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The Impact of Major Postoperative Complications on Long-Term Survival After Cardiac Surgery
Journal Pre-proof The Impact of Major Postoperative Complications on Long-Term Survival After Cardiac Surgery Laura Seese, M.D., Ibrahim Sultan, M.D., Thomas G. Gleason, M.D., Forozan Navid, M.D., Yisi Wang, M.P.H., Floyd Thoma, B.S., Arman Kilic, M.D PII:
S0003-4975(19)31748-5
DOI:
https://doi.org/10.1016/j.athoracsur.2019.09.100
Reference:
ATS 33254
To appear in:
The Annals of Thoracic Surgery
Received Date: 25 April 2019 Revised Date:
17 September 2019
Accepted Date: 30 September 2019
Please cite this article as: Seese L, Sultan I, Gleason TG, Navid F, Wang Y, Thoma F, Kilic A, The Impact of Major Postoperative Complications on Long-Term Survival After Cardiac Surgery, The Annals of Thoracic Surgery (2019), doi: https://doi.org/10.1016/j.athoracsur.2019.09.100. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 by The Society of Thoracic Surgeons
The Impact of Major Postoperative Complications on Long-Term Survival After Cardiac Surgery Running Title: Complications and Long-Term Survival
Laura Seese, M.D., Ibrahim Sultan, M.D., Thomas G. Gleason, M.D., Forozan Navid, M.D., Yisi Wang, M.P.H., Floyd Thoma, B.S., Arman Kilic, M.D.
From the (1) Division of Cardiac Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA USA
Key Words: Cardiac Surgery; Long-term Outcomes; Failure to Rescue, Postoperative Complications
Word Count: 4,490
Correspondence and Reprint Requests: Arman Kilic, MD Division of Cardiac Surgery University of Pittsburgh Medical Center 200 Lothrop Street Suite C-700 Pittsburgh, PA 15213 Email: [email protected]
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Abstract Background: This study evaluated the impact of postoperative complications on long-term survival after cardiac surgery. Methods: Adults undergoing an index cardiac operation from January 2010 to December 2017 were included. Patients were stratified by the number and type of Society of Thoracic Surgeons (STS)-defined major complications. Failure-to-rescue (FTR) was defined as mortality following a complication that occurred prior to hospital discharge. Long-term mortality among patients with complications (LMPC) was defined as a post-complication death occurring after hospital discharge. Multivariable Cox regression was used for risk-adjustment. Results: 9,532 patients were included in the study and 16.8% (n=1600) had a major postoperative complication. Operative mortality was 0.8% for those with no complications. Early FTR increased as the number of complications increased (7.5%, 28.1%, and 51.5% for 1, 2, and ≥3 complications, respectively; p<0.0001). Median length of intensive care unit and hospital stay ranged from 38 hours and 7 days in patients with no complications to 359 hours and 23 days in patients with ≥3 complications (p<0.0001). The adverse impact of complications on survival persisted at 1-year (3.5%, 18.8%, 52.1%, and 77.9%; p<0.0001) and 5-year followup (10.8%, 33.0%, 61.8%, and 77.9%; p<0.0001) in those with 0, 1, 2, or ≥3 complications, respectively. Risk-adjusted analysis confirmed these findings (p<0.0001). Furthermore, 5-year survival conditional on 30-day survival ranged from 85.1% to 41.5% for those with 0 versus ≥3 complications (p<0.0001). Conclusions: Postoperative complications following cardiac surgery, particularly when occurring in combination, have a profound impact on long-term survival, even after excluding early postoperative deaths.
Abstract Word Count: 249
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Traditionally the reporting of cardiac surgical outcomes has centered upon 30-day or inhospital events to guide performance metrics, assess quality of care and create risk models. An adjunct to outcomes assessments in cardiac surgery is failure-to-rescue (FTR), which refers to death in the presence of a postoperative complication [1]. Investigators have shown that the rates of postoperative complications are mostly influenced by patient-specific comorbidities, which leads to similar complication rates amongst highest and lowest performing centers in the country, with higher performance being defined as having lower observed to expected mortality and morbidity rates [2-4]. Despite similar complication rates, there are substantial inter-hospital differences in FTR that are associated with systems-based practices that allow for earlier recognition and treatment of postoperative complications in the highest performing centers [5]. While effective and timely management of complications in the early postoperative period is essential to improve survival, a major limitation when evaluating FTR is that most studies are confined to short periods of follow-up [6] Therefore, the effects of postoperative complications on long-term outcomes are less understood. The aim of this study was to evaluate the impact of major postoperative complications on long-term survival following cardiac surgery.
Patients and Methods Study Design All adult (≥18 years) patients undergoing a Society of Thoracic Surgeons (STS) index cardiac operation between January 2010 and December 2017 at a single academic institution were included. The operations included isolated coronary artery bypass (CABG), isolated aortic valve replacement (AVR), isolated mitral valve replacement (MVR), isolated mitral valve repair (MVr), concomitant CABG AVR, concomitant CABG MVR, and concomitant CABG MVr. The University of Pittsburgh institutional review board approved this study.
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Data Analysis The postoperative complications that were assessed included those defined by the STS as major morbidity: prolonged ventilation (>24 hours), acute renal failure, permanent stroke, deep sternal wound infection (DSWI), and all-cause reoperation. The clinical definitions for these complications were derived from the criteria set forth from the STS [7]. The impact of complications on outcomes was evaluated using both the number of complications as well as the type of complications as a means of stratification. FTR was defined as mortality, following a complication, that occurred within 30-days of surgery or prior to hospital discharge. Long-term mortality among patients with complications (LMPC) was defined as mortality that occurred at any time point following 30-days or hospital discharge. The primary endpoint was survival at 30days, 1-year and 5-years postoperatively. Patients who were alive were censored at the time of their last follow-up in the electronic health record, and the date of death in patients who died were obtained from the electronic health record and supplemented with data from the Social Security Death Index Master File. After stratifying patients based on the number of complications, the baseline characteristics and postoperative complication types were compared between the groups using analysis of variance (ANOVA) for continuous variables and Pearson’s Chi-squared test for categorical variables. Categorical variables are represented as percentage (number). Parametric continuous variables are represented as mean ± standard deviation and nonparametric continuous variables are represented as median with interquartile range [IQR]. Kaplan-Meier estimates and the log-rank test were used to compare the longitudinal survival between the groups. Multivariable Cox regression analyses incorporating univariate predictors (inclusion criteria of two-tailed p<0.05) were conducted to evaluate the risk-adjusted impact of the total number and types of postoperative complications on mortality at 30-days, 1-year and 5years. All baseline characteristics were evaluated for potential inclusion in these risk-adjusted models. Individual surgeon volume and year of surgery were included in the risk-adjusted 4
analyses as well. Complication types and combinations were forced into the multivariate models. Complication combinations with sample size less than 5 events were excluded and reported as insufficient events in the multivariate Cox regression models. Statistical analyses were performed with version 9.4 SAS software (SAS Institute, Cary, NC).
Results Study Cohort A total of 9,532 adult patients underwent an STS-indexed cardiac operation during the study period. Of these, 16.8% (n=1600) experienced at least one major postoperative complication with 56.0% (n=897) having an isolated complication, 18.0% (n=288) having 2 complications, and 4.3% (n=68) experiencing at least 3 complications. There were significant differences in the baseline characteristics amongst patients who experienced no complications compared to those with isolated, 2, or at least 3 complications (Table 1). Overall, the STS Predicted Risk of Operative Mortality (STS-PROM) was lowest in the patients who experienced no complications and highest in those with multiple complications.
