Clinical characteristics and long-term outcomes of patients undergoing combined heart-kidney transplantation: a single-center experience.

BACKGROUND: The purpose of the study was to describe clinical characteristics and long-term survival of patients undergoing combined heart-kidney transplant in a single center. METHODS: We conducted a retrospective analysis of 22 consecutive patients who underwent combined heart-kidney transplant at our institution between 1995 and 2013. Long-term outcomes were analyzed by means of the Kaplan-Meier method. RESULTS: Four patients underwent re-do transplant (2 cardiac re-transplants, 1 kidney re-transplant, and 1 combined heart-kidney re-transplant). Most frequent underlying cardiac conditions were coronary artery disease (54%), dilated cardiomyopathy (23%), and chronic rejection of a previous heart graft (18%). Known causes of chronic renal dysfunction were nephroangioesclerosis (23%), drug-related toxicity (14%), and Wegener granulomatosis (5%). Non-specified chronic renal dysfunction was present in 50% patients. In-hospital postoperative mortality rate was 5 of 22 (23%). Causes of early death were directly related to kidney transplant surgery in 4 of 5 (80%) patients. Among the remaining 17 patients who surmounted the postoperative period, long-term survival rates 1 year, 5 years, and 10 years after HKT were 88%, 82%, and 65%, respectively. Over a mean follow-up of 6.7 ± 6.4 years, cumulative incidences of cytomegalovirus infection, coronary allograft vasculopathy, malignancy, and acute cardiac graft rejection were 41%, 6%, 24%, and 41%, respectively. There was no episode of acute renal graft rejection. At the end of follow-up, all survivors (n = 11) were in functional New York Heart Association class I. Mean creatinine serum level was 1.68 mg/dL. CONCLUSIONS: In our experience, combined heart-kidney transplant is a feasible therapeutic option that yielded favorable long-term outcomes, with a low cumulative incidence of cardiac graft dysfunction. These results were obtained at the expense of a significant risk of early postoperative mortality, which was mainly related to complications of kidney transplant surgery.

Indoleamine, 2-3 dioxygenase activity could be an early marker of graft rejection in heart transplantation.

BACKGROUND: The indoleamine, 2-3 dioxygenase (IDO) is an inducible intracellular enzyme with immunosuppressive effects mainly on lymphocyte populations. It has been postulated that indirect determination of IDO serum activity may be a marker of renal graft rejection, but its potential usefulness in heart transplantation (HT) is unknown. METHODS: This longitudinal study included 98 HT patients (83% males) who survived ≥1 year. Mean age was 54.14 ± 11.57 years. Serum IDO activity was analyzed one month after HT by means of high performance liquid chromatography and correlated with the cumulative incidence of acute rejection (AR) during one-year follow-up. AR was defined as biopsy-proven ≥ ISHLT grade 2R rejection or empirically treated non-biopsy-proven rejection. The study sample was divided into two groups: AR group (n = 51), including patients who experienced at least one AR episode during the first year after HT; No-AR group (N = 47), including the remaining patients. RESULTS: Mean serum IDO activity one month after HT was significantly higher (P = .021) in the AR group (3.32 ± 1.56) than in the no-AR group (2.62 ± 1.35). No significant association between serum IDO activity and gender (male: 3.1 ± 1.56, women: 2.43 ± 0.99, P = .092), recipient age (r = -.07, P = .943) or donor age (r = 0.108, P = 0.293) was observed. By means of binary logistic regression, an odds ratio of 1.4 [CI 95%: 1.033-1.876, P = .03] per unit increase of act-IDO was estimated, with no significant modification upon forced adjustment for age and sex. Mean glomerular filtration rate 1 month after HT was 67.01 ± 28.51 mL/min/m(2). No significant correlation between this parameter and serum IDO activity was observed (r = .160, P = .117). CONCLUSIONS: Our study suggests that serum IDO activity one month after HT might be associated with a higher risk of AR during one-year follow-up. This association seems to be independent of recipient gender, age or renal function.

Percutaneous coronary interventions and bypass surgery in patients with cardiac allograft vasculopathy: a single-center experience.

