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Ann Thorac Surg 2002;74:458-463
© 2002 The Society of Thoracic Surgeons

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Original article: cardiovascular

Long-term survival of dialysis patients after coronary bypass grafting

^a Department of Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
^b Department of Surgery, Veterans Administration Medical Center, White River Junction, Vermont, USA
^c Department of Surgery, Maine Medical Center, Portland, Maine, USA
^d Department of Surgery, Beth-Israel Deaconess Medical Center, Boston, Massachusetts, USA
^e Department of Surgery, Catholic Medical Center, Manchester, New Hampshire, USA
^f Department of Surgery, Worcester Medical Center, Worcester, Massachusetts, USA
^g Departments of Medicine and Community & Family Medicine and the Center for the Evaluative Clinical Sciences, Dartmouth Medical School, Hanover, New Hampshire, USA
^h Department of Surgery, Eastern Maine Medical Center, Bangor, Maine, USA
ⁱ Department of Surgery, Fletcher Allen Health Care, Burlington, Vermont, USA

* Address reprint requests to Dr Dacey, Cardiothoracic Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA 03756-0001
e-mail: lawrence.j.dacey{at}dartmouth.edu

Presented at the Thirty-eighth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2002.

	Abstract

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Background. Dialysis patients are undergoing coronary artery bypass grafting (CABG) with increasing frequency. The long-term effect of preoperative dialysis-dependent renal failure on mortality after CABG has not been well studied.

Methods. We conducted a prospective regional cohort study of 15,574 consecutive patients undergoing isolated CABG in northern New England from 1992 to 1997. Patient records were linked to the National Death Index to assess mortality. Five-year survival and adjusted hazard ratios were calculated.

Results. During 32,589 person-years of follow-up 1298 deaths were recorded. Renal failure was present in 283 patients (1.8%), and 67.8% of patients with renal failure also had diabetes or peripheral vascular disease (PVD). The annual death rate was 3.8% for nonrenal failure patients, 16.9% for all renal failure patients, 7.7% for renal failure patients without diabetes or PVD, and 23.0% for renal failure patients with diabetes or PVD. Five-year survival was 83.5% for nonrenal failure patients, 55.8% for all renal failure patients, 78.5% for renal failure patients without diabetes or PVD, and 42.2% for renal failure patients with diabetes or PVD. After adjustment for differences in base line patient and disease characteristics, renal failure patients without diabetes or PVD had a statistically nonsignificant 57% increase rate of death compared with those without renal failure; renal failure patients with diabetes or PVD had more than a fourfold increased risk of death.

Conclusions. After adjustment for other risk factors, renal failure remains a highly significant predictor of decreased long-term survival in CABG patients. Patients with renal failure plus diabetes or PVD are at especially high risk of death.

	Introduction

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Estimates suggest that 350,000 patients will have end-stage renal disease by 2010 in the United States. The annual mortality rate for dialysis patients approaches 25% per year, with 50% of the patients dying of cardiovascular disease [1]. Survival of dialysis patients who have a myocardial infarction is poor; 1-year survival is 46.1% and 5-year survival is only 10.1% [2]. Increasingly, dialysis patients are being referred for coronary artery revascularization procedures in an attempt to improve long-term survival.

Outcomes of dialysis patients after coronary artery bypass grafting (CABG) have been shown to be superior to percutaneous intervention [3–6]. In-hospital outcomes of dialysis patients undergoing CABG have been described [7]. Several studies, mostly from single institutions, have attempted to identify risk factors in dialysis patients that contribute to their poor long-term survival after CABG [8, 9]. However, literature is scarce about long-term survival of dialysis patients undergoing CABG compared with nondialysis patients after adjustment for multiple comorbidities.

We conducted a prospective regional cohort study of 15,574 patients undergoing isolated CABG in northern New England from 1992 to 1997 and linked these records to the National Death Index to assess long-term mortality. Using patient-level data, we assessed the role of multiple comorbid conditions and the impact of dialysis-dependent renal failure on long-term survival.

	Material and methods

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Patients and setting
The Northern New England Cardiovascular Disease Study Group (NNECDSG) is a voluntary research consortium representing all medical centers in Maine, New Hampshire, and Vermont where CABG is performed, along with the Beth Israel Deaconess Medical Center (Boston, MA) and the Worcester Medical Center (Worcester, MA). Since 1987, the NNECDSG has maintained a prospective registry of all patients undergoing cardiac operations in the region. This multicenter study included 15,574 consecutive patients undergoing isolated CABG from January 1, 1992, to December 31, 1996 in northern New England.

