Physical Frailty Predicts Outcomes in Patients Undergoing Evaluation for Kidney Transplantation.

INTRODUCTION: An increasing number of older patients are undergoing evaluation for kidney transplantation; however, older patients experience increased rates of complications compared with younger patients, leading to the study of frailty assessments. Although many centers have evaluated the Fried Frailty Phenotype (FFP), less is known about the ability of the Short Performance Physical Battery (SPPB) to predict outcomes. METHODS: Frailty assessment by FFP and SPPB was introduced into routine outpatient evaluation for patients aged 55 years and older referred for transplantation. Transplant rate, length of stay, readmission up to 3 months posttransplant, and death were reviewed. Patients were evaluated in an initial cohort followed by a validation cohort by FFP and SPPB. Multivariate analysis correcting for demographic characteristics was applied. RESULTS: Patient cohorts reflected the racial and ethnic diversity of our population, including approximately 40% Hispanic patients. The first cohort of 514 patients demonstrated a significant association between frailty as measured by SPPB and transplantation (odds ratio [OR], 2.27; 95% CI, 1.38-3.83; p = .002). The second cohort of 1408 patients validated the association between frailty measured by SPPB and transplantation (OR, 2.81; 95% CI, 1.83-4.48; p < .001). In addition, there was a significant association between nonfrail status measured by SPPB and death (OR, 0.16; 95% CI, 0.04-0.62; p = .006). CONCLUSIONS: Frailty assessment is a potentially useful approach for the assessment of transplant candidates. Our real-world study examined the performance of 2 methods of frailty evaluation methods in a diverse population, demonstrating that SPPB but not FFP was predictive of clinical outcomes. Incorporation of frailty assessments into transplant evaluation may improve risk stratification and optimize outcomes for older patients.

Frailty and Age-Associated Assessments Associated with Chronic Kidney Disease and Transplantation Outcomes.

Background: Frailty is often defined as a decrease in physiological reserve and has been shown to be correlated with adverse health outcomes and mortality in the general population. This condition is highly prevalent in the chronic kidney disease (CKD) patient population as well as in kidney transplant (KT) recipients. Other age-associated changes include sarcopenia, nutrition, cognition, and depression. In assessing the contributions of these components to patient outcomes and their prevalence in the CKD and KT patient population, it can be determined how such variables may be associated with frailty and the extent to which they may impact the adverse outcomes an individual may experience. Objectives: We sought to perform a systematic literature review to review published data on frailty and associated age-associated syndromes in CKD and KT patients. Results: Over 80 references pertinent to frailty, sarcopenia, nutrition, cognition, or depression in patients with CKD or KT were identified. Systematic review was performed to evaluate the data supporting the use of the following approaches: Fried Frailty, Short Physical Performance Battery, Frailty Index, Sarcopenia Index, CT scan quantification of muscle mass, health-related quality of life, and assessment tools for nutrition, cognition, and depression. Conclusion: This report represents a comprehensive review of previously published research articles on this topic. The intersectionality between all these components in contributing to the patient's clinical status suggests a need for a multifaceted approach to developing comprehensive care and treatment for the CKD and KT population to improve outcomes before and after transplantation.

Patient-centered care in geriatric cardiology.

Geriatric cardiology involves providing cardiovascular care to older adults in relation to aging. Although cardiovascular diseases are the most common diseases faced by older adults, they often co-occur with numerous aging-related challenges, such as multimorbidity, frailty, polypharmacy, falls, functional and cognitive impairment, which present challenges to implementing standard disease-based treatment strategies. Faced with these complexities, patient-centered care in geriatric cardiology strives to direct all management toward the achievement of an individual's prioritized health and life goals by employing shared decision-making to align treatment with goals, utilizing stated goals to navigate situations of treatment uncertainty, and pro-actively mitigating aging-related risks. This fundamental change in cardiovascular medicine from disease-centered management to patient-centered goal-directed care is necessary to facilitate wellness, independence, and favorable quality of life outcomes in the older adult population.

Impact of frailty on mortality and quality of life in patients with a history of cancer undergoing transcatheter aortic valve replacement.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is increasingly offered for aortic stenosis (AS) treatment in patients with a history of cancer. The impact of frailty on outcomes in this specific patient population is not well described. HYPOTHESIS: Frailty is associated with mortality and poorer quality of life (QOL) outcomes in patients undergoing TAVR with a history of cancer. METHODS: This retrospective single center cohort study included AS patients who underwent TAVR from August 1, 2012 to May 15, 2020. Frailty was measured using serum albumin, hemoglobin, gait speed, functional dependence, and cognitive impairment. The primary outcome was a composite of all-cause mortality and QOL at 1 year. A poor primary outcome was defined as either all-cause mortality, Kansas City Cardiomyopathy Questionnaire overall summary (KCCQ-OS) score <45 or a KCCQ-OS score decline of ≥10 points from baseline. Regression analysis was used to determine the impact of frailty on the primary outcome. RESULTS: The study population was stratified into active/recent cancer (n = 107), remote cancer (n = 85), and non-cancer (n = 448). Univariate analysis of each cohort showed that frailty was associated with the primary outcome only in the non-cancer cohort (p = .004). Multivariate analysis showed that cancer history was not associated with a poor primary outcome, whereas frailty was (1.7 odds ratio, 95% confidence interval [CI]: 1.1-2.8; p = .028). CONCLUSIONS: Frailty is associated with mortality and poor QOL in the overall and non-cancer cohorts. Further investigation is warranted to understand frailty's effect on the cancer population. Frailty should be heavily considered during TAVR evaluation.

Predictive value of chart-based frailty evaluation for lung transplant candidates.

Frailty, defined as a state of decreased physiologic reserve, has been correlated with poorer outcomes after hospitalization or surgery. Studies in lung transplant patients have associated frailty with an increased risk of post-transplant mortality; however, a unified approach is lacking. The identification of frail patients can help clinicians pre-emptively target modifiable risk factors and may facilitate risk stratification. The Frailty Risk Score (FRS) is a chart review-based approach based on eight symptoms and four laboratory biomarkers. We applied this method in a retrospective study to investigate its utility in predicting post-transplant lung outcomes. Eighty-four lung transplant recipients were evaluated, including 51 older (≥ 60) and 33 younger (< 60) patients. Median FRS score was 3.9, with 63 categorized as frail (75%) and 21 as non-frail (25%), using a previously published cut-off of ≥3 to define frailty. A high FRS was associated with readmission in the first year after transplantation and with the number of readmissions. There was also an association between FRS score and death (p = .047). FRS may be a viable tool in the assessment of lung transplant candidates. Frail patients may benefit from earlier referral and targeted therapy prior to transplant, as well as close post-transplant follow-up.

Benefits of both physical assessment and electronic health record review to assess frailty prior to heart transplant.

INTRODUCTION: Frailty status affects outcomes after heart transplantation, but the optimal way to assess frailty prior to transplant remains unknown. METHODS: This single-center, observational study assessed 44 heart transplant candidates for frailty using three methods. The Short Physical Performance Battery (SPPB) and Fried Frailty Phenotype (FFP) were used as two physical assessments of frailty. The Frailty Risk Score (FRS) was used as a chart-review based assessment measuring 20 different biopsychosocial and functional components, including biomarkers, depression, cognitive impairment, and sleep. RESULTS: We determined the correlation between FRS, SPPB, and FFP and how each correlated with clinical outcomes. Of 44 participants, mean age was 60 years. FRS correlated with SPPB and FFP (P = .043, P < .001, respectively). Higher frailty as measured by SPPB and FRS was significantly associated with lack of achieving waitlist status (P = .022; P = .002) and not being transplanted (P = .026; P = .008). Higher frailty by SPPB and FFP was also associated with mortality (P = .010; P = .025). CONCLUSION: SPPB and chart-review FRS showed potential for predicting waitlist and transplant status of heart transplant candidates, while SPPB and FFP were associated with mortality. Additional studies may serve to validate these observations.

