Interact CardioVasc Thorac Surg 2008;7:90-95. doi:10.1510/icvts.2007.164483
© 2008 European Association of Cardio-Thoracic Surgery
Institutional report - Cardiac general |
Early and late outcomes of cardiac surgery in patients with moderate to severe preoperative renal dysfunction without dialysis
Farzan Filsoufi*,
Parwis B. Rahmanian,
Javier G. Castillo,
Joanna Chikwe,
Alain Carpentier and
David H. Adams
Department of Cardiothoracic Surgery, Mount Sinai School of Medicine, 1190 Fifth Avenue, New York, NY 10029-1028, USA
Received 3 August 2007;
received in revised form 31 October 2007;
accepted 1 November 2007
*Corresponding author. Tel.: +1 212 659 6820; fax: +1 212 659 6818.
E-mail address: farzan.filsoufi{at}mountsinai.org (F. Filsoufi).
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Abstract
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It is well known that end-stage renal failure requiring dialysis negatively impacts early and late outcome of cardiac surgery. However, data with respect to non-dialysis-dependent renal failure patients (NDRF) are limited. We retrospectively analyzed 6940 consecutive patients undergoing cardiac surgery from January 1998 to September 2006. Patients undergoing cardiac transplantation and ventricular assist device implantation (n=246) and dialysis dependent patients (n=245) were excluded. NDRF was present in 135 (2.1%) patients (mean age 64±14, 38% female). NRDF patients were more likely to present with cardiac related risk factors including ejection fraction <30% (P<0.001), prior myocardial infarction (P<0.001), congestive heart failure (P<0.001), active endocarditis (P<0.001) and hemodynamic instability (P<0.001). The estimated odds (OR) of hospital mortality in NDRF patients was 6.6 (P<0.001). Multivariate analysis retained NDRF as an independent factor for increasing the risk of hospital mortality among patients undergoing cardiac surgery (OR=5.1, P<0.001). Patients with NDRF were more likely to experience major postoperative complications when compared to the control group. One- and 5-year survival in NDRF patients was 82±4% and 63±6%, respectively, and significantly reduced compared to the control group. NDRF is a strong independent predictor of hospital mortality and morbidity in patients undergoing cardiac surgery. Preoperative renal dysfunction also adversely affects long-term survival in these patients.
Key Words: Renal dysfunction; Cardiac surgery; Mortality; Morbidity; Long-term survival
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1. Introduction
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The incidence of chronic renal disease is increasing with a current prevalence of an estimated 7% in the USA [1]. Chronic renal dysfunction is commonly associated with coronary atherosclerotic disease and occasionally with valvular heart disease [2]. During the last decade the number of patients with impaired renal function requiring cardiac surgery has steadily increased [3]. Although it is well known that end-stage renal failure requiring dialysis negatively impacts early and late outcome of patients undergoing cardiac surgery [2], data with respect to non-dialysis-dependent renal failure patients (NDRF) are more limited. Most recent studies looking specifically at the impact of NDRF on cardiac surgery outcome have included small numbers of patients and have mainly focused on early surgical results. These studies have provided very little information regarding long-term survival and its predictors in this population. In addition to the growing number of patients with renal failure, there has been a significant worsening in the overall risk profile of patients referred for cardiac surgery, and the findings of previous studies may therefore not be reliably applicable. This study was designed to investigate the effect of NDRF on early mortality and morbidity as well as late survival in a contemporary series of patients who underwent cardiac surgery at our institution.
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2. Material and methods
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We retrospectively analyzed a series of 6940 consecutive patients undergoing cardiac surgery from January 1998 to September 2006. Patients undergoing cardiac transplantation and ventricular assist device implantation (n=246) and dialysis dependent patients (n=245) were excluded. The protocol was approved by our institutional review board.
Clinical variables were prospectively entered into the New York State Department of Health (NYSDH) data registry and used for this retrospective analysis. NDRF was defined by the NYSDH as a baseline creatinine level >2.5 mg/dl without dialysis. The remaining patients with a creatinine <2.5 mg/dl served as control group. Appendix 1 describes patient demographic data, preoperative risk factors, intraoperative variables, postoperative complications and their definitions. In addition, the logistic EuroSCORE was used for risk stratification. Follow-up survival information was obtained by cross matching patients' social security numbers with the web based social security death index [4]. The details of surgical management have been extensively reported previously [5]. Operative procedures are summarized in Table 1.
