TEXT:
Sarcopenia, the age- or disease-related loss of muscle mass and function, is prevalent in older adults hospitalized for acute decompensated heart failure (ADHF) and associated with poor outcomes. The Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial showed that a 12-week early, transitional, tailored, progressive, multidomain physical rehabilitation intervention improved physical function and quality-of-life (QOL) in older adults hospitalized for ADHF.1 A REHAB-HF secondary analysis demonstrated that frail patients derived greater benefits from the intervention than pre-frail patients.2 However, sarcopenia, which often precedes frailty, may be more amenable to intervention if identified early.3 Unlike frailty, which is primarily a chronic condition, sarcopenia can develop acutely after hospitalization.4 Sarcopenia diagnosis can also be simpler when using functional measures without imaging, a concept that may be termed functional sarcopenia.5 While this approach may be less precise as it does not account for muscle mass, it offers a practical method for clinical assessment.
Therefore, in this secondary analysis of the REHAB-HF trial, we examined the impact of functional sarcopenia on response to the REHAB-HF intervention. The REHAB-HF trial was a multicenter, randomized, single-blind, attention-controlled trial of a rehabilitation intervention after ADHF hospitalization in patients ≥60 years of age, independent of ejection fraction (EF).1 Participants provided written informed consent, and the study received institutional review board approval at participating sites. Participants were categorized by functional sarcopenia status using the Sarcopenia Definition and Outcomes Consortium (SDOC) criteria of low muscle strength (handgrip <35.5 kg in males, <20 kg in females) and slow gait speed over 4 meters (<0.8 m/s).5 Those not meeting both criteria were defined as not having functional sarcopenia. Measures of body composition were not obtained in the trial. We compared the intervention effect on physical function, QOL, cognitive, psychological, and clinical events between groups using adjusted models.1
Of 343 participants with the baseline measurements used to define functional sarcopenia, 174 (50.7%) were identified as not having functional sarcopenia (87 control, 87 intervention) and 169 (49.3%) as having functional sarcopenia (83 control, 86 intervention). The mean age of the overall cohort was 72.6 (standard deviation [SD] 8.1) years, with 180 (52.5%) female and 167 (48.7%) non-White. Participants with functional sarcopenia were older (75.0 [SD 8.2] vs 70.3 [SD 7.3] years, p<0.001), had more comorbidities (5.6 [SD 2.1] vs 4.8 [SD 1.8], p<0.001), and lower baseline Short Physical Performance Battery (SPPB) scores (5.0 [SD 2.3] vs 7.1 [SD 2.6], p<0.001) compared to those without functional sarcopenia. There were no significant differences in EF, New York Heart Association class, or N-terminal pro-B-type natriuretic peptide levels.
The primary outcome measure, SPPB score at 3-month follow-up, was available in 299 participants, including 161 (92.5%) without functional sarcopenia (81 control, 80 intervention) and 138 (81.7%) with functional sarcopenia (70 control, 68 intervention). Among the 148 intervention participants with follow-up SPPB scores, the average number of intervention sessions attended was similar between participants without and with functional sarcopenia (26.6 [SD 10.5] vs 25.5 [SD 11.8] sessions, p=0.528). The intervention adherence rates, adjusted for missed sessions due to medical interruptions, were also similar between participants without and with functional sarcopenia (82.0% [SD 27.2] vs 77.0% [SD 32.3] adherence, p=0.299).
At 3-month follow-up, there was a significant, clinically meaningful improvement in SPPB score among participants with functional sarcopenia, with an intervention effect size of 1.6 (95%CI 0.8-2.5). While this effect was numerically larger than that observed in participants without functional sarcopenia (1.2, 95%CI 0.5-2.0), no significant functional sarcopenia-by-treatment arm interaction was observed (p=0.521). Individuals with functional sarcopenia also had greater improvements in 6-minute walk distance and the European Quality of Life visual analog scale. Functional sarcopenia status did not significantly modify the intervention's effects on clinical events at 6 months. Table 1 presents the effects of the intervention on physical function, quality of life, cognitive, psychological, and clinical outcomes.
Table 1.
