III/IV)%	15/39/41/5	22/37/34/7	0.360

Table 2: Clinical changes after 12 months of therapy

Endpoint	n	Before implantation	12 months of therapy (12 biventricular, 13 univentricular-LV, 4 univentricular-RV)	P
Oxygen uptake at peak exercise (ml/kg/min)	22	12.57 ± 0.63	15.63 ± 0.86	<0.001
Oxygen uptake at anaerobic threshold (ml/kg/min)	21	9.93 ± 0.46	11.45 ± 0.59	0.037
6-min walk distance (m)	25	357 ± 20	446 ± 15	<0.001
Quality-of-life score (Minnesota Living with Heart Failure)	28	48.6 ± 4.3	20.0 ± 4.1	<0.001
NYHA functional class (I/II/III/IV)%	29	0/0/86/14	34/38/28/0	<0.001

Sponsor
Guidant

Trial Status:  Completed