Circulating Biomarkers as Predictors of Improvement in Physical Function in Hospitalized Older Adults with Geriatric Syndromes: Findings from the REHAB-HF Trial

Introduction: Circulating biomarkers play an important role in patients with heart failure (HF) for risk stratification and mechanistic insights. We aimed to examine if a diverse set of biomarkers in the REHAB-HF trial would predict improvement in physical function following a 12-week tailored physical therapy rehabilitation intervention compared to attention control. Methods: The study population consisted of participants ≥60 years of age who were hospitalized with acute HF and randomized to a subsequent multidomain outpatient physical rehabilitation intervention vs. attention control with outcomes of 12-week functional change including the Short Physical Performance Battery (SPPB) and six-minute walk distance (6MWD). Blood was collected prior to randomization and at 12-weeks for cardiac, renal, and inflammatory biomarkers. Linear trends across progressively higher biomarker values versus improvement in functional outcomes based on treatment assignment were evaluated. Classification and regression trees (CART) were created to estimate optimal biomarker levels associated with differential improvement in the two functional outcomes. Results: A total of 242 of 349 participants (69%) had baseline biomarkers measured. In an adjusted regression model, higher baseline cardiac troponin (cTn) I and T were associated with greater gains in SPPB and 6MWD respectively with the rehabilitation intervention (P=0.04 and 0.03 for interaction) versus attention control. In the CART analysis of the physical rehabilitation and attention control participants, those with baseline C-reactive protein (CRP) ≥9.9 mg/L and hs-cTnT ≥36 ng/L receiving the rehabilitation intervention had a 129 m (95% CI 78-180m) greater 12-week 6MWD increase vs attention control. In contrast, for participants with CRP<9.9 mg/L there was no significant incremental 6MWD difference (30m, 95% CI -0.5m, 60.2m). For SPPB, a CRP ≥9.9 mg/L and creatinine ≥1.4 mg/dL optimally identified a differential improvement with the rehabilitation intervention versus attention control. The biomarkers (except for creatinine) decreased by 12 weeks post hospitalization but with no differences based on treatment assignment. Conclusion: Higher baseline levels of biomarkers of inflammation, cardiac injury, and renal dysfunction identified older adults after a HF hospitalization with the greatest differential improvement in physical function with a rehabilitation intervention. Biomarkers may help clinicians predict the benefits of this treatment.