The Society of Thoracic Surgeons Risk Model for Operative ... · The Society of Thoracic Surgeons...

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ATS-2012-350140-R1

The Society of Thoracic Surgeons Risk Model for Operative Mortality after Multiple Valve Surgery

J. Scott Rankin MD1, Xia He MS2, Sean M. O’Brien PhD2, Jeffrey P. Jacobs MD3, Karl F. Welke MD4, Giovanni Filardo PhD MPH5,

Cynthia M. Shewan PhD6, David M. Shahian MD7

1Centennial Medical Center, Vanderbilt University, Nashville, TN 2Duke Clinical Research Institute, Durham, NC 3The Congenital Heart Institute of Florida (CHIF), All Children’s Hospital, University of South Florida, Tampa, FL 4Seattle Children's Hospital and the University of Washington School of Medicine, Seattle, WA 5Inst.forHealth Care Research and Improvement, Baylor Health Care System, Dallas, TX 6 The Society of Thoracic Surgeons, Chicago, IL 7Massachusetts General Hospital, Harvard Medical School, Boston, MA Running Head: Multiple Valve Risk Model Keywords: Cardiac Valve Surgery; Statistical Risk Modeling; Outcome Assessment Abstract Word Count = 250 Text Word Count = 3,247 Table I + Figure 1 Word Count (minus Appendix Tables) = 1,085 Total Word Count = 4,332 Tables + Figures = 2 Appendix Tables A, B, C, D, and E are available on the STS website and also can be downloaded from: http://www.jsrmd.com/ftp/Final_MUV_Model.pdf Address correspondence to: J. Scott Rankin MD, (615) 969-1543, [email protected]

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Abstract

Background: This study was undertaken to develop STS mortality risk models for multiple valve

procedures, which comprise 12% of total valve operations.

Methods: Data were obtained from the STS Adult Cardiac Surgery Database for 50,231 patients undergoing

combinations of aortic (A), mitral (M), and tricuspid (T) surgery between January 1, 2004 and December 31,

2010, divided into developmental (2004-2009) and validation (2010) samples. Pulmonary valve operations,

aortic root replacements, and dissection procedures were excluded, and insufficient AT procedures were

available to model. Using stepwise logistic regression, the risk of operative mortality was estimated for each

valve surgery type [(AM; n=27,035), (MT; n=18,686), and (AMT; n=4,510)]. Two separate models were

estimated, one that included only patient characteristics and status at presentation, and thereby would be

suitable for performance profiling; and another that added discretionary operative variables such as

arrhythmia ablation or valve repair.

Results: Unadjusted operative mortality was 7.6% for MT, 9.4% for AM, and 13.1% for AMT procedures.

Significant risk factors for mortality included emergency presentation, advanced age, renal failure,

reoperation, endocarditis, diabetes, severe chronic lung disease, peripheral vascular disease, coronary artery

disease, and female sex. In models containing intraoperative variables, performance of arrhythmia ablation

and atrio-ventricular valve repair were protective for mortality. In the validation sample, the model exhibited

acceptable discrimination in each of the 3 procedural subgroups (C=0.711-0.727).

Conclusions: Risk models were developed to predict operative mortality for patients having multiple valve

procedures. These models may be useful for outcome assessment, quality improvement, patient counseling,

shared decision-making, and research.

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Introduction

The Society of Thoracic Surgeons (STS) has developed risk prediction models for various types of

cardiac surgery that have been useful for quality assessment and improvement, patient counseling, and

research (1-4). However, models currently are unavailable for procedures involving combinations of aortic

(A), mitral (M), and tricuspid (T) valves. Although multiple valve (MUV) surgery comprises only 12% of

valve procedures, MUV mortality is more than twice that of single valve operations and accounts for up to a

third of operative deaths after valve surgery (5,6). A risk model for MUV operative mortality would enable

benchmark comparisons among STS participants (usually cardiac surgical groups or hospital departments)

and facilitate shared decision-making with patients. Accordingly, the goal of this study was to develop a risk

model for operative mortality associated with MUV procedures within the STS Adult Cardiac Surgery

Database (STS-ACSD).

Methods

This study was approved by the Duke University Institutional Review Board.

Patient Population

The population consisted of 50,231 adult patients aged 20 to 100 years who underwent MUV surgery

in North America between January 1, 2004, and December 31, 2010. Data were collected using STS-ACSD

versions 2.52 and 2.61. Patients who received one of the following 3 MUV combinations were included:

aortic-mitral (AM; n=27,035), mitral-tricuspid (MT; n=18,686), and triple valve procedures (AMT;

n=4,510). Only 1,768 aortic-tricuspid procedures (AT) were recorded (180 deaths), and this group was

excluded because of insufficient sample size. Patients having concomitant coronary bypass grafting (CABG),

ventricular assist device, or arrhythmia surgery were included in the study. Patients having pulmonary valve

surgery, aortic root reconstruction, or repair of aortic dissection were excluded, as were patients who

underwent surgery for left ventricular aneurysm, ventricular or atrial septal defect, other congenital lesions,

the Batista procedure, surgical ventricular restoration, transmyocardial revascularization, cardiac trauma,

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cardiac transplant, aortic aneurysm, carotid endarterectomy, and other vascular, thoracic, or non-cardiac

procedures not listed on the data collection form. The final study population comprised 50,231 patient

operations from 970 STS participating provider groups (Appendix Table A).

Modeling Approach

MUV risk models were developed by clinicians and statisticians of the STS Quality Measurement

Task Force (QMTF). The endpoint was operative mortality, defined as: death during the same

hospitalization as surgery, regardless of timing or within 30 days of surgery regardless of venue. Because of

the large number of MUV patients in the STS-ACSD, sample sizes were adequate to develop separate

models for each of the 3 MUV categories. This decision was based on the concept that, when adequate

patients are available, relatively homogeneous categories produce models with better calibration and greater

face validity (4). For each type of MUV surgery, separate models were developed using only preoperative

variables (Preoperative models) and the combinations of preoperative and intraoperative variables

(Preoperative + Intraoperative models). Preoperative models included only those patient characteristics

present prior to the operation and are thus suitable for assessing STS ACSD participant performance.

Preoperative + Intraoperative models included additional information about discretionary aspects of the

procedure, such as arrhythmia ablation or valve repair versus replacement. Preoperative + Intraoperative

models allow risk estimates to be customized based on knowledge of the planned procedure. As noted in the

discussion section, readers are cautioned against using the Preoperative + Intraoperative model to estimate an

individual patient’s risk hypothetically under two different treatment options, as the observed difference in

risk may be partly explained by crossover or selection bias (7,8). As in previous models, all standard STS

candidate variables were assessed (www.sts.org), and multivariable logistic regression analyses were utilized

with stepwise forward selection of variables. The resulting models also included certain risk factors that were

forced into the models. Time trends were addressed by including surgery date as a candidate covariate. Lists

of candidate covariates and methods of modeling the continuous variables are given in Appendix Table B.

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Overall, 6 models were generated (3 valve populations x 2 models [Preoperative and Preoperative +

Intraoperative]). The 2004-2009 study period sample was used to develop the 6 models, which then were

validated with data from MUV patients operated during 2010. Model variables were selected by the QMTF

surgeon panel and initially included all important covariates from previous STS risk models (1-4). Decisions

were made after reviewing stepwise model selection, with the goal of significantly reducing the pool of

candidate predictors based on clinical knowledge. Missing data were rare and were imputed as described

previously (4). Multiple imputation was not used for these analyses because of the low rate of missing data

and because the method of imputation had minimal impact in previous STS risk model analyses.

Evaluation of Models

Calibration was assessed graphically by plotting observed versus predicted event rates within deciles

of predicted risk in the validation sample. Discrimination was evaluated by determining the c-statistic, also

known as the area under the receiver operating characteristic (ROC) curve. After choosing variables and

assessing model fit, development and validation samples subsequently were combined, and the final model

coefficients were estimated using the combined (development plus validation) data set.

Results

Baseline characteristics of the 3 populations are shown in Appendix Table A. Status at presentation

was non-elective in about 40% of cases. Patients requiring AM surgery were more often male and were more

likely to have coronary artery disease compared to other valve combinations. Two-thirds of all MUV patients

had congestive heart failure, and among those, nearly 80% were in NYHA Class III-IV. History of previous

valve surgery increased from AM to MT to AMT. Treated or active endocarditis was common (6-12%), with

the highest incidence in the AM group. Overall, about 80% of MUV patients had moderate to severe mitral

insufficiency, and 20% had mitral stenosis. Among patients undergoing tricuspid procedures, the incidence

of moderate to severe tricuspid insufficiency was more than 80%. Approximately 60% of AM and AMT

patients had aortic stenosis, and more than half had moderate to severe aortic insufficiency. Atrial fibrillation

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was present in half of MT and AMT patients, but only 30% of AM. Only about half of all MUV patients

with preoperative atrial fibrillation received ablation procedures. MT and AMT patients underwent CABG

less frequently (both about 29% versus 38% for AM; p<0.001). MT and AMT patients had tricuspid repairs

in 95% of cases, whereas repair procedures were performed in only 40-50% of patients undergoing mitral

surgery. Aortic valve repair was performed in about 2% of aortic valve cases. Average unadjusted operative

mortalities were: MT 7.6%, AM 9.4%, and AMT 13.1%.

Estimated odds ratios for Preoperative and Preoperative + Intraoperative models are shown in Table

1. The magnitude and ranking of risk factors were similar for all 3 procedural types, with emergency

presentation, advanced age, dialysis-dependent renal failure, reoperation, and endocarditis having the highest

odds ratios. Other important risk factors included female gender, insulin-dependent diabetes, severe chronic

lung disease, peripheral vascular disease, immunosuppression, and concomitant CABG. In the MT group,

recent myocardial infarction also was an important predictor. In Preoperative + Intraoperative models,

ablation procedures for atrial fibrillation were associated with reduced operative mortality in AM and AMT

subgroups, and replacement (versus repair) of mitral or tricuspid valves was associated with increased risk-

adjusted mortality in all 3 procedural categories (although few tricuspid replacement patients existed in this

more recent data set).

When the models fitted with the 2004-2009 developmental sample were validated with the 2010

cohort, each was well calibrated (Figure 1). The average absolute difference between observed versus

predicted death rates across the decile categories ranged from 1% for AM patients to 4% for AMT. A slight

tendency existed for the models to over-predict risk in the highest decile. In the validation sample, the c-

indices of the models ranged from 0.702 for AMT Preoperative to 0.727 for MT Preoperative +

Intraoperative. Individual c-indices are shown in Figure 1. Data from the full model for Preoperative and

Preoperative + Intraoperative analyses are given in Appendix Table C, and stepwise regression coefficients

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are shown in Appendix Table D. Finally, definitions of variables appearing in the final stepwise models are

given in Appendix Table E.

Discussion

The development of MUV surgery risk models was guided by several observations. First, MUV

mortality is more than twice that for single valve operations, and MUV cases contribute up to a third of total

deaths after valve surgery (5). Furthermore, although risk-adjusted mortalities for all valve procedures have

been progressively improving, MUV mortality rates are falling faster than those of single valves (5,6).

Because of the improving results, the present study was based on the most recent 6 years of available

procedures (2004-2010) and will provide surgeons and patients with the most contemporary estimates of

MUV risk. Finally, two types of models were developed, one of which used Preoperative variables only and

was thus appropriate for profiling. The other model type, containing both Preoperative + Intraoperative

variables, allowed more precise estimates of risk for a particular planned procedure on a specific patient.

Baseline patient characteristics are important determinants of outcome following valve surgery,

especially MUV procedures. Accounting for a particular provider’s distribution of patient risk factors is

critical in fairly assessing performance, since “expected” outcomes can vary widely depending on severity of

patient illness. In a previous study (6), observed STS operative mortality was less than 1% for single or

MUV cases with age < 65 years, elective presentation, and EF > 0.40. If only those 3 risk factors were

reversed (age > 65 years, urgent presentation, and EF < 0.40), single valve mortality increased to 10.7%, and

MUV mortality to 16.5%. If additional risk factors, such as renal failure and endocarditis, were involved (9,

10), “expected” mortalities could become quite high, and overall provider results could be impacted

significantly. These data emphasize the importance of risk models in evaluating outcomes with increasing

complexity of patient illness.

In this study, predictors of mortality were similar across MUV groups. Non-elective presentation was

strongly associated with mortality and has been shown in other reports to be increasing in frequency (5,11).

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Other important risk factors included advanced age, renal failure/dialysis, hemodynamic instability, and

reoperation. While studies have shown valve reoperation generally to be safe (12-14), reoperative valve

surgery (single or MUV) in the STS registry is associated with substantially increased risk. This finding

emphasizes the importance of designing MUV procedures that minimize the need for reoperation, such as

avoiding tissue valves in younger patients. In the AM and AMT Preoperative + Intraoperative models,

patients undergoing arrhythmia ablation procedures (15-17) had lower predicted mortality risk than patients

not receiving these procedures. Similarly, patients undergoing repair instead of replacement of the mitral or

tricuspid valves had lower predicted risk than patients undergoing valve replacement. Because of undefined

treatment selection biases and possible confounding variables, these data should be interpretted with caution

at this time, pending future research. However, these results are consistent with previous studies showing

improved results with repair of mitral, tricuspid, and aortic valves (18-21), and preliminary reports of repair

of all valves during MUV are showing low operative mortality (22-24). Further investigations of MUV

repair procedures seem indicated, perhaps involving examination of subgroups and linked data registries (25)

to assess longer-term outcomes.

Limitations

All risk models are imperfect representations of reality. Although STS risk models are based on

excellent data and large sample sizes, unmeasured confounding variables and treatment selection biases can

be present and may degrade the accuracy of risk estimates for some patients. Within the STS-ACSD,

participation remains voluntary, and the possibility exists that higher performing hospitals were more likely

to participate during earlier years. However, as the percentage of participating hospitals in North America

now approaches 95%, this consideration is less relevant. The risk models developed in this paper can be

useful for informing patients about surgical risk, but a proper interpretation is paramount. Predicted risk

estimates should be viewed as statistical averages derived from historical populations of patients with similar

measured risk factors undergoing similar procedures. An individual’s true risk may differ from the statistical

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estimate, because of individual-specific factors not included in the statistical model. Readers are cautioned

against using the Preoperative + Intraoperative model to estimate an individual patient’s risk hypothetically

under two different treatment options. Because treatments were not randomized, the apparent difference in

risk for two treatments may reflect differences in unmeasured risk factors not included in the statistical

model.

Conclusions

Six new STS risk models were developed for operative mortality after MUV surgery, and the models

were well calibrated with acceptable discrimination. Models containing only preoperative variables were

estimated for profiling, and separate models including both preoperative variables and discretionary

intraoperative factors (e.g., valve repair vs replacement, atrial ablation vs no ablation) were developed that

provided more tailored estimates of mortality based on the specific planned procedure. Information derived

from these models may be useful for accreditation, regulatory compliance, reimbursement, selective

referrals, quality improvement, clinical research, and patient counseling.

References

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6. Vassileva CM, Li S, O’Brien SM, et al. Outcome characteristics of multiple valve surgery: Comparison to

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dysfunction on isolated aortic and mitral valve surgery: A propensity score analysis. J Thorac Cardiovasc

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Valve Dis 2009;18:256-261.

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17. Lee R, McCarthy PM, Wang EC, et al. Mid-term survival in patients treated for atrial fibrillation: A

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with combined aortic and mitral valve replacement. Ann Thorac Surg 2007;84:1219-1225.

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superior to double valve replacement. J Thorac Cardiovasc Surg 2003;125:1372-1387.

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The Society of Thoracic Surgeons adult cardiac surgery database. Ann Thorac Surg2009;87:1431-1437.

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Society of Heart Valve Disease meeting, Barcelona, Spain, June 2011, JHVD, submitted.

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http://www.jsrmd.com/ftp/70_TRMUVR.ppt

24. Vohra H, Whistance R, De Kerchove L, et al. Long-term outcome of valve repair for concomitant aortic

and mitral insufficiency: Setting a new standard of care. Abstract presented at the European Association for

Cardio-Thoracic Surgery meeting, Barcelona Spain, October 2012, EJCTS, submitted.

