Physical Rehabilitation for Older Patients Hospitalized for Heart Failure

Kitzman DW, Whellan DJ, Duncan PW, et al. Physical rehabilitation for older patients hospitalized for heart failure. The New England Journal of Medicine. 2021;385(3):203-216. doi:10.1056/nejmoa2026141

Link to Original Article: https://www.nejm.org/doi/10.1056/NEJMoa2026141?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Key Points

- The REHAB-HF trial evaluated the effects of a tailored, progressive rehabilitation intervention in older patients hospitalized for acute decompensated heart failure.

- The intervention included four physical-function domains (strength, balance, mobility, and endurance) and was initiated during or after hospitalization and continued for 12 weeks after discharge.

- The primary outcome was the score on the Short Physical Performance Battery at 3 months, with higher scores indicating better physical function.

- The intervention group showed a significantly greater improvement in physical function compared to the control group.

- The intervention did not significantly reduce the rate of rehospitalization for any cause at 6 months.

- The intervention was well-tolerated and resulted in improvements in physical function, quality of life, and depression in older patients with heart failure.

Introduction

Acute decompensated heart failure is a major cause of hospitalization among older individuals in the United States and is associated with various negative outcomes. Previous intervention trials in this area have had neutral results, suggesting the need to explore overlooked mechanisms. Older patients with acute heart failure often have impaired physical function, high frailty rates, and comorbidities. Even those with stable and well-compensated heart failure can experience severe physical impairments due to aging, cardiovascular dysfunction, and skeletal-muscle dysfunction.

Transitioning to acute decompensated heart failure further worsens physical function, exacerbated by hospitalization and bed rest. These deficits often persist, leading to a loss of independence, increased risks of rehospitalization, and higher mortality rates. Unfortunately, current management guidelines do not address physical dysfunction in heart failure patients, and past exercise training trials have excluded recently hospitalized patients.

To address these gaps, the researchers conducted the Rehabilitation Therapy in Older Acuter Heart Failure Patients (REHAB-HF) trial, which evaluated the effects of the tailored rehabilitation intervention. The intervention aimed to improve physical function and reduce rehospitalization rates at the six-month mark. The study findings support the hypothesis that the intervention led to enhanced physical function and potentially reduced rehospitalization rates among older patients hospitalized for acute decompensated heart failure.

Methods

Trial Design and Oversight

The trial design and intervention methods have been previously detailed. The organizational structure of the trial is presented in the Supplementary Appendix of the research article. The trial was overseen by a steering committee, which designed the trial and managed its operations. The protocol for the trial was approved by the institutional review board at each site. Patient safety was evaluated by an independent data and safety monitoring committee. The authors of the paper vouch for the accuracy and completeness of the data and analyses and for the adherence of the trial to the protocol.

Patients and Randomization

The study included patients who were 60 years or older, admitted for acute decompensated heart failure, able to walk at least 4 m, functionally independent before admission, and expected to be discharged home. Patients provided written informed consent and completed baseline testing before being randomly assigned to either the rehabilitation intervention group or the usual care control group. Randomization was stratified based on ejection fraction (<45% or ≥45%) and clinical site using a web-based system. Both groups received usual care, including inpatient or outpatient physical therapy and standard cardiac rehabilitation.

Trial Procedures

The trial intervention for the intervention group was a physical rehabilitation program designed for frail, older patients with acute decompensated heart failure. The program focused on four physical-function domains (strength, balance, mobility, and endurance) and progressed through four functional levels within each domain, individualized based on each patient's performance. The main goal of the intervention group was to increase duration of walking (endurance). In order to improve endurance, deficits in balance, strength, and mobility were first addressed. The intervention began in the hospital and transitioned to an outpatient facility, with home-based sessions provided if needed. Outpatient sessions occurred three days per week for 12 weeks and were conducted at a 1:1 interventionist to patient ratio for 60 minutes. A low intensity home exercise was also included on “rest” days. The goal during the first three months was to prepare the patient for the independent maintenance phase (4 to 6 months post discharge), which included individualized exercise prescriptions and regular telephone contact. Patient retention and adherence to the intervention were closely monitored. Patients in the control group received regular telephone calls and in-person clinic visits at 1 months and 3 months, with no specific exercise recommendations but encouragement to adhere to prescribed usual-care therapy.