Data collection
Data were recorded prospectively for all patients. The collection of patient data included patient age, sex, comorbidities (diabetes, peripheral vascular disease [PVD], dialysis-dependent renal failure, chronic obstructive pulmonary disease [COPD], congestive heart failure, cancers, and liver disease), current cardiac condition (recent [< 7 days] myocardial infarction, current congestive heart failure), and previous cardiac operation. Dialysis-dependent renal failure, defined by the preoperative use of hemodialysis or peritoneal dialysis, was determined prospectively. Patients in whom dialysis was initiated after the operation were included in the nondialysis CABG population, not in the renal failure group. Peripheral vascular disease was defined as cerebrovascular disease (prior stroke, prior transient ischemic attack or amaurosis fugax, prior carotid surgery, carotid stenosis by history or radiographically documented, or carotid bruit), or lower extremity disease (claudication, prior lower extremity bypass, prior nontraumatic lower extremity amputation, absence of pedal pulses [recorded as absent if nonpalpable], or lower extremity ulcers). Diabetes was defined as documentation of diabetes (diet controlled, on oral medication, or on insulin) in the patient medical record or by patient history. Procedural data included cardiac catheterization variables (degree of left main coronary artery stenosis, total number of significantly diseased coronary arteries, left ventricular end-diastolic pressure, and ejection fraction) and priority of the operation. The priority of a patient’s operation was defined as emergency, urgent, or elective. Emergency indicated that medical factors relating to the patient’s cardiac disease dictated that the procedure be performed within hours to prevent morbidity or death. Urgent indicated that medical factors required the patient to stay in the hospital for the procedure before discharge. Elective was defined by medical factors that indicated the need for the procedure, but allowed the patient to be discharged from the hospital with readmission at a later date. Cardiac catheterizations were performed using standard methods during the course of regular clinical care. The number of diseased coronary vessels was assessed by use of criteria established by the National Heart, Lung, and Blood Institute Coronary Artery Surgery Study [10]. Complete definitions of these variables have been previously published [11].

Patient follow-up
The outcome measure for this study was all-cause mortality over a 5-year interval. Mortality through December 31, 1996, was determined by a probabilistic match of the regional registry to the National Death Index (US Department of Health and Human Services) [12] using a combination of name, social security number, date of birth, sex, date last known alive, and state of last known residence. The sensitivity of the National Death Index to identify deaths is between 92% and 99% depending on which identifiers are available [13].

Statistical analysis
Base line characteristics were summarized by percentages for the discrete variables and by means for the continuous variables. We used ² tests and t-tests to compare discrete and continuous variables of patients with and without dialysis-dependent renal failure. Survival analyses were completed with Kaplan-Meier techniques to determine the annual death rate and actuarial 5-year survival, and were compared using the log-rank statistic [14]. Predictor variables of mortality were selected based on prior analyses of our CABG database [15]. They included age, sex, prior cardiac operation, priority of operation, ejection fraction, number of diseased coronary vessels, diabetes, PVD, COPD, and dialysis-dependent renal failure. A Cox proportional hazard regression model was used to compare nonrenal failure patients with renal failure patients while adjusting for base line characteristics. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated. In addition, similar analyses were performed comparing nonrenal failure patients with renal failure patients without diabetes or PVD, and with renal failure patients with diabetes or PVD. Analyses were performed using Stata release 6.0 software (Stata Corp, College Station, TX).

	Results

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Patient characteristics
Table 1 lists base line patient and disease characteristics based on the presence or absence of renal failure. Overall, 283 of the 15,574 patients (1.8%) were on dialysis preoperatively. Compared with nonrenal failure CABG patients, renal failure patients were older (66.7 versus 64.8 years), were more likely to be female (33% versus 28%), and had slightly smaller body surface area (1.90 versus 1.96 m²). Renal failure patients were less likely to have undergone previous cardiac operations (3.5% versus 7.0%) and more likely to undergo emergency operation (11.0% versus 7.4%). They also had a poorer cardiac profile with a lower ejection fraction (0.477 versus 0.535), higher left ventricular end-diastolic pressure (19.9% versus 16.8%), higher incidence of left main stenosis (30.0% versus 24.5%) and unstable angina (57.6% versus 47.5%), and more diseased vessels (2.49 versus 2.36). In addition, renal failure patients were more likely to have comorbid conditions such as hypertension (88.2% versus 64.2%), diabetes (47.7% versus 28.0%), PVD (43.5% versus 15.6%), and COPD (26.9% versus 11.9%).

