REVIEW URRENT C OPINION
Frailty and prognosis in advanced heart failure Rebecca S. Boxer a, Khanjan B. Shah b, and Anne M. Kenny c
Purpose of review The frailty syndrome is characterized by an increased vulnerability to physiologic stress. Frailty is distinct from disability and disease states; however, there is a strong relationship between frailty and heart failure and the pathophysiology’s overlap. Heart failure exacerbations and hospitalizations likely accelerate the cycle of frailty. The following review summarizes the relationship between heart failure and frailty, and the utility of a frailty assessment in heart failure management. Recent findings A frailty assessment can help to stratify heart failure patients at high risk for adverse outcomes. Increasing availability of device therapies for patients with heart failure make prerisk assessment an important management strategy. Summary Furthermore, studies are necessary to understand the relationship between heart failure and frailty and to devise the best care strategies for these patients. Keywords aging, frailty, heart failure
INTRODUCTION Heart failure is the leading cause of hospitalizations and re-hospitalizations in older adults and represents a large burden on healthcare utilization. Frailty, defined as a vulnerability to withstand physiological stress, can help identify at-risk older adults and aid in decision-making for advance therapies and palliation.
FRAILTY AND HEART FAILURE Frailty is defined as a state of complex physiologic dysfunction that predisposes a person to poor clinical outcomes when confronted with stressors, such as acute illness, surgical procedures or psychosocial stress [1 ]. Although previously thought to be synonymous with ‘normal’ aging, frailty is a separate syndrome. The frailty cascade begins with normal age-related deterioration of physiologic process. These changes are compounded by the accumulation of chronic diseases. For the frail patient who has lost their physiologic resiliency, a stressful event such as a heart failure exacerbation can lead to functional decline, disability and dependency [2]. It is no surprise that a disease such as heart failure, which is common in older adults and has multisystem effects, is associated with frailty. The &&
Cardiovascular Health Study examined a cohort of 4735 community dwelling older adults and found 299 (6%) to be frail; having heart failure was the most strongly association with being frail (odds ratio ¼ 7.5) [3]. This study and many others have found frailty to be predictive of many adverse health outcomes including mortality, hospitalizations, disability and institutionalization.
CHARACTERISTICS OF THE FRAIL HEART FAILURE PATIENT Patients with heart failure deemed as frail are more likely to have diabetes, chronic obstructive pulmonary disease, atrial fibrillation, depression, anemia, chronic kidney disease and higher ejection fractions [4]. In general, older patients with heart failure are
a
Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, bInternal Medicine, Case Western Reserve University, Cleveland, Ohio and cProfessor of Medicine, Center on Aging, University of Connecticut, Farmington, Connecticut, USA Correspondence to Rebecca S. Boxer, MD, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, USA. Tel: +1 216 844 7726; e-mail: [email protected] Curr Opin Support Palliat Care 2014, 8:25–29 DOI:10.1097/SPC.0000000000000027
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Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Cardiac and circulatory problems
KEY POINTS Frailty is defined as physiological derangement that renders a patient unable to sustain various stressors. Heart failure is the most common chronic medical illness associated with a frail state. Symptoms of poorly controlled heart failure overlap with symptoms of frailty making diagnosis and effective therapeutic plans challenging. The Frailty Phenotype and Index are two measures of frailty, but both are cumbersome for routine outpatient visits. For this reason, walk tests are more easily employed clinically. More studies are needed to understand the relationship between heart failure and frailty and the effect of current heart failure therapies on patients who are frail.
