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Down syndrome is one of the most common genetic diseases, generally associated with an increased probability of congenital heart diseases. This increased risk contributes to escalated levels of morbidity and mortality. In this study, we sought to analyze nationwide data of pediatric and adult patients with Down syndrome and congenital heart disease over a 15-year period. Data obtained from the hospital discharge form between 2001 and 2016 of patients diagnosed with Down syndrome in Italy and at least one congenital heart disease were included. Information on 12362 admissions of 6527 patients were included. Age at first admission was 6.2 ± 12.8 years and was a predictor of mortality (HR = 1.51, 95% CI 1.13-2.03, p = 0.006). 3923 (60.1%) patients underwent only one admission, while 2604 (39.9%) underwent multiple (> 1) admissions. There were 5846 (47.3%) admissions for cardiac related symptoms. Multiple admissions (SHR: 3.13; 95% CI: 2.99, 3.27; P < 0.01) and cardiac admissions (SHR: 2.00; 95% CI: 1.92, 2.09; P < 0.01) were associated with an increased risk of additional potential readmissions. There was an increased risk of mortality for patients who had cardiac admissions (HR = 1.45, 95% CI: 1.08-1.94, p = 0.012), and for those who underwent at least 1 cardiac surgical procedure (HR = 1.51, 95% CI 1.13-2.03, p = 0.006)., Conclusions: A younger age at first admission is a predictor for mortality in patients with Down syndrome and congenital heart disease. If patients undergo more than one admission, the risk of further readmissions increases. There is a pivotal role for heart disease in influencing the hospitalization rate and subsequent mortality., What Is Known: • Down syndrome individuals often face an increased risk of congenital heart diseases. • Congenital heart diseases contribute significantly to morbidity and mortality in Down syndrome patients., What Is New: • This study analyzes nationwide data covering a 15-year period of pediatric and adult patients in Italy with Down syndrome and congenital heart disease. • It identifies a younger age at first admission as a predictor for mortality in these patients, emphasizing the criticality of early intervention. • Demonstrates a correlation between multiple admissions, particularly those related to cardiac issues, and an increased risk of further readmissions, providing insights into the ongoing healthcare needs of these individuals., (© 2024. The Author(s).)

Mitral regurgitation is one of the most prevalent valvulopathies with a disease burden that incurs significant healthcare costs globally. Surgical repair of the posterior mitral valve leaflet is a standard treatment, but approaches for repairing the anterior mitral valve leaflet are not widely established. Since anterior leaflet involvement is less common and more difficult to repair, fewer studies have investigated its natural history and treatment options. In this review, we discuss surgical techniques for repairing the anterior leaflet and their outcomes, including survival, reoperation, and recurrence of regurgitation. We show that most patients with mitral regurgitation from the anterior leaflet can be repaired with good outcomes if performed at centers with expertise. Additionally, equal consideration for early repair should be given to patients with mitral regurgitation from both anterior and posterior pathology. However, more studies to better evaluate the efficacy and safety of anterior mitral valve leaflet repair are needed., (Copyright © 2024 Hellenic Society of Cardiology. Published by Elsevier Inc. All rights reserved.)

