Skeletal Muscle Mitochondrial Respiration and Exercise Intolerance in Patients With Heart Failure With Preserved Ejection Fraction.

Importance: The pathophysiology of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely understood. Multiple lines of evidence suggest that abnormal skeletal muscle metabolism is a key contributor, but the mechanisms underlying metabolic dysfunction remain unresolved. Objective: To evaluate the associations of skeletal muscle mitochondrial function using respirometric analysis of biopsied muscle fiber bundles from patients with HFpEF with exercise performance. Design, Setting, and Participants: In this cross-sectional study, muscle fiber bundles prepared from fresh vastus lateralis biopsies were analyzed by high-resolution respirometry to provide detailed analyses of mitochondrial oxidative phosphorylation, including maximal capacity and the individual contributions of complex I-linked and complex II-linked respiration. These bioenergetic data were compared between patients with stable chronic HFpEF older than 60 years and age-matched healthy control (HC) participants and analyzed for intergroup differences and associations with exercise performance. All participants were treated at a university referral center, were clinically stable, and were not undergoing regular exercise or diet programs. Data were collected from March 2016 to December 2017, and data were analyzed from November 2020 to May 2021. Main Outcomes and Measures: Skeletal muscle mitochondrial function, including maximal capacity and respiration linked to complex I and complex II. Exercise performance was assessed by peak exercise oxygen consumption, 6-minute walk distance, and the Short Physical Performance Battery. Results: Of 72 included patients, 50 (69%) were women, and the mean (SD) age was 69.6 (6.1) years. Skeletal muscle mitochondrial function measures were all markedly lower in skeletal muscle fibers obtained from patients with HFpEF compared with HCs, even when adjusting for age, sex, and body mass index. Maximal capacity was strongly and significantly correlated with peak exercise oxygen consumption (R = 0.69; P < .001), 6-minute walk distance (R = 0.70; P < .001), and Short Physical Performance Battery score (R = 0.46; P < .001). Conclusions and Relevance: In this study, patients with HFpEF had marked abnormalities in skeletal muscle mitochondrial function. Severely reduced maximal capacity and complex I-linked and complex II-linked respiration were associated with exercise intolerance and represent promising therapeutic targets.

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.

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.

Severity of functional impairments by race and sex in older patients hospitalized with acute decompensated heart failure.

BACKGROUND: Older patients hospitalized with acute decompensated heart failure (ADHF) have marked functional impairments, which may contribute to their delayed and incomplete recovery and persistently poor outcomes. However, whether impairment severity differs by race and sex is unknown. METHODS: REHAB-HF trial participants (≥60 years) were assessed just before discharge home from ADHF hospitalization. Physical function [Short Physical Performance Battery; 6-min walk distance (6MWD)], frailty (Fried criteria), cognition [Montreal Cognitive Assessment (MoCA)], quality-of-life [Kansas City Cardiomyopathy Questionnaire, Short-Form-12, EuroQol-5D-5L], and depression [Geriatric Depression Scale (GDS)] were examined by race and sex. RESULTS: This prespecified subgroup cross-sectional analysis included 337 older adults (52% female, 50% Black). Black participants were on average younger than White participants (70.3 ± 7.2 vs. 74.7 ± 8.3 years). After age, body mass index, ejection fraction, comorbidity, and education adjustment, and impairments were similarly common and severe across groups except: Black male and Black and White female participants had more severely impaired walking function compared with White male participants [6MWD (m) 187 ± 12, 168 ± 9170 ± 11 vs. 239 ± 9, p < 0.001]; gait speed (m/s) (0.61 ± 0.03, 0.56 ± 0.02, 0.55 ± 0.02 vs. 0.69 ± 0.02, p < 0.001); White female participants had the highest frailty prevalence (72% vs. 47%-51%, p = 0.007); and Black participants had lower MoCA scores compared with White participants (20.9 ± 4.5 vs. 22.8 ± 3.9, p < 0.001). Depressive symptoms were common overall (43% GDS ≥5), yet underrecognized clinically (18%), especially in Black male participants compared with White male participants (7% vs. 20%). CONCLUSION: Among older patients hospitalized for ADHF, frailty and functional impairments with high potential to jeopardize patient HF self-management, safety, and independence were common and severe across all race and sex groups. Impairment severity was often worse in Black participant and female participant groups. Formal screening across frailty and functional domains may identify those who may require greater support and more tailored care to reduce the risk of adverse events and excess hospitalizations and death.

A consensus method for estimating physical activity levels in adults using accelerometry.

Identifying the best analytical approach for capturing moderate-to-vigorous physical activity (MVPA) using accelerometry is complex but inconsistent approaches employed in research and surveillance limits comparability. We illustrate the use of a consensus method that pools estimates from multiple approaches for characterising MVPA using accelerometry. Participants (n = 30) wore an accelerometer on their right hip during two laboratory visits. Ten individual classification methods estimated minutes of MVPA, including cut-point, two-regression, and machine learning approaches, using open-source count and raw inputs and several epoch lengths. Results were averaged to derive the consensus estimate. Mean MVPA ranged from 33.9-50.4 min across individual methods, but only one (38.9 min) was statistically equivalent to the criterion of direct observation (38.2 min). The consensus estimate (39.2 min) was equivalent to the criterion (even after removal of the one individual method that was equivalent to the criterion), had a smaller mean absolute error (4.2 min) compared to individual methods (4.9-12.3 min), and enabled the estimation of participant-level variance (mean standard deviation: 7.7 min). The consensus method allows for addition/removal of methods depending on data availability or field progression and may improve accuracy and comparability of device-based MVPA estimates while limiting variability due to convergence between estimates.

Quality of Life Trajectory and Its Mediators in Older Patients With Acute Decompensated Heart Failure Receiving a Multi-Domain Rehabilitation Intervention: Results From the Rehabilitation Therapy in Older Acute Heart Failure Patients Trial.

BACKGROUND: As patients with heart failure experience worsening of their condition, including acute decompensated heart failure, quality of life deteriorates. However, the trajectory of quality of life changes and their determinants in the context of the Rehabilitation Therapy in Older Acute Heart Failure Patients trial physical rehabilitation intervention are unknown. METHODS: Patients ≥60 years old admitted for acute decompensated heart failure (n=349) were randomized to either attention control or intervention. Quality of life outcomes (Kansas City Cardiomyopathy Questionnaire; 12-Item Short-Form Health Survey) were measured at baseline (inpatient), 1 month, and 3 months. Intervention effects were assessed using linear mixed effects regression, including covariates to model the main effects of the intervention and timing of outcome assessments. Mediation analysis determined if changes in Kansas City Cardiomyopathy Questionnaire were due to improvement in physical function (short physical performance battery, 6-minute walk distance). RESULTS: Baseline Kansas City Cardiomyopathy Questionnaire summary score was similarly poor in the intervention and control arms (40.2±20.6 versus 41.5±20.6). Although the intervention experienced nominally greater Kansas City Cardiomyopathy Questionnaire improvement than control at 1 month (64.7±1.9 versus 61.1±1.9, P=0.13), the difference was not statistically significant until 3 months (67.7±1.9 versus 60.8±1.9, P=0.004). Twelve-Item Short-Form Health Survey Physical and Mental Composite Scores increased in both arms at 1 month and continued improvement only in the intervention. The 3-month improvement in short physical performance battery score explained 64.1% of the improvement in Kansas City Cardiomyopathy Questionnaire (P<0.001). CONCLUSIONS: In older patients hospitalized for acute decompensated heart failure, quality of life improves in the first month after discharge. The quality of life benefit of a post-discharge physical rehabilitation intervention is detected early with large significant improvements at 3 months achieved primarily through improvement in short physical performance battery. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT02196038.

Obesity Status and Physical Rehabilitation in Older Patients Hospitalized With Acute HF: Insights From REHAB-HF.

BACKGROUND: In the REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) trial, a novel, early, transitional, multidomain rehabilitation intervention improved physical function, frailty, quality of life (QOL), and depression in older patients hospitalized for acute decompensated heart failure (ADHF), but the potential impact of baseline obesity on this intervention has not been studied. OBJECTIVES: This study assessed for treatment interactions by body mass index (BMI) subgroups for a novel rehabilitation intervention in ADHF. METHODS: Three-month outcomes including Short Physical Performance Battery (SPPB) (primary outcome), 6-minute walk distance (6MWD), and Kansas City Cardiomyopathy Questionnaire (KCCQ) were assessed by baseline BMI (≥30 kg/m2 vs <30 kg/m2). Six-month end points included all-cause rehospitalization and death. All analyses were adjusted for age, sex, clinical site, and ejection fraction category, and 3-month outcomes were also adjusted for baseline measure. The prespecified significance level for treatment interaction by BMI category was P ≤ 0.10. RESULTS: Of 349 trial participants, 204 (58%) had BMI ≥30 kg/m2 and 145 (42%) <30 kg/m2. Compared with patients with BMI <30 kg/m2, participants with BMI ≥30 kg/m2 were younger (age 71 ± 7 years vs 75 ± 9 years), more frequently women (57% vs 46%), and had significantly worse baseline physical function and QOL. Although interaction P values for 3-month outcomes by BMI were not significant (interaction P > 0.15 for overall measures), adjusted SPPB effect sizes were nominally larger for participants with BMI ≥30 kg/m2 compared with those with BMI <30 kg/m2: +1.7 (95% CI: 0.8-2.7) vs +1.1 (95% CI: -0.1 to 2.2). This difference in SPPB effect size was due largely to improvements in the balance component of the SPPB for participants with BMI ≥30 kg/m2: +0.6 (95% CI: 0.2-1.0) vs 0.0 (-0.6 to 0.5) for those with BMI <30 kg/m2 (interaction P = 0.02). In contrast, adjusted 6MWD and KCCQ effect sizes were smaller for participants with BMI ≥30 kg/m2 compared with those with BMI <30 kg/m2: +21 meters (-17 to 59) vs +53 meters (6-100), and +5.0 (-4 to 14) vs +11 (-0.5 to 22), respectively. There was no significant interaction by BMI for 6-month clinical outcomes (all interaction P > 0.30). CONCLUSIONS: Older patients with ADHF benefit from the rehabilitation therapy regardless of BMI. Benefits for patients with obesity may be more evident in the multidomain measure of physical function (SPPB), compared with the 6MWD or KCCQ, which may be driven, in part, by the unique aspects of the novel rehabilitation intervention. (A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients [REHAB-HF]; NCT02196038).

Intervention Adherence in REHAB-HF: Predictors and Relationship With Physical Function, Quality of Life, and Clinical Events.

Background The REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) trial showed that a novel, early, transitional, tailored, progressive, multidomain physical rehabilitation intervention improved physical function and quality of life in older, frail patients hospitalized for acute decompensated heart failure. This analysis examined the relationship between intervention adherence and outcomes. Methods and Results Adherence was defined as percent of sessions attended and percent of sessions attended adjusted for missed sessions for medical reasons. Baseline characteristics were examined to identify predictors of session attendance. Associations of session attendance with change in physical function (Short Physical Performance Battery [primary outcome], 6-minute walk distance, quality of life [Kansas City Cardiomyopathy Questionnaire], depression, and clinical events [landmarked postintervention]) were examined in multivariate analyses. Adherence was 67%±34%, and adherence adjusted for missed sessions for medical reasons was 78%±34%. Independent predictors of higher session attendance were the following: nonsmoking, absence of myocardial infarction history and depression, and higher baseline Short Physical Performance Battery. After adjustment for predictors, adherence was significantly associated with larger increases in Short Physical Performance Battery (parameter estimate: ß=0.06[0.03-0.10], P=0.001), 6-minute walk distance (ß=1.8[0.2-3.5], P=0.032), and Kansas City Cardiomyopathy Questionnaire score (ß=0.62[0.26-0.98], P=0.001), and reduction in depression (ß=-0.08[-0.12 to 0.04], P<0.001). Additionally, higher adherence was significantly associated with reduced 6-month all-cause rehospitalization (rate ratio: 0.97 [0.95-0.99], P=0.020), combined all-cause rehospitalization and death (0.97 [0.95-0.99], P=0.017), and all-cause rehospitalization days (0.96 [0.94-0.99], P=0.004) postintervention. Conclusions In older, frail patients with acute decompensated heart failure, higher adherence was significantly associated with improved patient-centered and clinical event outcomes. These data support the efficacy of the comprehensive adherence plan and the subsequent intervention-related benefits observed in REHAB-HF. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT02196038.

Left Atrial Stiffness Index Independently Predicts Exercise Intolerance and Quality of Life in Older, Obese Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is the fastest growing form of HF and is associated with high morbidity and mortality. The primary chronic symptom in HFpEF is exercise intolerance, associated with reduced quality of life. Emerging evidence implicates left atrial (LA) dysfunction as an important pathophysiologic mechanism. Here we extend prior observations by relating LA dysfunction to peak oxygen uptake (peak VO2), physical function (distance walked in 6 minutes [6MWD]) and quality of life (Kansas City Cardiomyopathy Questionnaire). METHODS AND RESULTS: We compared 75 older, obese, patients with HFpEF with 53 healthy age-matched controls. LA strain was assessed by magnetic resonance cine imaging using feature tracking. LA function was defined according to its 3 distinct phases, with the LA serving as a reservoir during systole, as a conduit during early diastole, and as a booster pump at the end of diastole. The LA stiffness index was calculated as the ratio of early mitral inflow velocity-to-early annular tissue velocity (E/e', by Doppler ultrasound examination) and LA reservoir strain. HFpEF had a decreased reservoir strain (16.4 ± 4.4% vs 18.2 ± 3.5%, P = .018), lower conduit strain (7.7 ± 3.3% vs 9.1 ± 3.4%, P = .028), and increased stiffness index (0.86 ± 0.39 vs 0.53 ± 0.18, P < .001), as well as decreased peak VO2, 6MWD, and lower quality of life. Increased LA stiffness was independently associated with impaired peak VO2 (ß = 9.0 ± 1.6, P < .001), 6MWD (ß = 117 ± 22, P = .003), and Kansas City Cardiomyopathy Questionnaire score (ß = -23 ± 5, P = .001), even after adjusting for clinical covariates. CONCLUSIONS: LA stiffness is independently associated with impaired exercise tolerance and quality of life and may be an important therapeutic target in obese HFpEF. REGISTRATION: NCT00959660.

