Precision Rehabilitation for Veterans With (HFpEF)

Small studies have suggested that supervised exercise training improves cardiorespiratory fitness (CRF) in some patients with heart failure with preserved ejection fraction (HFpEF), but the response rate to exercise is broad, and the impact of exercise on quality of life and physical functioning at the Veteran level are incompletely understood. More recently, HFpEF patients randomized to moderate levels of exercise (moderate continuous training; MCT) increased VO2Peak, the quatitative measure of CRF) but not to the very aggressive level specified by the study. As such, the findings were considered statistically insignificant. To address the clinical question utilizing accepted targets, fill the scientific gaps, and advance the understanding of how monitored exercise improves both HFpEF severity and the lives of Veterans with HFpEF, an adequately powered study is required to assess the role of MCT for improving CRF, HF symptoms, QOL, physical functioning, and myocardial structure and function. Identifying patients at baseline likely to respond to MCT is the subject of the second aim and will be important for maximizing VA resources and delivering timely and effective care to veterans with HFpEF. The investigators plan to enroll 4 patients to provide preliminary and feasibility data to refine the protocol for the intended study, a request of the review committee who have favorably scored the MERIT proposal.

The long-term strategy is to improve exercise tolerance and functional capacity of HFpEF patients by favorably altering cardiac structure and function and the microRNA signature driving myocardial fibrosis. The investigators intend to conduct a larger study to test the central hypothesis that monitored exercise training improves CRF, HF symptoms, QOL, and functional status in veterans with HFpEF and that the expression pattern of miRs critical for regulating fibrosis (miR-,-21,-29,-133) can identify HFpEF patients responsive to exercise training when integrated into a comprehensive predictive tool incorporating clinical characteristics along with sensitive echocardiographic measures of LV diastolic function. This project will provide feasibility and preliminary data in 4 patients for the future study.

Inclusion criteria

• New York Heart Association Class II or III HF symptoms
• History of hypertension
• EF≥50%
• LVH confirmed by echocardiography, Cardiac CT, or Cardiac MR
• Diastolic dysfunction which must include ≥2 of the following:

• Average E/e'>14
• Septal e'<7 cm/s or Lateral e' <10 cm/s
• TR velocity> 2.8 m/s
• LA computed volume index >34 mL/M2
• PCWP or LVEDP>15
• Ability to participate in an exercise program as determined by a research, cardiology, or primary care provider

Exclusion criteria

• Ejection Fraction < 50%
• Absence of LVH
• LV Dilation (LV end diastolic volume indexed to BSA > 75 ml/m2)
• Any Segmental wall motion abnormality
• Acute ST segment elevation myocardial infarction (STEMI)
• Significant valvular or other non-coronary heart disease
• Any non-cardiac disease or condition that could influence myocardial function (e.g., collagen-vascular disease, history of cardiotoxic cancer chemotherapy, amyloid)
• Anemia defined as Hgb < 11.0 g/dl in males, 10 g/dl in females
• Current accelerating angina, unstable angina, angina at rest, or NSTEMI within 3 months
• Chronic pulmonary disease requiring home oxygen or steroid therapy
• Significant non-CV organ disease: Chronic hepatic or renal disease (eGFR < 25 mL/min/1.73m2)
• Inability to provide informed consent
• Inability to perform exercise