more commonly women and more likely to have preserved ejection fraction (HFpEF) [5 ]. Unlike heart failure with reduced ejection fraction (HFrEF), relatively less is known about the appropriate treatment strategies for HFpEF. And although the overall survival for heart failure has improved with current medication and device treatments, the survival of HFpEF has remained unchanged over several decades [5 ]. The lack of evidence as to how to successfully medically manage older adults with HFpEF may contribute to the development of frailty. In HFrEF many older adults do not tolerate guideline medical therapy, which limits symptom control. As heart failure limits aerobic capacity and activity tolerance, poor symptom control likely accelerates physical limitations. The inability to tolerate activity results in underused skeletal muscle and sarcopenia. Chronic exercise intolerance and loss of muscle strength are also impacted by perturbations of inflammatory mediators and neurohormones. Multisystem dysregulation indicates the complexity of the frailty syndrome in patients with heart failure. Increasing complexity may be more important than any one diagnosis alone and also indicates that treatment for only one disorder may not impact overcome and reverse frailty [6]. Signs and symptoms typical of older heart failure patients are also those that define the frail state, which makes distinguishing between the two difficult. Both can result in fatigue, sarcopenia, poor activity tolerance and depression. However, treatment of heart failure with appropriate medication can result in improvement of symptoms. Treatment for frailty remains elusive; however, exercise is the most promising [7,8]. &
&
26
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NEUROENDOCRINE DYSREGULATION, INFLAMMATION AND SKELETAL MUSCLE DYSFUNCTION The syndromes of both heart failure and frailty have similar characteristics in neurohormone dysregulation, inflammation, catabolism and skeletal muscle dysfunction. The Cycle of Frailty [9] (Fig. 1) and the Muscle Hypothesis of Heart Failure [10] (Fig. 2) are depicted below. It is impossible to separate the two syndromes in that their pathophysiology’s overlap. It is not surprising that heart failure and frailty are closely associated in observational studies and it is likely that heart failure accelerates the frail state.
IDENTIFICATION OF FRAILTY IN PATIENTS WITH HEART FAILURE Identification of patients who are frail has increased in importance over the last 10 years. Frailty, chronic disease and disability overlap but are seen as distinct entities [12]. Identifying which heart failure patients are frail can assist in the decision-making process to pursue procedural therapies. Using a frailty measure, a patient can be risk stratified prior to being offered procedural therapies. Decisions to pursue advanced therapies such as implantable defibrillators, cardiac resynchronization devices and left ventricular assist devices incorporates many factors including a patient’s ability to tolerate and glean benefit from the procedure. Control of symptoms and improvement in quality of life are just as important as avoiding procedures in those at risk for adverse outcomes. The frail patient has a marked increased risk from surgical procedures and should be carefully considered by patient and physician before pursuing [13]. However, the frail state may be improved with better heart failure control, that is, improved volume control and activity tolerance. This factor makes the decision to pursue device therapy complex and requires careful patient evaluation, consideration and a shared decision-making approach [14]. In addition, it is important to conserve resources for the patients who will benefit most. At present, heart failure guidelines offer some guidance to those who are appropriate for device therapies, however, mostly by life-expectancy, which is very difficult to predict in heart failure [15,16] (Table 1). More research is needed to develop decision-making algorithms for device therapy based on functional and physiologic measures in patients with heart failure.
FRAILTY MEASURES There is no gold standard to measure frailty. There are multiple methods that range from physiologic measures to accumulation of health problems and there is great variability in the characteristics used Volume 8 Number 1 March 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Frailty and prognosis in advanced heart failure Boxer et al.
Disease Aging: senescent musculoskeletal changes
Chronic undernutrition
Neuroendocrine dysregulation
Negative energy balance
[Inadequate intake of protein and energy: micronutrient deficiencies]
Anorexia of aging
Weight loss Negative nitrogen balance
Loss of muscle mass
Sarcopenia
Total energy expenditure
Activity Walking speed
Resting metabolic rate
Strength and power
VO2 max
Disablity
Dependency
FIGURE 1. Cycle of frailty. The cycle of frailty demonstrates the multiple physiologic factors that contribute to the frail state. Reproduced with permission [9].
Reduced peripheral blood flow Left ventricular dysfunction
Vasoconstriction increased afterload
Catabolic state
Skeletal and respiratory myopathy
Sympathoexcitation
Increased ventilation
Tumour necrosis factor, insulin resistance, malnutrition, inactivity
Increased ergoreflex activity
Fatigue and dyspnoea
FIGURE 2. The muscle hypothesis of heart failure [11]. The muscle hypothesis of heart failure demonstrates the multiple physiologic factors that contribute to fatigue and dyspnea in the heart failure syndrome. Reproduced with permission [11]. 1751-4258 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.supportiveandpalliativecare.com
27
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Cardiac and circulatory problems Table 1. Recommendations from heart failure guidelines based on age, frailty and palliation Age cut off for device use?
