Exercise Training in Heart Failure: Changes in Cardiac Structure and Function

Exercise Training in Heart Failure: Structural and Functional Cardiac Remodeling

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02275819

Enrollment

Registered

2014-10-27

Start date

2016-06-06

Completion date

2019-04-23

Last updated

2021-03-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart Failure

Keywords

Heart Failure, Exercise, Echocardiography

Brief summary

This is a research study being conducted to better understand the impact of exercise training on changes on the structure and function of the heart. Exercise training in patients with heart failure has been shown to be beneficial at decreasing symptoms of heart failure and improving overall functional capacity or capacity to exercise. However the mechanisms responsible for this are still unclear. This study will look specifically at how exercise creates changes within the hearts filling ability, the hearts pumping strength as well as the hearts ability to rebuild.

Detailed description

Prevalence of systolic heart failure (HF) is high among the growing population of older adults. Progressive cardiac remodeling and deteriorating cardiac output have been implicated as key factors underlying HF-related exercise intolerance and quality of life. Even after implementing medical and device therapies that moderate remodeling, exercise tolerance remains impaired. While exercise training has been demonstrated to improve exercise capacity, mechanisms facilitating this benefit remain unclear. Peripheral adaptations in the skeletal muscle and vasculature provide at least some benefit, however reverse cardiac remodeling (beyond effects of pharmacological and device therapies) may be additive. The investigators propose to study the impact of 2 different types of exercise on cardiac morphology as well as systolic and diastolic performance and related functional gains. The investigators will compare traditional aerobic training to a novel regimen of inspiratory muscle training (IMT). IMT is a specific type of exercise training that may be particularly useful for frail, infirmed HF patients who are unlikely to tolerate aerobic training. Effects of IMT on remodeling have not been previously studied. The proposed echocardiography pilot study builds on a funded VA Merit F0834-R Exercise Therapy to Reduce Heart Failure Symptoms; Sorting Mechanisms of Benefit (Exercise therapy) PI, Forman that compares different modes of exercise training in older (age 50yrs) systolic (EF 45%) HF patients. The original study assesses peripheral mechanisms affected by exercise training, but was not designed to assess cardiac remodeling. The proposed pilot study provides a vital complementary analysis, i.e., it adds assessments of cardiac remodeling as well as related changes in systolic and diastolic performance.

Interventions

OTHERExercise

Exercise (walking 3 times a week for 60 minutes) or Inspiratory Muscle Therapy (breathing against an inspiratory resistive load 3 times a week for up to 60 minutes)

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Non-randomized case control study with two groups. One group received exercise and the controls did not.

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

Inclusion criteria

* New York Heart Association (NYHA) class II or III for the previous three months despite a minimum of 6 weeks of optimal treatment. * Age \>50 years. * Left Ventricular Ejection Fraction (LVEF)\<45% (by echocardiogram or radionucleotide imaging study within 6 months of enrollment). If a patient has initiated or received any therapy that might improve the ejection fraction, the qualifying EF must be assessed after the patient is on a stable dose of these therapies. Additionally the LVEF of \<45% will be confirmed with a brief echocardiogram prior to randomization. If LVEF is not 45%, the patient will not be enrolled in to the study. * Optimal therapy according to the American Heart Association (AHA)/American College of Cardiology (ACC) and the Heart Failure Society of America (HFSA) Heart Failure (HF) guidelines, including treatment with an angiotensin-converting-enzyme (ACE) Inhibitor (or an angiotensin receptor blocker) and beta-blocker therapy (for at least 6 weeks), or have documented reason for variation, including medication intolerance, contraindication, patient preference, or personal physician's judgment. In addition to the above we have now added patients with heart failure with preserved ejection fraction (similar to the parent study )pending Institutional Review Board (IRB) review.

Exclusion criteria

* Major cardiovascular event or procedure within the prior 6 weeks. * Dementia. * Severe chronic obstructive pulmonary disease (COPD) (FEV1\<50%), peripheral vascular disease (PVD), and/or Anemia. * End-stage malignancy. * Severe valvular heart disease. * Orthopedic exercise limitation. * Women who are pregnant, breastfeeding, or likely to become pregnant within the next 6 months. * Psychiatric hospitalization within the last 3 months. * Implantable Cardioverter Defibrillator (ICD) device with heart rate limits that prohibit exercise assessments or exercise training. Referring physicians will be provided with an opportunity to reprogram devices so that patients can participate. * Chronic ethyl alcohol (ETOH) or drug dependency.

Design outcomes

Primary

Measure	Time frame	Description
Change in Left Ventricular Systolic Function.	Baseline and endpoint at 3-5 months	Change in left ventricular ejection fraction.
Change in Left Ventricular Structure.	Baseline and endpoint at 3-5 months	Change in left ventricular mass.
Change in Diastolic Function.	Baseline and endpoint at 3-5 months	Change in mitral annular early diastolic velocity (e')
Change in Left Ventricular (LV) Diastolic Function	Baseline and endpoint at 3-5 months	Change in the ratio of early mitral in-flow velocity (E) to mitral annular early diastolic velocity (e')
Change in Right Ventricular Function	Baseline and endpoint at 3-5 months	Change in tricuspid annular tissue doppler velocity

Countries

United States

Participant flow

Recruitment details

Recruitment occurred at VA Boston Healthcare System cardiology related clinics from 6/6/2016 to 12/21/2018. As per the protocol the recruitment was supposed to begin in 2014. Unfortunately there were a number of issues including the fact that the parent study moved to Pittsburgh and we were not able to start recruitment till 2016.

Pre-assignment details

13 participants were consented but only 11 were enrolled. Two were excluded from randomization due to subsequent echocardiogram or pulmonary function screening not meeting enrollment criteria. One was withdrawn after enrollment due to increasing symptoms of heart failure. Due to the small number of participants enrolled in each of the active intervention arms we combined participants from both intervention groups and analyzed against the controls.

Participants by arm

Arm	Count
Control Will not receive intervention with exercise	5
Intervention Group 2 groups will receive 2 different types of exercise	5
Total	10

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	1

Baseline characteristics

Characteristic	Total	Control	Intervention Group
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	6 Participants	3 Participants	3 Participants
Age, Categorical Between 18 and 65 years	4 Participants	2 Participants	2 Participants
Age, Continuous	68.4 years STANDARD_DEVIATION 6.4	69.6 years STANDARD_DEVIATION 8.4	67.2 years STANDARD_DEVIATION 4.4
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	2 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	8 Participants	4 Participants	4 Participants
Region of Enrollment United States	10 Participants	5 Participants	5 Participants
Sex: Female, Male Female	0 Participants	0 Participants	0 Participants
Sex: Female, Male Male	10 Participants	5 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 5	0 / 5
other Total, other adverse events	0 / 5	1 / 5
serious Total, serious adverse events	0 / 5	4 / 5