Romano G

Role of Sildenafil in Acute Posttransplant Right Ventricular Dysfunction: Successful Experience in 13 Consecutive Patients

BACKGROUND Superimposed acute right ventricular dysfunction in the setting of preexisting pulmonary hypertension is a nearly fatal complication after heart transplantation. The optimal treatment modality remains a matter of debate. Recently, sildenafil citrate, a nonselective pulmonary vasodilator, has gained popularity in the treatment of pulmonary hypertension in transplant candidates. METHODS Herein we have presented a series of 13 patients in whom sildenafil was used to treat right ventricular dysfunction and pulmonary hypertension as detected by transesophageal echocardiography and Swan-Ganz right heart catheterization after heart transplant. Their characteristics were mean age 49+/-11.4 years; 38.4% with previous cardiac procedures, 30.8% status I, basal pulmonary vascular resistance index 10.4+/-4.6 WoodU, mean transpulmonary gradient 18.7+/-5.4 mmHg. In addition to conventional inodilator support, we administered 1 to 3 mg per kilogram of sildenafil. Complete hemodynamic measurements were obtained before and after the institution of the therapy and at 1-month follow-up. RESULTS Within the first 72 hours, acute right ventricular dysfunction resolved in all cases without untoward side effects or significant systemic impact. Sildenafil significantly decreased the transpulmonary gradient and pulmonary vascular resistance index relative to baseline values; 5.6+/-1.82 versus 10.4+/-4.6 WU, (P< .05), 13.5+/-3.4 mm Hg versus 18.7+/-5.4 mm Hg (P< .05), respectively. Improved indices of right ventricular function were observed on echocardiographic monitoring. After 1 month, sildenafil treatment was discontinued. CONCLUSION Management of acute right ventricular dysfunction in heart transplant recipients with pulmonary hypertension using sildenafil proved safe and effective.

Human leukocyte antigen-DR mismatch is associated with increased in-hospital mortality after a heart transplant

OBJECTIVES Although previous studies have investigated the effect of human leukocyte antigen matching on long-term outcomes after heart transplants, its role in the prognosis after a heart transplant remains unclear, particularly with respect to short-term survival. MATERIALS AND METHODS We evaluated the human leukocyte antigen mismatch on in-hospital mortality of 158 consecutive patients who had undergone a heart transplant between 2000 and 2008. Human leukocyte antigens-A, -B, and -DR were determined by means of serologic and molecular techniques. Univariate analysis and a multiple logistic regression models evaluated the effect of human leukocyte antigen variants on mortality, independent of clinical variables. RESULTS In-hospital mortality was 11.4%. Higher prevalence of acute kidney injury (50.0% vs 12.9%), higher levels of troponins 48 hours after transplant (15.6 ± 12.0 ng/mL vs 9.7 ± 9.4 ng/mL), prolonged ischemia (188.2 ± 32.5 min vs 162.6 ± 40.7 min), higher frequency of reoperation (61.1% vs 17.9%), and higher human leukocyte antigen-DR mismatch (1.61 ± 0.5 vs 1.30 ± 0.6) were found in patients who died. By logistic regression analysis, humanleukocyte antigen-DR mismatch is associated with in-hospital mortality (OR=5.159, 95% CI=1.348-19.754), independent of the effect of covariates such as recipient age, mismatch sex, mismatch human leukocyte antigen-A, human leukocyte antigen-B, acute kidney injury, reoperation, ischemia duration, and levels of troponins. CONCLUSIONS Human leukocyte antigen-DR mismatch is associated with in-hospital mortality in heart transplant.

Management of immunosuppression and antiviral treatment before and after heart transplant for HIV-associated dilated cardiomyopathy

Infection with HIV may lead to the development of cardiomyopathy as improved antiretroviral regimens continue to prolong patient life. However, advanced therapeutic options, such as heart transplant, have until recently been precluded to HIV-positive persons. A favorable long-term outcome has been obtained after kidney or liver transplant in HIV-positive recipients fulfilling strict virological and clinical criteria. We recently reported the first heart transplant in a HIV-infected patient carried out in our center. In this article, we detail the major challenges we faced with the management of antiretroviral and immunosuppressive treatments over the first 3 years post-transplant. The patient had developed dilated cardiomyopathy while on antiretroviral treatment with zidovudine, lamivudine and efavirenz. He was in WHO Stage 1 of HIV infection and had normal CD4+ count and persistently undetectable HIV-RNA. In spite of cardiac resynchronization therapy and maximal drug therapy, the patient progressed to end stage heart failure, requiring heart transplant. He was placed on a standard immune suppressive protocol including cyclosporine A and everolimus. Despite its potential pharmacokinetic interaction with efavirenz, everolimus was chosen to reduce the long-term risk of opportunistic neoplasia. Plasma levels of both drugs were monitored and remained within the target range, although high doses of everolimus were needed. There were no infectious, neoplastic or metabolic complications during a 3-year follow-up. In summary, our experience supports previous data showing that cardiac transplantation should not be denied to carefully selected HIV patients. Careful management of drug interactions and adverse events is mandatory.