key: cord-0062094-i4aeb162
authors: Chung, Kenneth Jordan Ng Cheong; Wilkinson, Chris; Veerasamy, Murugapathy; Kunadian, Vijay
title: Frailty Scores and Their Utility in Older Patients with Cardiovascular Disease
date: 2021-03-31
journal: Interv Cardiol
DOI: 10.15420/icr.2020.18
sha: 3716ab48b0f209c4f996a9b755bc94644b1a4d15
doc_id: 62094
cord_uid: i4aeb162

The world’s population is ageing, resulting in more people with frailty receiving treatment for cardiovascular disease (CVD). The emergence of novel interventions, such as transcatheter aortic valve implantation, has also increased the proportion of older patients being treated in later stages of life. This increasing population burden makes the assessment of frailty of utmost importance, especially in patients with CVD. Despite a growing body of evidence on the association between frailty and CVD, there is no consensus on the optimal frailty assessment tool for use in clinical settings. Previous studies have shown limited concordance between validated frailty instruments. This review evaluates the evidence on the utility of frailty assessment tools in patients with CVD, and the effect of frailty on different outcomes measured.

Frail originates from the French word frêle, meaning 'of little resistance', and from the Latin word fragilis, meaning 'easily broken'. In medicine, frailty is a condition in which there is a decline in biological reserves and deterioration in physiological mechanisms that render a person vulnerable to a range of adverse outcomes. 1 It is expected that the proportion of the world's population over 60 years of age will nearly double from 2015 to 2050. 2 Alongside this ageing population, an increased burden of frailty means that optimal clinical management of this vulnerable population is of key importance.

In recent years, there has been increasing interest in the clinical implications of frailty in patients with cardiovascular disease (CVD). There has also been an increase in the number of patients with frailty, which coexists in up to 60% of patients with CVD. 3 Following stressors such as acute coronary syndrome (ACS) and invasive procedures, patients with frailty are at risk of disadvantaged health outcomes, such as dependency, disability, falls, institutionalisation and mortality. [4] [5] [6] [7] More recently, the coronavirus disease 2019 (COVID-19) pandemic has put an additional stress on these patients, emphasising the importance of frailty assessment to help individualise care for older patients with CVD. 8 Frailty and disability, although interrelated, are considered distinct clinical entities. Frailty predicts disability, but disability may exacerbate frailty, 5 which may lead to co-occurrence and difficulty in the assessment of frailty. As such, frailty assessment is still not routinely conducted in cardiology practice, and there is a lack of consensus on which frailty assessment tool to use and in which setting. 9 This review summarises the latest evidence on common assessment tools used in people with CVD, with a particular focus on those patients with coronary and valvular diseases, and provides a synthesis of the utility of these tools in predicting outcomes in patients with CVD.

The concept of frailty has been described in various ways. A study identified 67 instruments that can be used to assess frailty. 10 Some of these instruments focus on physical and biological aspects, whereas others focus more holistically on physical, psychological and social domains.

The commonly used frailty instruments discussed in this review, and the components they evaluate, are summarised in Table 1 . Of note, mobility is assessed in all the multidomain tools.

The physical frailty phenotype, also called Fried's frailty scale, consists of five core domains: slowness, weakness, low physical activity, exhaustion and shrinking. 4 Patients meeting one or two criteria are considered as pre-frail, and those meeting three or more are considered frail. The physical frailty phenotype formed the basis of the Cardiovascular Health Study (CHS) frailty assessment and is the most frequently used instrument. Although Fried's scale accurately predicts mortality in patients with CVD, it is not readily measurable in acute clinical situations because it includes a measurement of grip strength, a walking test and a detailed quality of life questionnaire. 11 

The Short Physical Performance Battery (SPPB) measures a series of three timed physical performance tests, including gait speed, chair rises and tandem balance. 12 Performance on each test is scored from 0 to 4, with a total score ≤5 (of a possible 12) indicating frailty. The SPPB is relatively simple, cheap and takes approximately 10 minutes to complete. It does not require the presence of physicians, but may be difficult to administer in acute situations.

The Frailty Index (FI), also known as the Deficit Accumulation Index (DAI), considers frailty across multiple domains and may include physical, psychological and social components in addition to laboratory values. 13 The number of deficits identified in an individual is correlated with the level of frailty. The proportion of deficits over the number of items evaluated is expressed as a fraction, and an FI >score 0.25 is usually considered as frail. 14 

The Survey of Health Ageing and Retirement in Europe Frailty Index (SHARE-FI) is based on the Fried criteria, and evaluates exhaustion, appetite, ambulation, resistance, physical activity and handgrip strength measurement. 15 The SHARE-FI is easier to measure than the original Fried scale, because the questionnaire can be easily completed at the bedside and does not require the measurement of gait speed.

The Tilburg Frailty Indicator is a multidimensional structured questionnaire that evaluates the physical, psychological and social domains. 16 It consists of two parts. Part A has 10 questions on frailty determinants (age, sex, marital status, education level, social circumstances and lifestyle). Part B has 15 frailty elements across three domains: 1. Physical, consisting of eight items (physical health, unintentional weight loss, difficulty walking and problems with balance, hearing, vision, hand strength and physical tiredness).

2. Psychological, consisting of four items (cognition, depression, anxiety and coping). 3. Social, consisting of has three items (living alone, social relationships and social support).

Each item in Part B scores 1 point, and patients are considered frail if they score at least 5 of a possible 15.

The Clinical Frailty Scale (CFS) was designed for the CSHA and can be readily administered in most clinical settings. 17 The CFS is based on fitness, active disease, activities of daily living (ADL) and cognition, and the expanded scale ranges from 1 (very fit) to 9 (terminally ill). 17, 18 Because assessment relies upon the subjective judgement of a clinician, the measure is prone to interobserver variability. 17

The Edmonton Frail Scale (EFS) is another multidimensional scale, comprising 10 domains with 17 potential deficits covering cognition, general health status, functional independence, social support, medication use, nutrition, mood, continence and functional performance. 19 The EFS includes the clock test for assessment of cognitive impairment, and the Timed Get Up and Go (TUG) for balance and mobility. The cut-off point for frailty is 12 or more deficits. The EFS has good correlation with the opinion of a specialist following a Comprehensive Geriatric Assessment (CGA). 19 Because a CGA is time consuming, the EFS offers a rapid screening tool for the non-geriatric specialist.

The Reported Edmonton Frail Scale (REFS) includes nine frailty domains: cognition, general health status, functional independence, social support, medication use, nutrition, mood, continence and functional performance. 20 Compared with the EFS, the REFS is based on self-reported functioning, and is appropriate in patients able to complete a questionnaire. Frailty is identified by a score of at least 8. 

The Hospital Frailty Risk Score (HFRS) uses ICD-10 diagnostic codes from electronic healthcare records to identify frailty. It includes more than 100 variables derived from routinely collected data and has been validated against both the Fried scale and other FI measures. 21 Fatigue, Resistance, Ambulation, Illnesses and Loss of Weight Scale

The Fatigue, Resistance, Ambulation, Illnesses and Loss of weight (FRAIL) scale is a brief, interview-based screening tool. The FRAIL scale is commonly used in the acute setting because it does not include items that are difficult to measure (e.g., walk speed, handgrip strength, stand-up test). 22

The CGA is considered to be the gold standard for frailty assessment and involves a holistic, multidimensional and interdisciplinary assessment of an individual, culminating in the formulation of an individualised management plan. 23 The CGA is time consuming and is not part of the routine care of older people. Potentially useful brief screening tests include measuring 5 m gait speed, which is highly predictive of cardiovascular mortality, or handgrip strength. [24] [25] [26] [27] These frailty assessment tools are all different. Some scales, such as the FRAIL scale, FI and CFS, are based on interviews without objective assessment of physical performance and have a prognostic implication in patients with ACS. 28

The association between frailty and CVD is bidirectional, because frailty is associated with an increased risk of CVD and CVD mortality, 11, 29 and CVD is associated with an up to threefold increase in frailty. 3, 30, 31 Insights from the CHS have shown that subclinical CVD measures strongly predict frailty, even after adjustment for traditional CVD risk factors, whereas being overweight or obese and having a higher age-adjusted composite coronary artery score in midlife were associated with frailty 26 years later. 32, 33 This implies that frailty and CVD may also have long-term connections that should be recognised. 11 Frailty, which was found in 17.9%, was associated with an increased risk of CHD, heart failure and risk of cardiovascular mortality, whereas prefrailty carried a higher risk of heart failure and cardiovascular mortality. 11 Supplementary Table 1 summarises studies assessing the outcomes of patients with frailty and CVD.

