Clinical trial NCT02275819: Exercise Training in Heart Failure: Changes in Cardiac Structure and Function
Official title: Exercise Training in Heart Failure: Structural and Functional Cardiac Remodeling
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Failure
Keywords: Heart Failure
Exercise
Echocardiography
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2014-10-27
Enrollment: 11
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Non-randomized case control study with two groups. One group received exercise and the controls did not.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Left Ventricular Systolic Function.
timeFrame: Baseline and endpoint at 3-5 months
measure: Change in Left Ventricular Structure.
timeFrame: Baseline and endpoint at 3-5 months
measure: Change in Diastolic Function.
timeFrame: Baseline and endpoint at 3-5 months
measure: Change in Left Ventricular (LV) Diastolic Function
timeFrame: Baseline and endpoint at 3-5 months
measure: Change in Right Ventricular Function
timeFrame: Baseline and endpoint at 3-5 months
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
state: Massachusetts
Study officials:
affiliation: VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA
name: Jayashri Aragam, MD
role: PRINCIPAL_INVESTIGATOR
References: