A. Salvador

Tolerance Profile of the Proliferation Signal Inhibitors Everolimus and Sirolimus in Heart Transplantation

INTRODUCTION The side effects of proliferation signal inhibitors (PSIs) have been characterized as a class. However, it would be convenient to assess them according to the molecule. OBJECTIVE To assess prospectively the tolerance of PSIs among heart transplant (HT) patients. PATIENTS AND METHODS We studied 56 HT patients who sequentially received PSIs to either withdraw (77%) or reduce the dosage of a calcineurin inhibitor; 42 received everolimus (EVE) and 14 sirolimus (SRL). We analyzed the demographic variables, side effects, and need to withdraw the drug during a median follow-up period of 365 days. RESULTS No differences between groups were observed upon analysis of the clinical and demographic variables when the treatment was changed owing to renal dysfunction (67%) or tumor (32%). No difference between groups was observed over the follow-up period (P = .28). Infection was the most common side effect, 28.6%: EVE, 14.3% versus SRL, 71.4% (P < .0001). Edema occurred in 26.8% of patients: EVE, 14.3% versus SRL, 64.3% (P = .001); diarrhea in 5.4% of patients: EVE, 2.4% versus SRL, 14.3% (P = .15). Treatment was withdrawn in 23.2% of the patients due to intolerance: EVE, 11.9% versus SRL, 57.1% (P < .0001). EVE showed significantly better survival without edema or infections or used for drug withdrawal upon Kaplan-Meier analysis, (P = .01; P = .0005; P = .0097). Only SRL use was shown to be an independent predictor of side effects. CONCLUSION Edema and infections are the main problems caused by PSIs. EVE may display a better tolerance profile than SRL.

Randomized Prospective Study of the Evolution of Renal Function Depending on the Anticalcineurin Used

BACKGROUND Renal failure is one of the primary medium- to long-term morbidities in heart transplant (HT) recipients. To a great extent, this renal deterioration is associated with calcineurin inhibitors, primarily cyclosporine A (CsA). It has been suggested that tacrolimus provides better renal function in these patients. We assessed the medium-term evolution of renal function depending on the calcineurin inhibitor used after HT. PATIENTS AND METHOD We assessed 40 consecutive HT recipients over one year. Patients were randomized to receive CsA (n = 20) or tacrolimus (n = 20) in combination with mycophenolate mofetil (1 g/12 h) and deflazacort in decreasing dosages. We analyzed demographic variables before HT, creatinine values before and six months after HT and incidence of acute rejection. RESULTS No demographic, clinical, or analytical differences were observed were between the two groups before HT. Repeated measures analysis of variance of creatinine values showed no significant differences between the two groups (P = .98). Furthermore, no differences were observed in either the incidence of rejection (P = .02) or rejection-free survival (P = .14). CONCLUSION There seems to be no difference in efficacy profile and renal tolerability between CsA and tacrolimus therapy during the first months after HT.

Effect of Clinical Trials on Survival After Heart Transplantation

UNLABELLED The application of clinical trials (CTs) to daily practice is based on the assumption that the patients included in these trials are similar to those seen on a daily basis. We performed a retrospective study to evaluate patient survival depending on whether they were included in a CT. We studied 217 patients who underwent heart transplantation (HT) between January 2000 and September 2006. We excluded patients who received combination transplants, those who underwent repeat HT, and pediatric patients who underwent HT. In total, 54 patients were included in a CT and 163 were not (NCT). The statistical tests included the t test, the chi(2) test and the Kaplan-Meier method. RESULTS Patients in the NCT group were in worse condition at HT, with a greater percentage of inotropic treatments pre-HT (36% vs 17%; P = .005), emergency transplants procedures (30% vs 13%; P = .01), and worse functional status pre-HT (P = .03). The NCT group exhibited lower survival (80.37% vs 87.04%; P = 0.13, log-rank test). There were no significant differences in the other analyzed variables. CONCLUSIONS Patients included in CTs tend to have better long-term survival rates, for several reasons: patients in the CT group were more stable at HT (selection bias), and the close follow-up of patients in CTs makes it more likely that any complication will be detected and treated early (follow-up bias).

Study of the adrenergic heart innervation with iodine 123-metaiodobenzylguanidine in heart failure before transplantation.

BACKGROUND The incidence and prevalence of heart failure (HF) are constantly increasing. Heart failure depends on pump failure, inflammatory tracers, and the neurohormonal system. At advanced stages, the only treatment is heart transplantation (HT). We studied myocardial innervation in patients before HT. MATERIALS AND METHODS The study included 15 patients (11 men and 4 women; age range, 18-69 years) with a diagnosis of New York Heart Association class III-IV or IV HF. Planar thoracic images were obtained, at 15 minutes and 4 hours after injection of 10 mCi of iodine 123-metaiodobenzylguanidine ((123)I-MIBG). Adrenal activity was measured quantitatively using a heart-to-mediastinum count ratio and a myocardial washout rate. Pathologic results were considered if heart-to-mediastinum count ratio was less than 1.8 and washout rate was more than 35%. RESULTS The qualitative analysis revealed decreased (123)I-MIBG myocardial uptake in all patients. Using the quantitative scale, patients were classified into four groups, as follows: group 1, physiologic innervation, no patients; group 2, mild myocardial adrenergic involvement, one patient (6.7%); group 3, moderate myocardial adrenergic involvement, five patients (33.3%); and group 4, severe myocardial adrenergic involvement, 9 patients (60%). The washout rate was pathologic in 11 of the 15 patients (73.3%). CONCLUSIONS Scintigraphy using (123)I-MIBG is a useful method to evaluate prognosis in patients with advanced HF and can be used to assess transplantation priorities. It will be necessary to study a larger number of patients to confirm these findings.

Support Program for Heart Transplant Patients: Initial Experience

INTRODUCTION Trials of education and support in heart failure patients have shown an improvement in patient prognosis with favorable results in cost-benefit analysis. OBJECTIVES To assess the impact of a telephone support program for heart transplant patients during the first year after transplantation. PATIENTS AND METHODS We analyzed 30 consecutive heart transplant patients at our institution, who were randomized to either a standard care group or a group with the additional possibility of direct telephone contact with a cardiologist. We analyzed the time employed answering the calls, the reasons for consultation, and the number of hospital trips avoided. RESULTS Among the total sample, 15 patients were assigned to the intervention program. Over 194 +/- 103 days, we received 28 calls. The mean call duration was 10.2 +/- 3.9 minutes, with 39.3% of the consultations concerning medication dosages 28.6% lifestyle issues, 25% infectious symptoms, and the remaining 7%, medication side effects. Medication readjustments were made in 33% of the calls; 10.7% of the calls, all for infectious symptoms, required direct medical consultation. CONCLUSION Telephone support may be useful to improve therapeutic compliance, adjust the medications, and avoid treatment errors, as well as detect early complications during follow-up. In addition, it may avoid unnecessary medical visits.