INTRODUCTION: Cardiac allograft vasculopathy (CAV) remains a major impediment to long-term survival after heart transplantation (HT). Limited data exist regarding the impact of coronary revascularization in these patients. OBJECTIVE: To evaluate the outcomes of revascularization procedures in patients with CAV compared with patients who did not undergo revascularization. METHODS: Retrospective analysis of 249 patients who underwent HT at our center between June 1998 and December 2009 and who were examined by coronary angiography after HT. We included patients with moderate or severe CAV according to the International Society for Heart and Lung Transplantation (ISHLT) nomenclature to evaluated outcomes after revascularization or diagnostic angiography. Major adverse cardiovascular events (MACE) comprised death, acute coronary syndrome, coronary revascularization, admission because of heart failure not due to an acute rejection episode, and cardiac retransplantation. RESULTS: Moderate or severe CAV was detected in 43 patients. Twelve (27.9%) underwent coronary revascularization: eight percutaneous interventions and four bypass surgeries. Indications for revascularization were symptomatic ischemia or noninvasive evidence of ischemia (n = 6, 14.0%) or high-risk asymptomatic CAV (n = 6; 14.0%), namely, lesions located in the left main or proximal anterior descending arteries or multivessel disease with left ventricular dysfunction. The remaining 31 (72.1%), who did not undergo revascularization showed an absence of ischemia during exercise echocardiography (n = 11; 25.6%) or diffuse disease not amenable to revascularization (n = 20; 46.5%). During a mean follow-up of 3.0 ± 2.4 years, MACE occurred in three revascularized patients (25.0%), in one with absence of stress-induced ischemia (9.1%) and in 13 with nonrevascularizable disease (65%; P = .012). CONCLUSIONS: Revascularization procedures were effective in HT patients with evidence of ischemia or high-risk CAV. Patients with absence of stress-induced ischemia have a good prognosis without revascularization. On the other hand, diffuse nonrevascularizable CAV is associated with a poor prognosis.

Cumulative incidence of cytomegalovirus infection and disease after heart transplantation in the last decade: effect of preemptive therapy.

INTRODUCTION: Infection by cytomegalovirus (CMV) is a major concern in solid organ transplant (SOT). It increases morbidity and mortality. The prevalence of CMV asymptomatic infection and disease is variable among centers, partially related to immunosuppressive protocols and therapeutic strategies to treat CMV. Induction therapy with basiliximab is associated with fewer CMV infections than therapy with OKT3. In our center, universal prophylaxis is used in the first month post-heart transplant (HT) and preemptive therapy (PET) is used later, according to viral load monitoring. OBJECTIVE: To analyze the short- and long-term incidence of CMV infection and disease post-HT according to CMV status of recipient (R)/donor (D) in a cohort of patients who received induction therapy with basiliximab. MATERIALS AND METHODS: Retrospective analysis of 201 consecutive patients over 18 years of age who underwent HT between February 2001 (when induction therapy with basiliximab was initiated) and June 2011. Patients were divided in two risk subgroups of developing CMV disease: high-risk (D+/R- or D-/R- who received blood transfusions or R-, or donor with unknown serostatus) and low-risk (any other combination). RESULTS: Of 201 patients (mean age 53.81 ± 11.61 years, 81.1% men). 165 patients were classified in the low-risk and 36 in the high-risk group. The cumulative incidence of asymptomatic CMV infection during the first year post-HT was 47%: 46% in the low-risk and 50% in the high-risk group (P = .668). The incidence of CMV disease during the first year post-HT was 7.5%: 3.6% in the low-risk versus 25% in the high-risk group (P < .001). CONCLUSIONS: In our series, asymptomatic CMV infection after HT is frequent, affecting almost 50% of patients. However, the incidence of CMV disease is very low (7.5%), which confirms the effectiveness of PET. The higher incidence of disease in the high-risk group recommends closer monitoring of viral load in these patients or performing more prolonged universal prophylaxis.

Prevalence of donor-transmitted coronary artery disease and its influence on heart transplant outcomes.