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Appendix Table A. Distribution of Risk Factors, Operative Factors, and Mortality Outcomes in AM, MT and AMT Study Population, (2004-2010) AM MT AMT (n = 27,035) (n = 18,686) (n = 4,510)

Variable n % n % n % Demographics

Age, years <50 2767 10.2 2026 10.8 463 10.3 50 – 59 3837 14.2 2769 14.8 619 13.7 60 – 69 6310 23.3 4506 24.1 996 22.1 ≥70 14121 52.2 9385 50.2 2432 53.9

Median Age, years (25th, 75th)

70 (60, 78) 70 ( 59,

77) 71

70 (59, 77) 71 (60, 78) Sex Male 15058 55.7 6853 36.7 1892 42.0 Female 11974 44.3 11832 63.3 2615 58.0 Missing 3 0.0 1 0.0 3 0.1 Race/Ethnicity Caucasian 22165 82.0 14192 75.9 3532 78.3 Black 2306 8.5 2533 13.6 485 10.8 Hispanic 1227 4.5 853 4.6 209 4.6 Asian 528 2.0 486 2.6 132 2.9 Other 703 2.6 560 3.0 138 3.1 Missing 106 0.4 62 0.3 14 0.3 Risk Factors Body Surface Area (BSA), m2 <1.50 1166 4.3 1037 5.5 241 5.3 1.50 – 1.74 6272 23.2 5649 30.2 1344 29.8 1.75 – 1.99 10465 38.7 6986 37.4 1746 38.7 ≥2.00 9059 33.5 4959 26.5 1165 25.8 Missing 73 0.3 55 0.3 14 0.3 Diabetes No Diabetes 19858 73.5 13871 74.2 3340 74.1 Diabetes, noninsulin 4893 18.1 3154 16.9 788 17.5 Diabetes, insulin 2221 8.2 1602 8.6 369 8.2 Diabetes, other treatment 8 0.0 5 0.0 2 0.0 Diabetes, missing Treatment 25 0.1 29 0.2 7 0.2 Missing 30 0.1 25 0.1 4 0.1 Hypertension No 7048 26.1 5041 27.0 1291 28.6 Yes 19962 73.8 13627 72.9 3217 71.3 Missing 25 0.1 18 0.1 2 0.0 Renal Function Creatinine <1.00 mg/dL 9018 33.4 6463 34.6 1435 31.8 Creatinine 1.00 – 1.49 mg/dL 12543 46.4 8300 44.4 1999 44.3

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AM MT AMT (n = 27,035) (n = 18,686) (n = 4,510)

Variable n % n % n % Creatinine 1.50 – 2.00 mg/dL 2896 10.7 2090 11.2 536 11.9 Creatinine 2.00 – 2.50 mg/dL 677 2.5 575 3.1 159 3.5 Creatinine ≥2.5 mg/dL 467 1.7 347 1.9 90 2.0 Dialysis 1309 4.8 838 4.5 272 6.0 Missing 125 0.5 73 0.4 19 0.4 Chronic Lung Disease (CLD) None 19444 71.9 13350 71.4 3259 72.3 Mild 3808 14.1 2618 14.0 602 13.3 Moderate 2180 8.1 1509 8.1 376 8.3 Severe 1473 5.4 1117 6.0 254 5.6 Missing 130 0.5 92 0.5 19 0.4 Peripheral Vascular Disease (PVD) No 23704 87.7 16733 89.5 3987 88.4 Yes 3290 12.2 1922 10.3 519 11.5 Missing 41 0.2 31 0.2 4 0.1 Cerebrovascular Disease (CVD) No 22285 82.4 15682 83.9 3721 82.5 Yes 4714 17.4 2973 15.9 784 17.4 Missing 36 0.1 31 0.2 5 0.1 Cerebrovascular Accident (CVA) No CVA 24372 90.1 16891 90.4 4047 89.7 Remote CVA (> 2 weeks) 2341 8.7 1659 8.9 424 9.4 Recent CVA (≤ 2 weeks) 230 0.9 73 0.4 28 0.6 CVA - Missing Timing 17 0.1 9 0.0 4 0.1 Missing 75 0.3 54 0.3 7 0.2 Endocarditis No Endocarditis 23750 87.8 17637 94.4 4099 90.9 Treated Endocarditis 1284 4.7 529 2.8 199 4.4 Active Endocarditis 1945 7.2 473 2.5 202 4.5 Endocarditis - Missing Type 17 0.1 6 0.0 3 0.1 Missing 39 0.1 41 0.2 7 0.2 Immunosuppressive Treatment No 25763 95.3 17959 96.1 4296 95.3 Yes 1223 4.5 688 3.7 206 4.6 Missing 49 0.2 39 0.2 8 0.2 Previous Cardiovascular Interventions Previous Coronary Artery BypassSurgery No 24260 89.7 16394 87.7 3960 87.8 Yes 2713 10.0 2235 12.0 537 11.9 Missing 62 0.2 57 0.3 13 0.3 Previous Valve Surgery No 24403 90.3 15739 84.2 3712 82.3

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AM MT AMT (n = 27,035) (n = 18,686) (n = 4,510)

Variable n % n % n % Yes 2589 9.6 2912 15.6 790 17.5 Missing 43 0.2 35 0.2 8 0.2 Previous Other Cardiac Surgery No 26055 96.4 17574 94.0 4273 94.7 Yes 928 3.4 1062 5.7 232 5.1 Missing 52 0.2 50 0.3 5 0.1 Number of Previous CV Surgeries No Previous CV surgery 22156 82.0 13905 74.4 3295 73.1 1 Prior CV surgery 4226 15.6 4062 21.7 1002 22.2 2 Or More Prior CV Surgeries 600 2.2 689 3.7 209 4.6 Missing 53 0.2 30 0.2 4 0.1 Prior Percutaneous Coronary Interventions(PCI) No PCI 17476 64.6 12696 67.9 3090 68.5 PCI - within 6 hours 22 0.1 25 0.1 4 0.1 PCI - not within 6 hours 3446 12.7 2220 11.9 516 11.4 PCI - missing timing 21 0.1 12 0.1 3 0.1 Missing 6070 22.5 3733 20.0 897 19.9 PreoperativeCardiac Status Acuity Status Elective 16617 61.5 11827 63.3 2724 60.4 Urgent 9857 36.5 6548 35.0 1713 38.0 Emergent 498 1.8 273 1.5 65 1.4 Emergent Salvage 44 0.2 24 0.1 3 0.1 Missing 19 0.1 14 0.1 5 0.1 Myocardial Infarction (MI) No Prior MI 22073 81.6 15332 82.1 3841 85.2 MI >21 days 3305 12.2 2437 13.0 505 11.2 MI 8 – 21 days 481 1.8 273 1.5 54 1.2 MI 1 – 7 days 976 3.6 518 2.8 83 1.8 MI > 6 and < 24 hours 82 0.3 49 0.3 6 0.1 MI ≤ 6 hours 35 0.1 14 0.1 5 0.1 MI - Missing Timing 32 0.1 18 0.1 7 0.2 Missing 51 0.2 45 0.2 9 0.2 Angina No 19500 72.1 14513 77.7 3497 77.5 Yes 7123 26.3 3841 20.6 949 21.0 Missing 412 1.5 332 1.8 64 1.4 Cardiogenic Shock No 26487 98.0 18263 97.7 4417 97.9 Yes 513 1.9 393 2.1 84 1.9 Missing 35 0.1 30 0.2 9 0.2 Resuscitation

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AM MT AMT (n = 27,035) (n = 18,686) (n = 4,510)

Variable n % n % n % No 26820 99.2 18543 99.2 4478 99.3 Yes 166 0.6 101 0.5 21 0.5 Missing 49 0.2 42 0.2 11 0.2 Arrhythmia No Arrhythmia 17321 64.1 7436 39.8 1937 42.9 Atrial Fibrillation/Flutter 8117 30.0 9980 53.4 2277 50.5 Heart Block 363 1.3 167 0.9 50 1.1 Sustained Ventricular Tachycardia or Ventricular Fibrillation

272 1.0 180 1.0 50 1.1

Multiple Types 141 0.5 143 0.8 37 0.8 Arrhythmia - None of Above Types 690 2.6 709 3.8 144 3.2 Arrhythmia - Missing Type 89 0.3 41 0.2 9 0.2 Missing 42 0.2 30 0.2 6 0.1 PreoperativeIntra-Aortic Balloon Pump (IABP)

