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Pre-operative physical performance as a predictor of in-hospital outcomes in older patients undergoing elective cardiac surgery

  • Author Footnotes
    1 Equally contributed to conceptualizing, planning and conducting the present study.
    Samuele Baldasseroni
    Footnotes
    1 Equally contributed to conceptualizing, planning and conducting the present study.
    Affiliations
    Division of Geriatrics, Department of Medicine and Geriatrics, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
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  • Author Footnotes
    1 Equally contributed to conceptualizing, planning and conducting the present study.
    Alessandra Pratesi
    Footnotes
    1 Equally contributed to conceptualizing, planning and conducting the present study.
    Affiliations
    Research Unit of Medicine of Aging, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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  • Pierluigi Stefàno
    Affiliations
    Division of Cardiac Surgery, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
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  • Stefano Del Pace
    Affiliations
    Division of General Cardiology, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
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  • Valter Campagnolo
    Affiliations
    Division of Cardiac Anesthesiology, Department of Anesthesia, Careggi University Hospital, Florence, Italy
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  • Anna Chiara Baroncini
    Affiliations
    Research Unit of Medicine of Aging, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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  • Aldo Lo Forte
    Affiliations
    Research Unit of Medicine of Aging, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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  • Andrea Giosafat Marella
    Affiliations
    Division of Geriatrics, Department of Medicine and Geriatrics, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy
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  • Andrea Ungar
    Affiliations
    Division of Geriatrics, Department of Medicine and Geriatrics, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

    Research Unit of Medicine of Aging, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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  • Mauro Di Bari
    Correspondence
    Corresponding author at: Viale G. Pieraccini 6, 50139, Florence, Italy.
    Affiliations
    Division of Geriatrics, Department of Medicine and Geriatrics, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy

    Research Unit of Medicine of Aging, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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  • Niccolò Marchionni
    Affiliations
    Research Unit of Medicine of Aging, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Division of General Cardiology, Cardiothoracovascular Department, Careggi University Hospital, Florence, Italy
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  • on behalf of theItalian Society of Geriatric Cardiology (SICGe)
  • Author Footnotes
    1 Equally contributed to conceptualizing, planning and conducting the present study.
Open AccessPublished:October 31, 2020DOI:https://doi.org/10.1016/j.ejim.2020.10.021

      Highlights

      • Risk stratification of older patients before elective cardiac surgery needs improvement.
      • Short physical performance battery (SPPB) improves prediction of hospital outcomes.
      • SPPB should be used systematically to refine prognostic assessment.

      Abstract

      Objective

      Risk stratification of cardiac surgery patients is usually based on the Society of Thoracic Surgeons (STS) score, that has limited predictive value in older persons. We aimed assessing whether the Short Physical Performance Battery (SPPB) improves, beyond the STS score, assessment of hospital prognosis in older patients undergoing elective cardiac surgery.

      Methods

      All patients aged 75+ years referred for elective cardiac surgery to Careggi University Hospital (Florence, Italy) from April 2013 to March 2017 were evaluated pre-operatively. Participants were classified according to the STS-Predicted Risk Of Mortality (STS-PROM): low (<4%), intermediate (4 to 8%), and high risk (>8%). Primary study outcomes were hospital mortality and STS-defined major morbidity. Length of hospital stay was an additional outcome.

      Results

      Out of 235 participants (females: 46.5%; mean age: 79.6 years), 144 (61.3%) were at low, 67 (28.5%) at intermediate and 24 (10.2%) at high risk, based on the STS-PROM. SPPB (mean±SEM) was 8.8 ± 0.2, 7.0 ± 0.5, and 6.0 ± 0.8 in participants at low, intermediate, and high risk, respectively (p<0.001). The primary outcome occurred in 62 participants (26.4%). In low-risk participants, the SPPB score predicted the primary endpoint (adjusted OR 0.77, 95% CI 0.66–0.89 per each point increase; p<0.001) controlling for STS-Major Morbidity or Operative Mortality (STS-MM) score. This result was not observed in the intermediate-high risk group.

      Conclusions

      SPPB predicts mortality and major morbidity in older patients undergoing elective cardiac surgery, classified as low risk with the STS risk score. The SPPB, applied preoperatively, might improve risk stratification in older patients undergoing elective cardiac surgery.

      Graphical abstract

      Keywords

      Abbreviations:

      BADL (basic activities of daily living), CKD (chronic kidney disease), CI (confidence interval), eGFR (estimated glomerular filtration rate), EKG (electrocardiogram), EuroSCORE (EUROpean system for cardiac operative risk evaluation), GDS (geriatric depression scale), IDS (index of disease severity), IADL (instrumental activities of daily living), OR (odds ratio), PLOS (prolonged length of stay), SEM (standard erros of the mean), SPPB (short physical performance battery), SPSS (statistical package for social sciences), STS (society of thoracic surgeons), STS-MM (society of thoracic surgeons major morbidity or operative mortality), STS-PROM (society of thoracic surgeons predicted risk of mortality)

