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Introduction and Objectives: Posttransplant outcomes among recipients with a diagnosis of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM) remain controversial., Methods: Retrospective analysis of a nationwide registry of first-time recipients undergoing isolated heart transplant between 1984 and 2021. One-year and 5-year mortality in recipients with HCM and RCM were compared with those with dilated cardiomyopathy (DCM)., Results: We included 3703 patients (3112 DCM; 331 HCM; 260 RCM) with a median follow-up of 5.0 [3.1-5.0] years. Compared with DCM, the adjusted 1-year mortality risk was: HCM: HR, 1.38; 95%CI, 1.07-1.78; P=.01, RCM: HR, 1.48; 95%CI, 1.14-1.93; P=.003. The adjusted 5-year mortality risk was: HCM: HR, 1.17; 95%CI, 0.93-1.47; P=.18; RCM: HR, 1.52; 95%CI, 1.22-1.89; P<.001. Over the last 20 years, the RCM group showed significant improvement in 1-year survival (adjusted R 2 =0.95) and 5-year survival (R 2 =0.88); the HCM group showed enhanced the 5-year survival (R 2 =0.59), but the 1-year survival remained stable (R 2 =0.16)., Conclusions: Both RCM and HCM were linked to a less favorable early posttransplant prognosis compared with DCM. However, at the 5-year mark, this unfavorable difference was evident only for RCM. Notably, a substantial temporal enhancement in both early and late mortality was observed for RCM, while for HCM, this improvement was mainly evident in late mortality., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

A combination of human-induced pluripotent stem cells (hiPSCs) and 3D microtissue culture techniques allows the generation of models that recapitulate the cardiac microenvironment for preclinical research of new treatments. In particular, spheroids represent the simplest approach to culture cells in 3D and generate gradients of cellular access to the media, mimicking the effects of an ischemic event. However, previous models required incubation under low oxygen conditions or deprived nutrient media to recreate ischemia. Here, we describe the generation of large spheroids (i.e., larger than 500 μm diameter) that self-induce an ischemic core. Spheroids were generated by coculture of cardiomyocytes derived from hiPSCs (hiPSC-CMs) and primary human cardiac fibroblast (hCF). In the proper medium, cells formed aggregates that generated an ischemic core 2 days after seeding. Spheroids also showed spontaneous cellular reorganization after 10 days, with hiPSC-CMs located at the center and surrounded by hCFs. This led to an increase in microtissue stiffness, characterized by the implementation of a constriction assay. All in all, these phenomena are hints of the fibrotic tissue remodeling secondary to a cardiac ischemic event, thus demonstrating the suitability of these spheroids for the modeling of human cardiac ischemia and its potential application for new treatments and drug research.

Objectives: The objective was to analyse associations between obesity and outcomes after left ventricular assist device (LVAD) implantation., Methods: A retrospective analysis of the EUROMACS Registry was performed. Adult patients undergoing primary implantation of a continuous-flow LVAD between 2006 and 2019 were included (Medtronic HeartWare® HVAD®, Abbott HeartMate II®, Abbott HeartMate 3™). Patients were classified into 4 different groups according to body mass index at the time of surgery (body mass index <20 kg/m2: n = 254; 20-24.9 kg/m2: n = 1281; 25-29.9 kg/m2: n = 1238; ≥ 30 kg/m2: n = 691)., Results: The study cohort was comprised of 3464 patients. Multivariable Cox proportional cause-specific hazards regression analysis demonstrated that obesity (body mass index ≥30 kg/m2) was independently associated with significantly increased risk of mortality (body mass index ≥30 vs 20-24.9 kg/m2: hazard ratio 1.36, 95% confidence interval 1.18-1.57, overall P < 0.001). Moreover, obesity was associated with significantly increased risk of infection and driveline infection. The probability to undergo heart transplantation was significantly decreased in obese patients (body mass index ≥30 vs 20-24.9 kg/m2: hazard ratio 0.59, 95% confidence interval 0.48-0.74, overall P < 0.001)., Conclusions: Obesity at the time of LVAD implantation is associated with significantly higher mortality and increased risk of infection as well as driveline infection. The probability to undergo heart transplantation is significantly decreased. These aspects should be considered when devising a treatment strategy before surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: In the third report of the European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery, outcomes of patients receiving mechanical circulatory support are reviewed in relation to implant era., Methods: Procedures in adult patients (January 2011-June 2020) were included. Patients from centres with <60% follow-ups completed were excluded. Outcomes were stratified into 3 eras (2011-2013, 2014-2017 and 2018-2020). Adverse event rates (AERs) were calculated and stratified into early phase (<3 months) and late phase (>3 months). Risk factors for death were explored using univariable Cox regression with a stepwise time-varying hazard ratio (<3 vs >3 months)., Results: In total, 4834 procedures in 4486 individual patients (72 hospitals) were included, with a median follow-up of 1.1 (interquartile range: 0.3-2.6) years. The annual number of implants (range: 346-600) did not significantly change (P = 0.41). Both Interagency Registry for Mechanically Assisted Circulatory Support class (classes 4-7: 23, 25 and 33%; P < 0.001) and in-hospital deaths (18.5, 17.2 and 11.2; P < 0.001) decreased significantly between eras. Overall, mortality, transplants and the probability of weaning were 55, 25 and 2% at 5 years after the implant, respectively. Major infections were mainly noted early after the implant occurred (AER<3 months: 1.44 vs AER>3 months: 0.45). Bilirubin and creatinine levels were significant risk factors in the early phase but not in the late phase after the implant., Conclusions: In its 10 years of existence, EUROMACS has become a point of reference enabling benchmarking and outcome monitoring. Patient characteristics and outcomes changed between implant eras. In addition, both occurrence of outcomes and risk factor weights are time dependent., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): (1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); (2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast cancer patients (BC-patients); and (3) associates with LVD in ACC-induced heart failure patients (ACC-HF-patients). Echocardiography, serum PICP and biomarkers of cardiomyocyte damage were assessed in two independent cohorts of BC-patients: CUN (n = 87) at baseline, post-ACC, and 3m and 12m (n = 65)-post-ACC; and HULAFE (n = 70) at baseline, 3m and 12m-post-ACC. Thirty-seven ACC-HF-patients were also studied. Global longitudinal strain (GLS)-based sLVD (3m-post-ACC) and LV ejection fraction (LVEF)-based cardiotoxicity (12m-post-ACC) were defined according to guidelines. BC-patients: all biomarkers increased at 3m-post-ACC versus baseline. PICP was particularly increased in patients with sLVD (interaction-p < 0.001) and was associated with GLS (p < 0.001). PICP increase at 3m-post-ACC predicted cardiotoxicity at 12m-post-ACC (odds-ratio ≥ 2.95 per doubling PICP, p ≤ 0.025) in both BC-cohorts, adding prognostic value to the early assessment of GLS and LVEF. ACC-HF-patients: PICP was inversely associated with LVEF (p = 0.004). In ACC-treated BC-patients, an early increase in PICP is associated with early sLVD and predicts cardiotoxicity 1 year after ACC. PICP is also associated with LVD in ACC-HF-patients.

