Effects of Atrial Rate-adaptive Pacing on Exercise Capacity in Patients With Chronic Heart Failure Complicated by Chronotropic Incompetence

Study Overview
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Brief Summary
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Chronotropic incompetence consists of an insufficient increase in heart rate during effort, and its presence is recognized as a common feature in patients with heart failure due to left ventricular systolic dysfunction, apparently suggesting a worse prognosis. Little is known about the possible benefits of its reversal in such patients. The investigators working hypothesis is that the modulation of chronotropic response, as obtained by means of atrial rate-adaptive pacing may improve functional capacity in persons with chronic heart failure and chronotropic incompetence. To explore this hypothesis,the investigators will enroll 20 patients with NYHA II/III heart failure, low left ventricular ejection fraction (<40%) and chronotropic incompetence (Maximal heart rate <80% of predicted value in a symptom-limited incremental test), who already underwent implantation of dual-chamber implantable defibrillator for prevention of sudden cardiac death. The study will have a randomized, double-blind, cross-over design. The procedures, to be carried out at one month from each reprogramming (VVI backup pacing vs. AAI-R active pacing), will comprise: blood sampling for NT-proBNP, incremental symptom-limited cardiopulmonary exercise testing (CPX), constant-workload cardiopulmonary test (50% of max WR), quality-of-life questionnaire, 24-hour ECG monitoring. The primary end-point will be peak oxygen consumption on CPX. Secondary end-points will include acute response to reprogramming, and data derived from constant-WR tests, Holter monitoring and QoL.

Official Title
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Effects of Atrial Rate-adaptive Pacing on Exercise Capacity in Patients With Chronic Heart Failure Complicated by Chronotropic Incompetence

Conditions
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Heart Failure, Exercise Tolerance

Intervention / Treatment
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* Other: Rate-adaptive pacemaker programming
* Other: VVI at 40 bpm


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NYHA II/III chronic heart failure on optimal medical therapy Sinus Rhythm Left ventricular ejection fraction less than 40 % Chronotropic incompetence on maximal exercise testing (maximum heart rate < 80% of predicted value) Age 18-75 carrier of dual chamber ICD device Informed Consent Exclusion criteria: Unable to perform cardiopulmonary exercise testing (for any reason) Absolute contraindication to maximal exercise testing Moderate to severe anemia (Hb<10 g/dL) Diagnosis of Sick Sinus Syndrome or high-degree atrioventricular block recent hospitalization for acute decompensated heart failure (<1 month) recent acute coronary syndrome (<3 months) Active neoplastic disease Active myocarditis / endocarditis Acute decompensated heart failure during study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rate adaptive<br>Patients will have their ICD programmed in a AAI-R mode, with peak atrial rate set at 85% of age-adjusted predicted maximal HR | Other: Rate-adaptive pacemaker programming<br>* The ICD will be programmed in a AAI-R mode, with peak atrial stimulation rate set at 85% of maximal predicted heart rate, and ongoing protection VVI backup at 40 bpm<br>|
| Active Comparator: Control<br>ICDs will be programmed in the usual VVI backup pacing mode at 40 bpm | Other: VVI at 40 bpm<br>* ICDs will be programmed in VVI mode at 40 bpm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Oxygen consumption on cardiopulmonary exercise testing |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Heart Rate on Cardiopulmonary exercise testing |  | 1 month | 
| Quality of life as assessed by Minnesota Living with Heart Failure and SF-36 Questionnaires |  | 1 month | 
| Heart Rate Variability on Holter Monitoring |  | 1 month | 
| Acute Change in Peak Oxygen Consumption after reprogrammation |  | 1 hour | 
| NT-proBNP levels |  | 1 Month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac pacing, heart failure, oxygen consumption, ventricular dysfunction, left, exercise tolerance, chronotropic incompetence, pacemaker programming