Gen Thorac Cardiovasc Surg DOI 10.1007/s11748-015-0553-8
REVIEW ARTICLE
Frailty in cardiothoracic surgery: systematic review of the literature Hiroshi Furukawa1 • Kazuo Tanemoto1
Received: 3 March 2015 / Accepted: 18 April 2015 Ó The Japanese Association for Thoracic Surgery 2015
Abstract A preoperative surgical risk analysis is necessary and important for predicting clinical and surgical outcomes in a clinical setting. Various tools for evaluating the patient characteristics in order to forecast perioperative clinical outcomes have previously been described; however, an objective and precise preoperative risk assessment has not yet been established. In the last decade, the concept of frailty, which is a geriatric assessment that identifies disabilities and weaknesses in patients, has been used in order to predict clinical mortality and morbidity following invasive surgical interventions because the prevalence of elderly patients among those undergoing surgical interventions is increasing. Since there is currently no single generally accepted clinical definition of frailty, many clinical modalities are needed to evaluate the patients’ geriatric activity of daily living. Quantifying the quality of frailty is an evolving challenge for predicting surgical risks preoperatively. In recent years, with the development of transcatheter aortic valve implantation (TAVI), this newly definitive preoperative surgical risk assessment tool, frailty, has become more important and is attracting interest in cardiothoracic surgical settings. Thus, this review summarized current consideration on the preoperative risk analysis by frailty as well as future perspectives and the potential of an ideal frailty risk assessment in cardiothoracic surgery, including the management of elderly patients and high-risk aortic valve stenosis by TAVI.
& Hiroshi Furukawa [email protected] 1
Department of Cardiovascular Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan
Keywords Frailty Elderly patients Thoracic surgery Cardiac surgery Transcatheter aortic valve implantation
Introduction Since populations around the world are rapidly aging, the number of elderly patients who underwent cardiothoracic surgery has markedly increased in the last decade. Perioperative morbidity and mortality are higher in elderly patients in spite of advances in perioperative medical therapy and aggressive surgical management. Therefore, it is becoming increasingly difficult to predict potential risk factors for elderly patients scheduled to undergo cardiothoracic surgery because existing risk assessment tools are incomplete in a clinical setting. The concept of frailty, which is a term widely used to denote the multidimensional syndrome of the loss of reserves such as energy, physical ability, cognition, and vulnerability, has recently been established. Frailty is a geriatric syndrome of increased vulnerability to stressors that has been implicated as a causative and prognostic factor in patients with cardiothoracic diseases, and can be defined as a lack of physiological reserves across multiple organ systems. There is currently no standardized method for measuring physiological reserves in older surgical patients, and this has prompted many investigators to define the universal acceptance of frailty. Since a number of approaches have been used to assess frailty in surgical patients, frailty has been associated with a 3- to 13- fold higher risk of discharge to a facility [1]. The prevalence physical frailty was 9.9 % (15 studies, 44,894 participants) while that of the broad phenotype of frailty was 13.6 % (8 studies, 24,072 participants), and these prevalence increased with age and were higher in women than in men
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[1]. Improvements in the comparability of epidemiological and clinical studies on frailty were regarded as an important step forward by a systematic review of Collard et al. [2]. To assess the potential of frailty as a surgical risk analysis, we herein summarized the concept of frailty in cardiothoracic surgery.
General concept, assessment, and tools of frailty in surgery Frailty is a state of increased vulnerability to the poor resolution of homoeostasis after a stressor event such as surgical invasion. Frailty develops as a consequence of not only preoperative age-related declines in many physiological systems, but also disabilities, which increase the risk of adverse outcomes after surgery. Rockwood K and associates developed the clinical tool of frailty using the Canadian Study of Health and Aging (CSHA) frailty score in 2005 following their consistent studies in a clinical setting, and argued that the clinical frailty scale could predict death or the need for institutional care [3]. Frailty prevalence rates varied from 4.0 to 59.1 % and average prevalence rate was 9.9 % for frailty and 44.2 % for prefrailty when the reported rates were restricted to the studies that used the phenotype model [4]. Physical performance measures, such as gait speed, were also used as a standard tool to evaluate the preoperative frailty and disabilities of patients, as described later, and gait speed was associated with survival in older adults [5]. Table 1 shows the potential tools used to evaluate frailty. Patient activities such as gait speed, as revealed by the 6-minute walk test (6MWT) and 5-meter walk test (5MWT), and the strength of muscle activity, which was shown by the handgrip strength (HGS) test, were useful for evaluating and reflecting the degree of frailty. Serum albumin as well as serum creatinine levels reflect not only the nutrition status of patient, but also frailty. Thus, the concept of frailty as a surgical risk analysis has recently been established in a clinical setting; therefore, physicians and surgeons need to carefully consider it as useful clinical information.
Frailty and cardiac surgery In cardiac surgery, a preoperative surgical risk analysis has been developed using Society of Thoracic Surgeons’ (STS) score and EuroSCORE. However, these risk assessments were not sufficient to evaluate ideal and precise perioperative surgical risks because they sometimes overestimated or underestimated perioperative risks in a clinical setting. At the meeting of the European Association Cardio-Thoracic Surgery in 2011, the conventional
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EuroSCORE or logistic EuroSCORE was updated with new tools corresponding to the category of ‘‘poor activity’’. The accuracy of EuroSCORE II for predicting operative mortality was slightly higher than that of EuroSCORE [6]. Despite the renewal to EuroSCORE II, a significant overestimation of EuroSCORE II was observed in patients with isolated coronary artery bypass grafting (CABG) while a slight underestimation of predictions in high-risk patients was revealed by a meta-analysis of 22 studies involving 145,592 cardiac surgery procedures [7]. In 2014 AHA/ ACC guideline for the management of patients with valvular heart disease, frailty must be taken into consideration as an evaluation of surgical and interventional risk. The precise definition of frailty is still debated; therefore further research to enhance the predictive accuracy is encouraged in this universal guideline [8]. Sepehri and colleagues reviewed the clinical impact of frailty on surgical outcomes after cardiac surgery in 2014 [9], while we reviewed additional studies and summarized our findings in Table 2 including the most recent and novel studies on the clinical role of frailty as a preoperative assessment in patients with a ventricular assist device (VAD). In 2009, de Arenaza DP and co-workers initially presented the potential of frailty as the preoperative risk analysis by 6MWT in AVR patients. The preoperative additive prognostic value of 6MWT in AVR patients may have a pivotal role in predicting clinical outcomes [10]. Lee DH and colleagues subsequently showed that 157 (4.1 %) out of the 3826 patients who underwent cardiac surgery were frail, and these frail patients were older and more likely to be female. Frailty, which was evaluated using the Katz index as the activities of daily living, ambulation, or a documented history of dementia, was an independent predictor of in-hospital mortality, institutional discharge, and reduced midterm survival [11]. Afilalo et al. [12] published two unique and novel studies, and initially showed that gait speed was a simple and effective test that identified a subset of vulnerable elderly patients at an incrementally higher risk of mortality and major morbidity after cardiac surgery. They also demonstrated that a combined approach with frailty, disabilities, and risk scores was more beneficial for elderly patients who were referred for cardiac surgery and identified those at increased risk [13]. In cardiac surgery patients older than 74 years of age, the CAF score (the comprehensive assessment of frailty: grip strength, walking speed, balance, rise up from a chair, pick up a pen, put on and remove a jacket) and FORECAST (Frailty predicts One year after Elective Cardiac Surgery Test: chair rise, weak, stair, clinical frailty scale from the CSHA, creatinine) accurately predicted mortality [14]. The CAF score also predicted not only 30-day mortality, but also midterm outcomes and mortality in highrisk elderly patients [15]. The 5MWT has been
Gen Thorac Cardiovasc Surg Table 1 Major variable indices and scores to evaluate frailty for clinical implications of cardiothoracic surgery Category for evaluating frailty
Tools
Contents
Frailty criteria
First author for representative literature
Frailty index
CSHA
1: Very fit, 2: well, 3: well with treated comorbid disease, 4: apparently vulnerable, 5: mildly frail, 6: moderately frail, 7: severely frail
Dependent of measured data
Rockwood [3], Farhat [46]
CAF score
Grip strength, walking speed, balance, rise up from chair, pick up a pen, put on and remove a jacket Chair rise, weak, stair, clinical frailty scale, creatinine
Dependent of measured data Dependent of measured data
Su¨ndermann [14, 15] Su¨ndermann [15]
MGA
MMSE, MNA, TUG, BADL, IADL, and questions about pre-clinical mobility disability
Dependent of measured data
Stortecky [31]
EFS
Cognitive impairment, dependence in instrumental activities of daily living, recent burden of illness, self-perceived health, depression, weight loss, medication issues, incontinence, inadequate social support, and mobility difficulties
Scores range from 0 (not frail) to 17 (very frail)
Dasgupta [47]
ADL
Katz index
Bathing, dressing, toileting, transferring, continence, feeding
0 (dependent)–6 (independent) Patients with any deficiency in the Katz index were defined as frail.
Lee [11], Green [32], Puls [36]
Disability
HGS
Hand grip test was measured preoperatively at various time points
HGS was normalized for total body weight
Chung [21], Flint [23], Green [32]
Gait speed
6MWT
Walking distance in 6-minutes preoperatively
Dependent of measured data
de Arenaza [10], Green [35], Nakagawa [41]
5MWT
Time taken to walk 5 m at a comfortable pace
Dependent of measured data
Serum albumin
Preoperative serum albumin
Dependent of institutional criteria
Wilson [16], Afilalo [12, 13], Mack [28] Green [32]
Serum creatinine
Preoperative serum creatinine
Dependent of institutional criteria
Su¨ndermann [15]
FORECAST
Laboratory data
CSHA Canadian Study of Health and Aging, CAF: comprehensive geriatric assessment, FORECAST Frailty predicts One year after Elective Cardiac Surgery Test, MGA multidimensional geriatric assessment, EFS Edmonton Frail Scale, HGS handgrip strength, 6MWT 6-Minute Walk Test, 5MWT 5-Meter Walk Test, MMSE mini-mental state examination, MNA mini-nutritional assessment, TUG Time Get Up and Go test, BADL basic activities of daily living, IADL instrumental activities of daily living
recommended for use by the STS as an outcome measure in the Adult Cardiac Surgery Database to predict frailty in individuals who were candidates for cardiac surgery [16]. Bagnall and co-workers reviewed the clinical role of frailty in cardiac surgery and showed that it was an independent predictor of adverse outcomes following cardiac surgery. However, it was unclear whether frailty scoring could be used either separately or combined with conventional risk scores to predict survival and complications [17]. Although age is an extensively documented independent risk factor for mortality, morbidity and decreased quality of life (QOL) after cardiac surgery, excellent outcomes were still obtained after cardiac surgery in very elderly patients with frailty [18]. Since the shortage of donor organs has been consistent with the clinical need for VAD technologies, destination therapy (DT) by VAD has become a new standard strategy
for HF [19]. Among these paradigm shifts in the strategy of VAD, interest in whether preoperative frailty is associated with clinical outcomes after the implantation of VAD as DT is increasing. Among 99 patients with VAD, frailty, as defined using the deficit index including 31 impairments, disabilities and comorbidities before destination VAD implantation, was associated with an increased risk of death and may represent a significant patient selection consideration [20]. Chung et al. [21] had recently showed that reduced HGS was associated with increased patient frailty and higher morbidity and mortality, thereby HGS was evaluated as a marker of frailty for prediction of clinical outcomes after VAD implantation in patients with advanced HF. Flint and co-workers examined two subjects, and initially showed that a preoperative assessment of frailty was highly predictive of adverse outcomes in many medical and surgical populations, but had never been
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2009
2010
2010
2011
2011
2012
2013
2014
2014
de Arenaza [10]
Lee [11]
Afilalo [12]
Su¨ndermann [15]
Su¨ndermann [14]
Afilalo [13]
Wilson [16]
Chung [21]
Dunlay [20]
99
72
113
152
400
213
131
157
208
No. of patients
Patients undergoing VAD implantation
Scheduled cardiac surgery including CABG, valve replacement or valve repair by median sternotomy Advanced heart failure patients who received VAD
[70 years elderly patients undergoing scheduled CABG and/or valve surgery
N/A
N/A
N/A
99: Not frail, 95: moderately frail, 19: severely frail 199: Not frail, 170: moderately frail, 31: severely frail N/A
[74 years cardiac surgery patients, 25 %: isolated CABG, 35 %: isolated valve procedure, 26 %: combined procedure
[74 years cardiac surgery patients
N/A
157 (4.1 %) were frail
N/A
Frailty population
70 years of age or older who were scheduled CABG and/or valve replacement or repair
Of 3826 patients who underwent cardiac surgery
200 AVR patients with either a Medtronic Freestyle stentless or Medtronic Mosaic stented valve
Surgery
Frailty was assessed using the deficit index
The HGS test which was normalized for total body weight
Frailty: 5-meter gait speed, CHS frailty scale, modified CHS frailty scale, MSSA subdimensions, Disability: Nagi items, ADL, IADL, Comorbidity: Parsonnet score, STS-PROMM, STS-PROM, Logistic EuroSCORE, ACEF score 5MWT
CAF score (Grip strength, Walking speed, Balance, Rise up from chair, Pick up a pen, Put on and remove a jacket)
CAF score, FORECAST (Chair rise, Weak, Stair, CFS, Creatinine)
Gait speed: time taken to walk 5 m in [6 s was frailty; sixty patients (46 %) were classified as slow walkers
Katz index, ambulation, or a documented history of dementia
6MWT
Frailty evaluation
Patients with a handgrip strength\25 % of body weight were at an increased risk of mortality, had more postoperative complications, and lower survival after VAD implantation Patients who were intermediately frail (adjusted HR: 1.70) and frail (HR 3.08) were at a higher risk of death than those who were not frail
Significantly slower gait speeds were noted when a subject had an observable gait or postural deviation or used an assistive device
Compared with the Parsonnet score or STS-PROMM alone, the addition of frailty and disability provided incremental value and improved model discrimination
The rates of mortality and stroke were significantly higher in 6MWT distance \300 meters. In high-risk patients with 6MWT distance below 300 m who had Euroscore over 6, the rate of death, MI, and stroke was significantly high Frailty was an independent predictor of in-hospital mortality, institutional discharge, and reduced midterm survival Slow gait speed was significantly correlated with high mortality, prolonged postoperative length of stay, and discharge to a health care facility. Concomitant slow gait speed and high STS risk ([15 %) were remarkably associated with higher rate of mortality or major morbidity The CAF score had a good predictive ability concerning one-year mortality. CAF positively correlated with the length of ventilator assistance as well as EuroSCORE. Patients in the higher frailty group had a longer stay at the ICU The CAF score accurately predicted 30-day mortality
Clinical outcomes and associations
AVR aortic valve replacement, CABG coronary artery bypass grafting, VAD ventricular assist device, N/A not applicable, 6MWT 6-Minute Walk Test, CAF comprehensive assessment of frailty, FORECAST Frailty predicts One year after Elective Cardiac Surgery Test, CFS Clinical Frailty Scale, CHS Cardiovascular Health Study, MSSA MacArthur Study of Successful Aging, ADL activities of daily living, IADL instrumental activities of daily living, STS-PROMM Society of Thoracic Surgeons Predicted Risk of Mortality or Major Morbidity, STS-PROM Society of Thoracic Surgeons Predicted Risk of Mortality, ACEF age creatinine ejection fraction, 5MWT 5-Meter Walk Test, HGS handgrip strength, MI myocardial infarction, STS Society of Thoracic Surgeons, ICU intensive care unit
Year
First author
Table 2 Previous studies on frailty for cardiac surgery
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formally applied to patient selection for DT by VAD [22]. Frailty was a promising tool to evaluate VAD populations because it was an elegant evidence-based synthesis of a patient’s vulnerability to external stressors [23]. Among the 971,434 patients examined, Velanovich and associates showed that a simple 11-point FI correlated with both mortality and morbidity for all surgical specialties including cardiac surgery. Frailty appeared to have more of an impact on mortality in what were generally considered to be lower risk operations and may also affect a patents’ ability to recover from a complication once it had occurred [24]. Nakamura et al. [25] expected the clinical efficacy of early mobilization and cardiac rehabilitation to reduce the incidence of postoperative delirium and confusion and increased the return to the home directly in elderly patients; therefore, these perioperative managements need to be mandatory in order to take care of frail patients and improve clinical outcomes following cardiac surgery.
Frailty and transcatheter aortic valve implantation Consistent with paradigm shifts in the clinical use of prosthetic valves from mechanical to tissue valves in the aortic valve position [26], approximately three out of four patients with isolated AVR received bioprostheses [27]. Under these current clinical setting, transcatheter aortic valve implantation (TAVI) has been rapidly developed in recent few years for surgically high-risk elderly patients with symptomatic and advanced severe AS. Previous studies on frailty with TAVI are shown in Table 3. The further application of the objective measures of frailty to the population undergoing TAVI became necessary in order to determine whether it was predictive in this population [28]. Rodes-Cabau et al. [29] reported that frailty assessments of TAVI candidates had mainly been based on the traditional ‘‘eyeball’’ test, which was limited by its empirical nature; however, they indicated that a simple and objective evaluation of the frailty status may provide important prognostic information for TAVI candidates. A 2-year follow-up of patients in the PARTNER (Placement of aortic transcatheter valves) trial supported TAVI as an alternative to surgery in high-risk patients who could not undergo surgery [30]. Among the advantages of these catheter-based interventions for high-risk AS elderly patients, the concept of frailty has been gaining considerable interest as a predictive preoperative tool as well as standard preoperative surgical risk analysis scores. Since Stortecky and colleagues reported the role of frailty in patients who underwent TAVI, multidimensional geriatric assessment (MGA)-based risk scores predicted all-cause mortality and major adverse cardiovascular and
cerebral events in elderly patients undergoing TAVI [31]. In the PARTNER Trial, frailty scores based on grip strength, gait speed, activity of daily living, and serum albumin provided independent prognostic information about procedural outcomes [32]. Following evaluation of the relationship between 6MWT and clinical outcomes after TAVI among participants in the PARTNER trial, no significant differences were observed in 30-day outcomes among the 6MWT groups; however, the rate of death from any cause at 2 years was 42.5 % in those unable to walk, 31.2 % in slow walkers, and 28.8 % in fast walkers (p = 0.02) [33]. Another prospective cohort design study by Schoenenberger AW and colleagues showed that FI strongly predicted functional decline in univariate and bivariate analyses. FI more strongly predicted functional decline in univariate (OR: 1.57, p = 0.001) and bivariate analyses (OR: 1.56 p = 0.001 for EuroSCORE, OR: 1.53, p = 0.002 for STS score) than already established risk scores such as STS scores and EuroSCORE [34]. Kamga M and co-workers evaluated the role of frailty in 30 octogenarians after TAVI using ISAR (Identification of Senior At Risk) and the SHERPA (Score Hospitalier d’Evaluation du Risqu de Perte d’Autonomie) Score [35]. Puls et al. recently published the clinical impact of frailty, as measured by the Katz index of ADL, on short- and long-term mortality after TAVI. Early mortality was significantly higher in frail patients, and a Katz index of less than 6 was identified as a significant independent predictor of longterm all-cause mortality by a multivariate analysis [36]. Among inoperable patients with severe AS, TAVI resulted in significant improvements in health-related QOL that were maintained for at least 1 year, as reported by Reynolds et al. In this trial, QOL, which was assessed prospectively with the Kansas City Cardiomyopathy Questionnaire and Sort Form-12 General health Survey, improved after TAVI during the first year after the intervention; thus, QOL was markedly better in the TAVI group than in the control group in this clinical trial population [37].
Frailty and non-cardiac thoracic surgery The clinical concept of frailty has also recently been developed in a thoracic surgical setting such as lobectomy and esophagectomy, which is summarized in Table 4. Among 1940 open lobectomies, the modified FI identified patients at higher risk for morbidity and mortality postlobectomy. Therefore, preoperative selection may be important for minimizing morbidity and mortality and improving risk stratification for informed decision making in
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123
2012
2012
2013
2013
2013
2014
Green [32]
Stortecky [31]
Kamga [35]
Schoenenberger [34]
Green [33]
Puls [36]
144
484
106
30
100
159
No.of patients
Longer post-TAVI hospital stay frail: 9 days not frail: 6 days
Grip strength ADL status
Higher BNP level Anemia
Among 300 consecutive TAVI, 156 were not frail
Fast walkers: 133
Slow walkers: 133
Unable to walk: 218
N/A
Unable to walk, higher rate of previous BAV, oxygen dependent COPD, and lower male prevalence
Impairment in at least one ADL Katz index \6
6MWT
Frailty index (cognition, mobility, nutrition, instrumental and BADL)
Logistic Euro SCORE: 25.3 % STS score: 6.4 %, frailty index: 2.6
BADL
Mean age: 83.4 years
[70 years with severe AS (among 119 TAVI excluded 13 who died during the 6-month follow-up period)
ISAR SHERPA
16 males mean age: 86 years EuroSCORE 34 %
Frailty index
Pre-clinical mobility disability
IADL
BADL
MNA TUG
MMSE
Procedural mortality: 23 vs 6.4 % (p \ 0.0001)
30-day mortality: 17 vs 5.8 % (p = 0.002)
Immediate procedural mortality: 5.5 vs 1.3 % (p = 0.04)
The rate of death at 2 years from any cause was 42.5 % in those unable to walk, 31.2 % in slow walkers, and 28.8 % in fast walkers (p = 0.02)
The frailty index strongly predicted functional decline in univariate (OR: 1.57, p = 0.001) and bivariate analyses (OR: 1.56 p = 0.001 for Euro SCORE, OR: 1.53, p = 0.002 for STS score)
Survival at 1-year: 73 % SHERPA score: significantly higher in non-survivors than among survivors (7.8 vs 4.9, p = 0.001)
MGA-based risk scores including the Frailty index correlated with 30-day and 1-year mortality and MACCE
Associations between the Frailty index with 1-year mortality were similar with the STS score and EuroSCORE
1-year mortality frail: 22.4 % not frail: 8.4 % (p = 0.01)
Gait speed
Serum albumin level
30-day mortality frail: 5.3 % not frail: 4.8 % (NS)
Frailty score
Hyperlipidemia Previous PCI
N/A
Clinical outcomes and association
Frailty evaluation
Baseline characteristics of frail patients
Octogenarian
[70 years with severe symptomatic AS
Frail: 76, not frail: 83
Frailty population
AS aortic valve stenosis, TAVI transcatheter aortic valve implantation, PCI percutaneous coronary intervention, BNP brain natriuretic peptide, N/A not applicable, STS Society of Thoracic Surgeons, BAV balloon aortic valvuloplasty, COPD chronic obstructive pulmonary disease, ADL activities of daily living, MMSE mini-mental state examination, MNA mini-nutritional assessment, TUG Time Get Up and Go test, BADL basic activities of daily living, IADL instrumental activities of daily living, ISAR identification of seniors at risk, SHERPA Score Hospitalier d’Evaluation du Risque de Perte d’Autonomie, 6MWT 6-Minute Walk Test, MACCE major adverse cardiovascular and cerebral events
Year
First author
Table 3 Previous studies on frailty for transcatheter aortic valve implantation
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Gen Thorac Cardiovasc Surg Table 4 Previous studies on frailty for non-cardiac thoracic surgery First author
Year
No. of patients
Surgery
Frailty population
Frailty evaluation
Clinical outcomes and associations
Fukuse [40]
2005
120
Lung surgery
C 60 years of age PS [2: 8.2 %, ADL scale dependent: 10.3 %, MMSE dependent 8.6 %
CGA: PS by ECOG Barthel index of ADLs Folstein MMSE
Patients with dependence for performing ADLs and dementia were more likely to develop postoperative complications Dependence for the performance of ADLs and impaired cognitive conditions were important predictors of postoperative complications Dependent patients were more likely to have prolonged ventilation, reintubation, postoperative pneumonia, mortality. The preoperative functional status was independent predictors of both morbidity and mortality as well as severe wound infection and emergency procedures
Tsiouris [39]
2012
812
Lung surgery
Of 6373 patients, 812 had a preoperative dependent functional status
Independent, partially dependent, totally dependent
Tsiouris [38]
2013
1940
Open lobectomy
Dependent of modified frailty index
Modified frailty index based on the CSHA-FI (11 variables)
The modified FI may identify patients at higher risk for morbidity and mortality post-lobectomy
Hodari [45]
2013
2095
Esophagectomy
Dependent of modified frailty index
Modified frailty index based on the CSHA-FI
A higher frailty score was associated with morbidity and mortality rates. Only age and frailty were significant in a multivariate logistic regression analysis for mortality (odds ratio: 31.84 for frailty)
PS performance status, ECOG Eastern Cooperative Oncology Group, ADL activities of daily living, MMSE mini-mental state examination, CGA comprehensive geriatric assessment, CSHA-FI Canadian Study of Health and Aging-Frailty Index
rapidly aging populations [38]. Of the 6373 patients examined, 812 preoperative lower functional status and dependent patients had significantly higher rates of infection, other adverse events, and mortality [39]. Among 120 patients older than 60 years of age who underwent thoracic lung surgery, the patients with the dependence were more likely to develop postoperative complications and important predictors of postoperative complications, especially when the operation time was long [40]. 6MWT is a novel and useful tool for evaluating frailty, and Nakagawa et al. reported the clinical relevance of 6MWT and decreased oxygen saturation as preoperative physiological assessments in lung cancer surgery patients. Thus, these tools, which are useful for frailty assessment, need to be employed more in a clinical setting [41]. Ferguson MK and co-workers recently reported the controversial issues about frailty, which has been strongly associated with adverse outcomes, characteristics, diagnosis, and impact on surgical outcomes in thoracic surgical patients [42]. Among the 71 studies, the role of frailty scores in predicting the outcomes of patients undergoing thoracic surgery has been recently reviewed that the higher rates of postoperative complications and mortality were prevalent with increases in frailty. As frailty became more severe, the rates of major postoperative complications and mortality in patients with higher preoperative dependency also increased [43].
A multidisciplinary approach including surgery, radiotherapy, chemotherapy, and the perioperative management of esophageal cancer has been developed to improve prognoses [44]. In a retrospective study, the use of a modified FI was examined as a potential predictor of morbidity and mortality in esophagectomy patients. Higher frailty scores were associated with a significant increase in morbidity and mortality among 2095 patients. Using a large national database, the odds ratio was 31.84 for frailty and 1.05 for age; therefore a modified FI correlated with post-esophagectomy morbidity and mortality. These indices may assist in improving risk assessments and patient selection for esophagectomy [45].
Conclusion These comprehensive reviews on frailty in cardiothoracic surgery revealed that preoperative surgical risk assessment using frailty scores or indices may be useful tools and have the potential to consider surgical intervention for elderly patients. The further consideration of future perspectives of preoperative assessment by frailty alone or in combination with other tools is warranted. Conflict of interest
There is no conflict of interest to declare.
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17. Bagnall NM, Faiz O, Darzi A, Athanasiou T. What is the utility of preoperative frailty assessment for risk stratification in cardiac surgery. Interact CardioVasc Thorac Surg. 2013;17:398–402. 18. Chikwe J, Adams DH. Frailty: the missing element in predicting operative mortality. Semin Thoracic Surg. 2010;22:109–10. 19. Yamakawa M, Kyo S, Yamakawa S, Ono M, Kinugawa K, Nishimura T. Destination therapy: the new gold standard treatment for heart failure patients with left ventricular assist devices. Gen Thorac Cradiovasc Surg. 2013;61:111–7. 20. Dunlay SM, Park SJ, Joyce LD, Daly RC, Stulak JM, McNallan SM, et al. Frailty and outcomes after implantation of left ventricular assist device as destination therapy. J Heart Lung Transplant. 2014;33:359–65. 21. Chung CJ, Wu C, Jones M, Kato TS, Dam TT, Givens R, et al. Reduced handgrip strength as a marker of frailty predicts clinical outcomes in patients with heart failure undergoing ventricular assist device placement. J Cardiac Fail. 2014;20:310–5. 22. Flint KM, Matlock DD, Lindenfeld J, Allen LA. Frailty and the selection of patients for destination therapy left ventricular assist device. Cir Heart Fail. 2012;5:286–93. 23. Flint KM, Allen LA. Getting a grip on frailty: handgrip strength in patient selection for left ventricular assist device. J Cardiac Fail. 2014;20:316–8. 24. Velanovich V, Antoine H, Swartz A, Peters D, Rubinfeld I. Accumulating deficits model of frailty and postoperative mortality and morbidity: its application to a national database. J Surg Res. 2013;183:104–10. 25. Nakamura K, Nakamura E, Niina K, Kojima K. Outcome after valve surgery in octogenarians and efficacy of early mobilization with early cardiac rehabilitation. Gen Thorac Cardiovasc Surg. 2010;58:606–11. 26. Furukawa H, Tanemoto K. Current status and future perspectives of prosthetic valve selection for aortic valve replacement. Gen Thorac Cardiovasc Surg. 2014;62:19–23. 27. Masuda M, Kuwano H, Okumura M, Amano J, Arai H, Endo S, et al. Thoracic and cardiovascular surgery in Japan during 2012. Gen Thorac Cardiovasc Surg. 2014;62:734–64. 28. Mack M. Frailty and aortic valve disease. J Thorac Cardiovasc Surg. 2013;145:S7–10. 29. Rodes-Cabau J, Mok M. Working toward a frailty index in transcatheter aortic valve replacement. J Am Coll Cardiol Intv. 2012;5:982–3. 30. Kodali SK, Williams MR, Smith CR, Svensson LG, Webb JG, Makkar RR, et al. Two-year outcomes after transcatheter or surgical aortic-valve replacement. N Engl J Med. 2012;366:1686–95. 31. Stortecky S, Schoenenberger AW, Moser A, Kalesan B, Ju¨ni P, Carrel T, et al. Evaluation of multidimensional geriatric assessment as a predictor of mortality and cardiovascular events after transcatheter aortic valve implantation. J Am Coll Cardio Intv. 2012;5:489–96. 32. Green P, Woglom AE, Genereux P, Daneault B, Paradis JM, Schnell S, et al. The impact of frailty status on survival after transcatheter aortic valve replacement in older adults with severe aortic stenosis. J Am Coll Cardiol Intv. 2012;5:974–81. 33. Green P, Cohen DJ, Genereux P, McAndrew T, Arnold SV, Alu M, et al. Relation between six-minute walk test performance and outcomes after transcatheter aortic valve implantation (from the PARTNER trial). Am J Cardiol. 2013;112:700–6. 34. Schoenenberger AW, Stortecky S, Neumann S, Moser A, Ju¨ni P, Carrel T, et al. Predictors of functional decline in elderly patients undergoing transcatheter aortic valve implantation (TAVI). Eur Heart J. 2013;34:684–92. 35. Kamga M, Boland B, Cornette P, Beeckmans M, De Meester C, Chenu P, et al. Impact of frailty scores on outcome of octogenarian patients undergoing transcatheter aortic valve implantation. Acta Cardiol. 2013;68:599–606.
Gen Thorac Cardiovasc Surg 36. Puls M, Sobisiak B, Bleckmann A, Jacobshagen C, Danner BC, Hu¨nlich M, et al. Impact of frailty on short- and long-term morbidity and mortality after transcatheter aortic valve implantation: risk assessment by Katz index of activities of daily living. Eurointervention. 2014;10:609–19. 37. Reynolds MR, Magnuson EA, Lei Y, Leon MB, Smith CR, Svensson LG, et al. Health-related quality of life after transcatheter aortic valve replacement in inoperable patients with severe aortic stenosis. Circulation. 2011;124:1964–72. 38. Tsiouris A, Hammond ZT, Velanovick V, Hodari A, Borgi J, Rubinfeld I. A modified frailty index to assess morbidity and mortality after lobectomy. J Surg Res. 2013;183:40–6. 39. Tsiouris A, Horst HM, Paone G, Hodari A, Eichenhorn M, Rubinfeld I. Preoperative risk stratification for thoracic surgery using the American College of Surgeons National Surgical Quality Improvement Program data set: functional status predicts morbidity and mortality. J Sur Res. 2012;177:1–6. 40. Fukuse T, Satoda N, Hijiya K, Fujinaga T. Importance of a comprehensive geriatric assessment in prediction of complications following thoracic surgery in elderly patients. Chest. 2005;127:886–91. 41. Nakagawa T, Chiba N, Saito M, Sakaguchi Y, Ishikawa S. Clinical relevance of decreased oxygen saturation during 6-min
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47.
walk test in preoperative physiological assessment for lung cancer surgery. Gen Thorac Cardiovasc Surg. 2014;62:620–6. Ferguson MK, Farnan J, Hemmerich JA, Slawinski K, Acevedo J, Small S. The impact of perceived frailty on surgeons’ estimates of surgical risk. Ann Thorac Surg. 2014;98:210–6. Dunne MJ, Abah U, Sacrci M. Frailty assessment in thoracic surgery. Interact CardioVasc Thorac Surg. 2014;18:667–70. Yamasaki M, Miyata H, Miyazaki Y, Takahashi T, Kurokawa Y, Nakajima K, et al. Perioperative therapy for esophageal cancer. Gen Thorac Cardiovasc Surg. 2014;62:531–40. Hodari A, Hammoud ZT, Borgi JF, Tsiouris A, Rubinfeld IS. Assessment of morbidity and mortality after esophagectomy using a modified frailty index. Ann Thorac Surg. 2013;96:1240–5. Farhat JS, Velanovich V, Falvo AJ, Horst HM, Swartz A, Patton JH Jr, et al. Are the frail destined to frail? Frailty index as predictor of surgical morbidity and mortality in the elderly. J Trauma Acute Care Surg. 2012;72:1526–30. Dasgupta M, Rolfson DB, Stolee P, Borrie MJ, Speechley M. Frailty is associated with postoperative complications in older adults with medical problems. Arch Gerontol Geriatr. 2009;48:78–83.
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REVIEW ARTICLE
Frailty in cardiothoracic surgery: systematic review of the literature Hiroshi Furukawa1 • Kazuo Tanemoto1
Received: 3 March 2015 / Accepted: 18 April 2015 Ó The Japanese Association for Thoracic Surgery 2015
Abstract A preoperative surgical risk analysis is necessary and important for predicting clinical and surgical outcomes in a clinical setting. Various tools for evaluating the patient characteristics in order to forecast perioperative clinical outcomes have previously been described; however, an objective and precise preoperative risk assessment has not yet been established. In the last decade, the concept of frailty, which is a geriatric assessment that identifies disabilities and weaknesses in patients, has been used in order to predict clinical mortality and morbidity following invasive surgical interventions because the prevalence of elderly patients among those undergoing surgical interventions is increasing. Since there is currently no single generally accepted clinical definition of frailty, many clinical modalities are needed to evaluate the patients’ geriatric activity of daily living. Quantifying the quality of frailty is an evolving challenge for predicting surgical risks preoperatively. In recent years, with the development of transcatheter aortic valve implantation (TAVI), this newly definitive preoperative surgical risk assessment tool, frailty, has become more important and is attracting interest in cardiothoracic surgical settings. Thus, this review summarized current consideration on the preoperative risk analysis by frailty as well as future perspectives and the potential of an ideal frailty risk assessment in cardiothoracic surgery, including the management of elderly patients and high-risk aortic valve stenosis by TAVI.
& Hiroshi Furukawa [email protected] 1
Department of Cardiovascular Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki 701-0192, Japan
Keywords Frailty Elderly patients Thoracic surgery Cardiac surgery Transcatheter aortic valve implantation
Introduction Since populations around the world are rapidly aging, the number of elderly patients who underwent cardiothoracic surgery has markedly increased in the last decade. Perioperative morbidity and mortality are higher in elderly patients in spite of advances in perioperative medical therapy and aggressive surgical management. Therefore, it is becoming increasingly difficult to predict potential risk factors for elderly patients scheduled to undergo cardiothoracic surgery because existing risk assessment tools are incomplete in a clinical setting. The concept of frailty, which is a term widely used to denote the multidimensional syndrome of the loss of reserves such as energy, physical ability, cognition, and vulnerability, has recently been established. Frailty is a geriatric syndrome of increased vulnerability to stressors that has been implicated as a causative and prognostic factor in patients with cardiothoracic diseases, and can be defined as a lack of physiological reserves across multiple organ systems. There is currently no standardized method for measuring physiological reserves in older surgical patients, and this has prompted many investigators to define the universal acceptance of frailty. Since a number of approaches have been used to assess frailty in surgical patients, frailty has been associated with a 3- to 13- fold higher risk of discharge to a facility [1]. The prevalence physical frailty was 9.9 % (15 studies, 44,894 participants) while that of the broad phenotype of frailty was 13.6 % (8 studies, 24,072 participants), and these prevalence increased with age and were higher in women than in men
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[1]. Improvements in the comparability of epidemiological and clinical studies on frailty were regarded as an important step forward by a systematic review of Collard et al. [2]. To assess the potential of frailty as a surgical risk analysis, we herein summarized the concept of frailty in cardiothoracic surgery.
General concept, assessment, and tools of frailty in surgery Frailty is a state of increased vulnerability to the poor resolution of homoeostasis after a stressor event such as surgical invasion. Frailty develops as a consequence of not only preoperative age-related declines in many physiological systems, but also disabilities, which increase the risk of adverse outcomes after surgery. Rockwood K and associates developed the clinical tool of frailty using the Canadian Study of Health and Aging (CSHA) frailty score in 2005 following their consistent studies in a clinical setting, and argued that the clinical frailty scale could predict death or the need for institutional care [3]. Frailty prevalence rates varied from 4.0 to 59.1 % and average prevalence rate was 9.9 % for frailty and 44.2 % for prefrailty when the reported rates were restricted to the studies that used the phenotype model [4]. Physical performance measures, such as gait speed, were also used as a standard tool to evaluate the preoperative frailty and disabilities of patients, as described later, and gait speed was associated with survival in older adults [5]. Table 1 shows the potential tools used to evaluate frailty. Patient activities such as gait speed, as revealed by the 6-minute walk test (6MWT) and 5-meter walk test (5MWT), and the strength of muscle activity, which was shown by the handgrip strength (HGS) test, were useful for evaluating and reflecting the degree of frailty. Serum albumin as well as serum creatinine levels reflect not only the nutrition status of patient, but also frailty. Thus, the concept of frailty as a surgical risk analysis has recently been established in a clinical setting; therefore, physicians and surgeons need to carefully consider it as useful clinical information.
Frailty and cardiac surgery In cardiac surgery, a preoperative surgical risk analysis has been developed using Society of Thoracic Surgeons’ (STS) score and EuroSCORE. However, these risk assessments were not sufficient to evaluate ideal and precise perioperative surgical risks because they sometimes overestimated or underestimated perioperative risks in a clinical setting. At the meeting of the European Association Cardio-Thoracic Surgery in 2011, the conventional
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EuroSCORE or logistic EuroSCORE was updated with new tools corresponding to the category of ‘‘poor activity’’. The accuracy of EuroSCORE II for predicting operative mortality was slightly higher than that of EuroSCORE [6]. Despite the renewal to EuroSCORE II, a significant overestimation of EuroSCORE II was observed in patients with isolated coronary artery bypass grafting (CABG) while a slight underestimation of predictions in high-risk patients was revealed by a meta-analysis of 22 studies involving 145,592 cardiac surgery procedures [7]. In 2014 AHA/ ACC guideline for the management of patients with valvular heart disease, frailty must be taken into consideration as an evaluation of surgical and interventional risk. The precise definition of frailty is still debated; therefore further research to enhance the predictive accuracy is encouraged in this universal guideline [8]. Sepehri and colleagues reviewed the clinical impact of frailty on surgical outcomes after cardiac surgery in 2014 [9], while we reviewed additional studies and summarized our findings in Table 2 including the most recent and novel studies on the clinical role of frailty as a preoperative assessment in patients with a ventricular assist device (VAD). In 2009, de Arenaza DP and co-workers initially presented the potential of frailty as the preoperative risk analysis by 6MWT in AVR patients. The preoperative additive prognostic value of 6MWT in AVR patients may have a pivotal role in predicting clinical outcomes [10]. Lee DH and colleagues subsequently showed that 157 (4.1 %) out of the 3826 patients who underwent cardiac surgery were frail, and these frail patients were older and more likely to be female. Frailty, which was evaluated using the Katz index as the activities of daily living, ambulation, or a documented history of dementia, was an independent predictor of in-hospital mortality, institutional discharge, and reduced midterm survival [11]. Afilalo et al. [12] published two unique and novel studies, and initially showed that gait speed was a simple and effective test that identified a subset of vulnerable elderly patients at an incrementally higher risk of mortality and major morbidity after cardiac surgery. They also demonstrated that a combined approach with frailty, disabilities, and risk scores was more beneficial for elderly patients who were referred for cardiac surgery and identified those at increased risk [13]. In cardiac surgery patients older than 74 years of age, the CAF score (the comprehensive assessment of frailty: grip strength, walking speed, balance, rise up from a chair, pick up a pen, put on and remove a jacket) and FORECAST (Frailty predicts One year after Elective Cardiac Surgery Test: chair rise, weak, stair, clinical frailty scale from the CSHA, creatinine) accurately predicted mortality [14]. The CAF score also predicted not only 30-day mortality, but also midterm outcomes and mortality in highrisk elderly patients [15]. The 5MWT has been
Gen Thorac Cardiovasc Surg Table 1 Major variable indices and scores to evaluate frailty for clinical implications of cardiothoracic surgery Category for evaluating frailty
Tools
Contents
Frailty criteria
First author for representative literature
Frailty index
CSHA
1: Very fit, 2: well, 3: well with treated comorbid disease, 4: apparently vulnerable, 5: mildly frail, 6: moderately frail, 7: severely frail
Dependent of measured data
Rockwood [3], Farhat [46]
CAF score
Grip strength, walking speed, balance, rise up from chair, pick up a pen, put on and remove a jacket Chair rise, weak, stair, clinical frailty scale, creatinine
Dependent of measured data Dependent of measured data
Su¨ndermann [14, 15] Su¨ndermann [15]
MGA
MMSE, MNA, TUG, BADL, IADL, and questions about pre-clinical mobility disability
Dependent of measured data
Stortecky [31]
EFS
Cognitive impairment, dependence in instrumental activities of daily living, recent burden of illness, self-perceived health, depression, weight loss, medication issues, incontinence, inadequate social support, and mobility difficulties
Scores range from 0 (not frail) to 17 (very frail)
Dasgupta [47]
ADL
Katz index
Bathing, dressing, toileting, transferring, continence, feeding
0 (dependent)–6 (independent) Patients with any deficiency in the Katz index were defined as frail.
Lee [11], Green [32], Puls [36]
Disability
HGS
Hand grip test was measured preoperatively at various time points
HGS was normalized for total body weight
Chung [21], Flint [23], Green [32]
Gait speed
6MWT
Walking distance in 6-minutes preoperatively
Dependent of measured data
de Arenaza [10], Green [35], Nakagawa [41]
5MWT
Time taken to walk 5 m at a comfortable pace
Dependent of measured data
Serum albumin
Preoperative serum albumin
Dependent of institutional criteria
Wilson [16], Afilalo [12, 13], Mack [28] Green [32]
Serum creatinine
Preoperative serum creatinine
Dependent of institutional criteria
Su¨ndermann [15]
FORECAST
Laboratory data
CSHA Canadian Study of Health and Aging, CAF: comprehensive geriatric assessment, FORECAST Frailty predicts One year after Elective Cardiac Surgery Test, MGA multidimensional geriatric assessment, EFS Edmonton Frail Scale, HGS handgrip strength, 6MWT 6-Minute Walk Test, 5MWT 5-Meter Walk Test, MMSE mini-mental state examination, MNA mini-nutritional assessment, TUG Time Get Up and Go test, BADL basic activities of daily living, IADL instrumental activities of daily living
recommended for use by the STS as an outcome measure in the Adult Cardiac Surgery Database to predict frailty in individuals who were candidates for cardiac surgery [16]. Bagnall and co-workers reviewed the clinical role of frailty in cardiac surgery and showed that it was an independent predictor of adverse outcomes following cardiac surgery. However, it was unclear whether frailty scoring could be used either separately or combined with conventional risk scores to predict survival and complications [17]. Although age is an extensively documented independent risk factor for mortality, morbidity and decreased quality of life (QOL) after cardiac surgery, excellent outcomes were still obtained after cardiac surgery in very elderly patients with frailty [18]. Since the shortage of donor organs has been consistent with the clinical need for VAD technologies, destination therapy (DT) by VAD has become a new standard strategy
for HF [19]. Among these paradigm shifts in the strategy of VAD, interest in whether preoperative frailty is associated with clinical outcomes after the implantation of VAD as DT is increasing. Among 99 patients with VAD, frailty, as defined using the deficit index including 31 impairments, disabilities and comorbidities before destination VAD implantation, was associated with an increased risk of death and may represent a significant patient selection consideration [20]. Chung et al. [21] had recently showed that reduced HGS was associated with increased patient frailty and higher morbidity and mortality, thereby HGS was evaluated as a marker of frailty for prediction of clinical outcomes after VAD implantation in patients with advanced HF. Flint and co-workers examined two subjects, and initially showed that a preoperative assessment of frailty was highly predictive of adverse outcomes in many medical and surgical populations, but had never been
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2009
2010
2010
2011
2011
2012
2013
2014
2014
de Arenaza [10]
Lee [11]
Afilalo [12]
Su¨ndermann [15]
Su¨ndermann [14]
Afilalo [13]
Wilson [16]
Chung [21]
Dunlay [20]
99
72
113
152
400
213
131
157
208
No. of patients
Patients undergoing VAD implantation
Scheduled cardiac surgery including CABG, valve replacement or valve repair by median sternotomy Advanced heart failure patients who received VAD
[70 years elderly patients undergoing scheduled CABG and/or valve surgery
N/A
N/A
N/A
99: Not frail, 95: moderately frail, 19: severely frail 199: Not frail, 170: moderately frail, 31: severely frail N/A
[74 years cardiac surgery patients, 25 %: isolated CABG, 35 %: isolated valve procedure, 26 %: combined procedure
[74 years cardiac surgery patients
N/A
157 (4.1 %) were frail
N/A
Frailty population
70 years of age or older who were scheduled CABG and/or valve replacement or repair
Of 3826 patients who underwent cardiac surgery
200 AVR patients with either a Medtronic Freestyle stentless or Medtronic Mosaic stented valve
Surgery
Frailty was assessed using the deficit index
The HGS test which was normalized for total body weight
Frailty: 5-meter gait speed, CHS frailty scale, modified CHS frailty scale, MSSA subdimensions, Disability: Nagi items, ADL, IADL, Comorbidity: Parsonnet score, STS-PROMM, STS-PROM, Logistic EuroSCORE, ACEF score 5MWT
CAF score (Grip strength, Walking speed, Balance, Rise up from chair, Pick up a pen, Put on and remove a jacket)
CAF score, FORECAST (Chair rise, Weak, Stair, CFS, Creatinine)
Gait speed: time taken to walk 5 m in [6 s was frailty; sixty patients (46 %) were classified as slow walkers
Katz index, ambulation, or a documented history of dementia
6MWT
Frailty evaluation
Patients with a handgrip strength\25 % of body weight were at an increased risk of mortality, had more postoperative complications, and lower survival after VAD implantation Patients who were intermediately frail (adjusted HR: 1.70) and frail (HR 3.08) were at a higher risk of death than those who were not frail
Significantly slower gait speeds were noted when a subject had an observable gait or postural deviation or used an assistive device
Compared with the Parsonnet score or STS-PROMM alone, the addition of frailty and disability provided incremental value and improved model discrimination
The rates of mortality and stroke were significantly higher in 6MWT distance \300 meters. In high-risk patients with 6MWT distance below 300 m who had Euroscore over 6, the rate of death, MI, and stroke was significantly high Frailty was an independent predictor of in-hospital mortality, institutional discharge, and reduced midterm survival Slow gait speed was significantly correlated with high mortality, prolonged postoperative length of stay, and discharge to a health care facility. Concomitant slow gait speed and high STS risk ([15 %) were remarkably associated with higher rate of mortality or major morbidity The CAF score had a good predictive ability concerning one-year mortality. CAF positively correlated with the length of ventilator assistance as well as EuroSCORE. Patients in the higher frailty group had a longer stay at the ICU The CAF score accurately predicted 30-day mortality
Clinical outcomes and associations
AVR aortic valve replacement, CABG coronary artery bypass grafting, VAD ventricular assist device, N/A not applicable, 6MWT 6-Minute Walk Test, CAF comprehensive assessment of frailty, FORECAST Frailty predicts One year after Elective Cardiac Surgery Test, CFS Clinical Frailty Scale, CHS Cardiovascular Health Study, MSSA MacArthur Study of Successful Aging, ADL activities of daily living, IADL instrumental activities of daily living, STS-PROMM Society of Thoracic Surgeons Predicted Risk of Mortality or Major Morbidity, STS-PROM Society of Thoracic Surgeons Predicted Risk of Mortality, ACEF age creatinine ejection fraction, 5MWT 5-Meter Walk Test, HGS handgrip strength, MI myocardial infarction, STS Society of Thoracic Surgeons, ICU intensive care unit
Year
First author
Table 2 Previous studies on frailty for cardiac surgery
Gen Thorac Cardiovasc Surg
Gen Thorac Cardiovasc Surg
formally applied to patient selection for DT by VAD [22]. Frailty was a promising tool to evaluate VAD populations because it was an elegant evidence-based synthesis of a patient’s vulnerability to external stressors [23]. Among the 971,434 patients examined, Velanovich and associates showed that a simple 11-point FI correlated with both mortality and morbidity for all surgical specialties including cardiac surgery. Frailty appeared to have more of an impact on mortality in what were generally considered to be lower risk operations and may also affect a patents’ ability to recover from a complication once it had occurred [24]. Nakamura et al. [25] expected the clinical efficacy of early mobilization and cardiac rehabilitation to reduce the incidence of postoperative delirium and confusion and increased the return to the home directly in elderly patients; therefore, these perioperative managements need to be mandatory in order to take care of frail patients and improve clinical outcomes following cardiac surgery.
Frailty and transcatheter aortic valve implantation Consistent with paradigm shifts in the clinical use of prosthetic valves from mechanical to tissue valves in the aortic valve position [26], approximately three out of four patients with isolated AVR received bioprostheses [27]. Under these current clinical setting, transcatheter aortic valve implantation (TAVI) has been rapidly developed in recent few years for surgically high-risk elderly patients with symptomatic and advanced severe AS. Previous studies on frailty with TAVI are shown in Table 3. The further application of the objective measures of frailty to the population undergoing TAVI became necessary in order to determine whether it was predictive in this population [28]. Rodes-Cabau et al. [29] reported that frailty assessments of TAVI candidates had mainly been based on the traditional ‘‘eyeball’’ test, which was limited by its empirical nature; however, they indicated that a simple and objective evaluation of the frailty status may provide important prognostic information for TAVI candidates. A 2-year follow-up of patients in the PARTNER (Placement of aortic transcatheter valves) trial supported TAVI as an alternative to surgery in high-risk patients who could not undergo surgery [30]. Among the advantages of these catheter-based interventions for high-risk AS elderly patients, the concept of frailty has been gaining considerable interest as a predictive preoperative tool as well as standard preoperative surgical risk analysis scores. Since Stortecky and colleagues reported the role of frailty in patients who underwent TAVI, multidimensional geriatric assessment (MGA)-based risk scores predicted all-cause mortality and major adverse cardiovascular and
cerebral events in elderly patients undergoing TAVI [31]. In the PARTNER Trial, frailty scores based on grip strength, gait speed, activity of daily living, and serum albumin provided independent prognostic information about procedural outcomes [32]. Following evaluation of the relationship between 6MWT and clinical outcomes after TAVI among participants in the PARTNER trial, no significant differences were observed in 30-day outcomes among the 6MWT groups; however, the rate of death from any cause at 2 years was 42.5 % in those unable to walk, 31.2 % in slow walkers, and 28.8 % in fast walkers (p = 0.02) [33]. Another prospective cohort design study by Schoenenberger AW and colleagues showed that FI strongly predicted functional decline in univariate and bivariate analyses. FI more strongly predicted functional decline in univariate (OR: 1.57, p = 0.001) and bivariate analyses (OR: 1.56 p = 0.001 for EuroSCORE, OR: 1.53, p = 0.002 for STS score) than already established risk scores such as STS scores and EuroSCORE [34]. Kamga M and co-workers evaluated the role of frailty in 30 octogenarians after TAVI using ISAR (Identification of Senior At Risk) and the SHERPA (Score Hospitalier d’Evaluation du Risqu de Perte d’Autonomie) Score [35]. Puls et al. recently published the clinical impact of frailty, as measured by the Katz index of ADL, on short- and long-term mortality after TAVI. Early mortality was significantly higher in frail patients, and a Katz index of less than 6 was identified as a significant independent predictor of longterm all-cause mortality by a multivariate analysis [36]. Among inoperable patients with severe AS, TAVI resulted in significant improvements in health-related QOL that were maintained for at least 1 year, as reported by Reynolds et al. In this trial, QOL, which was assessed prospectively with the Kansas City Cardiomyopathy Questionnaire and Sort Form-12 General health Survey, improved after TAVI during the first year after the intervention; thus, QOL was markedly better in the TAVI group than in the control group in this clinical trial population [37].
