Frailty and Heart Failure
Frailty: How to Define and Measure
Frailty is a syndrome characterized by weakness, fatigue, and increased vulnerability to physiologic stressors. Although most often associated with aging, frailty is also a recognized component of chronic illness. As the prevalence of chronic disease increases with age, the role of frailty in disease diagnosis and management takes on additional importance.
Over 20 different scales have been proposed to define and measure the syndrome of frailty.3 The majority of these tools include a measure of at least one each of the five domains that make up the frailty phenotype.4
- Low physical activity
- Shrinking (decreased muscle mass)
Objective assessments of these domains:
- 5 m gait speed test (slowness)
- Handgrip/knee extensor strength test (weakness)
- Questionnaires related to exhaustion/anergia, physical activity and unintentional weight loss.
The Fried Frailty Index is one of the most widely used scales and incorporates all five criteria, with ≥3 of 5 required for a diagnosis of frailty.5 Other scales use the above dimensions to a greater or lesser degree, particularly gait speed and handgrip strength.6-8
The Aging Heart Failure Phenotype
The phenotype of heart failure (HF) changes with advancing age, creating unique challenges in the aging HF population with respect to diagnosis, prognosis, and outcomes. The prevalence of systolic dysfunction declines while the incidence of HF with preserved ejection fraction increases.9 Moreover, common geriatric issues such as frailty, polypharmacy, and multi-morbidity are encountered more frequently. As such, the typical elderly HF patient is one with preserved ejection fraction, multiple non-cardiac comorbidities, and concomitant frailty.9,10
Frailty and Heart Failure
The interplay between frailty and HF can be complex and significantly linked to aging. Almost 80% of HF patients are over age 65,1 with the incidence of HF doubling in each decade of life with an eventual rise to 20% in patients over 80 years old.2 Using validated frailty assessment tools, current research is working to define the impact of frailty on HF diagnosis, prognosis, and treatment. Recognizing frailty as a syndrome and using its presence to guide management may ultimately improve patient-centered outcomes.
In patients with HF, the presence of frailty is associated with significantly worse outcomes. The lack of physiologic reserve in frail patients allows for acute stressors to cause rapid functional deterioration and debility. In addition to a two-fold increase in mortality risk, frail HF patients experience greater rates of hospitalization, endure longer lengths of stay, have increased risk for rehospitalization, and report significantly lower scores with respect to quality of life.11-13 Interestingly, it has been shown that a multidimensional prognostic index generated from a comprehensive geriatric assessment (including evaluation of functional status, cognition, social support, nutritional status, and others), outperformed HF indices for 30 day mortality risk.14 This speaks to the difficulties of prognosis in this elderly population and suggests that outcomes are driven by multidimensional factors beyond disease-specific criteria.
In addition to prognosis, the presence of frailty results in complexities with respect to diagnosis and treatment of HF. The symptoms of frailty mirror those of HF and manifest as a constellation of weakness, fatigue, and breathlessness. Frailty assessments are recommended in elderly patients to help differentiate symptoms.15 Once HF is diagnosed, medical management is complicated by common geriatric maladies. Side effects of HF medications have the potential to exacerbate weakness, dizziness, and urinary incontinence, predisposing patients to adverse events such as syncope and falls. Additionally, polypharmacy in elderly patients is a known risk factor for negative outcomes. Due to underrepresentation in clinical trials, evidence is lacking for guideline directed medical management in this age group. Consequently, elderly frail patients are less likely to receive standard HF regimens.16 There is data, however, that suggests that frail HF patients benefit more than non-frail HF patients from an interdisciplinary approach to management.17 This approach utilizes cardiologists, primary care physicians, and specialized nurses in both inpatient and outpatient settings to optimize medical therapies, improve transitions of care, provide education, and monitor for development of HF signs and symptoms. Exercise programs have also been shown to have benefits with respect to functional capacity, quality of life, hospitalization and survival in HF.18-21
