Ann Thorac Surg 1998;65:1064
© 1998 The Society of Thoracic Surgeons
The Safety of Cardiac Operations in the Liver Transplant Recipient
Ganga Prabhakar, FRCSaa,
Giuliano Testa, MDaa,
Osman Abbasoglu, MDaa,
D. Rohan Jeyarajah, MDaa,
Robert M. Goldstein, MDaa,
Marlon F. Levy, MDaa,
Bo S. Husberg, MD, PhDaa,
Thomas A. Gonwa, MDaa,
Goran B. Klintmalm, MD, PhDaa
a Baylor Institute of Transplantation Sciences, Baylor University Medical Center, Dallas, Texas, USA
Accepted for publication November 14, 1997.
Address reprint requests to Dr Klintmalm, Baylor Institute of Transplantation Sciences, Baylor University Medical Center, 3500 Gaston Ave, 4 Roberts, Dallas, TX 75246
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Abstract
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Background. Advances in surgical techniques and immunosuppressive drugs have improved the survival of patients after orthotopic liver transplantation. Enhanced survival has resulted in an increased number of patients who require medical as well as surgical managment of diseases.
Methods. To contribute to the sparse literature on the surgical aspects, we reviewed our experience with 15 patients who underwent cardiac operation (1.25%) from a total of 1,200 liver transplant recipients at our center. The variables studied included the pretransplant cardiac evaluation, the interval from transplantation to cardiac operation, postoperative complications, the management of immunosuppression, and follow-up. The patients had a mean age of 52.9 years (range, 39 to 69 years) and 13 of them (86.6%) were men. Multiple cardiac risk factors were present in all 15 patients and chronic renal insufficiency was present in 7 patients. Cardiac operation was undertaken a mean of 30.4 months (range, 9 days to 62 months) after myocardial ischemia and valvular regurgitation had been ruled out at the time of transplantation. Myocardial revascularization was performed in 12 patients, 2 of whom underwent concurrent valve operation and 3 of whom underwent valve repair or replacement. Most patients had their immunosuppression regimen continued at baseline levels.
Results. There were no early deaths. Three patients had major complications and 4 had minor complications. There were no bleeding, infection, or healing complications. Postoperative renal parameters were persistently elevated in 5 patients and transiently elevated in 3. Liver function parameters were transiently elevated in 6 patients after the cardiac operation. No patient had hepatic rejection. A transient elevation or decrease in immunosuppressive drug levels was seen in 3 patients. Follow-up, obtained on all 15 patients, ranged from 6 to 83 months (mean, 26.5 months). There were 2 late deaths (13.3%), and 3 patients (25%) who underwent myocardial revascularization had recurrent angina.
Conclusions. Cardiac operations can be undertaken safely in liver transplant recipients with good intermediate-term results. The immunosuppression regimen can be continued at preoperative levels with no need for stress-dose steroids. There were no hepatic complications among our patients, although some patients can experience worsening of renal failure.
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Introduction
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Liver transplant recipients have improved survival as a result of advances in surgical techniques and better immunosuppression regimens. More than 22,000 liver transplantations have been performed since 1987, with a 5-year survival rate of about 68.8% [1]. Better survival has meant an increase in the number of patients who require medical as well as surgical treatment for other diseases. The literature on abdominal [2] and cardiac operations in liver transplant recipients is sparse [3, 4]. This led us to review our cardiac surgical experience in this subset of patients.
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Material and methods
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From January 1985 to March 1997, 1,200 patients underwent orthotopic liver transplantation at our center, with a 5-year survival rate of 75%. Data on these patients were obtained from a prospectively maintained database in which patient information from the pretransplantation evaluation is collected so that it can be analyzed statistically at a later time (Statistical Analysis System, Cary, NC). This detailed information on the patients was obtained by chart review. The charts were reviewed for the cardiac history before and after the liver transplantation, the pretransplantation cardiac work-up, and the interval from liver transplantation to cardiac operation. The perioperative immunosuppression regimen, morbidity, mortality, and any changes in liver or renal function were assessed from the database. All patients were followed up closely after their liver transplantation. Follow-up was obtained in all patients undergoing cardiac operation. Information regarding the patients’ current cardiac status was obtained by personal or telephone interview.
All patients who underwent cardiac operation after liver transplantation were included in the study. Patients who underwent simultaneous cardiac operation and liver transplantation, patients who experienced cardiac events that did not require intervention, and patients who underwent balloon angioplasty were excluded from the study. Since the inception of our transplant program, 15 (1.25%) of the 1,200 liver transplant recipients have required cardiac operation after their transplant. The mean age of the patients was 52.9 years (range, 39 to 69 years) and 13 of them (86.6%) were men. Four of the patients had undergone previous cardiac interventions, with 2 having undergone PTCA 1 week and 2 months, respectively, before transplantation. One patient had undergone balloon angioplasty and coronary artery bypass grafting (CABG) 10 years before the liver transplantation and 1 had undergone CABG 12 years before the transplantation.
