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

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.

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.

- 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 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.