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In this study Bioelectrical Impedance Analysis was performed in 5 patients with end stage heart failure in whom a left ventricular assist device (Novacor) was successfully implanted. Whole body measurements of bioelectrical indices resistance and reactance were taken before surgery and 3, 7, 12, and 15 days after it. After surgery there was a significant decrease in reactance, indicating a shift of body fluids from intra- to extra-cellular space.

Objectives: Increasing knowledge is required for a better comprehension of the etiology of thoracic aortic aneurysm (TAA). The aim of this study was to highlight the modulations in vascular cell phenotypes, including myofibroblasts (MFs), in human TAA specimens compared to healthy aortas. Methods: histology, RT-PCR and immunohistochemical analysis of a panel of molecules, including EDA Fibronectin (Fn), smoothelin, CD34 and alpha-smooth muscle actin (alpha-SMA), selected on the basis of their informative potential as markers of smooth muscle cells (SMCs) and MF phenotypic modulation, were performed on all samples. Results: The media of TAAs was characterized by the absence of smoothelin, the unaltered expression of alpha-SMA accompanied by an alteration of its distribution pattern, and by the activated expression of the ED-A isoform of Fn. We found a concentration of round-shaped cells exclusively in the adventitia and in the perivascular tissue of TAAs, also rich in vasa vasorum, largely expressing alpha-SMA, while a sub-population also expressed ED-A Fn and CD34. CD34 was expressed by several cells in the intima of TAAs, together with cells expressing cytoplasmatic EDA Fn and alpha-SMA in comparison to healthy aortas. Conclusion: TAA specimens show an altered expression and localization of SMC and MF differentiation markers in comparison to healthy aortas, with possible implications on remodeling.

The coronavirus disease 2019 (COVID-19) pandemic has profoundly affected all health care professionals. The outbreak required a thorough reorganization of the Italian regional local health care system to preserve resources such as ventilators, beds in intensive care units and surgical and anaesthesiological staff. Levels of priority were created, together with a rigorous triage procedure for patients with COVID-19, which led to postponement of all elective procedures. Urgent cases were discussed with the local heart team and percutaneous approaches were selected as the first treatment option to reduce hospital stay. COVID-19 and COVID-19-free pathways were created, including adequate preparation of the operating room, management of anaesthesiological procedures, transportation of patients and disinfection. It was determined that patients with chronic diseases were at increased risk of adverse outcomes. Systemic inflammation, cytokine storm and hypercoagulability associated with COVID-19 increased the risk of heart failure and cardiac death. In this regard, the early use of extracorporeal membrane oxygenation could be life-saving in patients with severe forms of acute respiratory distress syndrome or refractory heart failure. The goal of this paper was to report the Italian experience during the COVID-19 pandemic in the setting of cardiovascular surgery., Coronavirus disease 2019 (COVID-19) is a new pandemic infectious disease caused by a novel beta-coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1].

Background: Early pathogenesis of diabetic cardiomyopathy (DMCM) may involve lipotoxicity of cardiomyocytes in the context of hyperglycemia. There are many preclinical studies of DMCM pathogenesis, but the human evidence is still poorly understood. Objectives: By using a nondiabetic mellitus (non-DM) heart transplanted (HTX) in diabetes mellitus (DM) recipients, this study conducted a serial study of human heart transplant recipients evaluating cardiac effects of diabetic milieu (hyperglycemia and insulin resistance) on lipotoxic-mediated injury. We evaluated cardiomyocyte morpho-pathology by seriated biopsies of healthy implanted hearts in DM recipients during 12-month follow-up from HTX. Because metformin reduces ectopic lipid accumulation, we evaluated the effects of the drug in a nonrandomized subgroup. Methods: The DMCM-AHEAD (Diabetes and Lipid Accumulation and Heart Transplant) prospective ongoing study (NCT03546062) evaluated 158 first HTX recipients (82 non-DM, 76 DM of whom 35 [46%] were receiving metformin). HTX recipients were undergoing clinical standard evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsies). Biopsies evaluated immune response, Oil Red-O staining, ceramide, and triacylglycerol levels. Lipotoxic factors and insulin resistance were evaluated by reverse transcriptase–polymerase chain reaction. Results: There was a significant early and progressive cardiomyocyte lipid accumulation in DM but not in non-DM recipients (p = 0.019). In the subgroup receiving metformin, independently from immunosuppressive therapy that was similar among groups, lipid accumulation was reduced in comparison with DM recipients not receiving the drug (hazard ratio: 6.597; 95% confidence interval: 2.516 to 17.296; p < 0.001). Accordingly, lipotoxic factors were increased in DM versus non-DM recipients, and, relevantly, metformin use was associated with fewer lipotoxic factors. Conclusions: Early pathogenesis of human DMCM started with cardiomyocyte lipid accumulation following HTX in DM recipients. Metformin use was associated with reduced lipid accumulation independently of immunosuppressive therapy. This may constitute a novel target for therapy of DMCM.

Background The pathogenesis of experimental diabetic cardiomyopathy may involve the activator protein 1 (AP-1) member, JunD. Using non-diabetic heart transplant (HTX) in recipients with diabetes, we examined the effects of the diabetic milieu (hyperglycemia and insulin resistance) on cardiac JunD expression over 12 months. Because sodium/glucose cotransporter-2 inhibitors (SGLT2i) significantly reverse high glucose-induced AP-1 binding in the proximal tubular cell, we investigated JunD expression in a subgroup of type 2 diabetic recipients receiving SGLT2i treatment. Methods We evaluated 77 first HTX recipients (40 and 37 patients with and without diabetes, respectively). Among the recipients with diabetes, 17 (45.9%) were receiving SGLT2i treatment. HTX recipients underwent standard clinical evaluation (metabolic status, echocardiography, coronary computed tomography angiography, and endomyocardial biopsy). In the biopsy samples, we evaluated JunD, insulin receptor substrates 1 and 2 (IRS1 and IRS2), peroxisome proliferator-activated receptor-γ (PPAR-γ), and ceramide levels using real-time polymerase chain reaction and immunofluorescence. The biopsy evaluations in this study were performed at 1–4 weeks (basal), 5–12 weeks (intermediate), and up to 48 weeks (final, end of 12-month follow-up) after HTX. Results There was a significant early and progressive increase in the cardiac expression of JunD/PPAR-γ and ceramide levels, along with a significant decrease in IRS1 and IRS2 in recipients with diabetes but not in those without diabetes. These molecular changes were blunted in patients with diabetes receiving SGLT2i treatment. Conclusion Early pathogenesis in human diabetic cardiomyopathy is associated with JunD/PPAR-γ overexpression and lipid accumulation following HTX in recipients with diabetes. Remarkably, this phenomenon was reduced by concomitant therapy with SGLT2i, which acted directly on diabetic hearts.

Big Data, and the derived analysis techniques, such as artificial intelligence and machine learning, have been considered a revolution in the modern practice of medicine. Big Data comes from multiple sources, encompassing electronic health records, clinical studies, imaging data, registries, administrative databases, patient-reported outcomes and OMICS profiles. The main objective of such analyses is to unveil hidden associations and patterns. In cardiac surgery, the main targets for the use of Big Data are the construction of predictive models to recognize patterns or associations better representing the individual risk or prognosis compared to classical surgical risk scores. The results of these studies contributed to kindle the interest for personalized medicine and contributed torecognize the limitations of randomized controlled trials in representing the real world. However, the main sources of evidence for guidelines and recommendations remain RCTs and meta-analysis. The extent of the revolution of Big Data and new analytical models in cardiac surgery is yet to be determined.

Objectives: Dilated cardiomyopathy (DCM) is characterized by a specific transcriptome. Since the DCM molecular network is largely unknown, the aim was to identify specific disease-related molecular targets combining an original machine learning (ML) approach with protein-protein interaction network. Methods: The transcriptomic profiles of human myocardial tissues were investigated integrating an original computational approach, based on the Custom Decision Tree algorithm, in a differential expression bioinformatic framework. Validation was performed by quantitative real-time PCR. Results: Our preliminary study, using samples from transplanted tissues, allowed the discovery of specific DCM-related genes, including MYH6, NPPA, MT-RNR1 and NEAT1, already known to be involved in cardiomyopathies Interestingly, a combination of these expression profiles with clinical characteristics showed a significant association between NEAT1 and left ventricular end-diastolic diameter (LVEDD) (Rho = 0.73, p = 0.05), according to severity classification (NYHA-class III). Conclusions: The use of the ML approach was useful to discover preliminary specific genes that could lead to a rapid selection of molecular targets correlated with DCM clinical parameters. For the first time, NEAT1 under-expression was significantly associated with LVEDD in the human heart.

Aims The aim of this study was to investigate prospectively the effect of sacubitril/valsartan in advanced heart failure (HF) patients in waiting list for heart transplantation (HT) and the effect on physical frailty (PF). Methods and results We treated 37 consecutive patients with advanced HF with sacubitril/valsartan. Patients were followed up until HT, device implant, or last follow‐up visit after 2 years of follow‐up. At baseline, mean New York Heart Association (NYHA) class was 3.1 ± 0.4, with 64.9% in NYHA III and 35.1% NYHA IIIB. Left ventricular ejection fraction was 23.5 ± 5.8%, VO2 max was 10.3 ± 2.3 mL/kg/min, cardiac index was 2.3 ± 0.5 L/min/m2, and N‐terminal pro‐brain natriuretic peptide (NT‐pro‐BNP) was 4943.0 ± 5326.8 pg/mL. After a mean follow‐up of 17.1 ± 4.4 months, no deaths were observed, but NYHA class improved significantly with 56.8% in NYHA II, 40.5% in NYHA III, and 2.7% in NYHA IIIB (P < 0.001). VO2 max and 6 min walk test (6MWT) increased, whereas pulmonary systolic blood pressure, E/E′, VE/VCO2 slope, and NT‐pro‐BNP decreased. At right heart catheterization performed after 1 year of follow‐up, cardiac index and pulmonary vascular resistance remained stable, while a decrease in systolic pulmonary artery pressure and pulmonary capillary wedge pressure is observed. Furosemide dosage decrease from 102.7 ± 69.4 to 78.7 ± 66.3 mg (P = 0.040). PF decreased from 3.35 ± 1.0 at baseline to 1.57 ± 1.3 at the end of follow‐up (P < 0.001), with a reduction in all PF domains. Conclusions Our study showed a rapid improvement in PF in HT waiting list patients treated with sacubitril/valsartan. The improvement in all PF domains was paralleled by VO2 and 6MWT increase and together with an NT‐pro‐BNP reduction constant over the follow‐up.

Rationale About 50% of hospitalized coronavirus disease 2019 (COVID-19) patients with diabetes mellitus (DM) developed myocardial damage. The mechanisms of direct SARS-CoV-2 cardiomyocyte infection include viral invasion via ACE2-Spike glycoprotein-binding. In DM patients, the impact of glycation of ACE2 on cardiomyocyte invasion by SARS-CoV-2 can be of high importance. Objective To evaluate the presence of SARS-CoV-2 in cardiomyocytes from heart autopsy of DM cases compared to Non-DM; to investigate the role of DM in SARS-COV-2 entry in cardiomyocytes. Methods and results We evaluated consecutive autopsy cases, deceased for COVID-19, from Italy between Apr 30, 2020 and Jan 18, 2021. We evaluated SARS-CoV-2 in cardiomyocytes, expression of ACE2 (total and glycosylated form), and transmembrane protease serine protease-2 (TMPRSS2) protein. In order to study the role of diabetes on cardiomyocyte alterations, independently of COVID-19, we investigated ACE2, glycosylated ACE2, and TMPRSS2 proteins in cardiomyocytes from DM and Non-DM explanted-hearts. Finally, to investigate the effects of DM on ACE2 protein modification, an in vitro glycation study of recombinant human ACE2 (hACE2) was performed to evaluate the effects on binding to SARS-CoV-2 Spike protein. The authors included cardiac tissue from 97 autopsies. DM was diagnosed in 37 patients (38%). Fourth-seven out of 97 autopsies (48%) had SARS-CoV-2 RNA in cardiomyocytes. Thirty out of 37 DM autopsy cases (81%) and 17 out of 60 Non-DM autopsy cases (28%) had SARS-CoV-2 RNA in cardiomyocytes. Total ACE2, glycosylated ACE2, and TMPRSS2 protein expressions were higher in cardiomyocytes from autopsied and explanted hearts of DM than Non-DM. In vitro exposure of monomeric hACE2 to 120 mM glucose for 12 days led to non-enzymatic glycation of four lysine residues in the neck domain affecting the protein oligomerization. Conclusions The upregulation of ACE2 expression (total and glycosylated forms) in DM cardiomyocytes, along with non-enzymatic glycation, could increase the susceptibility to COVID-19 infection in DM patients by favouring the cellular entry of SARS-CoV2.

