Preoperative Frailty Assessment and Outcomes at 6 Months or Later in Older Adults Undergoing Cardiac Surgical Procedures

Approximately 500000 cardiac surgical procedures are performed each year in the United States, more than 50% of them in older adults (1). Because of the high burden of cardiovascular disease and evolution of minimally invasive surgical techniques, this number is expected to rise (24). Although older patients may benefit from these procedures, some die or have complications (510), functional decline (11, 12), and poor quality of life (1315). Identifying patients who are most or least likely to benefit from surgical procedures remains a significant challenge. One of the factors underlying the heterogeneity of health outcomes in older patients is frailty, which reflects an individual's reduced physiologic reserve, inability to tolerate stressful events (such as surgery), and vulnerability to adverse outcomes (16). Experts have developed several instruments to measure frailty by assessing gait speed, grip strength, or deficit accumulation (1723), but there is no consensus on how to best measure this vulnerability (24, 25). Despite the lack of agreement, accumulating evidence suggests that assessment by using any validated measures provides additional information about surgical risk and prognosis not captured by traditional risk assessment (510). However, most surgical risk scores do not include measures of frailty (2629). To incorporate frailty screening in the risk assessment before cardiac surgical procedures, it is essential to evaluate the feasibility and validity of frailty instruments in this setting. If preoperative frailty status predicts mortality, functional status, and quality of life, such information would be useful in making informed decisions about the procedures. This review evaluates the evidence regarding the feasibility of frailty instruments and their validity in predicting mortality or functional status in older patients who are having major or minimally invasive cardiac surgical procedures. Because several previous reviews (3035) reported short-term mortality and complications, we reviewed up-to-date literature on clinical outcomes at 6 months or later after cardiac procedures. Methods We developed but did not register a protocol for the review (Supplement 1) and prepared this report according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines (36). Supplement. Protocol and Data Data Sources and Searches We searched MEDLINE and EMBASE, without language restriction, for original research articles that evaluated any frailty measures in adults undergoing cardiac surgery, from the databases' inception to 2 May 2016, using the following keywords and their variations: aged and cardiac surgery and frailty, geriatric assessment, mobility, gait speed, muscle strength, grip strength, physical activity, exhaustion, weight loss, nutrition, cognitive function, functional status, activities of daily living (Supplement 1). We also examined reference lists of reviews (3035) and articles meeting inclusion criteria. Study Selection Two investigators (C.A.K. and S.P.) independently screened titles and abstracts and then texts of full-length articles passing the title and abstract screen. Disagreement was resolved by consensus involving a third investigator (D.H.K.). Original research articles published in any language were eligible if the mean age of study participants was 60 years or older; the surgical procedure was coronary artery bypass grafting (CABG), open valve surgery, or transcatheter aortic valve replacement (TAVR); the research was a cohort study with 6 months or more of follow-up; and mortality or functional status was reported according to preoperative frailty status. We considered any measure of physical function (mobility, muscle strength, physical activity, exhaustion, nutrition, balance, or disability) or any combination of measures as an acceptable screening method for frailty. We did not consider comorbidity or cognitive function alone as a measure of frailty if it was not combined with measures of physical function. Although the 6-minute walk test (6MWT) is a measure of endurance, we classified it under mobility because it is highly correlated with mobility (37, 38). Articles were excluded if the research used a design other than a cohort study, sample size was less than 100, or frailty measures were not assessed before surgery. If 2 or more articles originated from the same population, the study with the larger sample size or longer follow-up was included. Data Extraction Two investigators (C.A.K. and D.H.K.) independently extracted data on patient characteristics, type of procedure (major vs. minimally invasive), frailty assessment domains (Table 1 of Supplement 2), and outcomes (Supplement 1). Any disagreement was resolved by consensus. We classified CABG and open valve surgery as major procedures and TAVR as minimally invasive surgery. To determine the feasibility of a frailty assessment, we extracted