Frailty in Heart Failure: Implications for Management

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Abstract

Frailty is a complex clinical syndrome associated with ageing and chronic illness, resulting from multiple organ impairment; physiological reserves decrease and vulnerability to stressors increase. The role of frailty in cardiovascular disease has become increasingly recognised. Up to 79% of patients with heart failure are frail. Moreover, frailty is associated with a worse quality of life and poor prognosis. This review summarises the available literature on frailty in HF and highlights indications for its management.

Disclosure
The authors have no conflicts of interest to declare.
Correspondence
Cristiana Vitale, Centre for Clinical & Basic Research IRCCS San Raffaele Pisana, via della Pisana, 235, 00163 Rome, Italy. E: cristiana.vitale@sanraffaele.it
Received date
10 June 2018
Accepted date
06 July 2018
Citation
Cardiac Failure Review 2018;4(2):104–6.
DOI
https://doi.org/10.15420/cfr.2018.22.2

Because of the ageing population in industrialised countries, the prevalence of cardiovascular disease has dramatically increased.1 In particular, heart failure (HF) has become a major public health problem and the leading cause of morbidity, hospitalisation and mortality in older people.2,3

Patients with HF, especially the oldest, are often characterised by a “vulnerability status” due to the presence of several comorbidities and impaired functional capacity.4,5 The Cardiovascular Health Study,6 a US longitudinal cohort of older people living in the community, has defined this vulnerability status as the “frail phenotype”. This term indicates elderly people with multiple chronic morbidities, resulting in reduced autonomy in daily life activities.6 Of note, the Cardiovascular Health Study found frailty was associated with clinical cardiovascular disease, most strongly with HF. Indeed, almost half of patients with HF were frail, and this was independent of age or New York Heart Association functional classification. The frail phenotype was defined using five criteria: unintentional weight loss; self-reported exhaustion; low energy expenditure; slow gait speed; and weak grip strength. The study also demonstrated the relationships between frailty, comorbidity and disability found to predict and/or exacerbate each other.

Although the precise pathogenesis of frailty in HF has not been fully elucidated, shared pathophysiologic mechanisms may help explain the complex relationships among frailty, comorbidity and disability.7 According to the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults,8 a “dependency cascade” may occur. This term indicates a progressive series of damage across multiple organ systems, ranging from functional decline to disability and death. The most common deficits relate to mobility, strength, balance, motor processing, cognition, nutrition, endurance and physical activity.9

Domains of frailty are shown in Figure 1. As deficits in these domains accumulate, the capacity to cope with distress is diminished, and functional decline worsens.10,11 This self-reinforcing dependency cascade may be a consequence of impaired homeostatic maintenance/repair mechanisms.12 Disorders in neurohormonal, metabolic, immunologic and musculoskeletal systems may lead to an increased catabolic state that is typical of the frail phenotype in HF.4 For these reasons, patients who are frail experience sarcopenia, tissue wasting and cardiac cachexia, with consequent weakness, fatigue and reduced resistance to stressors.13

Therefore, frailty in HF is characterised not only by myocardial failure but also by concomitant metabolic failure.4 Frailty and the above-mentioned associated conditions, i.e. cachexia, sarcopenia and reduced functional capacity, are particularly prevalent in patients with advanced HF.14 It still has to be clarified whether therapies aimed at addressing neurohumoral overactivation and improving haemodynamics and cardiac and muscular metabolism may be effective in ameliorating these conditions.

