Heart retransplantation: the 25-year experience at a single institution.

BACKGROUND: The current critical shortage of cardiac allograft donors means that the decision to offer a patient repeat heart transplantation must be carefully considered. Since 1968, a total of 66 heart retransplantation procedures (63 first-time and three second-time) have been performed in 63 patients at Stanford. METHODS: There were 52 male and 11 female patients, ranging in age from 3 to 62 years with a mean age of 41 years. Indications for retransplantation were primary allograft failure in nine patients, acute rejection in 17, graft atherosclerosis in 37, and constrictive disease in three. Six of the seventeen patients (35%) who underwent retransplantation before 1981 died in the hospital, and none are currently alive. Of the 46 patients who underwent retransplantation since 1981 treated with cyclosporine-based immunosuppression, 11 (24%) died in the hospital. Actuarial survival estimates for the whole retransplantation group at 1, 5, and 10 years were 55% +/- 8%, 33% +/- 8%, and 22% +/- 7%, respectively. RESULTS: This survival was significantly worse (p < 0.05) than that in patients undergoing primary heart transplantation (81% +/- 2%, 62% +/- 2%, 44% +/- 13% at 1, 5, and 10 years). Those patients who underwent retransplantation for graft atherosclerosis since 1981 had a significantly better 1-year survival (p < 0.05) than those who underwent retransplantation for allograft rejection (69% +/- 10% versus 33% +/- 16%), but the 5-year survival was similar in both groups (34% +/- 11% versus 33% +/- 16%). Since 1981, actuarial freedoms from infection and rejection were 22% +/- 8% and 41% +/- 9%, respectively, at 1 year, and 7% +/- 7% and 36% +/- 9% at 5 years. Patients with cyclosporine-induced renal dysfunction (serum creatinine level of greater than 2.0 mg/dl) had a high probability of requiring postoperative dialysis and also of death after retransplantation. Three patients with significant cyclosporine-induced renal dysfunction underwent simultaneous kidney transplantation and heart retransplantation, and all were alive and well at the time this article was written. Sixteen patients were also currently alive at a mean follow-up of 44 months, and 15 were in New York Heart Association functional class I. CONCLUSIONS: We continue to list carefully selected candidates with good rehabilitation potential for heart retransplantation.

Randomized, prospective assessment of bioprosthetic valve durability. Hancock versus Carpentier-Edwards valves.

BACKGROUND: Although the major limitation of porcine valves is their finite durability, no controlled clinical data exist regarding the relative durability of the two porcine bioprostheses implanted most commonly today, the Carpentier-Edwards (C-E) and Medtronic Hancock I (H) valves. METHODS AND RESULTS: To assess this question, 174 patients undergoing aortic (AVR) or mitral (MVR) valve replacement with a bioprosthesis between March 1980 and March 1982 were randomized to receive either a C-E or a H valve. There were 102 AVRs (54 C-E and 48 H) and 74 MVRs (39 C-E and 35 H). For both the AVR and MVR cohorts, the average patient age was 58 +/- 14 years (+/- SD). The male/female ratio was 2.2:1 for AVR and 0.57:1 for MVR. Clinical follow-up was undertaken periodically; the most recent follow-up closing interval was July through October 1992, and current follow-up was 96% complete. Cumulative follow-up totaled 1369 patient-years (mean, 7.7 +/- 3.6 years; median, 9.1 years; maximum, 12.0 years). The main focus of this analysis was bioprosthetic durability, using the AATS/STS guidelines defining "Structural Valve Deterioration" (SVD). Multivariate analysis revealed that (younger) age was the only significant (P = .024) independent predictor of SVD. Valve manufacturer (C-E versus H) and valve site (aortic versus mitral) did not emerge as significant independent risk factors for SVD. Actuarial rates (Cutler-Ederer) expressed as percent free of SVD (+/- SEM) at 10 years (n = number of patients remaining at risk) were 71 +/- 7% and 59 +/- 9% for the C-E (n = 26) and H (n = 17) groups, respectively, for the AVR cohort; for the MVR cohort, these estimates were 60 +/- 10% (n = 12) and 72 +/- 10% (n = 11), respectively, but these differences were not statistically significant (P = NS, Lee-Desu). CONCLUSIONS: After 10 years, there was no statistically significant difference in durability or other valve-related complications between the H and C-E aortic or mitral valves. Based on current information, the choice of a porcine bioprosthesis should be based on factors other than durability, including ease of implantation, hemodynamic performance, and cost.