No 26507 98.0 18023 96.5 4427 98.2 Yes 495 1.8 634 3.4 81 1.8 Missing 33 0.1 29 0.2 2 0.0 Congestive Heart Failure (CHF) No 11001 40.7 6260 33.5 1366 30.3 Yes 16000 59.2 12401 66.4 3142 69.7 Missing 34 0.1 25 0.1 2 0.0 New York Heart Association Class (%CHF) I 531 3.3 353 2.8 81 2.6 II 3135 19.6 2296 18.5 507 16.1 III 7457 46.6 6029 48.6 1522 48.4 IV 4550 28.4 3479 28.1 980 31.2 Missing 327 2.0 244 2.0 52 1.7 Number of Diseased Coronary Vessels None 13989 51.7 11011 58.9 2625 58.2 One 4430 16.4 2521 13.5 718 15.9 Two 3442 12.7 1881 10.1 462 10.2 Three 4963 18.4 3105 16.6 671 14.9 Missing 211 0.8 168 0.9 34 0.8 Left Main Disease ≥ 50% No 24941 92.3 17454 93.4 4233 93.9 Yes 1870 6.9 1071 5.7 238 5.3 Missing 224 0.8 161 0.9 39 0.9 Ejection Fraction, % <25 1175 4.3 1018 5.4 236 5.2 25 – 34 2580 9.5 1754 9.4 413 9.2 35 – 44 3808 14.1 2601 13.9 663 14.7 45 – 54 5380 19.9 3931 21.0 926 20.5 ≥ 55 12776 47.3 8616 46.1 2085 46.2

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AM MT AMT (n = 27,035) (n = 18,686) (n = 4,510)

Variable n % n % n % Missing 1316 4.9 766 4.1 187 4.1 Aortic Stenosis No 10018 37.1 17864 95.6 1797 39.8 Yes 16884 62.5 623 3.3 2695 59.8 Missing 133 0.5 199 1.1 18 0.4 Mitral Stenosis No 20772 76.8 15005 80.3 3279 72.7 Yes 6067 22.4 3478 18.6 1203 26.7 Missing 196 0.7 203 1.1 28 0.6 Aortic Insufficiency None 6147 22.7 11814 63.2 834 18.5 Trivial 1905 7.0 2535 13.6 302 6.7 Mild 4493 16.6 2633 14.1 749 16.6 Moderate 6680 24.7 662 3.5 1358 30.1 Severe 7009 25.9 89 0.5 1165 25.8 N/A 616 2.3 748 4.0 81 1.8 Missing 185 0.7 205 1.1 21 0.5 Mitral Insufficiency None 2209 8.2 793 4.2 254 5.6 Trivial 693 2.6 243 1.3 99 2.2 Mild 2880 10.7 781 4.2 378 8.4 Moderate 8508 31.5 3165 16.9 1294 28.7 Severe 12314 45.5 13511 72.3 2438 54.1 N/A 333 1.2 129 0.7 39 0.9 Missing 98 0.4 64 0.3 8 0.2 Tricuspid Insufficiency None 12325 45.6 1518 8.1 342 7.6 Trivial 2768 10.2 238 1.3 74 1.6 Mild 5995 22.2 1495 8.0 429 9.5 Moderate 3600 13.3 6679 35.7 1634 36.2 Severe 730 2.7 8400 45.0 1961 43.5 N/A 1295 4.8 269 1.4 54 1.2 Missing 322 1.2 87 0.5 16 0.4 Operative Concomitant CABG Surgery No 16700 61.8 13341 71.4 3177 70.4 Yes 10319 38.2 5333 28.5 1332 29.5 Missing 16 0.1 12 0.1 1 0.0 Aortic Procedure No 0 0.0 18597 99.5 0 0.0 Replacement 26455 97.9 0 0.0 4389 97.3 Repair/Reconstruction 549 2.0 0 0.0 118 2.6

17

AM MT AMT (n = 27,035) (n = 18,686) (n = 4,510)

Variable n % n % n % Resuspension of Aortic Valve without replacement of ascending Aorta

31 0.1 0 0.0 3 0.1

Missing 0 0.0 89 0.5 0 0.0 Mitral Procedure Annuloplasty Only 7584 28.1 5072 27.1 1237 27.4 Replacement 14628 54.1 9517 50.9 2704 60.0 Reconstruction with Annuloplasty 3358 12.4 3860 20.7 467 10.4 Reconstruction without Annuloplasty 1465 5.4 237 1.3 102 2.3 Tricuspid Procedure No 26871 99.4 0 0.0 0 0.0 Annuloplasty Only 0 0.0 13575 72.6 3308 73.3 Replacement 0 0.0 899 4.8 211 4.7 Reconstruction with Annuloplasty 0 0.0 3028 16.2 613 13.6 Reconstruction without Annuloplasty 0 0.0 1180 6.3 376 8.3 Valvectomy 0 0.0 4 0.0 2 0.0 Missing 164 0.6 0 0.0 0 0.0 Atrial Fibrillation Correction Surgery None 22887 84.7 12369 66.2 3343 74.1 Standard Surgical Maze Procedure 901 3.3 1257 6.7 255 5.7 Other Surgical Ablative Procedure 2200 8.1 3248 17.4 573 12.7 Combination of Standard and Other Procedures 965 3.6 1757 9.4 323 7.2 Missing 82 0.3 55 0.3 16 0.4 Outcome Operative Mortality No 24490 90.6 17262 92.4 3917 86.9 Yes 2545 9.4 1424 7.6 593 13.1

18

Appendix Table B. Candidate Variables and Coding Preop Preop + Intraop

AM MT AMT AM MT AMT

Age ü1 ü1 ü2 ü1 ü1 ü2

Ejection fraction3 ü ü ü ü ü ü

Creatinine4 ü5 ü5 ü6 ü5 ü5 ü6

Number of prior CV operations (0, 1, 2 or more) ü ü ü ü ü ü

Date of surgery ü7 ü7 ü7 ü7 ü7 ü7

Dialysis ü ü ü ü ü ü

Concomitant CABG ü ü ü ü ü ü

CHF (yes, NYHA IV; yes, not NYHA IV; no) ü ü ü ü ü ü

Diabetes (yes, insulin; yes, non-‐insulin; no) ü ü ü ü ü ü

Preoperative IABP or inotropes ü ü ü ü ü ü

Active Infections endocarditis ü ü ü ü ü ü

Aortic insufficiency (at least moderate) ü ü ü ü ü ü

Mitral insufficiency (at least moderate) ü ü ü ü ü ü

Tricuspid insufficiency (at least moderate) ü ü ü ü ü ü

Aortic stenosis ü ü ü ü ü ü

Mitral stenosis ü ü ü ü ü ü

Peripheral vascular disease ü ü ü ü ü ü

Body surface area8 ü ü ü ü ü ü

Chronic lung disease (none, mild, moderate, severe) ü ü ü9 ü ü ü9

Interaction of sex and body surface area ü ü ü ü

Interaction of age and prior CV operations ü ü ü ü

Interaction of age and emergent status ü ü ü ü

19

Immunosuppressive treatment ü ü ü ü

Prior MI (>21 days, 1-‐21 days, >6 and <24 hours, ≤6 hours, none) ü ü ü ü

Cerebrovascular disease (yes, prior CVA; yes, no prior CVA; no) ü ü ü ü

Race/ethnicity (Black; Hispanic; Asian; White/Other) ü ü ü ü

Hypertension ü ü ü ü

PCI within 6 hours ü ü ü ü

Left main disease ü ü ü ü

Number of diseased vessels10 ü ü ü ü

Unstable angina without recent MI within 7 days ü ü ü ü

Female sex ü ü ü ü

Cardiogenic shock ü ü ü ü

Status (elective, urgent, emergent, salvage) ü ü ü ü

Status/Shock (elective; urgent; emergent or salvage or shock) ü ü

Atrial fibrillation ü ü ü

Atrial fibrillation/ablation (afib, ablation; afib, no ablation procedure; no afib) ü ü ü

