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Introduction: Heart transplantation has become the best available therapy for patients with refractory end-stage heart failure. Cyclosporine (CsA) and mycophenolate mofetil (MMF) are the 2 FDA-approved drugs to prevent posttransplant acute rejection episodes. The purpose of this study was to evaluate the result of heart transplantation treated with CsA and everolimus (EVL), compared with that of patients treated with CsA and MMF., Materials and Methods: From 2000 to 2009 heart transplantation was performed in 239 patients among whom we enrolled 93 patients with a serum creatinine values

Background: Cyclosporine (CsA) is widely used after heart transplantation. The purpose of this prospective randomized study was to evaluate the safety and efficacy of reduction of CsA blood level to one-half of the traditional blood concentration under a regimen of everolimus (EVL), CsA, and steroid., Materials and Methods: This prospective, 6 month, randomized, open-label study included adult (aged 18 to 65 years) recipients of a primary heart transplant with serum creatinine60 years old, had cold ischemia time>6 hours, or had plasma renin activity>or=25%. All patients received CsA (C2 blood level 1000-1400 ng/mL), EVL (C0 target 3-8 ng/mL), and corticosteroids to day 60, before random entry into one of 2 groups: SE (C2 blood level from days 60-149=800-1200 ng/mL, and days 150-180 C2=600-1000 ng/mL), or RE group with CsA reduced by one-half after 3 months (days 90-149 C2=400-600 ng/mL, and from days 150-180 C2=300-500 ng/mL)., Results: The 25 recipients eligible for this study included 13 patients in the SE and 12 in the RE group. There was no operative mortality in either group. No death or graft loss was noted within 6-months in either group. Mean serum creatinine at month 6 tended to be lower in the RE cohort (1.23+/-0.44 mg/dL versus 1.55+/-0.85 mg/dL; P=.093). Biopsy-proven acute rejection>or=grade 3A was observed in only 1 patient (7.7%), who was in the SE group. There were no acute rejection episodes associated with hemodynamic compromise. The incidences of adverse events in each group were similar., Conclusions: Concentration-controlled EVL (C0 target 3-8 ng/mL) in combination with reduced CsA exposure of one-half the usual concentration achieved good efficacy and safety over 6 months. The renal function at 6 months among the RE group showed a trend toward improvement, suggesting a benefit of halving the target CsA blood level after heart transplantation., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Simultaneous heart and kidney transplantation (SHKT) has become an accepted therapeutic option for patients with end-stage heart failure associated with end-stage renal disease. The immunosuppressive therapy is usually based upon a heart transplantation protocol using a calcineurin inhibitor (CNI). Sirolimus (SRL) is a potent nonnephrotoxic immunosuppressant with antiproliferative activity in nonimmune cells. Its use has recently been reported to show less nephrotoxicity among both heart and kidney transplants. However, the data for the SHKT are limited. We retrospectively examined the causes of 5 patients who received combined SRL-CNI immunosuppressive therapy with reduced CNI doses from 2003 to 2009. There was no mortality during follow-up. Two of the 3 patients who received a conversion regimen recovered renal function. One who suffered severe proteinuria after transplantation proceeded to hemodialysis at 3 years after conversion. Both of the patients who received the combined regimen de novo remained stable regarding their renal function. Cardiac function was stable in these patients; there was neither allograft rejection nor allograft coronary vasculopathy. We observed that patients without dyslipidemia or hyperuricemia before SHKT were less likely to develop these disorders under the combined regimen. Early medical intervention after close follow-up of lipid and uric acid values by dose adjustments resulted in a stable status of our patients., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Objective: In this study, we examined whether cyclosporine was effective when combined with everolimus in clinical heart transplantation (HT)., Patients and Methods: From August 2004 to July 2007, 108 adult patients underwent primary HT. The main exclusion criteria were: donors > 60 years; cold ischemia times > 6 hours; recipients of multiorgan transplantation or a previous transplantation; and panel-reactive antibodies > or = 25%. The cyclosporine plus everolimus regimen (group CE, n = 32) was suggested first; upon refusal or if the recipient or donor was positive for hepatitis B surface antigen or PCR + hepatitis C infection, then patient was randomly assigned to success cyclosporine plus mycophenolate mofetil (MMF; group CM, n = 24) or tacrolimus plus MMF (group TM, n = 25). All patients underwent similar operative procedures and postoperative care with protocol endomyocardial biopsies., Results: No 30-day mortality was noted in any group. The efficacy failure rates were 3%, 25%, and 16% in groups CE, CM, and TM, respectively (P = .04 between groups CE and CM). The 1-year survivals were 96.7% +/- 18.1%, 89.7% +/- 29.8%, and 81.0% +/- 35.5% for groups CE, CM, and TM, respectively (P = .04 between groups CE and TM). The 3-year survival rates were 91.9% +/- 28.3%, 79.8% +/- 46.0%, and 81.0% +/- 35.5% in groups CE, CM, and TM, respectively., Conclusions: The 3 immunosuppressive regimens offered good efficacy after HT. The cyclosporine plus everolimus regimen showed a significantly better result with less efficacy failure (compared with cyclosporine plus MMF: 3% vs 25%) and better 1-year survival compared with tacrolimus plus MMF: 96.7% vs 81.0%.