the administration time for frailty measures or, if not reported, approximated it based on the literature or our own experience (Supplement 1). The prevalence of frailty was estimated according to the study-specific definition. Our main outcome of interest was death or poor functional status at 6 months or later after surgery. We considered the following measures of functional status: activities of daily living (ADLs), instrumental ADLs, the Duke Activity Status Index (39), the Kansas City Cardiomyopathy Questionnaire (40), and New York Heart Association class. Our secondary outcome was major adverse cardiovascular and cerebrovascular events (MACCEs). We extracted the absolute risk and relative risk (RR) for each outcome and 95% CI according to frailty status, with or without adjustment for traditional surgical risk scores. If RR was not reported, we calculated it from the count data. Metrics to evaluate diagnostic tests or prediction models (such as sensitivity, specificity, calibration, and discrimination) were obtained, if reported. Data extracted from individual studies are provided in Table 2 of Supplement 2. Quality Assessment Two investigators (C.A.K and D.H.K.) independently evaluated each study for the following: representativeness of the study population, use of frailty measures that were validated in the general population of older adults, frailty status determination, loss to follow-up or amount of missing outcome data (death and functional status, separately), missing data on frailty measures, and validation of the risk prediction performance (Supplement 1). Any disagreement was resolved by consensus. We determined the overall quality of evidence for each frailty instrumentoutcome pair as high, moderate, low, or very low on the basis of the representativeness of study populations, risk of bias, consistency in the results across studies, and strength of associations (Supplement 1). Data Synthesis We qualitatively summarized the evidence by type of cardiac procedure (major vs. minimally invasive) and type of frailty instrument (single component vs. multicomponent). One study included both major and minimally invasive procedures without data stratified by procedure type (41). Because only 15% of patients had minimally invasive procedures in this study, the cardiac surgeries were categorized as major procedures. Substantial variation in frailty assessment and patient characteristics across the studies prevented the pooling of individual study estimates into a summary result. Role of the Funding Source This research was supported by the National Institute on Aging; National Heart, Lung, and Blood Institute; American Federation for Aging Research; John A. Hartford Foundation; and Atlantic Philanthropies. The funding sources had no role in the design, collection, analysis, or interpretation of the data; or in the decision to submit the manuscript for publication. Results We identified 25 studies that evaluated the association between frailty and death or functional status at 6 months or later in 18388 patients undergoing major cardiac surgical procedures (9 frailty instruments in 8 studies of CABG or open valve surgery) (4149) and 5177 patients undergoing minimally invasive cardiac surgery (13 instruments in 17 studies of TAVR) (1115, 5061) (Figure 1 of Supplement 2). Frailty Assessment in Major Cardiac Surgical Procedures Eight studies evaluated 4 single-component and 5 multicomponent frailty instruments in patients undergoing major cardiac surgical procedures (Figure and Table 1). Studies varied widely in terms of sample size (166 to 11815 patients), mean age (62 to 79 years), follow-up (7 to 65 months), and prevalence of frailty (4% to 70%). Mobility (5 studies), disability (4 studies), and nutrition (3 studies) were commonly assessed (Figure). Figure. Frailty assessment in cardiac procedures. Open circles indicate information obtained from self-report or medical records; solid circles indicate information obtained from performance tests. Prevalence of frailty was determined according to the study-specific definition. AVR = aortic valve replacement; CABG = coronary artery bypass grafting; FU = follow-up; NR = not reported; STS = Society of Thoracic Surgeons predicted risk for mortality; TAVR = transcatheter aortic valve replacement. Table 1. Frailty Assessment and Outcomes at 6 Months After Major Cardiac Procedures in Older Adults Single-Component Frailty Instruments Except for the 6MWT, single-component instruments could be administered within 5 minutes (Table 1). Distance on 6MWT (43), low albumin levels (44), and ADL dependence (45) were statistically significantly associated with a 2.4- to 3.6-fold risk for death or MACCEs. The study by Robinson and colleagues (42) was underpowered to detect a clinically significant mortality difference by performance on the Timed Up and Go (TUG) test. No studies examined functional status. Only the 6MWT (43) and ADL dependence (45) were evaluated in highly representative samples of routine clinic patient