Background: United Network for Organ Sharing (UNOS) allocation criteria changed in 2018 to accommodate the increased prevalence of patients on a ventricular assist device as a bridge to heart transplant and prioritize sicker people in anticipation of a heart graft. We aimed to assess the impact of patient age in the new allocation policy on mortality following heart transplantation. Secondary outcomes included the effect of age ≥70 on post-transplant events, including stroke, dialysis, pacemaker, and rejection requiring treatment., Methods: The UNOS Registry was queried to identify patients who underwent heart transplants alone in the US between 2000 and 2021. Patients were divided into groups according to their age (over 70 and under 70 years old)., Results: Patients aged over 70 were more likely to require dialysis during follow-up, but less likely to experience rejection requiring treatment, compared with patients aged <70. Age ≥70 in the new allocation system was a significant predictor of 1-year mortality (adjusted HR: 1.41; 95% CI: 1.05-1.91; p = .024), but its effect on 5-year mortality was not significant after adjusting for potential confounders (adjusted HR: 1.27; 95% CI:.97-1.66; p = .077). Undergoing transplantation under the new allocation policy vs the old allocation policy was not a significant predictor of mortality in patients over 70 years old., Conclusions: Age ≥70 is a significant predictor of 1-year mortality following heart transplantation, but not at 5 and 10 years; however, the new allocation does not seem to have changed the outcomes for this group of patients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The large incisions and long recovery periods that accompany traditional cardiac surgery procedures along with the constant patient demand for minimally invasive procedures have motivated cardiac surgeons to implement the robotic technologies in their armamentarium. The robotic systems have been utilized successfully in various cardiac procedures including atrial septal defect repair, left atrial myxoma resection, MAZE procedure and left ventricular lead placement, yet coronary artery bypass and mitral valve repair still comprise the vast majority of them. This review analyzes the development of the robot-assisted cardiac surgery in recent years, its outcomes, advantages, disadvantages, its patient selection criteria as well as its economic feasibility. Robotic endovascular surgery, albeit its limited applications, is presently considered an attractive alternative to conventional endovascular approaches. The increased flexibility and precision along with the wider range of accessible anatomy provided by the endovascular robotic systems, have increased the pool of patients that can be offered minimally invasive treatment options and have helped to overcome many limitations of the traditional endovascular procedures. With this review we aimed to summarize the applications of the commercially available endovascular robotic devices, as well as the limitations and the future perspectives in the field of endovascular robotic surgery., (Copyright © 2022. Published by Elsevier Inc.)

(1) Background: Heart failure is an extremely impactful health issue from both a social and quality-of-life point of view and the rate of patients with this condition is destined to rise in the next few years. Transplantation remains the mainstay of treatment for end-stage heart failure, but a shortage of organs represents a significant problem that prolongs time spent on the waiting list. In view of this, the selection of donor and recipient must be extremely meticulous, considering all factors that could predispose to organ failure. One of the main considerations regarding heart transplants is the risk of graft rejection and the need for immunosuppression therapy to mitigate that risk. In this study, we aimed to assess the characteristics of patients who need immunosuppression treatment for rejection within one year of heart transplantation and its impact on mid-term and long-term mortality. (2) Methods: The United Network for Organ Sharing (UNOS) Registry was queried to identify patients who solely underwent a heart transplant in the US between 2000 and 2021. Patients were divided into two groups according to the need for anti-rejection treatment within one year of heart transplantation. Patients' characteristics in the two groups were assessed, and 1 year and 10 year mortality rates were compared. (3) Results: A total of 43,763 patients underwent isolated heart transplantation in the study period, and 9946 (22.7%) needed anti-rejection treatment in the first year. Patients who required treatment for rejection within one year after transplant were more frequently younger (49 ± 14 vs. 52 ± 14 years, p < 0.001), women (31% vs. 23%, p < 0.001), and had a higher CPRA value (14 ± 26 vs. 11 ± 23, p < 0.001). Also, the rate of prior cardiac surgery was more than double in this group (27% vs. 12%, p < 0.001), while prior LVAD (12% vs. 11%, p < 0.001) and IABP (10% vs. 9%, p < 0.01) were more frequent in patients who did not receive anti-rejection treatment in the first year. Finally, pre-transplantation creatinine was significantly higher in patients who did not need treatment for rejection in the first year (1.4 vs. 1.3, p < 0.01). Most patients who did not require anti-rejection treatment underwent heart transplantation during the new allocation era, while less than half of the patients who required treatment underwent transplantation after the new allocation policy implementation (65% vs. 49%, p < 0.001). Patients who needed rejection treatment in the first year had a higher risk of unadjusted 1 year (HR: 2.25; 95% CI: 1.88-2.70; p < 0.001), 5 year (HR: 1.69; 95% CI: 1.60-1.79; p < 0.001), and 10 year (HR: 1.47; 95% CI: 1.41-1.54, p < 0.001) mortality, and this was confirmed at the adjusted analysis at all three time-points. (4) Conclusions: Medical treatment of acute rejection was associated with significantly increased 1 year mortality compared to patients who did not require anti-rejection therapy. The higher risk of mortality was confirmed at a 10 year follow-up. Further studies and newer follow-up data are required to investigate the role of anti-rejection therapy in the heart transplant population.

