Prognosis after heart transplant in patients with pulmonary hypertension secondary to cardiopathy.

INTRODUCTION: Pulmonary hypertension (PHT) is associated with greater posttransplant mortality. In the last few years, many vasodilator drugs have been developed and some patients have therefore been transplanted. However, conflicting data exist regarding the impact of reversible PHT on posttransplant outcomes. The aim of this study was to determine the evolution of our transplanted patients with reactive PHT and the causes of right cardiac insufficiency and perioperative mortality. MATERIAL AND METHODS: We performed a retrospective analysis of 39 consecutive heart transplant recipients from January 2005 to December 2006. We analyzed significant pretransplant PHT, the percentage of emergency transplants, surgical technique, as well as ischemia and extracorporeal circulation times. RESULTS: Before transplantation, significant PHT was present in 12 patients (30.8%), all of whom had a positive acute vasoreactivity test or response to oral treatment with pulmonary vasodilators. A nonsignificant tendency to increased posttransplant mortality was observed among patients with pretransplant PHT. We observed a significant increase in mortality in patients with prolonged operative times, over the third percentile, odds ratio (OR) for ECC of 21% (P = .001) and OR for prolonged ischemia time of 9.5% (P = .022). However, mortality did not increase significantly in cases of emergent transplantation (P = .08) or in the use of the Shumway bicaval surgical technique (P = .9). CONCLUSIONS: There seemed to be a slight tendency to increased mortality among patients with reversible HTP, suggesting that high-risk patients need closer monitoring but are not absolutely contraindicated for transplantation.

Preliminary experience with conversion from calcineurin inhibitors to everolimus in cardiac transplantation maintenance therapy.

INTRODUCTION: Everolimus has been prescribed both for initial and maintenance therapy after cardiac transplantation. Herein, we present our initial experience with everolimus as maintenance therapy after cardiac transplantation. METHODS: We retrospectively included all of our patients in whom therapy was changed from calcineurin inhibitors to everolimus between September 2006 and October 2007. We analyzed their baseline clinical characteristics, indications for conversion to everolimus therapy, and beneficial vs adverse effects of the maneuver. RESULTS: In 16 heart transplant recipients, therapy was changed to everolimus because of allograft vasculopathy (n = 8), renal failure (n = 4), or sirolimus toxicity (n = 4). Treatment with everolimus was initiated at a mean (SD) of 79.8 (52.7) months (range, 10-163 mo) after transplantation. The initial dose was 1.4 (0.2) mg (range, 1.0-1.5 mg), and the maintenance dose was 1 (0.31) mg (range, 0.5-1.5 mg). Follow-up was 7.28 (3.22) months (range, 0.5-13 mo). Observed side effects included hypertriglyceridemia, hypertension, and edema. Only 1 of 4 patients included because of sirolimus intolerance did not tolerate everolimus; renal dysfunction did not worsen in any of these 4 patients. No allograft vasculopathy was observed. CONCLUSIONS: Renal function seem to stabilize after conversion to everolimus therapy in patients with previous progressive dysfunction. The safety profile was proved in all patients, although conclusions cannot be established about the evolution of allograft vasculopathy.

Combination therapy with sildenafil and bosentan reverts severe pulmonary hypertension and allows heart transplantation: case report.

INTRODUCTION: Severe pulmonary hypertension with no response to vasodilators on an acute hemodynamic study is a contraindication to cardiac transplantation. The development of oral pulmonary vasodilators improves the prognosis in these patients. We present the case of a patient whose admission to the waiting list for cardiac transplantation was possible after 6 months of combination therapy with Sildenafil and Bosentan. CASE REPORT: The patient was a 50-year-old man with severe dilated alcohol-induced cardiomyopathy. A pretransplantation study, including a right hemodynamic analysis, revealed irreversible pulmonary hypertension, with 59 mm Hg mean pulmonary artery pressure and 6.4 Wood IU pulmonary vascular resistance, with no response to acute vasodilators with nitric oxide or prostacyclin. Initially, heart transplantation was not possible and the patient started treatment with oral Sildenafil. After 6 months there was no improvement in echocardiographic or hemodynamic parameters, and combination therapy with Bosentan was started. With the combination therapy, the patient progressively improved clinically and hemodynamically, the pressures becoming normal at the sixth month, at which time he was included on the waiting list for a heart transplantation. Eight months later he received a graft with a good posttransplantation course, no right ventricular failure in the acute phase, and absence of pulmonary hypertension on echocardiogrphic and invasive studies. CONCLUSION: Combinations of an oral pulmonary vasodilator with diverse action mechanisms may represent an alternative for patients with irreversible pulmonary hypertension who do not respond to monotherapy.

