Physiologic Accelerated Pacing as a Treatment in Patients With Heart Failure With Preserved Ejection Fraction

Heart Failure, Diastolic Clinical Trial

— PACE HFpEF  

Official title:

Physiologic Accelerated Pacing as a Treatment in Patients With Heart Failure With Preserved Ejection Fraction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04546555
• Other study ID #: 00000988
• Status: Completed
• Phase: N/A
• Start date: February 23, 2021
• Est. completion date: May 25, 2023

Study information

• Verified date: July 2023
• Source: University of Vermont
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: May 25, 2023
• Est. primary completion date: May 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure, Diastolic

Intervention

Device:
• Dual chamber pacemaker
Dual chamber pacemaker implantation with Bachmann's bundle lead and His bundle lead placement.

Other:
• Accelerated Physiologic Pacing
The lower rate limit will be programmed to an individualized heart rate.
• Nocturnal Pacing
In addition to adjustment of the lower rate limit to an individualized heart rate, nocturnal pacing a moderate HR elevation of 110bpm will be implemented between 8pm and 6am.

Locations

Country	Name	City	State
United States	University of Vermont Medical Center	Burlington	Vermont

Sponsors (2)

Lead Sponsor	Collaborator
Daniel L Lustgarten	Medtronic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Quantitative assessment of the risks of pacemaker implantation	Incidence of pocket hematoma, pocket infection phrenic or diaphragmatic stimulation, lead endocarditis, lead dysfunction/dislocation, pneumothorax, hemopericardium, mortality	1 month
Other	Doubling in baseline Troponin or NTproBNP		At 1 month, 2 months, 3 months, 4 months and 5 months
Other	>= 25% increase in systolic blood pressure		At 1 month, 2 months, 3 months, 4 months and 5 months
Primary	Change in composite Minnesota-Living-with-Heart-Failure-Questionnaire score	Total score can range from 0 to 105, with higher scores indicating more significant impairment in health-related quality of life	At 1 month, 2 months, 3 months, 4 months and 5 months
Primary	Percent change in NTproBNP		At 1 month, 2 months, 3 months, 4 months and 5 months
Secondary	Change in 6 minute walk test		At 1 month, 2 months, 3 months, 4 months and 5 months
Secondary	Incident AF		At 1 month, 2 months, 3 months, 4 months and 5 months
Secondary	Burden of AF		At 1 month, 2 months, 3 months, 4 months and 5 months
Secondary	Hemodynamic changes by Echo		At 3 months and at 5 months
Secondary	Change in left ventricular mass/volume ratio by cardiac MRI		5 months