Clinical trial NCT04546555: Physiologic Accelerated Pacing as a Treatment in Patients With Heart Failure With Preserved Ejection Fraction
Official title: Physiologic Accelerated Pacing as a Treatment in Patients With Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure, Diastolic
Keywords: Physiologic Pacing
His Bundle Pacing
Bachmann's Bundle Pacing
HFpEF
Lead sponsor: University of Vermont
Sponsor class: OTHER
Collaborators: name: Medtronic
First posted: 2020-09-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: Part I: Week 0-12: Quantify the effects of lower heart rate (HR) elevation on symptoms and function in patients with heart failure with preserved ejection fraction (HFpEF).

The investigators hypothesize that a personalized lower HR elevation employing physiological conduction system pacing in patients with HFpEF will decrease left atrial and left ventricular filling pressures. The investigators expect that this will result in a symptomatic and functional improvements and reduce NTproBNP levels. Additionally, HR elevation may have the potential to reduce the risk for heart failure hospitalization, atrial fibrillation (AF), and cerebrovascular stroke as these outcomes are increased in patients with a normal or preserved ejection fraction on HR lowering treatments.

After undergoing pacemaker implantation participants will be randomized to one out of three treatment arms (a) Bachmann's bundle pacing, (b) Bachmann's bundle and His bundle pacing, (c) no pacing with cross-over to alternative treatment arm at week 4 and 8, respectively. The lower pacing rate in arms a and b will be programmed to the personalized lower heart rate for 24 hours a day (the patient's intrinsic heart rate can exceed the personalized lower rate limit).

Part II: Week 13-20: Determine the effects of nocturnal heart rate elevation on symptoms and function in patients with HFpEF.

The investigators hypothesize that a moderate HR elevation to 110bpm delivered for 10 hours between 8PM to 6AM will provide additional hemodynamic benefits and will lead to beneficial ventricular remodeling.

After week 12 the participant will undergo randomization to one of two treatment arms (a) Bachmann's bundle and His bundle pacing, (b) Bachmann's bundle pacing, His bundle pacing and nocturnal pacing. The participant will cross-over to the other treatment arm after 4 weeks (study week 16).


Eligibility criteria: Inclusion Criteria:

* Left ventricular ejection fraction ≥ 55% (and diastolic volume \< 80ml/m2)
* Controlled blood pressure: average blood pressure \<130/80 mmHg on office visits in the last 30 days or on home blood pressure log or patient has completed up-titration of antihypertensive medications
* Heart failure hospitalization within the past 12 months OR Echocardiogram within the past 24 months that reported left ventricular hypertrophy AND an NTproBNP \>400 with at least one symptom of heart failure (dyspnea on exertion, orthopnea or paroxysmal nocturnal dyspnea) and at least one sign of heart failure in the past 12 months (pulmonary edema or pleural effusion on chest x-ray, lower extremity edema, jugular venous distention, rales).
* Study candidates are expected to remain available for follow-up visits.

Exclusion Criteria:

* Subject has an implanted cardiac pacemaker or defibrillator
* Life expectancy is less than 12 months
* Subject is unable or unwilling to perform the 6 Minute Walk Test and MLHFQ at all scheduled follow up visits
* Subject has any of the following: uncontrolled hypertension (average blood pressure of \>140/90 on office visits in the last 30 days or on home blood pressure log or actively undergoing uptitration of antihypertensive medication), more than moderate valvular disease, chronic hypoxic respiratory failure requiring supplemental oxygen, long-standing persistent atrial fibrillation
* Baseline ECG with non-LBBB morphology AND QRS \>150ms
* Subject is currently enrolled or planning to enroll in a potentially confounding trial during the course of the study

Primary outcomes:
measure: Change in composite Minnesota-Living-with-Heart-Failure-Questionnaire score
timeFrame: At 1 month, 2 months, 3 months, 4 months and 5 months
measure: Percent change in NTproBNP
timeFrame: At 1 month, 2 months, 3 months, 4 months and 5 months
Secondary outcomes:
measure: Change in 6 minute walk test
timeFrame: At 1 month, 2 months, 3 months, 4 months and 5 months
measure: Incident AF
timeFrame: At 1 month, 2 months, 3 months, 4 months and 5 months
measure: Burden of AF
timeFrame: At 1 month, 2 months, 3 months, 4 months and 5 months
measure: Hemodynamic changes by Echo
timeFrame: At 3 months and at 5 months
measure: Change in left ventricular mass/volume ratio by cardiac MRI
timeFrame: 5 months
Other outcomes:
measure: Quantitative assessment of the risks of pacemaker implantation
timeFrame: 1 month
measure: Doubling in baseline Troponin or NTproBNP
timeFrame: At 1 month, 2 months, 3 months, 4 months and 5 months
measure: >= 25% increase in systolic blood pressure
timeFrame: At 1 month, 2 months, 3 months, 4 months and 5 months
Locations:
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
Study officials:
References: