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Ann Thorac Surg 1997;63:1133-1137
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Perioperative Risk and Long-Term Results of Heart Transplantation After Previous Cardiac Operations

Clinic for Cardiovascular Surgery and Department of Cardiology, University Hospital Zürich, Zürich, Switzerland

Accepted for publication December 27, 1996.

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Operative Technique Results Comment References

 
Background. In recent years, there has been an increasing proportion of candidates for heart transplantation who have sustained one or several previous cardiac operations. This study analyzes the perioperative management and the long-term survival of patients undergoing orthotopic heart transplantation as a redo operation and compares the results with those obtained in patients undergoing transplantation as the first cardiac operation.

Methods. From October 1985 to October 1994, 204 heart transplantations were performed in 202 patients. Thirty-eight transplantations were performed in patients who had undergone prior cardiac operations because of coronary artery disease (n = 21) and valvular disease (n = 8) as well as one or several palliative or corrective procedures because of complex congenital heart disease (n = 9). These 38 patients were compared in a case-control fashion with 76 patients who underwent orthotopic cardiac transplantation as a primary cardiac procedure during the same period and using similar techniques. The majority of preoperative variables (hemodynamics, inotropic support, liver and renal function, coagulation, and priority to transplantation) were comparable in the two groups of patients. Mean age was significantly younger in the group of patients with a previous operation (42.2 ± 9.5 versus 50.1 ± 7.3 years; p < 0.001).

Results. Except the problem of more fastidious hemostasis, which is nowadays under better control since aprotinin has been routinely administered, the results show no significant difference in term of perioperative risk (hospital mortality: 5.2% in study group versus 7.8% in the control group) and long-term outcome. The 1-year survival rate was 92.7% ± 3.6% in the study group versus 90.8% ± 3.6% in the control group, and the 5-year survival rate was 79.4% ± 4.5% versus 74.8% ± 7.5%, respectively.

Conclusions. These results are very acceptable and confirm the fact that carefully selected candidates for transplantation are not exposed to a particularly high perioperative risk when a prior cardiac operation has been performed. The incidences of early and late rejection episodes as well as the numbers of postoperative infections are similar in the two groups. Although multiple prior procedures do constitute significant risk factors for perioperative morbidity and mortality in isolated lung and heart-lung transplantation, this is not the case in heart transplantation.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Operative Technique Results Comment References

 
Cardiac transplantation has evolved from a highly experimental procedure to an accepted modality for treatment of end-stage heart failure in infants, children, and adults. The obvious success of cardiac transplantation can be attributed to substantial improvements in different areas, including the preoperative management of recipients, donor management and organ preservation, prevention and treatment of rejection, and the early aggressive management of medical and infectious complications [1, 2].

In recent years, there has been an increasing proportion of candidates for heart transplantation who have sustained one or several previous cardiac operations [3, 4]. This study analyzes the perioperative problems (in terms of surgical, anesthesiologic, and intensive care characteristics, as well as early morbidity and mortality) and the long-term survival of patients undergoing orthotopic heart transplantation as a redo operation and compares the results with those obtained in patients undergoing transplantation as a primary cardiac operation.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Operative Technique Results Comment References

 
Patients
From October 1985 to October 1994, 204 heart transplantations were performed in 202 patients. Thirty-eight transplantations were performed in patients who had undergone a prior cardiac operation because of coronary artery disease (n = 21) and valvular disease (n = 8) as well as one or several palliative or corrective procedures because of complex congenital heart disease (n = 9):

Of the patients who had had prior myocardial revascularization, 15/21 had received at least one internal thoracic artery; in 5 of them bilateral internal thoracic artery grafting had been performed. These 38 patients were compared in a case-control fashion with 76 patients (the 1 before and the 1 after each redo heart transplantation patient) who underwent orthotopic cardiac transplantation as a primary cardiac procedure during the same period and using similar surgical and myocardial protection techniques: in the control group, the cause of end-stage heart failure was ischemic or valvular cardiopathy in 49 (64.5%) and idiopathic cardiomyopathy in 27 patients (35.5%).

For the assessment of panel cytotoxic reactive antibodies, we used the standard National Institutes of Health microlymphocytotoxicity assay (obtained from 56 healthy donors).