View larger version (13K): [in this window] [in a new window]   Fig 1. Proportion of dialysis patients surviving after coronary artery bypass grafting, with or without renal failure.

View larger version (16K): [in this window] [in a new window]   Fig 2. Proportion of dialysis patients surviving after coronary artery bypass grafting, by renal failure categories.

	Comment

Top Abstract Introduction Material and methods Results Comment Discussion References

We then examined the effects of diabetes and PVD on renal failure patients. Approximately one third of the renal failure patients did not have diabetes or PVD. When compared with nonrenal failure patients, they had a higher annual death rate (7.7% versus 3.8%) and decreased 5-year survival (78.5% versus 83.5%), but this difference did not achieve statistical significance (adjusted HR, 1.57; 95% CI, 0.90 to 2.71; p = 0.113). However, renal failure patients with diabetes or PVD had fared significantly worse, with an annual death rate of 23.0% and a 5-year survival of only 42.2% (adjusted HR, 4.23; 95% CI, 3.22 to 5.56; p < 0.001) compared with nonrenal failure patients.

Comparison with previous studies
In this study, in-hospital mortality for renal failure patients undergoing CABG was 12.1%, which is consistent with the 12.5% in-hospital mortality reported in a retrospective review using the United States Renal Data System national database of 7,419 renal failure patients undergoing CABG [4]. We found the 5-year survival of all renal failure patients to be 55.8%. Other studies with smaller numbers of patients reported 5-year survival rates of 32% to 71% [16–20].

Previous work using the United States Renal Data System database showed advanced age, diabetes, and PVD to be significant independent predictors of decreased 2-year survival [4]. Similarly, a study of 45 patients yielded a 5-year survival of 89.1% in 24 nondiabetic renal failure patients, but only 22.9% in diabetic renal failure patients [21]. We also found that associated comorbidities, specifically diabetes and PVD, significantly impacted survival. Renal failure patients without diabetes or PVD had an annual death rate twice as high as nonrenal failure patients and a decreased 5-year survival. Adjusting for base line patient and disease characteristics, this group had a 57% increased rate of death compared with patients without renal failure. This difference did not reach statistical significance, most likely because of the modest number of patients (n = 91) in this group. However, patients who had renal failure with diabetes or PVD had much poorer survival, with an annual death rate of 23% and a 5-year survival of only 42.2%.

Study limitations
There are several limitations of this study. First, because this study was observational, one or more factors for which we could not adjust might have affected survival. Second, this study was regional, thus the results may not be generalizable for the population as a whole. For instance, we did not collect information on ethnicity, but the overwhelming majority of our patients are white. Other authors have reported a 19% reduction in all-cause death and 20% reduction in cardiac death for African American patients compared with white renal failure patients after coronary revascularization [4]. Third, we have no information on exactly why the 283 renal failure patients in this study underwent CABG rather than catheter-based revascularization or medical therapy alone. The prognosis of renal failure patients with coronary disease is poor, and CABG has been shown to have better outcomes compared with angioplasty for similar groups of patients, but we do not know why these 283 were chosen for this intervention. Factors may exist (eg, surgeon preference) that we could not measure in these patients that make them more suitable for operative intervention, and thus our results may not apply to the renal failure population as a whole.

Conclusions
The primary cause of death in renal failure patients is cardiovascular disease. After adjustment for other risk factors, dialysis-dependent renal failure remains a highly significant predictor of decreased long-term survival in CABG patients. Overall, the 5-year survival for this group of dialysis patients who underwent CABG was improved over the general population of renal failure patients. The 5-year survival of renal failure patients without diabetes or PVD was surprisingly good at 78.5%. This finding suggests that this subgroup of renal failure patients may benefit from early screening and revascularization. Disappointingly, the 5-year survival of renal failure patients with diabetes or PVD appears to be no better the general dialysis population, with an annual death rate of 23% and a high perioperative mortality rate. Given their poor prognosis, indications for operation in these patients should be carefully considered.

	Discussion

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DR KEVIN A. ACCOLA (Orlando, FL): I congratulate the authors on an important review of the treatment scheme of these complex patients. We are often asked to consider these patients for preoperative renal transplantation, and I think this study has important implications for evaluating these patients as well.