Type of aortic procedure (repair, replacement) ü ü

Type of mitral procedure (repair, replacement) ü ü ü

Type of tricuspid procedure (repair, replacement) ü ü

Interaction of types of aortic and mitral procedures (repair, replacement) ü

Interaction of types of mitral and tricuspid procedures (repair, replacement) ü

(1) Modeled as piecewise-‐linear with possible slope changes at 50 and 70. (2) Modeled as linear. Values < 40 and > 85 are mapped to those values, respectively. (3) Modeled as linear. Values > 50 are mapped to 50. (4) Values <0.5 and >5.0 are mapped to those values, respectively. Creatinine is set to 2.5 for patients on dialysis. (5) Modeled as piecewise-‐linear with possible slope changes at 1.0 and 1.5. (6) Modeled as linear. (7) Number of days since start of study period; linear. (8) Modeled as quadratic polynomial. Values < 1.4 and > 2.6 are mapped to those values, respectively. All values are then centered by subtracting 1.8 from values after mapping. (9) ‘None’ and ‘mild’ are collapsed as the reference level. (10) Linear with values: 1 = zero or one diseased vessel, 2 = two diseased vessels, and 3 = three diseased vessels Afib = preoperative atrial fibrillation; AM = aortic-‐mitral; AMT = aortic-‐mitral-‐tricuspid; CHF = congestive heart failure; CV = cardiovascular; CVA = cerebrovascular accident (stroke); CVD = cerebrovascular disease; EF = ejection fraction; IABP = intra-‐aortic balloon pump; MI = myocardial infarction; MT = mitral-‐tricuspid; NYHA = New York Heat Association.

20

Table 1: Estimated Odds Ratios for Final Stepwise Models in AM, MT and AMT Populations

Variable AM Preop MT Preop AMT Preop AM

Preop+Intraop MT

Preop+Intraop AMT

Preop+Intraop

EF, per 10 percent decrease NS 1.08 (1.01, 1.15) NS NS 1.11 (1.04, 1.19) NS

CHF and NYHA class (versus no CHF)

CHF, not NYHA IV 1.14 (1.02, 1.27) (ref) (ref) 1.13 (1.01, 1.26) (ref) (ref)

CHF, NYHA IV 1.75 (1.51, 2.01) 1.56 (1.33, 1.83) 1.72 (1.35, 2.18) 1.72 (1.50, 1.98) 1.55 (1.33, 1.81) 1.69 (1.33, 2.14)

Age, yearsa

60 versus 50 1.38 (1.31, 1.46) 1.39 (1.30, 1.50) 1.19 (1.09, 1.30) 1.40 (1.32, 1.47) 1.34 (1.27, 1.43) 1.23 (1.13, 1.34)

70 versus 50 1.90 (1.70, 2.12) 1.94 (1.68, 2.25) 1.42 (1.19, 1.69) 1.95 (1.75, 2.18) 1.81 (1.60, 2.03) 1.51 (1.27, 1.79)

80 versus 50 2.62 (2.22, 3.09) 2.71 (2.17, 3.38) 1.69 (1.30, 2.20) 2.72 (2.31, 3.21) 2.43 (2.03, 2.90) 1.85 (1.43, 2.39)

Dialysis and creatinine

Creatinine 1.50 versus 1.00 1.60 (1.41, 1.82) 1.65 (1.45, 1.88) 1.30 (1.20, 1.39) 1.60 (1.40, 1.82) 1.62 (1.43, 1.84) 1.30 (1.20, 1.40)



Dialysis versus no dialysis and creatinine = 2.50 1.46 (1.22, 1.75) 1.75 (1.37, 2.23) NS 1.43 (1.19, 1.73) 1.70 (1.33, 2.16) NS

Status (versus elective)

Urgent 1.09 (0.98, 1.22) 1.41 (1.21, 1.65) 1.23 (1.01, 1.48) 1.09 (0.98, 1.21) 1.37 (1.17, 1.60) 1.22 (1.01, 1.48)

Emergent 2.05 (1.50, 2.78) 2.68 (1.87, 3.84)c NC 2.03 (1.50, 2.76) 2.60 (1.82, 3.71)c NC

Salvage 3.91 (2.21, 6.91) 2.68 (1.87, 3.84)c NC 3.88 (2.18, 6.91) 2.60 (1.82, 3.71)c NC

Emergent/Salvage/Shock NC NC 2.64 (1.65, 4.24) NC NC 2.62 (1.65, 4.18)

Female (at BSA=1.8m2) versus Male (at BSA=2.0m2) 1.58 (1.44, 1.72) NS NC 1.53 (1.40, 1.66) NS NC

Concomitant CABG procedure 1.54 (1.40, 1.70) 1.33 (1.16, 1.51) 1.48 (1.23, 1.77) 1.56 (1.42, 1.71) 1.34 (1.17, 1.53) 1.51 (1.26, 1.81)

Reoperation (versus no previous CV operation)b 2.22 (1.78, 2.76) 2.04 (1.58, 2.64) 1.52 (1.25, 1.84) 2.20 (1.77, 2.74) 1.48 (1.29, 1.71) 1.45 (1.19, 1.77)

Chronic lung disease (versus none)

Mild-Moderate 1.14 (1.02, 1.27) (ref) (ref) 1.14 (1.03, 1.27) (ref) (ref)

Severe 1.60 (1.35, 1.90) 1.41 (1.16, 1.71) 1.58 (1.15, 2.18) 1.60 (1.35, 1.89) 1.42 (1.17, 1.72) 1.54 (1.11, 2.12)

21


Preop+Intraop MT

Preop+Intraop AMT

Preop+Intraop

Diabetes (versus no diabetes)

Diabetes, non-insulin 1.13 (1.01, 1.27) 1.26 (1.10, 1.43)c (ref) 1.15 (1.02, 1.28) 1.26 (1.11, 1.43)c (ref)

Diabetes, insulin 1.44 (1.24, 1.66) 1.26 (1.10, 1.43)c 1.53 (1.14, 2.06) 1.43 (1.24, 1.65) 1.26 (1.11, 1.43)c 1.52 (1.13, 2.04)

Pre-op IABP or inotrope 1.61 (1.37, 1.90) 1.34 (1.10, 1.63) NS 1.61 (1.37, 1.89) NS NS

Immunosuppressive treatment 1.48 (1.24, 1.76) 1.43 (1.13, 1.82) NC 1.47 (1.23, 1.76) 1.45 (1.14, 1.83) NC

Active Infections endocarditis 1.95 (1.63, 2.33) NS NS 1.77 (1.48, 2.11) NS NS

Aortic insufficiency (≥ moderate) 0.92 (0.83, 1.01) 1.31 (1.02, 1.69) NS 0.92 (0.84, 1.02) 1.29 (0.99, 1.66) NS

Mitral insufficiency (≥ moderate) NS 0.79 (0.66, 0.95) NS NS 0.79 (0.66, 0.93) NS

Tricuspid insufficiency (≥ moderate) 1.19 (1.06, 1.34) NS NS 1.19 (1.06, 1.34) NS NS

Aortic stenosis 1.21 (1.08, 1.36) NS NS 1.25 (1.12, 1.39) NS NS

Mitral stenosis 1.31 (1.19, 1.45) 1.25 (1.06, 1.46) NS NS NS NS

Peripheral vascular disease 1.27 (1.13, 1.44) 1.24 (1.05, 1.47) NS 1.28 (1.13, 1.45) 1.23 (1.04, 1.45) NS

MI (vs. MI > 21 days or no MI)

1-21 days 1.25 (1.07, 1.46)c (ref) NC 1.29 (1.10, 1.51)c 1.37 (1.11, 1.71) NC

< 1 day 1.25 (1.07, 1.46)c 2.71 (1.41, 5.22) NC 1.29 (1.10, 1.51)c 3.06 (1.58, 5.93) NC

BSA, m2

1.6 versus 2.0 in male 1.44 (1.24, 1.67) 1.51 (1.34, 1.69) NS 1.43 (1.23, 1.66) 1.48 (1.32, 1.66) NS



1.6 versus 1.8 in female 1.12 (1.05, 1.20) 1.32 (1.22, 1.42) NS 1.12 (1.04, 1.19) 1.30 (1.21, 1.40) NS



Surgery date, per half-year increase 0.98 (0.97, 0.99) 0.97 (0.96, 0.99) NS 0.98 (0.97, 0.99) 0.97 (0.96, 0.99) NS