Recommendations for frail patients?
Does the device prolong life?
Does the device palliate symptoms?
Implantable defibrillator Indicated for patients with EF 35% despite 3 months of medical therapy
None, although life expectancy >1 year required
Unknown benefit in patients with advanced frailtya
Used to reduce the risk of sudden cardiac death due to ventricular arrhythmias
No specific use. Discontinue in patients with devicerefractory symptoms
Biventricular Pacemaker Indicated in symptomatic patients with EF 35% and QRS 150 (or QRS 120 and left bundle branch block)
None, although life expectancy >1 year required
Not recommended for patients whose advanced frailty may limit survivala
Reduce the risk of premature death.
Use to reduce hospitalisations. b Discontinue in patients with refractory symptoms
Left ventricular assist device indicated in patients with end-stage heart failure as bridge to cardiac transplant or in nontransplant candidates as destination therapy and with good functional status
None, although life expectancy >1 year required
No specific recommendations
Discontinued in patients with device-refractory symptoms
Used to improve symptoms and reduce hospitalizationsb
Device
Recommendations are from both American and European Heart Failure Guidelines. If only one Guideline addresses than indicated. Data from Refs [15,16]. a AHA/ACC Heart Failure Guidelines. b European Heart Failure Guidelines.
&&
[17 ]. There is no consensus on which measure is best, but several recent reviews report AUC information on mortality and function disability predictive accuracy [18–20]. Frailty measures are characterized by a biologic/physiologic base or comorbidity deficit count [21]. Of the biologic measures, the Frailty Phenotype is the most commonly used and studied [9]. The phenotype captures multiple components of the syndrome including weight loss, grip strength, walk time, depression and exhaustion. The Frailty Phenotype is predictive of mortality. However, the Frailty Phenotype is time consuming and can be cumbersome to use for the busy clinician. It has been shortened to three items and retains predictive ability for morbidity and mortality [22,23]. The Frailty Index is the most commonly used measure in the count of health deficits [24]. The original scale contained 70 items, but there have been several variants to the scale using few variables [25]. The Frailty index also has good discriminate ability for predicting morbidity and mortality [20], but can be long for a clinical setting. The debate on what measure might be used in a clinical setting is still in its infancy without a clear solution for how to effectively screen for frailty in a busy clinical practice [26].
Walk tests The Geriatric Advisory Panel to the International Academy on Nutrition and Aging felt that gait speed 28
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is a quick, inexpensive and reliable measure of frailty [27]. Gait speed is strongly associated with survival [28], and is commonly used as an outcome in studies of heart failure. Both grip strength and gait speed are risk factors for hospital admission for patients with heart failure [29]. From the clinical perspective, a walk test is fairly simple and easily performed in a clinician’s office. Most clinicians who care for those with heart failure are familiar with walk tests, most commonly the 6-min walk. The 6-min walk distance of less than 300 m is closely associated with poor outcomes in multiple heart failure trials [30–32]. In addition, the 6-min walk test has been compared with the frailty phenotype with moderate agreement between those who were frail and walking less than 300 m [33]. Walk tests may be the most important measure to identify a person who is frail [28].
THERAPIES FOR FRAIL PATIENTS WITH HEART FAILURE Identification of frailty as a marker of increased mortality in those with cardiovascular disease was recently shown in a meta-analysis [34], as frailty is associated with poor outcome in surgical and emergency room patients [35–37]. Few studies have been done to target treatment in those with frailty, but Pulignano et al. [38] found, in a pilot project, that intensive team-based heart failure therapy in those with moderate frailty improved multiple health Volume 8 Number 1 March 2014
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Frailty and prognosis in advanced heart failure Boxer et al.
outcomes and decreased care costs compared to those with no frailty or more advanced frailty. These results are promising. Treating heart failure by controlling symptoms, decreasing frequency of exacerbations and maintaining activity in older adults may be the key to preventing the advancement of frailty in these patients. As in both studies of heart failure and frailty interventions that improve physical performance, particularly increasing walk distance or time indicates improved outcomes.