2.1. Statistical analysis
Normally distributed continuous variables are presented as mean±S.D. or as median and interquartile range (IQR). Categorical variables are shown as the percentage of the sample. The  2-test was used to evaluate potential confounders of the relationship between renal failure group and hospital mortality and morbidities. Stepwise multivariate logistic regression was then performed to assess the influence of NDRF as an independent risk factor for hospital mortality and postoperative morbidities [6]. A P-value <0.05 was considered as significant for all statistical methods. Long-term survival was analyzed using Kaplan–Meier survival curves. Differences in patient characteristics were controlled by Cox proportional analysis. The statistical analyses were performed with the use of SPSS 15 (SPSS Inc., Chicago, Il, USA).
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3. Results
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A total of 6449 patients (mean age 64±14 years, 2423 (38%) female) were included in this study. NDRF was present in 135 (2.1%) patients. There were significant differences when comparing NDRF patients with the control group (Table 1). The two groups were similar with respect to the type of surgical procedure. Predicted operative mortality (EuroSCORE) was significantly higher in the NDRF group (19±16% vs. 11±12%, P<0.001).
3.1. Hospital mortality
The overall hospital mortality was 3.6% (231 patients). Patients with NDRF experienced a significantly increased hospital mortality (n=24, 17.8% vs. n=207, 3.3%; P<0.001) (Table 2). When patients were stratified by EuroSCORE, the observed mortality rate was higher for NDRF patients in all three predicted risk groups compared to the control group (P<0.001). Causes of death in NDRF patients were low cardiac output in 5 (21%), multi system organ failure in 7 (29%), mesenteric ischemia in 4 (17%), respiratory failure in 6 (25%), and sepsis in 2 (8%) patients.
The estimated odds of hospital mortality in NDRF patients relative to the control group was 6.6 (P<0.001). In multivariate analysis NDRF remained a statistically significant independent factor of hospital mortality (relative odds ratio (OR)=5.1, 95% confidence interval (CI)=2.9–8.7, P<0.001). Multivariate analysis also revealed hemodynamic instability (OR=4.0), acute myocardial infarction (OR=5.5), PVD (OR=2.4), reoperation (OR=1.8), endocarditis (OR=2.7), ejection fraction <30% (OR=1.8), age >70 years (OR=1.6), female gender (OR=1.5), congestive heart failure (OR=1.6), diabetes (OR=1.5), and aortic procedures (OR=2.4) as independent predictors of hospital mortality. In the subgroup of patients with NDRF, active endocarditis (OR=6.13) and hemodynamic instability (OR=5.6) were independent predictors of hospital mortality (Fig. 1).
3.2. Morbidity
In the group of patients with NDRF, 19 (14.1%) required postoperative hemodialysis compared to 120 (1.9%) in the control group (P<0.001). Patients with NDRF who developed postoperative dialysis were more likely to have undergone a previous cardiac operation (P=0.027), to present with hemodynamic instability on admission (P=0.011) or to undergo valve procedures (P=0.01). They were less likely to undergo CABG (P=0.026) compared to NDRF patients who did not require postoperative dialysis. The mortality in the group of NDRF patients with postoperative dialysis was 36.8% (7/19) compared to 14.7% (17/116) in patients without dialysis (P=0.027).
Patients with NDRF had a significantly higher rate of postoperative complications (Table 2).
In multivariate analysis, NDRF was the strongest independent predictor of postoperative RF with the need for dialysis (OR=5.7, CI=3.2–10.2, P<0.001). NDRF was also an independent predictor of respiratory failure (OR=2.2) and gastrointestinal complications (OR=3.2) (Table 3).
The median length of stay among patients with NDRF and the control group was 10 (IQR: 7–19) days and 7 (IQR: 5–11) days, respectively (P<0.001).
3.3. Long-term survival
Follow-up data were completed for all discharged patients with a mean of 3.9±2.5 years (range 6 months to 8.6 years). There were 879 (15.5%) late deaths. During follow-up, 33 (34%) patients died in the NDRF group vs. 846 (15.2%) patients in the control group (P<0.001). Multivariate analysis revealed NDRF (OR=2.2, P=0.001) to be an independent predictor of late mortality. Survival at 1 and 5 years was 82.0±4.0% and 62.5±6.0% in the NDRF group vs. 94.2±0.3% and 83.2±0.6% in the control group (P<0.001) (Fig. 2). When only patients with NDRF were analyzed, age >70 years (OR=21.7, P=0.003), PVD (OR=18.9, P=0.002), hypertension (OR=17.2, P=0.002), COPD (OR=15.5, P=0.041), and diabetes (OR=5.5, P=0.034) were identified as independent predictors of late survival (Table 4).
