Efficacy Study of Pacemakers to Treat Slow Heart Rate in Patients With Heart Failure

Inclusion Criteria

1. Age >18 years and able to provide informed consent to enroll in the trial, or consent
through a legal guardian or power of attorney.

2. Previous clinical diagnosis of HF with current NYHA Class II-III symptoms

3. At least one of the following: Hospitalization for decompensated HF, Acute treatment
for HF with intravenous loop diuretic or hemofiltration, Chronic treatment with a loop
diuretic for control of HF symptoms + left atrial enlargement on echocardiography

4. Left ventricular EF ≥50% within 12 months with clinical stability

5. Stable cardiac medical therapy for ≥30 days

6. Sinus rhythm

7. Chronotropic incompetence on recent (within 6 months) clinical or screening exercise
test, defined as heart rate reserve (HRR) <0.80

8. Meet both screening criteria on clinically-performed cardiopulmonary exercise testing
within 12 months. Peak VO2 ≤60% age/sex-adjusted normal value + peak respiratory
exchange ratio (RER) ≥1.05 One of the following: NT-proBNP ≥400 pg/mL or NT-proBNP
<400 pg/mL, with rest PCWP >20 mmHg and/or >25 mmHg with exercise

Exclusion Criteria

1. Inability to exercise, or non-cardiac condition that precludes exercise testing

2. Any contraindication to a pacemaker system

3. Non-cardiac condition limiting life expectancy to less than one year

4. Significant left sided structural valve disease (>mild stenosis, >moderate
regurgitation)

5. Hypertrophic cardiomyopathy

6. Infiltrative or inflammatory myocardial disease (amyloid, sarcoid)

7. Pericardial disease

8. Non-group 2 pulmonary arterial hypertension

9. Chronic stable exertional angina

10. Acute coronary syndrome or revascularization within 60 days

11. Other clinically important causes of dyspnea

12. Atrial fibrillation

13. PR interval >210 msec

14. Resting heart rate (HR) > 100 bpm

15. A history of reduced ejection fraction (EF<50%)

16. Advanced chronic kidney disease (GFR < 20 ml/min/1.73m2 by modified MDRD equation)

17. Women of child bearing potential without negative pregnancy test and effective
contraception

18. Severe anemia (Hemoglobin <10 g/dL)

19. Severe hepatic disease

20. Complex congenital heart disease

21. Listed for cardiac transplantation

22. Other class I indications for pacing