Is it possible to reduce the number of endomyocardial biopsies with new immunosuppressive drugs?

INTRODUCTION: Using previous immunosuppressive regimens the considerable number of rejections of heart transplantations required routine surveillance myocardial biopsies, particularly during the early months. More effective immunosuppressive regimens would probably allow routine biopsies to be reduced. Our objectives were to assess the incidence of and the time to rejection with a new immunosuppressive protocol, considering the possibility of reducing the number of routine biopsies. MATERIALS AND METHODS: We undertook a retrospective study of patients who had undergone heart transplantation from January 2002 to August 2005 and who received induction therapy with Daclizumab (two doses) and maintenance therapy with tacrolimus + mycophenolate + low doses of steroids. RESULTS: Among 42 patients, 13 (31%) showed myocardial rejection in the first 3 months. All episodes were grade 3A and none had hemodynamic consequences. After 3 months, three patients (7.1%) experienced 3A rejection and 1 (2.4%), grade 4 acute rejection after ceasing medical treatment. Each episode of rejection was predictable, either owing to reduction in immunosuppression therapy or to a previous history of rejection. CONCLUSIONS: The majority of rejection episodes occur in the first 3 months posttransplantation. After that time, the incidence of rejection is less and clinically predictable. Therefore, surveillance biopsies should be limited to the first 3 months, and performed later either in symptomatic patients (with a history of previous rejection) or in those whose immunosuppressive therapy needs to be reduced.

Sirolimus experience in heart transplantation.

INTRODUCTION: Sirolimus is a potent, nonnephrotoxic immunosuppressant with antiproliferative activity in nonimmune cells. Recent data support the conversion in late renal failure secondary to calcineurin inhibitors (CNIs), with limited experience in de novo regimens in patients with predictive factors of postoperative renal impairment. OBJECTIVE: We evaluated our experience of sirolimus-based immunosuppression administered to 25 heart transplant recipients. METHODS: A retrospective analysis of 25 heart transplant recipients who received sirolimus included 17 conversions due to late CNI-related chronic renal dysfunction, six patients with a de novo regimen, and two patients who developed posttransplant pulmonary neoplasms. The conversion from CNI to sirolimus was started with 2 mg, with an average time after transplantation of 78 +/- 43 months and a mean baseline serum creatinine level of 2.1 +/- 0.45 mg/dL. The mean clinical follow-up was 17 +/- 9 months postconversion, and included echocardiography and laboratory studies. In the de novo group successive endomyocardial biopsies were performed during the first semester. RESULTS: Serum creatinine fell from 2.1 +/- 0.45 mg/dL to 1.8 +/- 0.51 mg/dL (P = .012). Mean sirolimus levels were 15 +/- 9 ng/mL (doses 2.2 +/- 0.4 mg). This improvement continued until 3 months (creatinine 1.5 +/- 0.35 P < .01)/sirolimus levels 11.7 +/- 5 ng/mL [1.9 +/- 0.7 mg]), with maintenance at 6 months (1.58 +/- 0.3 mg/dL/14 +/- 4 ng/mL [1.85 +/- 0.7 mg]) and 1-year postconversion (1.53 +/- 0.39 mg/dL; P = .019/10.7 +/- 2.5 ng/mL [1.5 +/- 0.7 mg]). De novo, after a mean follow-up of 13 months (range 3 to 35), sirolimus appeared to increase the incidence of a moderate histological grade of rejection without hemodynamic compromise. Side effects were common (63%), including peripheral edema, skin eruptions, and pericardial effusion. Only one patient discontinued treatment, due to intestinal intolerance. Four patients died during follow-up: two because of lung neoplasms and two because of progressive graft vessel disease. CONCLUSION: Sirolimus improved late CNI-related chronic renal dysfunction. Kidney function was preserved using a de novo CNI-free immunosuppressive regimen for recent cardiac transplant recipients.