At a time of increased technological advancements in knowledge base and, per our nephrology colleagues, "healthier chronic renal patients," we are being asked to consider them for transplantation as well as coronary artery vascularization. More of these patients are being offered cardiac surgical procedures because of these issues. We must ask ourselves, are we truly benefiting these patients short-term or long-term, as these patients often come to us with critical disease and few, if any, other options.

It is interesting that the United States Renal Data System in 1998 reported a 7- to 10-year life span for patients 40 to 44 years of age and 4 to 5 years of life span for those patients 60 to 64 years of age, with cardiovascular disease being the most threatening disease process. The authors have clearly demonstrated prognostic indicators relative to the presence or absence of diabetes or peripheral vascular disease on survival of this patient population.

My questions to you are three. Number one, did you look at what happened to patients who were transplanted after CABG in your survival statistics? I think this would give us guidance in how to manage this complicated patient cohort. From your analysis, are there patients who we simply should not consider for bypass pretransplantation?

Number two, these patients often have poor anatomy and diffuse distal disease. Did you distinguish between these groups of patients and those with decent targets in your analysis regarding survival and completeness of revascularization in the alteration of results on these factors?

And finally, did you in your analysis of these data distinguish between more recent need of hemodialysis or peritoneal dialysis versus those patients who were on a chronic dialysis schedule? That is, is the duration of subsequent physiologic effects of hemodialysis significant to the outcomes of these patients?

Again, I would like to thank the Society for the opportunity to discuss this study and to participate in the program. Thank you.

DR PAUL KURLANSKY (Miami, FL): I think the Northern New England Study Group once again is to be congratulated on tackling a difficult question and a difficult group of patients. Since this group of patients clearly has a proclivity for accelerated atherosclerosis, both of the native vessels and the grafts, I was wondering if your data permitted you the opportunity to analyze the impact of the use of the internal mammary artery in this group of patients, for both single mammary grafting and potentially even bilateral mammary grafting?

Thank you very much, and, once again, congratulations.

DR ANTHONY P. FURNARY (Portland, OR): I have one question related to the survival curve for renal failure patients in total: there appears to be two different slopes for that survival. There is an early slope before 6 months that is steeper than the late slope. From your data it appears that the rate of mortality differs from 6 months to 5 years, compared with the mortality rate from the time of operation to 6 months. I was wondering if you had a chance to look back into the data and define what are the various risk factors that predispose a patient to dying early versus later?

Thanks very much for a great presentation.

DR DACEY: Thank you for all the comments. Doctor Accola, unfortunately, in our database we did not collect information about which of these patients subsequently went on to transplant, so I cannot answer that question.

As far as poor anatomy, these patients tend to present later. They do have more disease. Unfortunately, all we have for our information is the number of diseased vessels, not the quality of the vessels. We therefore cannot say if patients with poorer anatomy fared better or worse than patients with good targets.

I also cannot answer the question of whether how long the patient has been on dialysis prior to operation makes a difference. We only had a yes/no variable; was the patient on dialysis beforehand? I think we all think that making a transition to dialysis at the time of the CABG is ominous. Patients who develop renal failure immediately after CABG have an odds ratio for mortality of about 27. That ratio is based on a VA study of 42,000 patients[1]. So the closer a patient is to going into dialysis around the time of their operation, the worse the outcome is likely to be.

Doctor Kurlansky, the question concerning the internal mammary artery is important. In the US Renal Data System, use of the internal mammary artery has clearly been protective. We cannot say anything from our database because nearly every patient in our data set received an internal mammary artery graft, so we had few patients with different grafts to compare. But from the nationwide data, it is clear that if you are going to operate on these patients, it is almost imperative to use an internal mammary artery graft.

And Dr Furnary, thank you. You are right, I think two different things are going on in terms of survival. There is the early mortality of renal failure patients, that is, in-hospital or 30-day mortality, which is at least three times higher than with nonrenal failure patients after risk adjustment. For the renal failure patients without diabetes or peripheral vascular disease, the slope of the survival curve appears to parallel nonrenal failure patients. In patients with diabetes or peripheral vascular disease the slope continues to decline. So I think there are two different slopes: there is the higher up-front mortality and then that second part that continues to decline if the patient has associated comorbidities.

Reference

1. Chertow GM, Levy EM, Hammermeister KE, Grover F, Daley J. Independent association between acute renal failure and mortality following cardiac surgery. Am J Med 1998;104: 343-8.

	References

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