Comparison of the performance of the CRUSADE, ACUITY-HORIZONS, and ACTION bleeding risk scores in STEMI undergoing primary PCI: insights from a cohort of 1391 patients.

AIMS: To compare the performance of the CRUSADE, ACUITY-HORIZONS, and ACTION risk models in the ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). METHODS: We studied all consecutive patients with STEMI who underwent PPCI at our institution between 2006 and 2010 (n=1391). The CRUSADE, ACUITY-HORIZONS, and ACTION risk scores were calculated based on the patients' clinical characteristics. The occurrence of in-hospital major bleeding (defined as the composite of intracranial or intraocular bleeding, access site haemorrhage requiring intervention, reduction in haemoglobin ≥4 g/dl without or ≥3g/dl with overt bleeding source, reoperation for bleeding, or blood transfusion) reached 9.8%. Calibration and discrimination of the three risk models were evaluated by the Hosmer-Lemeshow test and the C-statistic, respectively. We compared the predictive accuracy of the risk scores by the DeLong non-parametric test. RESULTS: Calibration of the three risk scores was adequate, given the non-significant results of Hosmer-Lemeshow test for the three risk models. Discrimination of CRUSADE, ACUITY-HORIZONS, and ACTION models was good (C-statistic 0.77, 0.70, and 0.78, respectively). The CRUSADE and ACTION risk scores had a greater predictive accuracy than the ACUITY-HORIZONS risk model (z=3.89, p-value=0.0001 and z=3.51, p-value=0.0004, respectively). There was no significant difference between the CRUSADE and ACTION models (z=0.63, p=0.531). CONCLUSIONS: The CRUSADE, ACUITY-HORIZONS, and ACTION scores are useful tools for the risk stratification of bleeding in STEMI treated by PPCI. Our findings favour the CRUSADE and ACTION risk models over the ACUITY-HORIZONS risk score.

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.

Clinical scores and patient risk stratification in non-ST elevation acute coronary syndrome.

BACKGROUND: Risk stratification of patients with unstable angina or non-ST-segment elevation myocardial infarction (UA/NSTEMI) is problematic given the heterogeneous presentation of the condition. This study was undertaken to compare, in UA/NSTEMI patients, the prognostic value of two clinical risk scores (RS) (i.e. Thrombolysis in Myocardial Infarction (TIMI) and physician's risk assessment (PRA)) and to assess whether serum biomarkers can increase the prognostic accuracy of these RS. METHODS: We prospectively assessed 610 consecutive UA/NSTEMI patients, 217 (36%) UA and 393 (64%) NSTEMI. In all patients RS, high sensitivity C-reactive protein, CD40 ligand, IL6, IL10, IL18, E-selectin, P-selectin, white blood cell count, neopterin, myeloperoxidase, fibrinogen and NT proBNP were assessed at study entry. The primary study endpoint was death and non-fatal MI at 30 and 360 days of follow-up. RESULTS: At 1 year, 54 patients (8.9%) had reached the primary study endpoint (26 suffered a cardiac death (4.3%) and 34 (5.6%) a non-fatal MI). For both RS, the study endpoint occurred more commonly in patients at a "higher risk" compared to those classified as being at a "lower risk". Moreover, TIMI and PRA RS had similar discriminatory accuracy. TIMI RS, however, was a better predictor of events than PRA at both 30- and 360-day follow-up. The inflammatory biomarkers assessed in the study did not improve significantly the predictive value of RS. CONCLUSIONS: Our study suggests both that TIMI RS is a better marker of risk than PRA RS and inflammatory biomarkers do not increase the predictive value of these clinical risk scores.

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.

Gene expression profiling for monitoring graft rejection in heart transplant recipients.

Heart transplantation is a life-prolonging therapy for many patients with stage D heart failure and other forms of advanced heart disease. However, graft rejection and/or immunosuppression-related side effects are major causes of morbidity and death among heart transplant patients. Graft rejection monitoring remains a challenge. It would be desirable to be able to detect rejection early enough and specifically enough to prevent allograft dysfunction without unnecessary overimmunosuppression. Hitherto, the main technique employed in monitoring the rejection status of a transplanted heart has been endomyocardial biopsy (EMB), which allows rejection to be screened for and monitored on the basis of the extent and distribution of lymphocytic infiltrates and associated myocardial damage. However, EMB has significant limitations: it is invasive, its sensitivity is limited by sampling efficacy, and it suffers from considerable between-observer variability. Although many noninvasive techniques have been investigated, none so far has proved able to match the performance of EMB. Currently, a multiparametric approach is employed that comprises clinical examination for signs or symptoms of heart failure, EMBs, drug level monitoring, allograft function tests (mainly echocardiographic studies), and screening for allograft vasculopathy. Gene expression profiling may be a promising tool for this purpose.