Metformin Treatment in Old Rats and Effects on Mitochondrial Integrity.

Metformin, a commonly used well-tolerated treatment for type 2 diabetes, is being deployed in clinical trials to ameliorate aging in older nondiabetic humans. Concerningly, some experiments in model organisms have suggested that metformin use at old ages shortens life span and is toxic to mitochondria. The demonstrated safety of metformin therapy in humans and the conflicting data from model organisms compelled us to test the hypothesis that metformin treatment would be toxic to older rats. To define an effective dose in 30-month-old hybrid rats, we evaluated two doses of metformin (0.1%, 0.75% of the diet) and treated the rats for 4 months. Body mass decreased at the 0.75% dose. Neither dose affected mortality between 30 and 34 months of age. We assessed mitochondrial integrity by measuring mitochondrial DNA (mtDNA) copy number and deletion mutation frequency, and mitochondrial respiration in skeletal muscle and the heart. In skeletal muscle, we observed no effect of metformin on quadriceps mass, mtDNA copy number, or deletion frequency. In the heart, metformin-treated rats had higher mtDNA copy number, lower cardiac mass, with no change in mtDNA deletion frequency. Metformin treatment resulted in lower mitochondrial complex I-dependent respiration in the heart. We found that, in old rats, metformin did not compromise mtDNA integrity, did not affect mortality, and may have cardiac benefits. These data provide some reassurance that a metformin intervention in aged mammals is not toxic at appropriate doses.

Urinary Stress Hormones, Hypertension, and Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.

[Figure: see text].

Baseline pro-inflammatory gene expression in whole blood is related to adverse long-term outcomes after transcatheter aortic valve replacement: a case control study.

BACKGROUND: Age-associated inflammation and immune system dysfunction have been implicated as mechanisms that increase risk for adverse long-term procedural outcomes in older adults. The purpose of this study was to investigate relationships between baseline inflammatory and innate antiviral gene expression and outcomes after transcatheter aortic valve replacement (TAVR) in older adults with severe aortic stenosis. METHODS: We performed a retrospective case-control study comparing pre-procedural pro-inflammatory and Type 1 interferon (IFN) gene expression in 48 controls with favorable outcomes (alive 1 year after TAVR with improved quality of life [QoL]) versus 48 individuals with unfavorable outcomes (dead by 1 year or alive at 1 year but with reduced QoL). Gene expression was evaluated in whole blood via (1) pre-defined composite scores of 19 inflammation-associated genes and 34 Type I IFN response genes, and (2) pro-inflammatory and antiviral transcription factor activity inferred from promotor based bioinformatics analyses of genes showing > 25% difference in average expression levels across groups. All analyses were adjusted for age, gender, body mass index, diabetes, immunosuppression, cardiovascular disease (CVD), and frailty. RESULTS: Relative to controls, those with unfavorable outcomes demonstrated higher expression of the pro-inflammatory gene composite prior to TAVR (p < 0.01) and bioinformatic indicators of elevated Nuclear Factor kB (p < 0.001) and Activator Protein 1 (p < 0.001) transcription factor activity, but no significant differences in Type I IFN-related gene expression. CONCLUSIONS: These results demonstrate that a pro-inflammatory state prior to TAVR, independent of CVD severity and frailty status, is associated with worse long-term procedural outcomes.

Serum Aldosterone Concentration, Blood Pressure, and Coronary Artery Calcium: The Multi-Ethnic Study of Atherosclerosis.

