Chronotropic Incompetence, Heart Failure With Normal Ejection Fraction
Conditions
Keywords
Heart failure with preserved ejection fraction, Chronotropic incompetence, Functional capacity, Quality of life
Brief summary
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
Detailed description
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.
Interventions
DRUGControlled withdrawal of beta-blockers
Controlled withdrawal of previos doses of beta-blockers after diagnosis of chronotropic incompetence
DIAGNOSTIC_TESTCardiopulmonary Exercise Testing
Cardiopulmonary Exercise Testing to evaluate the chronotropic incompetence and the primary endpoint (functional capacity)
Sponsors
Fundación para la Investigación del Hospital Clínico de Valencia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Masking description
The examination tests will be performed by two blinded cardiologist to patients' allocation group
Intervention model description
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 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal functional capacity | The change in peak oxygen consumption will be measured at baseline, at 15-day and at 30-day | 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 . |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cognitive evaluation | The change in MMSE score will be measured at baseline, at 15-day and at 30-day | 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. |
| Quality of life evaluation | The change in MLHFQ score will be measured at baseline, at 15-day and at 30-day | 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 |
| Security: reporting on potential clinical adverse outcomes | Differences in the composite of adverse events between both arms will be measured at 15-day , at 30-day and 180-day | 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 |
Countries
Spain
Outcome results
None listed