The cyclosporine (CsA) blood concentration at 2 hours postdose (C2) has been shown to be better than trough level (C0) to predict acute cellular rejection (ACR) in solid organ transplantations. We tried to assess the superiority of C2 monitoring to C0 in heart transplantation (HTx). Prospective data were collected from the HTx recipients from November 1991 to April 2003. The 100 patients surviving longer than 3 months after HTx, provided 237 sample sets, with ACR graded by endomyocardial biopsy (EMB) and concurrent C0 and C2 levels. ACR was defined as International Society of Heart and Lung Transplantation (ISHLT) grade lb or higher. Nonparametric methods, logistic regression model, and receiver operating characteristic (ROC) analysis were used. There was no significant demographic heterogeneity between ACR and non-ACR groups. C2 was significantly lower in ACR than non-ACR groups (P = .0192) whereas C0 showed no significant difference. In the logistic regression model, C2 was a significant predictor against ACR (P = .026, odds ratio = 0.76 per 100 ng/mL), but C0 was not. ROC analysis showed that C2 of 600 ng/mL might provide the optimal cut-off point, with a sensitivity of 51.23% and a specificity of 71.43%, but C0 did not show this association. In conclusion, C2 monitoring is superior to C0 for predicting ACR in HTx. ACR should be suspected when the C2 value is below 600 ng/mL.

Abstract: Purpose: In addition to having a lipid-lowering effect, statins also have an anti-inflammatory effect that may reduce allograft dysfunction by preventing cardiac allograft vasculopathy (CAV) and play an immunomodulatory role. We studied the effect of statins on cardiac allograft survival at the National Taiwan University Hospital (NTUH). Materials and Methods: We retrospectively reviewed the patients undergoing heart transplantation at NTUH in the last 6 years. After transplantation, all patients received biochemical monitoring every month and echocardiographic examination regularly at NTUH. Protocol biopsy was performed in all except 18 pediatric patients. All patients received immunosuppressants, including tacrolimus or cyclosporine, everolimus or mycophenolate acid, and prednisolone. They were divided into statin and nonstatin groups according to whether or not a statin was taken. Results: At NTUH, from 2007 to 2012, 168 heart transplantations were performed. The ages of the patients ranged from 6 to 74 years old with male predominance. The etiology was mainly dilated cardiomyopathy (52.4%) and ischemic cardiomyopathy (39.3%), including 7 retransplantations from severe CAV with heart failure. Twenty-three patients (17%) suffered from acute rejection. The overall 1-year actuarial survival rate was 86% ± 2% and the 5-year survival rate was 79% ± 3%. Seventy-eight patients (57.4%) took statins and the statin group has a better 5-year survival rate and freedom from cardiac death survival rate (P < .01). Conclusion: Our study showed that the use of statins after transplantation was associated with better survival. [Copyright &y& Elsevier]

Abstract: Cardiac allograft vasculopathy (CAV) remains one of the leading causes of late graft failure and death. Cyclosporine microemulsion Neoral (CsA) had been used in heart transplantation (HTx) recipients. Meanwhile, Everolimus (EVL; Certican, Norvatis Pharmaceuticals; Basel, Switzerland) or mycophenolate mofetil (MMF) have been combined with CsA for maintenance treatment. We compared atherosclerosis in HTx patients showing CAV by intravascular ultrasound (IVUS) in two groups: the CE who received CsA, EVL, and steroid versus the CM group, who received CsA, MMF, and steroid. Materials and Methods: We explored IVUS parameters such as plaque thickness (PT), lumen circumference (LC), media adventitial circumference, lumen diameter (LD), and media adventitial diameter to characterize the atherosclerosis among CE versus CM groups. Results: In this study, both the CE and CM groups showed increased plaque thickening in the first year posttransplantation (P < .05). However, MMF significantly reduced LC and LD (P < .05) Upon multivariate linear regression analysis, the CE group seemed to show less effect on the maximal difference in PT between 2 and 12 months after adjusting for age at transplantation and gender (P < .05). There was no acute clinical adverse event of CAV reported in either both group during the follow-up. The atherosclerosis of CAV revealed by LC, LDmax, and LDmin was significantly less among patients treated with CE than CM. Conclusion: These results suggested that everolimus-treated patients showed benefits compared with MMF-treated subjects as extrapolated from these IVUS data. [Copyright &y& Elsevier]

Abstract: The cyclosporine (CsA) blood concentration at 2 hours postdose (C2) has been shown to be better than trough level (C0) to predict acute cellular rejection (ACR) in solid organ transplantations. We tried to assess the superiority of C2 monitoring to C0 in heart transplantation (HTx). Prospective data were collected from the HTx recipients from November 1991 to April 2003. The 100 patients surviving longer than 3 months after HTx, provided 237 sample sets, with ACR graded by endomyocardial biopsy (EMB) and concurrent C0 and C2 levels. ACR was defined as International Society of Heart and Lung Transplantation (ISHLT) grade lb or higher. Nonparametric methods, logistic regression model, and receiver operating characteristic (ROC) analysis were used. There was no significant demographic heterogeneity between ACR and non-ACR groups. C2 was significantly lower in ACR than non-ACR groups (P = .0192) whereas C0 showed no significant difference. In the logistic regression model, C2 was a significant predictor against ACR (P = .026, odds ratio = 0.76 per 100 ng/mL), but C0 was not. ROC analysis showed that C2 of 600 ng/mL might provide the optimal cut-off point, with a sensitivity of 51.23% and a specificity of 71.43%, but C0 did not show this association. In conclusion, C2 monitoring is superior to C0 for predicting ACR in HTx. ACR should be suspected when the C2 value is below 600 ng/mL. [Copyright &y& Elsevier]