Background: United Network for Organ Sharing (UNOS) allocation criteria changed in 2018 to accommodate the increased prevalence of ventricular assist device use as a bridge to heart transplant, which consequently prioritized sicker patients. We aimed to assess the impact of this new allocation policy on the length of stay following heart transplantation. Secondary outcomes include other risk factors for prolonged hospitalization and its effect on mortality and postoperative complications., Methods: The UNOS Registry was queried to identify patients who underwent isolated heart transplants in the United States between 2001 and 2023. Patients were divided into quartiles according to their respective length of stay., Results: A total of 57 020 patients were included, 15 357 of which were allocated with the new system. The median hospital length of stay was 15 days (mean 22.7 days). Length of stay was longer in the new allocation era (25 ± 30 vs. 22 ± 27 days, p < .001). The longer length of stay was associated with increased 5-year mortality in the new allocation system (aHR: 1.18; 95% CI: 1.15, 1.20; p-value: < .001)., Conclusion: Longer hospital stays and associated observed increased risk for mortality in the era after the allocation criteria change reflect the rationale of this shift which was to prioritize heart transplants for sicker patients. Further studies are needed to track the progress of surgical and perioperative management of these studies over time., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Cardiac graft failure may require repeat heart transplantation (HTx). Outcomes of patients that undergo repeat HTx have not been well described. We compared patients that received repeat HTx with patients that received initial HTx by inquiring the United Network for Organ Sharing (UNOS) database between 2015 and 2021. The primary endpoint was all-cause mortality, while the role of baseline characteristics was also investigated. Patients were stratified according to whether they received initial HTx (n = 19,727, 97%) or repeat HTx (n = 578, 3%). Among the study population, 10,860 (53.5%) patients received a HTx using the old UNOS allocation system, whereas 9445 (46.5%) patients received a HTx after the implementation of the new UNOS donor allocation system in October 2018. In this sub-group of HTx recipients in the new allocation system era, the adjusted 1-year survival of repeat HTx patients remained lower than that of initial HTx patients (hazard ratio (HR): 1.19; 95% confidence interval (CI): 1.15, 3.18; p = 0.013). When we compared the 1-year survival of repeat HTx patients before and after the implementation of the new allocation system, the adjusted 1-year survival was similar between groups (HR: 1.14; 95% CI: 0.71, 1.84; p = 0.591). The unadjusted risk of 30-day mortality was not significantly different in the new vs old allocation system. Mortality associated with repeat HTx remained higher than initial HTx but the new donor allocation system implementation did not affect outcomes.

Background: The 2018 United-Network-for-Organ-Sharing (UNOS) allocation-system changes resulted in greater recognition of mechanical circulatory support (MCS), leading to more heart transplantations (HTx) in patients with MCS. We aimed to investigate the effect of the new UNOS allocation system on the need for a permanent pacemaker and associated complications following HTx., Methods: The UNOS Registry was questioned, to identify patients that received HTx in the US between 2000 and 2021. The primary objectives were to identify risk factors for the need for a pacemaker implantation following HTx., Results: 49,529 HTx patients were identified, 1421 (2.9%) requiring a pacemaker post-HTx. Patients who required a pacemaker were older (53.9 ± 11.5 vs. 52.6 ± 12.8 years, p < 0.001), more frequently white (73% vs. 67%; p < 0.001) and less frequently black (18% vs. 20%; p < 0.001). In the pacemaker group, UNOS status 1A (46% vs. 41%; p < 0.001) and 1B (31% vs. 27%; p < 0.001) were more prevalent, and donor age was higher (34.4 ± 12.4 vs. 31.8 ± 11.5 years; p < 0.001). One-year survival was no different between the groups (HR: 1.08; 95% CI: 0.85, 1.37; p = 0.515). An era effect was observed (per year: OR: 0.97; 95% CI: 0.96, 0.98; p = 0.003), while ECMO pre-transplant was associated with lower risk of a pacemaker (OR: 0.41; 95% CI: 0.19, 0.86; p < 0.001)., Conclusions: While associated with various patient and transplant characteristics, pacemaker implantation does not seem to impact one-year survival after HTx. The need for pacemaker implantation was lower in the more recent era and in patients who required ECMO pre-transplant, a finding explained by recent advances in perioperative care.