Claudio Napoli,1 Paola Bontempo,2 Vittorio Palmieri,3 Enrico Coscioni,4 Ciro Maiello,5 Francesco Donatelli,6 Giuditta Benincasa1 1Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, 80138, Italy; 2Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Naples, 80138, Italy; 3Department of Cardiac Surgery and Transplantation, Heart Transplantation Unit in Adults of the ‘Ospedali dei Colli Monaldi-Cotugno-CTO’, Naples, Italy; 4Department of Cardiac Surgery, Azienda Ospedaliera Universitaria San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy; 5Department of Cardiovascular Surgery and Transplants, Monaldi Hospital, Azienda dei Colli, Naples, Italy; 6Chair of Cardiac Surgery, Department of Cardiothoracic Center, Istituto Clinico Sant’Ambrogio, University of Milan, Milan, ItalyCorrespondence: Giuditta BenincasaDepartment of Advanced Medical and Surgical Sciences (DAMSS), University of Campania “Luigi Vanvitelli”, Naples, ItalyTel +390815667916Email giuditta.benincasa@unicampania.itAbstract: Despite the current reductionist approach providing an optimal indication for diagnosis and treatment of patients with heart failure with reduced ejection fraction (HFrEF), there are no standard pharmacological therapies for heart failure with preserved ejection fraction (HFpEF). Although in its infancy in cardiovascular diseases, the epigenetic-based therapy (“epidrugs”) is capturing the interest of physician community. In fact, an increasing number of controlled clinical trials isevaluating the putative beneficial effects of: 1) direct epigenetic-oriented drugs, eg, apabetalone, and 2) repurposed drugs with a possible indirect epigenetic interference, eg, metformin, statins, sodium glucose transporter inhibitors 2 (SGLT2i), and omega 3 polyunsaturated fatty acids (PUFAs) in both HFrEF and HFpEF, separately. Apabetalone is the first and unique direct epidrug tested in cardiovascular patients to date, and the BETonMACE trial has reported a reduction in first HF hospitalization (any EF value) and cardiovascular death in patients with type 2 diabetes and recent acute coronary syndrome, suggesting a possible role in secondary prevention. Patients with HFpEF seem to benefit from supplementation to the standard therapy with statins, metformin, and SGLT2i owing to their ability in reducing mortality. In contrast, the vasodilator hydralazine, with or without isosorbide dinitrate, did not provide beneficial effects. In HFrEF, metformin and SGLT2i could reduce the risk of incident HF and mortality in affected patients whereas clinical trials based on statins provided mixed results. Furthermore, PUFAs diet supplementation was significantly associated with reduced cardiovascular risk in both HFpEF and HFrEF. Future large trials will reveal whether direct and indirect epitherapy will remain a work in progress or become a useful way to customize the therapy in the real-world management of HFpEF and HFrEF. Our goal is to discuss the recent advancement in the epitherapy as a possible way to improve personalized therapy of HF.Keywords: heart failure, personalized therapy, epidrugs

Background: The aim of this study was to assess the effect of continuing immune suppressive therapy in solid organ transplant recipients (SOTR) with coronavirus disease 2019 (COVID-19). Methods: Systematic review and meta-analysis of data on 202 SOTR with COVID-19, published as case reports or case series. We extracted clinical, hemato-chemical, imaging, treatment, and outcome data. Results: Most patients were kidney recipients (61.9%), males (68.8%), with median age of 57years. The majority was on tacrolimus (73.5%) and mycophenolate (65.8%). Mortality was 18.8%, but an equal proportion was still hospitalized at last follow up. Immune suppressive therapy was withheld in 77.2% of patients, either partially or completely. Tacrolimus was continued in 50%. One third of survivors that continued immunosuppressants were on dual therapy plus steroids. None of those who continued immunosuppressants developed critical COVID-19 disease. Age (OR 1.07, 95% CI 1-1.11, P=.001) and lopinavir/ritonavir use (OR 3.3, 95%CI 1.2-8.5, P=.013) were independent predictors of mortality while immunosuppression maintenance (OR 0.067, 95% CI 0.008-0.558, P=.012) and tacrolimus continuation (OR 0.3, 95% CI 0.1-0.7, P=.013) were independent predictors of survival. Conclusions: Our data suggest that maintaining immune suppression might be safe in SOTR with moderate and severe COVID-19. Specifically, receiving tacrolimus could be beneficial for COVID-19 SOTR. Because of the quality of the available evidence, no definitive guidance on how to manage SOTR with COVID-19 can be derived from our data.

BACKGROUND: Depression is highly prevalent in Heart Failure (HF). Treatment with sacubitril/valsartan improved quality of life and survival in HF patients. Aim of the study was to investigate prospectively the effect of sacubitril/valsartan on depression in advanced HF patients in waiting list for heart transplant (HT). METHODS: 37 consecutive patients with advanced HF in waiting list for HT were treated with sacubitril/valsartan. We analyzed data derived from the assessment performed the year before the beginning of sacubitril/valsartan, at study entry, and at one year of follow-up. Depression was assessed with Beck Depression Inventory II (BDI) scale. Cognitive function were assessed with Mini-Mental State Examination (MMSE). Functioning was evaluated measuring meters at 6 Minute Walking Test (6MWT) and maximum rate of oxygen consumption (VO2 max). RESULTS: At baseline, 64.9% of HF patients were in NYHA III and 35.1% NYHA IIIB, BDI was 15.2 ± 5.2 with 59.5% of patients with a score > 13. MMSE was 27.8 ± 2.6. After one year of follow-up NYHA class improved significantly, with 56.8% in NYHA II, 40.5% in NYHA III and 2.7% NYHA in IIIB (p 13. MMSE remain stable (28.2 ± 2.1) (p = 0.104). No statistical differences are observed between data collected in the evaluation 1-year before and soon before treatment with sacubitril/valsartan. Multivariate regression analysis demonstrate a relationship between reduction in BDI-II score and improvement in six-minute walking test independently by the effect of sex, age, selective serotonin reuptake inhibitors, VO2 max, NT-proBNP, PAPs, NYHA class differences evaluated at follow-up versus baseline. CONCLUSIONS: Our study showed a reduction in depressive symptomatology in heart transplant waiting list patients treated with sacubitril/valsartan. The improvement in depressive symptomatology was paralleled by 6MWT increase in the follow-up.