CONCLUSION Frailty is a complex syndrome that predisposes a patient to poor clinical outcomes. Patients with heart failure are at particularly high risk for frailty, and thus should be screened effectively. If determined to be frail, these patients may benefit from individualized therapeutic plans, but more evidence is needed. Acknowledgements None. Conflicts of interest The authors have no conflicts of interest to declare.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Harkness K, Heckman GA, McKelvie RS. The older patient with heart failure: high risk for frailty and cognitive impairment. Exp Rev Cardiovasc Ther 2012; 10:779–795. A concise review of frailty and its known relationship with heart failure. 2. Morley JE, Haren MT, Rolland Y, Kim MJ. Frailty. Med Clin North Am 2006; 90:837–847. 3. Newman AB, Gottdiener JS, McBurnie MA, et al. Associations of subclinical cardiovascular disease with frailty. J Gerontol A Biol Sci Med Sci 2001; 56:M158–166. 4. McNallan SM, Singh M, Chamberlain AM, et al. Frailty and healthcare utilization among patients with heart failure in the community. JACC Heart Fail 2013; 1:135–141. 5. Murad K, Kitzman DW. Frailty and multiple comorbidities in the elderly patient & with heart failure: implications for management. Heart Fail Rev 2012; 17:581–588. A description of frailty in relationship to other known comorbidities of the heart failure syndrome. 6. Fried LP, Xue QL, Cappola AR, et al. Nonlinear multisystem physiological dysregulation associated with frailty in older women: implications for etiology and treatment. J Gerontol A Biol Sci Med Sci 2009; 64:1049–1057. 7. Binder EF, Yarasheski KE, Steger-May K, et al. Effects of progressive resistance training on body composition in frail older adults: results of a randomized, controlled trial. J Gerontol A Biol Sci Med Sci 2005; 60:1425– 1431. 8. Chin APMJ, van Uffelen JG, Riphagen I, van Mechelen W. The functional effects of physical exercise training in frail older people: a systematic review. Sports Med 2008; 38:781–793. 9. 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–M156. 10. Piepoli MF, Coats AJ. The ’skeletal muscle hypothesis in heart failure’ revised. Eur Heart J 2013; 34:486–488.
&&
11. Coats AJ. The ‘muscle hypothesis’ of chronic heart failure. J Mol Cell Cardiol 1996; 28:2255–2262. 12. 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; 59:255–263. 13. Makary MA, Segev DL, Pronovost PJ, et al. Frailty as a predictor of surgical outcomes in older patients. J Am Coll Surg 2010; 210:901–908. 14. Allen LA, Stevenson LW, Grady KL, et al. Decision making in advanced heart failure: a scientific statement from the american heart association. Circulation 2012; 125:1928–1952. 15. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the american college of cardiology foundation/american heart association task force on practice guidelines. Circulation 2013; 62:e147–e239. 16. McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012; 33:1787– 1847. 17. Theou O, Brothers TD, Mitnitski A, Rockwood K. Operationalization of frailty && using eight commonly used scales and comparison of their ability to predict all-cause mortality. J Am Geriatr Soc 2013; 61:1537–1551. A large, multicenter secondary analysis comparing current major frailty scales and their ability to predict mortality. 18. Pijpers E, Ferreira I, Stehouwer CD, Nieuwenhuijzen Kruseman AC. The frailty dilemma. Review of the predictive accuracy of major frailty scores. Eur J Intern Med 2012; 23:118–123. 19. Shamliyan T, Talley KM, Ramakrishnan R, Kane RL. Association of frailty with survival: a systematic literature review. Ageing Res Rev 2013; 12:719–736. 20. Sterniczuk R, Theou O, Rusak B, Rockwood K. Sleep disturbance is associated with incident dementia and mortality. Curr Alzheimer Res 2013; 10:767–775. 21. Ferrucci L, Guralnik JM, Studenski S, et al. Designing randomized, controlled trials aimed at preventing or delaying functional decline and disability in frail, older persons: a consensus report. J Am Geriatr Soc 2004; 52:625–634. 22. Ensrud KE, Ewing SK, Cawthon PM, et al. A comparison of frailty indexes for the prediction of falls, disability, fractures, and mortality in older men. J Am Geriatr Soc 2009; 57:492–498. 