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.

Impact of frailty on mortality and morbidity in bridge to transplant recipients of contemporary durable mechanical circulatory support.

BACKGROUND: Frailty is associated with adverse outcomes in advanced heart failure. We studied the impact of frailty on postoperative outcomes in bridge to transplant (BTT) durable mechanical circulatory support (MCS) recipients. METHODS: Patients undergoing left ventricular assist device (LVAD, n = 96) or biventricular support (BiV, n = 11) as BTT underwent frailty assessment. Frailty was defined as ≥ 3 physical domains of the Fried's Frailty Phenotype (FFP) or ≥ 2 physical domains of the FFP plus cognitive impairment on the Montreal Cognitive Assessment (MoCA). RESULTS: No difference in mortality at 360 days was observed in frail (n = 6/38, 15.8%) vs non-frail (n = 4/58, 6.9%) LVAD supported patients, p = 0.19. However, there was a significant excess mortality in frail BiV (n = 4/5) vs non-frail BiV (n = 0/6) supported patients, p = 0.013. In all patients, frail patients compared to non-frail patients experienced longer intensive care unit stay, 12 vs 6 days (p < 0.0001) and hospital length of stay, 48 vs 27 days (p < 0.0001). There was no difference in hemocompatibility and infection related adverse events. The majority (n = 22/29, 75.9%) of frail patients became non-frail following MCS; contrastingly, a minority (n = 3/42, 7.1%) became frail from being non-frail (p = 0.0003). CONCLUSIONS: Abnormal markers of frailty are common in patients undergoing BTT-MCS support and those used herein predict mortality in BiV-supported patients, but not in LVAD patients. These findings may help us better identify patients who will benefit most from BiV-BTT therapy.

Frailty Measures in Patients Listed for Lung Transplantation.

BACKGROUND: The study aimed to determine whether the addition of cognitive impairment, depression, or both, to the assessment of physical frailty (PF) is associated with the risk of lung transplant (LTX) waitlist mortality. METHODS: Since March 2013, all patients referred for LTX evaluation underwent PF assessment. Cognition was assessed using the Montreal Cognitive Assessment and depression assessed using the Depression in Medical Illness questionnaire. We assessed the association of 4 composite frailty measures: PF ≥3 of 5 = frail, cognitive frailty (CogF ≥3 of 6 = frail), depressive frailty (DepF ≥3 of 6 = frail), and combined frailty (ComF ≥3 of 7 = frail) with waitlist mortality. RESULTS: The prevalence of PF was 78 (22%), CogF 100 (28%), DepF 105 (29%), and ComF 124 (34%). Waitlist survival in the non-PF group was 94% ± 2% versus 71% ± 7% in the PF group (P < 0.001). Cox proportional hazards regression analysis demonstrated that PF (adjusted hazard ratio [HR], 4.88; 95% confidence interval [CI], 2.06-11.56), mild cognitive impairment (adjusted HR, 3.03; 95% CI, 1.05-8.78), and hypoalbuminemia (adjusted HR, 0.89; 95% CI, 0.82-0.97) were independent predictors of waitlist mortality. There was no significant difference in the area under the curve of the 4 frailty measures. CONCLUSIONS: The addition of cognitive function and depression variables to the PF assessment increased the number of patients classified as frail. However, the addition of these variables does not strengthen the association with LTX waitlist mortality compared with the PF measure.

Validation of Cognitive Impairment in Combination With Physical Frailty as a Predictor of Mortality in Patients With Advanced Heart Failure Referred for Heart Transplantation.

BACKGROUND: The aim of this study was to validate our previous finding that frailty predicts early mortality in patients with advanced heart failure (AHF) and that including cognition in the frailty assessment enhances the prediction of mortality. METHODS: Patients with AHF referred to our Transplant Unit between November 2015 and April 2020 underwent physical frailty assessment using the modified Fried physical frailty (PF) phenotype as well as cognitive assessment using the Montreal Cognitive Assessment to identify patients who were cognitively frail (CogF). We assessed the predictive value of the 2 frailty measures (PF ≥ 3 of 5 = frail; CogF ≥ 3 of 6 = frail) for pretransplant mortality. RESULTS: Three hundred thirteen patients (233 male and 80 female; age 53 ± 13 y) were assessed. Of these, 224 patients (72%) were nonfrail and 89 (28%) were frail using the PF. The CogF assessment identified an additional 30 patients as frail: 119 (38%). Frail patients had significantly increased mortality as compared to nonfrail patients. Ventricular assist device and heart transplant-censored survival at 12 mo was 92 ± 2 % for nonfrail and 69 ± 5% for frail patients (P < 0.0001) using the CogF instrument. CONCLUSIONS: This study validates our previously published findings that frailty is prevalent in patients with AHF referred for heart transplantation. PF predicts early mortality. The addition of cognitive assessment to the physical assessment of frailty identifies an additional cohort of patients with a similarly poor prognosis.

The impact of frailty on mortality after heart transplantation.

BACKGROUND: Frailty is prevalent in the patients with advanced heart failure; however, its impact on clinical outcomes after heart transplantation (HTx) is unclear. The aim of this study was to assess the impact of pre-transplant frailty on mortality and the duration of hospitalization after HTx. METHODS: We retrospectively reviewed the post-transplant outcomes of 140 patients with advanced heart failure who had undergone frailty assessment within the 6-month interval before HTx: 43 of them were frail (F) and 97 were non-frail (NF). RESULTS: Post-transplant survival rates for the NF cohort at 1 and 12 months were 97% (93-100) and 95% (91-99) (95% CI), respectively. In contrast, post-transplant survival rates for the F cohort at the same time points were 86% (76-96) and 74% (60-84) (p < 0.0008 vs NF cohort), respectively. The Cox proportional hazards regression analysis demonstrated that pre-transplant frailty was an independent predictor of post-transplant mortality with a hazard ratio of 3.8 (95% CI: 1.4-10.5). Intensive care unit and hospital length of stay were 2 and 7 days longer in the F cohort (both p < 0.05), respectively, than in the NF cohort. CONCLUSIONS: Frailty within 6 months before HTx is independently associated with increased mortality and prolonged hospitalization after transplantation. Future research should focus on the development of strategies to mitigate the adverse effects of pre-transplant frailty.

Reversibility of Frailty after Lung Transplantation.

BACKGROUND: Frailty contributes to increased morbidity and mortality in patients referred for and undergoing lung transplantation (LTX). The study aim was to determine if frailty is reversible after LTX in those classified as frail at LTX evaluation. METHODS: Consecutive LTX recipients were included. All patients underwent modified physical frailty assessment during LTX evaluation. For patients assessed as frail, frailty was reassessed on completion of the post-LTX rehabilitation program. Frailty was defined by the presence of ≥ 3 domains of the modified Fried Frailty Phenotype (mFFP). RESULTS: We performed 166 lung transplants (frail patients, n = 27, 16%). Eighteen of the 27 frail patients have undergone frailty reassessment. Eight frail patients died, and one interstate recipient did not return for reassessment. In the 18 (66%) patients reassessed, there was an overall reduction in their frailty score post-LTX ((3.4 ± 0.6 to 1.0 ± 0.7), p < 0.001) with 17/18 (94%) no longer classified as frail. Improvements were seen in the following frailty domains: exhaustion, mobility, appetite, and activity. Handgrip strength did not improve posttransplant. CONCLUSIONS: Physical frailty was largely reversible following LTX, underscoring the importance of considering frailty a dynamic, not a fixed, entity. Further work is needed to identify those patients whose frailty is modifiable and establish specific interventions to improve frailty.

Evaluating the convergent and discriminant validity of three versions of the frailty phenotype in heart failure: results from the FRAME-HF study.

