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.
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 . 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 . 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. . 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 . Frailty prevalence rates varied from 4.0 to 59.1 % and average prevalence rate was 9.9 % for frailty and 44.2 % for pre-frailty when the reported rates were restricted to the studies that used the phenotype model . 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 . 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 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 . 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 . 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 . Sepehri and colleagues reviewed the clinical impact of frailty on surgical outcomes after cardiac surgery in 2014 , 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 . 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 . Afilalo et al.  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 . 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 . The CAF score also predicted not only 30-day mortality, but also midterm outcomes and mortality in high-risk elderly patients . The 5MWT has been 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 .
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 . 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 .
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 . 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 . Chung et al.  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 formally applied to patient selection for DT by VAD . 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 .
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 . Nakamura et al.  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 , approximately three out of four patients with isolated AVR received bioprostheses . 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 . Rodes-Cabau et al.  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 . 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 . 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 . 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) .
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 . 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 . 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 long-term all-cause mortality by a multivariate analysis . 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 .
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 post-lobectomy. Therefore, preoperative selection may be important for minimizing morbidity and mortality and improving risk stratification for informed decision making in rapidly aging populations . Of the 6373 patients examined, 812 preoperative lower functional status and dependent patients had significantly higher rates of infection, other adverse events, and mortality . 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 . 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 . 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 . 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 .
A multidisciplinary approach including surgery, radiotherapy, chemotherapy, and the perioperative management of esophageal cancer has been developed to improve prognoses . 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 .
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.
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Furukawa, H., Tanemoto, K. Frailty in cardiothoracic surgery: systematic review of the literature. Gen Thorac Cardiovasc Surg 63, 425–433 (2015). https://doi.org/10.1007/s11748-015-0553-8
- Elderly patients
- Thoracic surgery
- Cardiac surgery
- Transcatheter aortic valve implantation