Aldosterone is a steroid hormone regulating fluid and electrolyte homeostasis and is known to increase the risk of atherosclerosis. In this study, we examined the associations of serum aldosterone concentrations with subclinical atherosclerosis and all-cause mortality. This study included 948 adults aged 46 to 88 years from the MESA (Multi-Ethnic Study of Atherosclerosis) with measurements of serum aldosterone and plasma renin activity and not taking antihypertensive medications. Coronary calcification was longitudinally assessed using Agatston coronary artery calcium score from computed tomography scans. All-cause mortality was ascertained from the medical record. The average age (SD) was 62.3 (9.4) years and 53% were male. Among 700 subjects who had follow-up coronary artery calcium score (median follow-up of 6.4 years), higher aldosterone levels (per 100 pg/mL) were associated with higher coronary artery calcium (relative ratio, 1.17 [95% CI, 1.04-1.32]), with the association being stronger in individuals with suppressed plasma renin activity (≤0.5 µg/L/hr). Systolic or diastolic blood pressure mediated around 45% of the total effect of aldosterone on coronary artery calcium. Over a median follow-up of 12.5 years (120 deaths identified among 948 subjects), aldosterone was associated with the increased risk of all-cause mortality when plasma renin activity was suppressed; hazard ratio per 100 pg/mL, 1.70 (95% CI, 1.10-2.63). In this study, we found that higher aldosterone levels were associated with the increased risk of subclinical coronary atherosclerosis and all-cause mortality particularly when renin was suppressed. Our findings indicate the importance of aldosterone levels (even within the reference range) with respect to the cardiovascular system and overall health.

The aging transplant population and immunobiology: any therapeutic implication?

PURPOSE OF REVIEW: The aim of this review is to describe the latest investigations into the immunobiology of aging and the potential impact on outcomes after mechanical circulatory support implantation and heart transplantation. This information is relevant given the growing numbers of older patients with heart failure undergoing evaluation for mechanical circulatory support device (MCSD) or heart transplantation. RECENT FINDINGS: A host of aging-associated aspects of immune dysfunction have been described in the general population including T-cell senescence, exhaustion, and terminal dedifferentiation, as well as impaired function of innate immune cells. Another important consequence of T-cell senescence is inflammation, which is known to have a strong relationship with both heart failure and frailty in older patients. Recent data on the association between T-cell and monocyte phenotypes as well as evaluation of gene expression and adverse outcomes after MCSD suggests the potential value of immunologic assessment of MCSD and heart transplant candidates and recipients. Measurement of physical frailty represents another avenue for patient evaluation that may complement immunologic assessment. Determination of immune dysfunction and frailty prior to transplantation may have implications for choice of induction and dosing of maintenance immunosuppression. SUMMARY: As the age of transplant and MCSD candidates and recipients continues to increase, it is important for providers to recognize the potential impact of aging-associated immune dysfunction and how it may influence candidate selection, postintervention monitoring, and adjustment of immunosuppression.

Intergenerational mentoring, eudaimonic well-being and gene regulation in older adults: A pilot study.

To clarify the biological mechanisms underlying the relationship between pro-social behavior and health, this pilot study examined the impact of a 9-month intergenerational helping intervention on conserved transcriptional response to adversity (CTRA) gene expression profiles, which are characterized by up-regulation of genes involved in inflammation and down-regulation of genes involved in antiviral defenses. The Generation Xchange program trains and places older (age 50+) volunteers in K-3rd grade classrooms to aid students' academic development (reading and math) and address behavioral issues (e.g., inability to focus during class, behaviors that disrupt class). Volunteers were predominately women (89%) and African American (94%) from the neighborhoods around the schools. Repeated measures planned contrast analysis of 53 CTRA indicator transcripts in 50 blood samples collected from 18 individuals on 2-3 occasions revealed a significant reduction in CTRA gene expression from baseline to the average of 3- and 9-month follow-up. The magnitude of individual decrease in CTRA gene expression correlated with the magnitude of individual increase in eudaimonic well-being over time (net of changes in hedonic well-being). In addition to clarifying biological pathways through which pro-social behavior might impact health, these pilot data suggest that the GenX program may have favorable effects on immune cell gene regulation.

Compared to non-drinkers, individuals who drink alcohol have a more favorable multisystem physiologic risk score as measured by allostatic load.

