- Email: [email protected]
Late Noncardiac Surgery in Heart Transplant Patients
Late Noncardiac Surgery in Heart Transplant Patients R. Marzoa, M.G. Crespo-Leiro, M.J. Paniagua, I. Bendayán, R. Rios, R. Franco, J.A. Rodriguez, E. Barge, C. Naya, M. Gómez, J.J. Cuenca, A. Juffé, and A. Castro-Beiras ABSTRACT Introduction. Because of improved long-term survival of heart transplants (HT), patients often need noncardiac surgery (NCS). Immunosuppression may increase the infection rate. Inadequate management may increase the risk of dysfunction or acute rejection episodes (ARE). Long-term outcomes of NCS and optimal immunosuppressive management in the perioperative period are not well known. The objective of this study was to analyze the incidence, morbidity, and mortality of late NCS after HT. Methods. We retrospectively evaluated the incidence and type of late NCS as well as the risk factors for complications and the mortality among 207 HT patients. Immunosuppression and ARE rates were also analyzed. Results. One hundred and sixteen late NCS (84.5% elective) were performed in 72 HT patients (34.8%). Interventions were: 35 urologic (30.2%), 29 abdominal (25%), 14 vascular (12.1%), 13 ENT (11.2%), 11 skin and soft tissue (9.5%), and 7 orthopedic (6%). Malignancy was the main indication for NCS (33.6%). Only 4 patients (5.6%) died preoperatively. Mortality was higher among emergent vs elective procedures (16.6% vs 1%; P ⫽ .012) and among patients with preoperative high vs middle/low risk (26.6% vs 0%). Postsurgical infection was the most frequent complication (6.9%). However, there were no relevant complications in 82.8% of HT patients. Hospitalization time was ⬍15 days in two thirds of patients. Immunosuppression was modified in 33 patients (28.4%), especially when the surgical indication was neoplasia (P ⬍ .001). None of the patients with NCS displayed allograft dysfunction or an ARE. Conclusions: More than one-third of HT patients needed a late NCS. In our experience, elective surgical procedures with middle/low preoperative cardiovascular risk are safe. In this context, the risk of rejection was low when immunosuppression was carefully monitored to reduce the risk of infection.
S
EVERAL IMPROVEMENTS in posttransplantation immunosuppressive regimens and new surgical techniques have increased survival rates among heart transplant (HT) recipients. One- and 10-year survivals have been reported to be 75% and 50%, respectively.1 Patients who have undergone orthotopic heart transplantation are at risk to develop the same surgical diseases as the general population. Moreover, they may need surgical procedures for problems caused by immunosuppressive therapy. Several studies have reported the incidence, morbidity, and mortality of general surgical conditions in cardiac transplant recipients.2–7 The literature has suggested that this population displayed increased morbidity (⬇10%),4,6 since patients receiving chronic immunosuppressive therapy show a
greater risk of infection and an increased mortality rate when they require extramediastinal operative management. It has been reported that a high percentage of cardiac transplant recipients (15%– 40%) need late noncardiac surgical (NCS) procedures.2–7
From the Área del Corazón, Complejo Hospitalario Juan Canalejo, La Coruña, Spain. This study was supported by a grant from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, “Red Temática de Investigación Cardiovascular (RECAVA).” Address reprint requests to Raquel Marzoa Rivas, Servicio de Cardiología, Hospital Juan Canalejo, Xubias 84, 15006 La Coruña, Spain. E-mail: [email protected]
0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.07.064
© 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2382
Transplantation Proceedings, 39, 2382–2384 (2007)
LATE NONCARDIAC SURGERY IN HT PATIENTS
However, there is little available data regarding the outcome of patients who have undergone surgery after HT. There is no optimal preoperative evaluation or risk classification for there recipients. Recently, the guidelines for perioperative cardiovascular evaluation for NCS have been published by the American College of Cardiology (ACC)8 and the American Heart Association (AHA). These guidelines provide recommendations for pre-, intra-, and postoperative care of patients undergoing NCS, as well as a cardiac risk stratification scheme for NCS procedures: high, intermediate, or low risk. Knowledge of the etiology, complications, risk factors, immunosuppressive therapy, and current outcome of NCS procedures after HT may contribute to a favorable outcome of these surgical interventions. Recognizing clinical and laboratory predictors of increased perioperative risk and developing an optimal protocol with specific recommendations for immunotherapy in the perioperative period should help to inform the physician’s decision and are key factors for the optimal outcome of this population. METHODS We retrospectively evaluated 207 consecutive HT recipients with a minimum follow-up of 5 years, seeking to identify patients who had undergone one or more