Unadjusted Survival Mean follow-up was 3.5 ± 2.2 years. An increasing number of complications was associated with increasing overall mortality rates: 12.5% in patients with no complications, 36.3% in patients with 1 complication, 63.9% in patients with 2 complications and 78.4% of patients with at least 3 complications (p<0.0001). In patients who experienced complications, FTR rates increased as the number of complications increased (7.5% vs 28.1% vs 51.5%, p<0.0001) (Table 2). This effect was not limited to the index hospitalization and an increasing mortality trend for patients who experienced an increasing number of complications remained significant at 1-year (18.8% vs 52.1% vs 77.9%, p<0.0001) and 5-year follow-up (33.0% vs 61.8% vs 77.9%, p<0.0001) (Figure 1A and Table 3). Even after excluding early deaths and 5
conducting the analysis conditional on 30-day survival, the negative divergence in survival was still significant at all time intervals (Figure 1B, Supplemental Table 1). By comparison, patients experiencing no complications had 30-day, 1-year, and 5-year mortality rates of 0.8%, 3.5%, and 10.8% (Table 3). Length of intensive care unit stay also demonstrated similar trends, with median number of intensive care unit hours ranging from 38.0 hours (IQR 25.0-61.5 hours) in those with no complications to 358.5 hours (IQR 177.6-713.5 hours) in those with at least 3 complications (p<0.0001) (Table 3). Overall median length of stay ranged from 7 days (IQR 610 days) in those with no complications to 22.5 days (IQR 10-36 days) in those with at least 3 complications (p<0.0001).
Failure to Rescue by Complication Type In those with isolated postoperative complications, early FTR rates were highest with prolonged ventilation at 9.7% and stroke at 6.3% (Table 2). In patients with 2 complications, early FTR rates were highest in those with combined prolonged ventilation and renal failure at 38.4% and combined stroke and prolonged ventilation at 24.5%. In patients with at least 3 complications, early FTR rates were high across each combination ranging from 33.3% to 100%, although sample sizes within each possible combination were low. A composite assessment of all complications, isolated and combined, demonstrated early FTR rates to be highest in renal failure (29.6%), followed by prolonged ventilation (19.2%), stroke (18.4%), and DSWI (18.2%), with the lowest early FTR rate following reoperation (13.5%).
Risk-Adjusted Mortality An increasing number of complications was associated with increasing hazards for mortality at all time intervals in risk-adjusted analysis (Supplemental Table 2). When evaluating types of isolated complications, the greatest hazard for early FTR was prolonged ventilation (Hazard Ratio (HR) 7.8, 95% confidence interval (CI) 5.2-11.6, p<0.0001) while the greatest 6
hazard for LMPC, at 1-year and 5-years, was DSWI (HR 8.0, 95% CI 2.5-25.3, p=0.004 and HR 7.3, 95%CI 3.0-17.8, p<0.0001). When evaluating multiple complications, the greatest hazard for early FTR was prolonged ventilation, reoperation and renal failure (HR 33.0, 95% CI 19.555.8, p<0.0001) whereas combined stroke, prolonged ventilation, and renal failure was the greatest predictor of LMPC at both 1- and 5-year follow-up (HR 31.3, 95% CI 12.8, 77.0, p<0.0001 and HR 26.8, 95% CI 11.0-65.1, p<0.0001). These findings persisted even when adjusted for surgeon annual case volume as well as the year of surgery.
Comment The STS projects that approximately 13% of patients in the current era will experience at least 1 major complication following CABG with 10.5% succumbing to early FTR [6]. The type and number of postoperative complications incurred undoubtedly have important implications for early mortality and health care costs due to prolonged hospitalizations [8,9]. For instance, patients who experience postoperative renal failure, isolated or concomitant with other complications, following cardiac surgery have been reported to have the highest early FTR rates, ranging from 21% to 40%, when compared to other types of isolated postoperative complications [5,6,9]. Moreover, respiratory failure requiring prolonged intubation is also highly associated with mortality and in a propensity matched analysis had an 8-fold increase in FTR [12]. While isolated complications have varying influences on FTR, the effects of multiple complications are substantial. In fact, the negative effects of an increasing number of complications on early mortality have been shown to be multiplicative with profound increases in early FTR rates, exceeding 50%, in those with three or more complications [9]. While the timely and effective interventions necessary to prevent FTR are clearly important mechanisms in preventing early mortality, a crucial aspect of cardiac surgical outcomes that remains unexplored is the long-term survival of patients who survive postoperative complications. Many data registries have been unable to capture events that 7
occur following discharge from the index hospitalization due to logistical limitations such as outof-network care. As such, there are very few studies that explore longitudinal outcomes following cardiac surgery as it relates to postoperative adverse events. In the current era, increasing emphasis is placed on the preoperative risk assessment of cardiac surgical patients in order to provide more cost effective and rational care [10,11]. However, as early mortality and morbidity rates have improved, the longitudinal outcomes, especially as they relate to adverse events in the immediate postoperative period, have become increasingly relevant in evaluating cardiac surgical success [12].
Impact of Postoperative Complications on Long-Term Outcomes after Cardiac Surgery While the long-term impact of postoperative complications after cardiac surgery are not well understood, there are a few reports with 5-year follow-up in the areas of isolated postoperative renal failure, stroke, respiratory failure and infectious complications that have become available in recent years. In a multicenter retrospective study of 513 patients with postoperative renal failure who survived to discharge, the overall survival was 87.7% and the readmission rate was 39.9% at 5-years, with the highest mortality and readmission rates in those requiring acute dialysis postoperatively [13]. The duration and transiency of renal failure are also key components in long-term survival where the propensity-matched hazard for mortality at 5-years is nearly 5-fold greater in those with persistent acute kidney insufficiency or dialysis dependence at the time of discharge [14]. Strokes are one of the most devastating complications after cardiac surgery due to the resulting functional deficits that may necessitate long-term rehabilitative care. A multicenter retrospective study with 1,731 patients with strokes following cardiac surgery demonstrated significantly lower 5-year survival rates (25.1% vs 49.1%, p<0.001) compared to patients without strokes [15]. Patients with strokes also experienced higher rates of additional complications. Another study that evaluated 1,593 propensity matched pairs found that 8
infectious complications after cardiac surgery, including sepsis, DSWI, urinary tract infection, and pneumonia, were associated with reduced risk-adjusted survival, largely attributable to an early hazard for death that gradually resolved over the first year [16]. Prolonged ventilation was also shown in a propensity matched analysis to be associated with lower survival (56.1% vs 88.8%, p<0.001) at 5-year follow-up after cardiac surgery [17].