Three components of a modified Fried scale, namely low energy expenditure (p=0.03), exhaustion (p=0.01) and slow gait speed (p=0.03), were shown to be significantly associated with CVD onset, whereas two were not (unintentional weight loss and weakness). 34 An independent association was demonstrated between prefrailty and the development of CVD, with low gait speed the best predictor of future CVD. The risk was higher in those meeting two frailty criteria (HR In a secondary analysis of longitudinal data, 35 instruments were grouped into four domains, namely Fried phenotype, multidimensional, accumulation of deficits and disability. 35 The authors of that study showed that multidimensional frailty scores may have a stronger and more stable association with all-cause mortality and the incidence of cardiovascular events. 35 

The relationship between frailty and the risk of adverse outcome following ST-segment elevation MI (STEMI) and non-STEMI (NSTEMI) has been demonstrated by many studies using different frailty assessment tools (Supplementary Table 2 , Table 2 and Table 3 ). A recent systematic review and meta-analysis evaluated the prognostic value of frailty in 8,554 patients with ACS. 37 Similar findings were reported by another study on 629 patients who underwent PCI for coronary artery disease (CAD) but in whom frailty was assessed using the Fried scale. 50 The association of frailty with mortality or MI at 3 years was significant (HR 2.74; 95% CI [1.12-6.71]) and more prevalent compared with non-frail patients (28% versus 6%). In addition, frailty, comorbidity measured on the Charlson Index and quality of life measured by the 36-Item Short Form Health Survey (SF-36) were associated with adverse long-term outcomes after PCI, and all significantly improved the prognostic ability of the Mayo Clinic risk score. 50 Furthermore, using the Fried scale on patients with CAD undergoing PCI (11.9% STEMI, 15.4% NSTEMI) did not reveal any significant differences in 30-day outcomes (death, MI and revascularisation). 51 However, the authors of that study demonstrated that the 18.6% of patients who were frail had poorer health status than non-frail patients using the SF-36 and Seattle Angina Questionnaire, and that they had more multivessel or left main CAD than intermediate frail and non-frail patients (74% versus 68% and 60%, respectively; p=0.019). An association between severe frailty and mid-term mortality was also observed in STEMI patients undergoing PCI. 57 59 This shows the variety of frailty tools that can be used to predict worse outcomes in ACS patients and those undergoing invasive interventions. Table 3 summarises studies assessing frailty in patients with STEMI.

Frailty, as assessed by an FI based on assessment of cognition, mobility, nutrition and instrumental and basic ADL, has shown to be highly predictive of functional decline in older people undergoing transcatheter aortic valve implantation (TAVI). 60 Worse outcomes were also demonstrated in the 49% of patients who were identified as frail using a multidimensional geriatric assessment (MGA) consisting of Mini Mental State Examination, mini nutritional assessment, TUG, basic ADL, instrumental ADL and a preclinical mobility disability. 61 65 The EFT is comprised of four items: lower-extremity weakness, cognitive impairment, anaemia, and hypoalbuminaemia. Table 4 summarises the studies assessing frailty in patients with valvular heart diseases.

It is increasingly recognised that frailty assessment has the potential to contribute valuable prognostic information in order to inform shared decision making in patients with CVD. 9 However, the translation from research to clinical practice remains a challenge, and consensus is lacking on the best tool to use in routine clinical practice. 66 This review has summarised the features of frailty instruments used in cardiovascular studies and their utility in clinical practice. It also provides a detailed analysis of outcomes in patients with CVD, with a particular emphasis on coronary and valvular heart diseases.

The most appropriate tool to use is clearly setting dependent, although most frailty scores were developed in the community population. For example, the FI tends to be more commonly used in clinical research datasets, although this has been successfully implemented into routine clinical practice using electronic primary healthcare records. 67, 68 This has the advantage of enabling the estimation of a 'baseline' frailty state, calculated before an acute presentation. However, more accurate assessment is required because the 'baseline' frailty state may be independent of the clinical state at the time of hospital admission.