23. Ensrud KE, Ewing SK, Taylor BC, et al. Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women. Arch Intern Med 2008; 168:382–389. 24. Mitnitski AB, Mogilner AJ, Rockwood K. Accumulation of deficits as a proxy measure of aging. ScientificWorldJournal 2001; 1:323–336. 25. Rockwood K, Mitnitski A. Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriatr Med 2011; 27:17–26. 26. Lacas A, Rockwood K. Frailty in primary care: a review of its conceptualization and implications for practice. BMC Med 2012; 10:4. 27. Abellan van Kan G, Rolland Y, Bergman H, et al. The I.A.N.A task force on frailty assessment of older people in clinical practice. J Nutr Health Aging 2008; 12:29–37. 28. Studenski S, Perera S, Patel K, et al. Gait speed and survival in older adults. JAMA 2011; 305:50–58. 29. Chaudhry SI, McAvay G, Chen S, et al. Risk factors for hospital admission among older persons with newly diagnosed heart failure: findings from the cardiovascular health study. J Am Coll Cardiol 2013; 61:635–642. 30. Bittner V, Weiner DH, Yusuf S, et al. Prediction of mortality and morbidity with a 6-min walk test in patients with left ventricular dysfunction. SOLVD investigators. JAMA 1993; 270:1702–1707. 31. Rostagno C, Olivo G, Comeglio M, et al. Prognostic value of 6-min walk corridor test in patients with mild to moderate heart failure: comparison with other methods of functional evaluation. Eur J Heart Fail 2003; 5:247–252. 32. Cahalin LP, Mathier MA, Semigran MJ, et al. The six-minute walk test predicts peak oxygen uptake and survival in patients with advanced heart failure. Chest 1996; 110:325–332. 33. Boxer RS, Wang Z, Walsh SJ, et al. The utility of the 6-min walk test as a measure of frailty in older adults with heart failure. Am J Geriatr Cardiol 2008; 17:7–12. 34. Afilalo J, Karunananthan S, Eisenberg MJ, et al. Role of frailty in patients with cardiovascular disease. Am J Cardiol 2009; 103:1616–1621. 35. Brown NA, Zenilman ME. The impact of frailty in the elderly on the outcome of surgery in the aged. Adv Surg 2010; 44:229–249. 36. Robinson TN, Eiseman B, Wallace JI, et al. Redefining geriatric preoperative assessment using frailty, disability and co-morbidity. Ann Surg 2009; 250:449–455. 37. Hastings SN, Purser JL, Johnson KS, et al. Frailty predicts some but not all adverse outcomes in older adults discharged from the emergency department. J Am Geriatr Soc 2008; 56:1651–1657. 38. 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 costeffectiveness, pilot study. J Cardiovasc Med (Hagerstown) 2010; 11:739– 747.
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29
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Frailty and prognosis in advanced heart failure Rebecca S. Boxer a, Khanjan B. Shah b, and Anne M. Kenny c
Purpose of review The frailty syndrome is characterized by an increased vulnerability to physiologic stress. Frailty is distinct from disability and disease states; however, there is a strong relationship between frailty and heart failure and the pathophysiology’s overlap. Heart failure exacerbations and hospitalizations likely accelerate the cycle of frailty. The following review summarizes the relationship between heart failure and frailty, and the utility of a frailty assessment in heart failure management. Recent findings A frailty assessment can help to stratify heart failure patients at high risk for adverse outcomes. Increasing availability of device therapies for patients with heart failure make prerisk assessment an important management strategy. Summary Furthermore, studies are necessary to understand the relationship between heart failure and frailty and to devise the best care strategies for these patients. Keywords aging, frailty, heart failure
INTRODUCTION Heart failure is the leading cause of hospitalizations and re-hospitalizations in older adults and represents a large burden on healthcare utilization. Frailty, defined as a vulnerability to withstand physiological stress, can help identify at-risk older adults and aid in decision-making for advance therapies and palliation.