Prognostic Implications

Not only are elderly patients with HF at increased risk of developing frailty, but also frail older adults are more likely to develop new-onset HF.15 Therefore, the relationship between frailty and HF is bidirectional. This is thought to be due to the common underlying mechanisms of inflammation, metabolic dysfunction and hormonal dysregulation.16,17

Older adults with frailty and HF are at increased risk of poor clinical outcomes.15 Observational studies have found frailty to be associated with higher mortality rates and healthcare utilisation, including emergency department visits and hospitalisations, disability, falls and cognitive decline.15,18–22 In elderly patients with chronic HF, the presence of frailty was associated with an increased risk of mortality, hospital readmission and functional decline at one year.23

Furthermore, patients with HF and frailty have a worse quality of life since frailty accelerates the risk of developing a disability.6 The FRAIL-HF, a prospective cohort study including 450 non-dependent patients aged ≥70 years who had been hospitalised for HF,21 evaluated the relationships between the frailty phenotype and associated issues (i.e. comorbidities, coexistent geriatric syndromes, self-care and social support) with clinical, functional and quality-of-life outcomes. The study found that even in non-dependent patients, frailty was a risk factor for early disability, long-term mortality and hospital readmission.20

Assessment and Management of Frailty in HF

Recognising the frailty phenotype in patients with HF may help to detect those at risk of poor outcomes (i.e. disability, death, hospitalisation or institutionalisation)23,24 so identify those who need early intervention and close monitoring.25 The recognition of frailty is the first step for an accurate risk stratification and planning a tailored therapeutic plan.26,27

However, several knowledge gaps exist. First, a unique definition of this syndrome in patients with HF is still lacking.26 Second, most trials on HF have excluded elderly patients with comorbidities, who comprise the population at the highest risk of frailty.25 Third, an established frailty approach in HF is still missing.

Several measurements have been proposed to assess frailty, and a huge variety of methods and instruments are available.11,28,29 The most widely used tools to assess frailty are Fried’s phenotypic definition of frailty and the frailty index, described in detail elsewhere.3,11,30 There are also self-report questionnaires or instruments based on the assessment of single performances (i.e. single domains of frailty). However, a recent systematic review30 found inconsistencies in frailty measurements and identified that the only consistently represented domain across frailty instruments was physical function/mobility.

There is, therefore, a need for a consensus from the scientific community for a standard method – preferably user friendly and not time consuming – that can be used to accurately identify frailty in patients with cardiovascular conditions and reliably predict adverse clinical outcomes.

To date, the multidimensional interdisciplinary Comprehensive Geriatric Assessment (CGA) is the most used tool to measure frailty. However, this instrument may not adequately characterise frailty in patients with cardiac conditions. To date, there are no validated frailty instruments specific for HF or other cardiovascular conditions.31,32 A recent systematic review30 identified seven frailty assessment instruments that have been used in HF research so far. Of these seven instruments – the Frailty Phenotype, the Deficit Accumulation Index, the Tilburg Frailty Indicator, the CGA, the Frailty Staging System, the Canadian Health and Ageing Clinical Frailty Scale and the Survey of Health, Ageing and Retirement in Europe Frailty Index – none have been validated for use in HF. Assessing frailty with a validated instrument is a priority, international frailty guidelines recommend.33,34

An accurate assessment of frailty in older patients with HF should include its early identification, consideration of referral to specialists, such as cardiologists, primary care physicians and specialist nurses, and anticipation of care.9

The correct timing for the diagnosis of frailty in HF is yet to be established.35 A recent position paper from acute coronary care specialists suggests that, although challenging, the assessment of frailty should be performed during the acute phase of hospital admission.25 However, at this stage, several confounding factors may influence the detection of frailty. For now, self-reported assessments should be preferred, while objective performance measures may be used at discharge.25

Figure 1: Overlapping Domains of Frailty

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In any case, routine assessment of frailty should be part of a holistic management plan in patients with HF.30

Finally, given that health status is reduced in patients with HF and frailty, measuring patient-reported health status is pivotal for cardiovascular conditions, according to the American Heart Association (AHA).36 A position paper from the AHA, American College of Cardiology and American Geriatrics Society states that future guidelines should take into account the assessment of frailty domains as well as chronological age in the management of older patients with HF.37 As most older adults are not frail, chronological age is not a reliable indicator of biological age and health status. Frailty has been found to be a better predictor of age-dependent heart rhythm disorders than age.38

