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

Fundación para la Investigación del Hospital Clínico de Valencia52 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Heart Failure With Normal Ejection Fraction

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Maximal functional capacity

Maximal functional capacity measured by peak oxygen consumption in the cardiopulmonary exercise testing (CPET). The peak oxygen consumption is expressed in mL/kg/min.The investigators will measure the change of peak oxygen consumption .

Time frame: The change in peak oxygen consumption will be measured at baseline, at 15-day and at 30-day

Secondary Outcomes

Cognitive evaluation

We will asses the cognitive function by Mini Mental State Examination (MMSE) The MMSE is a cognitive test. The score is ranged from 0-30 (units of a scale). 30 points is the better outcome. The investigators will assess the change in the score.

Time frame: The change in MMSE score will be measured at baseline, at 15-day and at 30-day

Cognitive evaluation

We will asses the cognitive function by Montreal Cognitive Assessment (MoCa) The MoCa is a cognitive test. The score is ranged from 0-30 (units of a scale). 30 points is the better outcome. The investigators will assess the change in the score.

Time frame: The change in MoCa score will be measured at baseline, at 15-day and at 30-day

Quality of life evaluation

We will asses the quality of life by Minnesota living with heart failure questionnaire (MLHFQ). The MLHFQ is a quality of life questionnarie .The investigators will asses the changes in the full questionnarie. We will report the total score. The score is ranged from 0-105. 105 points is the worse outcome

Time frame: The change in MLHFQ score will be measured at baseline, at 15-day and at 30-day

Security: reporting on potential clinical adverse outcomes

Evaluation of adverse clinical outcomes during the study. The investigators will evaluate the composite of the following adverse events: mortality and/or readmissions due to cardiovascular reasons. The investigators will assess differences between both groups/arms

Time frame: Differences in the composite of adverse events between both arms will be measured at 15-day , at 30-day and 180-day