The incidence of chronic renal insufficiency (defined as a creatinine level >2 mg/dL or a glomerular filtration rate <70 mL/min) in the present study was 46.6% (7 of 15 patients) [5]. Among the entire group of liver transplant recipients, 58.8% had a creatinine level greater than 2 mg/dL and 82.4% had a glomerular filtration rate less than 70 mL/min. The incidence of diabetes controlled by oral diabetic agents or insulin was 28.8% and the incidence of hypertension was 51.1%. Multiple cardiac risk factors were present in all patients at cardiac operation, which was undertaken 9 days to 62 months (mean, 30.4 months) after the liver transplantation.
Patients with a history of cardiac disease and asymptomatic patients older than 40 years of age were seen by a cardiologist before their liver transplant procedure and underwent echocardiography and stress testing. Patients with a history of balloon angioplasty or CABG underwent cardiac catheterization before transplantation. If myocardial ischemia and significant valvular regurgitation were ruled out, they underwent liver transplantation. Follow-up cardiac testing after liver transplantation was performed only if the patients became symptomatic. The patients in the cardiac operation group did not have hypercholesterolemia or hypertriglyceridemia before or after transplantation. One of the patients, a 56-year man with no prior cardiac history, did not undergo pretransplantation cardiac evaluation because he had hepatorenal syndrome at the time of transplantation; unstable angina requiring CABG developed almost 5 years later.
Eleven of the patients underwent cardiac operation at our center and the other 4 underwent cardiac operation at four different centers. Complete information was obtained on all the patients who underwent cardiac operation at our center, but only partial information could be obtained on those who were treated at outside institutions. Immunosuppressive drug data were available on the 11 patients who underwent operation at our center. The procedures performed in the 15 patients are shown in Table 1. Nine patients were continued on their steady-state immunosuppression regimen over the course of their cardiac operation, with the medications usually administered through a nasogastric tube. In 1 patient, the medications were administered parenterally at the same dosage and in another, stress-dose steroids were administered.
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Results
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All the patients survived their cardiac operation. Seven (46.7%) experienced complications (Table 1). Two patients had significant postoperative bleeding, but they did not require reexploration. None of the patients had wound infections or problems with healing. The 3 patients who underwent valve operations for endocarditis did not have recurrence of the infective process. The results of intraoperative cultures were negative, perhaps as a result of successful preoperative antibiotic sterilization. The sternum remained stable in all the patients during follow-up. Six (50%) of the 12 patients for whom information was available had transient elevation of their liver function parameters, which reverted to normal before their discharge from the hospital. No patient had liver rejection within 30 days after their cardiac operation. The results of renal tests were available in 14 patients. One patient was dependent on hemodialysis. Eight patients (57.1%) had a rise in blood urea nitrogen and creatinine; this reverted to normal by the first follow-up examination in 3 patients (21.4%) but remained high in the other 5 (35.7%). Two of these patients required temporary hemodialysis. Daily cyclosporine and tacrolimus levels were available for 9 patients after cardiac operation, most of whom had had normal preoperative levels. Of the patients who received cyclosporine after cardiac operation, 2 had high cyclosporine levels (652 ng/mL and 932 ng/mL, respectively) and 1 had a low cyclosporine level (44 ng/mL). There was no evidence of toxicity in any of these patients; the first had no significant alteration in renal parameters and the second was one of the 3 patients in whom a transient postoperative rise in these measurements developed. Of the 2 patients who were taking tacrolimus, a high level (36 ng/mL) developed on the first postoperative day in 1 patient but had no adverse effect other than a transient rise in renal parameters. The drug levels normalized within 2 days.
Follow-up ranged from 6 to 83 months (mean, 26.5 months). One patient with an aortic homograft died at 18 months of respiratory failure after a cerebrovascular bleed with a normally functioning valve visible on transesophageal echocardiography. A second patient died at 42 months after CABG of ventricular fibrillation from dilated cardiomyopathy. The present cardiac status of the study patients is shown in Table 1; 2 patients have undergone balloon angioplasty for recurrent angina 2 and 6 months, respectively, after CABG, and 1 has minimal angina controlled with medical therapy.
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Comment
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Although patients undergoing liver transplantation receive a preoperative cardiac evaluation including a stress test, cardiac events can develop after the transplant. Immunosuppressive drugs can contribute indirectly to the development of cardiovascular events through hyperlipidemia, obesity, hypertension, and diabetes [6]. In a previous study, 65 (13.3%) of 487 patients undergoing liver transplantation experienced cardiac events; 8 (12.3%) had a pretransplantation cardiac history [7]. Of the 12 patients in our study who required myocardial revascularization, 6 (50%) had a pretransplantation cardiac history, 4 of whom had undergone either cardiac operation or balloon angioplasty. The mean interval between liver transplantation and myocardial revascularization in the patients with a prior cardiac history (31.7 months) was the same as in those without a prior cardiac history (30.5 months). Therefore, pretransplantation cardiac history is a poor predictor of the need for posttransplant cardiac operation.