FRAILTY AND HEART FAILURE Frailty is defined as a state of complex physiologic dysfunction that predisposes a person to poor clinical outcomes when confronted with stressors, such as acute illness, surgical procedures or psychosocial stress [1 ]. Although previously thought to be synonymous with ‘normal’ aging, frailty is a separate syndrome. The frailty cascade begins with normal age-related deterioration of physiologic process. These changes are compounded by the accumulation of chronic diseases. For the frail patient who has lost their physiologic resiliency, a stressful event such as a heart failure exacerbation can lead to functional decline, disability and dependency [2]. It is no surprise that a disease such as heart failure, which is common in older adults and has multisystem effects, is associated with frailty. The &&
Cardiovascular Health Study examined a cohort of 4735 community dwelling older adults and found 299 (6%) to be frail; having heart failure was the most strongly association with being frail (odds ratio ¼ 7.5) [3]. This study and many others have found frailty to be predictive of many adverse health outcomes including mortality, hospitalizations, disability and institutionalization.
CHARACTERISTICS OF THE FRAIL HEART FAILURE PATIENT Patients with heart failure deemed as frail are more likely to have diabetes, chronic obstructive pulmonary disease, atrial fibrillation, depression, anemia, chronic kidney disease and higher ejection fractions [4]. In general, older patients with heart failure are
a
Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, bInternal Medicine, Case Western Reserve University, Cleveland, Ohio and cProfessor of Medicine, Center on Aging, University of Connecticut, Farmington, Connecticut, USA Correspondence to Rebecca S. Boxer, MD, Harrington Heart and Vascular Institute, University Hospitals Case Medical Center, Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106, USA. Tel: +1 216 844 7726; e-mail: [email protected] Curr Opin Support Palliat Care 2014, 8:25–29 DOI:10.1097/SPC.0000000000000027
1751-4258 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.supportiveandpalliativecare.com
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Cardiac and circulatory problems
KEY POINTS Frailty is defined as physiological derangement that renders a patient unable to sustain various stressors. Heart failure is the most common chronic medical illness associated with a frail state. Symptoms of poorly controlled heart failure overlap with symptoms of frailty making diagnosis and effective therapeutic plans challenging. The Frailty Phenotype and Index are two measures of frailty, but both are cumbersome for routine outpatient visits. For this reason, walk tests are more easily employed clinically. More studies are needed to understand the relationship between heart failure and frailty and the effect of current heart failure therapies on patients who are frail.
more commonly women and more likely to have preserved ejection fraction (HFpEF) [5 ]. Unlike heart failure with reduced ejection fraction (HFrEF), relatively less is known about the appropriate treatment strategies for HFpEF. And although the overall survival for heart failure has improved with current medication and device treatments, the survival of HFpEF has remained unchanged over several decades [5 ]. The lack of evidence as to how to successfully medically manage older adults with HFpEF may contribute to the development of frailty. In HFrEF many older adults do not tolerate guideline medical therapy, which limits symptom control. As heart failure limits aerobic capacity and activity tolerance, poor symptom control likely accelerates physical limitations. The inability to tolerate activity results in underused skeletal muscle and sarcopenia. Chronic exercise intolerance and loss of muscle strength are also impacted by perturbations of inflammatory mediators and neurohormones. Multisystem dysregulation indicates the complexity of the frailty syndrome in patients with heart failure. Increasing complexity may be more important than any one diagnosis alone and also indicates that treatment for only one disorder may not impact overcome and reverse frailty [6]. Signs and symptoms typical of older heart failure patients are also those that define the frail state, which makes distinguishing between the two difficult. Both can result in fatigue, sarcopenia, poor activity tolerance and depression. However, treatment of heart failure with appropriate medication can result in improvement of symptoms. Treatment for frailty remains elusive; however, exercise is the most promising [7,8]. &
&
26
www.supportiveandpalliativecare.com
NEUROENDOCRINE DYSREGULATION, INFLAMMATION AND SKELETAL MUSCLE DYSFUNCTION The syndromes of both heart failure and frailty have similar characteristics in neurohormone dysregulation, inflammation, catabolism and skeletal muscle dysfunction. The Cycle of Frailty [9] (Fig. 1) and the Muscle Hypothesis of Heart Failure [10] (Fig. 2) are depicted below. It is impossible to separate the two syndromes in that their pathophysiology’s overlap. It is not surprising that heart failure and frailty are closely associated in observational studies and it is likely that heart failure accelerates the frail state.