      1. Introduction

      Improved surgical techniques and intensive care management have dramatically reduced perioperative complications and mortality after cardiac surgery over the last two decades [
      • Buth K.J.
      • Gainer R.A.
      • Legare J.F.
      • Hirsch G.M
      The changing face of cardiac surgery: practice patterns and outcomes 2001-2010.
      ]. Therefore, indications to cardiac surgery are nowadays increasingly extended to patients aged 80+ years [
      • Buth K.J.
      • Gainer R.A.
      • Legare J.F.
      • Hirsch G.M
      The changing face of cardiac surgery: practice patterns and outcomes 2001-2010.
      ], often in the past excluded due to unacceptable risk of death and major morbidity, as estimated by risk assessment scores of common use. Despite these remarkable improvements, perioperative complications and mortality, as well as long-term unfavorable outcomes, remain common in older persons [
      • Kawahito K.
      • Kimura N.
      • Yamaguchi A.
      • Aizawa K.
      • Misawa Y.
      • Adachi H
      Early and late outcomes of cardiac surgery in octogenarians.
      ].
      Risk assessment tools, such as the EUROpean System for Cardiac Operative Risk Evaluation (EuroSCORE II) [
      • Nashef S.A.
      • Roques F.
      • Sharples L.D.
      • Nilsson J.
      • Smith C.
      • Goldstone A.R.
      • et al.
      EuroSCORE II.
      ] and the Society of Thoracic Surgeons (STS) score [
      • Jr Ferguson TB
      • Jr Dziuban SW
      • Edwards F.H.
      • Eiken M.C.
      • Shroyer A.L.
      • Pairolero P.C.
      • et al.
      The STS national database: current changes and challenges for the new millennium. Committee to establish a national database in cardiothoracic surgery, the society of thoracic surgeons.
      ], have been shown to improve the accuracy of prognostic assessment in middle-aged individuals, but their validity is suboptimal in older persons [
      • Dupuis J.Y.
      Predicting outcomes in cardiac surgery: risk stratification matters?.
      ]. Indeed, surgical risk calculators do not take into account important non-cardiovascular variables, such as cognitive impairment, depression, functional decline, and sarcopenia, neither they are able to capture the “frail phenotype”, a powerful, independent predictor of mortality and complications after surgery [
      • Afilalo J.
      • Mottillo S.
      • Eisenberg M.J.
      • Alexander K.P.
      • Noiseux N.
      • Perrault L.P.
      • et al.
      Addition of frailty and disability to cardiac surgery risk scores identifies elderly patients at high risk of mortality or major morbidity.
      ]. Frailty is defined as a reduction in physiological homeostatic reserve, with consequent increased vulnerability to stressful events [
      • Walston J.
      • Hadley E.C.
      • Ferrucci L.
      • Guralnik J.M.
      • Newman A.B.
      • Studenski S.A.
      • et al.
      Research agenda for frailty in older adults: toward a better understanding of physiology and etiology: summary from the American Geriatrics Society/National Institute on Aging Research Conference on frailty in older adults.
      ]. Cardiac surgery represents a powerful stressor for vulnerable older adults, in whom the presence of frailty, variously defined, appears as a major prognostic determinant in this setting [
      • Sundermann S.
      • Dademasch A.
      • Rastan A.
      • Praetorius H.
      • Rodriguez H.
      • Walther T.
      • et al.
      One-year follow-up of patients undergoing elective cardiac surgery assessed with the comprehensive assessment of frailty test and its simplified form.
      ,
      • Afilalo J.
      • Kim S.
      • O'Brien S.
      • Brennan J.M.
      • Edwards F.H.
      • Mack M.J.
      • et al.
      Gait speed and operative mortality in older adults following cardiac surgery.
      ].
      Physical performance measures have been successfully applied to assess the prognosis of older patients with heart diseases. Gait speed has been tested in patients undergoing cardiac surgery [
      • Afilalo J.
      • Kim S.
      • O'Brien S.
      • Brennan J.M.
      • Edwards F.H.
      • Mack M.J.
      • et al.
      Gait speed and operative mortality in older adults following cardiac surgery.
      ], whereas the Short Physical Performance Battery (SPPB) [
      • Guralnik J.M.
      • Simonsick E.M.
      • Ferrucci L.
      • Glynn R.J.
      • Berkman L.F.
      • Blazer D.G.
      • et al.
      A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission.
      ] has been shown to predict long-term survival after hospitalization for heart failure exacerbation [
      • Chiarantini D.
      • Volpato S.
      • Fotini S.
      • Bartalucci F.
      • Del Bianco L.
      • Mangani I.
      • et al.
      Lower extremity performance measures predict long-term prognosis in older patients hospitalized for heart failure.
      ]. The SPPB objectively and quantitatively assesses balance, gait speed, and lower limbs strength (indirectly estimated from repeated chair standing), thus offering a thorough evaluation of lower extremity function, which is crucial to maintain autonomy [
      • Guralnik J.M.
      • Simonsick E.M.
      • Ferrucci L.
      • Glynn R.J.
      • Berkman L.F.
      • Blazer D.G.
      • et al.
      A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission.
      ]. Aim of the present study was to assess whether the SPPB can improve the prediction of hospital course (i.e., major clinical events and prolonged hospital stay) in older patients undergoing elective cardiac surgery, above and beyond the prognostic assessment obtained with the STS score.

      2. Materials and methods

      2.1 Study design

      The present study is a prospective, single-center cohort study conducted at Careggi University Hospital, Florence. Institutional Review Board approval was obtained. Before enrolment, participants gave their written informed consent.

      2.2 Population

      All patients aged 75+ years referred to the Cardiac Surgery Unit of Careggi Hospital for their first elective cardiac surgery procedure via standard sternotomy were screened for enrolment. All types of cardiac surgery (coronary aortic by-pass grafting, valvular surgery, or combined procedures) were initially evaluated, although only participants receiving a procedure considered by the STS calculator were eventually included. Patients undergoing an emergency/urgent procedure or clinically unstable, i.e. with an acute coronary syndrome, acute or worsening heart failure were excluded.

      2.3 Baseline evaluation

      Patients scheduled for elective procedures to the Cardiac Surgery Unit of Careggi Hospital and residing in the metropolitan area of Florence are routinely assessed by a multidisciplinary team composed by a cardiac surgeon, a cardiologist and an anesthesiologist. From April 1, 2013, to March 31, 2017 and limited to patients aged 75+ years, geriatricians participated to this evaluation procedure, although only twice a week because of limited resources. No specific criteria dictated assignment of patients to weekdays when the geriatrician was present. Age, weight, height, body mass index, medical history (including current symptoms and New York Heart Association – NYHA - class), EKG, echocardiographic parameters, and laboratory data were recorded, together with educational level, social network, and presence of a primary caregiver. The EuroSCORE II [
      • Nashef S.A.
      • Roques F.
      • Sharples L.D.
      • Nilsson J.
      • Smith C.
      • Goldstone A.R.
      • et al.
      EuroSCORE II.
      ] and the STS score [

      Society of Thoracic Surgeons. Available online at http://riskcalc.sts.org/stswebriskcalc/#/. Accessed December 8, 2019.

      ] were calculated. Participants were stratified into three groups according to their STS Predicted Risk Of Mortality (STS-PROM) score: low risk (STS-PROM <4%), intermediate risk (STS-PROM 4 to 8%), and high risk (STS-PROM >8%).
      Comprehensive geriatric assessment was conducted by an expert geriatrician, using the Basic [
      • Katz S.
      • Ford A.B.
      • Moskowitz R.W.
      • Jackson B.A.
      • Jaffe M.W
      Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function.
      ] and Instrumental [
      • Lawton M.P.
      • Brody E.M.
      Self-maintaining and instrumental activities of daily living.
      ] Activities of Daily Living (BADL, IADL) scales for functional status, the MiniCog test with the Seattle algorithm [
      • Scanlan J.M.
      • Borson S.
      The mini-cog. Receiver operating characteristics with expert and naive raters.
      ] and the 5-item Geriatric Depression Scale (GDS) [
      • Rinaldi P.
      • Mecocci P.
      • Benedetti C.
      • Ercolani S.
      • Bregnocchi M.
      • Menculini G.
      • et al.
      Validation of the five-item geriatric depression scale in elderly subjects in three different settings.
      ] for cognitive and affective status, respectively. Comorbidity was quantified with Greenfield's Index of Disease Severity (IDS) [
      • Greenfield S.
      • Apolone G.
      • McNeil B.J.
      • Cleary P.D
      The importance of co-existent disease in the occurrence of postoperative complications and one-year recovery in patients undergoing total hip replacement. Comorbidity and outcomes after hip replacement.
      ], which records a list of diseases with their corresponding level of severity (0= disease absent; 1= disease asymptomatic; 2= symptoms present but controlled by therapy; 3= symptoms poorly controlled by therapy; 4= symptoms uncontrolled or life-threatening disease). Renal function was evaluated from creatinine value and estimated Glomerular Filtration Rate (eGFR), obtained with the Cockroft-Gault Formula included in EuroSCORE II [
      • Nashef S.A.
      • Roques F.
      • Sharples L.D.
      • Nilsson J.
      • Smith C.
      • Goldstone A.R.
      • et al.
      EuroSCORE II.
      ]. Chronic Kidney Disease (CKD) was considered severe when eGFR was ≤30 ml/min/1.73 m2. Anemia was diagnosed from hemoglobin <12 g/dl in women and <13 g/dl in men.
      Finally, participants underwent the SPPB, according to standard procedures [
      • Guralnik J.M.
      • Simonsick E.M.
      • Ferrucci L.
      • Glynn R.J.
      • Berkman L.F.
      • Blazer D.G.
      • et al.
      A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission.
      ]. Briefly, each of the three performance tests included in the SPPB (balance, gait speed, and repeated chair standing) is scored from 0 (worse) to 4 (best), based upon comparison of test results with normative values from a reference population. A summary score is then calculated, ranging from 0 (severely impaired performance) to 12 (optimal performance). An SPPB score <7 is usually considered as indicative of moderately to severely impaired physical performance [
      • Guralnik J.M.
      • Ferrucci L.
      • Simonsick E.
      • Salive M.E.
      • Wallace R.B
      Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability.
      ].
      Because the study represented a preliminary phase propaedeutic to routine application of geriatric assessment in the management of older patients prior to a surgical procedure that had already been scheduled, surgeons and anesthesiologists remained blinded towards geriatricians’ findings.