Trial Outcomes

The Trial Outcomes section of the research paper focused on the assessment of physical and cognitive function in the participants. Independent personnel who were unaware of the group assignments assessed physical function, quality of life, depression, and cognitive function at baseline in the hospital and at 3 months.

The primary outcome measure was the score on the Short Physical Performance Battery (SPPB) at 3 months. SPPB is a standardized and validated measure of global physical function in older individuals, consisting of standing balance, gait-speed, and strength tests. Each section is scored on the scale of 0 to 4 and the sum of the total score range from 0 to 12. Score of 0 indicate severe physical dysfunction and score of 12 indicate no physical dysfunction.

The secondary outcome was the rate of rehospitalization for any cause at 6 months, with rehospitalization defined as a stay longer than 24 hours. An independent adjudicator, unaware of group assignments, categorized the reasons for rehospitalization as noncardiovascular cause, heart failure, or another cardiovascular cause.

Additional physical function outcomes included 6-minute walk distance, frailty status, hand-grip strength, and gait speed at 3 months. Quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) and the EQ-5D-5L visual-analogue scale. Depression was measured using the Geriatric Depression Scale-15, and cognitive function was assessed using the Montreal Cognitive Assessment score.

Overall, these outcome measures allowed researchers to evaluate the physical and cognitive function, quality of life, depression, and rehospitalization rates in the study participants. The information obtained from these assessments will contribute to understanding the impact of the intervention on various aspects of health and well-being.

Statistical Analysis

The Statistical Analysis section of the research paper outlines the methods used to analyze the data and determine the statistical significance of the results. The researchers estimated that 258 patients would be needed to detect a 10% difference in the Short Physical Performance Battery score at 3 months, while 334 patients would be needed to detect a 25% difference in the rate of rehospitalization at 6 months. Approximately 7% of patients were expected to withdraw from the trial.

Baseline characteristics were presented using means and standard deviations for continuous variables and counts and percentages for categorical variables. Joint models were used to assess differences between the intervention and control groups at 3 months, with adjustments for baseline measures and accounting for deaths and loss to follow-up. Similar joint models were used to assess differences in rehospitalization rates and duration, with adjustments for clinical site, ejection fraction category, age, and sex. Logistic regression was used to analyze binary clinical measures.

A two-tailed P value of less than 0.05 was considered statistically significant for the primary outcome. For other outcomes, effect size estimates and 95% confidence intervals were reported without P values. These confidence intervals were not adjusted for multiple comparisons, so they should not be used to infer definitive treatment effects. The analyses were performed using SAS Enterprise Guide and SAS software.

In summary, the Statistical Analysis section of the paper provides details on the sample size calculations, data analysis methods, and statistical significance thresholds used in the study.

Results

Trial Population and Baseline Characteristics

A total of 349 patients were enrolled and randomized into an intervention group (175 patients) and a control group (174 patients). The mean age of the patients was 72.7 years, with 52% being women and 49% belonging to non-White ethnicities, primarily Black. The majority of patients had either ischemic heart disease (35%) or preserved ejection fraction (53%) as the cause of heart failure. The patients had high rates of comorbidities, with around 45% having a previous hospitalization for any cause and about 25% having a previous hospitalization specifically for heart failure. Nearly all patients (97%) were assessed as frail or prefrail based on the modified Fried criteria. Common issues observed among the patients included urinary incontinence, falls, and depression. The intervention group had a higher incidence of diabetes mellitus compared to the control group (58% vs. 47%). Baseline assessments indicated severely impaired physical function, poor quality of life, and at least mild cognitive dysfunction among the patients. Data availability for analysis of primary and secondary outcomes was 87% and 99% respectively, indicating a high degree of completeness in the dataset.