Study Implications The current study was designed to evaluate the impact of major STS-tracked postoperative complications after cardiac surgery on longitudinal outcomes. For the past several decades, the emphasis on outcome optimization in cardiac surgery has mainly been focused on the in-hospital and 30-day postoperative period, and many programs have accordingly implemented STS systems-based quality metrics to improve these early outcomes [18]. Optimizing longitudinal cardiac surgical outcomes through post-discharge quality metrics have both patient-centered and healthcare economic benefits and understanding the long-term effects of complications on survival are essential in this process. There are several important findings from our analysis. Foremost, the majority of patients who had a major complication had an isolated complication. In those with a clustering of complications, prolonged ventilation tended to be the most frequently shared complication. This is clinically intuitive as patients experiencing major adverse events, particularly when severe, may have difficulty liberating from the ventilator. Examples would include patients with major stroke who are unable to protect their own airway. Another example is a patient who undergoes a reoperation for bleeding and is reintubated or remains intubated due to volume and blood product resuscitation and the necessity for an airway during the repeat procedure. Volume management in patients with acute renal failure postoperatively can be challenging and lead to pulmonary edema and prolonged ventilation. In some clinical scenarios, prolonged ventilation is not the subsequent complication but rather the inciting complication that leads to 9
other complications. For example, patients with chronic lung disease may have primary respiratory failure following cardiac surgery which then can lead to pneumonia and multiorgan dysfunction. Of interest is the fact that most patients in our study who experienced a complication had a single isolated complication, which may suggest that even in the occurrence of one of these adverse events, successful early recognition and aggressive management can potentially prevent subsequent complications, although this assumption would have to be evaluated in future studies. The finding that renal failure was associated with the highest unadjusted composite early FTR rates is consistent with prior reports [6,9]. Moreover, in an analysis of the STS National Database for isolated CABG, the occurrence of renal failure was associated with an early FTR rate of 22.3%, which was the highest of the major morbidities, although the authors did not evaluate DSWI due to its rare occurrence [6]. A single institution analysis of 2,477 cardiac surgical patients found that the early FTR rate for renal failure was 42% which was only surpassed by DSWI at 50% although there were only 4 patients who developed DSWI [9]. Similar to our findings, both of these prior analyses demonstrated that prolonged intubation was the most common major complication [6,9]. Perhaps the most provocative finding in our analysis relates to the impact of postoperative complications on long-term survival, an impact which is profound and persistent even after excluding early deaths. There are several plausible explanations for these findings. A patient who experiences a debilitating complication may survive the early postoperative period, but can be left with residual functional limitations that lead to impaired survival over the ensuing months or years. This can often be a result of more chronic issues like malnutrition and failure to thrive. These issues are likely more prevalent in patients experiencing multiple complications. Although the occurrence of complications is strongly linked to preoperative comorbidities, the occurrence of FTR is influenced heavily by systems-based and practice10
based factors. These factors include nursing-to-patient ratios, intensive care unit staffing, availability and expertise of consultative services, and infrastructure and clinical protocols leading to earlier intervention [5,6]. The relative impact of each of these factors varies as a function of time from the operation. For example, whereas intensive care unit staffing and resources play a vital role in early FTR, outpatient staffing and monitoring of patients for medication compliance as well as access to effective long-term rehabilitative services play more important roles in LMPC. Future studies will help delineate systems-based clinical enhancements and their contribution to improving late survival after cardiac surgery.
Limitations There are inherent limitations related to this study’s retrospective design. The severity and granular details of each complication were not evaluated but likely have an impact on outcomes [13-15]. For instance, in cases of stroke where mechanical thrombectomy is not available, patients with isolated small vessel occlusion have drastically different outcomes than patients with large vessel occlusion or hemorrhagic conversion [19]. The timing of complications was also not evaluated and therefore sequences of adverse events could not be identified. The specific causes of death were unavailable in our dataset, and therefore only associative relationships could be demonstrated with limited insight into causality. Finally, some combinations in the 3 or more complications category occurred infrequently and these groups may be subject to a type II error.
Conclusions This study evaluated 9,532 patients who underwent an index STS cardiac operation and demonstrated a profound association between an increasing number of major postoperative complications and increasing FTR and LMPC. The magnitude of this negative effect also varied by the type and combinations of various complications. Future studies are needed to 11
understand if systems-based factors are associated with the persistent impact postoperative complications have on longer-term survival after cardiac surgery.
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References 1. Ghaferi AA, Birkmeyer JD, Dimick JB. Variation in hospital mortality associated with inpatient surgery. N Engl J Med. 2009;361(14):1368-75. 2. Silber JH, Williams SV, Krakauer H, Schwartz JS. Hospital and patient characteristics associated with death after surgery. A study of adverse occurrence and failure to rescue. Med Care. 1992;30(7):615-29. 3. Gonzalez AA, Dimick JB, Birkmeyer JD, Ghaferi AA. Understanding the volume-outcome effect in cardiovascular surgery: the role of failure to rescue. JAMA Surg. 2014;149(2):119-23. 4. Silber JH, Rosenbaum PR, Schwartz JS, Ross RN, Williams SV. Evaluation of the complication rate as a measure of quality of care in coronary artery bypass graft surgery. JAMA. 1995;274(4):317-23. 5. Reddy HG, Shih T, Englesbe MJ, et al. Analyzing "failure to rescue": is this an opportunity for outcome improvement in cardiac surgery? Ann Thorac Surg. 2013;95(6):1976-81. 6. Edwards FH, Ferraris VA, Kurlansky PA, et al. Failure to Rescue Rates After Coronary Artery Bypass Grafting: An Analysis From The Society of Thoracic Surgeons Adult Cardiac Surgery Database. Ann Thorac Surg. 2016;102(2):458-64. 7. The Society of Thoracic Surgeons Cardiac Surgery Database: database data collection. Available at https://www.sts.org/registries-research-center/sts-national-database/adultcardiac-surgery-database/data-collection. Accessed July 3, 2019. 8. Khuri SF, Henderson WG, DePalma RG, Mosca C, Healey NA, Kumbhani DJ; Participants in the VA National Surgical Quality Improvement Program. Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg. 2005;242(3):326-41.
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9. Crawford TC, Magruder JT, Grimm JC, et al. Complications After Cardiac Operations: All Are Not Created Equal. Ann Thorac Surg. 2017;103(1):32-40. 10. Rahmanian PB, Adams DH, Castillo JG, Carpentier A, Filsoufi F. Predicting hospital mortality and analysis of long-term survival after major noncardiac complications in cardiac surgery patients. Ann Thorac Surg. 2010;90(4):1221-9. 11. D'Agostino RS, Jacobs JP, Badhwar V, et al. The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2018 Update on Outcomes and Quality. Ann Thorac Surg. 2018;105(1):15-23. 12. Shahian DM, O'Brien SM, Sheng S, et al. Predictors of long-term survival after coronary artery bypass grafting surgery: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (the ASCERT study). Circulation. 2012;125(12):1491-500. 13. Brown JR, Hisey WM, Marshall EJ, et al. Acute Kidney Injury Severity and Long-Term Readmission and Mortality After Cardiac Surgery. Ann Thorac Surg. 2016;102(5):14821489. 14. Brown JR, Kramer RS, Coca SG, Parikh CR. Duration of acute kidney injury impacts long-term survival after cardiac surgery. Ann Thorac Surg. 2010;90(4):1142-8. 15. Chen CC, Chen TH, Tu PH, et al. Long-Term Outcomes for Patients With Stroke After Coronary and Valve Surgery. Ann Thorac Surg. 2018;106(1):85-91. 16. Robich MP, Sabik JF 3rd, Houghtaling PL, et al. Prolonged effect of postoperative infectious complications on survival after cardiac surgery. Ann Thorac Surg. 2015;99(5):1591-9. 17. Rajakaruna C, Rogers CA, Angelini GD, Ascione R. Risk factors for and economic implications of prolonged ventilation after cardiac surgery. J Thorac Cardiovasc Surg. 2005;130(5):1270-7.
