C.-I. Tsao

Induction Immunosuppression With Basiliximab in Heart Transplantation

After clinical heart transplantation (HT), it is crucial to use appropriate immunosuppressive agents to prevent rejection. The use of basiliximab or rabbit anti-thymocyte globulin (RATG) for induction therapy has significantly reduced the incidence of acute rejection episodes after kidney transplantation. In this study we sought to examine the effects of basiliximab after HT. From June 2006 to July 2007, we performed 43 HT including patients 18-65 years old undergoing primary HT who were included in this study of basiliximab induction (20 mg intravenous [iv] on days 0 and 4). Cyclosporine and everolimus were given with basiliximab induction. All others received RATG induction (1.5-2.5 mg/kg iv infusion on days 0, 1, and 2) followed by cyclosporine or tacrolimus combined with mycophenolate mofetil. All patients underwent the same operative procedure, steroid-tapering protocol, and postoperative care with protocol endomyocardial biopsy. Basiliximab was well-tolerated and easy to use. There was only 1 operative mortality; the patient died of sepsis due to Enterobacter cloacae. All others survived the operation and are alive and in good health with a 2-year survival rate of 92.86%. No severe adverse events were noted during the first postoperative month. No acute rejection > or = grade 2R or rejection associated with hemodynamic compromise was noted during the whole course. Basiliximab as induction immunosuppressant was simple, safe, and effective after HT.

The Influence of Donor Characteristics on Survival After Heart Transplantation

With improved immunosuppressive regimens, transplantation techniques, and postoperative care, heart transplantation (HTx) has been established as a definite therapy for end-stage heart disease. Because of a donor shortage, we have accepted marginal individuals. In this study, we identified donor-related factors influencing survival after HTx by retrospective analysis of recipient data after primary HTx from February 2002 to December 2006. The Cox regression model was used to examine the effects of the following variables on survival of 112 heart transplant recipients: demographic data of gender, age, body weight, donor-recipient body weight ratio; history of smoking, alcohol drinking, diabetes mellitus, hypertension, hepatitis B surface antigen, anti-hepatitis C virus antibody; donor condication before transplantation including catecholamine doses, hypotension, cardiopulmonary resuscitation, creatine MB isoenzyme of creatine kinase (CK-MB), tropinin I, and cold ischemic time of the allograft. Catecholamines and smoking showed significant influences on HTx survival. In our series, the percentage of donors receiving inotropic support before donation was 88% (n = 99), and the percentage of donors with a history of smoking was 25% (n = 28). There was no influence of donor status of diabetes, hypertension, or hepatitis B or C infection on postoperative survival. Our results showed that inotropic support of and a history of smoking by the donor were significant factors influencing posttransplant survival.

Isolated cardiac sarcoidosis in heart transplantation

BACKGROUND Heart transplantation is the ultimate treatment for end-stage heart failure. Cardiac sarcoidosis has rarely been reported in heart transplantation worldwide. Their long-term prognosis after heart transplantation is unknown. Herein we have presented clinical and pathological observations among heart transplantation patients with isolated cardiac sarcoidosis. METHODS From 1987 to 2011, we performed 411 heart transplantations including five patients retrospectively reviewed due to the presence of sarcoidosis and giant-cell cardiomyopathy in the recipient heart. RESULTS Among the heart transplantations from 2003 to 2011, the four male and one female patients were ages 31 to 40 years. None of them had extra-cardiac sarcoidosis. All five subjects presented with dilated cardiomyopathy with patent coronary arteries. The commonest clinical presentations were atrioventricular block, ventricular arrhythmia, electrocardiographic findings of ST elevations, and poor left ventricular ejection fractions (17%-23%). All patients survived without allograft heart failure to date with the longest survivor at 8 years postoperatively. No recurrence of sarcoidosis has been observed clinically or among the post-heart transplantation endomyocardial biopsies. CONCLUSION Heart transplantation is a useful treatment for isolated cardiac sarcoidosis patients suffering end-stage heart failure. Often the diagnosis is difficult to establish before heart transplantation despite endomyocardial biopsy. No recurrence of sarcoidosis was observed among the allografted hearts.

Clinical Experience of Tacrolimus With Everolimus in Heart Transplantation

BACKGROUND Tacrolimus (Tac) in combination with mycophenolate mofetil is widely used after heart transplantation (HT). Everolimus (EVR), a new potent proliferation signal inhibitor can be used with a carcineurin inhibitor to reduce the occurrence of rejection. The purpose of this study was to evaluate the efficacy and safety of Tac combined with EVR in de novo HT. MATERIALS AND METHODS From January 2009 to April 2011, 33/62 patients who underwent HT were prescribed Tac and EVR as de novo immunosuppression. The main exclusion criteria were poor kidney function (serum creatinine > 2.8 mg/dL), panel-reactive antibodies > 25%, donors > 60 years old, or cold ischemia time > 6 hours. All patients received Tac (C0 blood level 5-10 ng/mL during the first 6 months, then 3-5 ng/mL), EVR (C0 target 3-8 ng/mL), and corticosteroids. After transplantation, routine examinations included echocardiogram and protocol endomyocardial biopsy. RESULTS There was no operative mortality. The 1- and 3-year actuarial survivals were 95.74% ± 3.49%. One patient who had undergone coronary artery bypass grafting previously and received intra-aortic balloon pumping and extracorporeal membrane oxygenator-assisted cardiopulmonary resuscitation before HT died of Aspergillus septicemia 58 days after HT. No biopsy-proven acute rejection > grade 2R or acute rejection associated with hemodynamic compromise was observed. Hyperlipemia was noted in 16 cases (48.5%), hypertension in 11 (33.3% 5%), and diabetes mellitus in 12 (36.4%). No other severe adverse events were noted. CONCLUSIONS Concentration-controlled EVR (C0 target 3-8 ng/mL) in combination with Tac achieved good efficacy and safety. The 1- and 3-year actuarial survivals were 95.74% ± 3.49%.