Follow-up and Trial Outcomes

The last follow-up visit for a rehabilitation intervention was conducted in March 2020. Out of the 175 patients randomly assigned to the intervention, 12 died before completing the intervention, 14 were lost to follow-up, and 16 permanently discontinued the intervention but were included in the analysis. Patient retention in the intervention group, excluding those who died, was 82%. The mean number of outpatient intervention sessions completed was 24.3, with an adherence rate of 67%. Patients showed improvement in functional levels and exercise endurance during the intervention. Among those patients who were assigned to the intervention group, the mean endurance doubled from 10.7 minutes to 22.0 minutes between the first session and last session. The Short Physical Performance Battery score at 3 months was significantly higher in the intervention group compared to the control group (8.3 vs 6.9), even after adjusting for baseline characteristics. The rate of rehospitalization at 6 months did not differ significantly between the intervention and control groups. Various exploratory outcomes, including 6-minute walk distance, gait speed, hand-grip strength, frailty status, quality of life, cognition, depression, falls, and rehospitalizations, were also assessed with the intervention group showing improvements in 6-minute walk test, gait speed, and KCCQ scores. There were no significant differences in the rates of death between the intervention and control groups, but cardiovascular deaths were higher in the intervention group. Adverse events such as chest pain, hypertension, dizziness, hyperglycemia, and hypoglycemia were more common in the intervention group, while falls and heart failure were more common in the control group.

Discussion

The discussion section of the research paper summarizes the findings of the REHAB-HF trial, which investigated the effects of a tailored rehabilitation intervention in frail, older patients hospitalized for acute decompensated heart failure. The intervention group showed significantly greater improvement in physical function, as measured by the Short Physical Performance Battery score at 3 months, compared to the control group. The analysis also indicated clinical benefits in terms of 6-minute walk distance, frailty status, quality of life, and depression. However, both groups had high rates of rehospitalization and death over a 6-month period. The trial aimed to address gaps in previous research, which often excluded recently hospitalized patients and lacked diversity and a control group. The enrolled patients in previous trials were typically younger, less frail, and focused on endurance exercise training. The REHAB-HF trial, in contrast, included older, frail patients with multiple coexisting conditions and implemented a tailored intervention. The authors note that the initiation of standard endurance training without first addressing deficits in balance and mobility in older patients can lead to increased risk of injuries and falls. The study provides important insights into rehabilitation for heart failure patients, particularly those who have recently been hospitalized, and the study reports the benefits seen in this trial exceeded previously reported values for the minimal clinically important difference by as large as three times. The intervention consisted of exercise sessions targeting four domains: balance, strength, mobility, and endurance. As the number of sessions increased, the percentage of patients performing at higher levels of functional ability generally increased, while those performing at lower levels decreased. Adherence to the intervention was low at 43%. The patients in the intervention group had more severe physical impairments than those in previous trials. The intervention group showed greater improvements in physical function compared to the control group, despite 43% of the control group receiving routine therapy. The benefits seen in physical function exceeded previously reported values for clinically important differences. The intervention also showed potential benefits in 6-minute walk distance and depression. However, there were more deaths in the intervention group, although the numbers were small and may have been due to chance. The trial had limitations, including no significant effect on clinical events, patient awareness of group assignment, and differences in usual care received by the control group. The long-term durability of the intervention's benefits was also uncertain. Overall, interventions that emphasized a transitional, tailored, progressive rehabilitation that began early after hospitalization resulted in significantly greater improvement in physical function than usual care.

Opportunities for Future Research

1. Investigate the long-term durability of the benefits of the transitional, tailored, progressive rehabilitation intervention in patients hospitalized for acute decompensated heart failure.

2. Examine the effects of the intervention on other clinical outcomes, such as mortality, rehospitalization rates, and quality of life, over a longer follow-up period.

3. Assess the cost-effectiveness of the intervention compared to usual care in older patients hospitalized for heart failure.

4. Investigate the optimal timing and duration of the rehabilitation intervention for maximizing physical function outcomes in older patients with heart failure.

5. Explore strategies to improve adherence to the rehabilitation intervention, such as incorporating behavioral change techniques or tele-rehabilitation approaches.

6. Evaluate the effects of the rehabilitation intervention on other domains of function, such as cognitive function and mental health, in older patients with heart failure.