BACKGROUND: It is uncertain whether donor-transmitted coronary artery disease (DTCAD) affects heart transplant (HT) recipients. METHODS: This retrospective analysis includes records of all patients who underwent a HT at our center over an 8-year period, who survived for at least 1 month, and who were examined by coronary angiography within 2 months post-HT. We distinguished angiographically from keep ultrasonography (IVUS) detected DTCAD. Major adverse cardiovascular events (MACE) comprised death, myocardial infarction, unstable angina, coronary revascularization, and admission because of heart failure not due to an acute rejection episode. RESULTS: Among the 171 patients of mean age 53±13 years and including 83% men, 65 (38%) were evaluated by IVUS. Donors were aged 40±14 years (range=14-73). Angiographic DTCAD affected seven patients (4.1%), and IVUS-detected DTCAD, 35 (53.8% of those examined by IVUS). DTCAD donors were older than non-DTCAD donors, by an average of 13 years (P=.001) for angiographic DTCAD and 18 years (P<.0001) for IVUS-detected DTCAD. Two patients underwent percutaneous revascularization upon detection of angiographic DTCAD. The angiographic- and IVUS-detected DTCAD groups did not differ significantly from the corresponding non-DTCAD groups as regards MACE incidence during 54±41 and 38±20 months follow-up, respectively. Cox regression analysis with adjustment for relevant confounders confirmed that IVUS-detected DTCAD was not a predictor of MACE (hazard ratio 1.2, 95% confidence interval 0.2-8.1). CONCLUSIONS: Among HT patients surviving≥1 month, angiographic- and IVUS-detected DTCAD showed prevalences of <10% and >50%, respectively. Neither detection method was associated with a greater long-term incidence of MACE.

Conversion of heart transplant patients from standard to sustained-release tacrolimus requires a dosage increase.

INTRODUCTION: It has been suggested that for adequate maintenance of tacrolimus levels, the total daily dosage should be increased when switching from the conventional twice-daily regimen tacrolimus (CT) to once-daily sustained-release tacrolimus (SR-T). OBJECTIVE: To evaluate the safety and efficacy of a 25% increase in daily dosage when switching heart transplant (HT) patients from CT to SR-T. METHODS: We switched 75 HT patients including 72% males and an overall mean age of 55.6 years from CT to SR-T using a 25% increase in daily dosage. We screened for adverse events by measurements of lipids, creatinine, glycemia, and tacrolimus in blood samples taken at 1, 3, 7, and 12 weeks after the conversion, as well as by repeated echocardiography and routine clinical examinations. RESULTS: Just two patients (2.7%) were returned to CT because of failure of SR-T to attain therapeutic levels. In the remainder of subjects, tacrolimus levels remained stable, with trough values of 8.7±3.2, 8.7±2.9, 8.3±2.6, and 7.5±2.0 mg/dL, respectively. Twenty-three patients (31%) required no dosage change in the first 3 months, but 44 (33%) required one or two changes. No departure from therapeutic levels was associated with rejection; there was no case of severe intercurrent infection. We did not observe significant changes in glycemia, creatinine, lipid profile, or blood pressure. CONCLUSIONS: Administration of SR-T at a dosage 25% higher than the daily dosage of CT was safe. It ensured adequate tacrolimus levels in one-third of patients. Nevertheless, strict analytical surveillance is necessary during the initial months to allow dosage adjustments and to detect the minority of patients for whom SR-T does not achieve therapeutic tacrolimus levels.

Long-term outcome in heart transplant patients with pretransplant malignancies.

INTRODUCTION: Neoplasms have classically been considered a contraindication for heart transplantation (HT) because of the possibility of recurrence during immunosuppressive therapy. There are few cases of patients who suffered a pretransplant malignancy (PTM); however the appropriate interval free of a malignancy (IFoM) before heart transplantation is unclear. Our study sought to determine the long-term outcomes after transplantation among patients who had suffered a prior neoplasm compared with our overall cohort. METHODS: This retrospective, single-center study included 595 heart transplant recipients ungrafted between 1991 and 2009. We determined PTM location, histology, and IFoM. We examined donor and recipient factors and post-HT data of rejections, infections, neoplasms, and survival associated with a poor prognosis. RESULTS: Twelve patients with different types, locations, and histological grades of PTM represented 66.7% women versus 16.1% women in the overall series (P<.01). There were no differences in recipient age or clinical characteristics (diabetes mellitus, arterial hypertension, previous renal failure, or New York Heart Association class), number of emergency cases, or graft ischemia time. Mean IFoM was 114.3 months (range=5.3-350.4). After heart transplantation, there were no significant differences between the number of infections (47.9%; n=[279] vs 33.3% n=4; P=.39), rejection episodes (44.4% [259] vs 50% [6], P=0.77) or post-HT malignancies (12.2% [70] vs 0%, P=0.37) between the overall series and the patients with PTM. None of the patients with PTM suffered a recurrence of the neoplasm. Actuarial survivals at 1, 3, and 5 years were 82%, 76%, and 70% among patients without PTM and 75%, 75%, and 56% among those with PTM (P=.70). CONCLUSION: Patients with PTM and an appropriate IFoM with regard to tumor lineage showed similar rates of survival and complications as those of the overall series. This series suggested that appropriately selected patients with a cured PTM can be candidates for HT.