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18. Chu D, Chan P, Wei LM, et al. The Effect of Comprehensive Society of Thoracic Surgeons Quality Improvement on Outcomes and Failure to Rescue. Ann Thorac Surg. 2015;100(6):2147-50. 19. Madeira M, Martins C, Koukoulis G, Marques M, Reis J, Abecassis M. Mechanical Thrombectomy for Stroke After Cardiac Surgery. J Card Surg. 2016;31(8):517-20
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Figure Legends Figure 1. Kaplan-Meier estimates demonstrating survival (A) and survival contingent on 30-day survival (B) stratified by the number of postoperative complications (notated as 0: no complications, 1: 1 complication, 2: 2 complications, 3: 3 or more complications). Figure 2. Forest plot displaying the adjusted hazard ratios for 5-year mortality in patients with various combinations of postoperative complications. Abbreviations: DSWI, deep sternal wound infection; PVT, prolonged ventilation; RF, renal failure; Reop, reoperation
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Table 1. Baseline characteristics stratified by the number of complications. Variable Age (years) Female Race Caucasian Black BMI (kg/m2) Hypertension Diabetes Mellitus Dialysis Dependence PVD CVD Previous MI Immunosuppression Prior heart failure COPD NYHA Class No heart failure I II III IV Operative status Elective Urgent Emergent Emergent salvage LVEF (%) Albumin (mg/dL) Creatinine (mg/dL) Preoperative IABP Type of Operation Isolated CABG Isolated MVr Isolated MVR Isolated AVR CABG + AVR CABG + MVr CABG + MVR STS-PROM (%) CPB time (min)
None (n=8279)
Isolated (n= 897)
Two (n= 288)
Multiple (≥3) (n= 68)
P-Value
66.56 ± 0.12 29.52% (2444)
69.12 ± 0.37 36.79% (330)
70.42 ± 0.66 33.33% (96)
69.41 ± 1.36 41.18% (28)
<0.0001 <0.0001
93.88% (7772) 4.01% (332) 29.85 ± 0.07 85.72% (7097) 40.25% (3332) 2.09% (173) 18.37% (1521) 20.57% (1703) 48.48% (4014) 5.27% (436) 17.48% (1447) 20.46% (1694)
91.97% (825) 5.91% (52) 30.24 ± 0.21 87.51% (785) 48.49% (435) 5.24% (47) 28.99% (260) 28.54% (256) 56.08% (503) 7.80% (70) 28.99% (260) 30.88% (277)
89.93% (259) 7.64% (22) 30.15 ± 0.36 88.89% (256) 53.13% (153) 1.04% (3) 30.21% (87) 35.76% (103) 61.46% (177) 8.68% (25) 31.94% (92) 35.42% (102)
92.65% (63) 5.88% (4) 31.07 ± 0.75 82.35% (56) 64.71% (44) 1.47% (1) 32.35% (22) 38.24% (26) 64.71% (44) 10.29% (7) 32.35% (22) 35.29% (24)
0.009 0.001 0.10 0.17 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 0.0005 <0.0001 <0.0001 <0.0001
78.25% (6478) 0.69% (57) 4.94% (409) 10.59% (877) 5.53% (458)
60.65% (544) 0.45% (4) 5.46% (49) 17.39% (156) 16.05% (144)
55.21% (159) 0.69% (2) 5.21% (15) 18.06% (52) 20.83% (60)
48.53% (33) 0.0% (0) 5.88% (4) 16.18% (11) 29.41% (20) <0.0001
46.85% (3878) 50.10% (4147) 250 (3.02%) 0.04% (3) 51.02 ± 0.14 3.65 ± 0.005 1.13 ± 0.02 3.97% (329)
35.23% (316) 54.85% (492) 86 (9.59%) 0.33% (3) 47.74 ± 0.41 3.48 ± 0.02 1.43 ± 0.03 11.82% (106)
32.99% (95) 55.21% (159) 33 (11.46%) 0.35% (1) 45.82 ± 0.73 3.42 ± 0.03 1.34 ± 0.06 11.81% (34)
23.53% (16) 61.76% (42) 13.24% (9) 1.47% (1) 48.72 ± 1.51 3.44 ± 0.06 1.23 ± 0.12 13.24% (9)
5282 (63.80%) 409 (4.94%) 147 (1.78%) 1297 (15.67%) 849 (10.25%) 238 (2.87%) 57 (0.69%) 2.66 ± 0.05 109.19 ± 0.43
487 (54.29%) 47 (5.24%) 32 (3.57%) 124 (13.82%) 128 (14.27%) 61 (6.80%) 18 (2.01%) 6.63 ± 0.16 123.40 ± 1.32
146 (50.69%) 6 (2.08%) 6 (2.08%) 39 (13.54%) 57 (19.79%) 24 (8.33%) 10 (3.47%) 8.28 ± 0.29 127.10 ± 2.32
33 (48.53%) 2 (2.94%) 3 (4.41%) 8 (11.76%) 11 (16.18%) 5 (7.35%) 6 (8.82%) 9.21 ± 0.59 138.98 ± 4.79
<0.0001 <0.0001 <0.0001 <0.0001 <0.0001
<0.0001 <0.0001 17
Ischemic time (min)
81.03 ± 0.44
92.32 ± 1.32
94.64 ± 2.33
101.96 ± 4.74
<0.0001
Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; CPB, cardiopulmonary bypass; CVD, cerebrovascular disease; PVD, peripheral vascular disease; LVEF, left ventricular ejection fraction; MI, myocardial infarction; STS-PROM, Society for Thoracic Surgeons Predicted Risk of Mortality.
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Table 2. Unadjusted early failure-to-rescue rates by complication type. Complication Types None of five complications Isolated Stroke Prolonged ventilation DSWI Reoperation Renal failure Total Isolated Two Complications Stroke + Prolonged ventilation Stroke + Unplanned reoperation Stroke + Renal failure Prolonged ventilation + DSWI Prolonged ventilation + Reoperation Prolonged ventilation + Renal failure DSWI + Reoperation Reoperation + Renal failure Total Two Complications Three Complications Stroke +Prolonged ventilation + Reoperation Stroke + Prolonged ventilation + Renal failure Prolonged ventilation + DSWI + Reoperation Prolonged ventilation + DSWI + Renal failure Prolonged ventilation + Reoperation + Renal failure Total Three Complications More than Three Complications Overall Total Composite Mortality Stroke Prolonged ventilation DSWI Reoperation Renal failure
No. 8279
Failure to Rescue % (n) 0.75% (62)
96 506 9 177 109 897
6.25% (6) 9.68% (49) 0% (0) 3.39% (6) 5.50% (6) 7.47% (67)
53 1 1 5 70 151 1 6 288
24.53% (13) 0% (0) 0% (0) 0% (0) 12.86% (9) 38.41% (58) 0% (0) 16.67% (1) 28.22% (81)
6 16 1 3 34 59 9 9532
33.33% (2) 50.00% (8) 100.00% (1) 33.33% (1) 52.94% (18) 50.85% (30) 55.56% (5) 2.57% (245)
179 853 22 304 328
18.44% (33) 19.23% (164) 18.18% (4) 13.49% (41) 29.57% (97)
Abbreviations: DSWI, deep sternal wound infection.
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Table 3. Length of stay and mortality stratified by number of complications. Variable
Time Interval
ICU Hours Median [IQR] Hospital LOS Median [IQR] Mortality Operative 1-year 5-years Overall
None (n=8279) 38.0 [25.0-61.5]
Isolated (n= 897) 108.0 [67.8-192.5]
Two (n= 288) 242.2 [126.0-504.0]
Multiple (≥3) (n= 68) 358.5 [177.6-713.5]
7 [6-10]
13 [9-20]
21.0 [12-31]
22.5 [10-36]
0.75% (62) 3.48% (288) 10.83% (897) 12.51% (1036)
7.47% (67) 18.84% (169) 33.00% (296) 36.34% (326)
28.13% (81) 52.08% (150) 61.81% (178) 63.89% (184)
51.47% (35) 77.94% (53) 77.94% (53) 79.41% (54)
P-Value <0.0001
<0.0001 <0.0001 <0.0001 <0.0001 <0.0001
Abbreviations: HR, Hazard Ratio; ICU, intensive care unit; LOS, length of stay.
