Cardiac Rehab Effects in HFpEF

Efficacy of Exercise Training in Patients With HFpEF

This research in Veterans with heart failure with preserved ejection fraction (HFpEF) will provide new information on the mechanisms determining the patients' exercise intolerance and the efficacy of regular physical activity to improve this shortcoming by alleviating the patients' neurocirculatory abnormalities. Specifically, the investigators will focus on the role of nerves originating in working limb muscles in determining the patients' exercise intolerance and compromised fatigue resistance before and after a chronic exercise intervention. By focusing on a specific mechanism, this project will evaluate the validity of exercise as an alternative treatment strategy with the overall purpose of improving the quality of life of Veterans with HFpEF.

Study Overview

• Status: Active, not recruiting
• Conditions: Heart Failure With Preserved Ejection Fraction
• Intervention / Treatment: Procedure: Afferent block

Detailed Description

Patients with heart failure with preserved ejection fraction (HFpEF) are characterized by exercise intolerance and premature fatigue during physical activity. An abnormal exercise pressor reflex mediated by neural feedback from mechano- and/or metabosensitive group III and IV muscle afferents may contribute to these debilitating symptoms. However, little is known about the role and relative contribution of group III/IV afferents in circulatory control and fatigue development in patients with HFpEF. By studying both patients with HFpEF and well-matched controls, the investigators will evaluate the contribution of these muscle afferents to circulatory control and fatigue development, factors recognized to be major contributors to exercise intolerance. The investigators will use lumbar intrathecal fentanyl to block the central projection of group III/IV muscle afferents during voluntary and passive exercise (no concomitant effect on feedforward drive). This proven approach will enable us to evaluate, and distinguish between, the effects of group III and IV muscle afferents on central and peripheral hemodynamics during exercise, the exercise-induced development of central and peripheral fatigue (femoral nerve stimulation techniques), and on exercise tolerance. The investigators will also study muscle morphometry, baroreflex and chemoreflex sensitivity, and investigate intramuscular metabolic changes of the quadriceps during exercise using 31phosphorus magnetic resonance spectroscopy to evaluate disease-related alterations in cardiovascular reflex sensitivity and intrinsic muscle characteristics as a potential factor determining alterations in circulatory control and fatigue resistance in patients with HFpEF. Finally, the investigators will repeat these studies after a supervised 12-week knee-extension exercise training program, allowing us to investigate the effect of chronic exercise on the role of group III/IV muscle afferents in the hemodynamic response to exercise, the development of fatigue, and, ultimately, exercise tolerance. If this project confirms a significant contribution of group III/IV muscle afferents to the exercise intolerance exhibited by patients with HFpEF, and that chronic exercise can alleviate these impairments, the proposed work will provide the scientific basis for a paradigm shift in the treatment of this growing population.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84148-0001
      • VA Salt Lake City Health Care System, Salt Lake City, UT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• heart failure with preserved ejection fraction

Exclusion Criteria:

• heart failure with reduced ejection fraction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Afferent effect on hemodynamics; Evaluate impact of group III/IV muscle afferents on femoral blood flow	Procedure: Afferent block; Block sensory feedback to evaluate hemodynamic and fatigue consequence of group III/IV muscle afferents
Experimental: Afferent effect on fatigue; Evaluate impact of group III/IV muscle afferents on exercise-induced changes in quadriceps twitch force	Procedure: Afferent block; Block sensory feedback to evaluate hemodynamic and fatigue consequence of group III/IV muscle afferents
Experimental: Effect of cardiac rehab; Evaluate effect of chronic exercise on influence of muscle afferents on limb blood flow	Procedure: Afferent block; Block sensory feedback to evaluate hemodynamic and fatigue consequence of group III/IV muscle afferents

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
femoral blood flow	Quantifying femoral blood flow during exercise with and without afferent blockade	1 hour

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
femoral blood flow	Impact of cardiac rehab on the influence of afferent blockade on femoral blood flow	12 weeks

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Markus Amann, PhD, VA Salt Lake City Health Care System, Salt Lake City, UT

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2022
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: August 6, 2020
• First Submitted That Met QC Criteria: August 6, 2020
• First Posted (Actual): August 10, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: E3343-R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No