Economic Outcomes of Rehabilitation Therapy in Older Patients With Acute Heart Failure in the REHAB-HF Trial: A Secondary Analysis of a Randomized Clinical Trial.

Importance: In the Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial, a novel 12-week rehabilitation intervention demonstrated significant improvements in validated measures of physical function, quality of life, and depression, but no significant reductions in rehospitalizations or mortality compared with a control condition during the 6-month follow up. The economic implications of these results are important given the increasing pressures for cost containment in health care. Objective: To report the economic outcomes of the REHAB-HF trial and estimate the potential cost-effectiveness of the intervention. Design, Setting, Participants: The multicenter REHAB-HF trial randomized 349 patients 60 years or older who were hospitalized for acute decompensated heart failure to rehabilitation intervention or a control group; patients were enrolled from September 17, 2014, through September 19, 2019. For this preplanned secondary analysis of the economic outcomes, data on medical resource use and quality of life (via the 5-level EuroQol 5-Dimension scores converted to health utilities) were collected. Medical resource use and medication costs were estimated using 2019 US Medicare payments and the Federal Supply Schedule, respectively. Cost-effectiveness was estimated using the validated Tools for Economic Analysis of Patient Management Interventions in Heart Failure Cost-Effectiveness Model, which uses an individual-patient simulation model informed by the prospectively collected trial data. Data were analyzed from March 24, 2019, to December 1, 2020. Interventions: Rehabilitation intervention or control. Main Outcomes and Measures: Costs, quality-adjusted life-years (QALYs), and the lifetime estimated cost per QALY gained (incremental cost-effectiveness ratio). Results: Among the 349 patients included in the analysis (183 women [52.4%]; mean [SD] age, 72.7 [8.1] years; 176 non-White [50.4%] and 173 White [49.6%]), mean (SD) cumulative costs per patient were $26 421 ($38 955) in the intervention group (excluding intervention costs) and $27 650 ($30 712) in the control group (difference, -$1229; 95% CI, -$8159 to $6394; P = .80). The mean (SD) cost of the intervention was $4204 ($2059). Quality of life gains were significantly greater in the intervention vs control group during 6 months (mean utility difference, 0.074; P = .001) and sustained beyond the 12-week intervention. Incremental cost-effectiveness ratios were estimated at $58 409 and $35 600 per QALY gained for the full cohort and in patients with preserved ejection fraction, respectively. Conclusions and Relevance: These analyses suggest that longer-term benefits of this novel rehabilitation intervention, particularly in the subgroup of patients with preserved ejection fraction, may yield good value to the health care system. However, long-term cost-effectiveness is currently uncertain and dependent on the assumption that benefits are sustained beyond study follow-up, which needs to be corroborated in future trials in this patient population.

Rehabilitation Intervention in Older Patients With Acute Heart Failure With Preserved Versus Reduced Ejection Fraction.

OBJECTIVES: This study assessed for treatment interactions by ejection fraction (EF) subgroup (≥45% [heart failure with preserved ejection fraction (HFpEF); vs <45% [heart failure with reduced ejection fraction (HFrEF)]). BACKGROUND: The REHAB-HF trial showed that an early multidomain rehabilitation intervention improved physical function, frailty, quality-of-life, and depression in older patients hospitalized with acute decompensated heart failure (ADHF). METHODS: Three-month outcomes were: Short Physical Performance Battery (SPPB), 6-min walk distance (6MWD), and Kansas City Cardiomyopathy Questionnaire (KCCQ). Six-month end points included all-cause rehospitalization and death and a global rank of death, all-cause rehospitalization, and SPPB. Prespecified significance level for interaction was P ≤ 0.1. RESULTS: Among 349 total participants, 185 (53%) had HFpEF and 164 (47%) had HFrEF. Compared with HFrEF, HFpEF participants were more often women (61% vs 43%) and had significantly worse baseline physical function, frailty, quality of life, and depression. Although interaction P values for 3-month outcomes were not significant, effect sizes were larger for HFpEF vs HFrEF: SPPB +1.9 (95% CI: 1.1-2.6) vs +1.1 (95% CI: 0.3-1.9); 6MWD +40 meters (95% CI: 9 meters-72 meters) vs +27 (95% CI: -6 meters to 59 meters); KCCQ +9 (2-16) vs +6 (-2 to 14). All-cause rehospitalization rate was nominally lower with intervention in HFpEF but not HFrEF [effect size 0.83 (95% CI: 0.64-1.09) vs 0.99 (95% CI: 0.74-1.33); interaction P = 0.40]. There were significantly greater treatment benefits in HFpEF vs HFrEF for all-cause death [interaction P = 0.08; intervention rate ratio 0.63 (95% CI: 0.25-1.61) vs 2.21 (95% CI: 0.78-6.25)], and the global rank end point (interaction P = 0.098) with benefit seen in HFpEF [probability index 0.59 (95% CI: 0.50-0.68)] but not HFrEF. CONCLUSIONS: Among older patients hospitalized with ADHF, compared with HFrEF those with HFpEF had significantly worse impairments at baseline and may derive greater benefit from the intervention. (A Trial of Rehabilitation Therapy in Older Acute Heart Failure Patients [REHAB-HF]; NCT02196038).