Nine patients presented with structural alterations of the cardiac anatomy: diagnosis included late systemic ventricular failure after Senning repair because of transposition of the great arteries (n = 2), congenitally corrected transposition with dextroposition or levoposition (n = 3), primitive ventricle with subaortic outlet chamber (n = 1), double-outlet right ventricle with D-transposition (n = 1), single ventricle with mitral atresia and pulmonary stenosis (n = 1), and tricuspid atresia with right ventricular hypoplasia (n = 1). A total of 15 previous operations had been performed in these patients 9 to 24 years before transplantation, including different forms of systemic-pulmonary or atriopulmonary connections (modified Blalock-Taussig shunt, Glenn-shunt, central Potts or Waterston shunts, and Blalock-Hanlon atrioseptectomy).

The remaining patients (n = 29) were scheduled for transplantation after they had undergone either isolated myocardial revascularization or valvular replacement several days to 14 years before; of these patients, 27 were in New York Heart Association functional class III or IV, whereas 2 patients were in New York Heart Association functional class II-III. Four patients received transplants as an extremely urgent option because of recurrent, therapy-refractory heart failure that necessitated prolonged inotropic treatment in the intensive care unit before transplantation. During transplantation, low-dose aprotinin has been used in every patient since September 1989 and consists of a single dose of 2 million KIU (280 mg) in the priming volume of the extracorporeal circulation [5].

Hemodynamic monitoring was carried out with central venous catheter and peripheral arterial catheter placement only; a pulmonary catheter was inserted only in patients with severe pulmonary hypertension with elevated pulmonary vascular resistance (more than 6 Wood units or 300 dynes•cm^-5/m²) but usually in every patient undergoing reoperation. Perioperative immunosuppression was similar in both groups of patients-with minor changes over the years-and consisted of preoperative azathioprine treatment (1 mg/kg body weight) and steroids (1,000 mg methylprednisolone) in the extracorporeal circulation immediately before the start of reperfusion. Postoperatively, all patients received a triple regimen including azathioprine (1 to 1.5 mg/kg), cyclosporine (4 mg/kg), and steroids starting with 50 mg daily and reducing the doses during the first months. Induction therapy with antithymocyte globulin was performed within the first 5 days.

	Operative Technique

Top Footnotes Abstract Introduction Patients and Methods Operative Technique Results Comment References

 
TRANSPLANTATION AS THE FIRST CARDIAC OPERATION.
After median sternotomy, cardiopulmonary bypass was instituted after aortic and bicaval cannulation and conducted in moderate hypothermia (32°C). After electrical induction of ventricular fibrillation, the recipient cardiectomy was performed. Until 1990, the most classic technique of transplantation using biatrial anastomoses was performed. In 1990 bicaval anastomosis technique was introduced to reduce the incidence of early postoperative conduction disturbance and decrease the rate of tricuspid and mitral valve regurgitation [6]. Since 1989, warm antegrade blood cardioplegia has been administered before the start of reperfusion. Weaning from extracorporeal circulation was performed under similar inotropic support as that applied to the multiorgan donor immediately before organ retrieval.

TRANSPLANTATION AFTER PREVIOUS CORONARY AND VALVULAR OPERATIONS.
In patients scheduled for cardiac transplantation after a prior coronary or valvular operation, median sternotomy was performed first routinely, except in patients with severe preoperative ventricular arrhythmias, in whom preliminary exposure of the femoral vessels was routinely performed, because severe hemodynamic instability or sudden ventricular fibrillation may develop in many recipients during sternotomy and dissection of the dense mediastinal and pericardial adhesions. With this additional precaution, femorofemoral cardiopulmonary bypass may be instituted very rapidly if needed.

Our common policy was to perform aortic and bicaval cannulation whenever possible and to proceed with femorofemoral bypass only exceptionally (eg, very short aorta with multiple venous graft anastomoses). In patients with previous mammary artery bypass grafting, this vessel was clipped when it crossed the pericardium. The technique of graft implantation was identical with that described above.

CONGENITAL DISEASE.
In cardiac recipients who have undergone previous operations, the donor cardiectomy is modified to include complete inflow and outflow tissue in the explant, and transplantation can mostly be performed without the use of prosthetic material. Due to the requirement of maintaining continuity of the left and the right main pulmonary arteries out to the hilum, lung retrieval was not possible in some of these cases.

Complete reconstruction of the interatrial septum with restoration of two posterior atrial cuffs was required in 1 patient after previous Senning repair; in a second patient, bicaval anastomosis was performed instead of right atrial anastomosis. Extensive mobilization of the main pulmonary artery behind the ascending aorta was performed and end-to-end anastomosis of the pulmonary artery was performed before aortic anastomosis without distortion of the vessel.

