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J Thorac Cardiovasc Surg 2007;133:1212-1219
© 2007 The American Association for Thoracic Surgery
Surgery for Acquired Cardiovascular Disease |
Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minn.
Read at the Thirty-second Annual Meeting of the Western Thoracic Surgical Association, Sun Valley, Idaho, June 21-24, 2006.
Received for publication June 22, 2006; revisions received November 15, 2006; accepted for publication November 28, 2006. * Address for reprints: Ranjit John, MD, Assistant Professor, Division of Cardiothoracic Surgery, University of Minnesota, Minneapolis, MN 55455. (Email: johnx008{at}umn.edu).
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Abstract |
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Methods: Seventy-four patients with previous abdominal transplants underwent cardiac surgery (93% coronary artery bypass grafting, 5.4% bypass grafting plus valve, and 1.4% valve) between 1995 and 2005. These recipients were compared with 895 adult nontransplant patients undergoing cardiac surgery between 2000 and 2005. Only kidney and kidney–pancreas recipients were included in the analysis (n = 70) because there were only 2 liver and pancreas alone transplants.
Results: As compared with nontransplant patients, kidney transplant patients were younger (mean age 52.1 ± 10 years vs 61 ± 13 years; P < .001) and had an increased incidence of diabetes (92.9% vs 39.1%; P < .001), peripheral vascular disease (37.1% vs 19.1%; P < .001), chronic kidney insufficiency (73.0% vs 13.4%; P < 0.001), and unstable angina (44.8% vs 25.7%; P = .005) There was no difference between the two groups in the complication rate at 30 days after surgery, except that transplant patients were more likely to have postoperative kidney dysfunction (32.6% vs 6.1%; P < .001) and require hemodialysis (11.7% vs 1.1%; P < .0001). Thirty-day postoperative mortality was similar between groups (1.4% vs 2.9%; P = not significant). By multivariable analysis, preoperative congestive heart failure, nonelective surgery, prolonged cardiopulmonary bypass times, peripheral vascular disease, and lower creatinine clearance were significant risk factors for postoperative mortality; however, prior kidney transplant was not an independent risk factor for 30-day postoperative mortality.
Conclusions: Despite their increased incidence of comorbid conditions, the postoperative outcomes of cardiac surgery in kidney transplant recipients are similar to those in the nontransplant population except for a higher incidence of kidney dysfunction in transplant patients.
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Introduction |
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In 1984, we1
first published our experience at the University of Minnesota with cardiac surgery in 14 kidney transplant recipients. Herein, we present our recent experience with cardiac surgery in a larger series of kidney transplant recipients. The objectives of this study were (1) to identify the characteristics and risk factors in kidney transplant recipients who underwent cardiac surgery and (2) to evaluate their early mortality and morbidity and changes in kidney function as compared with nontransplant patients.
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Patients and Methods |
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All patients were followed up until death or 30 days after surgery during the mean follow-up time of 29.5 days (range: 0–30). We collected patient data from both the hospital medical records and the institutional data reported to the Society of Thoracic Surgeons Database. All patients provided informed consent and the registry was approved by our institutional review board.
Clinical Data
For all patients, we analyzed the following characteristics: presence of heart disease symptoms, presence or absence of chronic or unstable angina, physician-defined symptoms of decompensated heart failure, percutaneous coronary intervention, percentage of left ventricular ejection fraction (LVEF) at the time of surgery, presence of comorbidities, including diabetes, dyslipidemia, hypertension, history of stroke, peripheral vascular disease, renal function (serum creatinine concentration [SCr] serum creatinine clearance calculated from Cockroft-Gault equation, chronic hemodialysis), elective versus urgent surgery; crossclamp and perfusion times, and postoperative complications. These included cardiac complications, such as tamponade, myocardial infarction, reoperation for occlusion or other causes, requirement of intra-aortic balloon pump support, renal dysfunction defined as rise of SCr above 2.5 mg/dL and/or a need for hemodialysis, ventilatory support, pneumonia, multiorgan failure, gastrointestinal complications, leg infection, sepsis, coma, and neurologic complications, and readmission within 30 days after surgery.
Preoperative Management
Antibiotics
All patients received preoperative antibiotics before skin incision, including cephalosporins for CABG surgery and vancomycin for valve operations. Antibiotics were continued for at least 24 hours postoperatively, barring other clinical indications for longer duration of therapy.