BACKGROUND: Frailty is an important predictive measure of mortality and rehospitalisation in people with heart failure. To date, there are no frailty instruments validated for use in people with heart failure. AIM: The aim of this study was to evaluate the convergent and discriminant validity of three versions of the frailty phenotype in those with heart failure. METHODS: A single site, prospective cohort study was undertaken among individuals with a confirmed diagnosis of heart failure. Frailty was assessed concurrently using three versions of the frailty phenotype: the original frailty phenotype and two modified versions; the Survey of Health, Ageing and Retirement in Europe frailty instrument (SHARE-FI) and the St Vincent's frailty instrument. Convergent and discriminant validity were assessed by reporting the correlations between each version and related heart failure subconstructs, and by evaluating the ability of each version to discriminate between normal and abnormal scores of other physical and psychosocial scales specific to heart failure-related subconstructs. RESULTS: The New York Heart Association classes were moderately correlated with the St Vincent's frailty instrument (r=0.47, P⩽0.001), SHARE-FI (r=0.42, P⩽0.001) and the frailty phenotype (r=0.42, P⩽0.001). The SHARE-FI and the St Vincent's frailty instrument were both able to discriminate consistently between normal and abnormal scores in three out of five of the physical and psychosocial subconstructs that were assessed. The SHARE-FI was also able to discriminate between inpatients and outpatients who were classified as frail. CONCLUSIONS: Both the SHARE-FI and the St Vincent's frailty instrument displayed good convergent and discriminant validity.

Frailty as a Predictor of Mortality in Patients With Interstitial Lung Disease Referred for Lung Transplantation.

BACKGROUND: Frailty is a clinically recognized syndrome of decreased physiological reserve and a key contributor to suboptimal clinical outcomes in various lung disease groups. Interstitial lung disease (ILD) is fast approaching chronic obstructive pulmonary disease as the number one indication for lung transplantation worldwide. Our aim was to assess whether frailty is a predictor of mortality in patients with ILD referred for lung transplantation in an Australian cohort. METHODS: Consecutive patients with ILD referred or on the waiting list for lung transplantation from May 2013 to December 2017 underwent frailty assessment using the modified Fried's frailty phenotype. Frailty was defined as a positive response to ≥3 of the following 5 components: weak grip strength, slowed walking speed, poor appetite, physical inactivity, and exhaustion. RESULTS: One hundred patients (82 male:18 female; age, 59 ± 7 y; range, 30-70) underwent frailty assessment. Twenty-four of 100 (24%) were assessed as frail. Frailty was associated with anemia, hypoalbuminemia, low creatinine, and the use of supplemental oxygen (all P < 0.05). Frailty was independent of age, gender, measures of pulmonary dysfunction (PaO2, forced vital capacity percentage predicted, total lung capacity, total lung capacity percentage predicted, DLCO, or DLCO percentage predicted), cognitive impairment, or depression. Frailty and DLCO % predicted were independent predictors of increased all-cause mortality: 1-year actuarial survival was 86 ± 4% in the nonfrail group compared with 58 ± 10% for the frail group (P = 0.002). CONCLUSIONS: Frailty is common among patients referred for lung transplant with a diagnosis of ILD and is associated with a marked increase in mortality.

Frailty in lung transplantation: a systematic review.

Introduction: Lung transplantation is an effective treatment for certain types of end-stage lung disease. Frailty is a complex clinical syndrome associated with decreased physiological reserve and an increased risk for suboptimal health outcomes.Area covered: This article reviews the current literature on frailty in lung transplantation, with an emphasis on frailty measures, prevalence and impact of frailty on morbidity and mortality prior to and following lung transplantation. Pubmed, EMBASE, CINAHL and Cochrane systematic review databases were searched to September 2019. The search included the MeSH terms 'frail elderly' or 'frailty' or 'sarcopenia' and 'lung disease' or 'lung transplantation'. Studies were included if: the population were undergoing evaluation for, listed for or received a lung transplant; frailty was prospectively assessed during lung transplant evaluation using systematically defined criteria; used human subjects and; published in English. The prevalence of frailty varied from 0% - 58%. The frailty phenotype and short physical performance battery were the most common measures. Frailty was associated with delisting and death pre-transplantation. Frailty was associated with an increased risk of early mortality post-lung transplantation.Expert opinion: Frailty is identified often in lung transplant candidates and is associated with adverse pre and post-transplantation outcomes. Further research is necessary to identify potential frailty interventions.