Taking down of previously fashioned shunts did not result in any technical complication in these particular patients. Central aortopulmonary shunts were closed from inside the aorta with a small polytetrafluoroethylene or pericardial patch. Lessons learned from the arterial switch operation have greatly facilitated the extensive mobilization necessary for orthotopic transplantation in patients with transposition of the great vessels to avoid distortion of the aortic and pulmonary anastomoses.

	Results

Top Footnotes Abstract Introduction Patients and Methods Operative Technique Results Comment References

 
The majority of preoperative variables (hemodynamics, need for inotropic support, liver and renal function, coagulation, and priority to transplantation) were comparable in the two groups of patients. Use of anticoagulants (warfarin, heparin, or salicylic acid) was similar in the two groups.

The incidence of preformed cytotoxic antibodies was not statistically significantly higher in the group of patients who had had previous cardiac operations (4/76 or 5.2% versus 1/38 or 2.6%). Mean age was significantly less in the group of patients undergoing redo operation (42.2 ± 9.5 versus 50.1 ± 7.3 years; p < 0.001). In the reoperation group, cardiopulmonary bypass had to be instituted through femorofemoral cannulas in 14/38 patients because of severe ventricular tachyarrhythmias in 8 patients, tear in the right ventricle in 2, and increasing low output condition during dissection of the dense pericardial adhesions in 4. The average cold ischemic interval and average operating time were somewhat longer in the patients from the reoperation group, but the values were not significantly different from those found in patients who underwent transplantation as a primary operation. Despite the more demanding operative technique, operative mortality was not higher in the reoperation group (2.6% versus 5.2% in the control group); likewise, the incidence of perioperative complications was comparable in the two groups.

The use of intraoperative and early postoperative inotropic support, usually started during reperfusion, did not exceed 3 to 6 µg/kg per minute dopamine, 2 to 5 µg/kg epinephrine, or a combination of the two, corresponding closely to the inotropic support of the donor. Eight patients presented with some different degrees of early graft failure, requiring more than the usual inotropic support: intraaortic balloon counterpulsation was necessary in 2 patients and a right ventricular assist device was implanted in 1 patient, but there was no significant difference between the two groups of the patients.

Surprisingly, the incidence of sternal wound healing problems was not higher in patients with prior sternotomy or in those who had sustained previous bypass operations with the use of the internal mammary artery.

Except for the problem of more fastidious hemostasis, which resulted in a greater transfusion requirement (Table 1) but which is nowadays under better control since aprotinin has been routinely administered, the results show no significant difference in term of perioperative risk (operative mortality = 2.6% in study group versus 5.2% in the control group) and long-term outcome. The 1-year survival rate was 92.7% ± 3.6% in the study group versus 90.8% ± 3.6% in the control group, and the 5-year survival rate was 79.4% ± 4.5% versus 74.8% ± 7.5%, respectively (Table 2).

	Comment

Top Footnotes Abstract Introduction Patients and Methods Operative Technique Results Comment References

 
Cardiac transplantation is currently an accepted treatment for intractable end-stage heart disease. Because the supply of donor hearts is limited, analysis of perioperative morbidity and mortality and identification of recipient risk factors for early and late death after transplantation may have an important role in identifying patients who may really benefit from this surgical therapy. In the present study, we focused our attention on patients who were selected for transplantation after a previous cardiac operation, including coronary bypass grafting, valvular replacement, or multiple surgical procedures for complex congenital disease. In our institution, the great majority of transplant candidates are presently between 40 to 60 years of age, and this group involves a considerable proportion of individuals who had prior cardiac operations.

Increasing progress in the treatment of neonates and infants with complex congenital heart diseases is nowadays best demonstrated by the high number of early definitive surgical operations. Adolescent and adult patients undergoing cardiac transplantation for congenital heart disease remain exceptional cases. Our experience shows that adolescent and adult patients with complex congenital heart disease can receive transplants with a very low perioperative risk, even after several previous palliative procedures or total repair. Better pretransplantation maintenance of these patients (eg, by afterload reduction) has markedly improved their condition at transplantation, thus decreasing the perioperative risk. A certain limitation of our series was the impossibility to compare fairly the group of patients with congenital heart disease, because practically no patient received a transplant for this reason without a previous palliative or corrective operation.

The operative technique must be adapted to the malformation. Our actual standard technique including end-to-end bicaval anastomoses seems to restore advantageous geometry, and extensive reconstruction of the pulmonary arteries can be performed with donor vessels only, occasionally precluding lung procurement. Some of the surgical techniques applied to the correction of congenital anomalies are innovative; some others are based on preexisting surgical concepts that have been modified and adapted to the special situation in which correction and transplantation are combined [7, 8].