Introduction and Objectives: Intrapatient blood level variability (IPV) of calcineurin inhibitors has been associated with poor outcomes in solid-organ transplant, but data for heart transplant are scarce. Our purpose was to ascertain the clinical impact of IPV in a multi-institutional cohort of heart transplant recipients., Methods: We retrospectively studied patients aged ≥18 years, with a first heart transplant performed between 2000 and 2014 and surviving≥ 1 year. IPV was assessed by the coefficient of variation of trough levels from posttransplant months 4 to 12. A composite of rejection or mortality/graft loss or rejection and all-cause mortality/graft loss between years 1 to 5 posttransplant were analyzed by Cox regression analysis., Results: The study group consisted of 1581 recipients (median age, 56 years; women, 21%). Cyclosporine immediate-release tacrolimus and prolonged-release tacrolimus were used in 790, 527 and 264 patients, respectively. On multivariable analysis, coefficient of variation> 27.8% showed a nonsignificant trend to association with 5-year rejection-free survival (HR, 1.298; 95%CI, 0.993-1.695; P=.056) and with 5-year mortality (HR, 1.387; 95%CI, 0.979-1.963; P=.065). Association with rejection became significant on analysis of only those patients without rejection episodes during the first year posttransplant (HR, 1.609; 95%CI, 1.129-2.295; P=.011). The tacrolimus-based formulation had less IPV than cyclosporine and better results with less influence of IPV., Conclusions: IPV of calcineurin inhibitors is only marginally associated with mid-term outcomes after heart transplant, particularly with the tacrolimus-based immunosuppression, although it could play a role in the most stable recipients., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

OBJECTIVE. This study aimed to evaluate the long-term prognostic value of coronary CTA (CCTA) in heart transplant recipients. MATERIALS AND METHODS. The records of 114 patients who had undergone a heart transplant (mean age, 61.7 ± 11.1 [SD] years; 83.3% men) and who underwent CCTA for the surveillance of coronary allograft vasculopathy (CAV) from June 2007 to December 2017 were retrospectively evaluated for the occurrence of major adverse cardiovascular events (MACEs) (cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, coronary revascularization, cardiac arrhythmias, stroke, and retransplant). Patients were classified according to the presence of nonobstructive CAV (lumen reduction < 50%) or obstructive disease (lumen reduction ≥ 50%) and using a coronary segment involvement score (SIS). Differences in MACE rate between groups were compared. RESULTS. Obstructive CAV was observed in 12 heart transplant recipients (10.5%). During a mean follow-up of 67.5 ± 41.4 months the overall rates of MACE were 50% and 14.7% in patients with obstructive and nonobstructive CAV, respectively ( p < .05), resulting in an odds ratio for MACE of 6 (95% CI, 1.7-21.2). Comparison of event-free survival showed a hazard ratio (HR) of 5 (95% CI, 1.95-13; p =. 004) for patients with obstructive disease. The presence of four or more stenotic coronary segments (SIS ≥ 4) was associated with a higher rate of events (HR, 3.46; 95% CI, 1.46-8.23). CONCLUSION. In patients who have undergone a heart transplant, CCTA offers a significant long-term prognostic impact on the prediction of MACEs.

Biological differences between males and females change the course of different diseases and affect therapeutic measures' responses. Heart failure is not an exception to these differences. Women account for a minority of patients on the waiting list for heart transplantation or other advanced heart failure therapies. The reason for this under-representation is unknown. Men have a worse cardiovascular risk profile and suffer more often from ischemic heart disease. Conversely, transplanted women are younger and more frequently have non-ischemic cardiac disorders. Women's poorer survival on the waiting list for heart transplantation has been previously described, but this trend has been corrected in recent years. The use of ventricular assist devices in women is progressively increasing, with comparable results than in men. The indication rate for a heart transplant in women (number of women on the waiting list for millions of habitants) has remained unchanged over the past 25 years. Long-term results of heart transplants are equal for both men and women. We have analyzed the data of a national registry of heart transplant patients to look for possible future directions for a more in-depth study of sex differences in this area. We have analyzed 1-year outcomes of heart transplant recipients. We found similar results in men and women and no sex-related interactions with any of the factors related to survival or differences in death causes between men and women. We should keep trying to approach sex differences in prospective studies to confirm if they deserve a different approach, which is not supported by current evidence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 García-Cosío, González-Vilchez, López-Vilella, Barge-Caballero, Gómez Bueno, Martínez-Selles, María Arizón, Rangel Sousa, González-Costello, Mirabet, Pérez-Villa, Molina, Rábago, Portolés Ocampo, de la Fuente Galán, Garrido and Delgado.)

The study of gender differences may lead into improvement in patient care. We have aimed to identify the gender differences in heart transplantation (HT) of adult HT recipients in Spain and their evolution in a study covering the years 1993-2017 in which 6740 HT (20.6% in women) were performed. HT indication rate per million inhabitants was lower in women, remaining basically unchanged during the 25-year study period. HT rate was higher in men, although this decreased over the 25-year study period. Type of heart disease differed in men versus women (p < .001): ischemic heart disease 47.6% versus 22.5%, dilated cardiomyopathy 41.3% versus 34.6%, or other 36% versus 17.8%, respectively. Men were more frequently diabetics (18% vs. 13.1% p < .001), hypertensives (33.1% vs. 24% p < .001), and smokers (21.7% vs. 12.9% p < .001), respectively. Women had more pre-HT malignancies (7.1% vs. 2.8% p < .001), and their clinical status was worse at HT due to renal function and mechanical ventilation. Adjusted survival (p = .198) and most of the mortality-related variables were similar in men and women. Death occurred more frequently in women due to rejection (7.9% vs. 5.1% p < .001) and primary failure (18.2% vs. 12.5% p < .001) and in men due to malignancies (15.1% vs. 6.6% p < .001)., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