Frailty is associated with both CVD mortality and non-CVD mortality, which highlights the importance of considering the competing risk of non-CVD mortality when assessing the benefit of CVD interventions in clinical practice. 9,69 This is particularly important in a population that is at particular risk of iatrogenic harm. However, the implementation of multidimensional or complex assessment tools, although accurate at predicting mortality in CVD patients, can be challenging in time-dependent situations. 35, 36, 70 Options for frailty assessment in the clinical setting include performance tests that assess the physical functioning of patients. Epidemiological data suggest that slow gait speed is the first domain of the frailty phenotype to manifest rather than weight loss, which tends to occur at a later stage, and the use of gait speed reliably identifies patients at risk of cardiovascular events and mortality. 27, 29, 34, 59, 71 A decrease in physiological reserve when evaluating physical functioning, or the presence of multisystem deficits, gives useful data on likely recovery after a stressor event, such as ACS or an invasive procedure. 60 The assessment of frailty on the Fried scale and EFS has been adapted in many studies evaluating patients with ACS and has consistently been associated with mortality. 38, 39, 42, 45, 47 However, the use of the Fried scale has been questioned in recent studies that found it inferior to other scales or different between sexes, although further analysis is needed to provide a definite answer. 45, 46 This shows there is no consensus as to which frailty assessment tool to use even though different studies evaluated similar outcomes. In these cases, the use of a well-established tool in the hospital setting may be recommended. However, in studies on patients with NSTEMI or STEMI undergoing PCI, the use of CFS and the FRAIL scale is more commonly seen, suggesting that their use seems more accepted in acute interventional cardiology, although further comparative studies are required to provide a better assessment. 54, [56] [57] [58] The ease and speed with which these assessments can be completed makes their use appealing. If these frailty scales consistently demonstrate reproducibility and efficacy at predicting outcomes, they could be considered as an ideal frailty instrument. There is also a dearth of evidence on the risk of cardiac interventions instead of medical management in patients with frailty. Although invasive interventions are associated with poor outcomes in patients with frailty, this should be weighed against the risk of not intervening, which may result in poorer quality of life with repeated hospitalisation. In these circumstances, frailty assessment for informed decision making requires more clarity. Alternatively, a multidimensional assessment of frailty may be needed. Social frailty was positively associated with physical frailty on the CHS score, whereas the FI and EFS have proved to most accurately predict mortality in comparative studies. 72, 73 Other frailty subtypes, such as nutritional frailty, may also have a crucial role in predicting outcomes in CVD patients. 74, 75 Worse quality of life has also been linked to frailty, which supports the importance of multidimensional assessment tools. 76 Many studies evaluating frailty in patients undergoing TAVI have included ADL as well as the use of serum biomarkers and assessment of physical frailty. 61,62 ADL have even been shown to be better than gait speed at predicting survival in TAVI patients, and may offer potential prognostic aspects in this setting. 63 However, the use of ADL or the DAI may not be fully representative of frailty, but partly an element of disability. Figure 1 summarises the different components present in the assessment of frailty in the different frailty assessment tools discussed in this review. It has been suggested that the progression to frailty may be slowed, which could potentially lead to better outcomes. Suggested interventions in older patients with frailty include increased physical activity, cardiac rehabilitation, a protein-rich diet, cognitive training and medication optimisation. [77] [78] [79] [80] [81] In addition, an exercise intervention has shown promising results in older patients after MI. 82 However, evidence is lacking that these measures have a significant effect on overall trajectory, especially in patients with CVD, and further investigation is certainly warranted in this area.

Frailty is common among patients with CVD and is associated with disadvantaged clinical outcomes. Knowledge of a person's frailty status provides valuable information on prognosis that may be useful in guiding informed shared decision making regarding treatment strategy. The frailty scales discussed are all useful, and personal preference and ease of implementation will play a role as to which one to use. Although the Fried criteria and FI are the most commonly used tools in research, perhaps the use of an easy and quick scale, such as the CFS and FRAIL, or one based on routinely collected data, such as the FI or HFRS, may be more feasible in clinical practice. Currently, however, there is no agreement on the optimal frailty assessment tool, and research into whether decision making based on the routine assessment of frailty improves patient outcomes in cardiology practice is ongoing. 

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