In analogy to our results, the series reported by Lammermeier and associates [4] presented no differences in survival but a trend to increased perioperative complication rate in patients from the reoperation group. Postoperative hemorrhage requiring reexploration was similar in the two groups, but blood component therapy was significantly increased in the reoperation group. This was confirmed by Prendergast and coworkers [9] in a well-defined manner. Although technically more demanding, the reoperations were not marked by a significant longer operative time. In the present series, the recorded ischemic times are very short in both groups, mainly because of a high incidence of local donors and the short distances from the secondary hospitals where multiorgan procurements were performed.

Technical difficulties and complex perioperative management encountered during high-risk reparative cardiac operations have to be compared with the overall risk after heart transplantation [10].

Surprisingly, the incidence of positive cytotoxic antibodies was not higher in the group of patients with previous operations. This may be due at least partially to the restrictive policy of blood transfusion in our institution during the last decade. Generally, patients with left ventricular ejection fraction greater than 0.4 and absence of significant pulmonary disease received transfusion only if the early postoperative hematocrit value decreased to less than 0.24.

Long-term survival analysis showed no difference between cardiac recipients who had suffered from cardiomyopathy, coronary disease, or congenital disease. This observation contrasts with results from other studies published at the beginning of the revival period of cardiac transplantation [1]. The incidence of early and late rejection episodes as well as the number of postoperative infections were similar in both groups of patients; this may well be expected, because the same protocol of routine scheduled endomyocardial biopsies was applied in all patients operated on in this time interval.

Our results are very acceptable and confirm the fact that candidates for cardiac transplantation are not exposed to a particular high perioperative risk when a prior operation has been performed. Likewise, long-term results are very promising in this particular subset of patients.

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Operative Technique Results Comment References

	References

Top Footnotes Abstract Introduction Patients and Methods Operative Technique Results Comment References

 

1. Kirklin JK, Naftel DC, McGriffin DC, McVay RF, Blackstone EH, Karp RB. Analysis of morbid events and risk factors for death after cardiac transplantation. J Am Coll Cardiol 1988;11:917–24.[Abstract]
2. Bourge RC, Naftel DC, Costanzo-Nordin M. Risk factors for death after cardiac transplantation: a multi-institutional study. J Heart Lung Transplant 1992;11:191–7.
3. Ott GY, Norman DJ, Hosenpud JD, Hershberger RE, Ratkovec RM, Cobanoglu A. Heart transplantation in patients with previous cardiac operations: excellent clinical results. J Thorac Cardiovasc Surg 1994;107:203–9.[Abstract/Free Full Text]
4. Lammermeier DE, Nakatani T, Sweeney MS, et al. Effect of prior cardiac surgery on survival after heart transplantation. Ann Thorac Surg 1989;48:168–72.[Abstract]
5. Carrel T, Bauer E, Laske A, von Segesser L, Turina M. Low-dose aprotinin for reduction of blood loss after cardiopulmonary bypass [Letter]. Lancet 1991;337:673.[Medline]
6. Laske A, Carrel T, Pasic M, et al. Orthotopic heart transplantation with bicaval anastomoses. Eur J Cardiothorac Surg 1995;9:120–6.[Abstract]
7. Carrel T, Neth J, Pasic M, Laske A, Jenni R, Turina M. Should cardiac transplantation for congenital heart disease be delayed until adult age? Eur J Cardiothorac Surg 1994;8:462–9.[Abstract]
8. Menkis AH, McKenzie FN, Novick RJ, et al. Expanding applicability of transplantation after multiple prior palliative procedures. Ann Thorac Surg 1991;52:722–6.[Abstract]
9. Prendergast TW, Furukawa S, Beyer AJ III, Elsen HJ, McClurken JB, Jeevanandam V. Defining the role of aprotinin in heart transplantation. Ann Thorac Surg 1996;62:670–4.[Abstract/Free Full Text]
10. Sanchez JA, Smith CR, Drusin RE. High-risk reparative surgery: a neglected alternative to heart transplantation. Circulation 1990;82(Suppl 4):302–5.[Free Full Text]

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Thierry Carrel Marko I. Turina Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carrel, T. Articles by Turina, M. I. Search for Related Content PubMed PubMed Citation Articles by Carrel, T. Articles by Turina, M. I.