IDENTIFICATION OF FRAILTY IN PATIENTS WITH HEART FAILURE Identification of patients who are frail has increased in importance over the last 10 years. Frailty, chronic disease and disability overlap but are seen as distinct entities [12]. Identifying which heart failure patients are frail can assist in the decision-making process to pursue procedural therapies. Using a frailty measure, a patient can be risk stratified prior to being offered procedural therapies. Decisions to pursue advanced therapies such as implantable defibrillators, cardiac resynchronization devices and left ventricular assist devices incorporates many factors including a patient’s ability to tolerate and glean benefit from the procedure. Control of symptoms and improvement in quality of life are just as important as avoiding procedures in those at risk for adverse outcomes. The frail patient has a marked increased risk from surgical procedures and should be carefully considered by patient and physician before pursuing [13]. However, the frail state may be improved with better heart failure control, that is, improved volume control and activity tolerance. This factor makes the decision to pursue device therapy complex and requires careful patient evaluation, consideration and a shared decision-making approach [14]. In addition, it is important to conserve resources for the patients who will benefit most. At present, heart failure guidelines offer some guidance to those who are appropriate for device therapies, however, mostly by life-expectancy, which is very difficult to predict in heart failure [15,16] (Table 1). More research is needed to develop decision-making algorithms for device therapy based on functional and physiologic measures in patients with heart failure.
FRAILTY MEASURES There is no gold standard to measure frailty. There are multiple methods that range from physiologic measures to accumulation of health problems and there is great variability in the characteristics used Volume 8 Number 1 March 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Frailty and prognosis in advanced heart failure Boxer et al.
Disease Aging: senescent musculoskeletal changes
Chronic undernutrition
Neuroendocrine dysregulation
Negative energy balance
[Inadequate intake of protein and energy: micronutrient deficiencies]
Anorexia of aging
Weight loss Negative nitrogen balance
Loss of muscle mass
Sarcopenia
Total energy expenditure
Activity Walking speed
Resting metabolic rate
Strength and power
VO2 max
Disablity
Dependency
FIGURE 1. Cycle of frailty. The cycle of frailty demonstrates the multiple physiologic factors that contribute to the frail state. Reproduced with permission [9].
Reduced peripheral blood flow Left ventricular dysfunction
Vasoconstriction increased afterload
Catabolic state
Skeletal and respiratory myopathy
Sympathoexcitation
Increased ventilation
Tumour necrosis factor, insulin resistance, malnutrition, inactivity
Increased ergoreflex activity
Fatigue and dyspnoea
FIGURE 2. The muscle hypothesis of heart failure [11]. The muscle hypothesis of heart failure demonstrates the multiple physiologic factors that contribute to fatigue and dyspnea in the heart failure syndrome. Reproduced with permission [11]. 1751-4258 ß 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins
www.supportiveandpalliativecare.com
27
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Cardiac and circulatory problems Table 1. Recommendations from heart failure guidelines based on age, frailty and palliation Age cut off for device use?
Recommendations for frail patients?
Does the device prolong life?
Does the device palliate symptoms?