Relationships Between Objectively Measured Physical Activity, Exercise Capacity, and Quality of Life in Older Patients With Obese Heart Failure and Preserved Ejection Fraction.

BACKGROUND: The relationship between physical activity (PA), exercise capacity, and quality of life (QOL) in obese heart failure with preserved ejection fraction is poorly understood. METHODS AND RESULTS: This was an ancillary study to a clinical trial. Accelerometers were used to measure light PA, moderate to vigorous PA, total PA, PA energy expenditure, and steps. Peak VO2, exercise time, and 6-minute walk distance, as well as QOL measures were obtained. Pearson correlations were performed to examine relationships between PA, exercise capacity, and QOL. Patients (n = 58) were 68.0 ± 5.7 years old, 78% female, 59% White, and obese (body mass index 39.1 ± 6.1 kg/m2). Patients had low levels of objectively measured PA as well as decreased exercise capacity and poor QOL. Light PA (r = 0.32, P = .014) and steps per day (r = 0.30, P = .022) were modestly correlated with peak VO2. All PA variables were modestly correlated with exercise time (r = 0.33-0.49, all P < .02) and 6-minute walk distance (r = 0.25-0.48, all P < .01). None of the PA variables were correlated with QOL. CONCLUSIONS: PA variables were modestly correlated with measures of exercise capacity and were not significantly correlated with QOL. Our findings indicate that PA, exercise capacity, and QOL assess different aspects of the patient experience in older obese patients with heart failure with preserved ejection fraction.

Physical Rehabilitation for Older Patients Hospitalized for Heart Failure.

BACKGROUND: Older patients who are hospitalized for acute decompensated heart failure have high rates of physical frailty, poor quality of life, delayed recovery, and frequent rehospitalizations. Interventions to address physical frailty in this population are not well established. METHODS: We conducted a multicenter, randomized, controlled trial to evaluate a transitional, tailored, progressive rehabilitation intervention that included four physical-function domains (strength, balance, mobility, and endurance). The intervention was initiated during, or early after, hospitalization for heart failure and was continued after discharge for 36 outpatient sessions. The primary outcome was the score on the Short Physical Performance Battery (total scores range from 0 to 12, with lower scores indicating more severe physical dysfunction) at 3 months. The secondary outcome was the 6-month rate of rehospitalization for any cause. RESULTS: A total of 349 patients underwent randomization; 175 were assigned to the rehabilitation intervention and 174 to usual care (control). At baseline, patients in each group had markedly impaired physical function, and 97% were frail or prefrail; the mean number of coexisting conditions was five in each group. Patient retention in the intervention group was 82%, and adherence to the intervention sessions was 67%. After adjustment for baseline Short Physical Performance Battery score and other baseline characteristics, the least-squares mean (±SE) score on the Short Physical Performance Battery at 3 months was 8.3±0.2 in the intervention group and 6.9±0.2 in the control group (mean between-group difference, 1.5; 95% confidence interval [CI], 0.9 to 2.0; P<0.001). At 6 months, the rates of rehospitalization for any cause were 1.18 in the intervention group and 1.28 in the control group (rate ratio, 0.93; 95% CI, 0.66 to 1.19). There were 21 deaths (15 from cardiovascular causes) in the intervention group and 16 deaths (8 from cardiovascular causes) in the control group. The rates of death from any cause were 0.13 and 0.10, respectively (rate ratio, 1.17; 95% CI, 0.61 to 2.27). CONCLUSIONS: In a diverse population of older patients who were hospitalized for acute decompensated heart failure, an early, transitional, tailored, progressive rehabilitation intervention that included multiple physical-function domains resulted in greater improvement in physical function than usual care. (Funded by the National Institutes of Health and others; REHAB-HF ClinicalTrials.gov number, NCT02196038.).

Relationship of physical function with quality of life in older patients with acute heart failure.