OBJECTIVE. The purpose of this study was to evaluate the feasibility, image quality, and radiation dose of high-pitch coronary CT angiography (CCTA) in orthotopic heart transplant (OHT) recipients. SUBJECTS AND METHODS. Twenty-two consecutive OHT recipients (16 men, six women; median age, 66.5 years [interquartile range, 51.3-70.3 years]; median heart rate, 91 beats/min [interquartile range, 79.3-97.3 beats/min]) underwent CCTA with a third-generation dual-source CT scanner in high-pitch mode to rule out coronary allograft vasculopathy. Data acquisition was triggered at 30% of the R-R interval. Two independent observers blindly assessed image quality on a per-segment, per-vessel, and per-patient basis using a 4-point scale (4, excellent; 1, not evaluative). Scores 2-4 indicated diagnostic quality. Studies were compared with previously performed retrospective ECG-gated examinations, when available. Interobserver agreement on the image quality was assessed with kappa statistics. Radiation dose was recorded. RESULTS. A total of 322 coronary segments were evaluated. Diagnostic image quality was observed in 97.5% of the segments. Interobserver agreement for image quality assessment was very good on a per-patient (κ = 0.82), per-vessel (κ = 0.83), and per-segment basis (κ = 0.89). The median per-patient image quality score was 4.0 (3.0-4.0) for the entire coronary tree. A comparison of image quality scores between high-pitch and retrospective ECG-gated CCTA examinations showed no significant differences, but the estimated mean radiation dose was significantly lower for the high-pitch mode (median dose-length product, 31.6 mGy × cm [interquartile range, 23.1-38.8 mGy × cm] vs 736.5 mGy × cm [interquartile range, 655.5-845.7 mGy × cm], p < 0.001). CONCLUSION. Performing single-heartbeat high-pitch CCTA during the systolic phase of the cardiac cycle in OHT recipients results in diagnostic image quality in coronary angiograms at very low radiation dose.

Myocardial fibrosis is a main contributor to the development of heart failure (HF). CT-1 (cardiotrophin-1) and Gal-3 (galectin-3) are increased in HF and associated with myocardial fibrosis. The aim of this study is to analyze whether CT-1 regulates Gal-3. Proteomic analysis revealed that Gal-3 was upregulated by CT-1 in human cardiac fibroblasts in parallel with other profibrotic and proinflammatory markers. CT-1 upregulation of Gal-3 was mediated by ERK (extracellular signal-regulated kinase) 1/2 and Stat-3 (signal transducer and activator of transcription 3) pathways. Male Wistar rats and B6CBAF1 mice treated with CT-1 (20 µg/kg per day) presented higher cardiac Gal-3 levels and myocardial fibrosis. In CT-1-treated rats, direct correlations were found between cardiac CT-1 and Gal-3 levels, as well as between Gal-3 and perivascular fibrosis. Gal-3 genetic disruption in human cardiac fibroblasts and pharmacological Gal-3 inhibition in mice prevented the profibrotic and proinflammatory effects of CT-1. Dahl salt-sensitive hypertensive rats with diastolic dysfunction showed increased cardiac CT-1 and Gal-3 expression together with cardiac fibrosis and inflammation. CT-1 and Gal-3 directly correlated with myocardial fibrosis. In HF patients, myocardial and plasma CT-1 and Gal-3 were increased and directly correlated. In addition, HF patients with high CT-1 and Gal-3 plasma levels presented an increased risk of cardiovascular death. Our data suggest that CT-1 upregulates Gal-3 which, in turn, mediates the proinflammatory and profibrotic myocardial effects of CT-1. The elevation of both molecules in HF patients identifies a subgroup of patients with a higher risk of cardiovascular mortality. The CT-1/Gal-3 axis emerges as a candidate therapeutic target and a potential prognostic biomarker in HF.

Introduction: We evaluate the ability of 2D non-contrast-enhanced echocardiography (CE-echo), 2DCE-echo, 3D-echo, 3D non-CE-echo, and 3DCE-echo to evaluate allograft function and dimensions in orthotropic heart transplantation (OHT). Cardiac resonance (CMR) was used as reference., Methods: Twenty six consecutive OHT-recipients were prospectively recruited. Bland-Altman, Spearman rank, and concordance-correlation coefficients (CCC) were determined., Results: Good CCCs were found between the four modalities and CMR for ejection fraction (r ≥ 0.72/P < 0.001; r ≥ 0.77/ P < 0.001; r ≥ 0.51/ P < 0.23; r ≥ 0.75/ P < 0.001, respectively). Highest intraclass correlation coefficient (ICC) was for 2D CE-echo(CCC = 0.77). End-diastolic volume(EDV) measurements statistically differed when 2D non-CE-echo, 2DCE-echo, and 3D non-CE-echo were compared with the cross-sectional imaging modalities, but they did not differ significantly from 3DCE-echo. End-systolic volume (ESV) and stroke volume (SV) differed statistically between the four modalities; however, SV measured by CMR and 3DCE-echo were comparable. Overall, 2D non-CE-echo, 2DCE-echo, and 3D non-CE-echo showed lower mean EDV, ESV, and SV than CMR. ICC was that of the ESV variable in the 4 techniques, with the values of the ICC of the 3DCE-echo technique superior to the rest. Overall, the best CCC were found for 3DCE(r = 0.88, 0.92 and 0.76 for EDV, ESV and SV, respectively)., Conclusion: Routine use of 3DCE-echo may allow more comprehensive cardiac assessment in cardiac transplant recipients., (© 2018 Wiley Periodicals, Inc.)

Heart failure (HF) is a progressively debilitating disease that considerably decreases the life expectancy and quality of life. It has become an important area of focus since it remains one of the most common reasons for admission in patients over the age of 65. Importantly, the incidence of HF has not declined within the past 20 years, but the survival after onset has increased in younger patients and men. This has been in part due to the growing interest in therapies that may decrease morbidity, mortality, along with the substantial health care expenditures associated with the disease. It can be said that over the past 50 years, there have been three distinct eras relating to HF management; a) the non-pharmacologic era, focused its treatments on fluid restriction; b) the pharmacologic era, marked by the increased use of inotropes and diuretics and the discovery of vasodilators, and the posterior discovery of medications relating to neurohormonal pathways; c) the device era, with the discovery, acceptance, and increased use of implantable cardioverter defibrillators, cardiac resynchronization therapy (CRT), and left ventricular assist devices (LVADs) among others. A new forth era could be about to arrive, with the advent of regenerative therapies. In this review article will discuss new therapeutic discoveries as well as provide insight into future therapies., (Copyright © 2019 IMSS. Published by Elsevier Inc. All rights reserved.)