The literature on cardiac operation in the liver transplant recipient is limited to isolated case reports [4, 8] and one series of 3 patients [3]. This prompted us to review our 12-year experience with liver transplant recipients. The review was undertaken to determine whether there is an increased incidence of complications or death in this subset of the transplant population. We also evaluated the incidence of bleeding problems, infection rates, pulmonary and cardiac complications, and healing difficulties. Because most of these patients have renal or hepatic dysfunction, which can be aggravated by cardiac operation, we examined this factor. Five of our patients underwent valve operation, so we also examined the special problems that choosing a replacement valve could present.
There were no operative deaths in our series, as has been the experience with other, similar patients. Bleeding was not a significant problem; none of the patients required reexploration for bleeding. There were no significant abnormalities in coagulation or platelet counts. There were no wound infection problems in the early or late postoperative periods. Sternal and wound healing were not an issue in the 15 patients studied. Pulmonary complications were predominant in our patients, with 2 patients having noncardiogenic pulmonary edema and 1 having significant bibasilar atelectasis. The incidence of cardiac arrhythmia did not appear to be higher in this patient population; dysrhythmias developed in only 2 patients.
The low incidence of infection and healing problems can be attributed to the relatively late occurrence of cardiac operation after liver transplantation and the immunosuppression regimen we used during the perioperative period. A stress dose of steroids was used in only 1 patient. In all the other patients, the previously stabilized corticosteroid dosage was continued through either the enteral or parenteral route. The avoidance of a stress dose in patients receiving steroids probably helps to reduce problems with infection and healing [9]. This observation is supported by an extensive study in our patients who underwent general, thoracic, vascular, and orthopedic surgical procedures after having received a liver transplant. There were no episodes of postoperative adrenal insufficiency in the patients who did not receive preoperative and perioperative steroid boluses [10]. Therefore, liver transplant recipients can undergo myocardial revascularization as well as valve replacement operations safely, with low morbidity and mortality.
Hepatic rejection was not seen in any of our patients after cardiac operation, and none required liver biopsy. However, liver function abnormalities occurred in 6 (50%) of the 12 patients for whom information was available. All the abnormalities returned to normal either during the hospitalization or in the early follow-up period. Renal function parameters behaved differently. Many patients have impaired renal function before liver transplantation, and it may decline by a further 40% as a result of the renal effects of immunosuppressive drugs given during the first posttransplant year. This decline in renal function remains stable over the ensuing years [5]. An immunosuppression regimen that includes cyclosporine or tacrolimus contributes to the nephrotoxicity. Almost two thirds of our patients had a transient decrease in renal function, and the laboratory values remained high at follow-up in one third of these patients.
The increased drug levels seen in 3 of our patients immediately after cardiac operation did not seem to be a significant problem because the elevation was transient. The change in drug levels was a problem only on the first day after operation, and we believe that obtaining daily levels is not necessary after the early postoperative period. The drug levels probably should be checked twice during the first postoperative week. If absorption of the drugs from the enteral route becomes unpredictable, the change to intravenous cyclosporine or tacrolimus, steroids, or azathioprine may require the involvement of experts in their use. Daily liver function tests also are not warranted in the liver transplant recipient if the laboratory values are normal on the day after cardiac operation, unless clinically indicated.
The choice of a replacement cardiac valve is difficult in liver transplant recipients. Bioprosthetic valves have the advantage of not requiring anticoagulation therapy in this patient population, in whom multiple liver biopsies may be required. The use of tissue valves has to be tempered by the fact that the patients tend to be young and are likely to live a long time in view of improving survival rates. Degeneration of these tissue valves would be accelerated by renal failure. Mechanical valves provide durability but are limited by their requirement for lifelong anticoagulation therapy, which would be a concern at the time of liver biopsy. With 1 in 4 of our liver transplant recipients undergoing other surgical procedures, the use of a mechanical prosthesis with lifelong anticoagulation therapy warrants careful consideration. The choice of a prosthesis has to be made after extensive discussion with the patient. Valve repair obviously is ideal when feasible. Homograft valves are the next best choice because they do not require anticoagulation therapy and have increased resistance to infection [11].
In summary, cardiac operation can be undertaken safely in the liver transplant recipient with minimal morbidity. Although it is important that the immunosuppression regimen be continued, stress-dose steroids are not necessary; this may reduce the incidence of complications while avoiding liver rejection. Liver dysfunction usually is a transient occurrence, but renal failure can be a significant problem because of its common coexistence. The benefits of cardiac operation for the liver transplant recipient in the intermediate term appear to be satisfactory. Cardiac operations in liver transplant recipients should be undertaken with healthy respect but not with fear [2].
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References
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- Johnston T.D., Katz S.M. Surgical considerations in the transplant patient requiring other surgery. Surg Clin North Am 1995;74:1211-1221.
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- Haydock D., Barratt-Boyes B., Macedo T., Kirklin J.W., Blackstone E. Aortic valve replacement for active infectious endocarditis in 108 patients. A comparison of freehand allograft valves with mechanical prosthesis and bioprosthesis. J Thorac Cardiovasc Surg 1992;103:130-139.[Abstract]
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Abstract
Introduction
