β-blockers Withdrawal in Patients With HFpEF and Chronotropic Incompetence: Effect on Functional Capacity (Preserve-HR)

Betablockers Withdrawal in Patients With Heart Failure With Preserved Ejection Fraction and Chronotropic Incompetence: Effect on Functional Capacity Rationale and Study Design of a Prospective, Randomized, Controlled Trial

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) is complex and multifactorial. Chronotropic incompetence has emerged as a crucial mechanism, particularly in elderly patients. Betablockers, drugs with negative chronotropic effect, are commonly used in HFpEF, despite current evidence does not support its routine use in these patients. The aim of this work is to evaluate the effect of betablockers withdrawal in patients with HFpEF and chronotropic incompetence on functional capacity assessed by the peak oxygen consumption at maximal exercise (peakVO2) at 15 and 30 days after the intervention

This is a prospective, crossover, randomized (1:1) and single center study. After randomization, clinical and cardiac rhythm will be continuously registered during 30 days. The primary endpoint (peakVO2) will be assessed by cardiopulmonary exercise testing (CPET) at 15 and 30-day in both groups. Patients with HFpEF, functional class NYHA II-III, chronic treatment with betablockers, and chronotropic incompetence will be enrolled. A sample size estimation [alfa: 0.05, power: 90%, a 15% loss rate, and delta change of mean peakVO2: +1.2 mL/kg/min (SD±2.5)] of 52 patients would be necessary to test our hypothesis.

In conclusion, optimizing therapy that improve quality of life and autonomy has become a health care priority in HFpEF. The investigators believe this study will add important knowledge for the treatment of a subgroup of HFpEF.

Inclusion Criteria:

• Stable symptomatic patients with heart failure and preserved ejection fraction (NYHA class II-III).
• NT-proBNP >125 pg/mL in the last month
• Previous treatment with beta-blockers during the last 3 months
• Documented chronotropic incompetence, defined as: [(heart rate at peak exercise- heart rate at baseline)] / [(220 - age) - (heart rate at baseline)] < 0.62

Exclusion Criteria:

• Moderate to severe valvulopathy or miocardiopathy associated
• Patient with heart failure with recovered ejection fraction
• Acute Coronary Syndrome in the previous 12 months
• Angina or signs of myocardial ischemia on cardiopulmonary exercise testing
• Baseline heart rate>75 bpm.
• Uncontrolled hypertension, defined as >140mmHg systolic blood pressure and/or >90 mmHg diastolic blood pressure.
• Moderate to severe pulmonary disease associated
• Extracardiac comorbidity with a life expentancy less than 1 year.
• Unable to perform an adequate cardiopulmonary exersice test
• Previous treatment with digitalis or calcium channel blockers