      2.4 Study outcomes

      The primary outcome was a composite endpoint as defined by STS Major Morbidity or Operative Mortality (STS-MM) in STS Risk Model Outcomes [

      Society of Thoracic Surgeons. Available online at http://riskcalc.sts.org/stswebriskcalc/#/. Accessed December 8, 2019.

      ]: operative mortality, stroke, renal failure, prolonged mechanical ventilation, deep sternal wound infection, and reoperation. Operative mortality was all-cause death occurring during surgery-related hospitalization or within the following 30 days. Permanent stroke was defined according to STS risk score, as any confirmed neurological deficit of abrupt onset caused by a disturbance in blood supply to the brain, persisting ≥ 24 h or until death. Acute or worsening renal failure was defined as an increase in serum creatinine up to ≥4.0 mg/dl, rising of at least 0.5 mg/dl or with threefold-increase from the most recent preoperative level, or requiring postoperative dialysis. Prolonged ventilation was time until extubation above 24 h, including any additional hours following reintubation. Deep sternal wound infection, defined according to the Centers for Disease Control and Prevention criteria, was taken into account when occurring within 30 days from operation. Reoperation included any intervention for cardiac or non-cardiac reasons.
      Secondary outcome was length of stay exceeding 14 days (prolonged length of stay, PLOS), as in the STS risk score model.

      2.5 Statistical analysis

      Statistical analysis was performed using SPSS® version 25.0 (SPSS, Inc., Chicago, IL). Data distribution was preliminarily observed, to verify whether parametric tests could be applied. Continuous variables are expressed as means (±SEM) and categorical variables as percentages. Descriptive analyses were conducted to compare baseline characteristics across the three STS-defined risk groups. Continuous variables were compared using Student's t-test for independent samples or ANOVA, whereas the chi-square test was applied to evaluate differences in proportions; p-values for trend were taken into account as appropriate. In order to identify independent predictors, variables with a significant association with the endpoint in bivariate analyses were entered into multivariable logistic models, with backward deletion (p out >0.1) of redundant variables. The predicted probability of the composite endpoint, obtained from separate logistic regression models, was used to estimate discrimination as the area under the ROC curve. Analyses were conducted in the entire study sample and separately in the two STS-defined groups at low- and intermediate-high risk. Additional analyses tested the predictive ability of each SPPB individual test.
      Protection from type I error was set at an α level of 0.05.