BACKGROUND: Older patients with acute decompensated heart failure (ADHF) have severely impaired physical function (PF) and quality of life (QOL). However, relationships between impairments in PF and QOL are unknown but are relevant to clinical practice and trial design. METHODS: We assessed 202 consecutive patients hospitalized with ADHF in the multicenter Rehabilitation Therapy in Older Acute HF Patients (REHAB-HF) Trial. PF measures included Short Physical Performance Battery (SPPB) and 6-min walk distance (6MWD). Disease-specific QOL was assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ). General QOL was assessed by the Short Form-12 (SF-12) and EuroQol-5D-5L. PF was evaluated as a predictor of QOL using stepwise regression adjusted for age, sex, race, and New York Heart Association class. RESULTS: Participants were 72 ± 8 years, 54% women, 55% minority race, 52% with reduced ejection fraction, and body mass index 33 ± 9 kg/m2 . Participants had severe impairments in PF (6MWD 185 ± 99 m, SPPB 6.0 ± 2.5 units) and disease-specific QOL (KCCQ Overall Score 41 ± 21 and Physical Score 47 ± 24) and general QOL (SF-12 Physical Score 28 ± 9 and EuroQol Visual Analog Scale 57 ± 23). There were modest, statistically significant correlations between 6MWD and KCCQ Overall, KCCQ Physical Limitation, and SF-12 Physical Scores (r = 0.23, p < 0.001; r = 0.30, p < 0.001; and r = 0.24, p = 0.001, respectively); and between SPPB and KCCQ Physical and SF-12 Physical Scores (r = 0.20, p = 0.004, and r = 0.19, p = 0.007, respectively). Both 6MWD and SPPB were correlated with multiple components of the EuroQol-5D-5L. 6MWD was a significant, weak predictor of KCCQ Overall Score and SF-12 Physical Score (estimate = 0.05 ± 0.01, p < 0.001 and estimate = 0.05 ± 0.02, p = 0.012, respectively). SPPB was a significant, weak predictor of KCCQ Physical Score and SF-12 Physical Score (estimate = 1.37 ± 0.66, p = 0.040 and estimate = 0.54 ± 0.25, p = 0.030, respectively). CONCLUSION: In older, hospitalized ADHF patients, PF and QOL are both severely impaired but are only modestly related, suggesting that PF and QOL provide complementary information and assessment of both should be considered to fully assess clinically meaningful patient-oriented outcomes.

Left ventricular diastolic dysfunction and exercise intolerance in obese heart failure with preserved ejection fraction.

This study tested the hypothesis that early left ventricular (LV) relaxation is impaired in older obese patients with heart failure with preserved ejection fraction (HFpEF), and related to decreased peak exercise oxygen uptake (peak V̇o2). LV strain and strain rate were measured by feature tracking of magnetic resonance cine images in 79 older obese patients with HFpEF (mean age: 66 yr; mean body mass index: 38 kg/m2) and 54 healthy control participants. LV diastolic strain rates were indexed to cardiac preload as estimated by echocardiography derived diastolic filling pressures (E/e'), and correlated to peak V̇o2. LV circumferential early diastolic strain rate was impaired in HFpEF compared with controls (0.93 ± 0.05/s vs. 1.20 ± 0.07/s, P = 0.014); however, we observed no group differences in early LV radial or longitudinal diastolic strain rates. Isolating myocardial relaxation by indexing all three early LV diastolic strain rates (i.e. circumferential, radial, and longitudinal) to E/e' amplified the group difference in early LV diastolic circumferential strain rate (0.08 ± 0.03 vs. 0.13 ± 0.05, P < 0.0001), and unmasked differences in early radial and longitudinal diastolic strain rate. Moreover, when indexing to E/e', early LV diastolic strain rates from all three principal strains, were modestly related with peak V̇o2 (R = 0.36, -0.27, and 0.35, respectively, all P < 0.01); this response, however, was almost entirely driven by E/e' itself, (R = -0.52, P < 0.001). Taken together, we found that although LV relaxation is impaired in older obese patients with HFpEF, and modestly correlates with their severely reduced peak exercise V̇o2, LV filling pressures appear to play a much more important role in determining exercise intolerance.NEW & NOTEWORTHY Using a multimodal imaging approach to uncouple tissue deformation from atrial pressure, we found that left ventricular (LV) relaxation is impaired in older obese patients with HFpEF, but only modestly correlates with their severely reduced peak V̇o2. In contrast, the data show a much stronger relationship between elevated LV filling pressures and exercise intolerance, refocusing future therapeutic priorities.

Cognition, Physical Function, and Quality of Life in Older Patients With Acute Decompensated Heart Failure.

