A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF)

REHAB-HF: A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients, is a multicenter, randomized, attention-controlled, single-blind trial designed to examine the hypothesis that, in addition to standard care, a novel, tailored, progressive, multi-domain rehabilitation intervention administered to older patients with acute decompensated heart failure (ADHF) beginning early during hospitalization and continuing for 12 weeks will improve physical function and key clinical outcomes, including the rate of rehospitalization.

There will be three lead centers, Wake Forest Baptist Health along with Thomas Jefferson University and Hospital-Co-Investigator Dr. David Whellan, and Duke University Medical Center-Co-Investigator Dr. Christopher O'Connor. Each center may recruit up to 3 geographically close, tightly affiliated 'satellite' sites under their management and budgetary control. Together, these sites will recruit a total of 352 consenting patients ≥ 60 years old hospitalized with ADHF. Following informed consent and baseline testing, the participants will be randomized in a 1:1 fashion to receive a 12-week novel, progressive, multi-domain rehabilitation and exercise training intervention or attention control. The multi-domain rehabilitation intervention will include endurance, mobility, strength, and balance training and will be tailored based on participant performance in each of these domains. It will begin upon randomization during the hospitalization and will continue 3 times per week in an outpatient setting. Participants randomized to the attention control arm will receive all services ordered by their primary physician and will be contacted bi-weekly by study staff. All participants will undergo measures of physical function and quality of life at baseline, 1 month, and 3 months. Clinical events will be monitored for 6 months following the index hospitalization.

The Short Physical Performance Battery is scored on a scale of 0-12, with a higher score indicating better physical function.

Exploratory outcome. Frailty is assessed by the Fried criteria consisting of 5 components: low physical activity, exhaustion, weakness, slowness, and unintentional weight loss. Presence of 3 or more Fried criteria indicates frailty, 1-2 criteria indicates pre-frailty, and 0 criteria indicates no frailty.

Exploratory outcome. The KCCQ Overall Summary Summary Score is a heart failure disease-specific quality of life measure encompassing domains of physical limitation, HF symptoms, quality of life, and social limitation scored on a scale of 0-100 with higher scores indicating better health status.

Exploratory outcome. The Physical Limitation Score of the KCCQ questionnaire is a subscore evaluating disease-specific physical limitation. Scores range 0-100 with a higher score indicating less physical limitation.

Exploratory outcome. The SF-12 is a quality of life assessment with 2 component scores (Physical Composite Score and Mental Composite Score) ranging 0-100 with higher scores indicating better health status.

Exploratory outcome. The EQ-5D-5L is a quality of life tool with 5 components designed to detect health utilities: mobility, usual activities, self-care, pain/discomfort, and anxiety/depression. All components are rated on a scale of 1-5 with higher scores indicating worse health status.

Exploratory outcome. The Geriatric Depression Scale is a 15-item questionnaire evaluating depressive symptoms. Scores range from 0-15 with a higher score indicating more severe depressive symptoms.

Exploratory outcome. The Montreal Cognitive Assessment is a tool for assessing multiple domains of cognitive function. Scores range 0-30 with higher scores indicating better cognitive function. A score greater than or equal to 26 is considered normal cognitive function.

Exploratory outcome. Number of all-cause rehospitalizations 1 month post index hospitalization discharge.

Exploratory outcome. Number of all-cause rehospitalizations 3 months after discharged from index hospitalization

Exploratory outcome. Combined number of all-cause rehospitalizations and death 6 months after discharge from index hospitalization

Exploratory outcome. Number of heart failure rehospitalizations 6 months after discharge from index hospitalization

Exploratory outcomes. Total days alive spent outside of hospital, observation unit, acute rehab setting, and skilled nursing facility 6 months after discharge from index hospitalization.

Exploratory outcome. Number of observation unit stays <24 hours 6 months after discharge from index hospitalization

Exploratory outcome. Number of unscheduled urgent medical visits after discharge from index hospitalization

Exploratory outcome. The global rank composite outcome combines non-commensurate endpoints including death, number of all-cause rehospitalizations, and month 3 SPPB into a single non-parametric outcome in a hierarchical manner with death being ranked first and SPPB being ranked last. Participants are ranked from the most adverse response (lowest rank) to the most favorable response (highest rank).

Exploratory outcome. Number of placements at skilled nursing facilities after discharge from index hospitalization.

Exploratory outcome. Physical activity assessed by accelerometry quantified in moderate-vigorous physical activity minutes per day.

Exploratory outcome. The Life Orientation Test-Revised is a assessment of generalized optimism scored on a scale of 0-24 with higher scores indicating higher optimism.

Assess direct medical costs, direct non-medical costs, indirect patient time costs, short-term cost-analysis, long-term cost analysis, and sustainability of the intervention.

Two well-accepted biomarkers of HF disease severity and prognosis, NT-proBNP and galectin-3, and increased biomarkers in older HF patients Tumor necrosis factor alpha, C-reactive protein, and interleukin-6.

Inclusion Criteria: Age ≥ 60 years old In the hospital setting >24 hours for the management of ADHF, or diagnosed with ADHF after being hospitalized for another reason. ADHF will be confirmed by the study physician, and will be defined according to the Food and Drug Administration definition of hospitalized heart failure as a combination of symptoms, signs, and HF-specific medical treatments. Exclusion Criteria: Acute myocardial infarction Planned discharge other than to home or a facility where the participant will live independently Already actively participating in formal, facility-based cardiac rehabilitation

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Peters AE, Kitzman DW, Chen H, Nelson MB, Pastva AM, Duncan PW, Reeves GR, Upadhya B, Whellan DJ, Mentz RJ. Obesity Status and Physical Rehabilitation in Older Patients Hospitalized With Acute HF: Insights From REHAB-HF. JACC Heart Fail. 2022 Dec;10(12):918-927. doi: 10.1016/j.jchf.2022.07.008. Epub 2022 Sep 7.

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Reeves GR, Whellan DJ, O'Connor CM, Duncan P, Eggebeen JD, Morgan TM, Hewston LA, Pastva A, Patel MJ, Kitzman DW. A Novel Rehabilitation Intervention for Older Patients With Acute Decompensated Heart Failure: The REHAB-HF Pilot Study. JACC Heart Fail. 2017 May;5(5):359-366. doi: 10.1016/j.jchf.2016.12.019. Epub 2017 Mar 8.