Purpose Candidate selection and donor allocation should promote equitable access to heart transplantation (HTX) according to patients’ needs, avoiding HTX in patients (pts) who are too well or too sick to get benefit. The national HTX database was analyzed to identify which variables were related to the competing events of getting HTX or dying on the waiting list (WL), and to post-transplant survival. Methods Pts aged 14 years or more, who were listed for primary HTX from May 2012 and December 2016, were followed until January 2018, death or delisting for worsening. The incidence of death on the WL or of HTX were analyzed according to Aalen-Johansen method. Post-HTX survival was evaluated with Kaplan-Meyer method. Univariate and multivariate cause-specific Cox proportional hazard model was used to identify candidates’ variables related to access to HTX or death on the WL, and preoperative recipients’ variables related to post-HTX mortality. Results Of 1611 listed pts (males 78%, median age 54 y), 10% died and 45% received HTX within 1 year. At the end of follow-up 932 pts (males 73%, median age 53y) had undergone HTX: 13% were bridged with LVAD, 17% were on short-term mechanical circulatory support (MCS), 28% received HTX with emergency heart allocation, and 42% were medically treated outpatients. One-, 3- and 5-years post-HTX survival was 78%, 72% and 69% respectively. Variables which were significantly related to study outcomes at univariate and multivariate analysis are shown in the Table. Conclusion The higher risk of WL mortality associated with variables that reflect disease severity and medical urgency is limited by allocation rules. Blood type 0 pts are disadvantaged in the current system. 1-y probability of both getting HTX and dying on the WL was lower in LVAD pts. Short term MCS and emergency HTX were associated with higher rate of death after HTX only at univariate analysis: predictors of post-HTX death should be analyzed separately in these high-risk subgroups.

Introduction Berlin Heart EXCOR® pediatric ventricular assist device is a mechanical circulatory support device currently used in pediatric patients. Sotos syndrome is a well-described multiple anomaly syndrome characterized by overgrowth, distinctive craniofacial appearance, cardiac abnormalities, and variable learning disabilities. Case presentation We describe a 7-year-old female Caucasian child with classic Sotos syndrome features subjected to implantation of Berlin Heart EXCOR® pediatric biventricular assist device mechanical support. A heart transplant was carried out after a support time of 459 days. After 5 years of follow-up, our patient is clinically stable and the performance of the transplanted heart is excellent. Conclusion This case confirms that Berlin Heart EXCOR® pediatric ventricular assist device can provide satisfactory and safe circulatory support for children with end-stage heart diseases, even in those with Sotos syndrome. The syndrome is not a contraindication to implantation, since the complications are the same as those observed in patients without the syndrome and the prognosis is not affected by the disease.

Chronic hepatitis B is prevalent in the transplant setting and may cause significant complications. Effective control of viral replication is needed. Besides lamivudine, very little data are available on safety and efficacy of other drugs. We describe our experience with adefovir dipivoxil (ADV) in eight heart transplant recipients. Studies included a baseline liver biopsy, thrice-monthly clinical, biochemical, and virological evaluations, including genotyping and viral load, polymerase gene sequencing for resistance mutations, liver and kidney function tests, and liver ultrasound. Of eight patients, six had fibrosis score ≤2 and negative HBeAg and seven had hepatitis B virus (HBV) genotype D. Upon ADV start, median HBV-DNA was 5.8 logs IU/mL and alanine aminotransferase (ALT) levels were mostly normal. All patients had prior mild-to-moderate renal functional impairment. Seven of eight patients started ADV after a previous course of lamivudine. Five of these seven patients became HBV-DNA undetectable within eight months. One patient with low baseline viremia started ADV de novo and suppressed HBV-DNA. Median treatment duration was 66 months. ADV daily dose was halved in one patient due to renal function worsening. No ALT flares, hypophosphatemia, liver decompensation, liver cancer, or emergence of resistance was observed. Our data suggest that ADV may be a safe and effective rescue treatment for heart transplant recipients with lamivudine-resistant chronic hepatitis B.

In the last decades, due to remarkable technological improvements in ceramics production cycles and materials, the manufacturing and the commercialization of large-sized ceramic slabs have risen. While some phases of the process are well defined, there are some routines that lack systematic procedures and rely uniquely on the internal know-how of the single companies. In particular, this paper focuses on the handling and transportation of large-sized ceramic slabs, which are, in the vast majority of cases, performed by suction cups-based gripping devices. The scope of this paper is to investigate how the type of suction cup pattern and its geometrical parameters affect slab stresses and deformations and to provide a guideline for the choice of the pattern, in order to cope with some critical aspects associated with wide surface and small thickness of the slabs. In particular, some of the most common large slab sizes and thicknesses available on the market are considered, and the most suitable suction cup patterns (and their geometrical parameters) for handling them are evaluated in order to minimize slab stresses and deformations.

The aim of the study was to analyze possible correlations between strain echocardiography (STE) and PET myocardial perfusion in a population of heart transplantation (HTx) recipients showing preserved left ventricular (LV) ejection fraction. By STE, LV global longitudinal strain (LV GLS) was lower in HTx. PET showed no transient or chronic ischemia in 83 of 115 HTx (73%). Fixed perfusion defects were observed in 17% of HTx and reversible ischemia in 10%. Significant coronary stenosis was observed only in 10 cases. GLS was independently associated with age at HTx and fixed perfusion defects (HR 0.41; P

We sought to analyze the prevalence, clinical course, and risk profile of left ventricular systolic dysfunction in adolescents with idiopathic dilated cardiomyopathy. Patients with clinical onset at 19 years (n = 14) of age and/or patients followed up for or =250 pg/ml (are under the curve 0.88) showed 100% sensitivity, 77% specificity, 62% positive predictive value, and 100% negative predictive value. In conclusion, compared to other clinical, echocardiographic, and biochemical parameters, the combination of advanced NYHA class, electrocardiographic atrial enlargement, and NT-pro-BNP > or =250 pg/ml seem to better predict the risk of adverse events in adolescent with long-term systolic dysfunction.