NCS. Late NCS was defined as an extramediastinal surgical procedure performed at 1 month or more posttransplantation. We analyzed the incidence and type of the late NCS procedures, as well as the type of postoperative complications and potential risk factors: emergent/elective surgery, basal immunosuppressive regimen, medical site in which the NCS was performed, and cardiac risk stratification. Mortality in the perioperative period, immunosuppressive management, and acute rejection episodes (ARE) were analyzed in this population. NCS procedures were classified retrospectively according to the high, intermediate, and low preoperative risk scale for each group following the ACC/AHA guidelines8 to evaluate the risk of mortality. Immunosuppressive regimen management followed our protocol. Usually, the dose of immunosuppression was not modified during the preoperative phase. When patients did not tolerate a diet, the immunosuppressive drugs were administered intravenously. Thus, the dosage of cyclosporine was calculated using the equivalence between intravenous and oral dosage (cyclosporine oral dosage ⫽ 1/3 of cyclosporine IV). When patients were taking mycophenolate mofetil and intravenous administration was not feasible, the drug was replaced by azathioprine (50 mg twice a day IV). All patients received a “stress” dosage of actocortina (100 mg IV) 30 minutes before NCS and an equivalent dosage of oral prednisone administered intravenously in the perioperative period. When patients were able to take oral immunosuppressive therapy again, the initial dosage was the same as what the patient was taking after the surgery. Immunosuppressive drug blood levels were carefully monitored until analytic stabilization was reached.
Statistical Analysis The results are presented as mean values ⫾ 1 SD for continuous normally distributed variables or as medians (interquartile range) for continuous non-normally distributed data, or as percentages for categorical data. Analysis of normality was performed with the Kolmogorov- Smirnov or Shapiro-Wilk test. Categorical data and
2383 proportions were analyzed using the chi-square test or Fisher exact test as required. Comparisons of continuous variables were analyzed using unpaired student t tests or the Mann-Whitney U test as appropriate. The Spearman 2-way test was used to assess the relation between 2 quantitative variables with non-normal distribution. The Pearson 2-way test was used to assess relationships between 2 quantitative variables with normal distributions. Differences were considered to be statistically significant if the null hypothesis was rejected with ⬎95% confidence. The SPSS 13.0 statistical software package was used for all calculations. For patients on treatment with mTOR inhibitors (sirolimus or everolimus) needing surgery, these drugs must be transitorily stopped during the perioperative period for avoiding problems related with wound healing. Mycophenolate mofetil or azathioprine are the agents used in the interim.
RESULTS
Seventy-two HT patients (34.8%) required 116 late NCS. Median follow-up was 3800 ⫾ 772 days (range, 2533–5566 days). Elective surgery was observed in a high percentage of cases (84.5%) with emergent surgery only necessary in a minority of cases. Late operations were performed on 92 occasions (79.3%) at our institution and 24 times at a nontransplant center. Retrospectively, 16 procedures were considered low-risk NCS and 85 intermediate risk (both with a reported cardiac risk generally lower than 5%). Fifteen NCS interventions were performed in the high-risk group who had a reported cardiac risk often greater than 5%: 14 of 116 (12.1%) interventions were performed within the first year posttransplantation, and the rest conducted ⬎1 year posttransplantation. There were 35 urologic interventions (30.2%), 29 abdominal procedures (25%), 14 vascular interventions (12.1%), 13 otolaryngology and oral operations (11.2%), 11 skin and soft tissue and 7 major orthopedic procedures (9.5% and 6%, respectively). Malignant neoplasms were the most frequent indication for NCS (39 cases of 116 interventions; 33.6%). Four patients died during the postoperative period (5.6% of 72; 1.9% of all 207). Mortality was significantly higher followup emergent than elective procedures (16.6% vs 1%; P ⫽ .012). Preoperative high-risk HT patient mortality was 26.6%; however, none of the HT patients with middle and low perioperative cardiovascular risk died. The center where the surgery was performed, basal immunosuppressive regimen, and demographic characteristics were not significantly related to mortality risk. Postsurgical infection, especially wound infection, was the most frequent complication during the postoperative period (8 cases of 116; 6.9%). Temporary renal dysfunction (2.6%), postoperative bleeding (1.7%), reintervention (1.7%), and hemodynamic instability (2.6%) were complications observed in the cohort under study. However, there were no relevant complications in 82.8% of HT patients. Hospitalization time was ⬍15 days in two thirds of patients. Of the 116 NCS interventions, basal immunosuppressive therapy was cyclosporine, mycophenolate and prednisone in 45 (38.8%); prednisone and cyclosporine (19.8%); ta-