CVD (versus No CVD) NS 1.28 (1.11, 1.49) NC NS 1.28 (1.11, 1.49) NC

Cardiogenic shock NS 1.67 (1.23, 2.27) NC NS 1.81 (1.36, 2.42) NC

22


Preop+Intraop MT

Preop+Intraop AMT

Preop+Intraop

Expanded Covariates:

Afib ablation (in patients with preop afib)d NC NC NC 0.85 (0.73, 0.98) NS 0.77 (0.60, 0.99)

Aortic and mitral procedures

Both valves replaced (versus at least 1 repair) NC NC NC 1.68 (1.52, 1.86) NC NC

Mitral and tricuspid procedures (versus repair, repair)

Mitral repair, tricuspid replacement NC NC NC NC 1.60 (1.25, 2.05) NC

Mitral replacement, tricuspid repair NC NC NC NC 1.45 (1.26, 1.67) NC

Mitral replacement, tricuspid replacement NC NC NC NC 2.32 (1.73, 3.11) NC

Mitral procedure (versus repair)

Mitral replacement NC NC NC NC NC 1.41 (1.16, 1.71) Interaction in both AM models and MT preop model not shown in the table: age and any reoperation. aReported odds ratio for age represents effect in patients without prior operations, in models with interaction between age and any reoperation. bReported odds ratio for reoperation represents effect in patients 50 years old, in models with interaction between age and any reoperation. cOdds ratios for two adjacent categories are identical because categories were collapsed during model development dThe afib/ablation variable is modeled as 3 categories (afib, ablation; afib, no ablation procedure; no afib) and the first 2 categories were collapsed during selection and so the reported odds ratio is also the OR for afib with ablation vs. no afib. (ref) indicates subgroup is merged into the reference level during model development Afib = preoperative atrial fibrillation; AM = aortic-mitral; BSA = body surface area; AMT = aortic-mitral-tricuspid; CHF = congestive heart failure; CV = cardiovascular; CVD = cerebrovascular disease; EF = ejection fraction; IABP = intra-aortic balloon pump; MI = myocardial infarction; MT = mitral-tricuspid; NC = not a candidate; NS = not selected in the model; NYHA = New York Heat Association.

23

Appendix Table C: Estimated Odds Ratios for Mortality from Full Models in AM, MT and AMT populations


Preop+Intraop MT

Preop+Intraop AMT

Preop+Intraop

EF, per 10 percent decrease 0.97 (0.92, 1.03) 1.07 (1.00, 1.15) 0.91 (0.82, 1.02) 1.01 (0.95, 1.07) 1.10 (1.03, 1.19) 0.94 (0.84, 1.04)

Unstable angina and no recent MI (≤ 7 days) 1.08 (0.92, 1.27) 1.07 (0.85, 1.36) NC 1.09 (0.93, 1.28) 1.10 (0.87, 1.39) NC

CHF and NYHA class (versus no CHF)

CHF, not NYHA IV 1.14 (1.02, 1.28) 1.17 (0.98, 1.40) 1.20 (0.96, 1.51) 1.12 (1.00, 1.26) 1.15 (0.96, 1.37) 1.19 (0.94, 1.49)

CHF, NYHA IV 1.73 (1.49, 2.00) 1.70 (1.38, 2.10) 1.97 (1.50, 2.60) 1.68 (1.45, 1.94) 1.65 (1.34, 2.03) 1.91 (1.46, 2.51)

Agea

60 versus 50 1.28 (1.14, 1.43) 1.29 (1.14, 1.47) 1.21 (1.11, 1.33) 1.30 (1.16, 1.45) 1.31 (1.15, 1.49) 1.23 (1.13, 1.35)

70 versus 50 1.63 (1.31, 2.04) 1.67 (1.29, 2.16) 1.47 (1.23, 1.77) 1.68 (1.34, 2.10) 1.72 (1.33, 2.22) 1.52 (1.27, 1.81)

80 versus 50 2.43 (1.98, 2.97) 2.61 (2.03, 3.37) 1.79 (1.36, 2.35) 2.53 (2.06, 3.11) 2.66 (2.06, 3.43) 1.87 (1.43, 2.44)

Dialysis and creatinine




Dialysis versus no dialysis, creatinine = 2.50 1.44 (1.20, 1.73) 1.72 (1.35, 2.20) 1.16 (0.80, 1.68) 1.41 (1.17, 1.70) 1.71 (1.34, 2.19) 1.17 (0.81, 1.70)

Status (versus elective)b

Urgent 1.08 (0.97, 1.21) 1.33 (1.13, 1.56) 1.18 (0.97, 1.44) 1.07 (0.96, 1.20) 1.30 (1.10, 1.53) 1.16 (0.95, 1.41)

Emergent 2.14 (1.37, 3.35) 2.63 (1.50, 4.61) NC 2.08 (1.32, 3.26) 2.49 (1.41, 4.38) NC

Salvage 3.72 (1.91, 7.26) 4.74 (2.11,10.68) NC 3.60 (1.83, 7.10) 4.39 (1.96, 9.86) NC

Emergent/Salvage/Shock NC NC 2.37 (1.45, 3.87) NC NC 2.31 (1.41, 3.78)

Female (at BSA=1.8m2) versus Male (at BSA=2.0m2)

1.61 (1.44, 1.80) 1.22 (1.04, 1.43) NC 1.56 (1.39, 1.75) 1.21 (1.03, 1.42) NC

Concomitant CABG procedure 1.48 (1.32, 1.66) 1.23 (1.05, 1.42) 1.55 (1.30, 1.86) 1.48 (1.32, 1.66) 1.25 (1.07, 1.45) 1.58 (1.32, 1.90)

Reoperation (versus no previous CV operation)c

24


Preop+Intraop MT

Preop+Intraop AMT

Preop+Intraop

1 previous operation 2.14 (1.71, 2.68) 1.97 (1.51, 2.56) 1.45 (1.17, 1.79) 2.10 (1.68, 2.63) 1.79 (1.37, 2.33) 1.37 (1.10, 1.71)

2 or more previous operations 2.60 (1.93, 3.51) 2.18 (1.59, 3.00) 1.56 (1.10, 2.21) 2.55 (1.88, 3.45) 1.89 (1.36, 2.62) 1.45 (1.02, 2.04)

Chronic lung disease (versus none)

Mild 1.14 (1.01, 1.29) 1.02 (0.84, 1.23) (ref) 1.14 (1.01, 1.29) 1.01 (0.83, 1.22) (ref)

Moderate 1.15 (0.98, 1.34) 1.23 (0.99, 1.52) 1.28 (0.94, 1.73) 1.15 (0.98, 1.35) 1.20 (0.97, 1.50) 1.26 (0.93, 1.71)

Severe 1.62 (1.37, 1.93) 1.45 (1.19, 1.77) 1.61 (1.16, 2.23) 1.61 (1.36, 1.91) 1.44 (1.18, 1.75) 1.57 (1.14, 2.18)

Diabetes (versus no diabetes)

Diabetes, non-insulin 1.13 (1.01, 1.26) 1.12 (0.96, 1.31) 1.06 (0.83, 1.34) 1.13 (1.01, 1.27) 1.12 (0.96, 1.30) 1.05 (0.83, 1.33)

Diabetes, insulin 1.43 (1.24, 1.65) 1.37 (1.13, 1.66) 1.53 (1.14, 2.06) 1.42 (1.23, 1.64) 1.38 (1.14, 1.67) 1.52 (1.12, 2.06)

Pre-op IABP or Inotrope 1.54 (1.29, 1.83) 1.31 (1.08, 1.60) 1.18 (0.82, 1.70) 1.52 (1.28, 1.81) 1.28 (1.05, 1.56) 1.17 (0.81, 1.69)

Immunosuppressive treatment 1.49 (1.24, 1.78) 1.39 (1.09, 1.76) NC 1.47 (1.23, 1.77) 1.41 (1.11, 1.78) NC

Active Infections endocarditis 1.94 (1.62, 2.33) 1.36 (0.99, 1.87) 1.20 (0.79, 1.81) 1.82 (1.52, 2.19) 1.23 (0.90, 1.69) 1.14 (0.75, 1.74)

Aortic insufficiency (≥ moderate) 0.93 (0.84, 1.02) 1.31 (1.02, 1.68) 0.84 (0.69, 1.03) 0.93 (0.85, 1.03) 1.28 (1.00, 1.65) 0.84 (0.68, 1.03)