A comprehensive approach to manage frailty in HF should therefore start from a multidimensional assessment.39 The domains should include mobility, strength, balance, motor processing, cognition, nutrition, endurance and physical activity.9,39 According to the European Society of Cardiology guidelines, the management of older adults with HF includes the monitoring of frailty over time, taking into account its reversible causes to prevent increasing frailty.40 In particular, optimisation of symptom control may improve exercise tolerance, with improvements in skeletal muscle function and sarcopenia, which ameliorate functional status.41 Exercise training may reduce the frequency of HF exacerbations and hospitalisations, and improve functional capacity, quality of life and survival in HF patients.42

Hormonal treatment with testosterone has been shown to improve functional capacity and quality of life in elderly patients with HF in both sexes but this therapeutic approach needs to be specifically tested in frail patients with HF.43,44

Therefore, frailty may be a dynamic state when its cardiovascular and non-cardiovascular causes may be reversed.40 In addition, rehabilitative programmes may be used to delay or prevent functional decline. In particular, exercise training has a positive effect on physical function and functional capacity in elderly people who are frail.45

Summary

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In addition, frailty poses special challenges for patients needing end-of-life care. As reviewed in detail elsewhere,46 palliative care should be provided by an interdisciplinary team, with the aims of relieving symptoms (in particular, pain control) and offering psychological support to patients and caregivers to improve quality of life. Under-nutrition and unintentional weight loss are key issues for these patients.47 Therefore, correction of nutrition is a main component of frailty management, although it still remains to be clarified whether vitamin/mineral supplements and/or hormone supplements may be beneficial.45

Conclusions

Frailty is a dynamic and potentially reversible state. An accurate assessment may allow a tailored, individualised healthcare programme of management to prevent adverse outcomes in HF. Therefore, a consensual and multidimensional assessment is needed.

Future trials should include methods to select and stratify participants with frailty as they are an especially high-risk group.25 Finally, upcoming studies should aim to clarify an age threshold for subjects’ inclusion in future research.48

Managing frailty may help improve quality of life and have a substantial impact on prognosis in HF. Considering the role of frailty in clinical management of HF is therefore pivotal.