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S0003-4975(19)31748-5
DOI:
https://doi.org/10.1016/j.athoracsur.2019.09.100
Reference:
ATS 33254
To appear in:
The Annals of Thoracic Surgery
Received Date: 25 April 2019 Revised Date:
17 September 2019
Accepted Date: 30 September 2019
Please cite this article as: Seese L, Sultan I, Gleason TG, Navid F, Wang Y, Thoma F, Kilic A, The Impact of Major Postoperative Complications on Long-Term Survival After Cardiac Surgery, The Annals of Thoracic Surgery (2019), doi: https://doi.org/10.1016/j.athoracsur.2019.09.100. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 by The Society of Thoracic Surgeons
The Impact of Major Postoperative Complications on Long-Term Survival After Cardiac Surgery Running Title: Complications and Long-Term Survival
Laura Seese, M.D., Ibrahim Sultan, M.D., Thomas G. Gleason, M.D., Forozan Navid, M.D., Yisi Wang, M.P.H., Floyd Thoma, B.S., Arman Kilic, M.D.
From the (1) Division of Cardiac Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA USA
Key Words: Cardiac Surgery; Long-term Outcomes; Failure to Rescue, Postoperative Complications
Word Count: 4,490
Correspondence and Reprint Requests: Arman Kilic, MD Division of Cardiac Surgery University of Pittsburgh Medical Center 200 Lothrop Street Suite C-700 Pittsburgh, PA 15213 Email: [email protected]
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Abstract Background: This study evaluated the impact of postoperative complications on long-term survival after cardiac surgery. Methods: Adults undergoing an index cardiac operation from January 2010 to December 2017 were included. Patients were stratified by the number and type of Society of Thoracic Surgeons (STS)-defined major complications. Failure-to-rescue (FTR) was defined as mortality following a complication that occurred prior to hospital discharge. Long-term mortality among patients with complications (LMPC) was defined as a post-complication death occurring after hospital discharge. Multivariable Cox regression was used for risk-adjustment. Results: 9,532 patients were included in the study and 16.8% (n=1600) had a major postoperative complication. Operative mortality was 0.8% for those with no complications. Early FTR increased as the number of complications increased (7.5%, 28.1%, and 51.5% for 1, 2, and ≥3 complications, respectively; p<0.0001). Median length of intensive care unit and hospital stay ranged from 38 hours and 7 days in patients with no complications to 359 hours and 23 days in patients with ≥3 complications (p<0.0001). The adverse impact of complications on survival persisted at 1-year (3.5%, 18.8%, 52.1%, and 77.9%; p<0.0001) and 5-year followup (10.8%, 33.0%, 61.8%, and 77.9%; p<0.0001) in those with 0, 1, 2, or ≥3 complications, respectively. Risk-adjusted analysis confirmed these findings (p<0.0001). Furthermore, 5-year survival conditional on 30-day survival ranged from 85.1% to 41.5% for those with 0 versus ≥3 complications (p<0.0001). Conclusions: Postoperative complications following cardiac surgery, particularly when occurring in combination, have a profound impact on long-term survival, even after excluding early postoperative deaths.
Abstract Word Count: 249
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Traditionally the reporting of cardiac surgical outcomes has centered upon 30-day or inhospital events to guide performance metrics, assess quality of care and create risk models. An adjunct to outcomes assessments in cardiac surgery is failure-to-rescue (FTR), which refers to death in the presence of a postoperative complication [1]. Investigators have shown that the rates of postoperative complications are mostly influenced by patient-specific comorbidities, which leads to similar complication rates amongst highest and lowest performing centers in the country, with higher performance being defined as having lower observed to expected mortality and morbidity rates [2-4]. Despite similar complication rates, there are substantial inter-hospital differences in FTR that are associated with systems-based practices that allow for earlier recognition and treatment of postoperative complications in the highest performing centers [5]. While effective and timely management of complications in the early postoperative period is essential to improve survival, a major limitation when evaluating FTR is that most studies are confined to short periods of follow-up [6] Therefore, the effects of postoperative complications on long-term outcomes are less understood. The aim of this study was to evaluate the impact of major postoperative complications on long-term survival following cardiac surgery.
Patients and Methods Study Design All adult (≥18 years) patients undergoing a Society of Thoracic Surgeons (STS) index cardiac operation between January 2010 and December 2017 at a single academic institution were included. The operations included isolated coronary artery bypass (CABG), isolated aortic valve replacement (AVR), isolated mitral valve replacement (MVR), isolated mitral valve repair (MVr), concomitant CABG AVR, concomitant CABG MVR, and concomitant CABG MVr. The University of Pittsburgh institutional review board approved this study.
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Data Analysis The postoperative complications that were assessed included those defined by the STS as major morbidity: prolonged ventilation (>24 hours), acute renal failure, permanent stroke, deep sternal wound infection (DSWI), and all-cause reoperation. The clinical definitions for these complications were derived from the criteria set forth from the STS [7]. The impact of complications on outcomes was evaluated using both the number of complications as well as the type of complications as a means of stratification. FTR was defined as mortality, following a complication, that occurred within 30-days of surgery or prior to hospital discharge. Long-term mortality among patients with complications (LMPC) was defined as mortality that occurred at any time point following 30-days or hospital discharge. The primary endpoint was survival at 30days, 1-year and 5-years postoperatively. Patients who were alive were censored at the time of their last follow-up in the electronic health record, and the date of death in patients who died were obtained from the electronic health record and supplemented with data from the Social Security Death Index Master File. After stratifying patients based on the number of complications, the baseline characteristics and postoperative complication types were compared between the groups using analysis of variance (ANOVA) for continuous variables and Pearson’s Chi-squared test for categorical variables. Categorical variables are represented as percentage (number). Parametric continuous variables are represented as mean ± standard deviation and nonparametric continuous variables are represented as median with interquartile range [IQR]. Kaplan-Meier estimates and the log-rank test were used to compare the longitudinal survival between the groups. Multivariable Cox regression analyses incorporating univariate predictors (inclusion criteria of two-tailed p<0.05) were conducted to evaluate the risk-adjusted impact of the total number and types of postoperative complications on mortality at 30-days, 1-year and 5years. All baseline characteristics were evaluated for potential inclusion in these risk-adjusted models. Individual surgeon volume and year of surgery were included in the risk-adjusted 4
analyses as well. Complication types and combinations were forced into the multivariate models. Complication combinations with sample size less than 5 events were excluded and reported as insufficient events in the multivariate Cox regression models. Statistical analyses were performed with version 9.4 SAS software (SAS Institute, Cary, NC).
Results Study Cohort A total of 9,532 adult patients underwent an STS-indexed cardiac operation during the study period. Of these, 16.8% (n=1600) experienced at least one major postoperative complication with 56.0% (n=897) having an isolated complication, 18.0% (n=288) having 2 complications, and 4.3% (n=68) experiencing at least 3 complications. There were significant differences in the baseline characteristics amongst patients who experienced no complications compared to those with isolated, 2, or at least 3 complications (Table 1). Overall, the STS Predicted Risk of Operative Mortality (STS-PROM) was lowest in the patients who experienced no complications and highest in those with multiple complications.