Although clearly interrelated, the pathophysiologic mechanism linking HF and frailty is incompletely understood. Patients with HF are up to six times more likely to be frail, and frail patients have a significantly increased risk of developing new onset HF.22,23 This relationship is thought to rest on a shared mechanism of inflammation, metabolic dysfunction, and hormonal dysregulation. The presence of inflammatory markers such as C-reactive protein, interleukin-6, and tumor necrosis factor-α correlate both with incident HF events as well as development frailty components such as muscle wasting and weakness.24-25 Frailty and HF are also both associated with insulin resistance, abnormal cortisol patterns, and steroid hormone deficiencies.4 Potentially, the inflammation, metabolic derangements, and hormone deficiencies contribute to subclinical cardiovascular disease, which in turn acts as foundation for development of overt cardiovascular disease, frailty, or both.4
It is important to note that although linked to aging, frailty is not synonymous with it. With age, people accumulate functional and physiologic deficits, but the degree to which these deficits affect each person varies widely. Chronological age alone does not predict vulnerability to adverse outcomes and, as a corollary, a younger age does not preclude the presence of frailty in the setting of a chronic disease. Sorting out those aspects of chronic illness (reduced functional capacity, susceptibility to infectious disease) that are due to the illness itself, rather than frailty, can be a difficult task.26 It has been proposed that frailty as a phenotype is made up of potentially reversible and non-reversible aspects.27 In HF patients, if appropriately timed interventions can be undertaken (e.g., advanced HF therapies; minimally invasive valve repairs), it may be possible to reverse the disease-specific aspects of the perceived frail patient, and therefore reverse the frailty phenotype. This hypothesis is currently under study in a multi-center trial evaluating patients receiving left ventricular assist devices (LVAD) as destination therapy.
Frailty and Consideration of Advanced Therapies for Heart Failure
In addition, consideration of advanced HF therapies (e.g., LVADs, heart transplantation) may be complicated by underlying frailty and concern for clinical outcomes.28 In a study at a major transplant center, patients referred or waitlisted for heart transplant were evaluated for frailty. Of these patients, 33% were determined to be frail. Frailty was associated with NYHA Class IV symptoms, lower BMI, higher intracardiac filling pressures and lower cardiac index, cognitive impairment and depression. Most interestingly, frailty was not associated with sex, age, LVEF or HF duration. Frailty was an independent predictor of increased all-cause mortality. Similar findings have been reported in patients undergoing lung transplantation.29,30 A determination of frailty as an independent marker of outcomes should therefore be considered as part of the evaluation process of patients for advanced HF therapies.
Overall, the therapeutic implication for elderly HF patients with frailty is to deliver patient-centered goal-oriented care.14 In this generally older population, treatments plans may prioritize symptom management, functional status, and quality of life over survival. A comprehensive assessment, including that of frailty, is therefore an essential component to patient evaluation, as it provides meaningful information with respect to diagnosis, prognosis, and management. Additionally, an interdisciplinary care team approach targeting the multidimensional aspects of health may ultimately improve health-related quality of life and overall well-being in this complex patient population.
- Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation 2013;127:e6-245.
- Bui AL, Horwich TB, Fonarow GC. Epidemiology and risk profile of heart failure. Nat Rev Cardiol 2011;8:30-41.
- De Vries NM, Staal JB, van Ravensberg CD, Hobbelen JS, Olde Rikkert MG, Nijhuis-van der Sanden MW. Outcome instruments to measure frailty: a systematic review. Ageing Res Rev 2011;10:104-14.
- Afilalo J, Alexander KP, Mack MJ, et al. Frailty assessment in the cardiovascular care of older adults. J Am Coll Cardiol 2014;63:747-62.
- Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146-56.
- Abellan van Kan G, Rolland Y, Andrieu S, et al. Gait speed at usual pace as a predictor of adverse outcomes in community-dwelling older people an International Academy on Nutrition and Aging (IANA) Task Force. J Nutr Health Aging 2009;13:881-9.
- Dumurgier J, Elbaz A, Ducimetiere P, Tavernier B, Alperovitch A, Tzourio C. Slow walking speed and cardiovascular death in well functioning older adults: prospective cohort study. BMJ 2009;339:b4460.
- Ling CH, Taekema D, de Craen AJ, Gussekloo J, Westendorp RG, Maier AB. Handgrip strength and mortality in the oldest old population: the Leiden 85-plus study. CMAJ 2010;182:429-35.
- Stein GY, Kremer A, Shochat T, et al. The diversity of heart failure in a hospitalized population: the role of age. J Card Fail 2012;18:645-53.
