Heterotopic heart transplantation: the United States experience.

INTRODUCTION: More than 3 decades have passed since the first heterotopic heart transplantation (HHT) was reported. Nowadays, this surgical technique is used rarely, and only in patients who do not qualify for standard orthotopic heart transplantation (OHT). Current indications mainly comprise refractory pulmonary hypertension and a donor-recipient size mismatch (>20%). The objective of this study was to analyze the United States experience with HHT. PATIENTS AND METHODS: The United Network for Organ Sharing (UNOS) database between 1987 and 2007 was analyzed. Patients who underwent heart transplantation were enrolled in this study. Patients with missing transplant dates or history of retransplantation were excluded. RESULTS: A total of 41,379 patients underwent OHT and 178 HHT; 32,361 and 111 patients, respectively, were enrolled. Overall 1-, 5-, and 10-year survival was significantly (P < .001) better in OHT (87.7%, 74.4%, 54.4%) than HHT patients (83.8%, 59%, 35.1%). Survival in patients with transpulmonary gradients (TPG) >15 mmHg was 86.6 %, 73.3%, and 57.4% in the OHT and 93.8%, 64.8%, and 48.6% in the HHT group (P = .35). Pretransplant criteria (HHT versus OHT) with statistically significant differences (P < .05) were as follows (mean + SD): recipient weight, 78.9 + 19.9 versus 74.1 + 23.4 kg; recipient height, 174.9 + 13.9 versus 168 + 25.1 cm; and TPG 12.1 + 7.2 versus 9.6 + 6.3 mmHg. CONCLUSIONS: The results show that HHT remains a feasible option in a highly selected patient population, with overall good results.

Heterotopic heart transplantation: an expanding role in the twenty-first century?

BACKGROUND: Heterotopic heart transplantation was first performed in humans in 1974, the main advantage being the continuing function of the patient's native heart, in the event of life-threatening acute rejection. The effect of cyclosporine on acute rejection saw the heterotopic transplantation technique wane. Our unit revisited heterotopic transplantation in response to a growing number of waiting list patients with high pulmonary artery pressures. We also anticipated an increased cardiac allograft utilization, and improvement of our waiting list times. METHODS: We retrospectively analyzed 151 patients undergoing heart transplantation by our unit between August 1997 and September 2003. Twenty received allografts in the heterotopic position. This cohort was compared with the 131 contemporary orthotopic heart transplant recipients with respect to their outcomes. RESULTS: The indication for transplantation was ischemic cardiomyopathy in 14 (70%) of the heterotopic cohort and 47 (36%) of the orthotopic cohort (p = 0.004), and dilated cardiomyopathy in 3 (15%) and 48 (37%) in the heterotopic and orthotopic groups, respectively (p = 0.06). Heterotopic recipients were significantly older than orthotopic recipients, and they had higher pulmonary artery pressures. The heterotopic donors were also older and the ischemic times were longer. A subgroup analysis was made among those patients who had high pulmonary artery pressures as these groups were better matched. Major morbidity in the heterotopic heart transplantation group consisted of reversible allograft dysfunction in 4 patients, renal dysfunction requiring hemofiltration in 3 patients, profound myopathy in 4 patients, and cerebrovascular events in 2 patients. There were two early deaths in the heterotopic transplant group and eight in the orthotopic group (p = 0.87). Kaplan-Meier survival analysis of survival was performed. CONCLUSIONS: Heterotopic heart transplantation is a viable transplant option for selected high-risk heart transplant recipients in spite of somewhat poorer outcomes.

The histology of subcutaneously implanted donor bronchial rings correlates with rejection scores of lung allografts in a primate lung transplant model.