Grip strength predicts cardiac adverse events in patients with cardiac disorders: an individual patient pooled meta-analysis.

OBJECTIVE: Grip strength is a well-characterised measure of weakness and of poor muscle performance, but there is a lack of consensus on its prognostic implications in terms of cardiac adverse events in patients with cardiac disorders. METHODS: Articles were searched in PubMed, Cochrane Library, BioMed Central and EMBASE. The main inclusion criteria were patients with cardiac disorders (ischaemic heart disease, heart failure (HF), cardiomyopathies, valvulopathies, arrhythmias); evaluation of grip strength by handheld dynamometer; and relation between grip strength and outcomes. The endpoints of the study were cardiac death, all-cause mortality, hospital admission for HF, cerebrovascular accident (CVA) and myocardial infarction (MI). Data of interest were retrieved from the articles and after contact with authors, and then pooled in an individual patient meta-analysis. Univariate and multivariate logistic regression was performed to define predictors of outcomes. RESULTS: Overall, 23 480 patients were included from 7 studies. The mean age was 62.3±6.9 years and 70% were male. The mean follow-up was 2.82±1.7 years. After multivariate analysis grip strength (difference of 5 kg, 5× kg) emerged as an independent predictor of cardiac death (OR 0.84, 95% CI 0.79 to 0.89, p<0.0001), all-cause death (OR 0.87, 95% CI 0.85 to 0.89, p<0.0001) and hospital admission for HF (OR 0.88, 95% CI 0.84 to 0.92, p<0.0001). On the contrary, we did not find any relationship between grip strength and occurrence of MI or CVA. CONCLUSION: In patients with cardiac disorders, grip strength predicted cardiac death, all-cause death and hospital admission for HF. TRIAL REGISTRATION NUMBER: CRD42015025280.

#Frailty: A snapshot Twitter report on frailty knowledge translation.

OBJECTIVES: The objectives of this short report are to: (i) explore #Frailty Twitter activity over a six-month period; and (ii) provide a snapshot Twitter content analysis of #Frailty usage. METHODS: A mixed-method study was conducted to explore Twitter data related to frailty. The primary search term was #Frailty. Objective 1: data were collected using Symplur analytics, including variables for total number of tweets, unique tweeters (users) and total number of impressions. Objective 2: a retrospectively conducted snapshot content analysis of 1500 #Frailty tweets was performed using TweetReach™ . RESULTS: Over a six-month period (1 January 2017-31 June 2017), there was a total of 6545 #Frailty tweets, generating 14.8 million impressions across 3986 participants. Of the 1500 tweets (814 retweets; 202 replies; 484 original tweets), 56% were relevant to clinical frailty. The main contributors ('who') were as follows: the public (29%), researchers (25%), doctors (21%), organisations (18%) and other allied health professionals (7%). Tweet main message intention ('what') was public health/advocacy (41%), social communication (28%), research-based evidence/professional education (24%), professional opinion/case studies (15%) and general news/events (7%). CONCLUSIONS: Twitter is increasingly being used to communicate about frailty. It is important that thought leaders contribute to the conversation. There is potential to leverage Twitter to promote and disseminate frailty-related knowledge and research.

Frailty assessment instruments in heart failure: A systematic review.

BACKGROUND: Frailty is an independent predictor of mortality across many conditions. Reported rates of frailty in heart failure range from 15% to 74%. There are several instruments available to assess frailty; however, to date there has been no consensus on the most appropriate instrument for use in individuals with heart failure. AIMS: To identify how frailty is assessed in individuals with heart failure and to elucidate which domains of frailty are most frequently assessed. METHODS: Key electronic databases were searched (MEDLINE, COCHRANE Central and CINAHL) to identify studies that assessed frailty in individuals with heart failure using a formal frailty instrument. RESULTS: Twenty studies published in 24 articles were included, for which a total of seven unique frailty instruments were identified. The most commonly used instrument was the Frailty Phenotype ( n= 11), with the majority of studies using a modified version of the Frailty Phenotype ( n= 8). The second most commonly used instrument identified was the Comprehensive Geriatric Assessment ( n= 4). CONCLUSION: There is an increasing interest in the assessment of frailty, but, to date, there is no frailty instrument validated specifically in the heart failure population.