      3. Results

      3.1 Study population

      In the enrollment timeframe, 457 patients fulfilled the selection criteria and were eligible for the study. This figure represented approximately 22% of those aged 75+ and scheduled for elective cardiac surgery in the Careggi Hospital Unit, most of whom were not eligible because of a non-STS compatible surgical procedure or residence outside the Florence metropolitan area. Of those eligible, 193 could not be enrolled because their preoperative assessment was scheduled when the geriatrician was unavailable, whereas other 29 were enrolled but could not be considered for the study because of missing data. Thus, the final study sample included 235 participants (51.4% of the eligible patients), whose mean age (±SEM) was 79.6 ± 0.2 years; 105 (44.7%) participants were aged 80+ years and women were 109 (46.4%). Isolated CABG was performed in 38 patients (16.2%), isolated aortic or mitral valve surgery in 90 (38.3%), and combined CABG plus aortic or mitral valve surgery in 107 (45.5%). In comparison to the 235 who were eventually enrolled, the 222 who were not had comparable age (79.8 ± 0.3 years; p = 0.548) and proportion of men (62.2%; p = 0.064); conversely, more participants received coronary and valve surgery combined (39.0%), compared to isolated CABG (6.8%) and valve surgery (54.2%; p<0.001).
      One hundred forty-four participants (61.3%) were classified by STS-PROM score as low-risk, 67 (28.5%) as intermediate-risk and 24 (10.2%) as high-risk. The SPPB score was 8.0 ± 0.2 in the whole series and increased with decreasing STS-PROM risk status, being 6.0 ± 0.8 in high, 7.0 ± 0.5 in intermediate, and 8.8 ± 0.2 in low-risk participants (p<0.001). Sixty-two participants (26.4%) could be defined as more severely impaired because of an SPPB score <7; their prevalence was greater in the high-risk class (p<0.001), whose participants were also older, more functionally dependent and with more comorbidities (Table 1).
      Table 1Demographic and clinical characteristics according to STS-PROM risk category (low risk: <4%; intermediate risk: 4–8%; high risk: >8%).
      STS-PROM risk categoryp value
      Low (n = 144)Intermediate (n = 67)High (n = 24)
      Age, years78.5 ± 0.381.1 ± 0.581.7 ± 0.7<0.001
      Male90 (63)24 (36)12 (50)0.008
      BMI, kg/m226.1 ± 0.3025.7 ± 0.625.4 ± 0.80.370
      Type of surgery
      - CABG32 (22)4 (6)2 (8)<0.001
      - Isolated valve surgery67 (47)18 (27)5 (21)
      - Combined surgery45 (31)45 (67)17 (71)
      EuroSCORE II,%3.0 ± 0.15.9 ± 0.312.7 ± 1.6<0.001
      STS-PROM,%2.4 ± 0.15.6 ± 0.114.0 ± 2.1<0.001
      STS-MM,%16.3 ± 0.428.3 ± 0.749.7 ± 3.2<0.001
      Hypertension119 (83)58 (87)21 (88)0.410
      Type 2 Diabetes30 (21)16 (24)10 (42)0.052
      Insulin-requiring Diabetes10 (7)6 (9)7 (29)0.004
      History of CAD67 (47)34 (51)17 (71)0.048
      Heart failure76 (53)46 (69)22 (92)<0.001
      NYHA class III-IV50 (35)31 (47)19 (79)<0.001
      History of stroke9 (6)9 (13)2 (8)0.266
      Chronic kidney disease33 (23)23 (34)16 (67)0.001
      Atrial fibrillation27 (19)24 (36)7 (29)0.031
      COPD12 (8)17 (25)3 (13)0.039
      PAD11 (7)4 (6)2 (8)0.905
      LVEF58.7 ± 0.855.2 ± 1.346.8 ± 3.3<0.001
      TAPSE, mm22.6 ± 0.421.6 ± 0.520.1 ± 0.70.0043
      Hemoglobin, g/dl12.8 ± 0.112.1 ± 0.211.5 ± 0.4<0.001
      Anemia62 (43)37 (55)16 (67)0.014
      Creatinine, mg/dl0.96±0.031.14±0.061.38±0.11<0.001
      eGFR, ml/min/1.73 m269.1 ± 5.349.1 ± 2.239.5 ± 3.20.001
      Total SPPB8.8 ± 0.27.0 ± 0.56.0 ± 0.8<0.001
      IDS score8.7 ± 0.310.8 ± 0.412.0 ± 0.9<0.001
      BADL lost0.2 ± 0.00.3 ± 0.10.5 ± 0.10.032
      IADL lost0.9 ± 0.11.4 ± 0.22.4 ± 0.4<0.001
      Abnormal MiniCog63 (44)41 (61)17 (71)0.002
      GDS1.1 ± 0.11.3 ± 0.11.4 ± 0.30.128
      Number of drugs5.8 ± 0.26.6 ± 0.38.0 ± 0.4<0.001
      Data are mean (SEM) or n (%).
      Abbreviations. BMI: Body Mass Index; CABG: Coronary Artery Bypass Grafting; STS-PROM: Society of Thoracic Surgeons - Predicted Risk Of Mortality; STS-MM: Society of Thoracic Surgeons - Major Morbidity or Operative Mortality; STS-LLS: STS Long Length of stay; CAD: Coronary Artery Disease; NYHA: New York Heart Association; CKD: Chronic Kidney Disease; COPD: Chronic Obstructive Pulmonary Disease; PAD: Peripheral Artery Disease; LVEF: Left Ventricular Ejection Fraction; TAPSE: Tricuspid Annular Plane Systolic Excursion; eGFR: estimated Glomerular Filtration Rate; SPPB: Short Physical Performance Battery; IDS: Index of Disease Severity; BADL: Basic Activities of Daily Living; IADL: Instrumental Activities of Daily Living; GDS: Geriatric Depression Scale 5-item.
      P-values are from ANOVA (continuous variables) or chi square (categorical variables) tests for trend.
      Five participants died in-hospital, 17 required prolonged invasive ventilation, 8 were re-operated, 40 had acute kidney failure and six a stroke; no deep sternal wound infection or mediastinitis were observed. Overall, 62 participants (26.4%) experienced one or more of the events included in the primary composite endpoint, with a total of 76 major complications as above defined. As shown in Table 2, the composite endpoint, as well as some of the individual complications contributing to it (prolonged invasive ventilation, reoperation, and acute kidney failure), occurred progressively more often across the three classes of risk defined by the STS-PROM.
      Table 2Hospital outcomes, according to STS risk category, as defined in Table 1.
      STS-PROM risk categoryp value
      Low (n = 144)Intermediate (n = 67)High (n = 24)
      ICU length of stay, hours47.2 ± 8.250.7 ± 8.170.2 ± 11.80.288
      ICU staying >72 h15 (10)10 (15)8 (33)0.006
      Duration of invasive ventilation, hours15.9 ± 7.713.2 ± 2.825.9 ± 9.70.723
      Invasive ventilation >24 h6 (4)4 (6)7 (29)<0.001
      Length of stay, days14.3 ± 0.615.9 ± 0.820.8 ± 3.50.001
      Prolonged length of stay58 (41)33 (49)14 (58)0.074
      Death2 (1)2 (3)1 (4)0.306
      Stroke4 (3)2 (3)00.566
      Reoperation3 (2)2 (3)3 (13)0.030
      Acute kidney failure14 (10)16 (24)10 (42)0.001
      Deep sternal wound infection000
      Composite endpoint27 (19)23 (34)12 (50)<0.001
      Data are mean (SEM) or n (%).
      Abbreviations. ICU: Intensive Care Unit.
      P-values are from ANOVA (continuous variables) or chi square (categorical variables) tests for trend.