BACKGROUND: The diagnosis of acute rejection in lung transplantation generally relies on transbronchial biopsies. This invasive procedure may be associated with bronchial bleeding or pneumothorax and may not be feasible in patients with severely compromised lung function. The hypothesis of the current study was that histopathological findings of donor bronchial segments implanted into the subcutaneous tissue of lung allograft recipients would predict lung tissue rejection scores, thus providing the clinician with an alternate source of information. METHODS: Unilateral left lung transplantation was performed in 34 cynomolgus monkeys as part of a drug efficacy study. After completion of the transplant procedure, 4 bronchial ring segments of the explanted recipient left lung and 4 bronchial ring segments of the non-transplanted right donor lung were implanted subcutaneously in the abdominal region. Lung allograft rejection was evaluated by open lung biopsies of the allograft performed on postoperative (PO) Day 14 and during sacrifice on PO Day 28. At the time of each biopsy, 2 donor and 2 recipient subcutaneous bronchial rings were explanted. Histologic evaluation of the lung tissue samples was performed according to the working formulation of the International Society for Heart and Lung Transplantation. Bronchial rings were independently evaluated by assessing the degree of airway narrowing; percentage of intact epithelial coverage as well as its specific histology (respiratory ciliated, flattened cuboidal, squamous); presence of lymphocytes, macrophages or spindle cells; and presence of peribronchial inflammation, luminal fibrosis, lymphocytic bronchitis or luminal mucous. Statistical analysis was performed by logistic regression. RESULTS: In the recipient bronchial rings, there was no evidence of airway narrowing. There was 98% epithelial coverage, 71% that were respiratory ciliated cells, and there was no inflammation. Donor bronchial rings showed no airway narrowing for monkeys with grade A0 to A2 rejection in tissue biopsies and a maximum narrowing (41.2%) with A4 rejection. Epithelial cell coverage was approximately 100% with grade A0-A2 and 44+/-11% with A4 rejection. Lymphocytic bronchitis was most severe in A4 rejection and minimal in A0 to A2 rejection. By logistic regression analysis, independent predictors of a likelihood of rejection were the degree of airway obliteration, the percentage of epithelial cell coverage, the degree of lymphocytic bronchitis and the product of respiratory and flattened cuboidal cell coverage. CONCLUSIONS: The current data show that histologic alterations of subcutaneously implanted donor bronchial rings correlate with lung tissue biopsy scores based on the ISHLT working formulation. Because subcutaneous bronchial rings can be explanted under local anesthesia, they may provide useful information for the diagnosis of acute allograft rejection in patients with impaired lung function, patients that obtaining lung tissue samples may not be feasible.

Variations in cardiac transplantation: comparisons between the United Kingdom and the United States.

BACKGROUND: International practice variations have been documented in various health care specialties. This study compares cardiac transplantation in the UK with practice in the US. METHODS: UK data were from an ongoing multi-center prospective study, the UK Cardiothoracic Transplant Audit. The UK population comprised 620 listings and 463 transplants. US data were obtained from UNOS and comprised 3946 listings and 4704 transplants. RESULTS: There was a mean of 14 transplants per center per year in the US compared with 34 in the UK. Notable differences in practice include rarity of listing in the UK of patients > 65 years (0.2% vs 4.1% in US) and patients with previous transplants (UK 0.9%, US 3.2%). Patients listed in the US were more likely to be on ventricular assist devices (odds ratio 8.0, 95% CI 3.0-21.7) or inotropes (odds ratio 4.9, 95% CI 3.7-6.4). Living donor (domino) transplants, although comprising 7% of transplants in the UK, are virtually non-existent in the US (1 domino in 4704 transplants). Heterotopic transplants were more common in the UK (4.4% vs 0.5%). Indications for transplant were similar (except retransplantation). The donor age was > 35 years in 43% of UK donors vs 33% of US donors. CONCLUSION: This study reveals substantial practice differences between the UK and US. Further studies are required to examine the reasons for these practice differences, the influence on transplant outcome, and their ethical and economic implications.

Symposium Trasplante de órganos en México: Trasplante de hígado: estado actual y experiencia en el Instituto Nacional de la Nutrición "Dr. Salvador Zubirán" / Liver transplantation

Objetivo. Revisar y actualizar algunos aspectos del trasplante de hígado e informar la experiencia con el mismo en el Instituto Nacional de la Nutrición "Dr. Salvador Zubirán" (INNSZ). Sede. Departamento de Trasplantes del INNSZ (México, D.F.) Diseño. Estudio retrospectivo, observacional y longitudinal. Revisión de la literatura. Antecedentes. Existen tres tipos de trasplante: A) heterotópico o auxiliar, B) ortotópico y C) trasplante de hepatocitos. Las indicaciones más frecuentes para trasplante en el adulto son: hepatitis crónica autoinmune, enfermedad hepática colestásica y cirrosis postnacrótica y por alcohol. En niños: atresia de vías biliares y los errores congénitos del metabolismo. La evaluación pre-operatoria del receptor incluye: estudios generales, hematológicos, hepáticos, renales, gastrointestinales, cardiovasculares, pulmonares, nutricionales e inmunológicos. Actualmente se obtiene una preservación adecuada del injerto hepático "ex vivo" hasta por 24 hs empleando la solución denominada Universidad de Wisconsin. Como terapia inmunosupresora puede utilizarse: ciclosporina, prednisona, azathioprina, suero antilinnfocitos y FK506. Las complicaciones post-operatorias incluyen: falla primaria del injerto, problemas técnicos, rechazo, complicaciones renales, respiratorias e infecciones. Resultados. En el INNSZ hemos operado 10 pacientes, 4 varones y 6 mujeres, con edades de 15 a 56 años (promedio de 35.5); en 8 de ellos la idicación fue cirrosis hepática (post-necrótica en 4, post alcohólica en 2 y biliar primaria en otros 2), en uno hepatitis crónica autoinmune y en otro hipercolesterolemia familiar tipo II. El tiempo de espera del receptor varió entre 3 y 16 meses (promedio 8.9), en 8 empleamos la solución tipo Universidad de Wisconsin y en dos la Euro-Collins. En los 10 sujetos el trasplate fue de tipo ortotópico, con tiempo de isquemia de injerto de 4 a 18 hr (promedio de 12.5 hr) y un tiempo operatorio de 7 a 15 hr (promedio de 11.2 hr). Todas las reconstrucciones venosas fueron porta y cava término-terminal; las arteriales, arteria hepática término terminal en 9 y biliares, todas colédoco-colédoco término-terminal. El fenómeno de rechazo agudo se presentó entre 8 días y 3 años en 7 pacientes y en todos se resolvió adecuadamente. Actualmente tres pacientes tienen sobrevivencia de 22 a 60 meses. Los fallecidos tuveron sobrevivencia de 1 día a 12 meses.