Reversibility of Frailty After Bridge-to-Transplant Ventricular Assist Device Implantation or Heart Transplantation.

BACKGROUND: We recently reported that frailty is independently predictive of increased mortality in patients with advanced heart failure referred for heart transplantation (HTx). The aim of this study was to assess the impact of frailty on short-term outcomes after bridge-to-transplant ventricular assist device (BTT-VAD) implantation and/or HTx and to determine if frailty is reversible after these procedures. METHODS: Between August 2013 and August 2016, 100 of 126 consecutive patients underwent frailty assessment using Fried's Frailty Phenotype before surgical intervention: 40 (21 nonfrail, 19 frail) BTT-VAD and 77 (60 nonfrail, 17 frail) HTx-including 17 of the 40 BTT-VAD supported patients. Postprocedural survival, intubation time, intensive care unit, and hospital length of stay were compared between frail and nonfrail groups. Twenty-six frail patients were reassessed at 2 months or longer postintervention. RESULTS: Frail patients had lower survival (63 ± 10% vs 94 ± 3% at 1 year, P = 0.012) and experienced significantly longer intensive care unit (11 vs 5 days, P = 0.002) and hospital (49 vs 25 days, P = 0.003) length of stay after surgical intervention compared with nonfrail patients. Twelve of 13 frail patients improved their frailty score after VAD (4.0 ± 0.8 to 1.4 ± 1.1, P < 0.001) and 12 of 13 frail patients improved their frailty score after HTx (3.2 ± 0.4 to 0.9 ± 0.9, P < 0.001). Handgrip strength and depression improved postintervention. Only a slight improvement in cognitive function was seen postintervention. CONCLUSIONS: Frail patients with advanced heart failure experience increased mortality and morbidity after surgical intervention with BTT-VAD or HTx. Among those who survive frailty is partly or completely reversible underscoring the importance of considering this factor as a dynamic not fixed entity.

Handle with care: A systematic review on frailty in cardiac care and its usefulness in heart transplantation.

BACKGROUND: There is growing consensus that frailty, a state of vulnerability and a decline in functioning across multiple physiological body systems, is a valuable criterion to guide clinicians' risk prediction for poor outcomes in adult transplant candidates. In its 2016 listing criteria for heart transplantation the International Society for Heart Lung Transplantation recommends frailty assessment. We aimed to summarize the usefulness of frailty assessment in heart transplant candidates or recipients reported throughout the literature. METHODS: We performed a systematic literature search in PubMed to identify papers reporting on frailty in transplantation, chronic heart failure, and ventricualr assist device implantation published over the last 10 years in English. Additionally, a hand search was conducted, including manually searching the reference lists and a citation search of relevant papers. RESULTS: Eleven primary research articles were included in this systematic review. Frailty is a risk factor for morbidity, hospitalization, and mortality in patients with advanced heart failure and individuals being considered for ventricualr assist device implantation. Of the patients being considered for transplantation, 33% are frail. The Frailty Phenotype by Fried is a particularly useful tool to quickly identify higher risk patients for adverse outcomes. CONCLUSION: A lack of standardization and limited evidence on frailty in transplantation limit its use as a definitive listing criterion. Future research efforts should focus on systematic integration of frailty measures in transplant practice.

Cognitive impairment improves the predictive validity of physical frailty for mortality in patients with advanced heart failure referred for heart transplantation.