Adverse effects of mammalian target of rapamycin inhibitors during the postoperative period after cardiac transplantation.

INTRODUCTION: Safety of treatment with mammalian target of rapamycin inhibitors (mTORi) in the postoperative period after heart transplantation (HT) is controversial. METHODS: We evaluated the incidence of postoperative complications (pericardial, pleural, and surgical wound complications) among nine de novo heart transplant recipients treated with mTORi compared with 19 patients who did not receive them during the same period (control group). RESULTS: No significant differences were observed between the two groups regarding sex, age, body mass index, pretransplant diagnosis, history of diabetes mellitus, prior cardiac surgery, or baseline renal function. The main laboratory parameters at 1 month were also similar. During the first 2 months after HT, four patients (44%) in the mTORi group developed severe pericardial effusions requiring drainage, compared to 1 (5%) in the control group (P = .026). All patients presenting this complication in the mTORi group received everolimus. In addition, two cases of sternal dehiscence were observed in the mTORi group, compared to none in the control group (P = .09); one patient on everolimus required sternal reopening and debridement for clinically suspected mediastinitis. Duration of chest tube drainage, quantity of collected pleural fluid, and need for thoracentesis were similar in both groups. CONCLUSIONS: In our series, patients receiving mTORi-particularly everolimus-during the postoperative period after HT showed a higher incidence of severe pericardial effusion requiring drainage, as well as a trend toward a higher incidence of sternal dehiscence, as compared to a group not receiving mTORi. The use of mTORi during the early postcardiac transplant period should be individualized.

The efficacy and safety of ezetimibe for treatment of dyslipidemia after heart transplantation.

INTRODUCTION: Statins, although the treatment of choice for dyslipidemia after heart transplantation (HT), are not always well tolerated or effective. In such cases, administration of ezetimibe may be useful. AIM: The aim of this study was to assess the efficacy and safety of ezetimibe, with or without statins, after HT. METHOD: Thirty-six HT patients, 97% of whom were males of overall mean age of 57 +/- 13 years, were all unable to reach target lipid levels with statins alone and/or were intolerant of statins. They were prescribed ezetimibe, with or without a statin. Efficacy and safety were evaluated after 1, 3, 6, and 12 months. RESULTS: Thirty-four patients were evaluated at 1 month and 12 months. Ezetimibe was prescribed to 27 patients (75%) because of statin inefficacy, and to 9 patients (25%) because of statin intolerance, manifested by myalgia in 4 cases (11%), hepatotoxicity in 2 cases (6%), and rhabdomyolysis in 3 cases (8%). Lipid levels (mg/dL; baseline vs 1 year) were as follows: cholesterol, 235 +/- 49 versus 167 +/- 32 (P = .013); LDL cholesterol, 137 +/- 47 versus 89 +/- 29 (P = .001); HDL cholesterol, 54 +/- 13 versus 51 +/- 10 (P = .235); and triglycerides, 243 +/- 187 versus 143 +/- 72 (P = .022). There were no cases of liver toxicity, renal dysfunction, or significant alteration of immunosuppressive pharmacokinetics. Ezetimibe was withdrawn from 2 patients because of hand edema or asymptomatic recurrence of rhabdomyolysis first caused by statins. CONCLUSIONS: With or without a statin, ezetimibe was generally well tolerated, reducing total cholesterol, LDL cholesterol, and triglyceride levels with no long-term alteration of HDL cholesterol levels. CPK surveillance is recommended because of a slight continued risk of adverse effects. Further studies should evaluate the benefit for survival.

Reversal of cardiac cirrhosis following orthotopic heart transplantation.