Extracoporeal Membrane Oxygenation to Rescue Cardiopulmonary Failure After Heart Transplantation: A Single-Center Experience

Extracorporeal membrane oxygenation (ECMO) can provide excellent mechanical circulatory support (MCS). Some case reports use ECMO to rescue heart transplantation (HTx) recipients with posttransplant cardiopulmonary failure. Herein reported a series of use of ECMO to rescue HTx recipients with refractory cardiopulmonary failure have during the posttransplant period. The causes of cardiopulmonary failure were right ventricular failure, primary graft failure, acute rejection, or sepsis. A retrospective review of 366 consecutive HTx recipients revealed 40 cases of cardiopulmonary failure requiring ECMO rescue in the posttransplant period. There were 14 patients diagnosed as right ventricular cardiopulmonary failure; 7 primary graft failure with a stunned donors myocardium, 8 as acute cellular or humoral rejection, and 11 as sepsis with positive blood cultures. ECMO-related variables were evaluated for association with mortality. The HTx recipients included 35 males and 5 females with overall median age of 42.3 years (range, 0.48-65.22). The weaning rate was 72.5% (29/40) and survival, 52.5% (21/40). ECMO provided temporary MCS rescuing some HTx recipients with posttransplant cardiopulmonary failure. None of the patients receiving ECMO support for >4 days survived.

Can Cyclosporine Blood Level Be Reduced to Half After Heart Transplantation

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 creatinine<or=2.8 mg/dL. Among 52 patients who underwent heart transplantation from December 2004 to March 2006 we excluded those who were hepatitis B or C carriers, who were recipients of organs from donors>60 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.

Tuberculosis After Heart Transplantation: Twenty Years of Experience in a Single Center in Taiwan

The incidence of tuberculosis is slightly higher among heart transplantation cases than in the general population in Taiwan. Tuberculosis shows a high mortality rate ranging from 22% to 31% in transplant recipients. From October 1987 to October 2007, we performed 315 heart transplantations. Clinical records were reviewed for demographic data, clinical presentation, treatment, and outcome. Tuberculosis was diagnosed by cultures of any body sample in association with compatible symptoms and signs. Mortality was related to tuberculosis if there was evidence of active tuberculosis at the time of death and no other etiology accounted for death. Ten patients who had received heart transplants were diagnosed as tuberculosis. There were seven pulmonary lesions and seven extrapulmonary lesions. Treatment consisted of isoniazid, rifampin, ethambutol, pyrazinamide, streptomycin, ciprofloxacin, and levofloxacin. Seven patients completed the antituberculosis treatment: the median treatment duration was 1 year. Three patients developed hepatitis. There was no tuberculosis-related mortality. Ten out of a total of 315 patients (3.17%) represented a tuberculosis rate higher than that reported for the general Taiwan population (67/100,000). This high mortality of infection may be completely treated by a combination of at least three drugs except pyrzinamide because of side effects and tolerance.

Heart transplantation under cyclosporine or tacrolimus combined with mycophenolate mofetil or everolimus.

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%.

Cardiac Allograft Vasculopathy Compared by Intravascular Ultrasound Sonography: Everolimus to Mycophenolate Mofetil—One Single-Center Experience

UNLABELLED 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.

Twenty-four Year Single-Center Experience of Hepatitis B Virus Infection in Heart Transplantation

OBJECTIVE Hepatitis B virus (HBV) infection is hyperendemic in Taiwan. We have reported the outcome of (1) recipients with hepatitis B surface antigen (HBsAg)-positive; HBsAg-negative recipients who receive donor hearts from HBsAg-positive donors; and treatment with lamivudine of hepatitis B flare-ups after heart transplantation, using case numbers that range from 100 to 200. METHODS From July 1987 to May 2011, all 412 orthotopic heart transplant recipients and donors underwent routine preoperative screening for hepatitis B virus markers and liver function parameters. Lamivudine was prescribed prophylactically for recipients with elevated serum enzyme levels or an HBV DNA virus load before transplantation, or when there was evidence of hepatitis B flare-up after transplantation. Postoperative HBV markers and liver function parameters were collected over a mean follow-up time of 7.8 years. RESULTS Thirty-four recipients were HBsAg-positive before heart transplantation, and 23 experiencing HBV reactivation upon follow-up requiring lamivudine treatment. Clinical responses were achieved in all of them: 15 were complete and two, slow partial responses. Twenty-six recipients with an HBV naïve status at the time of heart transplantation, and three patients received donor hearts from an HBsAg-positive donor under perioperative hepatitis B immunoglobulin prophylaxis. HBV infection was successfully prevented in two patients, but the other one contracted HBV hepatitis, which was successfully treated with lamivudine. CONCLUSIONS HBV reactivation after the heart transplantation was common but usually well controlled with lamivudine treatment. Although posttransplantation liver function deteriorated for a period, there was no HBV infection-related morbidity or mortality. Perioperative hepatitis B immunoglobulin prophylaxis can successfully prevent HBV naïve recipients from infection in some cases, but HBsAg-positive donors should only be considered in high risk situations.