Frailty Status Modifies the Efficacy of ICD Therapy for Primary Prevention Among Patients With HF.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy is recommended to reduce mortality risk in patients with heart failure with reduced ejection fraction (HFrEF). Frailty is common among patients with HFrEF and is associated with increased mortality risk. Whether the therapeutic efficacy of ICD is consistent among frail and nonfrail patients with HFrEF remains unclear. OBJECTIVES: The aim of this study was to evaluate the effect modification of baseline frailty burden on ICD efficacy for primary prevention among participants of the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial). METHODS: Participants in SCD-HeFT with HFrEF randomized to ICD vs placebo were included. Baseline frailty was estimated using the Rockwood Frailty Index (FI), and participants were stratified into high (FI > median) vs low (FI ≤ median) frailty burden groups. Multivariable Cox models with multiplicative interaction terms (frailty × treatment arm) were constructed to evaluate whether baseline frailty status modified the treatment effect of ICD for all-cause mortality. RESULTS: The study included 1,676 participants (mean age: 59 ± 12 years, 23% women) with a median FI of 0.30 (IQR: 0.23-0.37) in the low frailty group and 0.54 (IQR: 0.47-0.60) in the high frailty group. In adjusted Cox models, baseline frailty status significantly modified the treatment effect of ICD therapy (Pinteraction = 0.047). In separate stratified analysis by frailty status, ICD therapy was associated with a lower risk of all-cause mortality among participants with low frailty burden (HR: 0.56; 95% CI: 0.40-0.78) but not among those with high frailty burden (HR: 0.86; 95% CI: 0.68-1.09). CONCLUSIONS: Baseline frailty modified the efficacy of ICD therapy with a significant mortality benefit observed among participants with HFrEF and a low frailty burden but not among those with a high frailty burden.

Assessing and managing frailty in advanced heart failure: An International Society for Heart and Lung Transplantation consensus statement.

Frailty is increasingly recognized as a salient condition in patients with heart failure (HF) as previous studies have determined that frailty is highly prevalent and prognostically significant, particularly in those with advanced HF. Definitions of frailty have included a variety of domains, including physical performance, sarcopenia, disability, comorbidity, and cognitive and psychological impairments, many of which are common in advanced HF. Multiple groups have recently recommended incorporating frailty assessments into clinical practice and research studies, indicating the need to standardize the definition and measurement of frailty in advanced HF. Therefore, the purpose of this consensus statement is to provide an integrated perspective on the definition of frailty in advanced HF and to generate a consensus on how to assess and manage frailty. We convened a group of HF clinicians and researchers who have expertise in frailty and related geriatric conditions in HF, and we focused on the patient with advanced HF. Herein, we provide an overview of frailty and how it has been applied in advanced HF (including potential mechanisms), present a definition of frailty, generate suggested assessments of frailty, provide guidance to differentiate frailty and related terms, and describe the assessment and management in advanced HF, including with surgical and nonsurgical interventions. We conclude by outlining critical evidence gaps, areas for future research, and clinical implementation.

Relationship of Race With Functional and Clinical Outcomes With the REHAB-HF Multidomain Physical Rehabilitation Intervention for Older Patients With Acute Heart Failure.

Background The REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) randomized trial demonstrated that a 3-month transitional, tailored, progressive, multidomain physical rehabilitation intervention improves physical function, frailty, depression, and health-related quality of life among older adults with acute decompensated heart failure. Whether there is differential intervention efficacy by race is unknown. Methods and Results In this prespecified analysis, differential intervention effects by race were explored at 3 months for physical function (Short Physical Performance Battery [primary outcome], 6-Minute Walk Distance), cognition, depression, frailty, health-related quality of life (Kansas City Cardiomyopathy Questionnaire, EuroQoL 5-Dimension-5-Level Questionnaire) and at 6 months for hospitalizations and death. Significance level for interactions was P≤0.1. Participants (N=337, 97% of trial population) self-identified in near equal proportions as either Black (48%) or White (52%). The Short Physical Performance Battery intervention effect size was large, with values of 1.3 (95% CI, 0.4-2.1; P=0.003]) and 1.6 (95% CI, 0.8-2.4; P<0.001) in Black and White participants, respectively, and without significant interaction by race (P=0.56). Beneficial effects were also demonstrated in 6-Minute Walk Distance, gait speed, and health-related quality of life scores without significant interactions by race. There was an association between intervention and reduced all-cause rehospitalizations in White participants (rate ratio, 0.73 [95% CI, 0.55-0.98]; P=0.034) that appears attenuated in Black participants (rate ratio, 1.06 [95% CI, 0.81-1.41]; P=0.66; interaction P=0.067). Conclusions The intervention produced similarly large improvements in physical function and health-related quality of life in both older Black and White patients with acute decompensated heart failure. A future study powered to determine how the intervention impacts clinical events is required. REGISTRATION URL: https://www.clinicaltrials.gov. Identifier: NCT02196038.