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Fig. 2. Unadjusted (a) and adjusted (b) long-term survival. NDRF, non-dialysis-dependent renal failure.
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4. Discussion
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4.1. Mortality
This is one of the largest single center studies to analyze the early and late outcome of cardiac surgery in patients with preoperative non-dialysis dependent renal dysfunction. The main finding was patients with NDRF are over five times as likely to die perioperatively as patients without a history of renal failure. There was an additional excess mortality in NDRF patients who required postoperative dialysis. A large review from the Society of Thoracic Surgeons National Database showed that a creatinine level >2 mg/dl was associated with an increased operative mortality (OR=2.0) [7]. More recently a few groups have focused specifically on the cohort of patients with preoperative renal failure undergoing cardiac surgery and have analyzed the impact of varying degrees of renal dysfunction on surgical outcome following CABG [8, 9]. Anderson et al. analyzed the Veterans Affairs database entries of 3954 CABG patients and identified a baseline creatinine >1.5 mg/dl as an independent predictor of hospital mortality [9]. In their subgroup analysis, patients with baseline creatinine of 1.5–3.0 mg/dl had an operative mortality of 6.8% compared to 3.0% in the control group (creatinine <1.5 mg/dl) (P<0.001). Weerasinghe et al. reported a mortality rate of 7.6% among 66 patients with a creatinine level of 1.5–1.7 mg/dl increasing to 18.5% in 54 patients with a creatinine >1.7 mg/dl (P<0.001) [8]. In our study, using the NYSDH definition of renal failure without dialysis (baseline serum creatinine >2.5 mg/dl), we found that the hospital mortality in NDRF patients undergoing all types of cardiac procedures was over five times higher than that of control patients (17.8% compared to 3.3%, P<0.001). In the subgroup of patients who underwent CABG, the adjusted mortality was three times higher in NDRF patients. These findings suggest that despite the improvements in the outcome of cardiac surgery achieved during the last decade through incremental improvements in surgical techniques and peri-operative management, the mortality rate in NDRF patients remains high. One potential explanation for this is the burden of diffuse atherosclerotic disease involving multiple organs, in combination with impairment of myocardial function in this patient population. In our series, the cause of death in 17 out of 24 (71%) patients was directly related to perioperative hemodynamic compromise and low cardiac output in the setting of atherosclerotic disease. Fourteen of these patients presented with cardiovascular risk factors such as PVD, diabetes, advanced age, left ventricular dysfunction, previous myocardial infarction or stroke. Hemodynamic instability and acute endocarditis were found to be additional risk factors for hospital mortality in the NDRF group. These findings suggest that, in this high-risk group of patients, it is particularly important to optimize perioperative hemodynamic status and to prevent prolonged low cardiac output, which is associated with a fatal outcome in a high proportion of patients.
4.2. Morbidity
In addition to increased mortality, we demonstrate that NDRF is associated with postoperative dialysis, respiratory failure and gastrointestinal complications. In our study, NDRF was the strongest predictor of postoperative dialysis confirming the findings of previous studies [2, 9, 10]. In our cohort, patients with NDRF had a 5.6-times higher adjusted risk for postoperative dialysis compared to patients without preoperative renal dysfunction. The occurrence of this complication was associated with a significant increase in mortality (37%). These patients were also significantly more likely to present with complications such as respiratory failure, gastrointestinal complications, sepsis and stroke.
Patients with NDRF were at over three times higher adjusted risk for postoperative gastrointestinal complications compared to the control group. Gastrointestinal complications occurred in ten NDRF patients, with ischemic etiology in the majority of cases. It has been suggested that cardiopulmonary bypass contributes to mesenteric ischemia by affecting regional differences in intestinal blood flow [11]. These changes in flow pattern may be exacerbated by contributing factors such as endogenous and pressor mediated vasoconstriction, and low cardiac output in the setting of pre-existing mesenteric atherosclerosis. The associated atherosclerotic burden in patients with renal failure may therefore explain the increased incidence of ischemic GI events in this patient population [5, 11]. This is supported by Mangi et al. who reported a creatinine >1.4 mg/dl as a predictor of gastrointestinal events in a large cohort of patients undergoing cardiac surgery [11].