Perioperative anemia is an important risk factor for cardiac surgery-associated acute kidney injury (CSA-AKI). Nonetheless, the severity of the anemia and the time in the perioperative period in which the hemoglobin level should be considered as a risk factor is conflicting. The present study introduces the concept of perioperative hemoglobin area under the curve (pHb-AUC) as a surrogate marker of the evolution of perioperative hemoglobin concentration. Through a retrospective analysis of prospectively collected data, we assessed this new variable as a risk factor for the development of acute kidney injury after cardiac surgery in 966 adult patients who underwent cardiac surgery with cardiopulmonary bypass, at twenty-three academic hospitals in Spain. Exclusion criteria were patients on renal replacement therapy, who needed a reoperation because of bleeding and/or with missing perioperative hemoglobin or creatinine values. Using a multivariate regression analysis, we found that a pHb-AUC <19 g/dL was an independent risk factor for CSA-AKI even after adjustment for intraoperative red blood cell transfusion (OR 1.41, p <0.05). It was also associated with mortality (OR 2.48, p <0.01) and prolonged hospital length of stay (4.67 ± 0.99 days, p <0.001).

This retrospective study evaluates the impact of rituximab on PTLD response and survival in a single-centre cohort. PTLD cases between 1984 and 2009, including heart, kidney, liver and lung transplant recipients, were included. Survival was analysed taking into account the type of PTLD (monomorphic vs. polymorphic), EBV infection status, IPI score, Ann Arbor stage and use of rituximab. Among 1335 transplanted patients, 24 developed PTLD. Median age was 54 yr (range 29-69), median time to diagnosis 50 months (range 0-100). PTLD type was predominantly late/monomorphic (79% and 75%), mostly diffuse large B-cell type. Overall response rate (ORR) was 62% (66% rituximab vs. 50% non-rituximab; P = 0.5). R-CHOP-like regimens were used most frequently (72% of patients treated with rituximab). Median overall survival was 64 months (CI 95% 31-96). OS was significantly increased in patients treated with rituximab (P = 0.01; CI 95% rituximab 58-79 months; non-rituximab 1-30 months). Post-transplant immunosuppression regimen had no effect on survival or time to PTLD, except for cyclosporine A (CyA), which associated with increased time to PTLD (P = 0.02). Rituximab was associated with increased survival in our single-centre series, and it should be considered as first-line therapy for PTLD patients. The possible protective effect of CyA for development of PTLD should be prospectively evaluated., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Concomitant heart transplantation and ascending aorta replacement is infrequent. In the few cases where this simultaneous procedure was performed, most patients were diagnosed with Marfan syndrome. We report the combined procedure of heart transplantation and ascending aorta replacement using the donor's ascending aorta, in a 70-year-old man who was not diagnosed with Marfan syndrome. This combined procedure can be performed successfully, providing a potentially life-saving heart transplant for patients with aortic disease of different etiologies., (© The Author(s) 2015.)

Objectives: Cystatin C has been shown to be associated with heart failure with preserved ejection fraction (HFPEF). In addition, myocardial fibrosis has been involved in diastolic dysfunction in HFPEF. Therefore, we hypothesized that increased cystatin C levels may be associated with altered collagen metabolism, contributing to diastolic dysfunction in patients with HFPEF., Methods: One hundred and forty-one elderly hypertensive patients with HFPEF were included. Cardiac morphology and function was assessed by echocardiography. Circulating levels of cystatin C, biomarkers of collagen type I synthesis (carboxy-terminal propeptide of procollagen type I) and degradation [matrix metalloproteinase-1 (MMP-1) and its inhibitor TIMP-1] and osteopontin were analyzed by ELISA. Twenty elderly sex-matched patients with no identifiable cardiac disease were used as controls. In-vitro studies were performed in human cardiac fibroblasts., Results: Compared with controls, cystatin C was increased (P < 0.001) in patients with HFPEF, even in those with a normal estimated glomerular filtration rate (eGFR; P < 0.05). Cystatin C was directly correlated with the estimated pulmonary capillary wedge pressure (P < 0.01), TIMP-1 and osteopontin (P < 0.001) and inversely correlated with MMP-1:TIMP-1 (P < 0.01), but not with carboxy-terminal propeptide of procollagen type I or MMP-1 in all patients with HFPEF. These associations were independent of eGFR. In vitro, osteopontin (P < 0.01) and TIMP-1 (P < 0.001) increased in the supernatant of cardiac fibroblasts exposed to cystatin C., Conclusion: In patients with HFPEF of hypertensive origin, cystatin C is increased and associated with diastolic dysfunction and alterations in collagen metabolism independently of eGFR. An excess of cystatin C might contribute to diastolic dysfunction in HFPEF by facilitating myocardial fibrosis via accumulation of osteopontin and TIMP-1.

Aim: To determine the clinical reasons for conversion to everolimus (EVL) and long-term outcomes in heart transplant (HT) recipients., Methods: A retrospective 12-mo study has been carried out in 14 Spanish centres to assess the efficacy and safety of conversion to EVL in maintenance HT recipients., Results: Two hundred and twenty-two patients were included (mean age: 53 ± 10.5 years; mean time from HT: 8.1 ± 4.5 years). The most common reasons for conversion were nephrotoxicity (30%), chronic allograft vasculopathy (20%) and neoplasms (17%). The doses and mean levels of EVL at baseline (conversion to EVL) and after one year were 1.3 ± 0.3 and 1.2 ± 0.6 mg/d and 6.4 ± 3.4 and 5.6 ± 2.5 ng/mL, respectively. The percentage of patients receiving calcineurin inhibitors (CNIs) at baseline and on the final visit was 95% and 65%, respectively. The doses and mean levels of CNIs decreased between baseline and month 12 from 142.2 ± 51.6 to 98.0 ± 39.4 mg/d (P < 0.001) and from 126.1 ± 50.9 to 89.2 ± 47.7 ng/mL (P < 0.001), respectively, for cyclosporine, and from 2.9 ± 1.8 to 2.6 ± 1.9 mg/d and from 8.3 ± 4.0 to 6.5 ± 2.7 ng/mL (P = 0.011) for tacrolimus. In the subgroup of patients converted because of nephrotoxicity, creatinine clearance increased from 34.9 ± 10.1 to 40.4 ± 14.4 mL/min (P < 0.001). There were 37 episodes of acute rejection in 24 patients (11%). The most frequent adverse events were oedemas (12%), infections (9%) and gastrointestinal problems (6%). EVL was suspended in 44 patients (20%). Since the database was closed at the end of the study, no further follow-up data is available., Conclusion: Conversion to EVL in maintenance HT recipients allowed minimisation or suspension of the CNIs, with improved kidney function in the patients with nephrotoxicity, after 12 mo.