Immunosuppression
Immunosuppressive protocols for our transplant recipients have been described in detail.2 Maintenance immunosuppression was not changed before cardiac surgery. Doses were held while patients were under nothing-by-mouth orders and restarted within 24 hours after surgery. If the recipient was not tolerating oral medications within 24 hours, intravenous doses were given. Dosing of calcineurin inhibitors was also held if there was significant postoperative kidney dysfunction. Immunosuppressive drug levels were monitored and adjusted when necessary. Prophylactic stress doses of corticosteroids were given to all patients receiving long-term steroid therapy.
Cardiac Surgery
In all patients, cardiac surgery was performed with standard surgical techniques through a median sternotomy using cardiopulmonary bypass with membrane oxygenation and moderate systemic hypothermia (temperature range, 28°C to 32°C). In renal transplant recipients, a higher mean perfusion pressure was maintained to optimize kidney perfusion. Cold antegrade blood cardioplegia was used for all patients with retrograde blood cardioplegia in some patients for myocardial preservation. Anticoagulation was achieved before cardiopulmonary bypass with heparin (300–400 U/kg) to achieve activated clotting times greater than 400 seconds.
Perioperative Care
Standard intensive care unit protocols were used in the immediate postoperative care of these patients, including inotropic support with dopamine or milrinone. All patients had hemodynamic monitoring with a Swan–Ganz catheter (Edwards LifeSciences, Irvine, Calif) to closely monitor cardiac function and intravascular volume status.
Patients who were dialysis-dependent underwent their usual maintenance hemodialysis the day before surgery. During surgery, large-volume hemofiltration was carried out by the perfusion team during cardiopulmonary bypass. Additionally, these patients were closely followed up by the kidney service to determine the frequency and timing of postoperative dialysis, in conjunction with the cardiothoracic surgical team.
Follow-up
All patients were seen by the surgical team about 2 weeks after discharge. They were also routinely followed up by the appropriate transplant and cardiology services.
Complications and Causes of Death
Adverse events and causes of death were characterized by the attending physician. Autopsy results were not available.
Statistical Analysis
Differences between the two groups were examined by the 
2 or Fisher exact test. Continuous variables were compared by a Student t test if normally distributed; if not, a Wilcoxon rank-sum test was used. Survival estimates were based on the Kaplan–Meier method and compared with log-rank statistics. To identify preoperative risk factors for perioperative 30-day mortality after cardiac surgery, we entered parameters (Table 1) into our univariate analysis model. The covariates, which correlated with end points on univariate analysis at P value < .15, were entered and allowed to stay in a stepwise multiple logistic regression model at a P value of < .15. Values are reported as mean ± standard deviation. All data were analyzed by the SAS system software version 9.0 (SAS Institute, Inc, Cary, NC).
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Results |
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Kidney Function
The majority (68.6%) of transplant recipients who underwent cardiac surgery had abnormal kidney function—SCr was greater than 2 mg/dL in 30% and 38.6% had returned to hemodialysis (Table 2). As compared with nontransplant patients, transplant recipients had significantly worse kidney function. Transplant recipients were also four times more likely to be receiving hemodialysis before their cardiac surgery.
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Cardiac Surgery
The majority (98.5%) of the 70 kidney transplant recipients underwent CABG surgery (with or without concomitant valve surgery) and 1.4% underwent valve surgery alone. Of these cardiac operations, most were elective. Only 8.6% of patients had a significant (>50%) left main coronary artery lesion. For revascularization, the internal thoracic artery was used in 62.3% of those who underwent CABG surgery. As compared with 895 nontransplant patients, kidney transplant recipients were more likely to undergo elective surgery (68.6% vs 55.9%; P = .04), more likely to undergo CABG surgery rather than valve surgery alone (98.5% vs 78.1%; P = .002), less likely to have significant left main coronary disease (8.6% vs 18%; P = .04), and less likely to have the internal thoracic artery graft for revascularization (62.3% vs 88.3%; P < .001). Transplant recipients also had shorter crossclamp time (95.3 + 46.3 minutes vs 112.7 + 52 minutes; P = .009) and shorter perfusion time (141.3 + 54.8 minutes vs 160 + 68.4 minutes; P = .01).
Outcomes of Cardiac Surgery
Nonrenal complications
During the first 30 postoperative days, nearly half (47%) of transplant recipients who underwent cardiac surgery had at least one postoperative nonrenal complication. The most common included need for ventilatory support (11.4%), systemic infection or sepsis (2.9%), postoperative myocardial infarction (2.9%), neurologic complication or coma (2.9%), pneumonia (1.4%), multiorgan failure (1.4%), gastrointestinal complications (1.4%), and limb ischemia (1.4%) (Table 4).