BACKGROUND: Older adults with acute decompensated heart failure have persistently poor clinical outcomes. Cognitive impairment (CI) may be a contributing factor. However, the prevalence of CI and the relationship of cognition with other patient-centered factors such a physical function and quality of life (QOL) that also may contribute to poor outcomes are incompletely understood. METHODS AND RESULTS: Older (≥60 years) hospitalized patients with acute decompensated heart failure were assessed for cognition (Montreal Cognitive Assessment [MoCA]), physical function (Short Physical Performance Battery [SPPB], 6-minute walk distance [6MWD]), and QOL (Kansas City Cardiomyopathy Questionnaire, Short Form-12). Among patients (N = 198, 72.1 ± 7.6 years), 78% screened positive for CI (MoCA of <26) despite rare medical record documentation (2%). Participants also had severely diminished physical function (SPPB 6.0 ± 2.5 units, 6MWD 186 ± 100 m) and QOL (scores of <50). MoCA positively related to SPPB (ß = 0.47, P < .001), 6MWD ß = 0.01, P = .006) and inversely related to Kansas City Cardiomyopathy Questionnaire Overall Score (ß = -0.05, P < .002) and Short Form-12 Physical Component Score (ß = -0.09, P = .006). MoCA was a small but significant predictor of the results on the SPPB, 6MWD, and Kansas City Cardiomyopathy Questionnaire. CONCLUSIONS: Among older hospitalized patients with acute decompensated heart failure, CI is highly prevalent, is underrecognized clinically, and is associated with severe physical dysfunction and poor QOL. Formal screening may reduce adverse events by identifying patients who may require more tailored care.

Frailty Among Older Decompensated Heart Failure Patients: Prevalence, Association With Patient-Centered Outcomes, and Efficient Detection Methods.

OBJECTIVES: This study sought to assess the prevalence of frailty, its associations with physical function, quality of life (QoL), cognition, and depression and to investigate more efficient methods of detection in older patients hospitalized with acute decompensated heart failure (ADHF). BACKGROUND: In contrast to the outpatient population with chronic HF, much less is known regarding frailty in older, hospitalized patients with ADHF. METHODS: Older hospitalized patients (N = 202) with ADHF underwent assessment of frailty (using Fried criteria), short physical performance battery (SPPB), 6-min walk test (6-MWT) distance, quality of life (QoL using the Kansas City Cardiomyopathy Questionnaire), cognition (using the Montreal Cognition Assessment), and depression (using the Geriatric Depression Screen [GDS]). The associations of frailty with these patient-centered outcomes were assessed by using adjusted linear regression models. Novel strategies to identify frailty were examined. RESULTS: A total of 50% of older, hospitalized patients with ADHF were frail, 48% were pre-frail, and 2% were non-frail. Female sex, burden of comorbidity, and prior HF hospitalization were significantly associated with higher likelihood of frailty. Frailty (vs. pre-frail status) was associated with a significantly worse SPPB score (5 ± 2.2 vs. 7 ± 2.4, respectively), 6-MWT distance (143 ± 79 m vs. 221 ± 99 m, respectively), QoL (35 ± 19 vs. 46 ± 21, respectively), and more depression (GDS score: 5.5 ± 3.5 vs. 4.2 ± 3.3, respectively) but similar cognition. These associations were unchanged after adjustment for age, sex, race, total comorbidities, and body mass index. Slow gait speed plus low physical activity signaled frailty status as well (C-statistic = 0.85). CONCLUSIONS: Ninety-eight percent of older, hospitalized patients with ADHF are frail or pre-frail. Frailty (vs. pre-frail status) is associated with worse physical function, QoL, comorbidity, and depression. The simple 4-m walk test combined with self-reported physical activity may quickly and efficiently identify frailty in older patients with ADHF.

Physical Function, Frailty, Cognition, Depression, and Quality of Life in Hospitalized Adults ≥60 Years With Acute Decompensated Heart Failure With Preserved Versus Reduced Ejection Fraction.

