Personalized Pacing: A New Paradigm for Patients With Diastolic Dysfunction or Heart Failure With Preserved Ejection Fraction

Study Overview
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Brief Summary
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Recent exploratory studies suggest that pacemaker patients with diastolic dysfunction (DD) or heart failure with preserved ejection fraction (HFpEF) may benefit from a higher backup heart rate (HR) setting than the factory setting of 60 beats per minute (bpm). In this prospective double-blinded randomized controlled study, pacemaker patients with DD or overt HFpEF and either 1) intrinsic ventricular conduction or 2) conduction system or biventricular pacing will be enrolled and randomized to either a personalized lower HR setting (myPACE group, based on a height-based HR algorithm) or to the standard 60bpm backup setting (control group) for 1 year.

Official Title
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Personalized Pacing: A New Paradigm for Patients With Diastolic Dysfunction or Heart Failure With Preserved Ejection Fraction

Conditions
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Pacemaker, Diastolic Dysfunction, Diastolic Heart Failure

Intervention / Treatment
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* Device: Adjustment of lower rate limit
* Device: Maintenance of lower rate limit


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Implanted pacemaker with either 1) intrinsic ventricular conduction or 2) conduction system or biventricular pacing or 3) RV pacing <2% and paced QRS duration <150ms Clinical evidence of heart failure with preserved ejection fraction or diastolic dysfunction, based on: dyspnea with exertion or NYHA Class ≥ II heart failure or pulmonary edema on prior chest imaging or documented on exam or is taking loop diuretics for heart failure or had NTproBNP >400 ng/ml in the last 24 months or a heart failure hospitalization in the last 2 years or has diastolic dysfunction on echo or has left ventricular hypertrophy on echo or has left atrial (LA) dilation (LA volume/BSA index >28ml/m2) Exclusion Criteria: Left ventricular ejection fraction < 50% Life expectancy < 12 months Symptomatic pulmonary disease on home oxygen Uncontrolled hypertension as defined by blood pressure >160/100 mmHg on two checks ≥15 minutes apart Hypertrophic cardiomyopathy More than moderate valvular disease Aortic valve replacement < 1 year Angina pectoris Creatinine > 2 Hemoglobin < 8 g/dL Participation in another clinical trial or registry study Inability to follow up for regularly scheduled pacemaker appointments or to follow up for this study Pregnant patients or patients of childbearing age without reliable contraceptive agent (intra-uterine device, birth control implant, compliance with contraception injections or contraception pills) for the duration of study participation

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Interventional Model Description: Patients are randomized to either a personalized pacemaker lower heart rate setting based on a resting heart rate algorithm or to the conventional pacemaker lower rate setting of 60bpm.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lower rate set to a higher, personalized backup heart rate (myPACE)<br>Patients randomized to this group will have their pacemaker lower heart rate setting programmed to a personalized lower rate based on a resting heart rate algorithm. | Device: Adjustment of lower rate limit<br>* Patients with preserved ejection fraction (EF >50%) and implanted pacemakers will have the lower rate limit adjusted to a personalized heart rate based on a heart rate algorithm.<br>|
| Active Comparator: Lower rate left at 60 beats-per-minute<br>Patients randomized to this group will have their pacemaker lower heart rate setting left at or programmed to the conventional pacemaker lower rate setting of 60bpm. | Device: Maintenance of lower rate limit<br>* Lower rate limit will be maintained at 60 beats-per-minute<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minnesota Living with Heart Failure Questionnaire Score | Change in score from baseline (at enrollment) to 1 month and 12 months after enrollment. | Baseline, 1 month, and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| NTproBNP | Change in NTproBNP level from baseline to 1 month | Baseline, 1 month | 
| Hospitalization or invasive outpatient intervention for heart failure |  | At 12 months | 
| Atrial Arrhythmia Burden | On pacemaker reports | At 12 months | 
| Loop diuretic initiation or up-titration |  | At 12 months | 
| Anti-arrhythmic initiation or up-titration |  | At 12 months | 
| Pacemaker-detected activity levels |  | At 12 months | 
| hospitalizations or invasive outpatient intervention for heart failure exacerbation, atrial tachyarrhythmias, cerebrovascular accident, or myocardial infarction |  | At 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart failure with preserved ejection fraction, Diastolic dysfunction, Resting heart rate, Personalized, Lower rate setting