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Kidney dysfunction
The likelihood of postoperative kidney dysfunction developing within 30 days after surgery was higher in transplant than nontransplant recipients. Among patients who were not hemodialysis-dependent at the time of surgery, postoperative kidney dysfunction defined by a need for hemodialysis or a rise of SCr greater than 2 mg/dL developed in 32.6% of transplant recipients (14/43) as compared with 6% of nontransplant patients (50/827) (P < .001).
The likelihood that kidney allograft function would worsen after cardiac surgery correlated with the baseline preoperative SCr. In transplant patients with SCr greater than 2 mg/dL, 47.6% (10/21) had a postoperative SCr elevation versus 18.2% (4/22) of those with preoperative SCr of 2 mg/dL or less (P = .04). Similar trends were observed in nontransplant patients; of those with baseline SCr greater 2 mg/dL, 21.7% (10/46) had a postoperative SCr rise versus 5% (40/781) of patients with baseline SCr of 2 mg/dL or less (P < .001).
Long-term kidney function
Of the 14 transplant patients who had postoperative kidney dysfunction (defined as a need for hemodialysis or a rise of SCr > 2 mg/dL), 3 required temporary hemodialysis and 11 had a rise in SCr greater than 2 mg/dL. The 3 who required hemodialysis all regained kidney function and were alive at 5 years of follow-up with a functioning allograft. Of the 11 patients with a rise in SCr greater than 2 mg/dL, 4 lost allograft function 1 year after cardiac surgery and required permanent hemodialysis; of the remaining 7, 1 died within 1 year, but 6 were alive at 5 years of follow-up with a functioning allograft. Thus, the overall 5-year dialysis-free survival of transplant recipients in whom kidney dysfunction developed after cardiac surgery was 64.2% (9/14).
Reoperation and readmission
Overall, only 8.6% of transplant recipients required cardiac reoperation (including for bleeding) and 8.6% of patients required readmission within 30 days after surgery. There were no differences in the incidence of cardiac reoperation between transplant and nontransplant patients (Table 5). However, there was a nonsignificant trend toward lower rates of readmission in transplant patients (8.6% vs 15.1%; P = .14).
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Risk factors for 30-day mortality
Using multivariate analysis, we identified the following factors to be significant predictors for 30-day mortality: perfusion time greater than 180 minutes (relative risk [RR] = 7.18; P < .001), symptoms of congestive heart failure (RR = 3.47; P < .001), urgent or emergency cardiac surgery versus elective surgery (RR = 3.33; P = .002), and LVEF less than 40% at time of surgery (RR = 2.89; P = .04) (Table 6). Additionally, a trend toward increased risk of 30-day mortality was seen in patients with a history of peripheral vascular disease (RR = 2.95; P = .06) and those with SCr clearance less than 60 mL · kg–1 · min–1 (RR = 2.27; P = .07). Importantly, a previous kidney transplant was not an independent risk factor for 30-day postoperative mortality.
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Discussion |
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TopAbstractIntroductionPatients and MethodsResultsDiscussionReferences |
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Between 1997 and1999, the death rate for US dialysis patients was 239 per 1000 patient-years, and cardiac disease accounted for 44% of all causes of death.5 In a retrospective study of 2694 adult kidney transplant recipients at the University of Minnesota, the overall incidence of adverse cardiovascular events, including myocardial infarction, within 30 days after transplant was 6.1%.6
In addition to the short-term risks, cardiovascular events are the most common cause of death with functioning kidney allografts. In a study of our recipient population, 17% of deaths in kidney transplant recipients with functioning grafts were due to myocardial infarction and 15% were due to sudden death (presumably due to arrhythmias).7 Kidney transplant recipients are at markedly increased risk for cardiovascular disease for numerous reasons.8 For many recipients (eg, those with diabetes or hypertension), the primary disease itself is associated with increased cardiovascular risk. In other recipients hypertension, hyperlipidemia, and hyperhomocysteinemia develop in association with kidney failure. Excess risk also may be due to the hemodynamic and metabolic factors that occurred during the pretransplant interval of chronic renal insufficiency (eg, anemia, proteinuria, increased extracellular volume, electrolyte imbalance, and higher levels of thrombogenic factors).9 Patients in kidney failure are at higher risk for mitral and aortic valve calcification, as well as for coronary artery calcification.10 Postransplant hyperlipidemia, diabetes, and hypertension related to immunosuppressive regimens continue to place these recipients at increased risk.11
Reports show that simultaneous kidney–pancreas transplantation prolongs the survival of patients with end-stage renal disease as compared with kidney transplantation alone, possibly by decreasing cardiac causes of death.12 Several studies have shown that the presence of a functioning pancreas graft has favorable effects on lipid profiles, reduces the progression of coronary atherosclerosis, improves cardiac function, and reduces death rates from cardiovascular causes when compared with kidney-alone transplant recipients.13-15 Patients after liver transplant, a group without the traditional risk factors for cardiovascular disease as seen in kidney transplant recipients, have a greater than 10% incidence of adverse cardiovascular events after transplantation.16 Thus, it is not surprising that recipients of solid organ abdominal transplants have a high incidence of cardiovascular disease, often necessitating cardiac surgery.
