Exercise Lower-body Negative Pressure in Heart Failure With Preserved Ejection Fraction

NCT05582044 | Recruiting DMC

• 1 other identifier: H22-01882
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The heart is a pump that must both fill and empty effectively to move blood; if it cannot move enough, heart failure may ensue. Approximately half of all adults living with heart failure have a form where the heart stiffens, which impairs its ability to fill. This form of heart failure particularly affects females and older adults. When people exercise, extra blood returns to the heart. The healthy heart can easily fill and move this extra blood to the muscles. However, when the heart's ability to fill is impaired, the extra blood can back up and pool in the lungs. Blood pooling in the lungs makes people feel breathless, although the investigators do not fully understand why, and this form of heart failure has a high risk of hospitalization and death, but few effective treatments are available. Exercise is one of the few treatments that works well if enough exercise is performed regularly. However, many people with this form of heart failure can only tolerate a small amount before stopping due to severe breathlessness, which can put them off from exercising regularly. The study's goal is to help these people perform more exercise. The investigators will use a novel form of stationary cycling with a plastic chamber around the lower body that seals at the waist. The chamber can apply suction to the lower body during exercise which will reduce how much extra blood returns and prevent the heart and lungs from being overloaded. Participants will attend 5 visits, including 3 where they will perform a submaximal exercise test for as many minutes as possible with or without light suction. In each of these tests, the investigators will record how long they exercise and ask them to rate how breathless they feel. The investigators will also study their breathing pattern, using a mouthpiece and pressure sensor, and heart function, using ultrasound imaging. This work will help adults living with heart failure exercise more and improve their health, and help researchers understand what causes breathlessness and develop new treatments.

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

Heart Failure; Diastolic Dysfunction; Exercise Intolerance; Dyspnea; Pulmonary Congestion; Pulmonary Hemodynamics

Outcome Measures

Primary Outcomes (1)

• Time to exercise limitation (Tlim)

  Exercise will be performed to exhaustion or symptom limitation, and the Tlim will be recorded at the time of cessation to the second

  Within 30 minutes of exercise onset

Secondary Outcomes (1)

• Dyspnea intensity and unpleasantness

  Within 30 minutes of exercise onset

Other Outcomes (3)

• Left ventricular stroke volume

  Within 30 minutes of exercise onset

• Left ventricular filling pressure

  Within 30 minutes of exercise onset

• Dynamic lung compliance

  Within 30 minutes of exercise onset

Study Arms (2)

Heart Failure with Preserved Ejection Fraction (40 Participants)

EXPERIMENTAL

Lower-body negative pressure (-15 and -25 mmHg) and neutral pressure (0 mmHg)

Other: Lower-body Negative Pressure (-25 mmHg); Other: Lower-body Negative Pressure (-15 mmHg); Other: Lower-body Neutral Pressure (0 mmHg)

Healthy Controls (20 Participants)

ACTIVE COMPARATOR

Lower-body negative pressure (-15 and -25 mmHg) and neutral pressure (0 mmHg)

Other: Lower-body Negative Pressure (-25 mmHg); Other: Lower-body Negative Pressure (-15 mmHg); Other: Lower-body Neutral Pressure (0 mmHg)

Interventions

Lower-body Negative Pressure (-25 mmHg) OTHER

The LBNP chamber will be sealed at the waist prior to Control measures, and the vacuum system will be activated to coincide with the onset of exercise, applying -25mmHg LBNP.

Healthy Controls (20 Participants); Heart Failure with Preserved Ejection Fraction (40 Participants)

Lower-body Negative Pressure (-15 mmHg) OTHER

The LBNP chamber will be sealed at the waist prior to Control measures, and the vacuum system will be activated to coincide with the onset of exercise, applying -15mmHg LBNP.

Healthy Controls (20 Participants); Heart Failure with Preserved Ejection Fraction (40 Participants)

Lower-body Neutral Pressure (0 mmHg) OTHER

In this placebo trial, the LBNP chamber will be sealed at the waist prior to Control measures, and the vacuum system will be activated to coincide with the onset of exercise, but the chamber will be vented to atmosphere.

Healthy Controls (20 Participants); Heart Failure with Preserved Ejection Fraction (40 Participants)

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults with a clinical diagnosis of HFpEF (LV ejection fraction ≥50%) measured in the year prior to Visit 1 (and confirmed at Visit 1), who are New York Heart Association Functional Class II-III (mild-moderate symptoms), ambulatory, receiving guideline-directed medical therapy unchanged for ≥2 months, and clinically stable for ≥3 months.
• Symptom(s) of heart failure requiring treatment within the year prior to Visit 1
• NT-proBNP \>50 pmol/L (sinus rhythm) or \>150 pmol/L (atrial fibrillation in year prior)
• Diastolic dysfunction based on at least one of the following echocardiographic findings:
• Left atrial enlargement (diameter \>4 cm or volume index \>28 mL/m2); or
• e' \<10 cm/s (lateral) or \<8 cm/s (septal), or
• E/e' \>10 (lateral), or \>15 (septal)
• \- Healthy sedentary or recreationally active adults from the community

You may not qualify if:

• Any prior measurement demonstrated LV ejection fraction ≤40%
• Primary pulmonary, metabolic, renal, hepatic, neuromuscular, or malignant disease
• Primary pulmonary vascular, complex congenital, or \> mild valvular heart disease
• Documented infiltrative cardiomyopathy
• Documented valvular or coronary disease requiring intervention
• Myocarditis, pericardial effusion, acute coronary syndrome, or revascularization in the last 3 months
• Resting seated systolic blood pressure \>160 mmHg or \<100 mmHg
• Jugular venous pressure \>12 cm
• Inferior vena cava \>2 cm with no inspiratory collapse, or severe right ventricular dysfunction by echo
• Ambulatory supplemental oxygen
• Current or recent participation in \>150 min. per week of moderate intensity exercise
• Current or recent (within the past 6 months) smoking
• Body mass index \>35 kg/m2
• Contraindication to exercise or otherwise unable to perform cycle ergometry
• Poor echocardiographic imaging windows

Sponsors & Collaborators

• University of British Columbia: lead

Study Sites (1)

University of British Columbia

Kelowna, British Columbia, V1V1V7, Canada

RECRUITING

MeSH Terms

Conditions

Heart Failure; Dyspnea

Interventions

Lower Body Negative Pressure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Decompression; Therapeutics

Study Officials

• Neil D Eves, PhD

  The University of British Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stephen P Wright, PhD

CONTACT

(250) 807-8860; stephen.wright@ubc.ca

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Double-blind; participants and outcome assessors are blinded to the intervention until data entry and analysis are completed
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Model Details: Double-blind, placebo-controlled with randomized repeated measures

Study Record Dates

• First Submitted: October 12, 2022
• First Posted: October 17, 2022
• Study Start: January 25, 2023
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: April 4, 2025

Record last verified: 2025-04

Locations

CA (1)