*Adjusted comparison of 3-month physical function, quality of life, cognitive, and psychological outcome measures, and 6-month adverse clinical events, in the control vs intervention arms by baseline functional sarcopenia status.
| No functional sarcopenia | Effect size (95% CI) |
P- value |
Functional sarcopenia | Effect size (95% CI) |
P-value | P-value for interaction † |
|||
|---|---|---|---|---|---|---|---|---|---|
| Attention control |
Rehab intervention |
Attention control |
Rehab intervention |
||||||
| 3-month physical function outcome measures | |||||||||
| SPPB score | 6.8 (0.3) | 8.1 (0.3) | 1.2 (0.5, 2.0) | 0.002 | 6.2 (0.3) | 7.8 (0.3) | 1.6 (0.8, 2.5) | <0.001 | 0.52 |
| Standing balance score | 2.9 (0.1) | 3.2 (0.1) | 0.3 (−0.1, 0.6) | 0.12 | 2.6 (0.1) | 3.0 (0.2) | 0.4 (0.0, 0.8) | 0.038 | 0.62 |
| 4-meter walk score | 2.7 (0.1) | 3.0 (0.1) | 0.3 (0.0, 0.6) | 0.04 | 2.3 (0.1) | 2.8 (0.1) | 0.6 (0.2, 0.9) | 0.001 | 0.30 |
| Chair rise score | 1.5 (0.1) | 2.1 (0.1) | 0.7 (0.3, 1.0) | <0.001 | 1.2 (0.1) | 1.8 (0.1) | 0.6 (0.2, 0.9) | 0.002 | 0.77 |
| 6-min walk distance, m | 285 (13) | 297 (12) | 12 (−17, 41) | 0.42 | 218 (13) | 274 (13) | 56 (23, 90) | 0.001 | 0.05 |
| Gait speed, m/s | 0.71 (0.03) | 0.81 (0.02) | 0.1 (0.04, 0.16) | 0.001 | 0.67 (0.03) | 0.80 (0.03) | 0.13 (0.06, 0.19) | <0.001 | 0.56 |
| Handgrip strength, kg | |||||||||
| Males | 31.7 (1.3) | 30.3 (1.2) | −1.5 (−4.5, 1.6) | 0.35 | 29.4 (1.3) | 29.9 (1.1) | 0.5 (−2.5, 3.4) | 0.761 | 0.3 |
| Females | 21.9 (1.0) | 21.8 (0.9) | −0.1 (−2.2, 2.0) | 0.91 | 21.0 (1.1) | 20.7 (1.3) | −0.3 (−2.9, 2.4) | 0.833 | 0.92 |
| Modified Fried frailty score | 1.5 (0.1) | 1.2 (0.1) | −0.3 (−0.7, −0.0) | 0.048 | 2.0 (0.2) | 1.8 (0.2) | −0.2 (−0.6, 0.2) | 0.290 | 0.60 |
| 3-month quality of life outcome measures | |||||||||
| KCCQ overall score | 65.9 (2.9) | 72.2 (2.7) | 6.3 (−0.7, 13.3) | 0.08 | 55.9 (2.9) | 63.0 (3.0) | 7.2 (−0.6, 14.9) | 0.069 | 0.87 |
| EQ-5D-5L VAS score | 69.7 (2.6) | 72.7 (2.5) | 3.0 (−3.3, 9.3) | 0.35 | 57.0 (2.6) | 68.8 (2.7) | 11.8 (4.8, 18.8) | 0.001 | 0.067 |
| 3-month cognitive and psychological outcome measures | |||||||||
| MoCA score | 23.0 (0.5) | 22.3 (0.4) | −0.7 (−1.8, 0.4) | 0.19 | 22.3 (0.5) | 22.6 (0.5) | 0.3 (−0.9, 1.6) | 0.602 | 0.21 |
| GDS-15 score | 3.9 (0.3) | 3.2 (0.3) | −0.7 (−1.5, 0.1) | 0.10 | 4.7 (0.3) | 3.9 (0.4) | −0.8 (−1.7, 0.2) | 0.103 | 0.91 |
| 6-month adverse clinical events | |||||||||
| All-cause rehospitalization | 83 (0.99) | 90 (1.07) | 0.99 (0.73, 1.34) | 0.94 | 127 (1.62) | 102 (1.32) | 0.86 (0.66, 1.11) | 0.248 | 0.48 |
| All-cause death | 5 (0.06) | 5 (0.06) | 0.99 (0.29, 3.44) | 0.99 | 11 (0.14) | 16 (0.21) | 1.37 (0.63, 2.97) | 0.422 | 0.66 |
| All-cause rehospitalization and death | 88 (1.05) | 95 (1.12) | 0.99 (0.74, 1.33) | 0.97 | 138 (1.76) | 118 (1.52) | 0.90 (0.71, 1.16) | 0.423 | 0.63 |
| HF rehospitalization | 45 (0.54) | 38 (0.45) | 0.74 (0.48, 1.15) | 0.18 | 63 (0.80) | 54 (0.70) | 0.94 (0.65, 1.35) | 0.726 | 0.42 |
| Injurious falls | 28 (0.33) | 23 (0.26) | 0.74 (0.38, 1.43) | 0.37 | 32 (0.39) | 24 (0.28) | 0.62 (0.32, 1.20) | 0.16 | 0.72 |
Follow-up data are presented as least-squares means with standard errors 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. Adverse clinical event data presented as count (6-month rate) adjusted for clinical site, age, sex, and ejection fraction category; all-cause rehospitalization was also adjusted for baseline SPPB score. Injurious falls presented as number (proportion). Effect sizes are shown as odds ratio for binary outcomes (injurious falls) and rate ratio for count-based outcomes (all others). Abbreviations: CI, confidence interval; SPPB, Short Physical Performance Battery; KCCQ, Kansas City Cardiomyopathy Questionnaire; EQ-5D-5L VAS, European Quality of Life 5-Dimension 5-Level visual analog scale; MoCA, Montreal Cognitive Assessment Score; GDS-15, Geriatric Depression Scale-15; HF, heart failure.
P-value for interaction of baseline functional sarcopenia status x intervention arm.
Our findings expand upon the previous REHAB-HF frailty analysis by focusing on functional sarcopenia, which may develop more acutely and be more amenable to early intervention. The REHAB-HF intervention significantly benefits individuals diagnosed with functional sarcopenia using simple muscle strength and function measures, complementing the frailty-focused analysis. Of the 343 participants, 42 (12.2%) had functional sarcopenia only, 61 (17.8%) had frailty only by the Fried phenotype model, 127 (37.0%) had both, and 113 (32.9%) had neither. The finding of functional sarcopenia without frailty supports that these two measures can provide complementary information and identify a subset of patients with early, potentially reversible functional decline.
In conclusion, older adults with ADHF and SDOC-defined functional sarcopenia derived clinically meaningful benefits from the REHAB-HF intervention. This approach may offer a practical method for the early identification of at-risk patients. However, our study has limitations, including the lack of quantitative muscle mass measures and potential discrepancies between intervention focus and sarcopenia classification criteria. Further research is warranted to investigate whether early identification and intervention for functional sarcopenia can prevent frailty progression and improve long-term outcomes in this population. The data supporting this study's findings are available from the corresponding author upon reasonable request.
Sources of Funding:
This study was supported, in part, by the following research grant awards from the National Institutes of Health (NIH): R01AG045551, R01AG18915, U01AG076928, R01AG078153, U24AG059624, and U01HL160272. It was also supported, in part, by the Kermit Glenn Phillips II Chair in Cardiovascular Medicine at Wake Forest School of Medicine (DWK), the Claude D. Pepper Older Americans Independence Center NIH Grants P30AG021332 (DWK, SK) and P30AG028716 (AMP), and the Wake Forest Clinical and Translational Science Award NIH Grant UL1TR001420. Saeid Mirzai is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) (T32HL076132).
Abbreviation list:
- ADHF
acute decompensated heart failure
- REHAB-HF
Rehabilitation Therapy in Older Acute Heart Failure Patients
- EF
ejection fraction
- SDOC
Sarcopenia Definition and Outcomes Consortium
- SD
standard deviation
- SPPB
Short Physical Performance Battery
Footnotes
Disclosures: DWK has been a consultant for AstraZeneca, Pfizer, Corvia Medical, Bayer, Boehringer-Ingleheim, Novo Nordisk, Rivus, and St. Luke’s Medical Center; received grant support from Novartis, AstraZeneca, Bayer, Pfizer, Novo Nordisk, Rivus, and St. Luke’s Medical Center; and owns stock in Gilead Sciences.
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