A transplant recipient is considered to be a high-risk candidate for cardiac surgery because of numerous risk factors, including coexisting immunosuppression (including long-term steroid use with its attendant complications), the inherent possibility of other end-organ dysfunction, and varying degrees of primary allograft dysfunction. In addition, cardiac surgery itself could adversely affect graft function and possibly lead to graft loss. Our current study found that 30-day mortality and morbidity rates were similar in transplant recipients and nontransplant patients. Smaller single-center studies have similarly reported low mortality after cardiac surgery in kidney transplant recipients.17-22 However, a large study from the United States Renal Data System database involving 1100 kidney transplant recipients undergoing CABG reported an in-hospital mortality rate of 5.0% with and 9.4% without internal thoracic artery use.23 Despite the higher mortality rates noted in this study, long-term survival was better after surgical revascularization than after percutaneous coronary intervention.
In our current study, we noted low rates of re-exploration for bleeding in transplant versus nontransplant patients. This low rate may be due to the use of dialysis on the day before surgery as well as hemofiltration during cardiopulmonary bypass. The beneficial effect of aprotinin on postoperative bleeding must be balanced in view of the recently reported adverse kidney effects in patients having cardiac surgery.24 Even though we did not use off-pump approaches for coronary revascularization in this experience, this technique has theoretical benefits of reduced incidence of bleeding and neurologic complications.25 Some studies have suggested, however, that off-pump surgery could be associated with incomplete coronary revascularization and reduced graft patency, and the need for and the risk-benefits of this approach must be decided on an individual basis.26,27 A recent large study also reported a morbidity and mortality benefit with the use of off-pump CABG in patients undergoing dialysis.28
Of note, increasing evidence supports the short- and long-term morbidity and mortality benefits of maintaining normoglycemia in patients undergoing CABG.29 In the past 5 years, in all of our cardiac patients, we have established strict blood sugar control protocols, which may have helped keep our morbidity rates low. In contrast to our low morbidity rate, our increased incidence of postoperative kidney dysfunction in the transplant recipients was alarming. In both our study and others, preoperative kidney insufficiency was a significant risk factor for postoperative kidney failure. In patients with preoperative kidney insufficiency, the incidence of acute allograft failure is as high as 30%.21 Our high incidence of kidney complications leaves much room for improvement. One study reports a lower incidence of kidney dysfunction in kidney transplant patients who had off-pump coronary revascularization.21 Improved strategies with the use of possible kidney protective agents during cardiopulmonary bypass are necessary to reduce the morbidity associated with postoperative kidney dysfunction.
Most patients who have kidney dysfunction after cardiac surgery, including those who require temporary hemodialysis, will have return of allograft function. Encouragingly, our study showed that 64.2% of such patients were alive and dialysis-free 5 years after cardiac surgery. Aggressive attempts to preserve kidney function, avoidance of nephrotoxic medications, and the continued involvement of the kidney transplant team are imperative to allow for maximal return of function.
Our study has all the limitations inherent to a retrospective study. In addition, although results on early morbidity and short-term survival are important, longer-term follow-up would be valuable, including data on graft patency and freedom from valve degeneration. A significant proportion of our transplant recipients were already receiving hemodialysis, raising the question of whether or not these patients should be included in the transplant cohort. We included them because, even though they had graft failure and were receiving hemodialysis, it is our practice to keep them on maintenance immunosuppression.
In conclusion, our study provides useful data on the patient characteristics and on postoperative morbidity and mortality. It represents the largest single-center report of cardiac surgery in kidney and kidney–pancreas transplant recipients. Although the transplant recipients had an increased incidence of preoperative high risk factors, their postoperative mortality was low. Importantly, our multivariable analysis showed that a previous kidney transplant was not a risk factor for increased mortality after cardiac surgery.
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Acknowledgments |
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Footnotes |
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References |
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