Background: Patients on the waiting list for heart transplantation (HT) can become inactive or made status seven because of medical reasons, such adverse events, complications, or psychosocial circumstances. If the condition that caused the inactivation is resolved, patients are re- activated. Information about the prognostic implications of Status 7 in the new donor heart allocation system has not been described. To bridge this knowledge gap, we performed an analysis of the United Network of Organ Sharing (UNOS) registry., Methods: Data on adult patients who underwent HT between October 18th, 2018 and October 2021, were queried from the UNOS registry. The main outcomes were post- transplant all-cause mortality, 1-year all-cause mortality and treated acute rejection. Since re-transplantation is a competing event for all-cause mortality, we performed competing risk survival analysis and reported sub distribution hazard ratios (SHR) from the Fine and Gray model to examine the relationship between inactive status and all-cause mortality., Results: A total of 5267 adult patients underwent HT and were previously listed as Status 1 or Status 2 in the new allocation system. We identified 946 HT recipients temporarily inactivated while on HT list (18%). The number of temporarily inactive patients remained stable since the implementation of the new donor allocation system (p = .37). Approximately, two-thirds of temporarily inactive patients (65.9%) were inactivated for being too sick, whereas other frequent justifications for inactivity included left ventricular assist device implantation (7.8%) and insurance related issues (4.8%). Temporarily inactive HT recipients were more likely to be African Americans, males, have a higher body mass index (BMI) and significantly longer waiting time (391.6 ± 600 vs. 72.3 ± 223 days, p < .001) compared with never inactivated patients. In the unadjusted analyses 30-day mortality did not differ between groups, but both 1-year and overall all-cause mortality was significantly higher in temporarily inactive patients (1-year: SHR: 1.3; 95% confidence intervals [CI]: 1.03, 1.64; p = .028, overall mortality SHR: 1.31; 95% CI: 1.06, 1.64; p = .014). After adjustment for donor and recipient characteristics, a trend towards higher 1-year and overall mortality remained (1-year: SHR 1.32; 95% CI .99, 1.76, p = .006, overall mortality SHR: 1.29; 95% CI: .98-1.68, p = .065). No differences in treated acute allograft rejection at 1 year were found between groups., Conclusions: Temporary inactive status while waiting for HT occurs in approximately one in five HT recipients listed in higher urgency categories after the implementation of the new allocation system. A signal of adverse long-term outcomes was found, and this could be explained by differences in recipient characteristics. Further research is required to elucidate pathways involved and possible implications for clinical practice., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Competing Interests: Disclosures The authors have no conflicts of interest to declare.

Background: Machine learning (ML) is increasingly being applied in Cardiology to predict outcomes and assist in clinical decision-making. We sought to develop and validate an ML model for the prediction of mortality after heart transplantation (HT) in adults with congenital heart disease (ACHD)., Methods: The United Network for Organ Sharing (UNOS) database was queried from 2000 to 2020 for ACHD patients who underwent isolated HT. The study cohort was randomly split into derivation (70%) and validation (30%) datasets that were used to train and test a CatBoost ML model. Feature selection was performed using SHapley Additive exPlanations (SHAP). Recipient, donor, procedural, and post-transplant characteristics were tested for their ability to predict mortality. We additionally used SHAP for explainability analysis, as well as individualized mortality risk assessment., Results: The study cohort included 1033 recipients (median age 34 years, 61% male). At 1 year after HT, there were 205 deaths (19.9%). Out of a total of 49 variables, 10 were selected as highly predictive of 1-year mortality and were used to train the ML model. Area under the curve (AUC) and predictive accuracy for the 1-year ML model were .80 and 75.2%, respectively, and .69 and 74.2% for the 3-year model, respectively. Based on SHAP analysis, hemodialysis of the recipient post-HT had overall the strongest relative impact on 1-year mortality after HΤ, followed by recipient-estimated glomerular filtration rate, age and ischemic time., Conclusions: ML models showed satisfactory predictive accuracy of mortality after HT in ACHD and allowed for individualized mortality risk assessment., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Reduced mitochondrial function increases myocardial susceptibility to ischemia-reperfusion injury (IRI) in diabetic hearts. Mitochondrial transplantation (MT) ameliorates IRI, however, the cardioprotective effects of MT may be limited using diabetic mitochondria. Zucker Diabetic Fatty (ZDF) rats were subjected to temporary myocardial RI and then received either vehicle alone or vehicle containing mitochondria isolated from either diabetic ZDF or non-diabetic Zucker lean (ZL) rats. The ZDF rats were allowed to recover for 2 h or 28 days. MT using either ZDF- or ZL-mitochondria provided sustained reduction in infarct size and was associated with overlapping upregulation of pathways associated with muscle contraction, development, organization, and anti-apoptosis. MT using either ZDF- or ZL-mitochondria also significantly preserved myocardial function, however, ZL- mitochondria provided a more robust long-term preservation of myocardial function through the mitochondria dependent upregulation of pathways for cardiac and muscle metabolism and development. MT using either diabetic or non-diabetic mitochondria decreased infarct size and preserved functional recovery, however, the cardioprotection afforded by MT was attenuated in hearts receiving diabetic compared to non-diabetic MT., (© 2022. The Author(s).)