Mitral insufficiency (≥ moderate) 0.98 (0.88, 1.09) 0.80 (0.67, 0.96) 0.86 (0.66, 1.11) 0.96 (0.86, 1.07) 0.82 (0.69, 0.99) 0.86 (0.66, 1.12)

Tricuspid insufficiency (≥ moderate) 1.19 (1.06, 1.34) 1.01 (0.87, 1.17) 0.99 (0.78, 1.26) 1.19 (1.06, 1.34) 1.02 (0.87, 1.18) 1.00 (0.78, 1.27)

Aortic stenosis 1.22 (1.09, 1.36) 1.18 (0.90, 1.55) 0.94 (0.75, 1.18) 1.23 (1.11, 1.38) 1.14 (0.87, 1.50) 0.95 (0.75, 1.20)

Mitral stenosis 1.31 (1.18, 1.45) 1.25 (1.06, 1.47) 1.15 (0.93, 1.43) 1.10 (0.98, 1.23) 1.12 (0.94, 1.33) 1.04 (0.83, 1.31)

Peripheral vascular disease 1.27 (1.12, 1.44) 1.20 (1.02, 1.43) 1.07 (0.82, 1.39) 1.28 (1.12, 1.45) 1.20 (1.01, 1.42) 1.07 (0.82, 1.39)

MI (versus MI > 21 days or no MI)

1-21 days 1.21 (1.03, 1.42) 1.27 (1.02, 1.59) NC 1.23 (1.05, 1.46) 1.30 (1.04, 1.63) NC

> 6 and <24 hrs 1.75 (1.04, 2.94) 3.62 (1.68, 7.80) NC 1.79 (1.07, 2.99) 3.76 (1.74, 8.12) NC

≤6 hrs 1.65 (0.66, 4.13) 1.31 (0.38, 4.48) NC 1.81 (0.73, 4.51) 1.25 (0.37, 4.17) NC

BSA, m2

1.6 versus 2.0 in male 1.49 (1.23, 1.80) 1.51 (1.10, 2.07) NC 1.47 (1.21, 1.78) 1.50 (1.09, 2.05) NC


25


Preop+Intraop MT

Preop+Intraop AMT

Preop+Intraop


1.6 versus 1.8 in female 1.11 (1.02, 1.20) 1.26 (1.15, 1.38) NC 1.11 (1.02, 1.20) 1.25 (1.14, 1.36) NC



1.6 versus 2.0 NC NC 1.31 (1.09, 1.58) NC NC 1.29 (1.07, 1.56)

1.8 versus 2.0 NC NC 1.07 (0.99, 1.16) NC NC 1.06 (0.98, 1.15)

2.2 versus 2.0 NC NC 1.07 (0.95, 1.20) NC NC 1.07 (0.95, 1.21)

Surgery date, per half-year increase 0.98 (0.96, 0.99) 0.97 (0.96, 0.99) 0.99 (0.96, 1.02) 0.98 (0.97, 0.99) 0.97 (0.96, 0.99) 0.99 (0.96, 1.02)

CVD/CVA (versus No CVD)

CVD without CVA 0.95 (0.82, 1.11) 1.20 (0.97, 1.47) NC 0.95 (0.82, 1.10) 1.21 (0.99, 1.49) NC

CVD with CVA 0.94 (0.81, 1.08) 1.32 (1.11, 1.57) NC 0.94 (0.81, 1.08) 1.31 (1.10, 1.57) NC

Race and Ethnicity (versus Caucasian/other/missing)

Hispanic 1.11 (0.88, 1.39) 1.02 (0.76, 1.36) NC 1.10 (0.87, 1.38) 1.00 (0.75, 1.34) NC

Black 1.03 (0.87, 1.21) 0.83 (0.69, 1.00) NC 1.02 (0.87, 1.21) 0.82 (0.68, 0.99) NC

Asian 0.96 (0.67, 1.36) 1.36 (1.05, 1.77) NC 0.94 (0.66, 1.33) 1.31 (1.01, 1.72) NC

Hypertension 1.11 (0.98, 1.25) 0.99 (0.86, 1.14) NC 1.12 (0.99, 1.26) 1.01 (0.88, 1.16) NC

Number of Diseased Vessels 1.04 (0.97, 1.11) 1.07 (0.98, 1.18) NC 1.05 (0.98, 1.13) 1.10 (1.00, 1.20) NC

Cardiogenic Shock 1.33 (1.00, 1.77) 1.54 (1.13, 2.09) NC 1.34 (1.01, 1.78) 1.52 (1.11, 2.07) NC

PCI ≤ 6 hours 0.75 (0.21, 2.61) 1.66 (0.55, 4.97) NC 0.78 (0.24, 2.53) 1.67 (0.54, 5.16) NC

Left main disease 1.09 (0.92, 1.29) 0.99 (0.79, 1.25) NC 1.09 (0.93, 1.29) 1.00 (0.79, 1.26) NC

Afib 1.03 (0.94, 1.14) 0.97 (0.85, 1.10) 0.98 (0.82, 1.17) NC NC NC

Expanded Covariates:

Afib without ablation (versus no Afib) NC NC NC 1.09 (0.97, 1.21) 1.01 (0.86, 1.18) 1.10 (0.90, 1.34)

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Preop+Intraop MT

Preop+Intraop AMT

Preop+Intraop

Afib ablation vs. no ablation (in Afib patients) NC NC NC 0.81 (0.68, 0.95) 0.90 (0.76, 1.06) 0.72 (0.55, 0.96)

Aortic and Mitral procedures (versus repair, repair)

Aortic repair, Mitral replacement NC NC NC 0.76 (0.37, 1.59) NC NC

Aortic replacement, Mitral repair NC NC NC 0.79 (0.52, 1.21) NC NC

Aortic replacement, Mitral replacement NC NC NC 1.32 (0.86, 2.01) NC NC

Mitral and Tricuspid procedures (versus repair, repair)

Mitral repair, Tricuspid replacement NC NC NC NC 2.24 (1.39, 3.60) NC

Mitral replacement, Tricuspid repair NC NC NC NC 1.42 (1.22, 1.65) NC

Mitral replacement, Tricuspid replacement NC NC NC NC 2.05 (1.50, 2.81) NC

Aortic, Mitral and Tricuspid procedures

Aortic replacement (versus repair) NC NC NC NC NC 0.87 (0.47, 1.60)

Mitral replacement (versus repair) NC NC NC NC NC 1.28 (1.03, 1.59)

Tricuspid replacement (versus repair) NC NC NC NC NC 1.31 (0.92, 1.88) aReported odds ratio for age represents effect in patients whose status were elective and without prior operations. bReported odds ratio for emergent status represents effect in patients 50 years old. cReported odds ratio for reoperation represents effect in patients 50 years old. (ref) indicates subgroup is merged into the reference as the candidate variables are defined.

Afib = preoperative atrial fibrillation; AM = aortic-mitral; BSA = body surface area; AMT = aortic-mitral-tricuspid; CHF = congestive heart failure; CV = cardiovascular; CVA = cerebrovascular accident (stroke); CVD = cerebrovascular disease; EF = ejection fraction; IABP = intra-aortic balloon pump; MI = myocardial infarction; MT = mitral-tricuspid; NC = not a candidate; NYHA = New York Heat Association.