AIMS: Alcohol use is associated with both positive and negative effects on individual cardiovascular risk factors, depending upon which risk factor is assessed. The present analysis uses a summative multisystem index of biologic risk, known as allostatic load (AL), to evaluate whether the overall balance of alcohol-associated positive and negative cardiovascular risk factors may be favorable or unfavorable. METHODS: This analysis included 1255 adults from the Midlife in the United States (MIDUS) biomarker substudy. Participants, average age 54.5 (±11) years, were divided into 6 alcohol-use categories based on self-reported drinking habits. Current non-drinkers were classified as lifelong abstainers and former light drinkers, former moderate drinkers, or former heavy drinkers. Current alcohol users were classified as light, moderate, or heavy drinkers. A total AL score was calculated using 24 biomarkers grouped into 7 physiologic systems including cardiovascular, inflammation, glucose metabolism, lipid metabolism, sympathetic and parasympathetic nervous systems, and the hypothalamic-pituitary-adrenal axis. Mixed-effects regression models were fit to determine the relationship between alcohol use categories and AL with controls for covariates that may influence the relationship between alcohol use and AL. RESULTS: 468 (37.6%) individuals were current non-drinkers while 776 (62.4%) were current drinkers. In adjusted mixed-effects regression models, all 3 groups of current drinkers had significantly lower average AL scores than the lifelong abstainer/former light drinker group (light: -0.23, 95% CI -0.40, -0.07, p < 0.01; moderate: -0.20, 95% CI -0.38, -0.02, p < 0.05; heavy: -0.30, 95% CI -0.57, -0.04, p < 0.05), while the average AL scores of former moderate and former heavy drinkers did not differ from the lifelong abstainer/former light drinker group. CONCLUSIONS: Current alcohol use is associated cross-sectionally with a favorable multisystem physiologic score known to be associated with better long-term health outcomes, providing evidence in support of long-term health benefits related to alcohol consumption.

Perspectives on Implementing a Multidomain Approach to Caring for Older Adults With Heart Failure.

BACKGROUND/OBJECTIVES: The American College of Cardiology (ACC) Geriatric Cardiology Section Leadership Council recently outlined 4 key domains (which are composed of 14 subdomains) that are important to assess in older adults with heart failure (HF). We sought to determine which geriatric domains/subdomains are routinely assessed, how they are assessed, and how they impact clinical management in the care of ambulatory older adults with HF. DESIGN: Survey. SETTING: Ambulatory. PARTICIPANTS: Fifteen active ACC member physicians from the geriatric cardiology community. MEASUREMENTS: Electronic survey assessing which domains/subdomains are currently assessed in these selected real-world practices, how they are assessed, and how they are incorporated into clinical management. RESULTS: Of 15 clinicians, 14 responded to the survey. The majority routinely assess 3 to 4 domains (median, 3; interquartile range, 3-4) and a range of 4 to 12 subdomains (median, 8; interquartile range, 6-11). All respondents routinely assess the medical and physical function domains, 71% routinely assess the mind/emotion domain, and 50% routinely assess the social domain. The most common subdomains included comorbidity burden (100%), polypharmacy (100%), basic function (93%), mobility (86%), falls risk (71%), frailty (64%), and cognition (57%). Sensory impairment (50%), social isolation (50%), nutritional status (43%), loneliness (7%), and financial means (7%) were least frequently assessed. There was significant heterogeneity with regard to the tools used to assess subdomains. Common themes for how the subdomains influenced clinical care included informing prognosis, informing risk-benefit of pharmacologic therapy and invasive procedures, and consideration for palliative care. CONCLUSIONS: While respondents routinely assess multiple domains and subdomains and view these as important to clinical care, there is substantial heterogeneity regarding which subdomains are assessed and the tools used to assess them. These observations provide a foundation that inform a research agenda with regard to providing holistic and patient-centered care to older adults with HF. J Am Geriatr Soc 67:2593-2599, 2019.

An interdisciplinary approach to the older transplant patient: strategies for improving clinical outcomes.