Irreversible hepatic cirrhosis greatly increases the risks attending heart transplantation (HT), and is accordingly considered to be an absolute contraindication for HT unless combined heart and liver transplantation can be performed. It is now recognized that hepatic cirrhosis can undergo regression if the source of insult is removed, but no cases of post-HT regression of cirrhosis of cardiac origin have hitherto been reported. Here we report a case of cardiac cirrhosis that underwent complete regression following orthotopic HT, and we discuss the implications of this case.

Late steroid withdrawal after heart transplantation and incidence of acute rejection.

BACKGROUND: Steroid withdrawal (SW) after heart transplantation (HT) reduces steroid-associated side effects, although it can increase acute rejection episodes (ARE). Patient selection criteria for SW and the time elapsed after HT for this maneuver are controversial issues. The objective of this study was to assess the safety of late SW after HT with regard to the occurrence of ARE and to analyze risk factors resulting in a poor evolution. METHODS: We studied a cohort of 24 patients who underwent SW late after HT. All of them had gone at least 4 years without any ARE. Independent variables were time after HT, general recipient and donor data, risk factors for ARE, and immunosuppression. The dependent variables were occurrence of ARE (proven or not proven with endomyocardial biopsy) and time and severity of ARE. RESULTS: Among 24 HT patients including 96% men with an overall mean age of 57 years who underwent SW, the mean follow-up was 2.32 +/- 0.86 years. Six patients (25%) displayed an ARE >or=2R according to the International Society for Heart and Lung Transplantation (ISHLT) at 5 +/- 3 months after SW. There were no deaths. Time from the last rejection episode to SW was 6.6 +/- 2 years. All ARE were treated with steroid boluses (mean total dose 1583 +/- 1044 mg). Among the HT patients with ARE, 5 (85%) had never experienced ARE after HT. Upon long-term follow-up, there were 2 deaths: 1 sudden death at 30 months after SW and 1 due to allograft vasculopathy at 20 months post-SW. Currently 92% are New York Heart Association (NYHA) functional class I with a mean left ventricular ejection fraction of 67% +/- 10%. CONCLUSIONS: In our series of HT with late SW after HT (even among an HT population with a low risk of rejection), there was a 25% rate of ARE. This study did not allow us to identify risk factors for ARE after SW. We believe that based upon these observations SW should be implemented with caution.

Late noncardiac surgery in heart transplant patients.

OBJECTIVE: Because of improved long-term survival of heart transplants (HT), patients often need noncardiac surgery (NCS). Immunosuppression may increase the infection rate. Inadequate management may increase the risk of dysfunction or acute rejection episodes (ARE). Long-term outcomes of NCS and optimal immunosuppressive management in the perioperative period are not well known. The objective of this study was to analyze the incidence, morbidity, and mortality of late NCS after HT. METHODS: We retrospectively evaluated the incidence and type of late NCS as well as the risk factors for complications and the mortality among 207 HT patients. Immunosuppression and ARE rates were also analyzed. RESULTS: One hundred and sixteen late NCS (84.5% elective) were performed in 72 HT patients (34.8%). Interventions were: 35 urologic (30.2%), 29 abdominal (25%), 14 vascular (12.1%), 13 ENT (11.2%), 11 skin and soft tissue (9.5%), and 7 orthopedic (6%). Malignancy was the main indication for NCS (33.6%). Only 4 patients (5.6%) died preoperatively. Mortality was higher among emergent vs elective procedures (16.6% vs 1%; P = .012) and among patients with preoperative high vs middle/low risk (26.6% vs 0%). Postsurgical infection was the most frequent complication (6.9%). However, there were no relevant complications in 82.8% of HT patients. Hospitalization time was <15 days in two thirds of patients. Immunosuppression was modified in 33 patients (28.4%), especially when the surgical indication was neoplasia (P < .001). None of the patients with NCS displayed allograft dysfunction or an ARE. CONCLUSIONS: More than one-third of HT patients needed a late NCS. In our experience, elective surgical procedures with middle/low preoperative cardiovascular risk are safe. In this context, the risk of rejection was low when immunosuppression was carefully monitored to reduce the risk of infection.

WITHDRAWN: Accuracy of Peak Treadmill Exercise Echocardiography to Detect Multivessel Coronary Artery Disease: Comparison with Post-exercise Echocardiography.

The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 182-190, . The duplicate article has therefore been withdrawn.

Independent predictors of renal dysfunction after heart transplantation in patients with normal pretransplant renal function.