Background: Obesity, dyslipidemia, hypertension, and diabetes mellitus are common features after heart transplantation and they lead to coronary artery disease and graft loss. Aim: To determine the effects of a dietary intervention on nutritional status and metabolic outcome of two groups enrolled during or after the first year from the transplant. Methods: Forty two subjects (mean age 51.36±12.4 yr) were studied; 20 were enrolled during the first year by the transplant, 22 were enrolled after the first year from the transplant (7.9±3.86 and 56.86±38.6 months after surgery, respectively). According to diet compliance both groups were divided into two subgroups and they were prospectively followed for 4 years. Anthropometric measurements, biochemical nutritional markers, and dietary records were collected at baseline (T0) and after a 12-month follow-up period (T12) and a 48-month follow-up period (T48). Body composition was performed at T0 and T12. Results: Diet compliance was associated with a decrease in total cholesterol, triglycerides and glucose plasma level and with a weight loss mainly due to a decrease in fat mass. Conclusion: Our study shows the efficacy of dietary intervention to obtain an early and late weight and metabolic control after heart transplant.

Aims In dilated cardiomyopathy (DCM), attenuation of left atrial (LA) booster pump function has been observed, and attributed both to altered LA loading conditions owing to left ventricular (LV) diastolic dysfunction and to LA involvement in the myopathic process. The aim of the present study was to detect LA systolic dysfunction in DCM using speckle-tracking two-dimensional strain echocardiography (2DSE), and to assess the effects of cardiac resynchronization therapy (CRT) on LA myocardial strain during 6 month follow-up. Methods and results A total of 90 patients (aged, 52.4+10.2 years) with either idiopathic (n = 47) or ischaemic (n = 43) DCM underwent standard Doppler echo and 2DSE analysis of atrial longitudinal strain in the basal segments of LA septum and LA lateral wall, and in LA roof. The two groups were comparable for clinical variables (NYHA class: III in 72.2%; IV in 27.8%). LV volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler transmitral inflow measurements. LA diameter and maximal volume were also similar between the two groups. Conversely, LA active emptying volume and fraction were both lower in patients with idiopathic DCM. Peak systolic myocardial atrial strain was significantly compromised in patients with idiopathic DCM compared with ischaemic DCM in all the analysed atrial segments (P , 0.001). At follow-up, 64 patients (71.1%) (37 idiopathic and 27 ischaemic) were responders, and 26 (28.9%) (10 idiopathic; 16 ischaemic) were non-responders to CRT (responder: decrease of LV end-systolic volume .15%). A significant improvement in LA systolic function was obtained only in patients with ischaemic DCM responders to CRT (P , 0.001). By multivariable analysis, in the overall population, it was found that ischaemic aetiology of DCM (b-cofficient = 0.62; P , 0.0001) and positive response to CRT (b-cofficient = 0.42; P , 0.01) were the only independent determinants of LA lateral wall systolic strain. Conclusions Two-dimensional strain represents a promising non-invasive technique to assess LA atrial myocardial function in patients with DCM. LA pump and reservoir function at baseline and after CRT are more depressed in idiopathic compared with ischaemic DCM patients. Future longitudinal studies are warranted to understand further the natural history of LA myocardial function, the extent of reversibility of LA dysfunction with CRT, and the possible prognostic impact of such indexes in patients with congestive heart failure.

Objective: To review outcomes and quality of life following two surgical strategies for severe left ventricular dysfunction due to ischemic dilated cardiomyopathy. Methods: Hospital and follow-up records of 111 patients with extensive ischemic cardiomyopathy (mean age 57.3G 8.4) referring to our institution between January 1996 and December 2003 were reviewed. Group A included 42 patients (mean age 62.4G7.9) with morphological and functional cardiac parameters allowing for ventricular restoration (including endoventricular circular patch plasty, coronary artery by-pass grafting, and, when needed, mitral surgery). Group B included 69 patients (mean age 54.3G7.2), undergoing cardiac transplantation. Hospital mortality, treatment-related late mortality, incidence of cardiac events, freedom from cardiac failure, freedom from hospital re-admission, functional recovery at follow-up (3075.2 pts/months; 100% complete) and quality of life (WHOQOL test) were assessed. Results: Hospital mortality was 19% in group A and 8.7% in group B (PZ0.143). No treatment-related late deaths were observed in group A, while six deaths (9.5%) occurred in group B (PZ0.063). Incidence of cardiac events was comparable. At 60 months, freedom from cardiac failure was 93.5G0.04 and 86.2G0.05%, respectively (PZ0.23), freedom from hospital re-admission was 93.5G0.04 and 61.3G0.07% (PZ0.002). Exertion dyspnea was present in 40% patients in group A versus 13% in group B (PZ0.006). WHOQOL test showed a satisfying quality of life in both groups, although patients undergoing restoration reached higher scores in the psychological and social domains. Conclusions: Selected patients with ischemic cardiomyopathy, potentially eligible for transplantation, can be managed by ventricular restoration. In those patients post-operative quality of life is satisfactory, with comparable survival and low risk of re-hospitalization. q 2004 Elsevier B.V. All rights reserved.