PURPOSE OF REVIEW: To describe the latest investigations into the role of frailty and assessment of other aging-related issues in the solid organ transplant candidate and recipient. This information is relevant for all involved in the care of transplant patients, but is especially relevant in infectious diseases, given the increased burden of infection seen in older and frailer patients. RECENT FINDINGS: The Fried Frailty Phenotype (FFP) and Short Performance Physical Battery (SPPB) are well validated tools for measuring frailty in older adults. Recently, these frailty tools have also been used to predict a range of clinical outcomes in adults with endstage organ disease undergoing advanced therapies including mechanical circulatory device (MCSD) or transplantation including death on the waiting list, length of hospital stay, need for readmission, infection, and death. Frailty may also be estimated by chart review and comorbidity assessment. Other aging-related evaluations of interest are cognitive function, sarcopenia, and nutritional status. The strength of association for each tool varies by the type of end organ disease, although there are many findings in common across organ types. SUMMARY: As trends in the aging of the population continue to impact transplant and MCSD candidates and recipients, it is increasingly important for providers to be cognizant of the methods for assessment of aging-associated dysfunction including frailty and sarcopenia.

Interleukin-10 as a predictor of major adverse cardiovascular events in a racially and ethnically diverse population: Multi-Ethnic Study of Atherosclerosis.

PURPOSE: To understand if baseline levels of the anti-inflammatory cytokine interleukin-10 (IL-10) are associated with either subclinical atherosclerosis or risk for adverse cardiovascular (CV) events. METHODS: The study included 930 adults from the Multi-Ethnic Study of Atherosclerosis (MESA) ancillary Stress Study. Participants, age 48-90 years at enrollment, were followed for an average of 10.2 years. IL-10 level was measured at the initial Stress Study visit. Cardiovascular outcomes were defined as composite CV death, myocardial infarction, stroke, stroke death, and resuscitated cardiac arrest. Coronary calcification was determined by Agatston coronary artery calcium (CAC) score. The association between IL-10 level and CV event risk was evaluated by Cox proportional hazard modeling, while that of IL-10 level and CAC presence and amount was determined with prevalence risk ratio (PRR) and linear regression modeling, respectively. Models were adjusted for CV risk factors and proinflammatory biomarkers. RESULTS: After full adjustment, IL-10 level did not predict CV events (HR 1.19, 95%CI 0.89, 1.60) and was not associated with CAC prevalence (PRR 1.00, 95%CI 0.94, 1.07), nor amount of CAC in those with nonzero CAC (ß -0.01, 95%CI -0.23, 0.21). CONCLUSION: In individuals without clinical heart disease, baseline IL-10 level appears unrelated to risk of CV events and is a poor marker of subclinical coronary atherosclerosis.

The Frailty Risk Score predicts length of stay and need for rehospitalization after kidney transplantation in a retrospective cohort: a pilot study.

BACKGROUND: Frailty is a widely used measure in older patients as a predictor of poor outcomes after hospitalization and surgery. There is a growing body of data in kidney transplantation suggesting frailty can predict adverse outcomes. There is interest in using chart review measures of frailty and multimorbidity, as they may be equally predictive as physical measurement. This approach holds promise for patient evaluation, identifying candidates for prehabilitation, and targeting resources towards those anticipated to have an increased rate of clinical challenges after kidney transplantation. Frail patients who are often older may place a large resource and economic burden on transplant programs. METHODS: We applied a previously published chart review-based approach in a retrospective, pilot study to calculate the Frailty Risk Score (FRS) utilizing a cohort of kidney transplant patients. We reviewed concurrent comorbidities using the Charlson comorbidity (CM) score to determine the feasibility and utility of applying this approach in transplant patients to predict post-transplant outcomes such as length of hospitalization and the need for rehospitalization. RESULTS: Sixty kidney transplant recipients were evaluated by chart review, 23 characterized as older (> = 60) and 37 younger (ages 30-59). Median FRS score was 3 (range 1-7). Higher FRS was significantly associated with increased patient age (high FRS 19% in younger patients, 43% in older patients). Increased CM score was also associated with increased patient age. Patients with a high FRS stayed in the hospital for an average of 8 days, compared with 5.7 days for a low FRS. Patients with high FRS were readmitted an average of 2.9 times compared with an average of 1.1 for those with a low FRS. FRS score remained significant for predicting outcomes after adjustment for patient age. CONCLUSION: Elevated FRS prior to transplantation was associated with increased hospital stay and the need for readmission in kidney transplant recipients. This analysis demonstrates the potential strength of chart review in evaluating frailty prior to transplantation, permitting risk stratification and targeting of resources for rehabilitation and close post-transplant monitoring. Frail patients may benefit from targeted "prehabilitation" to attenuate the associated adverse clinical outcomes.