      In bivariate analyses, many pre-operative variables were associated with the composite endpoint (Table 3). A multivariable logistic regression model was built, which included age, gender, and all the variables that, at bivariate comparisons, were significantly associated with the composite endpoint. In the final model, after backward removal of redundant variables, the SPPB total score resulted an independent predictor of the composite endpoint in the entire study population, controlling for STS-MM score. Using the probability of the composite endpoint, as predicted by this logistic regression model, to estimate discrimination in ROC plots, an area under the ROC curve (AUC) of 0.741 was obtained.
      Table 3Bivariate predictors of the composite endpoint (CE) in the whole study sample and in low risk participants, as defined in Table 1.
      Whole study sampleLow risk
      CE no (173)CE yes (62)p valueCE no (117)CE yes (27)p value
      Age, years79.6 ± 0.379.5 ± 0.50.90778.8 ± 0.377.6 ± 0.50.071
      Male88 (51)38 (61)0.15872 (62)18 (69)0.620
      BMI, kg/m226.0 ± 0.325.7 ± 0.40.61226.0 ± 0.326.4 ± 0.70.573
      Type of surgery
      - CABG33 (19)5 (8)0.08028 (24)4 (14)0.405
      - Isolated valve surgery67 (39)23 (37)55 (47)12 (46)
      - Combined surgery73 (42)34 (55)34 (29)11 (42)
      EuroSCORE II,%4.2 ± 0.36.5 ± 0.70.0042.9 ± 0.13.5 ± 0.40.157
      STS-PROM,%3.8 ± 0.26.8 ± 1.00.0052.4 ± 0.12.7 ± 0.10.109
      STS-MM,%20.6 ± 0.730.0 ± 2.1<0.00115.8 ± 0.418.3 ± 0.90.007
      Hypertension139 (80)59 (95)0.00693 (80)26 (100)0.038
      Type 2 Diabetes37 (21)19 (31)0.14222 (19)8 (31)0.212
      Insulin-requiring Diabetes14 (8)9 (15)0.1447 (6)3 (12)0.345
      History of CAD86 (50)32 (52)0.79755 (47)12 (46)0.810
      Heart failure102 (59)42 (68)0.22362 (53)14 (54)0.915
      NYHA class III-IV67 (39)33 (53)0.05140 (34)10 (39)0.779
      History of stroke10 (6)10 (16)0.0126 (5)3 (12)0.247
      CKD44 (25)28 (45)0.00422 (19)11 (42)0.014
      Atrial fibrillation38 (22)20 (32)0.10722 (19)5 (19)0.973
      COPD20 (12)12 (19)0.1258 (7)4 (15)0.176
      PAD8 (5)9 (15)0.0105 (4)6 (23)0.002
      LVEF,%57.3 ± 0.854.4 ± 1.60.10558.9 ± 0.858.0 ± 2.00.666
      TAPSE, mm22.3 ± 0.321.4 ± 0.50.14822.7 ± 0.422.3 ± 0.80.663
      Hemoglobin, mg/dl12.6 ± 0.111.9 ± 0.20.00612.9 ± 0.112.3 ± 0.40.122
      Anemia74 (43)41 (66)0.00246 (39)16 (62)0.059
      Creatinine, mg/dl1.0 ± 0.01.3 ± 0.1<0.0010.9 ± 0.01.1 ± 0.10.043
      eGFR, ml/min/1.73 m263.9 ± 4.550.4 ± 2.60.08270.9 ± 6.561.2 ± 3.90.478
      SPPB total score8.5 ± 0.26.7 ± 0.5<0.0019.3 ± 0.27.0 ± 0.70.004
      IDS score9.1 ± 0.211.3 ± 0.5<0.0018.4 ± 0.39.9 ± 0.70.029
      BADL lost0.3 ± 0.00.3 ± 0.10.7900.2 ± 0.00.1 ± 0.10.193
      IADL lost1.0 ± 0.11.7 ± 0.20.0110.7 ± 0.11.4 ± 0.40.032
      Abnormal MiniCog85 (49)35 (57)0.36251 (44)12 (46)0.936
      GDS1.2 ± 0.11.3 ± 0.20.5351.0 ± 0.11.4 ± 0.30.095
      Number of drugs6.1 ± 0.26.6 ± 0.30.2085.7 ± 0.26.1 ± 0.40.376
      Data are mean (SEM) or n (%).
      Abbreviations as in Table 1.
      When analyses were repeated separately for participants with STS-PROM indicative of low (<4%) or medium-high risk, the predictive value of SPPB was enhanced in the formers, whereas was lost in the latter. In the first subgroup, for each point increase in the SPPB score, the risk of the composite outcome increased by 23%, controlling for STS-MM score; all the other potential predictors were backward removed as redundant (Table 4). The ROC AUC based on the predicted probability from this logistic regression model was 0.747.
      Table 4Multivariable prediction of the composite endpoint, separately in the whole study population and in low risk participants, as defined in Table 1. Logistic regression models with backward deletion of redundant variables.
      Whole study sampleLow-risk participants
      OR (95% CI)p valueOR (95% CI)p value
      STS-MM,%1.05 (1.03–1.08)<0.0011.16 (1.04–1.29)0.007
      SPPB total score0.90 (0.83–0.99)0.0300.77 (0.66–0.89)0.001
      Abbreviations as in Table 1.
      Variables backward removed from the model in the whole study population: EuroSCORE II, STS-PROM, hypertension, chronic obstructive pulmonary disease, peripheral artery disease, hemoglobin, left ventricular ejection fraction, creatinine, estimated glomerular filtration rate, Index of Disease Severity. Variables backward removed from the model in the low risk population: hypertension, peripheral artery disease, hemoglobin, anemia, creatinine, Index of Disease Severity, Instrumental Activities of Daily Living, chronic kidney disease, Geriatric Depression Scale.
      The results of the additional analyses conducted to examine the role of each SPPB individual test are summarized in an online-only Appendix. All the three tests showed significant differences across the three STS-PROM risk categories (Appendix, Table A1), as well between participants who did and did not reach the composite endpoint in bivariate comparisons (Appendix, Table A2). The 4-m walk and the repeated chair standing, but not the balance test, resulted as significant independent predictors of the composite endpoint, both in the entire study sample and in the low-risk subgroup, always together with the STS-MM score (Appendix, Tables A3 and A4).
      An alternative model was also tested, where the STS-MM score was not included and peripheral artery disease and creatinine – two variables that contribute to the STS-MM score and that resulted as predictors in our bivariate comparisons – were conversely entered. The SPPB was confirmed as a significant predictor also in this model, with an OR (95% CI) of 0.73 (0.62–0.86) per each unit increase (p<0.001). Peripheral artery disease and creatinine remained significant predictors of the combined outcome, with ORs (95% CI) of 5.81 (1.31–25.3) and 5.46 (1.29–23.15) and p values of 0.023 and 0.019, respectively. Hypertension, hemoglobin, presence of anemia, IDS, GDS and IADL scores, and history of chronic kidney disease, entered in various combinations, were always removed as redundant from the final parsimonious model, which achieved a ROC AUC of 0.790 (3-variable Model; Fig. 1). The SPPB was not associated with the composite endpoint in the medium-high risk group (SPPB mean score 5.0 ± 0.5 vs. 5.5 ± 0.6, p = 0.523), which was predicted only by the STS-MM and IDS scores, creatinine, male gender and presence of anemia.
      Fig. 1
      Fig. 1Area under the ROC curve for composite endpoint in low-risk population based on the predicted probability obtained from STS-Major Morbidity or Operative Mortality (STS-MM), STS-MM and Short Physical Performance Battery and from the 3-variable Model.