References
  1. Nichols M, Townsend N, Scarborough P, et al. Trends in age-specific coronary heart disease mortality in the European Union over three decades: 1980–2009. Eur Heart J 2013;34:3017–27.
    Crossref | PubMed
  2. Roger VL, Weston SA, Redfield MM, et al. Trends in heart failure incidence and survival in a community-based population. JAMA 2004;292:344–50.
    Crossref | PubMed
  3. Shinmura K. Cardiac senescence, heart failure, and frailty: a triangle in elderly people. Keio J Med 2016;65:25–32.
    Crossref | PubMed
  4. Joseph SM, Rich MW. Targeting frailty in heart failure. Curr Treat Options Cardiovasc Med 2017;19:31.
    Crossref | PubMed
  5. Carlson C, Merel SE, Yukawa M. Geriatric syndromes and geriatric assessment for the generalist. Med Clin North Am 2015;99:263–79.
    Crossref | PubMed
  6. Newman AB, Gottdiener JS, McBurnie MA, et al. Associations of subclinical cardiovascular disease with frailty. J Gerontol A Biol Sci Med Sci 2001;56:M158–66.
    Crossref | PubMed
  7. Fried LP, Ferrucci L, Darer J, et al. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J Gerontol A Biol Sci Med Sci 2004;59:255–63.
    Crossref | PubMed
  8. Walston J, Hadley EC, Ferrucci L, et al. Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Frailty in Older Adults. J Am Geriatr Soc 2006;54:991–1001.
    Crossref | PubMed
  9. Singh M, Alexander K, Roger VL, et al. Frailty and its potential relevance to cardiovascular care. Mayo Clin Proc 2008;83:1146–53.
    Crossref | PubMed
  10. Rockwood K, Song X, Mitnitski A. Changes in relative fitness and frailty across the adult lifespan: evidence from the Canadian National Population Health Survey. CMAJ 2011;183:E487–94.
    Crossref | PubMed
  11. Rajabali N, Rolfson D, Bagshaw SM. Assessment and utility of frailty measures in critical illness, cardiology, and cardiac surgery. Can J Cardiol 2016;32:1157–65.
    Crossref | PubMed
  12. Topinkova E. Aging, disability and frailty. Ann Nutr Metab 2008;52 Suppl 1:6–11.
    Crossref | PubMed
  13. Clegg A, Young J, Iliffe S, et al. Frailty in elderly people. Lancet 2013;381:752–62.
    Crossref | PubMed
  14. Joyce E. Frailty in advanced heart failure. Heart Fail Clin 2016;12:363–74.
    Crossref | PubMed
  15. Goldwater DS, Pinney SP. Frailty in advanced heart failure: a consequence of aging or a separate entity? Clin Med Insights Cardiol 2015;9:39–46.
    Crossref | PubMed
  16. 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.
    Crossref | PubMed
  17. 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. PMCid:PMC3267799 .
    Crossref | PubMed
  18. Butrous H, Hummel SL. Heart failure in older adults. Can J Cardiol 2016;32:1140–7.
    Crossref | PubMed
  19. McNallan SM, Singh M, Chamberlain AM, et al. Frailty And healthcare utilization among patients with heart failure in the community. JACC Heart Fail 2013;1:135–41.
    Crossref | PubMed
  20. Vidan MT, Blaya-Novakova V, Sanchez E, et al. Prevalence and prognostic impact of frailty and its components in non-dependent elderly patients with heart failure. Eur J Heart Fail 2016;18:869–75.
    Crossref | PubMed
  21. Vidan MT, Sanchez E, Fernandez-Aviles F, et al. Frail–Hf, a study to evaluate the clinical complexity of heart failure in nondependent older patients: rationale, methods and baseline characteristics. Clin Cardiol 2014;37:725–32.
    Crossref | PubMed
  22. Afilalo J, Karunananthan S, Eisenberg MJ, et al. Role of frailty in patients with cardiovascular disease. Am J Cardiol 2009;103:1616–21.
    Crossref | PubMed
  23. Rodriguez-Pascual C, Paredes-Galan E, Ferrero-Martinez AI, et al. The frailty syndrome is associated with adverse health outcomes in very old patients with stable heart failure: a prospective study in six Spanish hospitals. Int J Cardiol 2017;236:296–303.
    Crossref | PubMed
  24. Sternberg SA, Wershof Schwartz A, Karunananthan S, et al. The identification of frailty: a systematic literature review. J Am Geriatr Soc 2011;59:2129–38.
    Crossref | PubMed
  25. Walker DM, Gale CP, Lip G, et al. Editor’s choice – frailty and the management of patients with acute cardiovascular disease: a position paper from the acute cardiovascular care association. Eur Heart J Acute Cardiovasc Care 2018;7:176–93.
    Crossref| PubMed