The results of studies on the association between sex mismatch and survival after heart transplantation are conflicting. Data from the Spanish Heart Transplantation Registry. From 4625 recipients, 3707 (80%) were men. The donor was female in 943 male recipients (25%) and male in 481 female recipients (52%). Recipients of male hearts had a higher body mass index (25.9 ± 4.1 vs. 24.3 ± 3.7; P < 0.01), and male donors were younger than female donors (33.4 ± 12.7 vs. 38.2 ± 12.3; P < 0.01). No further relevant differences related to donor sex were detected. In the univariate analysis, mismatch was associated with mortality in men (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.06-1.32; P = 0.003) but not in women (HR, 0.91; 95% CI 0.74-1.12; P = 0.4). A significant interaction was detected between sex mismatch and recipient gender (P = 0.02). In the multivariate analysis, sex mismatch was associated with long-term mortality (HR, 1.14; 95% CI 1.01-1.29; P = 0.04), and there was a tendency toward significance for the interaction between sex mismatch and recipient gender (P = 0.08). In male recipients, mismatch increased mortality mainly during the first month and in patients with pulmonary gradient >13 mmHg. Sex mismatch seems to be associated with mortality after heart transplantation in men but not in women., (© 2014 Steunstichting ESOT.)

Cardiotrophin-1 has been shown to be profibrogenic in experimental models. The aim of this study was to analyze whether cardiotrophin-1 is associated with left ventricular end-diastolic stress and myocardial fibrosis in hypertensive patients with heart failure. Endomyocardial biopsies from patients (n=31) and necropsies from 7 control subjects were studied. Myocardial cardiotrophin-1 protein and mRNA and the fraction of myocardial volume occupied by collagen were increased in patients compared with controls (P<0.001). Cardiotrophin-1 overexpression in patients was localized in cardiomyocytes. Cardiotrophin-1 protein was correlated with collagen type I and III mRNAs (r=0.653, P<0.001; r=0.541, P<0.01) and proteins (r=0.588, P<0.001; r=0.556, P<0.005) in all subjects and with left ventricular end-diastolic wall stress (r=0.450; P<0.05) in patients. Plasma cardiotrophin-1 and N-terminal pro-brain natriuretic peptide and serum biomarkers of myocardial fibrosis (carboxy-terminal propeptide of procollagen type I and amino-terminal propeptide of procollagen type III) were increased (P<0.001) in patients compared with controls. Plasma cardiotrophin-1 was correlated with N-terminal pro-brain natriuretic peptide (r=0.386; P<0.005), carboxy-terminal propeptide of procollagen type I (r=0.550; P<0.001), and amino-terminal propeptide of procollagen type III (r=0.267; P<0.05) in all subjects. In vitro, cardiotrophin-1 stimulated the differentiation of human cardiac fibroblast to myofibroblasts (P<0.05) and the expression of procollagen type I (P<0.05) and III (P<0.01) mRNAs. These findings show that an excess of cardiotrophin-1 is associated with increased collagen in the myocardium of hypertensive patients with heart failure. It is proposed that exaggerated cardiomyocyte production of cardiotrophin-1 in response to increased left ventricular end-diastolic stress may contribute to fibrosis through stimulation of fibroblasts in heart failure of hypertensive origin.