Objective: Restoration of biventricular circulation is an alternative management strategy in unbalanced atrioventricular canal defects (uAVCDs), especially in patients with risk factors for single-ventricle palliation (SVP) failure. When ventricular volume is inadequate for biventricular circulation, recruitment procedures may accommodate its growth. In this study, we review our uAVCD experience with biventricular conversion (BIVC) after prior SVP., Methods: This is a single-institution, retrospective cohort study of uAVCD patients who underwent BIVC after SVP, with staged recruitment (staged) or primary BIVC (direct) between 2003 to 2018. Mortality, unplanned reinterventions, imaging, and catheterization data were analyzed., Results: Sixty-five patients underwent BIVC from SVP (17 stage 1, 42 bidirectional Glenn, and 6 Fontan). Decision for conversion was based on poor SVP candidacy (n = 43) or 2 adequately sized ventricles (n = 22). Of the 65 patients, 20 patients underwent recruitment before conversion. The staged group had more severe ventricular hypoplasia than the direct group, reflected in prestaging end-diastolic volume z scores (-4.0 vs -2.6; P  < .01), which significantly improved after recruitment (-4.0 to -1.8; P  < .01). Median follow-up time was 1.0 years. Survival and recatheterizations were similar between both groups (hazard ratio, 0.9; 95% CI, 0.2-3.7; P  = .95 and hazard ratio, 1.9; 95% CI, 0.9-4.1; P  = .09), but more reoperations occurred with staged approach (hazard ratio, 3.1; 95% CI, 1.3-7.1; P  = .01)., Conclusions: Biventricular conversion from SVP is an alternative strategy to manage uAVCD, particularly when risk factors for SVP failure are present. Severe forms of uAVCDs can be converted with staged BIVC with acceptable mortality, albeit increased reinterventions, when primary BIVC is not possible., (© 2022 The Author(s).)

Background: Available literature indicates the possible detrimental effect of sex mismatching on mortality in patients undergoing heart transplantation. Our objective was to examine the role of sex and heart mass (predicted heart mass [PHM]) mismatch on mortality and graft rejection in patients undergoing heart transplantation in the US., Methods: Data on adult patients who underwent heart transplantation between January 2015 and October 2021 were queried from the United Network of Organ Sharing (UNOS) registry. The main outcomes were all-cause mortality, 1-year all-cause mortality and treated acute rejection., Results: A total of 19 805 adult patients underwent heart transplant during the study period. 92.2% of the patients in the female graft to male group had a PHM mismatch <25%, while only 38.5% had such a mismatch in the male graft to female group. In male to male and female to female groups, 79% and 76% of the patients had a PHM mismatch <25% (p = .122). Proportion of PHM mismatch was similar throughout the study period. Unadjusted analysis showed that male recipients of female grafts had increased risk for all-cause mortality (hazard ratio [HR]: 1.13; 95% confidence intervals [CI]: 1.02, 1.27; p = .026) and 1-year mortality (HR: 1.26; 95% CI: 1.09, 1.45; p = .002) compared to male recipients of male grafts. Graft failure incidence was also higher (HR: 1.12; 95% CI: 1.01, 1.25; p = .041). However, all these associations were non- significant after risk factor adjustment., Conclusions: Sex mismatching is associated with post-transplant mortality with transplantation of female donor grafts to male recipients demonstrating worse outcomes, although this association disappears after risk factor adjustment. Further research is required to elucidate the need for potential changes in clinical practice., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Concerns about the impact of the new donor heart allocation system on posttransplant outcomes have emerged after its implementation. We sought to evaluate the characteristics and outcomes of left ventricular assist device (LVAD) recipients transplanted before and after the implantation of the new policy on October 18, 2018., Methods: Data on bridge to transplantation of adult patients with LVAD between January 2015 and October 2021, with durable LVAD as a (BTT), was queried from the United Network of Organ Sharing (UNOS) registry. The main outcomes were 30-day all-cause mortality, 30-day fatal