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Ann Thorac Surg 2002;73:534-537
© 2002 The Society of Thoracic Surgeons
a Department of Cardiac and Thoracic Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
b VA Tennessee Valley Healthcare System Nashville Campus, Nashville, Tennessee, USA
Accepted for publication September 22, 2001.
* Address reprint requests to Dr Merrill, Surgical Service (112), VA Tennessee Valley Healthcare System Nashville Campus, 1310 24 Ave S, Nashville, TN 37212, USA
e-mail: walter.merrill{at}vanderbilt.edu
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Abstract |
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Methods. The medical records of all adult and pediatric cardiac transplant recipients who underwent a subsequent cardiac procedure at our institution were reviewed.
Results. Three hundred sixty patients have undergone primary orthotopic transplantation in our institution. Seventeen patients (12 adults, 5 children) underwent a subsequent procedure requiring cardiopulmonary bypass including cardiac retransplantation (10), coronary artery bypass grafting (3), ascending aortic replacement (2), tricuspid valve repair (1), and myotomy and myomectomy (1 patient). Mean interval from time of transplantation to second procedure was 8.3 years. There was one perioperative death. Two patients, both retransplants, died late postoperatively at 22 and 84 months, respectively. Overall mean follow-up in the late survivors is 26.6 months. All survivors are currently asymptomatic and doing well.
Conclusions. A variety of subsequent cardiac procedures, in addition to retransplantation, can be performed safely in carefully selected cardiac transplant recipients. The intermediate term results are gratifying in terms of survival and freedom from symptoms.
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Introduction |
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Cardiac allograft vasculopathy (CAV) is a well-documented intermediate and late complication of cardiac transplantation that threatens graft function [1–3]. Some of the patients who develop CAV are relegated to standard medical therapy consisting of continuing immunosuppressive therapy and adding calcium channel or ß-blockers, nitrates, and antiplatelet agents. Typically, this form of therapy is selected due to the severity and the diffuse nature of the coronary lesions that develop [3]. In this situation the only alternative to medical therapy is retransplantation. Patients who develop a small number of more discrete proximal lesions may receive percutaneous catheter-based interventions [1, 2]. In addition, there are some patients with more limited disease who seem to be reasonable candidates for revascularization by using coronary artery bypass grafting.
There are additional cardiovascular lesions that may develop late postoperatively in association with cardiac allografts, and these conditions may also require cardiac surgical intervention. Therefore, subsequent procedures may be indicated to treat transplant-related complications as well as other diseases that may develop related to allografts. The purpose of this study is to review a single center experience with the spectrum of problems requiring late cardiovascular operation after cardiac transplantation in both pediatric and adult recipients.
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Material and methods |
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Typically in postoperative follow-up, heart transplant recipients undergo periodic surveillance supplemented by annual cardiac catheterization and coronary angiography. In those patients with elevated serum creatinine there is increased concern regarding the risk of exposure of the patient to even small amounts of contrast material at the time of coronary angiography. Dobutamine stress echocardiography is sometimes used as an alternative to angiography due to its high sensitivity for the detection of coronary allograft vasculopathy [4]. If it is negative, coronary arteriography is usually not performed. Assessment of the severity of coronary artery disease is performed by careful analysis of coronary arteriograms. Intravascular ultrasonography is not performed unless the patient is enrolled in a study protocol or unless there is difficulty in interpreting the significance of coronary vasculopathy. From time to time, at least annually, routine transthoracic echocardiographic evaluation is undertaken to determine overall cardiac function and valvular function. Patients who receive consideration for a possible cardiac reoperative procedure are evaluated in the same manner as patients who have not previously undergone cardiac transplantation, with particular emphasis on symptoms, cardiac allograft function, and the details of cardiac allograft vasculopathy. In addition, special attention is devoted to renal function, cyclosporin level, and the presence or absence of rejection, as assessed by endocardial biopsy.
It is most unusual for patients who have undergone cardiac transplantation to experience angina in postoperative follow-up, even in the presence of severe cardiac allograft vasculopathy. Even in the absence of symptoms those patients with myocardial ischemia documented on dobutamine echocardiography and allograft vasculopathy demonstrated at coronary arteriography are considered candidates for intervention. If left ventricular function is severely compromised or if coronary artery disease is so severe and diffuse as to preclude attempts at revascularization by coronary artery bypass grafting, then the patient is evaluated for possible repeat transplantation. In those patients with reasonably well preserved left ventricular function and better quality distal targets, coronary artery bypass grafting is usually undertaken.
Reoperative procedures are performed in standard fashion. The heart is approached through a repeat sternotomy. Cardiopulmonary bypass with moderate systemic hypothermia is used. After aortic clamping myocardial protection is accomplished with multidose cold blood cardioplegia administered antegrade and retrograde.
Perioperative antibiotics, usually cephalosporins, are administered, generally for 48 hours. Cyclosporin is administered either by nasogastric tube or orally, and intravenous infusions are avoided. Stress doses of corticosteroids are given for 24 hours, and all immunosuppressive medications are administered at baseline levels as promptly as possible, except in retransplant procedures, higher doses of steroids are administered and weaned slowly subsequently. Low-dose dopamine infusion and diuretic administration are used perioperatively in an attempt to provide adequate diuresis.
We retrospectively analyzed the collected data to assess interval between transplant and second procedure, early and late survival, major morbidity, postoperative length of stay, and status at follow-up. Follow-up was obtained through clinic visits or telephone interview or the medical record.
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Results |
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The age range at reoperation was 4.9 to 66 years, with a mean age of 39.3 years. The mean interval between the time of the primary transplant procedure and reoperation was 8.3 years (range, 1.7 to 11.4 years) for all patients. The average interval for adult recipients was 8.5 years, and for children, it was 7.6 years.
The most common indication for reoperation was cardiac allograft vasculopathy, which was present in 13 patients. None of these patients experienced typical or atypical symptoms of angina pectoris. In those patients who underwent dobutamine stress echocardiography, it was positive for myocardial ischemia in each instance. All had severe cardiac allograft vasculopathy documented by coronary arteriography. Other reasons for reoperation included acute ascending aortic dissection in 2 patients, severe tricuspid valve regurgitation associated with refractory symptoms of right heart failure in 1, and asymmetric septal hypertrophy with symptomatic left ventricular outflow tract obstruction in 1 patient. This patient had severe limitations of exercise capacity and moderately severe dyspnea on exertion despite an extensive trial of medical therapy and insertion of a dual chamber pacemaker. The reoperative procedures performed were cardiac retransplantation in 10 patients, coronary arterial bypass grafting in 3, ascending aortic replacement in 2, tricuspid valve repair with annuloplasty in 1, and myotomy and myomectomy in the patient with asymmetric septal hypertrophy. None of the patients required a concomitant operative procedure.
There was one intraoperative death in an adult patient undergoing coronary revascularization. Death in the operating room was due to poor myocardial function related to inadequate revascularization secondary to severe and diffuse distal vessel disease. The extent of allograft vasculopathy found at operation was much more severe than had been appreciated preoperatively, despite careful evaluation of the coronary arteriogram. There was an overall 94% (16 of 17 patients) operative survival rate. Hospital morbidity included acute renal failure requiring hemodialysis in 2 patients, and atrial flutter in 1 patient. Other complications included one superficial sternal wound infection and one instance of gram-positive bacteremia of unknown source, both of which were managed with intravenous antibiotics. One or more major postoperative morbid events occurred in 3 of the 16 operative survivors.
The mean length of hospital stay for all survivors was 13.7 days, with 15.1 days for retransplants and 11.3 days for all other cardiac procedures. Among patients who underwent retransplantation, adults had a longer average length of stay than children, 17.7 days versus 11.3 days, respectively.
There were two late deaths after reoperation, one at 22 months and one at 7 years subsequent to the second procedure. One adult patient who underwent retransplantation without perioperative complication had a fairly uneventful late follow-up but died of sudden cardiac death secondary to extensive, inoperable cardiac allograft vasculopathy. The other patient had several late complications of retransplantation, including leukemia, and this patient eventually died of sepsis due to the development of acute mesenteric ischemia.
The mean length of follow-up among operative survivors was 2.5 years, and the range was from 1 month to 7 years. The median follow-up was 15 months. Currently, all long-term survivors have minimal symptoms and improved functional status compared with their preoperative status.
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Comment |
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Long-term results of revascularization strategies are not yet available. A variety of reports, including the present one, suggest that revascularization may be accomplished with reasonably good results in those patients with limited distal vessel disease. Revascularization strategies, including coronary artery bypass, may be used as a method to delay the only definitive treatment of cardiac allograft vasculopathy, which is retransplantation [6].