Background: Primary graft failure (PGF) is the leading cause of early heart transplantation (HT) mortality. Our aim was to analyze PGF currently and explore the ability of a dedicated score for PGF risk stratification., Methods: After applying a dedicated PGF definition, we analyzed its incidence, mortality, and associated factors in a multicenter cohort of 857 HTs performed in 2006 to 2009. We used the following criteria: recipient right (R) atrial pressure ≥ 10 mm Hg; age (A) ≥ 60 years; diabetes (D) mellitus, and inotrope (I) dependence; donor age (A) ≥ 30 years, and length (L) of ischemia ≥ 240 minutes to calculate the RADIAL score for PGF risk prediction., Results: PGF incidence was 22%. The right ventricle was almost always affected, alone (45%) or as part of biventricular failure (47%). Mechanical circulatory support was used in 55%. Mortality attributable to PGF was 53% and extended through the third month after HT, but thereafter, PGF had little influence in long-term outcome. The RADIAL score was higher in PGF patients (2.78 ± 1.1 vs. 2.42 ± 1.1, p = 0.001) and stratified 3 groups with incremental PGF incidence: low risk (12.1%), intermediate risk (19.4%), and high risk (27.5%, p = 0.001)., Conclusions: PGF had a strong impact, with an incidence of 22% and a mortality exceeding 50% that extends through the third post-HT month. The RADIAL score classified patients into 3 groups with incremental risk for PGF and may be useful for its prevention and early therapy., (Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: To establish the accuracy and reliability of cardiac dual-source CT (DSCT) and two-dimensional contrast-enhanced echocardiography (CE-Echo) in estimating left ventricular (LV) parameters with respect to cardiac magnetic resonance imaging (CMR) as the reference standard., Methods: Twenty-five consecutive heart transplant recipients (20 male, mean age 62.7±10.4 years, mean time since transplantation 8.1±5.9 years) were prospectively recruited. Two blinded readers independently assessed LV ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and stroke volume (SV) for each patient after manual tracing of the endo- and epicardial contours in DSCT, CE-Echo and CMR cine images. Student's t-test for paired samples for differences, and Bland and Altman plots and Lin's concordance-correlation coefficients (CCC) for agreement were calculated., Results: There was no statistical difference between left ventricular parameters determined by DSCT and CMR. CE-Echo resulted in significant underestimation of left ventricular volumes (mean difference EDV: 15.94±14.19 ml and 17.1±17.06 ml, ESV: 8.5±9.3 and 7.32±9.14 ml with respect to DSCT and CMR), and overestimation of EF compared with the cross-sectional imaging modalities (3.78±8.47% and 2.14±8.35% with respect to DSCT and CMR). Concordance correlation coefficients for LV parameters using DSCT and CMR were higher (CCC≥0.75) than CCC values observed between CE-Echo and DSCT- or CMR-derived data (CCC≥0.54 and CCC≥0.49, respectively). Interobserver agreement was higher for DSCT and CMR values (CCC≥0.72 and CCC≥0.87, respectively)., Conclusion: In orthotopic heart transplantation cardiac DSCT allows accurate and reliable estimation of LV parameters compared with CMR, whereas CE-Echo seems to be insufficient to obtain precise measurements., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: A prolonged-release formulation of tacrolimus for once-daily administration (tacrolimus QD) has been developed. This phase II, open-label, multicenter, prospective single-arm study compared the pharmacokinetics (PK) of tacrolimus in stable heart transplant patients before and after conversion from twice-daily tacrolimus (tacrolimus BID) to tacrolimus QD., Methods: Heart transplant recipients (≥6 months after transplant), previously maintained on tacrolimus BID-based therapy, received tacrolimus BID from Days 1 to 7 and were converted on a 1:1 (mg/mg) basis to tacrolimus QD. Five 24-hour PK profiles were collected (Days 1, 7, 8, 14, 21). Safety parameters were also evaluated., Results: Of 85 patients, 45 (50.6%) completed all 5 evaluable PK profiles. Steady-state tacrolimus area under the curve, 0 to 24 hours (AUC(0-24)) and minimum concentration (C(min)) were comparable for both formulations, with treatment ratio means of 90.5% (90% confidence intervals [CI], 86.4%-94.6%) and 87.4% (95% CI, 82.9%-92.0%), respectively (acceptance interval, 80%-125%). There was good correlation between AUC(0-24) and C(min) for tacrolimus QD (r = 0.94) and BID (r = 0.91). The relationship between these 2 parameters was also similar., Conclusions: This study provides evidence for successful conversion from tacrolimus BID to QD on a 1:1 (mg/mg) total daily dose basis. Approximately one-third of patients may require dose adjustments. Both formulations were well tolerated, with stable renal function during the study. Adverse events were reported by approximately one-tenth of patients receiving tacrolimus BID and a quarter of those who received QD., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Introduction: To compare left atrial performance with dual-source CT (DSCT) with respect to magnetic resonance imaging (MRI) in orthotopic heart transplant recipients., Methods: Twenty-nine consecutive heart transplant recipients (27 male; mean age 64.1 +/- 13 years; mean time from transplantation 122.8 +/- 69.7 months) referred for exclusion of cardiac allograft vasculopathy underwent cardiac DSCT and MRI. Standard biatrial technique was employed in 13 subjects whereas 16 were transplanted after the bicaval technique. Axial 5-mm slice-thickness DSCT datasets reconstructed in 5% steps of the cardiac cycle and axial 5-mm SSFP-MRI images were analyzed. Two blinded readers manually traced left atrial contours in random order to estimate end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF). Parameters were compared with a paired sample Student t test. Concordance correlation coefficient (CCC) was calculated to determine measurement agreement between techniques and observers., Results: Left atrial volumes were significantly higher with cardiac DSCT (EDV: 170.9 +/- 78.1 mL; ESV: 139.5 +/- 76.6 mL) than with MRI (EDV: 158.2 +/- 72.5 mL; ESV: 124.2 +/- 68.2 mL), whereas left atrial EF was lower with DSCT (EF: 20.8% +/- 7.5% vs. 23.6% +/- 7.7%) (P < 0.05). Measurement agreement between DSCT and MRI was excellent for all parameters (CCC > or =0.82). Individuals operated with the biatrial anastomosis technique presented significantly higher left atrial volumes and lower EF compared with subjects with bicaval anastomosis. Interobserver agreement was excellent for all parameters (CCC > or =0.80)., Conclusion: Even if DSCT slightly overestimates left atrial volumes with respect to MRI, results remain clinically valid. Bicaval surgical technique offers improved left atrial performance compared with standard biatrial anastomosis. DSCT may be used as a reliable tool to estimate left atrial parameters in orthotopic heart transplant recipients.

Objective: Prolonged bleeding during cardiovascular surgery presents a risk for the patient and increases the time and cost of surgery. TachoSil is a ready-to-use haemostatic agent that consists of an equine collagen patch coated with human fibrinogen and thrombin. This trial evaluated the efficacy and safety (< or =30 days post-surgery) of TachoSil surgical patch compared with standard haemostatic fleece for the control of bleeding in patients undergoing cardiovascular surgery., Methods: Patients scheduled for elective surgery on the heart, ascending aorta or aortic arch requiring cardiopulmonary bypass were eligible for this open-label multicentre trial. After primary haemostatic measures, patients were randomised to TachoSil or conventional haemostatic fleece if an area of persisting haemorrhage was identified (target area). After the application of trial treatment, haemostasis was evaluated at 3 min (primary endpoint). If haemostasis was not achieved, trial treatment was re-applied and haemostasis assessed at 6 min (secondary endpoint)., Results: A total of 120 patients were randomised and 119 received trial treatment (TachoSil, n=59; standard treatment, n=60). Twenty-six percent of patients were female and the mean age was 67 years (range: 23-86 years). Baseline characteristics were similar in both the groups. Bleeding occurred mainly from the aorta (56%), right ventricle (16%) or right atrium (13%), more often from a vessel (68%) than tissue (32%), and was assessed to be arterial in 74% of cases. TachoSil was significantly superior to standard haemostatic fleece in controlling bleeding after insufficient primary haemostasis, with 75% (95% confidence interval (CI): 0.64-0.86) of the TachoSil group achieving haemostasis at 3 min compared with only 33% (95% CI: 0.21-0.45) of the standard treatment group (p<0.0001). This difference persisted at 6 min, with 95% of patients achieving haemostasis in the TachoSil group compared with 72% in the standard treatment group (p=0.0006). Three (5%) TachoSil patients compared with 17 (28%) standard treatment patients failed to achieve haemostasis at 6 min and received rescue treatment. TachoSil was well tolerated with adverse events generally similar in the two treatment groups., Conclusions: TachoSil was significantly superior to standard haemostatic fleece material in obtaining effective and fast intra-operative haemostasis in cardiovascular surgical procedures. TachoSil was safe and well tolerated.