BACKGROUND: Older hospitalized acute decompensated heart failure (HF) patients have persistently poor outcomes and delayed recovery regardless of ejection fraction (EF). We hypothesized that impairments in physical function, frailty, cognition, mood, and quality of life (QoL) potentially contributing to poor clinical outcomes would be similarly severe in acute decompensated HF patients ≥60 years of age with preserved versus reduced EF (HFpEF and HFrEF). METHODS AND RESULTS: In 202 consecutive older (≥60 years) hospitalized acute decompensated HF patients in a multicenter trial, we prospectively performed at baseline: short physical performance battery, 6-minute walk distance, frailty assessment, Geriatric Depression Scale, Montreal Cognitive Assessment, and QoL assessments. Older acute decompensated HFpEF (EF ≥45%, n=96) and HFrEF (EF <45%, n=106) patients had similar impairments in all physical function measures (short physical performance battery [5.9±0.3 versus 6.2±0.2]; 6-minute walk distance [184±10 versus 186±9 m]; and gait speed [0.60±0.02 versus 0.61±0.02 m/s]) and rates of frailty (55% versus 52%; P=0.70) and cognitive impairment (77% versus 81%; P=0.56) when adjusted for differences in sex, body mass index, and comorbidities. However, depression and QoL were consistently worse in HFpEF versus HFrEF. Depression was usually unrecognized clinically with 38% having Geriatric Depression Scale ≥5 and no documented history of depression. CONCLUSIONS: Patients ≥60 years hospitalized with acute decompensated HF patients have broad, marked impairments in physical function and high rates of frailty and impaired cognition: these impairments are similar in HFpEF versus HFrEF. Further, depression was common and QoL was reduced, and both were worse in HFpEF than HFrEF. Depression was usually unrecognized clinically. These findings suggest opportunities for novel interventions to improve these important patient-centered outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02196038.

Raw and Count Data Comparability of Hip-Worn ActiGraph GT3X+ and Link Accelerometers.

To enable inter- and intrastudy comparisons it is important to ascertain comparability among accelerometer models. PURPOSE: The purpose of this study was to compare raw and count data between hip-worn ActiGraph GT3X+ and GT9X Link accelerometers. METHODS: Adults (n = 26 (n = 15 women); age, 49.1 ± 20.0 yr) wore GT3X+ and Link accelerometers over the right hip for an 80-min protocol involving 12-21 sedentary, household, and ambulatory/exercise activities lasting 2-15 min each. For each accelerometer, mean and variance of the raw (60 Hz) data for each axis and vector magnitude (VM) were extracted in 30-s epochs. A machine learning model (Montoye 2015) was used to predict energy expenditure in METs from the raw data. Raw data were also processed into activity counts in 30-s epochs for each axis and VM, with Freedson 1998 and 2011 count-based regression models used to predict METs. Time spent in sedentary, light, moderate, and vigorous intensities was derived from predicted METs from each model. Correlations were calculated to compare raw and count data between accelerometers, and percent agreement was used to compare epoch-by-epoch activity intensity. RESULTS: For raw data, correlations for mean acceleration were 0.96 ± 0.05, 0.89 ± 0.16, 0.71 ± 0.33, and 0.80 ± 0.28, and those for variance were 0.98 ± 0.02, 0.98 ± 0.03, 0.91 ± 0.06, and 1.00 ± 0.00 in the X, Y, and Z axes and VM, respectively. For count data, corresponding correlations were 1.00 ± 0.01, 0.98 ± 0.02, 0.96 ± 0.04, and 1.00 ± 0.00, respectively. Freedson 1998 and 2011 count-based models had significantly higher percent agreement for activity intensity (95.1% ± 5.6% and 95.5% ± 4.0%) compared with the Montoye 2015 raw data model (61.5% ± 27.6%; P < 0.001). CONCLUSIONS: Count data were more highly comparable than raw data between accelerometers. Data filtering and/or more robust raw data models are needed to improve raw data comparability between ActiGraph GT3X+ and Link accelerometers.

Strategies for supporting intervention fidelity in the rehabilitation therapy in older acute heart failure patients (REHAB-HF) trial.

INTRODUCTION: Acute decompensated heart failure (ADHF) is the leading cause of hospitalization in older adults. Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial is a multi-site clinical trial to determine if physical rehabilitation intervention in older patients with ADHF improves physical function and reduces rehospitalizations. The REHAB-HF intervention aims to improve functional performance utilizing reproducible and progressive exercises that are individually tailored to the patient's physiological and physical capabilities. Fidelity of the intervention is essential to the trial's integrity and success. Maintaining fidelity is challenged by the complex, multi-domain design of the intervention implemented across multiple sites and delivered to an older, heterogeneous participant pool with severe underlying disease and multi-morbidity. METHODS/DESIGN: Given the dynamic nature of the REHAB-HF intervention, rigorous fidelity strategies were formulated. In this paper we summarize the specific strategies that REHAB-HF is using to meet the National Institutes of Health (NIH) Behavior Change Consortium Treatment Fidelity Workgroup recommendations in 5 key areas: 1) ensuring the intervention dose is consistent across participants, 2) standardizing interventionist training, 3) monitoring intervention delivery, 4) evaluating participants' understanding of information provided, and 5) ensuring that participants use the skills taught in the intervention. DISCUSSION: Effective intervention fidelity strategies are essential to the reliability and validity of physical function intervention trials. The REHAB-HF trial has developed comprehensive, specific strategies to ensure intervention fidelity despite a challenging study population and a complex intervention to meet NIH recommendations. This experience provides a strong working model for future physical function intervention trials.