Is Posthospital Syndrome a Result of Hospitalization-Induced Allostatic Overload?

After discharge from the hospital, patients face a transient period of generalized susceptibility to disease as well as an elevated risk for adverse events, including hospital readmission and death. The term posthospital syndrome (PHS) has been used to describe this time of enhanced vulnerability. Based on data from bench to bedside, this narrative review examines the hypothesis that hospitalrelated allostatic overload is a plausible etiology of PHS. Resulting from extended exposure to stress, allostatic overload is a maladaptive state driven by overuse and dysregulation of the hypothalamic-pituitary-adrenal axis and the autonomic nervous system that ultimately generates pathophysiologic consequences to multiple organ systems. Markers of allostatic overload, including elevated levels of cortisol, catecholamines, and inflammatory markers, have been associated with adverse outcomes after hospital discharge. Based on the evidence, we suggest a possible mechanism for postdischarge vulnerability, encourage critical contemplation of traditional hospital environments, and suggest interventions that might improve outcomes.

Can a Left Ventricular Assist Device in Individuals with Advanced Systolic Heart Failure Improve or Reverse Frailty?

BACKGROUND/OBJECTIVES: Frailty, characterized by low physiological reserves, is strongly associated with vulnerability to adverse outcomes. Features of frailty overlap with those of advanced heart failure, making a distinction between them difficult. We sought to determine whether implantation of a left ventricular assist device (LVAD) would decrease frailty. DESIGN: Prospective, cohort study. SETTING: Five academic medical centers. PARTICIPANTS: Frail individuals (N = 29; mean age 70.6 ± 5.5, 72.4% male). MEASUREMENTS: Frailty, defined as having 3 or more of the Fried frailty criteria, was assessed before LVAD implantation and 1, 3, and 6 months after implantation. Other domains assessed included quality of life, using the Kansas City Cardiomyopathy Questionnaire; mood, using the Patient Health Questionnaire; and cognitive function, using the Trail-Making Test Part B. RESULTS: After 6 months, three subjects had died, and one had undergone a heart transplant; of 19 subjects with serial frailty measures, the average number of frailty criteria decreased from 3.9 ± 0.9 at baseline to 2.8 ± 1.4 at 6 months (P = .003). Improvements were observed after 3 to 6 months of LVAD support, although 10 (52.6%) participants still had 3 or more Fried criteria, and all subjects had at least one at 6 months. Changes in frailty were associated with improvement in QOL but not with changes in mood or cognition. Higher estimated glomerular filtration rate at baseline was independently associated with a decrease in frailty. CONCLUSION: Frailty decreased in approximately half of older adults with advanced heart failure after 6 months of LVAD support. Strategies to enhance frailty reversal in this population are worthy of additional study.

Frailty in Advanced Heart Failure: A Consequence of Aging or a Separate Entity?

There are over 5 million Americans with heart failure (HF), the majority of whom are over age 65. Frailty is a systemic syndrome associated with aging that produces subclinical dysfunction across multiple organ systems and leads to an increased risk for morbidity and mortality. The prevalence of frailty is about 10% in community-dwelling elderly and 20% in those with advanced HF, and increases in both cohorts with age. Yet the relationship between the primary frailty of aging and frailty secondary to HF remains poorly defined. Whether the frailty of these two populations share similar etiologies or exist as separate entities is unknown. Teasing apart potential molecular, cellular, and functional differences between the frailty of aging and that of advanced HF has implications for risk stratification, quality of life, and pharmacological and therapeutic interventions for advanced HF patients.