Randomized trials showed that mTOR inhibitors prevent early development of cardiac allograft vasculopathy (CAV). However, the action of these drugs on CAV late after transplant is controversial, and their effectiveness for CAV prevention in clinical practice is poorly explored. In this observational study we included 143 consecutive heart transplant recipients who underwent serial intravascular ultrasound (IVUS), receiving either everolimus or mycophenolate as adjunctive therapy to cyclosporine. Ninety-one recipients comprised the early cohort, receiving IVUS at weeks 3–6 and year 1 after transplant, and 52 the late cohort, receiving IVUS at years 1 and 5 after transplant. Everolimus independently reduced the odds for early CAV (0.14 [0.01–0.77]; p = 0.02) but it did not appear to influence late CAV progression. High-dose statins were found to be associated with reduced CAV progression both early and late after transplant (p ≤ 0.05). Metabolic abnormalities, such as high triglycerides, were associated with late, but not with early CAV progression. By highlighting a differential effect of everolimus and metabolic abnormalities on early and late changes of graft coronary morphology, this observational study supports the hypothesis that everolimus may be effective for CAV prevention but not for CAV treatment, and that risk factors intervene in a time-dependent sequence during CAV development.

Coronary allograft vasculopathy (CAV) is the main cause of graft failure after heart transplantation (HT). Clinical trials showed that everolimus (EVE) prevents early CAV. However, if this property can be replicated in clinical practice and on long-term CAV progression is unexplored.

Pulmonary hypertension (PH) in heart transplant (HT) candidates is associated with increased post-transplant mortality, and may represent a contraindication to HT. Vasorectivity studies test PH reversibility, but how their results match post-HT outcome is unexplored. In addition, data guiding organ allocation in recipients with PH are lacking.

Cyclosporine (CsA) nephrotoxicity negatively impacts long-term management of heart transplant (HT) recipients. Thus, we designed the SHIRAKISS randomized study to compare two CNI lowering strategies on the progression of renal dysfunction (NCT00420537). Herein we report the 24 months outcome of the patients initially randomized in the study.

Cancer is a leading cause of death in adult heart transplant (HT) recipients. Whereas large registries identified several risk factors involved in the development of post-transplant malignancies, data about factors influencing the outcome after malignancy onset are lacking.

Statin therapy reduces cardiac allograft vasculopathy (CAV) development and cardiovascular events in heart transplant (HT) recipients. However, the optimal lipid target to be aimed at in these patients is unknown. In addition, safety concerns regarding the interaction between statins and immunosuppressive drugs may limit the use of high statins doses, potentially reducing the efficacy of this therapy. This randomized study aims to assess safety and efficacy of a fixed high dose of fluvastatin (80mg) vs. a low-density-lipoproteins (LDL)-driven approach based on low dose (20mg) adjustments targeting 100mg/dl.

Although the concept of antibody mediated rejection (AMR) has been associated with poor outcome in heart transplant (HT) recipients since long ago, only recently pathological criteria for its diagnosis have been standardized. Nevertheless, clinical correlates of criteria for AMR in endomyocardial biopsies (EMB) are poorly characterized. In this report, we analyzed the association of intravascular C4d detection with morphological criteria for AMR, hemodynamic features, and survival in mid and long-term HT recipients.

Potena, L; Fabbri, F; Magnani, G; Coccolo, F; Fallani, F; Masetti, M; Russo, A; Arpesella, G; Grigioni, F; Branzi, A Author Information

Assay of plasma natriuretic peptides and measurements gained from right heart catheterization (RHC) bear independent prognostic informations in patients with heart failure (HF). However, their interplay in stratifying the outcome in patients referred for heart transplantation (HT) is not fully elucidated.

Although cytomegalovirus (CMV) infection is a recognized risk factor for cardiac allograft vasculopathy (CAV), it is still unknown which CMV-prevention strategy is more effective in delaying CAV development. Thus, we designed this observational study to compare the effect of pre-emptive vs. prophylaxis approach on intravascular ultrasound (IVUS)-detected CAV.

Although statins have proven efficacy in lowering lipids and improving survival in heart transplantation (HT) recipients, potential drug interactions may limit efficacy and reduce tolerability. This observational study explored the efficacy and tolerability of ezetimibe (10 mg/day) combined with simvastatin (10 or 20 mg/day) prescribed to HT recipients with intolerance to statins (n = 11) or inadequate lipid control despite high-dose statins (n = 14). Substantial reductions in lipid levels were apparent after 2 months (total cholesterol, -22%; low-density lipoproteins, -28%; triglycerides, -31%) and were maintained at 6 months. Reductions were significant in both subgroups of recipients; the vast majority (12 of 14, 85%) of recipients with a history of statins intolerance were able to tolerate ezetimibe plus low-dose simvastatin. This study provides suggestive evidence that treatment with ezetimibe plus low-dose simvastatin is well tolerated by HT recipients and may be effective for treatment of dyslipidemia in HT recipients with statins intolerance or resistance.

Purpose: Although heart transplantation (HT) represents the best therapeutic approach for end-stage chronic heart failure (CHF), the limited number of donors and the costs related to this procedure necessarily imply careful selection of the most appropriate candidates. Therefore, given increasing prevalence of CHF with age, the weight of age in the decision-making process for the selection of HT candidates requires cautious evaluation.

Purpose: Although improvement of immunosuppressive therapy, acute rejection is still a major threat in heart transplant recipients. In the effort to simplify diagnosis, ISHLT rejection criteria have been revised by combining previous grades 1A, 1B and 2 in only one category, named grade 1R. The clinical correlate of this new classification is that only grades ≥3A (now 2R and 3R) require treatment. However, many transplant centres modulate immunosuppression (e.g. stop steroids tapering, increase cyclosporine, or oral steroid load) when mild diffuse (i.e. 1B) grades are detected. Moreover, recent studies from our and others groups suggest that 1B has a genomic signature indicating a greater immunological activation as compared to 1A, potentially triggering more severe rejections. This report investigates whether 1B and 2 grades have different clinical relevance as compared to 1A, by analyzing rates of progression in biopsies collected in two transplant centres with different attitude towards mild rejection treatment