BACKGROUND: The aim of this study was to identify whether the addition of cognitive impairment, depression, or both, to the assessment of physical frailty provides better outcome prediction in patients with advanced heart failure referred for heart transplantation (HT). METHODS: Beginning in March 2013, all patients with advanced heart failure referred to our Transplant Unit have undergone a physical frailty assessment using the Fried frailty phenotype. Cognition was assessed with the Montreal Cognitive Assessment and depression with the Depression in Medical Illness questionnaire. We assessed the value of 4 composite frailty measures: physical frailty (PF ≥ 3 of 5 = frailty), "cognitive frailty" (CogF ≥ 3 of 6 = frail), "depressive frailty" (DepF ≥ 3 of 6 = frail), and "cognitive-depressive frailty" (ComF ≥ 3 of 7 = frail) in predicting outcomes. RESULTS: Frailty was assessed in 156 patients (109 men, 47 women), aged 53 ± 13 years, and with a left ventricular ejection fraction of 27% ± 14%. Inclusion of cognitive impairment or depression in the definition of frailty increased the proportion classified as frail from 33% using PF to 42% using ComF. During follow-up, 28 patients died before ventricular assist device implantation or HT. Frailty was associated with significantly lower ventricular assist device- and HT-free survival, with CogF best capturing early mortality: 12-month survival for non-frail and frail cohorts was 81% ± 5% vs 58% ± 10% (p < 0.02) using PF and 85% ± 5% vs 56% ± 9% (p < 0.002) using CogF. Combining the Depression in Medical Illness score with PF or CogF did not strengthen the relationship between frailty and mortality. CONCLUSIONS: The addition of cognitive impairment to the assessment of PF strengthened its capacity to identify advanced heart failure patients referred for HT who are at high risk of early death.

The Prevalence and Prognostic Significance of Frailty in Patients With Advanced Heart Failure Referred for Heart Transplantation.

BACKGROUND: Frailty is a clinically recognized syndrome of decreased physiological reserve. The heightened state of vulnerability in these patients confers a greater risk of adverse outcomes after even minor stressors. Our aim was to assess the prevalence and prognostic significance of the frailty phenotype in patients referred for heart transplantation. METHODS: Consecutive patients referred or on the waiting list for heart transplantation from March 2013 underwent frailty assessment. Frailty was defined as a positive response to 3 or more of the following 5 components: weak grip strength, slowed walking speed, poor appetite, physical inactivity, and exhaustion. In addition, markers of disease severity were obtained, and all patients underwent cognitive (Montreal Cognitive Assessment) and depression (Depression in Medical Illness-10) screening. RESULTS: One hundred twenty patients (83 men:37 women; age, 53 ± 12 years, range, 16-73 years; left ventricular ejection fraction, 27 ± 14%) underwent frailty assessment. Thirty-nine of 120 patients (33%) were assessed as frail. Frailty was associated with New York Heart Association class IV heart failure, lower body mass index, elevated intracardiac filling pressures, lower cardiac index, anemia, hypoalbuminemia, hyperbilirubinemia, cognitive impairment, and depression (all ρ < 0.05). Frailty was independent of age, sex, heart failure duration, left ventricular ejection fraction, or renal function. Frailty was an independent predictor of increased all-cause mortality: 1 year actuarial survival was 79 ± 5% in the nonfrail group compared with only 54 ± 9% for the frail group (P < 0.005). CONCLUSIONS: Frailty is prevalent among patients with advanced symptomatic heart failure referred for heart transplantation and is associated with increased mortality.

Frailty in advanced heart failure: a systematic review.

Frailty is a common geriatric syndrome of increased vulnerability to adverse events. The prevalence of frailty among chronic heart failure (CHF) is high and confers a greater risk of adverse events including falls, hospitalisation and mortality. There have been few studies assessing frailty in CHF. A review of the key databases was conducted from 2004 to 2014 including the key search terms 'frail elderly' and 'heart failure'. The following electronic databases were searched: Medline, Cumulative Index for Nursing and Allied Health and Academic Search Complete, with reference lists being manually searched. Articles were included if frailty was assessed using a valid measuring tool in a population with a confirmed diagnosis of CHF. The search yielded a total of 393 articles with 8 articles being selected for review. The prevalence of frailty among those with CHF was high, ranging from 18 to 54 %. The frailty phenotype and geriatric assessments tools were the most common frailty measures utilised; high rates of co-morbidity, hospitalisation and mortality were identified. Frailty is common in CHF and is associated with adverse outcomes.