Frailty and non-cardiac thoracic surgery The clinical concept of frailty has also recently been developed in a thoracic surgical setting such as lobectomy and esophagectomy, which is summarized in Table 4. Among 1940 open lobectomies, the modified FI identified patients at higher risk for morbidity and mortality postlobectomy. Therefore, preoperative selection may be important for minimizing morbidity and mortality and improving risk stratification for informed decision making in
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123
2012
2012
2013
2013
2013
2014
Green [32]
Stortecky [31]
Kamga [35]
Schoenenberger [34]
Green [33]
Puls [36]
144
484
106
30
100
159
No.of patients
Longer post-TAVI hospital stay frail: 9 days not frail: 6 days
Grip strength ADL status
Higher BNP level Anemia
Among 300 consecutive TAVI, 156 were not frail
Fast walkers: 133
Slow walkers: 133
Unable to walk: 218
N/A
Unable to walk, higher rate of previous BAV, oxygen dependent COPD, and lower male prevalence
Impairment in at least one ADL Katz index \6
6MWT
Frailty index (cognition, mobility, nutrition, instrumental and BADL)
Logistic Euro SCORE: 25.3 % STS score: 6.4 %, frailty index: 2.6
BADL
Mean age: 83.4 years
[70 years with severe AS (among 119 TAVI excluded 13 who died during the 6-month follow-up period)
ISAR SHERPA
16 males mean age: 86 years EuroSCORE 34 %
Frailty index
Pre-clinical mobility disability
IADL
BADL
MNA TUG
MMSE
Procedural mortality: 23 vs 6.4 % (p \ 0.0001)
30-day mortality: 17 vs 5.8 % (p = 0.002)
Immediate procedural mortality: 5.5 vs 1.3 % (p = 0.04)
The rate of death at 2 years from any cause was 42.5 % in those unable to walk, 31.2 % in slow walkers, and 28.8 % in fast walkers (p = 0.02)
The frailty index strongly predicted functional decline in univariate (OR: 1.57, p = 0.001) and bivariate analyses (OR: 1.56 p = 0.001 for Euro SCORE, OR: 1.53, p = 0.002 for STS score)
Survival at 1-year: 73 % SHERPA score: significantly higher in non-survivors than among survivors (7.8 vs 4.9, p = 0.001)
MGA-based risk scores including the Frailty index correlated with 30-day and 1-year mortality and MACCE
Associations between the Frailty index with 1-year mortality were similar with the STS score and EuroSCORE
1-year mortality frail: 22.4 % not frail: 8.4 % (p = 0.01)
Gait speed
Serum albumin level
30-day mortality frail: 5.3 % not frail: 4.8 % (NS)
Frailty score
Hyperlipidemia Previous PCI
N/A
Clinical outcomes and association
Frailty evaluation
Baseline characteristics of frail patients
Octogenarian
[70 years with severe symptomatic AS
Frail: 76, not frail: 83
Frailty population
AS aortic valve stenosis, TAVI transcatheter aortic valve implantation, PCI percutaneous coronary intervention, BNP brain natriuretic peptide, N/A not applicable, STS Society of Thoracic Surgeons, BAV balloon aortic valvuloplasty, COPD chronic obstructive pulmonary disease, ADL activities of daily living, MMSE mini-mental state examination, MNA mini-nutritional assessment, TUG Time Get Up and Go test, BADL basic activities of daily living, IADL instrumental activities of daily living, ISAR identification of seniors at risk, SHERPA Score Hospitalier d’Evaluation du Risque de Perte d’Autonomie, 6MWT 6-Minute Walk Test, MACCE major adverse cardiovascular and cerebral events
Year
First author
Table 3 Previous studies on frailty for transcatheter aortic valve implantation
Gen Thorac Cardiovasc Surg
Gen Thorac Cardiovasc Surg Table 4 Previous studies on frailty for non-cardiac thoracic surgery First author
Year
No. of patients
Surgery
Frailty population
Frailty evaluation
Clinical outcomes and associations
Fukuse [40]
2005
120
Lung surgery
C 60 years of age PS [2: 8.2 %, ADL scale dependent: 10.3 %, MMSE dependent 8.6 %
CGA: PS by ECOG Barthel index of ADLs Folstein MMSE
Patients with dependence for performing ADLs and dementia were more likely to develop postoperative complications Dependence for the performance of ADLs and impaired cognitive conditions were important predictors of postoperative complications Dependent patients were more likely to have prolonged ventilation, reintubation, postoperative pneumonia, mortality. The preoperative functional status was independent predictors of both morbidity and mortality as well as severe wound infection and emergency procedures
Tsiouris [39]
2012
812
Lung surgery
Of 6373 patients, 812 had a preoperative dependent functional status
Independent, partially dependent, totally dependent
Tsiouris [38]
2013
1940
Open lobectomy
Dependent of modified frailty index
Modified frailty index based on the CSHA-FI (11 variables)
The modified FI may identify patients at higher risk for morbidity and mortality post-lobectomy
Hodari [45]
2013
2095
Esophagectomy
Dependent of modified frailty index
Modified frailty index based on the CSHA-FI
A higher frailty score was associated with morbidity and mortality rates. Only age and frailty were significant in a multivariate logistic regression analysis for mortality (odds ratio: 31.84 for frailty)
PS performance status, ECOG Eastern Cooperative Oncology Group, ADL activities of daily living, MMSE mini-mental state examination, CGA comprehensive geriatric assessment, CSHA-FI Canadian Study of Health and Aging-Frailty Index
rapidly aging populations [38]. Of the 6373 patients examined, 812 preoperative lower functional status and dependent patients had significantly higher rates of infection, other adverse events, and mortality [39]. Among 120 patients older than 60 years of age who underwent thoracic lung surgery, the patients with the dependence were more likely to develop postoperative complications and important predictors of postoperative complications, especially when the operation time was long [40]. 6MWT is a novel and useful tool for evaluating frailty, and Nakagawa et al. reported the clinical relevance of 6MWT and decreased oxygen saturation as preoperative physiological assessments in lung cancer surgery patients. Thus, these tools, which are useful for frailty assessment, need to be employed more in a clinical setting [41]. Ferguson MK and co-workers recently reported the controversial issues about frailty, which has been strongly associated with adverse outcomes, characteristics, diagnosis, and impact on surgical outcomes in thoracic surgical patients [42]. Among the 71 studies, the role of frailty scores in predicting the outcomes of patients undergoing thoracic surgery has been recently reviewed that the higher rates of postoperative complications and mortality were prevalent with increases in frailty. As frailty became more severe, the rates of major postoperative complications and mortality in patients with higher preoperative dependency also increased [43].
A multidisciplinary approach including surgery, radiotherapy, chemotherapy, and the perioperative management of esophageal cancer has been developed to improve prognoses [44]. In a retrospective study, the use of a modified FI was examined as a potential predictor of morbidity and mortality in esophagectomy patients. Higher frailty scores were associated with a significant increase in morbidity and mortality among 2095 patients. Using a large national database, the odds ratio was 31.84 for frailty and 1.05 for age; therefore a modified FI correlated with post-esophagectomy morbidity and mortality. These indices may assist in improving risk assessments and patient selection for esophagectomy [45].
Conclusion These comprehensive reviews on frailty in cardiothoracic surgery revealed that preoperative surgical risk assessment using frailty scores or indices may be useful tools and have the potential to consider surgical intervention for elderly patients. The further consideration of future perspectives of preoperative assessment by frailty alone or in combination with other tools is warranted. Conflict of interest
There is no conflict of interest to declare.
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