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Appendix Table D: Regression Coefficients of Final Stepwise Models Preop Preop + Intraop

AM MT AMT AM MT AMT

Intercept -‐4.515051 -‐5.299773 -‐4. 388223 -‐4.754703 -‐5.325053 -‐4.735681

Active Infections endocarditis 0.665872 NS NS 0.569136 NS NA

Afib ablation NC NC NC -‐0.164310 NS -‐0.262531

Age by reoperation function -‐0.014497 -‐0.013014 NC -‐0.015201 NC NC

Age function 1 NC NC 0.017561 NC NC 0.020484

Age function 2 0.032137 0.033223 NC 0.033377 0.029530 NC

Aortic and mitral replacements NC NC NC 0.520321 NC NC

Aortic insufficiency, at least moderate -‐0.084596 0.270068 NS -‐0.081360 0.250907 NS

Aortic stenosis 0.191954 NS NS 0.222723 NS NS

BSA function 1 -‐0.913553 -‐1.022723 NS -‐0.885707 -‐0.980693 NS

BSA function 2 1.922609 1.726040 NS 1.947127 1.697886 NS

CHF and NYHA IV 0.556843 0.446420 0.543116 0.542992 0.436354 0.526573

CHF but not NYHA IV 0.130967 NS NS 0.123779 NS NS

Chronic lung disease, mild or moderate 0.131439 NS NS 0.134322 NS NS

Chronic lung disease, severe 0.471134 0.341147 0.459010 0.467877 0.351191 0.431054

Concomitant CABG 0.432559 0.282039 0.388643 0.442838 0.293072 0.410346

Creatinine function 1 NS 1.006715 0.517765 NS 0.964149 0.519512

Creatinine function 2 0.944258 NS NC 0.938136 NS NC

Creatinine function 3 -‐0.748339 -‐0.677222 NC -‐0.743395 -‐0.634013 NC

CVD NS 0.249567 NC NS 0.250440 NC

Diabetes, insulin 0.361806 0.228334 0.425895 0.357971 0.229544 0.413794

Diabetes, non-‐insulin 0.125724 0.228334 NS 0.135430 0.229544 NS

Dialysis 0.378615 0.557590 NS 0.360251 0.528482 NS

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Ejection fraction function NS -‐0.007388 NS NS -‐0.010457 NS

Female 0.349015 NS NC 0.322833 NS NC

Female by BSA function 1 0.736923 NS NC 0.726381 NS NC

Immunosuppressive treatment 0.389429 0.359168 NC 0.386145 0.369129 NC

Mitral insufficiency, at least moderate NS -‐0.232722 NS NS -‐0.242037 NS

Mitral replacement NC NC NC NS 0.372739 0.341860

Mitral stenosis 0.271795 0.219442 NS NS NS NS

Preoperative IABP or Inotrope 0.477936 0.291596 NS 0.477381 NS NS

Prior CV operation 0.796906 0.713775 0.414991 0.789676 0.395824 0.370365

Prior MI 1 to 21 days 0.224411 NS NC 0.256165 0.317806 NC

Prior MI <24 hours 0.224411 0.998745 NC 0.256165 1.119814 NC

PVD 0.242246 0.216727 NS 0.249515 0.206665 NS

Cardiogenic shock NS 0.512578 NC NS 0.593779 NC

Status, emergent 0.716239 0.985924 NC 0.709347 0.955014 NC

Status, emergent or salvage or shock NC NC 0.878336 NC NC 0.871090

Status, salvage 1.362575 0.985924 NC 1.355095 0.955014 NC

Status, urgent 0.089696 0.343576 0.195183 0.083647 0.313965 0.189849

Tricuspid insufficiency, at least moderate 0.176221 NS NS 0.173983 NS NS

Tricuspid replacement NC NC NC NC 0.469732 NS

Afib = preoperative atrial fibrillation; AM = aortic-‐mitral; BSA = body surface area; AMT = aortic-‐mitral-‐tricuspid; CHF = congestive heart failure; CV = cardiovascular;CVD = cerebrovascular disease; EF = ejection fraction; IABP = intra-‐aortic balloon pump; MI = myocardial infarction; MT = mitral-‐tricuspid; NC = not a candidate; NS = not selected in the model; NYHA = New York Heat Association; PVD = peripheral vascular disease.

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Appendix Table E: Definitions of Variables Appearing in Final Stepwise Models

Variable Definition

Intercept = 1 for all patients

Active Infections endocarditis = 1 if patient has active endocarditis, = 0 otherwise

Afib/ablation = 1 if patient had afib symptoms within 2 weeks and their operation includes an afib ablation procedure, = 0 otherwise

Age by reoperation function = Age function 2 if patient had at least 1 prior CV operation, = 0 otherwise

Age function 1 = max(min(age,85),40)

Age function 2 = max(age function 1 -‐ 50, 0)

Aortic and mitral replacements = 1 if patient’s aortic and mitral procedures are replacements, = 0 otherwise

Aortic insufficiency, at least moderate = 1 if patient has at least moderate aortic insufficiency, = 0 otherwise

Aortic stenosis = 1 if patient has aortic stenosis, = 0 otherwise

BSA function 1 = max(min(BSA,2.6),1.4) -‐ 1.8

BSA function 2 = (BSA function 1) x (BSA function 1)

CHF and NYHA IV = 1 if patient has CHF and is NYHA class IV, = 0 otherwise

CHF but not NYHA IV = 1 if patient has CHF and is not NYHA class IV, = 0 otherwise

Chronic lung disease, mild or moderate = 1 if patient has mild or moderate chronic lung disease, = 0 otherwise

Chronic lung disease, severe = 1 if patient has severe chronic lung disease, = 0 otherwise

Concomitant CABG = 1 if operation includes CABG, = 0 otherwise

Creatinine function 1 = min(max(creatinine, 0.5), 5.0) if patient is not on dialysis, = 2.5 otherwise

Creatinine function 2 = max(creatinine function 1-‐1.0, 0)

Creatinine function 3 = max(creatinine function 1-‐1.5, 0)

CVD = 1 if patient has history of cerebrovascular disease, = 0 otherwise

Diabetes, insulin = 1 if patient has diabetes treated by insulin, = 0 otherwise

Diabetes, non-‐insulin = 1 if patient has diabetes not treated by insulin, = 0 otherwise

Dialysis = 1 if patient requires dialysis preoperatively, = 0 otherwise

Ejection fraction function = min(ejection fraction-‐50, 0)

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Female = 1 if patient is female, = 0 otherwise

Female by BSA function 1 = BSA function 1 if female, = 0 otherwise

Immunosuppressive treatment = 1 if patient was given immunosuppressive therapy within 30 days of operation,

= 0 otherwise

Mitral insufficiency, at least moderate = 1 if patient has at least moderate mitral insufficiency, = 0 otherwise

Mitral replacement = 1 if patient’s mitral procedure is a replacement, = 0 otherwise

Mitral stenosis = 1 if patient has mitral stenosis, = 0 otherwise

Preoperative IABP or Inotrope = 1 if patient requires IABP or inotropes preoperatively, = 0 otherwise

Prior CV operation = 1 if patient has had at least 1 prior cardiovascular operation, = 0 otherwise

Prior MI <24 hours = 1 if history of MI <24 hours prior to operation, = 0 otherwise

Prior MI 1 to 21 days = 1 if history of MI 1 to 21 days prior to operation, = 0 otherwise

PVD = 1 if patient has peripheral vascular disease, = 0 otherwise

Cardiogenic shock = 1 if patient was in shock at time of procedure, = 0 otherwise

Status, emergent = 1 if status is emergent, = 0 otherwise

Status, emergent or salvage or shock = 1 if status is emergent or salvage or patient was in shock at time of procedure,

= 0 otherwise

Status, salvage = 1 if status is salvage, = 0 otherwise

Status, urgent = 1 if status is urgent, = 0 otherwise

Tricuspid insufficiency, at least moderate = 1 if patient has at least moderate tricuspid insufficiency, = 0 otherwise

Tricuspid replacement = 1 if patient’s tricuspid procedure is a replacement, = 0 otherwise

Afib = preoperative atrial fibrillation; AM = aortic-‐mitral; BSA = body surface area; AMT = aortic-‐mitral-‐tricuspid; CHF = congestive heart failure; CV = cardiovascular;CVD = cerebrovascular disease; EF = ejection fraction; IABP = intra-‐aortic balloon pump; MI = myocardial infarction; MT = mitral-‐tricuspid; NA = variance not applicable to this model; NYHA = New York Heat Association; PVD = peripheral vascular disease.

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Figure and Figure Legend

Figure 1: Calibration curves for AM, MT, and AMT analyses. “Preoperative” models are on the left, and “Preoperative + Intraoperative” models on the right.

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Abbreviations

A = Aortic

ACSD = Adult Cardiac Surgery Database

CABG = Coronary Artery Bypass Grafting

EF = Ejection Fraction

M = Mitral

MUV = Multiple Valve

NYHA = New York Heart Association

QMTF = Quality Measurement Task Force

ROC = Receiver Operating Characteristic

STS = Society of Thoracic Surgeons

T = Tricuspid

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