graft failure, 1-year all-cause mortality, treated acute rejection at 1 year and renal replacement therapy (RRT) for acute renal failure., Results: In our study, 7096 patients met the inclusion criteria including 2435 in the new allocation system. The transplanted patients in the new allocation system era had older donor age, longer ischemic time, and higher proportion of newer generation LVADs. Adjusted 30-day all-cause mortality was significantly lower for LVAD recipients in the new allocation system era (2.5% vs. 3.6%; sub-hazard ratio [SHR] 0.36, 95% Confidence intervals [CI] 0.27-0.48, p < 0.001) without differences in the risk of fatal graft failure and 1-year mortality (7.8% vs. 9.6%). Significantly lower adjusted 30-day mortality with HVAD and HM3 devices than HM2 in the new allocation system era was found, without differences in 1-year mortality. Acute allograft rejection requiring treatment was significantly lower (Odds Ratio 0.78, 95% CI 0.65-0.94, p = 0.01), whereas a trend toward higher risk of renal failure requiring RRT was identified., Conclusions: Despite changing donor characteristics and longer ischemic times, posttransplant outcomes in LVAD recipients have not worsened with the implementation of the new allocation system and this finding is related to the use of newer generation continuous flow LVADs., (© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Purpose of Review: To summarize the contemporary practice of pericardiectomy and pericardial window. We discuss the indications, preoperative planning, procedural aspects, postprocedural management, and outcomes of each procedure., Recent Findings: Surgical approaches for the treatment of pericardial disease have been around even before the emergence of cardiopulmonary bypass. Since the forthcoming of cardiopulmonary bypass, there have been significant changes in the epidemiology and diagnostic approach of pericardial diseases as well as advancements in the surgical techniques and perioperative management used in the care of these patients. Pericardiectomy has an average mortality of almost 7% and is typically performed in patients with advanced symptoms from constrictive pericarditis and relatively few comorbidities. Pericardial window is a safe procedure for the treatment of pericardial effusion that can be performed with different approaches., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Right ventricular failure (RVF) continues to affect patients supported with durable left ventricular assist devices (LVAD) and results in increased morbidity and mortality. Information regarding the impact of right ventricular response to pre-operative optimization on outcomes is scarce. Methods: Single-center retrospective analysis of consecutive patients who underwent first continuous flow LVAD implantation between 2006 and 2020. Patients with bi-ventricular support before LVAD or without hemodynamic data were excluded. Invasive hemodynamics at baseline and after pre-operative medical and/or temporary circulatory support were recorded. Patients were grouped in the following categories: A: No Hemodynamic RV dysfunction (RVD) at baseline; B: RVD with achievement of RV hemodynamic optimization goals; C: RVD without achievement of RV optimization goals. The main outcomes were right ventricular failure defined as inotropes >14 days after implantation, or postoperative right ventricular mechanical support, and all-cause mortality. Results: Overall, 128 patients were included in the study. The mean age was 58 ±12.5 years, 74.2% were males and, 68.7% had non-ischemic cardiomyopathy. Hemodynamic RVD was present in 70 (54.7%) of the patients at baseline. RV hemodynamic goals were achieved in 46 (79.31%) patients with RVD and in all the patients without RVD at baseline. Failure to achieve hemodynamic optimization goals was associated with a significantly higher risk of RVF after LVAD implantation (adjusted OR 4.37, 95% CI 1.14−16.76, p = 0.031) compared with no RVD at baseline and increased 1-year mortality compared with no RVD (adjusted HR 4.1, 95% CI 1.24−13.2, p = 0.02) and optimized RVD (adjusted HR 6.4, 95% CI 1.6−25.2, p = 0.008).Conclusion: Among patients with RVD, the inability to achieve hemodynamic optimization goals was associated with higher rates of RV failure and increased 1-year all-cause mortality post LVAD implantation.