      3.2 Predictors of prolonged length of stay

      PLOS occurred in 104 (45.2%) participants, without significant differences in the three STS-PROM classes (p = 0.202; Table 2). Many pre-operative variables were associated to PLOS in bivariate analyses in the whole series, but only the SPPB and the MiniCog maintained their predictive ability also in the subgroup of low-risk participants (Table 5). Bivariate predictors were entered into a multivariable logistic regression model predicting PLOS, whose final, parsimonious version showed that the SPPB score remained a strong independent predictor (OR 0.84; 95% CI 0.76–0.94; p = 0.002), together with MiniCog (OR 2.02; 95% CI 1.08–3.79; p = 0.027), number of drugs (OR 1.15; 95% CI 1.00–1.31; p = 0.048) and male gender (OR 0.49; 95% CI 0.25–0.95; p = 0.035). When this set of variables was tested in two logistic regression models, separately for participants at low or intermediate-high risk as defined above, the SPPB remained predictive of PLOS in both subgroups: the risk of PLOS was reduced by 20% (OR 0.80; 95%CI 0.67–0.95; p = 0.010) and 13% (OR 0.87; 95% CI 0.76–0.99; p = 0.036) for each point increase in the SPPB score, respectively. Neither STS-long length of stay nor EuroSCORE II predicted this outcome in either subgroup.
      Table 5Bivariate predictors of prolonged length of stay in the whole study sample and in low risk participants (as defined in Table 1).
      Whole study sampleLow-risk participants
      PLOS no (n = 126)PLOS yes (n = 104)p valuePLOS no (n = 83)PLOS yes (n = 59)p value
      Age, years79.6 ± 0.379.4 ± 0.30.72278.5 ± 0.378.6 ± 0.40.811
      Male62 (49)62 (60)0.11547 (57)41 (70)0.077
      BMI, kg/m226.3 ± 0.425.5 ± 0.30.15826.6 ± 0.425.4 ± 0.40.047
      Type of surgery
      - CABG22 (17)16 (15)0.00218 (22)14 (24)0.085
      - Isolated valve surgery59 (47)28 (27)44 (53)21 (36)
      - Combined surgery45 (36)60 (58)21 (25)24 (41)
      EuroSCORE II,%4.3 ± 0.35.4 ± 0.50.0692.8 ± 0.23.2 ± 0.20.177
      STS-PROM,%4.0 ± 0.35.2 ± 0.60.0792.4 ± 0.12.5 ± 0.10.500
      STS-MM,%21.1 ± 0.925.3 ± 1.40.01115.7 ± 0.517.0 ± 0.60.105
      STS-LLS,%10.0 ± 0.613.5 ± 1.20.0086.8 ± 0.57.1 ± 0.30.612
      Hypertension102 (81)91 (88)0.17967 (81)50 (85)0.535
      Type 2 Diabetes25 (20)30 (29)0.11117 (20)12 (20)0.983
      Insulin-requiring Diabetes8 (6)15 (14)0.0425 (6)5 (9)0.574
      History of CAD49 (39)66 (63)<0.00133 (40)33 (56)0.057
      Heart failure76 (60)63 (61)0.96844 (53)30 (51)0.799
      NYHA class III-IV46 (37)50 (48)0.08525 (30)23 (39)0.271
      History of stroke6 (5)13 (13)0.0343 (4)6 (10)0.114
      CKD40 (32)29 (28)0.52519 (23)13 (22)0.904
      Atrial fibrillation26 (21)29 (28)0.20013 (16)13 (22)0.333
      COPD13 (10)18 (17)0.1226 (7)5 (9)0.784
      PAD10 (8)7 (7)0.7286 (7)5 (9)0.784
      LVEF,%58.2 ± 0.954.6 ± 1.20.01559.8 ± 0.957.3 ± 1.30.106
      TAPSE, mm22.6 ± 0.421.5 ± 0.40.06023.4 ± 0.521.2 ± 0.60.023
      Hemoglobin, mg/dl12.7 ± 0.212.2 ± 0.20.04112.9 ± 0.212.6 ± 0.20.313
      Anemia53 (42)57 (55)0.05430 (36)30 (51)0.080
      Creatinine, mg/dl1.0 ± 0.01.3 ± 0.10.3481.0 ± 0.01.0 ± 0.00.567
      eGFR, ml/min/1,73m263.5 ± 6.257.3 ± 1.0.37473.3 ± 9.163.3 ± 2.10.366
      SPPB total score8.9 ± 0.37.1 ± 0.3<0.0019.5 ± 0.38.1 ± 0.40.002
      IDS score9.0 ± 0.310.3 ± 0.40.0088.5 ± 0.39.0 ± 0.40.412
      BADL lost0.3 ± 0.00.3 ± 0.10.9310.2 ± 0.10.2 ± 0.10.747
      IADL lost1.1 ± 0.21.2 ± 0.20.5690.8 ± 0.21.0 ± 0.20.509
      Abnormal MiniCog54 (43)64 (62)0.00529 (35)32 (54)0.022
      GDS1.0 ± 0.11.3 ± 0.10.0740.8 ± 0.11.4 ± 0.20.005
      Drug number5.9 ± 0.26.6 ± 0.20.0205.5 ± 0.26.1 ± 0.30.162
      Abbreviations: STS-LLS: STS Long Length of stay; other abbreviations as in Table 1.