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.

Clinical Predictors of Adherence to Exercise Training Among Individuals With Heart Failure: THE HF-ACTION STUDY.

PURPOSE: Suboptimal adherence is a major limitation to achieving the benefits of exercise interventions, and our ability to predict and improve adherence is limited. The purpose of this analysis was to identify baseline clinical and demographic characteristics predicting exercise training adherence in the HF-ACTION study cohort. METHODS: Adherence to exercise training, defined by the total duration of exercise performed (min/wk), was evaluated in 1159 participants randomized to the HF-ACTION exercise intervention. More than 50 clinical, demographic, and exercise testing variables were considered in developing a model of the min/wk end point for 1-3 mo (supervised training) and 10-12 mo (home-based training). RESULTS: In the multivariable model for 1-3 mo, younger age, lower income, more severe mitral regurgitation, shorter 6-min walk test distance, lower exercise capacity, and Black or African American race were associated with poorer exercise intervention adherence. No variable accounted for >2% of the variance and the adjusted R2 for the final model was 0.14. Prediction of adherence was similarly limited for 10-12 mo. CONCLUSIONS: Clinical and demographic variables available at the initiation of exercise training provide very limited information for identifying patients with heart failure who are at risk for poor adherence to exercise interventions.

Physical activity and relationship to physical function, quality of life, and cognitive function in older patients with acute decompensated heart failure.

BACKGROUND: Volitional physical activity level is predictive of a variety of health outcomes, but has not been examined in patients recently hospitalized for acute decompensated HF (ADHF). METHODS: Ten to 14 days after index hospitalization for ADHF, 93 participants wore a wrist-mounted triaxial accelerometer (ActiGraph GT3X+) to objectively quantify sedentary behavior, light physical activity, and moderate-to-vigorous physical activity. Levels were compared to 2 groups of age-matched NHANES participants: healthy and chronic, stable HF. The relationship between physical activity levels and physical function [Short Physical Performance Battery (SPPB)], HF-specific quality-of-life (QOL) [Kansas City Cardiomyopathy Questionnaire (KCCQ)], and cognition [Montreal Cognitive Assessment (MOCA)] were examined. RESULTS: ADHF participants accumulated a median 1,008 (IQR 896, 1,109) minutes of sedentary time, 88 (57, 139) minutes of light physical activity, and 10 (6, 25) minutes of moderate-to-vigorous physical activity per day. Sedentary time, light physical activity, or moderate-to-vigorous activity did not differ by sex or EF subtype. ADHF participants spent only 9% of awake time nonsedentary, compared to 34% and 27% for healthy adults and adults with chronic, stable HF, respectively. Among ADHF participants, SPPB, KCCQ, and MOCA scores did not differ among quartiles of total physical activity. CONCLUSIONS: Older patients recently hospitalized for ADHF have very low levels of physical activity and high levels of sedentary time, both of which may be potential targets for interventions in this high-risk population. Physical activity level was not significantly associated with objectively measured physical function, QOL, or cognition, suggesting that this measure provides independent information regarding the patient experience of living with HF. TRIAL REGISTRATION: NCT02196038, https://clinicaltrials.gov/ct2/show/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.

Frailty Status Modifies the Efficacy of Exercise Training Among Patients With Chronic Heart Failure and Reduced Ejection Fraction: An Analysis From the HF-ACTION Trial.

BACKGROUND: Supervised aerobic exercise training (ET) is recommended for stable outpatients with heart failure (HF) with reduced ejection fraction (HFrEF). Frailty, a syndrome characterized by increased vulnerability and decreased physiologic reserve, is common in patients with HFrEF and associated with a higher risk of adverse outcomes. The effect modification of baseline frailty on the efficacy of aerobic ET in HFrEF is not known. METHODS: Stable outpatients with HFrEF randomized to aerobic ET versus usual care in the HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training) trial were included. Baseline frailty was estimated using the Rockwood frailty index (FI), a deficit accumulation-based model of frailty assessment; participants with FI scores >0.21 were identified as frail. Multivariable Cox proportional hazard models with multiplicative interaction terms (frailty × treatment arm) were constructed to evaluate whether frailty modified the treatment effect of aerobic ET on the primary composite end point (all-cause hospitalization or mortality), secondary end points (composite of cardiovascular death or cardiovascular hospitalization, and cardiovascular death or HF hospitalization), and Kansas City Cardiomyopathy Questionnaire score. Separate models were constructed for continuous (FI) and categorical (frail versus not frail) measures of frailty. RESULTS: Among 2130 study participants (age, 59±13 years; 28% women), 1266 (59%) were characterized as frail (FI>0.21). Baseline frailty burden significantly modified the treatment effect of aerobic ET (P interaction: FI × treatment arm=0.02; frail status [frail versus nonfrail] × treatment arm=0.04) with a lower risk of primary end point in frail (hazard ratio [HR], 0.83 [95% CI, 0.72-0.95]) but not nonfrail (HR, 1.04 [95% CI, 0.87-1.25]) participants. The favorable effect of aerobic ET among frail participants was driven by a significant reduction in the risk of all-cause hospitalization (HR, 0.84 [95% CI, 0.72-0.99]). The treatment effect of aerobic ET on all-cause mortality and other secondary endpoints was not different between frail and nonfrail patients (P interaction>0.1 for each). Aerobic ET was associated with a nominally greater improvement in Kansas City Cardiomyopathy Questionnaire scores at 3 months among frail versus nonfrail participants without a significant treatment interaction by frailty status (P interaction>0.2). CONCLUSIONS: Among patients with chronic stable HFrEF, baseline frailty modified the treatment effect of aerobic ET with a greater reduction in the risk of all-cause hospitalization but not mortality.