Unadjusted Survival Mean follow-up was 3.5 ± 2.2 years. An increasing number of complications was associated with increasing overall mortality rates: 12.5% in patients with no complications, 36.3% in patients with 1 complication, 63.9% in patients with 2 complications and 78.4% of patients with at least 3 complications (p<0.0001). In patients who experienced complications, FTR rates increased as the number of complications increased (7.5% vs 28.1% vs 51.5%, p<0.0001) (Table 2). This effect was not limited to the index hospitalization and an increasing mortality trend for patients who experienced an increasing number of complications remained significant at 1-year (18.8% vs 52.1% vs 77.9%, p<0.0001) and 5-year follow-up (33.0% vs 61.8% vs 77.9%, p<0.0001) (Figure 1A and Table 3). Even after excluding early deaths and 5
conducting the analysis conditional on 30-day survival, the negative divergence in survival was still significant at all time intervals (Figure 1B, Supplemental Table 1). By comparison, patients experiencing no complications had 30-day, 1-year, and 5-year mortality rates of 0.8%, 3.5%, and 10.8% (Table 3). Length of intensive care unit stay also demonstrated similar trends, with median number of intensive care unit hours ranging from 38.0 hours (IQR 25.0-61.5 hours) in those with no complications to 358.5 hours (IQR 177.6-713.5 hours) in those with at least 3 complications (p<0.0001) (Table 3). Overall median length of stay ranged from 7 days (IQR 610 days) in those with no complications to 22.5 days (IQR 10-36 days) in those with at least 3 complications (p<0.0001).
Failure to Rescue by Complication Type In those with isolated postoperative complications, early FTR rates were highest with prolonged ventilation at 9.7% and stroke at 6.3% (Table 2). In patients with 2 complications, early FTR rates were highest in those with combined prolonged ventilation and renal failure at 38.4% and combined stroke and prolonged ventilation at 24.5%. In patients with at least 3 complications, early FTR rates were high across each combination ranging from 33.3% to 100%, although sample sizes within each possible combination were low. A composite assessment of all complications, isolated and combined, demonstrated early FTR rates to be highest in renal failure (29.6%), followed by prolonged ventilation (19.2%), stroke (18.4%), and DSWI (18.2%), with the lowest early FTR rate following reoperation (13.5%).
Risk-Adjusted Mortality An increasing number of complications was associated with increasing hazards for mortality at all time intervals in risk-adjusted analysis (Supplemental Table 2). When evaluating types of isolated complications, the greatest hazard for early FTR was prolonged ventilation (Hazard Ratio (HR) 7.8, 95% confidence interval (CI) 5.2-11.6, p<0.0001) while the greatest 6
hazard for LMPC, at 1-year and 5-years, was DSWI (HR 8.0, 95% CI 2.5-25.3, p=0.004 and HR 7.3, 95%CI 3.0-17.8, p<0.0001). When evaluating multiple complications, the greatest hazard for early FTR was prolonged ventilation, reoperation and renal failure (HR 33.0, 95% CI 19.555.8, p<0.0001) whereas combined stroke, prolonged ventilation, and renal failure was the greatest predictor of LMPC at both 1- and 5-year follow-up (HR 31.3, 95% CI 12.8, 77.0, p<0.0001 and HR 26.8, 95% CI 11.0-65.1, p<0.0001). These findings persisted even when adjusted for surgeon annual case volume as well as the year of surgery.
Comment The STS projects that approximately 13% of patients in the current era will experience at least 1 major complication following CABG with 10.5% succumbing to early FTR [6]. The type and number of postoperative complications incurred undoubtedly have important implications for early mortality and health care costs due to prolonged hospitalizations [8,9]. For instance, patients who experience postoperative renal failure, isolated or concomitant with other complications, following cardiac surgery have been reported to have the highest early FTR rates, ranging from 21% to 40%, when compared to other types of isolated postoperative complications [5,6,9]. Moreover, respiratory failure requiring prolonged intubation is also highly associated with mortality and in a propensity matched analysis had an 8-fold increase in FTR [12]. While isolated complications have varying influences on FTR, the effects of multiple complications are substantial. In fact, the negative effects of an increasing number of complications on early mortality have been shown to be multiplicative with profound increases in early FTR rates, exceeding 50%, in those with three or more complications [9]. While the timely and effective interventions necessary to prevent FTR are clearly important mechanisms in preventing early mortality, a crucial aspect of cardiac surgical outcomes that remains unexplored is the long-term survival of patients who survive postoperative complications. Many data registries have been unable to capture events that 7
occur following discharge from the index hospitalization due to logistical limitations such as outof-network care. As such, there are very few studies that explore longitudinal outcomes following cardiac surgery as it relates to postoperative adverse events. In the current era, increasing emphasis is placed on the preoperative risk assessment of cardiac surgical patients in order to provide more cost effective and rational care [10,11]. However, as early mortality and morbidity rates have improved, the longitudinal outcomes, especially as they relate to adverse events in the immediate postoperative period, have become increasingly relevant in evaluating cardiac surgical success [12].
Impact of Postoperative Complications on Long-Term Outcomes after Cardiac Surgery While the long-term impact of postoperative complications after cardiac surgery are not well understood, there are a few reports with 5-year follow-up in the areas of isolated postoperative renal failure, stroke, respiratory failure and infectious complications that have become available in recent years. In a multicenter retrospective study of 513 patients with postoperative renal failure who survived to discharge, the overall survival was 87.7% and the readmission rate was 39.9% at 5-years, with the highest mortality and readmission rates in those requiring acute dialysis postoperatively [13]. The duration and transiency of renal failure are also key components in long-term survival where the propensity-matched hazard for mortality at 5-years is nearly 5-fold greater in those with persistent acute kidney insufficiency or dialysis dependence at the time of discharge [14]. Strokes are one of the most devastating complications after cardiac surgery due to the resulting functional deficits that may necessitate long-term rehabilitative care. A multicenter retrospective study with 1,731 patients with strokes following cardiac surgery demonstrated significantly lower 5-year survival rates (25.1% vs 49.1%, p<0.001) compared to patients without strokes [15]. Patients with strokes also experienced higher rates of additional complications. Another study that evaluated 1,593 propensity matched pairs found that 8
infectious complications after cardiac surgery, including sepsis, DSWI, urinary tract infection, and pneumonia, were associated with reduced risk-adjusted survival, largely attributable to an early hazard for death that gradually resolved over the first year [16]. Prolonged ventilation was also shown in a propensity matched analysis to be associated with lower survival (56.1% vs 88.8%, p<0.001) at 5-year follow-up after cardiac surgery [17].
Study Implications The current study was designed to evaluate the impact of major STS-tracked postoperative complications after cardiac surgery on longitudinal outcomes. For the past several decades, the emphasis on outcome optimization in cardiac surgery has mainly been focused on the in-hospital and 30-day postoperative period, and many programs have accordingly implemented STS systems-based quality metrics to improve these early outcomes [18]. Optimizing longitudinal cardiac surgical outcomes through post-discharge quality metrics have both patient-centered and healthcare economic benefits and understanding the long-term effects of complications on survival are essential in this process. There are several important findings from our analysis. Foremost, the majority of patients who had a major complication had an isolated complication. In those with a clustering of complications, prolonged ventilation tended to be the most frequently shared complication. This is clinically intuitive as patients experiencing major adverse events, particularly when severe, may have difficulty liberating from the ventilator. Examples would include patients with major stroke who are unable to protect their own airway. Another example is a patient who undergoes a reoperation for bleeding and is reintubated or remains intubated due to volume and blood product resuscitation and the necessity for an airway during the repeat procedure. Volume management in patients with acute renal failure postoperatively can be challenging and lead to pulmonary edema and prolonged ventilation. In some clinical scenarios, prolonged ventilation is not the subsequent complication but rather the inciting complication that leads to 9
other complications. For example, patients with chronic lung disease may have primary respiratory failure following cardiac surgery which then can lead to pneumonia and multiorgan dysfunction. Of interest is the fact that most patients in our study who experienced a complication had a single isolated complication, which may suggest that even in the occurrence of one of these adverse events, successful early recognition and aggressive management can potentially prevent subsequent complications, although this assumption would have to be evaluated in future studies. The finding that renal failure was associated with the highest unadjusted composite early FTR rates is consistent with prior reports [6,9]. Moreover, in an analysis of the STS National Database for isolated CABG, the occurrence of renal failure was associated with an early FTR rate of 22.3%, which was the highest of the major morbidities, although the authors did not evaluate DSWI due to its rare occurrence [6]. A single institution analysis of 2,477 cardiac surgical patients found that the early FTR rate for renal failure was 42% which was only surpassed by DSWI at 50% although there were only 4 patients who developed DSWI [9]. Similar to our findings, both of these prior analyses demonstrated that prolonged intubation was the most common major complication [6,9]. Perhaps the most provocative finding in our analysis relates to the impact of postoperative complications on long-term survival, an impact which is profound and persistent even after excluding early deaths. There are several plausible explanations for these findings. A patient who experiences a debilitating complication may survive the early postoperative period, but can be left with residual functional limitations that lead to impaired survival over the ensuing months or years. This can often be a result of more chronic issues like malnutrition and failure to thrive. These issues are likely more prevalent in patients experiencing multiple complications. Although the occurrence of complications is strongly linked to preoperative comorbidities, the occurrence of FTR is influenced heavily by systems-based and practice10
based factors. These factors include nursing-to-patient ratios, intensive care unit staffing, availability and expertise of consultative services, and infrastructure and clinical protocols leading to earlier intervention [5,6]. The relative impact of each of these factors varies as a function of time from the operation. For example, whereas intensive care unit staffing and resources play a vital role in early FTR, outpatient staffing and monitoring of patients for medication compliance as well as access to effective long-term rehabilitative services play more important roles in LMPC. Future studies will help delineate systems-based clinical enhancements and their contribution to improving late survival after cardiac surgery.
Limitations There are inherent limitations related to this study’s retrospective design. The severity and granular details of each complication were not evaluated but likely have an impact on outcomes [13-15]. For instance, in cases of stroke where mechanical thrombectomy is not available, patients with isolated small vessel occlusion have drastically different outcomes than patients with large vessel occlusion or hemorrhagic conversion [19]. The timing of complications was also not evaluated and therefore sequences of adverse events could not be identified. The specific causes of death were unavailable in our dataset, and therefore only associative relationships could be demonstrated with limited insight into causality. Finally, some combinations in the 3 or more complications category occurred infrequently and these groups may be subject to a type II error.
Conclusions This study evaluated 9,532 patients who underwent an index STS cardiac operation and demonstrated a profound association between an increasing number of major postoperative complications and increasing FTR and LMPC. The magnitude of this negative effect also varied by the type and combinations of various complications. Future studies are needed to 11
understand if systems-based factors are associated with the persistent impact postoperative complications have on longer-term survival after cardiac surgery.
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References 1. Ghaferi AA, Birkmeyer JD, Dimick JB. Variation in hospital mortality associated with inpatient surgery. N Engl J Med. 2009;361(14):1368-75. 2. Silber JH, Williams SV, Krakauer H, Schwartz JS. Hospital and patient characteristics associated with death after surgery. A study of adverse occurrence and failure to rescue. Med Care. 1992;30(7):615-29. 3. Gonzalez AA, Dimick JB, Birkmeyer JD, Ghaferi AA. Understanding the volume-outcome effect in cardiovascular surgery: the role of failure to rescue. JAMA Surg. 2014;149(2):119-23. 4. Silber JH, Rosenbaum PR, Schwartz JS, Ross RN, Williams SV. Evaluation of the complication rate as a measure of quality of care in coronary artery bypass graft surgery. JAMA. 1995;274(4):317-23. 5. Reddy HG, Shih T, Englesbe MJ, et al. Analyzing "failure to rescue": is this an opportunity for outcome improvement in cardiac surgery? Ann Thorac Surg. 2013;95(6):1976-81. 6. Edwards FH, Ferraris VA, Kurlansky PA, et al. Failure to Rescue Rates After Coronary Artery Bypass Grafting: An Analysis From The Society of Thoracic Surgeons Adult Cardiac Surgery Database. Ann Thorac Surg. 2016;102(2):458-64. 7. The Society of Thoracic Surgeons Cardiac Surgery Database: database data collection. Available at https://www.sts.org/registries-research-center/sts-national-database/adultcardiac-surgery-database/data-collection. Accessed July 3, 2019. 8. Khuri SF, Henderson WG, DePalma RG, Mosca C, Healey NA, Kumbhani DJ; Participants in the VA National Surgical Quality Improvement Program. Determinants of long-term survival after major surgery and the adverse effect of postoperative complications. Ann Surg. 2005;242(3):326-41.
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9. Crawford TC, Magruder JT, Grimm JC, et al. Complications After Cardiac Operations: All Are Not Created Equal. Ann Thorac Surg. 2017;103(1):32-40. 10. Rahmanian PB, Adams DH, Castillo JG, Carpentier A, Filsoufi F. Predicting hospital mortality and analysis of long-term survival after major noncardiac complications in cardiac surgery patients. Ann Thorac Surg. 2010;90(4):1221-9. 11. D'Agostino RS, Jacobs JP, Badhwar V, et al. The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2018 Update on Outcomes and Quality. Ann Thorac Surg. 2018;105(1):15-23. 12. Shahian DM, O'Brien SM, Sheng S, et al. Predictors of long-term survival after coronary artery bypass grafting surgery: results from the Society of Thoracic Surgeons Adult Cardiac Surgery Database (the ASCERT study). Circulation. 2012;125(12):1491-500. 13. Brown JR, Hisey WM, Marshall EJ, et al. Acute Kidney Injury Severity and Long-Term Readmission and Mortality After Cardiac Surgery. Ann Thorac Surg. 2016;102(5):14821489. 14. Brown JR, Kramer RS, Coca SG, Parikh CR. Duration of acute kidney injury impacts long-term survival after cardiac surgery. Ann Thorac Surg. 2010;90(4):1142-8. 15. Chen CC, Chen TH, Tu PH, et al. Long-Term Outcomes for Patients With Stroke After Coronary and Valve Surgery. Ann Thorac Surg. 2018;106(1):85-91. 16. Robich MP, Sabik JF 3rd, Houghtaling PL, et al. Prolonged effect of postoperative infectious complications on survival after cardiac surgery. Ann Thorac Surg. 2015;99(5):1591-9. 17. Rajakaruna C, Rogers CA, Angelini GD, Ascione R. Risk factors for and economic implications of prolonged ventilation after cardiac surgery. J Thorac Cardiovasc Surg. 2005;130(5):1270-7.