2384
crolimus and prednisone (4.3%); tacrolimus, mycophenolate, and prednisone (0.9%); tacrolimus, azathioprine, and prednisone (1.7%); cyclosporine, prednisone, and azathioprine (0.9%). In 83 NCS procedures there was no modification of the immunosuppressive regimen. In 21 of 116 cases (18.1%), the surgery was followed by a dose reduction, and 12 cases (10.3%) required a change of immunosuppressive therapy; the majority of these were cases of neoplasms as the surgical indication. All patients received “stress” corticoid dosages and immunosuppressive therapy was intravenously administered when oral administration was not possible. Immunosuppressive regimen management was performed following a protocol in all cases; related adverse effects were not observed. None of the 72 HT patients who underwent general surgical procedures showed signs or clinical manifestations of dysfunction or acute rejection during the perioperative period. DISCUSSION
Consistent with the results of previous studies,2–7 we observed that HT patients showed a high incidence of late NCS procedures. These patients required a variety of NCS, involving most surgical specialties, with one third of the NCS potentially related to adverse effects of immunosuppressive therapy. Nevertheless, the majority of procedures were due to “common” conditions frequently affecting the general population. Recently, it was observed in 39 autopsied HT patients9 that 8% of deaths were attributed to complications after NSC. However, since NCS comprises a heterogeneous group of interventions, attributing an overall mortality risk for all of them is not possible. We have observed that the mortality rate is significantly higher in emergent interventions and in NCS with preoperative high cardiac risk. In this sense, identifying HT patients with a higher risk of developing general surgical conditions and then performing an adequate preoperative evaluation and risk stratification may permit timely intervention decisions to decrease morbidity and mortality in this population. Fazel et al10 observed that a pretransplantation diagnosis of ischemic heart disease and previous history of a general surgical procedure were 2 independent risk factors that predisposed HT recipients to develop general surgical conditions. However, preoperative cardiac function was not related to greater development of postoperative complications in previous studies. Currently, the ACC/AHA guidelines8 of perioperative cardiovascular evaluation for NCS may be useful for cardiac risk stratification (high, intermediate, and low risk) for HT patients who undergo NCS procedures. Knowledge of cardiac risk degree by cardiologists, anesthetists, and
MARZOA, CRESPO-LEIRO, PANIAGUA ET AL
surgeons may be important for strict, close monitoring of high-risk patients in the perioperative period. It is known that chronically immunosuppressed patients show a greater risk of postoperative infection, but careful management of immunosuppressive therapy may minimize the risk of perioperative complications. At this moment, no protocol exists for immunosuppressive therapy management for HT patients undergoing NCS procedures. Administration of “stress” corticoid dosage after extramediastinal surgery and intravenous administration of basal immunosuppressive therapy appear to be a safe strategy. None of the studied cohort presented graft dysfunction or acute rejection. Decisions should be made on an individual basis for each patient; however, we believe that in a high percentage of HT patients with surgical indication, expectant therapy is not justified because the benefit of an invasive procedure is usually greater than the risk. Preoperative risk stratification and identification of HT patients with a high risk of developing general surgical conditions may optimize the outcomes among this population. REFERENCES 1. Almenar L: Registro español de trasplante cardiaco. XVII Informe oficial de la sección de Insuficiencia cardiaca, trasplante cardiaco y otras alternativas terapéuticas de la Sociedad Española de Cardiologı´a (1984 –2005). Rev Esp Cardiol 59:1283, 2006 2. Yee J, Petsikas D, Ricci MA, et al: General surgical procedures after heart transplantation. Can J Surg 33:185, 1990 3. Bhatia DS, Bowen JC, Money SR, et al: The incidence, morbidity, and mortality of surgical procedures after orthotopic heart transplantation. Ann Surg 225:686, 1997 4. Velanovich V, Ezzat W, Horn C, et al: Surgery in heart and lung transplant patients. Am J Surg 187:501, 2004 5. Merhav H, Eisner S, Nakache R: Analysis of late operations in transplant patients. Transplant Proc 36:3083, 2004 6. Mueller XM, Tevaearai HT, Stumpe F, et al: Extramediastinal surgical problems in heart transplant recipients. J Am Coll Surg 189:380, 1999 7. Melendez JA, Delphin E, Lamb J, et al: Noncardiac surgery in heart transplant recipients in the cyclosporine era. J Cardiothorac Vasc Anesth 5:218, 1991 8. Berger PB, Calkins H, Chaitman BR, et al: ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery. Executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Circulation 105:1257, 2002 9. Alexander RT, Steenbergen C: Cause of death and sudden cardiac death after heart transplantation. An autopsy study. Am J Clin Pathol 119:740, 2003 10. Fazel S, Everson EA, Stitt LW, et al: Predictors of general surgical complications after heart transplantation. J Am Coll Surg 193:52, 2001