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).

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.).

Contrast-Enhanced Ultrasound of Muscle Perfusion May Indicate Patient Response to Left Ventricular Assist Device Therapy.

PURPOSE: Left ventricular assist device (LVAD) support is associated with peripheral vascular abnormalities beyond those associated with heart failure (HF). These abnormalities are associated with persistent functional impairments that adversely impact quality of life (QoL). Methods for measuring peripheral vascular function in this population are needed. METHODS: This pilot study investigated the use of contrast-enhanced ultrasound (CEUS) using standardized protocols to estimate changes in peripheral (quadriceps) muscle perfusion among patients with HF (INTERMACS profile 3) undergoing LVAD implantation (n = 7). Patients were then stratified by those who did ("responders", n = 4) and did not ("nonresponders", n = 3) report QoL improvement with LVAD support. RESULTS: Serial measurements obtained preoperatively and 3 months following LVAD implantation showed no significant change (P > .23) in muscle perfusion by all CEUS-based measures at rest or with an exercise stimulus for the overall population. Responders exhibited improved muscle perfusion at rest (P = .043) and decreased time to peak contrast enhancement (P = .010) at 3 months compared with baseline, suggesting improved delivery of blood to the extremities post-LVAD. Nonresponders showed unchanged resting muscle perfusion (P > .99), time to peak contrast enhancement (P = .59), and response to exercise stimulus (P > .99) following LVAD therapy. CONCLUSION: Our findings suggest that CEUS evaluation is a promising noninvasive, quantitative modality for real-time assessment of peripheral vasculature and muscle perfusion as an indication of treatment response in LVAD recipients and that this modality may capture perfusion measures important to QoL following LVAD implantation.

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.

Left Ventricular Assist Device Decommissioning Compared with Explantation for Ventricular Recovery: A Systematic Review.

Left ventricular assist device (LVAD) withdrawal with ventricular recovery represents the optimal outcome for patients previously implanted with an LVAD. The aim of this systematic review was to examine the patient outcomes of device withdrawal via minimally invasive pump decommissioning as compared with reoperation for pump explantation. An electronic search was performed to identify all studies in the English literature assessing LVAD withdrawal. All identified articles were systematically assessed for inclusion and exclusion criteria. Overall, 44 studies (85 patients) were included in the analysis, of whom 20% underwent decommissioning and 80% underwent explantation. The most commonly used LVAD types included the HeartMate II (decommissioning 23.5% vs. explantation 60.3%; p = 0.01) and HeartWare HVAD (decommissioning 76.5% vs. explantation 17.6%; p < 0.001). At median follow-up of 389 days, there were no significant differences in the incidence of cerebrovascular accidents (p = 0.88), infection (p = 0.75), and survival (p = 0.20). However, there was a trend toward a higher recurrence of heart failure in patients who underwent decommissioning as compared with explantation (decommissioning 15.4% vs. explantation 8.2%, cumulative hazard; p = 0.06). Decommissioning appears to be a feasible alternative to LVAD explantation in terms of overall patient outcomes.

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.

Cardiac Rehabilitation in Older Adults with Heart Failure: Fitting a Square Peg in a Round Hole.

Cardiac rehabilitation (CR) is a structured exercise and lifestyle program that improves mortality and quality of life in patients with heart failure (HF) with reduced ejection fraction. However, significant gaps remain in optimizing CR for older adults with HF. This review summarizes the state of the science and specific knowledge gaps regarding older adults with HF. The authors discuss the importance of geriatric complexities in the design and implementation of CR, summarize promising future research in this area, and provide a clinical framework for current CR clinicians to follow when considering the specific needs of older adults with HF.

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.