Background Bartonella henselae is the etiologic agent of cat-scratch disease. B. henselae infections are responsible for a widening spectrum of human diseases, although often symptomless, ranging from self-limited to life-threatening and show different courses and organ involvement due to the balance between host and pathogen. The role of the host immune response to B. henselae is critical in preventing progression to systemic disease. Indeed in immunocompromised patients, such as solid organ transplant patients, B. henselae results in severe disseminated disease and pathologic vasoproliferation. The purpose of this study was to determine the seroprevalence of B. henselae in patients awaiting heart transplant compared to healthy individuals enrolled in the Regional Reference Laboratory of Transplant Immunology of Second University of Naples. Methods Serum samples of 38 patients awaiting heart transplant in comparison to 50 healthy donors were examined using immunfluorescence assay. Results We found a B. henselae significant antibody positivity rate of 21% in patients awaiting heart transplant ( p = 0.002). There was a positive rate of 8% ( p > 0.05) for immunoglobulin (Ig)M and a significant value of 13% ( p = 0.02) for IgG, whereas controls were negative both for IgM and IgG antibodies against B. henselae . The differences in comorbidity between cases and controls were statistically different (1.41 ± 0.96 vs 0.42 ± 0.32; p = 0.001). Conclusions Although this study was conducted in a small number of patients, we suggest that the identification of these bacteria should be included as a routine screening analysis in pretransplant patients.

Objectives Although previous studies have investigated the effect of human leukocyte antigen matching on long-term outcomes after heart transplants, its role in the prognosis after a heart transplant remains unclear, particularly with respect to short-term survival. Materials and methods We evaluated the human leukocyte antigen mismatch on in-hospital mortality of 158 consecutive patients who had undergone a heart transplant between 2000 and 2008. Human leukocyte antigens-A, -B, and -DR were determined by means of serologic and molecular techniques. Univariate analysis and a multiple logistic regression models evaluated the effect of human leukocyte antigen variants on mortality, independent of clinical variables. Results In-hospital mortality was 11.4%. Higher prevalence of acute kidney injury (50.0% vs 12.9%), higher levels of troponins 48 hours after transplant (15.6 ± 12.0 ng/mL vs 9.7 ± 9.4 ng/mL), prolonged ischemia (188.2 ± 32.5 min vs 162.6 ± 40.7 min), higher frequency of reoperation (61.1% vs 17.9%), and higher human leukocyte antigen-DR mismatch (1.61 ± 0.5 vs 1.30 ± 0.6) were found in patients who died. By logistic regression analysis, humanleukocyte antigen-DR mismatch is associated with in-hospital mortality (OR=5.159, 95% CI=1.348-19.754), independent of the effect of covariates such as recipient age, mismatch sex, mismatch human leukocyte antigen-A, human leukocyte antigen-B, acute kidney injury, reoperation, ischemia duration, and levels of troponins. Conclusions Human leukocyte antigen-DR mismatch is associated with in-hospital mortality in heart transplant.

Adult human heart hosts a population of cardiac primitive CD117-positive cells (CPCs), which are responsible for physiological tissue homeostasis and regeneration. While the bona fide stem cells express telomerase, their progenies are no longer able to preserve telomeric DNA; hence the balance between their proliferation and differentiation has to be tightly controlled in order to prevent cellular senescence and apoptosis of CPCs before their maturation can be accomplished. We have examined at cellular and molecular level the proliferation, apoptosis and commitment of CPCs isolated from normal (CPC-N) and age-matched pathological adult human hearts (CPC-P) with ischemic heart disease. In the CPC-P, genes related to early stages of developmental processes, nervous system development and neurogenesis, skeletal development, bone and cartilage development were downregulated, while those involved in mesenchymal cell differentiation and heart development were upregulated, together with the transcriptional activation of TGFβ/BMP signaling pathway. In the pathological heart, asymmetric division was the prevalent type of cardiac stem cell division. The population of CPC-P consisted mainly of progenitors of cardiac cell lineages and less precursors; these cells proliferated more, but were also more susceptible to apoptosis with respect to CPC-N. These results indicate that CPCs fail to reach terminal differentiation and functional competence in pathological conditions. Adverse effects of underlying pathology, which disrupts cardiac tissue structure and composition, and cellular senescence, resulting from cardiac stem cell activation in telomere dysfunctional environment, can be responsible for such outcome.

BACKGROUND: The right heart is a major determinant of prognosis in cardiac transplant recipient patients. AIM: To investigate right ventricular morphology and function and their relationship with exercise capacity in cardiac transplant recipient patients using standard tranthoracic echocardiography and a new three-dimensional echocardiographic software adapted for right ventricular analysis. METHODS: One hundred fifteen relatively stable cardiac transplant recipient patients (71 men; 58.3 ± 5.8 years; 7.8 ± 4.5 years after transplantation) and 80 healthy age-comparable and sex-comparable controls underwent standard echocardiography, tissue Doppler imaging (TDI), and three-dimensional echocardiography, focused on the right ventricular analysis. Along with left heart parameters, right ventricular measurements included end-diastolic diameters at basal and mid-cavity level; base-to-apex length; tricuspid annulus plane systolic excursion (TAPSE); TDI right ventricular systolic peak velocity (Sm); and three-dimensional ejection fraction. Using the peak systolic tricuspid regurgitation velocity (TRV) and the end-diastolic pulmonary regurgitation velocity, the modified Bernoulli equation was used to calculate the pulmonary artery systolic (PASP) and diastolic pressures. Pulmonary artery vascular conductance (PAVC) was estimated by left ventricular stroke volume/4 × (TRV - pulmonary regurgitation velocity). RESULTS: Left ventricular diameters and ejection fraction did not significantly differ between the two groups, whereas mass index was increased in cardiac transplant recipient patients (P

OBJECTIVES: Unresponsive pulmonary hypertension (PH) may contraindicate heart transplant since it implies poor early outcomes. The present study reports the effectiveness of oral perioperative sildenafil in allowing heart transplant candidacy and surgery in a selected group of patients initially deemed ineligible because of PH. METHODS: Between May 2005 and December 2009, 31 consecutive patients (5 females, 9 with a history of idiopatic cardiomyopathy and 16 with a history of coronary artery disease, 10 with previous sternotomies, 71.42 ± 27.69 ml/min/m 2 mean pre-operative epidermal growth factor receptor) were qualified for oral sildenafil because of unresponsive PH at baseline right heart catheterization (RHC). After a 12-week trial, RHC disclosed PH reversibility (mean pulmonary vascular resistance index: 9.57 ± 4.07 WU, mean transpulmonary gradient 14.47 ± 5.66 mmHg and mean systolic pulmonary artery pressure: 68.96 ± 15.15 mmHg), allowing listing despite a higher risk for early post-transplant RV failure. Transplant protocol included donor/recipient size matching ≥0.8 and inhaled nitric oxide in the early post-operative period followed by reinstitution of oral sildenafil. RESULTS: All patients underwent heart transplantation. Mean overall graft ischaemic time was 179 ± 47min; mean donor recipient weight ratio was 1.04 ± 0.17. Right ventricular failure developed in three patients (9.6%) and hospital mortality was 3.2%. Protocol RHC disclosed pulmonary haemodynamic profile normalization within the third post-operative month allowing weaning from sildenafi li n the 30 hospital survivors. One-year RHC confirmed PH reversal (n= 29 patients, all who survived up to 1year). CONCLUSIONS: This pilot prospective uncontrolled trial suggests that oral sildenafil is effective in allowing candidacy, safe transplantation and post-operative pulmonary profile normalization in potential recipients initially disqualified because of PH.