Implantable defibrillator Indicated for patients with EF 35% despite 3 months of medical therapy
None, although life expectancy >1 year required
Unknown benefit in patients with advanced frailtya
Used to reduce the risk of sudden cardiac death due to ventricular arrhythmias
No specific use. Discontinue in patients with devicerefractory symptoms
Biventricular Pacemaker Indicated in symptomatic patients with EF 35% and QRS 150 (or QRS 120 and left bundle branch block)
None, although life expectancy >1 year required
Not recommended for patients whose advanced frailty may limit survivala
Reduce the risk of premature death.
Use to reduce hospitalisations. b Discontinue in patients with refractory symptoms
Left ventricular assist device indicated in patients with end-stage heart failure as bridge to cardiac transplant or in nontransplant candidates as destination therapy and with good functional status
None, although life expectancy >1 year required
No specific recommendations
Discontinued in patients with device-refractory symptoms
Used to improve symptoms and reduce hospitalizationsb
Device
Recommendations are from both American and European Heart Failure Guidelines. If only one Guideline addresses than indicated. Data from Refs [15,16]. a AHA/ACC Heart Failure Guidelines. b European Heart Failure Guidelines.
&&
[17 ]. There is no consensus on which measure is best, but several recent reviews report AUC information on mortality and function disability predictive accuracy [18–20]. Frailty measures are characterized by a biologic/physiologic base or comorbidity deficit count [21]. Of the biologic measures, the Frailty Phenotype is the most commonly used and studied [9]. The phenotype captures multiple components of the syndrome including weight loss, grip strength, walk time, depression and exhaustion. The Frailty Phenotype is predictive of mortality. However, the Frailty Phenotype is time consuming and can be cumbersome to use for the busy clinician. It has been shortened to three items and retains predictive ability for morbidity and mortality [22,23]. The Frailty Index is the most commonly used measure in the count of health deficits [24]. The original scale contained 70 items, but there have been several variants to the scale using few variables [25]. The Frailty index also has good discriminate ability for predicting morbidity and mortality [20], but can be long for a clinical setting. The debate on what measure might be used in a clinical setting is still in its infancy without a clear solution for how to effectively screen for frailty in a busy clinical practice [26].
Walk tests The Geriatric Advisory Panel to the International Academy on Nutrition and Aging felt that gait speed 28
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is a quick, inexpensive and reliable measure of frailty [27]. Gait speed is strongly associated with survival [28], and is commonly used as an outcome in studies of heart failure. Both grip strength and gait speed are risk factors for hospital admission for patients with heart failure [29]. From the clinical perspective, a walk test is fairly simple and easily performed in a clinician’s office. Most clinicians who care for those with heart failure are familiar with walk tests, most commonly the 6-min walk. The 6-min walk distance of less than 300 m is closely associated with poor outcomes in multiple heart failure trials [30–32]. In addition, the 6-min walk test has been compared with the frailty phenotype with moderate agreement between those who were frail and walking less than 300 m [33]. Walk tests may be the most important measure to identify a person who is frail [28].
THERAPIES FOR FRAIL PATIENTS WITH HEART FAILURE Identification of frailty as a marker of increased mortality in those with cardiovascular disease was recently shown in a meta-analysis [34], as frailty is associated with poor outcome in surgical and emergency room patients [35–37]. Few studies have been done to target treatment in those with frailty, but Pulignano et al. [38] found, in a pilot project, that intensive team-based heart failure therapy in those with moderate frailty improved multiple health Volume 8 Number 1 March 2014
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Frailty and prognosis in advanced heart failure Boxer et al.
outcomes and decreased care costs compared to those with no frailty or more advanced frailty. These results are promising. Treating heart failure by controlling symptoms, decreasing frequency of exacerbations and maintaining activity in older adults may be the key to preventing the advancement of frailty in these patients. As in both studies of heart failure and frailty interventions that improve physical performance, particularly increasing walk distance or time indicates improved outcomes.
CONCLUSION Frailty is a complex syndrome that predisposes a patient to poor clinical outcomes. Patients with heart failure are at particularly high risk for frailty, and thus should be screened effectively. If determined to be frail, these patients may benefit from individualized therapeutic plans, but more evidence is needed. Acknowledgements None. Conflicts of interest The authors have no conflicts of interest to declare.
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