S
EVERAL IMPROVEMENTS in posttransplantation immunosuppressive regimens and new surgical techniques have increased survival rates among heart transplant (HT) recipients. One- and 10-year survivals have been reported to be 75% and 50%, respectively.1 Patients who have undergone orthotopic heart transplantation are at risk to develop the same surgical diseases as the general population. Moreover, they may need surgical procedures for problems caused by immunosuppressive therapy. Several studies have reported the incidence, morbidity, and mortality of general surgical conditions in cardiac transplant recipients.2–7 The literature has suggested that this population displayed increased morbidity (⬇10%),4,6 since patients receiving chronic immunosuppressive therapy show a
greater risk of infection and an increased mortality rate when they require extramediastinal operative management. It has been reported that a high percentage of cardiac transplant recipients (15%– 40%) need late noncardiac surgical (NCS) procedures.2–7
From the Área del Corazón, Complejo Hospitalario Juan Canalejo, La Coruña, Spain. This study was supported by a grant from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III, “Red Temática de Investigación Cardiovascular (RECAVA).” Address reprint requests to Raquel Marzoa Rivas, Servicio de Cardiología, Hospital Juan Canalejo, Xubias 84, 15006 La Coruña, Spain. E-mail: [email protected]
0041-1345/07/$–see front matter doi:10.1016/j.transproceed.2007.07.064
© 2007 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
2382
Transplantation Proceedings, 39, 2382–2384 (2007)
LATE NONCARDIAC SURGERY IN HT PATIENTS
However, there is little available data regarding the outcome of patients who have undergone surgery after HT. There is no optimal preoperative evaluation or risk classification for there recipients. Recently, the guidelines for perioperative cardiovascular evaluation for NCS have been published by the American College of Cardiology (ACC)8 and the American Heart Association (AHA). These guidelines provide recommendations for pre-, intra-, and postoperative care of patients undergoing NCS, as well as a cardiac risk stratification scheme for NCS procedures: high, intermediate, or low risk. Knowledge of the etiology, complications, risk factors, immunosuppressive therapy, and current outcome of NCS procedures after HT may contribute to a favorable outcome of these surgical interventions. Recognizing clinical and laboratory predictors of increased perioperative risk and developing an optimal protocol with specific recommendations for immunotherapy in the perioperative period should help to inform the physician’s decision and are key factors for the optimal outcome of this population. METHODS We retrospectively evaluated 207 consecutive HT recipients with a minimum follow-up of 5 years, seeking to identify patients who had undergone one or more NCS. Late NCS was defined as an extramediastinal surgical procedure performed at 1 month or more posttransplantation. We analyzed the incidence and type of the late NCS procedures, as well as the type of postoperative complications and potential risk factors: emergent/elective surgery, basal immunosuppressive regimen, medical site in which the NCS was performed, and cardiac risk stratification. Mortality in the perioperative period, immunosuppressive management, and acute rejection episodes (ARE) were analyzed in this population. NCS procedures were classified retrospectively according to the high, intermediate, and low preoperative risk scale for each group following the ACC/AHA guidelines8 to evaluate the risk of mortality. Immunosuppressive regimen management followed our protocol. Usually, the dose of immunosuppression was not modified during the preoperative phase. When patients did not tolerate a diet, the immunosuppressive drugs were administered intravenously. Thus, the dosage of cyclosporine was calculated using the equivalence between intravenous and oral dosage (cyclosporine oral dosage ⫽ 1/3 of cyclosporine IV). When patients were taking mycophenolate mofetil and intravenous administration was not feasible, the drug was replaced by azathioprine (50 mg twice a day IV). All patients received a “stress” dosage of actocortina (100 mg IV) 30 minutes before NCS and an equivalent dosage of oral prednisone administered intravenously in the perioperative period. When patients were able to take oral immunosuppressive therapy again, the initial dosage was the same as what the patient was taking after the surgery. Immunosuppressive drug blood levels were carefully monitored until analytic stabilization was reached.