- Murad K, Kitzman DW. Frailty and multiple comorbidities in the elderly patient with heart failure: implications for management. Heart Fail Rev 2012;17:581-8.
- Volpato S, Cavalieri M, Sioulis F, et al. Predictive value of the Short Physical Performance Battery following hospitalization in older patients. J Gerontol A Biol Sci Med Sci 2011;66:89-96.
- Lupon J, Gonzalez B, Santaeugenia S, et al. Prognostic implication of frailty and depressive symptoms in an outpatient population with heart failure. Rev Esp Cardiol 2008;61:835-42.
- Afilalo J, Karunananthan S, Eisenberg MJ, Alexander KP, Bergman H. Role of frailty in patients with cardiovascular disease. Am J Cardiol 2009;103:1616-21.
- Pilotto A, Addante F, Franceschi M, et al. Multidimensional Prognostic Index based on a comprehensive geriatric assessment predicts short-term mortality in older patients with heart failure. Circ Heart Fail 2010;3:14-20.
- Goldfarb M, Sheppard R, Afilalo J. Prognostic and therapeutic implications of frailty in older adults with heart failure. Curr Cardiol Rep 2015;17:92.
- Wright RM, Sloane R, Pieper CF, et al. Underuse of indicated medications among physically frail older US veterans at the time of hospital discharge: results of a cross-sectional analysis of data from the Geriatric Evaluation and Management Drug Study. Am J Geriatr Pharmacother 2009;7:271-80.
- Pulignano G. Del Sindaco D, Di Lenarda A, et al. Usefulness of frailty profile for targeting older heart failure patients in disease management programs: a cost-effectiveness, pilot study. J Cardiovasc Med 2010;11:739-47.
- Piepoli MF, Davos C, Francis DP, Coats AJ, ExTraMATCH Collaborative. Exercise training meta-analysis of trials in patients with chronic heart faiolure (ExTraMATCH). BMJ 2004;328:189.
- Davies EJ, Moxham T, Rees K, et al. Exercise training for systolic heart failure: Cochrane systematic review and meta-analysis. Eur J Heart Fail 2010;12:706-15.
- Taylor RS, Sagar VA, Davies EJ, et al. Exercise-based rehabilitation for heart failure. Cochrane Database Syst Rev 2014:CD003331.
- O'Connor CM, Whellan DJ, Lee KL, et al. Efficacy and safety of exercise training in patients with chronic heart failure: HF-ACTION randomized controlled trial. JAMA 2009;301:1439-50.
- Khan H, Kalogeropoulos AP, Georgiopoulou VV, et al. Frailty and risk for heart failure in older adults: the health, aging, and body composition study. Am Heart J 2013;166;887-94.
- Woods NF, LaCroix AZ, Gray SL, et al. Frailty: emergence and consequences in women aged 65 and older in the Women's Health Initiative Observational Study. J Am Geriatr Soc 2005;53:1321-30.
- Kalogeropoulos A, Georgiopoulou V, Psaty BM, et al. Inflammatory markers and incident heart failure risk in older adults: the Health ABC (Health, Aging, and Body Composition) study. J Am Coll Cardiol 2010;55:2129-37.
- Cesari M, Penninx BW, Pahor M, et al. Inflammatory markers and physical performance in older persons; the InCHIANTI study. J Gerontol A Biol Sci Med Sci 2004;59:242-8.
- Bergman H, Ferrucci L, Guralnik J, et al. Frailty: an emerging research and clinical paradigm--issues and controversies. J Gerantol A Biol Sci Med Sci 2007;62:731-7.
- Flint KM, Matlock DD, Lindenfeld J, Allen LA. Frailty and the selection of patients for destination therapy left ventricular assist device. Circ Heart Fail 2012;5:286-93.
- Jha SR, Hanna MK, Chang S, et al. The prevalence and prognostic significance of frailty in patients with advanced heart failure referred for heart transplantation. Transplantation 2016;100:429-36.
- Wilson ME, Vakil AP, Kandel P, Undavalli C, Dunlay SM, Kennedy CC. Pretransplant frailty is associated with decreased survival after lung transplantation. J Heart Lung Transplant 2016;35:173-8.
- Singer JP, Diamond JM, Gries CJ, et al. Frailty is associated with pre-operative delisting and death in lung transplant candidates. J Heart Lung Transplant 2015;34:S15.
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