BACKGROUND: Renal dysfunction (RD) is a common complication after heart transplantation (HT), but predictors of post-HT RD have not been clearly identified. METHODS: We studied 262 HT patients (mean age 54 years, 221 men) with normal baseline renal function. Potential risk factors examined were age, sex, pre-HT ischemic cardiomyopathy, pre- and post-HT diabetes mellitus, pre- and post-HT arterial hypertension, initial immunosuppressive protocol (before 1998 [high cyclosporine, azathioprine, and prednisone] vs after 1998 [low cyclosporine, mycophenolate mofetil, and prednisone]), occurrence of rejection episodes > or =ISHLT Grade 3A, and creatinine level 1 month after HT. RD was considered mild if creatinine level was 1.5 to 2.5 mg/dl, moderate if creatinine level was >2.5 mg/dl, and severe if dialysis or kidney transplant was required. RESULTS: The cumulative incidence of RD (creatinine >1.5 mg/dl) was 35% at 12 months, 42% at 24 months, and 47% at 60 months (mean follow-up 59 +/- 31 months). Only 1% of patients had severe RD 60 months after HT. Independent predictors of RD 24 months after HT were older age (odds ratio [OR] 1.1 [95% confidence interval (95% CI) 1.0-1.1]; p = 0.001), male sex (OR 3.3 [95% CI 1.3-8.1]; p = 0.008), pre-1998 immunosuppressive protocol (OR 2.8 [95% CI 1.4-5.4]; p = 0.003), and creatinine level 1 month after HT (OR 3.2 [95% CI 1.0-5.4]; p < 0.0001). CONCLUSIONS: The cumulative incidence of RD in HT patients treated with calcineurin inhibitors increased with time after HT. Age, male sex, an immunosuppressive protocol with relatively high cyclosporine levels and creatinine level 1 month after HT were independent predictors of the presence of RD 24 months after HT.

Long-term results of heart transplant in recipients older and younger than 65 years: a comparative study of mortality, rejections, and neoplasia in a cohort of 445 patients.

BACKGROUND: Whether being older than 65 years should be considered an absolute counterindication to heart transplant (HT), as it is in some centers, is controversial. In our centre, patients older than 65 years are accepted for HT if they satisfy stringent conditions. The aim of this study was to examine whether heart recipients older than 65 years have a greater risk of rejection, neoplasia, or mortality than younger ones. METHODS: We studied 445 patients who underwent HT between April 1991 and December 2003, 42 of whom were older than 65 years and 403 who were 65 years or younger. The parameters evaluated were the cumulative incidences of neoplasias and rejections (ISHLT grade > or = 3A), and the survival rates 1 month, 1 year, and 5 years post-HT. RESULTS: The two groups had similar percentages of patients with at least one rejection episode (< or =65 years 56.9%, >65 years 51.3%; P > .05), and although there were proportionally almost twice as many tumors in the older group (14.2%) as in the younger (7.9%), this difference was not statistically significant either. Nor were there any significant differences in survival, the 1-month, 1-year, and 5-year rates being 87.8%, 82.1%, and 68.8%, respectively, in the younger group and 85.7%, 78.6%, and 73.4%, respectively, in the older. CONCLUSIONS: Among carefully selected patients aged more than 65 years, HT can be performed without incurring greater risk of rejection, malignancy, or death than is found among recipients younger than 65 years.

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.

Severe cardiac allograft dysfunction without endomyocardial biopsy signs of cellular rejection: incidence and management.

Acute dysfunction of cardiac allograft without evidence of cellular rejection is a potentially fatal complication of heart transplantation that suggests a humoral origin. In clinical practice, humoral rejection (HR) is suspected when there is evidence of severe allograft dysfunction but endomyocardial biopsy (EMB) shows no evidence of cellular rejection. Between April 1991 and August 2003, 12 patients (2.74%) among 438 heart transplants displayed this condition. Time post-heart transplant (HT) was 21.3 +/- 24.7 months (range 2 to 72 months). Immunofluorescence studies using classic markers were negative. All patients were treated with methylprednisolone "bolus" and plasmapheresis until clinical recovery, after which their immunosuppressive regimens were modified. Eleven of the 12 patients recovered satisfactory allograft function. In this series the incidence of suspected HR was low. Unlike other studies, we observed HR not only soon but also even years after HT. Plasmapheresis seems to be an effective treatment.