Statistical Analysis The results are presented as mean values ⫾ 1 SD for continuous normally distributed variables or as medians (interquartile range) for continuous non-normally distributed data, or as percentages for categorical data. Analysis of normality was performed with the Kolmogorov- Smirnov or Shapiro-Wilk test. Categorical data and
2383 proportions were analyzed using the chi-square test or Fisher exact test as required. Comparisons of continuous variables were analyzed using unpaired student t tests or the Mann-Whitney U test as appropriate. The Spearman 2-way test was used to assess the relation between 2 quantitative variables with non-normal distribution. The Pearson 2-way test was used to assess relationships between 2 quantitative variables with normal distributions. Differences were considered to be statistically significant if the null hypothesis was rejected with ⬎95% confidence. The SPSS 13.0 statistical software package was used for all calculations. For patients on treatment with mTOR inhibitors (sirolimus or everolimus) needing surgery, these drugs must be transitorily stopped during the perioperative period for avoiding problems related with wound healing. Mycophenolate mofetil or azathioprine are the agents used in the interim.
RESULTS
Seventy-two HT patients (34.8%) required 116 late NCS. Median follow-up was 3800 ⫾ 772 days (range, 2533–5566 days). Elective surgery was observed in a high percentage of cases (84.5%) with emergent surgery only necessary in a minority of cases. Late operations were performed on 92 occasions (79.3%) at our institution and 24 times at a nontransplant center. Retrospectively, 16 procedures were considered low-risk NCS and 85 intermediate risk (both with a reported cardiac risk generally lower than 5%). Fifteen NCS interventions were performed in the high-risk group who had a reported cardiac risk often greater than 5%: 14 of 116 (12.1%) interventions were performed within the first year posttransplantation, and the rest conducted ⬎1 year posttransplantation. There were 35 urologic interventions (30.2%), 29 abdominal procedures (25%), 14 vascular interventions (12.1%), 13 otolaryngology and oral operations (11.2%), 11 skin and soft tissue and 7 major orthopedic procedures (9.5% and 6%, respectively). Malignant neoplasms were the most frequent indication for NCS (39 cases of 116 interventions; 33.6%). Four patients died during the postoperative period (5.6% of 72; 1.9% of all 207). Mortality was significantly higher followup emergent than elective procedures (16.6% vs 1%; P ⫽ .012). Preoperative high-risk HT patient mortality was 26.6%; however, none of the HT patients with middle and low perioperative cardiovascular risk died. The center where the surgery was performed, basal immunosuppressive regimen, and demographic characteristics were not significantly related to mortality risk. Postsurgical infection, especially wound infection, was the most frequent complication during the postoperative period (8 cases of 116; 6.9%). Temporary renal dysfunction (2.6%), postoperative bleeding (1.7%), reintervention (1.7%), and hemodynamic instability (2.6%) were complications observed in the cohort under study. However, there were no relevant complications in 82.8% of HT patients. Hospitalization time was ⬍15 days in two thirds of patients. Of the 116 NCS interventions, basal immunosuppressive therapy was cyclosporine, mycophenolate and prednisone in 45 (38.8%); prednisone and cyclosporine (19.8%); ta-
2384
crolimus and prednisone (4.3%); tacrolimus, mycophenolate, and prednisone (0.9%); tacrolimus, azathioprine, and prednisone (1.7%); cyclosporine, prednisone, and azathioprine (0.9%). In 83 NCS procedures there was no modification of the immunosuppressive regimen. In 21 of 116 cases (18.1%), the surgery was followed by a dose reduction, and 12 cases (10.3%) required a change of immunosuppressive therapy; the majority of these were cases of neoplasms as the surgical indication. All patients received “stress” corticoid dosages and immunosuppressive therapy was intravenously administered when oral administration was not possible. Immunosuppressive regimen management was performed following a protocol in all cases; related adverse effects were not observed. None of the 72 HT patients who underwent general surgical procedures showed signs or clinical manifestations of dysfunction or acute rejection during the perioperative period. DISCUSSION