Efficacy and tolerance of different types of prophylaxis for prevention of early aspergillosis after heart transplantation.

BACKGROUND: The incidence of aspergillosis (ASP) after heart transplantation (HTx) is low (<4%-5%), but the mortality is high (>78%). AIM: To determine the incidence of ASP in the first 3 months post-HTx according to the type of prophylaxis and assess the tolerance to these regimens. METHODS: This retrospective study of 571 adult HTx patients engrafted from 1991 to December 2009 included 83% males with an overall group age of 54.9±11 years. Three types of prophylaxis were compared: group A was no prophylaxis (n=99; 1991-1994); group B, itraconazole for 3 months (n=352; 1995-November 2004); and group C, inhaled amphotericin for 3 months (n=120; December 2004-2009). The dependent variables were the presence and severity or tracheobronchitis and invasive/disseminated disease as well as, prognosis of Aspergillus infection and tolerance to the regimen. RESULTS: The incidences of aspergillosis were 5% in group A (n=5); 1.4% in group B (n=5); and 0% in group C. Significant differences were observed between groups A versus B (P=.030) and between groups A versus C (P=.013), but there were no differences between groups B versus C. In terms of severity, there were no significant differences among the five cases of tracheobronchitis (20% group A/80% group B), five of invasive/disseminated disease (80% group A/20% group B). There were two deaths (20%) from invasive/disseminated ASP at 0.67 months after diagnosis. The mean time from HTx to ASP was 0.98±0.40 months. There were no adverse effects associated with itraconazole, but they occurred in 3/120 patients (2.5%) treated with inhaled amphotericin, all of whom were on mechanical ventilation, developing respiratory failure requiring amphotericin withdrawal. CONCLUSIONS: Prophylaxis with itraconazole or inhaled amphotericin was effective for the prevention and severity of pulmonary ASP in the first 3 months post-HTx. Although the incidence of early ASP was low in our series, the 20% mortality rate justified the use of preventive measures. Tolerance to both prophylactic treatments was good.

Safety of statins when response is carefully monitored: a study of 336 heart recipients.

BACKGROUND: Statins are used as first-line drugs against hypercholesterolemia after heart transplantation. Randomized clinical trials have shown that they reduce cholesterol levels, and the incidence of rejection and coronary vasculopathy. Adverse effects have been related to the use of certain statins, high statin dosages, comorbidities, and coadministration with cyclosporine. However, estimation of the risk of adverse effects for a given patient is difficult. The aims of this study were to determine the incidence of various kinds of adverse effect of statins; to evaluate certain potential risk factors; and to assess the efficacy of early response to signs of adverse effects. METHODS: Between April 1991 and December 2003, we retrospectively evaluated 336 heart transplant patients (including 55 women) with regard to the occurrence of possible adverse effects of statins (rhabdomyolysis, myalgia, hepatotoxicity, high CK without muscle symptoms, and others). Resolution on reduction of dosage or discontinuance and/or change of statin were deemed to constitute confirmation of cause. Relations were sought between adverse effects and age, sex, immunosuppressive therapy, kidney failure, body mass index (BMI), arterial hypertension, and diabetes mellitus. RESULTS: Possible adverse events of statins were suffered by 60 patients, all of them men. The causal role of statins was confirmed in 41 (12.2% of all 336): hepatotoxicity was suffered by 13, high CK without muscle ache or weakness by 18, rhabdomyolysis by 5, myalgia by 3, and other effects by 2. The incidence of confirmed statin-related complications was higher among patients with BMI >29 kg/m(2) than among those with lower BMI (P = .055). None of the patients with confirmed statin-related complications needed dialysis, none died, and permanent suspension of statin treatment was only necessary in 13 cases (3.9% of the 336). CONCLUSIONS: Some 10% to 20% of HT patients appear to suffer adverse side effects of initial statin therapy. However, early detection of such effects through diligent clinical and analytical monitoring allows the therapy to be modified in time to minimize the appearance of severe complications. In only a minority of cases permanent suspension of statin therapy is necessary.