  26. Uchmanowicz I, Lisiak M, Wontor R, et al. Frailty syndrome in cardiovascular disease: clinical significance and research tools. Eur J Cardiovasc Nurs 2015;14:303–9.
    Crossref | PubMed
  27. Hill E, Taylor J. Chronic heart failure care planning: considerations in older patients. Card Fail Rev 2017;3:46–51.
    Crossref | PubMed
  28. 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.
    Crossref | PubMed
  29. Dent E, Kowal P, Hoogendijk EO. Frailty measurement in research and clinical practice: a review. Eur J Intern Med 2016;31:3–10.
    Crossref | PubMed
  30. McDonagh J, Martin L, Ferguson C, et al. Frailty assessment instruments in heart failure: a systematic review. Eur J Cardiovasc Nurs 2018;17:23–35.
    Crossref | PubMed
  31. Forman DE, Alexander KP. Frailty: a vital sign for older adults with cardiovascular disease. Can J Cardiol 2016;32:1082–7.
    Crossref | PubMed
  32. McDonagh J, Ferguson C, Newton PJ. Frailty assessment in heart failure: an overview of the multi-domain approach. Curr Heart Fail Rep 2018;15:17–23.
    Crossref | PubMed
  33. Dent E, Lien C, Lim WS, et al. The Asia-Pacific Clinical Practice Guidelines for the Management of Frailty. J Am Med Dir Assoc 2017;18:564–75.
    Crossref | PubMed
  34. Morley JE, Vellas B, van Kan GA, et al. Frailty consensus: a call to action. J Am Med Dir Assoc 2013;14:392–7.
    Crossref | PubMed
  35. Sutton JL, Gould RL, Daley S, et al. Psychometric properties of multicomponent tools designed to assess frailty in older adults: a systematic review. BMC Geriatr 2016;16:55.
    Crossref | PubMed
  36. Rumsfeld JS, Alexander KP, Goff DC, Jr, et al. Cardiovascular health: the importance of measuring patient-reported health status: a scientific statement from the American Heart Association. Circulation 2013;127:2233–49.
    Crossref | PubMed
  37. Rich MW, Chyun DA, Skolnick AH, et al. Knowledge gaps in cardiovascular care of the older adult population: a scientific statement from the American Heart Association, American College of Cardiology, and American Geriatrics Society. J Am Coll Cardiol 2016;67:2419–40.
    Crossref | PubMed
  38. Cheol Cho H. Age is just a number: frailty better evaluates age-dependent heart rhythm defects. J Physiol 2013;594:6805.
    Crossref | PubMed
  39. Gorodeski EZ, Goyal P, Hummel SL, et al. Domain management approach to heart failure in the geriatric patient: present and future. J Am Coll Cardiol 2018;71:1921–36.
    Crossref | PubMed
  40. Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the Special Contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016;18:891–975.
    Crossref | PubMed
  41. Dharmarajan K, Dunlay SM. Multimorbidity in older adults with heart failure. Clin Geriatr Med 2016;32:277–89.
    Crossref | PubMed
  42. Cooper LB, Mentz RJ, Sun JL, et al. Psychosocial factors, exercise adherence, and outcomes in heart failure patients: insights from heart failure: a controlled trial investigating outcomes of exercise training (HF–ACTION). Circ Heart Fail 2015;8:1044–51.
    Crossref | PubMed
  43. Caminiti G, Volterrani M, Iellamo F, et al. Effect of long-acting testosterone treatment on functional exercise capacity, skeletal muscle performance, insulin resistance, and baroreflex sensitivity in elderly patients with chronic heart failure a double-blind, placebo-controlled, randomized study. J Am Coll Cardiol 2009;54:919–27.
    Crossref | PubMed
  44. Iellamo F, Volterrani M, Caminiti G, et al. Testosterone therapy in women with chronic heart failure: a pilot double-blind, randomized, placebo-controlled study. J Am Coll Cardiol 2010;56:1310–6.
    Crossref | PubMed
  45. Lang PO, Michel JP, Zekry D. Frailty syndrome: a transitional state in a dynamic process. Gerontology 2009;55:539–49.
    Crossref | PubMed
  46. Koller K, Rockwood K. Frailty in older adults: implications for end-of-life care. Cleve Clin J Med 2013;80:168–74.
    Crossref | PubMed
  47. Chin APMJ, de Groot LC, van Gend SV, et al. Inactivity and weight loss: effective criteria to identify frailty. J Nutr Health Aging 2003;7:55–60.
  48. Rodriguez-Manas L, Feart C, Mann G, et al. Searching for an operational definition of frailty: a Delphi method based consensus statement: the frailty operative definition-consensus conference project. J Gerontol A Biol Sci Med Sci 2013;68:62–7.
    Crossref | PubMed