Embarazo combinado o heterotópico

El embarazo heterotópico es una entidad rara caracterizada por embarazo ectópico asociado a embarazo intrauterino. Su mayor incidencia se origina en la práctica creciente de la fertilización asistida. Aunque sobre este procedimiento se ejerce un adecuado seguimiento, ello no garantiza un diagnóstico fácil y oportuno

Registry report: International Society for Heart and Lung Transplantation.

Orthotopic heart transplantation continues to be a highly successful therapy for end-stage cardiac disease. Recent advances have extended the benefits of this procedure to neonatal patients. The number of patients undergoing single- and double-lung transplantation increases steadily and the indications for transplantation are being expanded. Evaluation of the early results indicates that patients undergoing lung transplantation for vascular disease do not fare as well as those undergoing transplantation for parenchymal disease. Presently, the results of retransplantation are far inferior to primary transplantation and require ongoing evaluation.

The center effect in heart transplantation.

Transplantation outcomes vary across centers, prompting interest in the notion of a "center effect." The components of this effect are not well understood, although experience is often regarded as the primary factor. Most studies, however, have failed to confirm an association between transplant program activity level and outcome. While there have been several published reports on the kidney transplant center effect, only 1 such (unpublished) report exists concerning heart transplantation. Data for this analysis were obtained from several sources that include: the Registry of the International Society for Heart and Lung Transplantation; the Medicare Provider Analysis and Review data maintained by the Health Care Financing Administration (HCFA), various hospital-specific data compiled by the American Hospital Association (AHA); and finally, 91% of all eligible heart programs participated in a special purpose survey intended to obtain critical data on transplant center characteristics. These 4 data sources were combined into a single data base representing 1,602 patients at 114 centers. The data were then analyzed using a discrete piecewise exponential hazards model. This is a nonparametric approach toward the modeling of risk, wherein no assumption is made about the shape of the survival curve. Risk was assessed up to 2 years posttransplant. Overall 1-year patient survival was 82.4%. In the multivariate models, neither recipient nor donor sociodemographic characteristics were associated with patient survival. Clinical characteristics were the most critical predictors of outcome, including use of an artificial device and retransplantation, both of which had a strong adverse effect. This was predictable based upon univariate analyses alone. The results of this analysis suggest that experience is positively related to heart transplant patient survival; however, due to sample size and other considerations, the experience effect did not achieve statistical significance. Nevertheless, while outcomes did vary by center, the extent of variation was not nearly as great as some commentators have argued. This suggests that heart transplantation is a technology that can be acceptably applied in diverse settings with excellent outcomes.

Cardiac transplantation at the University of Pittsburgh: 1980 to 1991.

When examining survival rates following cardiac transplantation, it is important to examine the risk factors for both early (30-day) and late (greater than 30-day) survival as they may well be different. Factors affecting early survival appear related more to the preoperative condition of the patient (including degree of pulmonary hypertension) as well as advances that have been made in postoperative care. It is not immediately obvious why gender has such a profound effect on early survival and why primary graft failure rates appear higher in this group. Donor organ factors did not appear to relate to this difference. On the other hand, late survival appears to be influenced mainly by immunologic factors such as panel reactive antibody level and immunosuppressive protocol. A less dramatic effect of transpulmonary gradient appears to have a lasting effect on recipients even when they survive the initial 30-day period. Thus, pulmonary hypertension may have prolonged effects on the cardiac allograft which as yet we do not understand completely. The majority of late mortality is still due to graft atherosclerosis, infection, and acute cellular rejection, the latter 2 occurring most frequently within the first year after transplantation whereas death from graft atherosclerosis becomes most prominent beyond 5 years. Despite persistent improvements in 30-day survival, late survival following cardiac transplantation will only improve with the advent of better tissue matching and improved immunosuppression. The results with FK506, for example, are promising.