Objective: To evaluate reliability of global left ventricular (LV) function and mass quantification in heart transplant recipients undergoing cardiac dual-source computed tomography examinations by means of manual contour tracing and using a region-growing-based semiautomatic segmentation analysis software tool., Materials and Methods: Twenty-six consecutive heart transplant recipients undergoing cardiac dual-source computed tomography examinations with tube current modulation were included. Double-oblique short-axis 8-mm slice thickness multiphase image reconstructions were used for manual contouring and axial 0.75 mm slices were used for the semiautomated segmentation. LV ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, cardiac output, and myocardial mass were assessed by both segmentation methods. Length of time needed for manual contour tracing and for the semiautomated software was recorded. Contrast-to-noise ratio was calculated in end-diastolic and end-systolic images., Results: No statistically significant differences were observed in LV functional parameters derived from semiautomatic contour detection algorithm as compared with manual contouring, with excellent agreement (concordance-correlation coefficient >or=0.80). The semiautomated contour detection algorithm overestimated LV mass (mean difference 12.84+/-3.39) (P<0.001). The evaluated software allowed to quantify LV parameters in a significantly shorter period of time (mean difference 201.68+/-121.98 s, P<0.001). Contrast-to-noise ratio in end-systole and end-diastole statistically differed (mean difference 5.29+/-2.94 Hounsfield units; P<0.01) but did not significantly hamper the semiautomated segmentation., Conclusions: Objective quantification of LV volumes using the evaluated semiautomated segmentation software is precise, reproducible, and time effective.

The image quality and optimal reconstruction interval for coronary arteries in heart transplant recipients undergoing non-invasive dual-source computed tomography (DSCT) coronary angiography was evaluated. Twenty consecutive heart transplant recipients who underwent DSCT coronary angiography were included (19 male, one female; mean age 63.1 +/- 10.7 years). Data sets were reconstructed in 5% steps from 30% to 80% of the R-R interval. Two blinded independent observers assessed the image quality of each coronary segments using a five-point scale (from 0 = not evaluative to 4 = excellent quality). A total of 289 coronary segments in 20 heart transplant recipients were evaluated. Mean heart rate during the scan was 89.1 +/- 10.4 bpm. At the best reconstruction interval, diagnostic image quality (score > or = 2) was obtained in 93.4% of the coronary segments (270/289) with a mean image quality score of 3.04 +/- 0.63. Systolic reconstruction intervals provided better image quality scores than diastolic reconstruction intervals (overall mean quality scores obtained with the systolic and diastolic reconstructions 3.03 +/- 1.06 and 2.73 +/- 1.11, respectively; P < 0.001). Different systolic reconstruction intervals (35%, 40%, 45% of RR interval) did not yield to significant differences in image quality scores for the coronary segments (P = 0.74). Reconstructions obtained at the systolic phase of the cardiac cycle allowed excellent diagnostic image quality coronary angiograms in heart transplant recipients undergoing DSCT coronary angiography.

The purpose of this study was to compare LV function and mass quantification derived from cardiac dual-source CT (DSCT) exams with those obtained by MRI in heart transplant recipients. Twelve heart transplant recipients who underwent cardiac DSCT and MRI examination were included. Double-oblique short-axis 8-mm slice thickness images were evaluated. Left ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, cardiac output and myocardial mass were manually assessed for each patient by two blinded readers. A systematic overestimation of all left ventricular volumes by DSCT when compared with MRI was observed. Mean difference was 16.58 +/- 18.61 ml for EDV, 4.9 4 +/- 6.84 ml for ESV, 11.64 +/- 13.58 ml for SV and 5.73 +/- 1.14 l/min for CO. Slightly lower values for left ventricular ejection fraction with DSCT compared with MRI were observed (mean difference 0.34 +/- 3.18%, p = 0.754). Correlation between DSCT and MRI for left ventricular mass was excellent (rho = 0.972). Bland and Altman plots and CCC indicated good agreement between DSCT and MRI left ventricular function and mass measurements. The interobserver correlation was good. In conclusion, DSCT accurately estimates left ventricular ejection fraction, volumes and mass in heart transplant recipients.

Objective: The purpose of this study was to evaluate the quality of dual-source CT images of the coronary arteries in heart transplant recipients with high heart rates., Subjects and Methods: Contrast-enhanced dual-source CT coronary angiography was performed on 23 heart transplant recipients (20 men, three women; mean age, 61.1 +/- 12.8 years). Data sets were reconstructed in 5% steps from 30% to 80% of the R-R interval. Two blinded independent readers using a 5-point scale (0, not evaluative; 4, excellent quality) assessed the quality of images of coronary segments., Results: The mean heart rate during scanning was 89.2 +/- 10.4 beats/min. Interobserver agreement on the quality of images of the whole coronary tree was a kappa value of 0.78 and for selection of the optimal reconstruction interval was a kappa value of 0.82. The optimal reconstruction interval was systole in 17 (74%) of the 23 of heart transplant recipients. At the best reconstruction interval, diagnostic image quality (score >or= 2) was obtained in 92.1% (303 of 329) of the coronary artery segments. The mean image quality score for the whole coronary tree was 3.1 +/- 1.01. No significant correlation between mean heart rate (rho = 0.31) or heart rate variability (rho = 0.23) and overall image quality score was observed (p = not significant)., Conclusion: Dual-source CT acquisition yields coronary angiograms of diagnostic quality in heart transplant recipients. Mean heart rate and heart rate variability during scanning do not have a negative effect on the overall quality of images of the coronary arteries.

Background: Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma., Methods: This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti-interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003., Results: Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used., Conclusions: Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.

Background: Metabolic syndrome (MS) is a cluster of cardiovascular risk factors highly prevalent in patients with ischemic heart disease (IHD), the main etiologic cause for heart transplantation (HT)., Methods: Data for 111 HT patients of a single institution were collected. The assessment of MS was made, according to the ATP III criteria, when 3 of the following diagnostic criteria were present: waist circumference >102 cm (men) or >88 cm (women); triglycerides > or =150 mg/dl; HDL-cholesterol <40 mg/dl (men) or <50 mg/dl (women); blood pressure > or =130/85 mm Hg; and fasting glucose > or =110 mg/dl, or diabetes mellitus previously diagnosed. Renal function was assessed by glomerular filtration rate, as estimated by the MDRD abbreviated equation., Results: Mean age of the 111 HT patients was 63.0 (11.0) years and 101 (91.0%) were men. The median time since transplant was 7.0 (3.0 to 13.0) years, and IHD was the primary cause for HT (56.8%). The prevalence of MS was 42.3% and was statistically higher in patients with IHD prior to HT (52.4% vs 27.2%; p = 0.007). Patients with MS were older but had the same time of follow-up since their HT. An analysis of the sample in tertiles of years since HT showed that MS was more prevalent in subjects who received HT due to IHD only in the lowest and highest tertile. Fifty-three patients (47.7%) had abdominal obesity, 47 (43.2%) were overweight and 22 (19.8%) were obese; most patients with abdominal obesity were diagnosed with MS (82.6%). Multivariate analysis showed a strong association between abdominal obesity and MS (odds ratio [OR] 6.2, 95% confidence interval [CI] 1.9 to 19.8), even after adjustment for body mass index, and also showed an independent association of MS with severe renal dysfunction (OR 9.8; p = 0.02)., Conclusions: MS is highly prevalent in HT patients and abdominal obesity is the leading cause of this clustering. IHD status and time since HT are major determinants in the prevalence of MS in HT patients.