Clinical trial of cefamandole, cefazolin, and cefuroxime for antibiotic prophylaxis in cardiac operations.

A relatively large number of comparative trials of antibiotic prophylaxis in cardiac surgery have been published, many of which have serious design flaws. Despite the large number of studies, no single antibiotic regimen has emerged as clearly superior in preventing postoperative site infections. To determine if a superior regimen could be identified with a study designed to avoid flaws found in previous studies, we undertook a randomized, double-blind clinical trial of three cephalosporins. From March 1987 to February 1990, 2759 adults underwent median sternotomies: 1641 completed study participation, 203 were enrolled but were dropped from the study for protocol violations, and 815 were excluded. The characteristics of all 2759 patients were recorded with respect to case mix and infection risk factors, and the patients were followed-up by the same nurse throughout hospitalization and for 6 weeks after discharge for the assessment of infection outcome status. Of the 1641 participants, 141 (8.6%) had one or more operative site infections: 46 of 549 (8.4%) cefamandole recipients, 46 of 547 (8.4%) cefazolin recipients, and 49 of 545 (9.0%) cefuroxime recipients (p = 0.92). The sites of infection and the depth of tissue involvement were not significantly different across groups. Because no differences in effectiveness in preventing postoperative site infections were demonstrated in a rigorously designed trial, the costs of the drugs, including the costs of their preparation and delivery, may be the only variables by which to choose among these three antibiotic prophylaxis regimens.

Assessment of myocardial blood flow by real-time infrared imaging.

In order to evaluate the applicability of infrared imaging for the assessment of myocardial perfusion, 10 open-chested dogs were studied by a real-time infrared imaging system. The left anterior descending coronary artery was occluded for 90 min followed by 210 min of reperfusion. During the experiment, myocardial surface temperature was mapped by an infrared imaging system with a thermal resolution power of 0.1 degree C and correlated with regional myocardial blood flow measured using radiolabeled microspheres. Following the experiment, acute myocardial injury was evaluated using triphenyltetrazolium chloride staining. After 90 min of ischemia, there was a significant correlation between myocardial blood flow and myocardial surface temperature (R = 0.694, P less than 0.001). After reperfusion, temperature did not correlate with blood flow, but there was a significant correlation between temperature and ischemic myocardial injury (R = 0.551, P less than 0.05). Temperature changes during acute regional ischemia and reperfusion may be regulated by the changes in myocardial blood flow and myocardial metabolism. Temperature analysis using real-time infrared imaging may be a useful means for the evaluation of myocardial blood flow and myocardial injury during ischemia and reperfusion.

Present expectations in cardiac transplantation.

The clinical introduction of cyclosporine has resulted in increased enthusiasm for cardiac transplantation. Since July, 1983, 61 patients (50 male and 11 female) have undergone orthotopic cardiac transplantation for cardiomyopathy (48 patients), ischemic heart disease (11), or congenital heart disease (2). Mean age was 39 years (range, 1.5 to 57 years). Median hospital stay was 26 days (range, 4 to 60 days). Maintenance immunosuppression consisted primarily of prednisone and cyclosporine; it was modified in 9 patients because of a pre-existing clinical condition. The incidence of rejection was 0.44 episode/patient-month within 3 months of cardiac transplantation and 0.10 episode/patient-month subsequently. The incidence of infection was 0.05 episode/patient-month. Major side effects of cyclosporine included renal dysfunction (63%) and hypertension (61%). No recipient required dialysis for renal dysfunction. Ten patients died (rejection, 4; infection, 3; carcinoma, 1; lymphoma, 1; and pulmonary hemorrhage, 1); actuarial survival at 1 and 2 years was 84 +/- 6% and 76 +/- 8%, respectively. Patient follow-up (cumulative, 719 patient-months) revealed that 96% of recipients were rehabilitated and 50% had returned to work. With increasing understanding of cyclosporine immunosuppression, recipients can continue to look forward to an extended life with nearly complete rehabilitation.