Other indications for reoperation may be related to complications of the primary transplantation or may be due to lesions intrinsic to the allografts but unknown at the time of original transplant. There were 2 patients who had acute dissection that occurred in the native portion of the recipient’s residual ascending aorta. Perhaps these instances of dissection were due to a combination of the pretransplant disease in the native vessel and the posttransplant hypertension seen in many recipients [7]. Persistent hypertension is a known risk factor for the development of aortic dissection. Additional factors that could play a role include abnormal stress placed on the residual aorta by the transplanted heart, a collagen weakening effect of immunosuppressive therapy, or increased tissue collagenase due to major operative procedures [8]. Presumably the one instance of severe tricuspid valve regurgitation requiring reoperation was due to complications arising from multiple serial endomyocardial biopsies. The one case of late development of asymmetric septal hypertrophy requiring reoperation was unexpected and not readily explained, as the donor, the recipient, and the donor’s family had a negative history for this disease entity. Early postoperative echocardiograms of the recipient and the pretransplant echocardiogram of the donor documented normal septal thickness and no evidence of asymmetric septal hypertrophy. We speculate that the late development of asymmetric septal hypertrophy could possibly be due to steroids or cyclosporin, unmasking of a mutation in the cardiac allograft, or extrinsic factors placing stress on the allograft such as donor/recipient size disparity or hypertension.
Cardiac allograft vasculopathy and its ischemic sequelae remain major complications of orthotopic cardiac transplantation and threaten long-term survival of cardiac allograft recipients. Indeed, 1 patient with extensive and unreconstructible CAV after retransplantation died of sudden cardiac death, presumably related to ischemia. Because of the diffuse nature of the lesions in CAV [3], standard revascularization strategies, such as percutaneous transluminal coronary angioplasty or coronary arterial bypass grafting, are often not possible. Many of the patients with advanced CAV have retransplantation as their only surgical option. Cardiac retransplantation is the most common reoperative procedure in this study. In all the patients who required cardiac retransplantation, the indication for retransplantation was extensive CAV with severely compromised left ventricular function or coronary artery disease so severe and diffuse as to preclude revascularization by coronary artery bypass grafting.
All of the patients who underwent retransplantation had severe allograft disease and were otherwise generally in good condition. None exhibited any evidence of a contraindication to transplantation. As a group they did well; all survived their retransplant procedure, late death occurred infrequently, and long-term follow-up documented return to an excellent overall health status in the survivors. Nonetheless, retransplantation raises many medical, ethical, and fiscal issues. Is it possible to select those candidates who are most appropriate and most likely to benefit from a repeat transplant procedure? As a general rule, as pointed out in other studies, patients are less likely to survive after a repeat transplant. In the face of a limited donor supply, is it fair for a patient to receive a second transplant? Are repeat transplants cost effective [9]?
Although these issues continue to be evaluated and debated, there are some data available that provide assistance in deliberations on these and related issues. The International Society for Heart and Lung Transplantation Registry [10] has reported four factors that are predictive of survival after repeat heart transplantation: accelerated coronary artery disease as the cause of allograft failure, an interval greater than 6 months between procedures, no need for mechanical ventilatory assistance before retransplantation, and retransplantation after 1985. These data have been corroborated by a recent report from the same registry focusing on cardiac retransplantation [11]. In this study survival was lower when the intertransplant interval was short. Additional independent risk factors for mortality included overall cardiac transplant center volume, the use of a ventricular assist device or ventilator, the patient being in the intensive care unit, and recipient age.
The early results, in terms of survival, after retransplantation in this small series compare favorably with the 55% 1-year survival reported in the Stanford series [12], the 45.5% 1-year survival in the French study [13], and 66% 1-year survival in the Columbia study [14]. This current report also suggests that the 1-year survival of patients who undergo heart retransplantation is comparable to the 1-year survival of patients who undergo primary heart transplantation at our institution. This is in contradistinction to the results of other reports and from the International Society for Heart and Lung Transplantation Registry, all of which suggested that the 1-year and 5-year survival after retransplantation is inferior to that of primary transplantation [12–15]. This study indicates that cardiac retransplantation can be a safe and effective treatment of cardiac allograft vasculopathy.
In terms of other cardiac conditions that may develop after cardiac transplantation, it appears that a spectrum of problems may arise. We believe that meticulous, detailed postoperative follow-up is necessary subsequent to the initial transplant procedure to assess the general health and status of recipients and to search for complicating factors and conditions that might arise. A variety of standard techniques such as echocardiogram, computed tomographic scanning, and cardiac catheterization may be used as indicated. Several reoperative procedures may be used in addition to retransplantation. These procedures appear to be feasible and safe in terms of overall survival, and they seem to provide reasonably effective long-term palliation.
In conclusion, there is a spectrum of cardiovascular diseases that may require cardiac surgical intervention after orthotopic cardiac transplantation, with cardiac allograft vasculopathy being the most common. It is reasonably safe and effective to perform a variety of cardiac procedures, including cardiac retransplantation, on cardiac transplant recipients. The intermediate term results are gratifying in terms of survival and symptomatic improvement.
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