CD117-positive cells contributing to cardiac cell turnover in normal and pathological conditions have recently been described in adult human heart. Since the precise spatial and temporal expression of extracellular matrix proteins and their receptors is critical for organ formation, we compared the distribution of cardiac primitive CD117-positive cells in the human adult normal and pathological hearts with ischemic cardiomyopathy, with respect to localization and expression of laminin and integrin isoforms. In the pathological hearts, CD117-positive cells were significantly more numerous than in the normal hearts. They were localized mainly in the atria and were up to 38-fold more numerous in the subepicardium than in the myocardium. Compared with normal hearts, most CD117-positive cells in the subepicardium of pathological hearts were α6 integrin-positive. Laminin-1, typical of developing heart, was found predominantly in the subepicardium of adult heart. Immunoblotting revealed its highest expression in the normal atrium and pathological left ventricle. Both laminin isoforms reduced apoptosis and increased proliferation and migration of CD117-positive cells in vitro with respect to control, but the effects of laminin-1 significantly outweighed those of laminin-2. Signaling mediated by α6 integrin was implicated in the migration and protection from apoptosis, as documented by transfection with specific small interfering RNA. These data reveal that the increase in the number of cardiac CD117-positive cells and the expression of laminin-1 are observed in ischemic cardiomyopathy. Subepicardial localization of CD117-positive cells and expression of laminin-1 and α6 integrin subunits may all correspond to the activation of regeneration involving an epithelial-mesenchymal transition recently described in adult heart. Disclosure of potential conflicts of interest is found at the end of this article.

Celsior solution has already proved effective in heart graft preservation because it reduces myocardial edema, prevents free radical damage, and limits calcium overload. The aim of this study was to evaluate the effectiveness of Celsior solution as myocardial protection in high-risk transplantation. Hospital charts and follow-up data of 200 consecutive heart recipients (162 males, 38 females, mean age 47.4 ± 12.6 years) were reviewed. Patients were divided into two groups: group A (73 patients) included recipients of high-risk grafts (at least two of the following: age >45; female sex; high preretrieval inotropic support, viz. dobutamine or dopamine >10 µg/kg per minute and/or infusion of norepinephrine regardless of its dosage; size mismatch >20%; ischemia time >180 min) and group B (127 patients) included recipients of standard grafts. Quality of preservation was assessed through enzyme release, echocardiographic evaluation, the need for inotropic support or pacemaker, and histology of biopsy samples. Hospital and 1-year mortality were also evaluated. Comparisons between the two groups were made through univariate analysis. Study groups proved homogeneous as to recipient age, pretransplant cardiomyopathy, status at transplantation, mean panel reactive antibodies, and redo cardiac surgery. Hospital mortality was 8% (11% vs 6.3%, P = 0.18) while 1-year mortality reached 12% (15.1% vs 10.2%, P = 0.6) without significant difference between groups. Graft performance as described by the need for inotropic support and/or pacemaker as well as echocardiography (left and right ventricular ejection fraction) proved comparable. There were no significant differences as to histology findings and patterns of enzyme release. Celsior provides optimal myocardial preservation in both standard and high-risk procedures. Such advances help to enhance donor pool expansion.

Objective This retrospective single-center report sought to evaluate the relation of immunosuppressive regimen with the incidence and characteristics of cytomegalovirus (CMV) infection from 1999 to 2003. Patients and methods Immunosuppression consisted of cyclosporine microemulsion (Neoral), azathioprine (AZA), and prednisolone associated with either thymoglobulin or ATG high-dosage induction from 1999 to 2000 (AZA, 64 patients [AZA-Thymo = 38 patients and AZA-ATG 26 patients]), or cyclosporine microemulsion (Neoral), mycophenolate mofetil (MMF), and prednisolone with low-dose thymoglobulin induction from 2001 onward (n = 52 patients). Ganciclovir preemptive therapy was guided by pp65 antigenemia monitoring without CMV prophylaxis. Results The study groups were homogeneous with respect to major perioperative risk factors. Comparing the two AZA subgroups no difference emerged as to percentage of pp65 antigenemia-positive, preemptively treated patients reflecting CMV disease incidence and relapses. AZA-Thymo patient showed significantly shorter time to first positive pp65-antigenemia and higher viral load (AZA-Thymo vs AZA-ATG, P = .004 and P = .009). The two subgroups did not differ with regard to incidence of rejection, superinfection, and graft coronary disease. By shifting from AZA to MMF no difference emerged as to incidence and characteristics of CMV infections, but there was a significant reduction in acute rejection and superinfection (AZA vs MMF P = .001 and P = .008). Conclusions The distinct immunological properties of thymoglobulin versus ATG significantly altered the pattern of CMV expression. MMF with reduced-dose induction did not engender a higher CMV morbidity.