Cardiac transplantation in perspective for the future. Survival, complications, rehabilitation, and cost.

Two hundred twenty-seven cardiac transplant procedures have been performed in 206 patients from January, 1968, to April, 1981. Postoperative survival rates, calculated by the actuarial method for program years 1968 to 1973 (66 patients), are 44%, 33%, 27%, 21%, and 18% at 1, 2, 3, 4, and 5 years after transplantation, respectively. Postoperative survival rates for program years 1974 to 1981 (140 patients) are 63%, 55%, 51, 44%, and 39% at 1, 2, 3, 4, and 5 years after transplantation, respectively. This increase results primarily from improvement in survival achieved in the first 3 postoperative months (59% +/- 7%, 1968 to 1973, versus 80% +/- 40%, 1974 to 1980), reflecting improved patient management. Infection remains the primary cause of death following transplantation (76/131 patients, 58%), followed by acute rejection (24/181, 18.3%), graft arteriosclerosis (14/131, 10.7%), and malignancy (6/131, 4.6%). The development of graft arteriosclerosis has been examined in 85 one-year survivors studied by annual coronary arteriograms. Coronary lesions of varying severity have developed in 21 patients. HLA-A2 incompatibility was associated with a higher incidence of graft arteriosclerosis than was apparent for all other A locus incompatibilities (p less than 0.0003). Lymphoma has been shown to be associated with younger recipient age, a primary disease diagnosis of idiopathic cardiomyopathy, and retransplantation. One hundred six patients have survived at least 1 year after transplantation; 97% were in NYHA Class 1 at that time interval and 82% returned to employment or activity of choice. The longest survival time is new 11 years, 3 months. Cardiac transplantation can be considered "reasonable and therapeutic treatment to extend life" in selected individuals.

Therapeutic efficacy of intraaortic balloon pump counterpulsation. Analysis with concurrent "control" subjects.

During a 7-year period, intraaortic balloon pumping (IABP) was attempted in 319 cardiac surgical patients. The indications for IABP were stringent and consisted of unsuccessful discontinuation of cardiopulmonary bypass (39%), anticipated failure (40%) to wean from cardiopulmonary bypass, postoperative low cardiac output, or intractable ventricular tachyarrhythmias (15%). IABP support was successfully instituted in 280 patients and was unsuccessful in 39 patients ("controls"). These two groups were comparable except for an older mean age and a higher ejection fraction in controls. Operative mortality rates were 45% and 62% for IABP and control groups, respectively (p = 0.077). This difference was most evident in coronary artery bypass patients, in whom the decision to institute IABP counterpulsation was made intraoperatively before attempted discontinuation of cardiopulmonary bypass. Two years postoperatively the actuarial survival rate was 45 +/- 3% for the IABP group and 23 +/- 9% for the control group (p = 0.006). After exclusion of operative deaths, however, these survival rates were 81 +/- 3% and 60 +/- 20%, respectively (p = NS). The average hospital charge incurred by IABP patients was threefold greater than that of uncomplicated cardiac surgical procedures. We conclude that IABP counterpulsation is therapeutic for some cardiac surgical patients, but its benefits cannot be defined easily. The long-term survival rates for patients with advanced disease requiring IABP support perioperatively are poor and warrant continued development of more effective methods of mechanical circulatory assistance and heart replacement.