Objective: Our aim was to compare the efficacy of surgical versus percutaneous administration of skeletal myoblasts (SkM) in a swine model of chronic myocardial infarction and to determine the mechanism(s) involved in their beneficial effect., Methods: Two months after induction of myocardial infarction (MI), Goettingen miniature pigs underwent autologous SkM transplant either by direct surgical injection (n=6) or percutaneous access and intramyocardial delivery under fluoroscopic and echocardiographic guidance (n=6). Control animals received media alone (n=4). Functional analysis was performed by 2D echocardiography. Myoblast engraftment, in vivo cell differentiation, vessel formation, fibrosis, and the ratio between collagen type I/III deposition were analyzed in the infarct (IA) and non-infarct area (NIA) by immunohistochemistry., Results: Animals received a median of 407.55+/-115x10(6) BrdU-labeled autologous SkM. Myoblast transplant was associated with a statistically significant increase in left ventricular ejection fraction (p<0.01), increased vasculogenesis and decreased fibrosis (p<0.05), and reduced collagen type I/III ratio in the IA and NIA areas as compared with control animals. No differences were found between groups receiving SkM by percutaneous or surgical access., Conclusions: Our results indicate that increased vasculogenesis and changes in matrix remodeling with decreased fibrosis are associated with the beneficial effect of SkM transplant in chronic MI. The equivalent benefit observed from surgical and percutaneous delivery has important clinical implications.

Cytomegalovirus (CMV) infection remains an important complication of transplantation. The last decade has been characterized by improvements to management that has reduced its morbidity and mortality. The advance has been particularly important in the diagnosis and prevention. Several techniques have been developed that allow the increasingly rapid and sensitive diagnosis. The different preventive strategies include use of appropriate blood products, immune globulin, and antiviral agents either as prophylaxis or pre-emptive therapy. The development of effective oral drugs as valganciclovir also represents a new advance. It is necessary to summarize these advances to facilitate the development of local policies reflecting recent changes. The Group of Study of Infections in Transplantation (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) has therefore produced actual recommendations in the management of CMV infection after transplantation.

The aim of this investigation was to assess organ injury provoked by a new pulsatile pump for cardiopulmonary bypass (CPB) with respect to a conventional centrifugal pump. Eight pigs in the pulsatile group (PG) and five in the centrifugal group (CG) underwent a partial CPB lasting 180 min. The animals were sacrificed 180 min after CPB was suspended, and a morphological study of fragments of ventricular wall, liver, lung, and kidney was performed. In CG, centrilobular hepatic necrosis was observed accompanied by sinusoidal dilatation and congestion, multiple focuses of myocardial ischemia, and minor to moderate pulmonary interstitial edema. In PG, diffuse centrilobular sinusoidal congestion in the liver, congestion and capillary dilatation of low intensity in the ventricular wall, and nonsignificant pulmonary interstitial septal edema was observed. In the kidney, both groups showed degenerative changes of the tubular cells and nonsignificant tubular dilatation. These results suggest a better peripheral circulation in the pulsatile group.

Aim: Experimental animal studies suggest that the use of skeletal myoblast in patients with myocardial infarction may result in improved cardiac function. The aim of the study was to assess the feasibility and safety of this therapy in patients with myocardial infarction., Methods and Results: Twelve patients with old myocardial infarction and ischaemic coronary artery disease underwent treatment with coronary artery bypass surgery and intramyocardial injection of autologous skeletal myoblasts obtained from a muscle biopsy of vastus lateralis and cultured with autologous serum for 3 weeks. Global and regional cardiac function was assessed by 2D and ABD echocardiogram. 18F-FDG and 13N-ammonia PET studies were used to determine perfusion and viability. Left ventricular ejection fraction (LVEF) improved from 35.5+/-2.3% before surgery to 53.5+/-4.98% at 3 months (P=0.002). Echocardiography revealed a marked improvement in regional contractility in those cardiac segments treated with skeletal myoblast (wall motion score index 2.64+/-0.13 at baseline vs 1.64+/-0.16 at 3 months P=0.0001). Quantitative 18F-FDG PET studies showed a significant (P=0.012) increased in cardiac viability in the infarct zone 3 months after surgery. No statistically significant differences were found in 13N-ammonia PET studies. Skeletal myoblast implant was not associated with an increase in adverse events. No cardiac arrhythmias were detected during early follow-up., Conclusions: In patients with old myocardial infarction, treatment with skeletal myoblast in conjunction with coronary artery bypass is safe and feasible and is associated with an increased global and regional left ventricular function,improvement in the viability of cardiac tissue in the infarct area and no induction of arrhythmias.

The deep inferior epigastric perforator (DIEP) flap has been shown to be a valid option for breast reconstruction, as it has certain advantages over the free TRAM flap, including lower morbidity in the donor area, conservation of abdominal wall function, and reduced postoperative pain. However, some cases of venous congestion in using the DIEP flap have been described. The authors present a case in which the venous return in a DIEP flap objectively (by measurement with a flux meter) presented a marked improvement (from 4 ml/min to 13.9 ml/min) after venous drainage was increased by means of the supplementary anastomosis of a comitant vein from the deep inferior epigastric pedicle to the intercostal branch of the internal mammary vein. The preservation of this branch is a simple and effective technique to improve the venous drainage of DIEP flaps, whether signs of congestion are present or not.

We describe the surgical procedure of orthotopic heart transplantation (OHT) in a recipient with persistent left superior vena cava (LSVC) and isolated noncompaction of the left ventricle. The bicaval anastomosis technique was performed using and isolating his native coronary sinus to let the left superior vena cava drain into his own inferior vena cava through the native coronary sinus.