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18. Chu D, Chan P, Wei LM, et al. The Effect of Comprehensive Society of Thoracic Surgeons Quality Improvement on Outcomes and Failure to Rescue. Ann Thorac Surg. 2015;100(6):2147-50. 19. Madeira M, Martins C, Koukoulis G, Marques M, Reis J, Abecassis M. Mechanical Thrombectomy for Stroke After Cardiac Surgery. J Card Surg. 2016;31(8):517-20
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Figure Legends Figure 1. Kaplan-Meier estimates demonstrating survival (A) and survival contingent on 30-day survival (B) stratified by the number of postoperative complications (notated as 0: no complications, 1: 1 complication, 2: 2 complications, 3: 3 or more complications). Figure 2. Forest plot displaying the adjusted hazard ratios for 5-year mortality in patients with various combinations of postoperative complications. Abbreviations: DSWI, deep sternal wound infection; PVT, prolonged ventilation; RF, renal failure; Reop, reoperation
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Table 1. Baseline characteristics stratified by the number of complications. Variable Age (years) Female Race Caucasian Black BMI (kg/m2) Hypertension Diabetes Mellitus Dialysis Dependence PVD CVD Previous MI Immunosuppression Prior heart failure COPD NYHA Class No heart failure I II III IV Operative status Elective Urgent Emergent Emergent salvage LVEF (%) Albumin (mg/dL) Creatinine (mg/dL) Preoperative IABP Type of Operation Isolated CABG Isolated MVr Isolated MVR Isolated AVR CABG + AVR CABG + MVr CABG + MVR STS-PROM (%) CPB time (min)
None (n=8279)
Isolated (n= 897)
Two (n= 288)
Multiple (≥3) (n= 68)
P-Value
66.56 ± 0.12 29.52% (2444)
69.12 ± 0.37 36.79% (330)
70.42 ± 0.66 33.33% (96)
69.41 ± 1.36 41.18% (28)
<0.0001 <0.0001
93.88% (7772) 4.01% (332) 29.85 ± 0.07 85.72% (7097) 40.25% (3332) 2.09% (173) 18.37% (1521) 20.57% (1703) 48.48% (4014) 5.27% (436) 17.48% (1447) 20.46% (1694)
91.97% (825) 5.91% (52) 30.24 ± 0.21 87.51% (785) 48.49% (435) 5.24% (47) 28.99% (260) 28.54% (256) 56.08% (503) 7.80% (70) 28.99% (260) 30.88% (277)
89.93% (259) 7.64% (22) 30.15 ± 0.36 88.89% (256) 53.13% (153) 1.04% (3) 30.21% (87) 35.76% (103) 61.46% (177) 8.68% (25) 31.94% (92) 35.42% (102)
92.65% (63) 5.88% (4) 31.07 ± 0.75 82.35% (56) 64.71% (44) 1.47% (1) 32.35% (22) 38.24% (26) 64.71% (44) 10.29% (7) 32.35% (22) 35.29% (24)
0.009 0.001 0.10 0.17 <0.0001 <0.0001 <0.0001 <0.0001 <0.0001 0.0005 <0.0001 <0.0001 <0.0001
78.25% (6478) 0.69% (57) 4.94% (409) 10.59% (877) 5.53% (458)
60.65% (544) 0.45% (4) 5.46% (49) 17.39% (156) 16.05% (144)
55.21% (159) 0.69% (2) 5.21% (15) 18.06% (52) 20.83% (60)
48.53% (33) 0.0% (0) 5.88% (4) 16.18% (11) 29.41% (20) <0.0001
46.85% (3878) 50.10% (4147) 250 (3.02%) 0.04% (3) 51.02 ± 0.14 3.65 ± 0.005 1.13 ± 0.02 3.97% (329)
35.23% (316) 54.85% (492) 86 (9.59%) 0.33% (3) 47.74 ± 0.41 3.48 ± 0.02 1.43 ± 0.03 11.82% (106)
32.99% (95) 55.21% (159) 33 (11.46%) 0.35% (1) 45.82 ± 0.73 3.42 ± 0.03 1.34 ± 0.06 11.81% (34)
23.53% (16) 61.76% (42) 13.24% (9) 1.47% (1) 48.72 ± 1.51 3.44 ± 0.06 1.23 ± 0.12 13.24% (9)
5282 (63.80%) 409 (4.94%) 147 (1.78%) 1297 (15.67%) 849 (10.25%) 238 (2.87%) 57 (0.69%) 2.66 ± 0.05 109.19 ± 0.43
487 (54.29%) 47 (5.24%) 32 (3.57%) 124 (13.82%) 128 (14.27%) 61 (6.80%) 18 (2.01%) 6.63 ± 0.16 123.40 ± 1.32
146 (50.69%) 6 (2.08%) 6 (2.08%) 39 (13.54%) 57 (19.79%) 24 (8.33%) 10 (3.47%) 8.28 ± 0.29 127.10 ± 2.32
33 (48.53%) 2 (2.94%) 3 (4.41%) 8 (11.76%) 11 (16.18%) 5 (7.35%) 6 (8.82%) 9.21 ± 0.59 138.98 ± 4.79
<0.0001 <0.0001 <0.0001 <0.0001 <0.0001
<0.0001 <0.0001 17
Ischemic time (min)
81.03 ± 0.44
92.32 ± 1.32
94.64 ± 2.33
101.96 ± 4.74
<0.0001
Abbreviations: BMI, body mass index; COPD, chronic obstructive pulmonary disease; CPB, cardiopulmonary bypass; CVD, cerebrovascular disease; PVD, peripheral vascular disease; LVEF, left ventricular ejection fraction; MI, myocardial infarction; STS-PROM, Society for Thoracic Surgeons Predicted Risk of Mortality.
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Table 2. Unadjusted early failure-to-rescue rates by complication type. Complication Types None of five complications Isolated Stroke Prolonged ventilation DSWI Reoperation Renal failure Total Isolated Two Complications Stroke + Prolonged ventilation Stroke + Unplanned reoperation Stroke + Renal failure Prolonged ventilation + DSWI Prolonged ventilation + Reoperation Prolonged ventilation + Renal failure DSWI + Reoperation Reoperation + Renal failure Total Two Complications Three Complications Stroke +Prolonged ventilation + Reoperation Stroke + Prolonged ventilation + Renal failure Prolonged ventilation + DSWI + Reoperation Prolonged ventilation + DSWI + Renal failure Prolonged ventilation + Reoperation + Renal failure Total Three Complications More than Three Complications Overall Total Composite Mortality Stroke Prolonged ventilation DSWI Reoperation Renal failure
No. 8279
Failure to Rescue % (n) 0.75% (62)
96 506 9 177 109 897
6.25% (6) 9.68% (49) 0% (0) 3.39% (6) 5.50% (6) 7.47% (67)
53 1 1 5 70 151 1 6 288
24.53% (13) 0% (0) 0% (0) 0% (0) 12.86% (9) 38.41% (58) 0% (0) 16.67% (1) 28.22% (81)
6 16 1 3 34 59 9 9532
33.33% (2) 50.00% (8) 100.00% (1) 33.33% (1) 52.94% (18) 50.85% (30) 55.56% (5) 2.57% (245)
179 853 22 304 328
18.44% (33) 19.23% (164) 18.18% (4) 13.49% (41) 29.57% (97)
Abbreviations: DSWI, deep sternal wound infection.
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Table 3. Length of stay and mortality stratified by number of complications. Variable
Time Interval
ICU Hours Median [IQR] Hospital LOS Median [IQR] Mortality Operative 1-year 5-years Overall
None (n=8279) 38.0 [25.0-61.5]
Isolated (n= 897) 108.0 [67.8-192.5]
Two (n= 288) 242.2 [126.0-504.0]
Multiple (≥3) (n= 68) 358.5 [177.6-713.5]
7 [6-10]
13 [9-20]
21.0 [12-31]
22.5 [10-36]
0.75% (62) 3.48% (288) 10.83% (897) 12.51% (1036)
7.47% (67) 18.84% (169) 33.00% (296) 36.34% (326)
28.13% (81) 52.08% (150) 61.81% (178) 63.89% (184)
51.47% (35) 77.94% (53) 77.94% (53) 79.41% (54)
P-Value <0.0001
<0.0001 <0.0001 <0.0001 <0.0001 <0.0001
Abbreviations: HR, Hazard Ratio; ICU, intensive care unit; LOS, length of stay.
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