Clinical studies indicate that indices of glomerular filtration rate (GFR) as serum creatinine or creatinine clearance can predict the risk of death in congestive heart failure (CHF) and in heart transplantation. The study reports data on creatinine clearance before and after heart transplantation in 160 patients followed-up for 5 years at our Unit. Pre-transplant creatinine clearance averaged 83.5*32 mL/min * 1.73 m2 and was not significantly associated with 5-year mortality. Creatinine clearance significantly decreased after heart transplantation with a linear trend up to 3 years for patients with complete follow-up. Data suggest that the relation between kidney function and mortality after heart transplantation is affected by several confounders with inclusion of cause of heart disease, co-morbidity, anemia, and post-transplant decrease in kidney function. Clinical studies indicate that indices of glomerular filtration rate (GFR) as serum creatinine or creatinine clearance can predict the risk of death in congestive heart failure (CHF) and in heart transplantation. The study reports data on creatinine clearance before and after heart transplantation in 160 patients followed-up for 5 years at our Unit. Pre-transplant creatinine clearance averaged 83.5±32 mL/min × 1.73 m 2 and was not significantly associated with 5-year mortality. Creatinine clearance significantly decreased after heart transplantation with a linear trend up to 3 years for patients with complete follow-up. Data suggest that the relation between kidney function and mortality after heart transplantation is affected by several confounders with inclusion of cause of heart disease, co-morbidity, anemia, and post-transplant decrease in kidney function. © 2005 Elsevier Inc. All rights reserved.

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.

This study adds another category of patients to those amenable to body impedance analysis (BIA). BIA measurements were obtained for the first time in 23 male patients with end-stage heart failure who were waiting for heart transplantation, and the data were compared with those obtained in 69 healthy controls matched for age, sex, height and weight. The data indicate that in end-stage heart failure there is an increased reactance (p

Acute or chronic valvular diseases, acute myocardial infarction and its complications, dilated cardiomyopathies, all may became the cause of heart failure leading to different degrees of cardiogenic edema. Today cardiac failure is treated from its the early stage by medical and/or surgical therapy. Thereafter, in a small population of patients, heart failure may became unresponsive to any kind of standard medical treatment. Conventional surgical procedures are often inadequate and carry a high risk of perioperative mortality. This study analyzes the outcome of 139 patients with end-stage cardiomyopathy who underwent heart transplantation between January 1988 and October 1996. We found that patients transplanted while on severe decompensation are at a higher perioperative mortality due to irreversible multi-organ failure. The study also suggests that the implantation of a left ventricle assist device as a bridge to transplantation is a promising maneuver for the most severe patients.

To evaluate the impact of early ischemic necrosis (IN) on the early and late outcome of heart transplantation, we reviewed our 11-year experience. Between January 1988 and June 1999, 207 heart transplants were performed in 205 patients (174 male and 31 female). Criteria for donor and recipient selection, and protocols for postoperative immunosuppression and rejection monitoring have remained unchanged over this period. Three different cardioplegic solutions were employed in graft preservation: St. Thomas Hospital solution in the earliest 31 cases (15%), University of Wisconsin solution in 96 cases (46.4%), and Celsior solution in the last 80 cases (38.6%). All patients who underwent at least one endomyocardial biopsy (176 patients) were divided into two groups according to the findings of IN within the early 3 postoperative months (group A, 49 patients with IN; group B, 127 patients without IN). The following variables were estimated in each group: donor and recipient age, ischemic time, type of cardioplegia, late mortality for cardiac causes, incidence of grade >2 rejection within the first 6 postoperative months, late incidence of grade >2 rejection, late incidence of NYHA class >II. No significant difference was found in any parameter between the two groups, except for the type of cardioplegic solution. A significantly higher incidence of ischemic necrosis in hearts preserved with St. Thomas solution was found (P < 0.001). Although pathology findings show that extracellular solutions carried a higher risk of early IN, no associated significant impairment in terms of late survival and event-free rate was observed in recipients with early IN.

Advances in donor and recipient selection and postoperative management of patients undergoing a heart transplant have improved survival after cardiac transplantation; nevertheless, late complications are still the main cause of mortality. Between January 1988 and March 1999, 200 heart transplants and 2 retransplants were performed at our Institution. The actuarial survival rate was 84.45% at 1 month, 75.22% at 1 year, and 69.48% at 5 years. One-hundred forty-five patients reached at least 6 months of follow-up. In this group of patients we reviewed all available pathological specimens from endomyocardial biopsies, autopsies, and hearts retrieved at retransplantation. The most frequent late complications have been: malignancies (9 patients), allograft coronary artery disease (ACAD) (6 patients), and infections (6 patients). All patients with ACAD had serological evidence of cytomegalovirus (CMV) infection and 5 of them (83.3%) of hepatitis C virus (HCV) infection. Squamous cell lung carcinoma and Kaposi's sarcoma were the most frequent neoplasms (3 patients). Twenty-six out of 145 patients died during the follow-up: sudden death occurred in 10 patients (38.46%), infections caused death in 6 patients (23.08%). ACAD in 4, and cancer in 4. Causes and rates of late mortality in patients with a cardiac transplant differ from those of early mortality. Development of infections, ACAD, or cancer is associated with a high late mortality rate. A striking correlation has been found between ACAD and HCV and/or CMV positivity. suggesting that such viruses may play a role in the development of vascular late complications in transplanted hearts.

Infection with HIV may lead to the development of cardiomyopathy as improved antiretroviral regimens continue to prolong patient life. However, advanced therapeutic options, such as heart transplant, have until recently been precluded to HIV-positive persons. A favorable long-term outcome has been obtained after kidney or liver transplant in HIV-positive recipients fulfilling strict virological and clinical criteria. We recently reported the first heart transplant in a HIV-infected patient carried out in our center. In this article, we detail the major challenges we faced with the management of antiretroviral and immunosuppressive treatments over the first 3 years post-transplant. The patient had developed dilated cardiomyopathy while on antiretroviral treatment with zidovudine, lamivudine and efavirenz. He was in WHO Stage 1 of HIV infection and had normal CD4+ count and persistently undetectable HIV-RNA. In spite of cardiac resynchronization therapy and maximal drug therapy, the patient progressed to end stage heart failure, requiring heart transplant. He was placed on a standard immune suppressive protocol including cyclosporine A and everolimus. Despite its potential pharmacokinetic interaction with efavirenz, everolimus was chosen to reduce the long-term risk of opportunistic neoplasia. Plasma levels of both drugs were monitored and remained within the target range, although high doses of everolimus were needed. There were no infectious, neoplastic or metabolic complications during a 3-year follow-up. In summary, our experience supports previous data showing that cardiac transplantation should not be denied to carefully selected HIV patients. Careful management of drug interactions and adverse events is mandatory. Copyright © by BIOLIFE, s.a.s.