Tatiana A.D. Theodoropoulos

Switch from calcineurin inhibitors to sirolimus- induced renal recovery in heart transplant recipients in the midterm follow-up

Background. Calcineurin inhibitor (CI)-based immunosuppression has prolonged the survival of heart transplant recipients. However, CI-induced renal injury remains as a major problem in these patients. Sirolimus is an immunosuppressant with no significant impact on renal function. A limited number of recent papers have showed that the switch from CI to sirolimus improved renal function in late follow-up of heart transplant patients with CI-related nephrotoxicity. Methods. Ten heart transplant recipients with CI-induced nephrotoxicity (creatinine 3.9±1.8 mg/dl) at a median of 701 (465 to 1325) days posttransplant had CI switched to sirolimus (target though levels 10 to 14 ng/ml) while mycophenolate mofetil (MMF, 3g/day) was maintained and adjusted according to white blood cell count. Results. This maneuver caused a marked decrease in serum creatinine (P<0.00001) at 30 (1.2±0.4 mg/dl), 90 (1.3±0.4 mg/dl) and 180 (1.3±0.4 mg/dl) days postconversion and a significant decrease in serum potassium levels (5.1±0.5 at baseline vs. 3.9±0.3 at 180 days, P<0.00005). After the drugs switch no changes in hemoglobin levels, white blood cell count, platelets count, blood glucose and glutamic oxaloacetic transaminase plasma levels were observed. Total cholesterol increased from 242±28 to 290±117 mg/dl (P>0.05) after 90 days and decreased to 216±58 mg/dl at day 180 (P>0.05) after statins dose adjustment. Rejection and infection rates were not modified by sirolimus. Conclusions. Conversion to a sirolimus-based immunosuppression regimen associated with MMF allowed striking renal function recovery in heart transplant recipients with calcineurin inhibitor-induced renal impairment at midterm follow-up.

Treatment of chronic systolic heart failure secondary to Chagas heart disease in the current era of heart failure therapy

The treatment of chronic heart failure secondary to Chagas disease has been based on extrapolation of data achieved in the treatment of non-Chagas disease heart failure. Because beta-blockers decrease the incidence of sudden cardiac death in non-Chagas disease heart failure and sudden cardiac death occurs preferentially in patients with mild Chagas disease heart failure, beta-blockers may be administered first to class I/II patients with Chagas disease heart failure. In advanced Chagas disease heart failure, angiotensin-converting enzyme inhibitor and diuretics may be given at first to compensate for congestive symptoms. After clinical status improvement, beta-blockers should be given at targeted doses, if necessary reducing angiotensin-converting enzyme inhibitor doses. Primary and secondary prevention of sudden cardiac death may be accomplished with implantable cardioverter defibrillators because of the high recurrence of life-threatening arrhythmias despite amiodarone administration. In refractory heart failure, heart transplantation is the treatment of choice.