      4. Discussion

      In our older participants candidate to elective cardiac surgery, the SPPB improved the short-term risk stratification (morbidity and mortality, PLOS), compared to the STS, in particular in low-risk participants.
      Hospital mortality after cardiac surgery has remained unchanged over the years, being nowadays around 5% [
      • Buth K.J.
      • Gainer R.A.
      • Legare J.F.
      • Hirsch G.M
      The changing face of cardiac surgery: practice patterns and outcomes 2001-2010.
      ,
      • Scandroglio A.M.
      • Finco G.
      • Pieri M.
      • Ascari R.
      • Calabrò M.G.
      • Taddeo D.
      • et al.
      Cardiac surgery in 260 octogenarians: a case series.
      ]; conversely, serious post-operative complications remain very frequent, possibly because of the increasing age and, hence, growing complexity of patients [
      • Wang W.
      • Bagshaw S.M.
      • Norris C.M.
      • Zibdawi R.
      • Zibdawi M.
      • MacArthur R.
      Approach investigators. Association between older age and outcome after cardiac surgery: a population-based cohort study.
      ]. In frail older patients, hospitalization is per se associated with declining muscle strength and mass [
      • Van Ancum J.M.
      • Scheerman K.
      • Jonkman N.H.
      • Smeenk H.E.
      • Kruizinga R.C.
      • Meskers C.G.M.
      • et al.
      Change in muscle strength and muscle mass in older hospitalized patients: a systematic review and meta-analysis.
      ], incident sarcopenia [
      • Martone A.M.
      • Bianchi L.
      • Abete P.
      • Bellelli G.
      • Bo M.
      • Cherubini A.
      • et al.
      The GLISTEN study. The incidence of sarcopenia among hospitalized older patients: results from the GLISTEN study.
      ], and loss of functional autonomy [
      • Brown C.J.
      • Friedkin R.J.
      • Inouye S.K
      Prevalence and outcomes of low mobility in hospitalized older patients.
      ], especially in the presence of complications and PLOS. Therefore, more than pure survival, disability-free survival and good quality of the residual life are desirable goals of care and of prognostic assessment in these patients [
      • Myles P.S.
      Meaningful outcome measures in cardiac surgery.
      ].
      In line with major international reports [
      • Buth K.J.
      • Gainer R.A.
      • Legare J.F.
      • Hirsch G.M
      The changing face of cardiac surgery: practice patterns and outcomes 2001-2010.
      ,
      • Scandroglio A.M.
      • Finco G.
      • Pieri M.
      • Ascari R.
      • Calabrò M.G.
      • Taddeo D.
      • et al.
      Cardiac surgery in 260 octogenarians: a case series.
      ], hospital mortality in our sample was as low as 2.1%, with no differences across the three risk groups; conversely, complications contributing to the composite endpoint and PLOS were observed in as many as 26.4% and 45.1% of our participants, respectively. Although STS-PROM was shown to provide good initial risk screening in respect to these important endpoints, other variables added substantial predictive power. In detail, in patients defined as at low-risk by the STS-PROM, the SPPB, creatinine levels and peripheral artery disease improved the prediction of major complications, as shown by the AUC of 0.790.
      Robust evidence has been provided that comprehensive geriatric assessment [
      • Abete P.
      • Cherubini A.
      • Di Bari M.
      • Vigorito C.
      • Viviani G.
      • Marchionni N.
      • et al.
      Does comprehensive geriatric assessment improve the estimate of surgical risk in elderly patients? An Italian multicenter observational study.
      ], and measures of physical performance in particular [
      • Sundermann S.
      • Dademasch A.
      • Rastan A.
      • Praetorius H.
      • Rodriguez H.
      • Walther T.
      • et al.
      One-year follow-up of patients undergoing elective cardiac surgery assessed with the comprehensive assessment of frailty test and its simplified form.
      ,
      • Guralnik J.M.
      • Simonsick E.M.
      • Ferrucci L.
      • Glynn R.J.
      • Berkman L.F.
      • Blazer D.G.
      • et al.
      A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission.
      ,
      • Chiarantini D.
      • Volpato S.
      • Fotini S.
      • Bartalucci F.
      • Del Bianco L.
      • Mangani I.
      • et al.
      Lower extremity performance measures predict long-term prognosis in older patients hospitalized for heart failure.
      ,
      • Abete P.
      • Cherubini A.
      • Di Bari M.
      • Vigorito C.
      • Viviani G.
      • Marchionni N.
      • et al.
      Does comprehensive geriatric assessment improve the estimate of surgical risk in elderly patients? An Italian multicenter observational study.
      ], may add clinically valuable predictive information. Physical performance is one of the cornerstones of the frailty framework [
      • Katz S.
      • Ford A.B.
      • Moskowitz R.W.
      • Jackson B.A.
      • Jaffe M.W
      Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function.
      ,
      • Myles P.S.
      Meaningful outcome measures in cardiac surgery.
      ]. In a prospective multicenter cohort of patients aged 70+ years, the addition of frailty and disability, defined by gait speed and Nagi score, respectively, improved the prediction of postoperative mortality and major morbidity over STS PROM score, with AOUCs increasing from 0.68 to 0.73 [
      • Afilalo J.
      • Mottillo S.
      • Eisenberg M.J.
      • Alexander K.P.
      • Noiseux N.
      • Perrault L.P.
      • et al.
      Addition of frailty and disability to cardiac surgery risk scores identifies elderly patients at high risk of mortality or major morbidity.
      ]. Among others, gait speed is the most commonly investigated performance measure: a recent original investigation conducted in a large cohort of patients with median age of 71 years demonstrated that each 0.1 m/s reduction in gait speed confers an 11% relative increase in mortality [
      • Afilalo J.
      • Kim S.
      • O'Brien S.
      • Brennan J.M.
      • Edwards F.H.
      • Mack M.J.
      • et al.
      Gait speed and operative mortality in older adults following cardiac surgery.
      ]. However, few studies have investigated if pre-operative measures were able to predict the onset of in-hospital complications [
      • Wang W.
      • Bagshaw S.M.
      • Norris C.M.
      • Zibdawi R.
      • Zibdawi M.
      • MacArthur R.
      Approach investigators. Association between older age and outcome after cardiac surgery: a population-based cohort study.
      ]. Afilalo et al. for the first time demonstrated that preoperatively slow-walker patients (≥6 s to walk 5 m) had an independent higher risk of 30-day mortality and major morbidity for any given levels of STS-Predicted Risk score [
      • Afilalo J.
      • Kim S.
      • O'Brien S.
      • Brennan J.M.
      • Edwards F.H.
      • Mack M.J.
      • et al.
      Gait speed and operative mortality in older adults following cardiac surgery.
      ]. The same authors have recently developed and tested, in a large cohort of patients undergoing aortic valve replacement, a frailty score [
      • Afilalo J.
      • Lauck S.
      • Kim D.H.
      • Lefèvre T.
      • Piazza N.
      • Lachapelle K.
      • et al.
      Frailty in older adults undergoing aortic valve replacement: the frailty-AVR study.
      ] that includes chair standing, a simple cognitive test, hemoglobin, and serum albumin.
      The SPPB offers a combined assessment of balance, gait speed, and strength of lower limbs, thus including both the physical performance measures separately tested by Afilalo. Initially shown to predict incident mobility disability in unselected older persons in the community [
      • Guralnik J.M.
      • Simonsick E.M.
      • Ferrucci L.
      • Glynn R.J.
      • Berkman L.F.
      • Blazer D.G.
      • et al.
      A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission.
      ], the SPPB has been subsequently used also in the clinical arena, where it was able to predict long-term survival of older patients discharged from the hospital after an episode of acute heart failure, independent of NYHA class, left ventricular ejection fraction, and comorbidity [
      • Chiarantini D.
      • Volpato S.
      • Fotini S.
      • Bartalucci F.
      • Del Bianco L.
      • Mangani I.
      • et al.
      Lower extremity performance measures predict long-term prognosis in older patients hospitalized for heart failure.
      ]. It therefore appears that the tool reflects thoroughly the burden of functional limitations, due to multimorbidity or to other age-related changes, including sarcopenia [
      • Landi F.
      • Cherubini A.
      • Cesari M.
      • Calvani R.
      • Tosato M.
      • Sisto A.
      • et al.
      Sarcopenia and frailty: from theoretical approach into clinical practice.
      ], whose association with clinical outcomes in non-cardiac surgery has been proven [
      • Friedman J.
      • Lussiez A.
      • Sullivan J.
      • Wang S.
      • Englesbe M
      Implications of sarcopenia in major surgery.
      ].
      Our data show that, for each point decrease in SPPB score, the risk of the composite endpoint increased respectively by 10% in the whole study sample and by 23% in the STS-PROM low-risk group. SPPB score was able to predict also PLOS, whose risk increased by 16% in the whole study sample and by 20% in the STS-PROM low-risk group for each 1-point decrease in SPPB score. Walking speed has already been shown to influence length of hospital stay among 1123 older adults admitted to acute care wards [
      • Vetrano D.L.
      • Landi F.
      • De Buyser S.L.
      • Carfì A.
      • Zuccalà G.
      • Petrovic M.
      • et al.
      Predictors of length of hospital stay among older adults admitted to acute care wards: a multicentre observational study.
      ]; in fact, patients with a gait speed ≥0.8 m/s were less likely to stay in hospital more than ten days. Similarly, SPPB was significantly and inversely associated with length of hospital stay in 90 older patients admitted to acute wards (b=−0.36, SEM 0.15, p = 0.02) [
      • Fisher S.
      • Ottenbacher K.J.
      • Goodwin J.S.
      • Graham J.E.
      • Ostir G.V
      Short physical performance battery in hospitalized older adults.
      ]. Therefore, we would offer that SPPB might contribute to better allocate hospital resources, by identifying persons at an increased risk of PLOS.
      The lower predictive ability of the SPPB in intermediate-high risk patients seems to suggest that conventional risk stratification is adequate in patients with poor global health status and severe comorbidity, in whom adding assessment of physical performance might offer limited advantage. However, this issue deserves further studies. Older patients deemed to be at a low-risk are the only ones in whom cardiac surgery is strictly recommended, whereas percutaneous procedures are preferable in intermediate- and high-risk patients in the most recent European guidelines [
      • Baumgartner H.
      • Falk V.
      • Bax J.J.
      • De Bonis M.
      • Hamm C.
      • Holm P.J.
      • et al.
      ESC scientific document group. 2017 ESC/EACTS guidelines for the management of valvular heart disease.
      ]. However, an extension of percutaneous techniques to low-risk patients (STS<4) is to be expected in the next future, after the recent PARTNER 3 [
      • Mack M.J.
      • Leon M.B.
      • Thourani V.H.
      • Makkar R.
      • Kodali S.K.
      • Russo M.
      • et al.
      PARTNER 3 investigators. Transcatheter aortic-valve replacement with a balloon-expandable valve in low-risk patients.
      ] and Evolut Low Risk [
      • Popma J.J.
      • Deeb G.M.
      • Yakubov S.J.
      • Mumtaz M.
      • Gada H.
      • O'Hair D.
      • et al.
      Evolut low risk trial investigators. Transcatheter aortic-valve replacement with a self-expanding valve in low-risk patients.
      ] trials, in which transcatheter aortic valve replacement was respectively superior and non-inferior to surgery in this subset, for the composite outcome of all-cause mortality, major stroke and re-operation. Thus, our findings on how to improve risk stratification in low-risk patients may provide particularly important information in the choice between the two alternatives, should this new evidence be confirmed and incorporated in updated guidelines. Furthermore, our findings may help select patients in whom pre-habilitation, i.e. structured preoperative programs combining nutritional and physiotherapy interventions [
      • Sandhu M.S.
      • Akowuah E.F.
      Does prehabilitation improve outcomes in cardiac surgical patients?.
      ], may be particularly effective.