Consistent with the results of previous studies,2–7 we observed that HT patients showed a high incidence of late NCS procedures. These patients required a variety of NCS, involving most surgical specialties, with one third of the NCS potentially related to adverse effects of immunosuppressive therapy. Nevertheless, the majority of procedures were due to “common” conditions frequently affecting the general population. Recently, it was observed in 39 autopsied HT patients9 that 8% of deaths were attributed to complications after NSC. However, since NCS comprises a heterogeneous group of interventions, attributing an overall mortality risk for all of them is not possible. We have observed that the mortality rate is significantly higher in emergent interventions and in NCS with preoperative high cardiac risk. In this sense, identifying HT patients with a higher risk of developing general surgical conditions and then performing an adequate preoperative evaluation and risk stratification may permit timely intervention decisions to decrease morbidity and mortality in this population. Fazel et al10 observed that a pretransplantation diagnosis of ischemic heart disease and previous history of a general surgical procedure were 2 independent risk factors that predisposed HT recipients to develop general surgical conditions. However, preoperative cardiac function was not related to greater development of postoperative complications in previous studies. Currently, the ACC/AHA guidelines8 of perioperative cardiovascular evaluation for NCS may be useful for cardiac risk stratification (high, intermediate, and low risk) for HT patients who undergo NCS procedures. Knowledge of cardiac risk degree by cardiologists, anesthetists, and
MARZOA, CRESPO-LEIRO, PANIAGUA ET AL
surgeons may be important for strict, close monitoring of high-risk patients in the perioperative period. It is known that chronically immunosuppressed patients show a greater risk of postoperative infection, but careful management of immunosuppressive therapy may minimize the risk of perioperative complications. At this moment, no protocol exists for immunosuppressive therapy management for HT patients undergoing NCS procedures. Administration of “stress” corticoid dosage after extramediastinal surgery and intravenous administration of basal immunosuppressive therapy appear to be a safe strategy. None of the studied cohort presented graft dysfunction or acute rejection. Decisions should be made on an individual basis for each patient; however, we believe that in a high percentage of HT patients with surgical indication, expectant therapy is not justified because the benefit of an invasive procedure is usually greater than the risk. Preoperative risk stratification and identification of HT patients with a high risk of developing general surgical conditions may optimize the outcomes among this population. REFERENCES 1. Almenar L: Registro español de trasplante cardiaco. XVII Informe oficial de la sección de Insuficiencia cardiaca, trasplante cardiaco y otras alternativas terapéuticas de la Sociedad Española de Cardiologı´a (1984 –2005). Rev Esp Cardiol 59:1283, 2006 2. Yee J, Petsikas D, Ricci MA, et al: General surgical procedures after heart transplantation. Can J Surg 33:185, 1990 3. Bhatia DS, Bowen JC, Money SR, et al: The incidence, morbidity, and mortality of surgical procedures after orthotopic heart transplantation. Ann Surg 225:686, 1997 4. Velanovich V, Ezzat W, Horn C, et al: Surgery in heart and lung transplant patients. Am J Surg 187:501, 2004 5. Merhav H, Eisner S, Nakache R: Analysis of late operations in transplant patients. Transplant Proc 36:3083, 2004 6. Mueller XM, Tevaearai HT, Stumpe F, et al: Extramediastinal surgical problems in heart transplant recipients. J Am Coll Surg 189:380, 1999 7. Melendez JA, Delphin E, Lamb J, et al: Noncardiac surgery in heart transplant recipients in the cyclosporine era. J Cardiothorac Vasc Anesth 5:218, 1991 8. Berger PB, Calkins H, Chaitman BR, et al: ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac surgery. Executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Circulation 105:1257, 2002 9. Alexander RT, Steenbergen C: Cause of death and sudden cardiac death after heart transplantation. An autopsy study. Am J Clin Pathol 119:740, 2003 10. Fazel S, Everson EA, Stitt LW, et al: Predictors of general surgical complications after heart transplantation. J Am Coll Surg 193:52, 2001