4.3. Long-term survival
There is limited data on long-term survival of NDRF patients following cardiac surgery. Our study has shown that 1–5-year survival is significantly reduced in NDRF patients compared to the control group. In multivariate analysis, NDRF was an independent predictor of decreased long-term survival. The impact of associated atherosclerotic risk factors on long-term survival of NDRF patients after cardiac surgery has not been well investigated. In our study, when NDRF patients were analyzed, risk factors such as advanced age, diabetes, hypertension, and PVD were found to be independently associated with decreased late survival. Stratifying patients by EuroSCORE, a system based on multiple preoperative risk factors, which heavily weighted the presence of atherosclerotic disease, appears to support these findings. In this very high-risk group of patients with multiple comorbidities, aggressive management of cardiovascular risk factors may offer a route to improving long-term survival.
4.4. Strengths and limitations
This is the largest contemporary single center analysis of outcomes in NDRF patients undergoing cardiac surgery. The data provided were collected from a state mandated database with external audit and, therefore, provides very accurate description of perioperative variables. This study does, however, present certain limitations. Firstly, given that this is a retrospective observational study, conclusions are necessarily limited in their application. Secondly, clinical outcomes are limited to major postoperative morbidity and mortality with no information on late complications, quality of life, cause of death during follow-up, or cost-analysis.
4.5. Summary
NDRF is a strong independent predictor of operative mortality in patients undergoing cardiac surgery. NDRF patients who require dialysis postoperatively experience considerable excess mortality. Long-term survival is significantly reduced in NDRF patients, particularly those with atherosclerotic risk factors such as advanced age, diabetes, hypertension and peripheral vascular disease. These results emphasize the need for a focused therapeutic approach to NDRF in order to optimize hemodynamic status, as well as aggressive management of cardiovascular risk factors to improve long-term survival.
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Appendix 1 Variables included in this study
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References
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- Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol 1998; 9:S16–S23.[CrossRef][Medline]
- Frenken M, Krian A. Cardiovascular operations in patients with dialysis-dependent renal failure. Ann Thorac Surg 1999; 68:887–893.[Abstract/Free Full Text]
- Ferguson TB Jr, Hammill BG, Peterson ED, De Long ER, Grover FL. A decade of change — risk profiles and outcomes for isolated coronary artery bypass grafting procedures, 1990–1999: a report from the STS National Database Committee and the Duke Clinical Research Institute. Society of Thoracic Surgeons. Ann Thorac Surg 2002; 73:480–489. discussion 489–490.[Abstract/Free Full Text]
- Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999; 16:9–13.[Abstract/Free Full Text]
- Filsoufi F, Rahmanian PB, Castillo JG, Scurlock C, Legnani PE, Adams DH. Predictors and outcome of gastrointestinal complications in patients undergoing cardiac surgery. Ann Surg 2007; 246:323–329.[CrossRef][Medline]
- Hosmer DW, Lemeshow S. Applied logistic regression1989;New York: Wiley.
- Shroyer AL, Coombs LP, Peterson ED, Eiken MC, De Long ER, Chen A, Ferguson Jr TB, Grover FL, Edwards FH. The Society of Thoracic Surgeons: 30-day operative mortality and morbidity risk models. Ann Thorac Surg 2003; 75:1856–1864. discussion 1864–1855.[Abstract/Free Full Text]
- Weerasinghe A, Hornick P, Smith P, Taylor K, Ratnatunga C. Coronary artery bypass grafting in non-dialysis-dependent mild-to-moderate renal dysfunction. J Thorac Cardiovasc Surg 2001; 121:1083–1089.[Abstract/Free Full Text]
- Anderson RJ, O'Brien M, Ma Whinney S, Villa Nueva CB, Moritz TE, Sethi GK, Henderson WG, Hammermeister KE, Grover FL, Shroyer AL. Renal failure predisposes patients to adverse outcome after coronary artery bypass surgery. VA Cooperative Study #5. Kidney Int 1999; 55:1057–1062.[CrossRef][Medline]
- Mangano CM, Diamondstone LS, Ramsay JG, Aggarwal A, Herskowitz A, Mangano DT. Renal dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resource utilization. The multi-center study of perioperative ischemia research group. Ann Intern Med 1998; 128:194–203.[Abstract/Free Full Text]
- Mangi AA, Christison-Lagay ER, Torchiana DF, Warshaw AL, Berger DL. Gastrointestinal complications in patients undergoing heart operation: an analysis of 8709 consecutive cardiac surgical patients. Ann Surg 2005; 241:895–901. discussion 901–894.[CrossRef][Medline]
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Abstract
1. Introduction