      4.1 Study limitations

      This study has several limitations. The sample size was numerically limited, also because we focused on patients who were expected to receive surgical procedures included in STS risk scores calculator, whereas older persons often receive more complex interventions. On the other hand, compared to other studies, mean age of our participants was remarkably high. Testing the prognostic value of geriatric assessment, including the SPPB, in the large share of older patients that receive procedures not suitable to risk stratification with the STS may represent an additional venue of future research. Our limited resources did not allow us to perform geriatric assessment systematically in all potential candidates. However, patients were scheduled for pre-operative surgical evaluation independent of the presence of geriatricians and, indeed, patients who met the inclusion criteria had comparable demographics. The different distribution of surgical procedures between patients enrolled and not enrolled might have, at most, introduced a conservative bias, because our participants more often received combined, more complex procedures. Details on surgical procedures were not consistently available in the database and, therefore, could not be used in the analyses. Finally, only in-hospital endpoints were considered, whereas other outcomes, such as functional and cognitive status after hospital discharge, which are very important in a geriatric perspective, could not be considered.

      5. Conclusions

      In our cohort of older persons, the SPPB independently predicted hard, short-term outcomes such as mortality, morbidity, and PLOS in patients otherwise considered at low risk, according to standard cardiac surgery stratification systems. Therefore, this tool may provide useful to improve preoperative risk stratification. Further studies are needed to confirm these findings in wider populations and with extended follow-up, to detect changes in independency as well as in functional and cognitive status, which are particularly relevant in a geriatric perspective.

      Declaration of Competing Interest

      As far as the manuscript entitled “Pre-operative physical performance as a predictor of in-hospital outcomes in older patients undergoing elective cardiac surgery”, which has been submitted to the European Journal of Internal Medicine, all the authors reported below declare no conflict of interest.

      Acknowledgements

      This paper is dedicated to the memory of our dear friend and colleague, Dr. Alessandra Rossi, prematurely and grimly passed away, whose contribution was crucial to the development and conduction of this study.
      With the unconditional support of A.R. Card Onlus Foundation.

      Appendix

      Tables A1, A2, A3, A4.
      Table A1Comparison of individual SPPB test scores across STS risk categories.
      STS-PROM risk categoryp value
      Low (n = 144)Intermediate (n = 67)High (n = 24)
      Balance3.4 ± 0.82.8 ± 0.22.4 ± 0.3<0.001
      4-m walk3.3 ± 0.12.6 ± 0.22.2 ± 0.3<0.001
      Repeated chair standing2.3 ± 0.11.6 ± 0.21.5 ± 0.30.011
      Data are mean (SEM).
      P-values are from ANOVA test for trend.
      Table A2Comparison of individual SPPB test scores between participants who did or did not reach the composite endpoint (CE), separately in the whole study population and in low risk participants.
      Whole study sampleLow risk
      CE no (173)CE yes (62)p valueCE no (117)CE yes (27)p value
      Balance3.2 ± 0.12.9 ± 0.20.0773.5 ± 0.13.0 ± 0.30.025
      4-m walk3.2 ± 0.092.4 ± 0.17<0.0013.4 ± 0.82.6 ± 0.30.004
      Repeated chair standing2.2 ± 0.101.4 ± 0.17<0.0012.5 ± 0.11.4 ± 0.3<0.001
      Data are mean (SEM).
      P-values are from t-test for independent samples.
      Table A3Multivariable prediction of the composite endpoint, separately in the whole study population and in low risk participants, based on the 4-m walk test score. Logistic regression models with backward deletion of redundant variables.
      Whole study sampleLow-risk participants
      OR (95% CI)p valueOR (95% CI)p value
      Gender (F vs. M)0.47 (0.24–0.94)0.031——NS
      Age, years——-NS0.81 (0.67–0.98)0.026
      STS-MM,%1.05 (1.02–1.08)0.0041.16 (1.04–1.29)0.007
      SPPB 4-m walk0.70 (0.54–0.91)0.0090.42 (0.26–0.66)<0.001
      Variables backward removed from the model in the whole study population: age, EuroSCORE II, STS-PROM, hypertension, chronic obstructive pulmonary disease, peripheral artery disease, hemoglobin, left ventricular ejection fraction, creatinine, estimated glomerular filtration rate, Index of Disease Severity. Variables backward removed from the model in the low risk population: anemia, Index of Disease Severity, Instrumental Activities of Daily Living, chronic kidney disease, estimated glomerular filtration rate, Clock Drawing Test score.
      Table A4Multivariable prediction of the composite endpoint, separately in the whole study population and in low risk participants, based on the repeated chair standing score. Logistic regression models with backward deletion of redundant variables.
      Whole study sampleLow-risk participants
      OR (95% CI)p valueOR (95% CI)p value
      Gender (F vs. M)0.47 (0.24–0.94)0.031——-NS
      STS-MM,%1.05 (1.02–1.08)0.0041.17 (1.05–1.32)0.005
      Repeated chair standing0.70 (0.54–0.91)0.0090.47 (0.31–0.71)<0.001
      Abbreviations as in Table 1.
      Variables backward removed from the model in the whole study population: age, EuroSCORE II, STS-PROM, hypertension, chronic obstructive pulmonary disease, peripheral artery disease, hemoglobin, left ventricular ejection fraction, creatinine, estimated glomerular filtration rate, Index of Disease Severity. Variables backward removed from the model in the low risk population: anemia, Index of Disease Severity, Instrumental Activities of Daily Living, chronic kidney disease, estimated glomerular filtration rate, Clock Drawing Test score.
      In logistic regression models with backward deletion of redundant variables, the balance test did not result as a multivariable predictor of the composite endpoint, nor in the whole study population neither in low risk participants (data not shown).

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