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Randomized Controlled Trial
. 2023 Feb 1;8(2):167-176.
doi: 10.1001/jamacardio.2022.4903.

Frailty and Effects of a Multidomain Physical Rehabilitation Intervention Among Older Patients Hospitalized for Acute Heart Failure: A Secondary Analysis of a Randomized Clinical Trial

Ambarish Pandey  1 , Dalane W Kitzman  2   3 , M Benjamin Nelson  2 , Amy M Pastva  4 , Pamela Duncan  5 , David J Whellan  6 , Robert J Mentz  7 , Haiying Chen  8 , Bharathi Upadhya  2 , Gordon R Reeves  9
Affiliations
Randomized Controlled Trial

Frailty and Effects of a Multidomain Physical Rehabilitation Intervention Among Older Patients Hospitalized for Acute Heart Failure: A Secondary Analysis of a Randomized Clinical Trial

Ambarish Pandey et al. JAMA Cardiol. .

Abstract

Importance: Frailty is common among older patients with acute decompensated heart failure (ADHF) and is associated with worse quality of life (QOL) and a higher risk of clinical events. Frailty can also limit recovery and response to interventions. In the Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial, a 3-month innovative, early, transitional, tailored, multidomain physical rehabilitation intervention improved physical function and QOL (vs usual care) in older patients with ADHF.

Objective: To evaluate whether baseline frailty modified the benefits of the physical rehabilitation intervention among patients with ADHF enrolled in the REHAB-HF trial and to assess the association between changes in frailty with the risk of adverse clinical outcomes on follow-up.

Design, setting, and participants: This prespecified secondary analysis of the REHAB-HF trial, a multicenter randomized clinical trial, included 337 patients 60 years and older hospitalized for ADHF. Patients were enrolled from September 17, 2014, through September 19, 2019. Participants were stratified across baseline frailty strata as assessed using modified Fried criteria. Data were analyzed from July 2021 to September 2022.

Interventions: Physical rehabilitation intervention or attention control.

Main outcomes and measures: Primary outcome was the Short Physical Performance Battery (SPPB) score at 3 months. Clinical outcomes included all-cause hospitalization or mortality at 6 months.

Results: This prespecified secondary analysis included 337 participants; 181 (53.7%) were female, 167 (49.6%) were Black, and the mean (SD) age was 72 (8) years. A total of 192 (57.0%) were frail and 145 (43.0%) were prefrail at baseline. A significant interaction was observed between baseline frailty status and the treatment arm for the primary trial end point of overall SPPB score, with a 2.6-fold larger improvement in SPPB with intervention among frail patients (2.1; 95% CI, 1.3-2.9) vs prefrail patients (0.8; 95% CI, -0.1 to 1.6; P for interaction = .03). Trends consistently favored a larger intervention effect size, with significant improvement among frail vs prefrail participants for 6-minute walk distance, QOL, and the geriatric depression score, but interactions did not achieve significance.

Conclusions and relevance: In this prespecified secondary analysis of the REHAB-HF trial, patients with ADHF with worse baseline frailty status had a more significant improvement in physical function in response to an innovative, early, transitional, tailored, multidomain physical rehabilitation intervention than those who were prefrail.

Trial registration: Clinical Trials.gov Identifier: NCT02196038.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Pandey has received research grant support from the National Institute on Aging, National Institute on Minority Health and Disparities, Gilead Sciences Research Scholar Program, Myovista, and Applied Therapeutics; personal fees from Tricog Health, Lilly, Rivus, Cytokinetics, Pieces Technologies, Palomarin, Emmi Solutions, and Roche Diagnostics; and nonfinancial support from Pfizer and Merck outside the submitted work. Dr Kitzman has received personal fees from Bayer, Merck, Medtronic, Relypsa, Corvia Medical, Boehringer Ingelheim, Novo Nordisk, AstraZeneca, Rivus, Pfizer, and Novartis as well as grants from Novartis, Bayer, Novo Nordisk, and AstraZeneca outside the submitted work and has stock ownership in Gilead Sciences. Dr Pastva reported receiving grants from the National Institute on Aging during the conduct of the study. Dr Duncan has received grant funding from the National Institute of Neurological Disorders and Stroke, Patient-Centered Outcomes Research Institute, and Agency for Healthcare Research and Quality outside the submitted work; owns stock in Care Directions; is owner of Start UP; and has a patent with royalties paid from Kansas University Medical Center. Dr Whellan has received research support and consulting fees from Amgen, CVRx, Cytokinetics, Fibrogen, Novartis, and Novo Nordisk. Dr Mentz has received research support and personal fees from Abbott, American Regent, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Fast BioMedical, Gilead, Innolife, Eli Lilly, Medtronic, Medable, Merck, Novartis, Pharmacosmos, Relypsa, Respicardia, Roche, Sanofi, Vifor, Windtree Therapeutics, and Zoll. Dr Reeves reported receiving grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Short Physical Performance Battery Distribution Among Study Participants at Baseline and Follow-up Stratified by Frailty Status and Treatment Arm
Distribution of Short Physical Performance Battery (SPPB) scores at baseline and follow-up among prefrail (A) and frail (B) participants randomized to physical rehabilitation intervention and attention control groups. The midline indicates the median; diamond, mean; box, IQR; and whiskers, 95% CIs.
Figure 2.
Figure 2.. Adjusted Analysis Comparing 3-Month Functional Outcomes in the Intervention vs Attention Control Arm Stratified by Baseline Frailty Status
Adjusted measures of Short Physical Performance Battery (SPPB) score at 3-month follow-up, relative changes in SPPB from baseline to 3-month follow-up, and adjusted measures of Kansas City Cardiomyopathy Questionnaire (KCCQ) score and 6-minute walk distance at 3-month follow-up among intervention and attention control group participants stratified by frail and prefrail status at baseline. Follow-up data are presented as least-squares means with SEs adjusted for baseline value, clinical site, age, sex, and ejection fraction category. Effect size represents the difference in least-squares means between the intervention and attention control groups. P for interaction (prefrail vs frail × intervention arm) was significant for SPPB score and percentage change in SPPB score but was nonsignificant for all other outcomes. Error bars indicate 95% CIs.
Figure 3.
Figure 3.. Adjusted Analysis Comparing Components of Short Physical Performance Battery (SPPB) at 3-Month Follow-up in the Intervention vs Attention Control Arm Stratified by Baseline Frailty Status
Adjusted measures of different components of SPPB score at 3-month follow-up among intervention and attention control group participants stratified by frail and prefrail status at baseline. Follow-up data are presented as least-squares means with SEs adjusted for baseline value, clinical site, age, sex, and ejection fraction category. Effect size represents the difference in least-squares means between the intervention and attention control groups. P for interaction (prefrail vs frail × intervention arm) was significant for 4-m walk score but was nonsignificant for all other outcomes. Error bars indicate 95% CIs.
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