Objective: Το perform a systematic review with meta-analysis of published data comparing outcomes between a percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in dialysis-dependent patients., Methods: We searched PubMed, Scopus, and Cochrane databases for studies including dialysis-dependent patients who underwent either CABG or PCI. This meta-analysis follows the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We conducted one-stage and two-stage meta-analysis with Kaplan-Meier-derived individual patient data for overall survival and meta-analysis with the random-effects model for the in-hospital mortality and repeat revascularization., Results: Twelve studies met our eligibility criteria, including 13,651 and 28,493 patients were identified in the CABG and PCI arms, respectively. Patients who underwent CABG had overall improved survival compared with those who underwent PCI at the one-stage meta-analysis (hazard ratio [HR]: 1.12, 95% confidence interval [CI]: 1.09-1.16, p < .0001) and the two-stage meta-analysis (HR: 1.15, 95% CI: 1.08-1.23, p < .001, I 2  = 30.0%). Landmark analysis suggested that PCI offers better survival before the 8.5 months of follow-up (HR: 0.96, 95% CI: 0.92-0.99, p = .043), while CABG offers an advantage after this timepoint (HR: 1.3, 95% CI: 1.22-1.32, p < .001). CABG was associated with increased odds for in-hospital mortality (odds ratio [OR]: 1.70, 95% CI: 1.50-1.92, p < .001, I 2  = 0.0%) and decreased odds for repeat revascularization (OR: 0.22, 95% CI: 0.14-0.34, p < .001, I 2  = 58.08%)., Conclusions: In dialysis-dependent patients, CABG was associated with long-term survival but a higher risk for early mortality. The risk for repeat revascularization was higher with PCI., (© 2022 Wiley Periodicals LLC.)

Background The clinical characteristics of mTOR (mammalian target of rapamycin) inhibitors use in heart transplant recipients and their outcomes have not been well described. Methods and Results We compared patients who received mTOR inhibitors within the first 2 years after heart transplantation to patients who did not by inquiring the United Network for Organ Sharing (UNOS) database between 2010 and 2018. The primary end point was all-cause mortality with retransplantation as a competing event. Rejection, malignancy, hospitalization for infection, and renal transplantation were secondary end points. There were 1619 (9%) and 15 686 (81%) mTOR inhibitors+ and mTOR inhibitors- patients, respectively. Body mass index, induction, cardiac allograft vasculopathy, calculated panel reactive antibody, and fewer days in 1A status were independently associated with mTOR inhibitors+ status. Over a follow-up of 10.4 years, there was no difference in all-cause mortality after adjusting for donor and recipient characteristics (adjusted subdistribution hazard ratio, 1.03 [0.90-1.19]; P =0.66). mTOR inhibitors+ were independently associated with increased risk for rejection (odds ratio [OR], 1.43 [1.11-1.83]; P =0.005) and basal skin cancer (OR, 1.35 [1.19-1.51]; P =0.012) but not for infection or renal transplantation. Conclusions mTOR inhibitors are used in <10% patients in the first 2 years after heart transplantation and are noninferior to contemporary immunosuppression regimens in terms of all-cause mortality, infection, malignancy, or renal transplantation. They are associated with risk for rejection.

Kynurenic acid (KynA) is tissue protective in cardiac, cerebral, renal, and retinal ischemia models, but the mechanism is unknown. KynA can bind to multiple receptors, including the aryl hydrocarbon receptor, the a7 nicotinic acetylcholine receptor (a7nAChR), multiple ionotropic glutamate receptors, and the orphan G protein-coupled receptor GPR35. Here, we show that GPR35 activation was necessary and sufficient for ischemic protection by KynA. When bound by KynA, GPR35 activated G i - and G 12/13 -coupled signaling and trafficked to the outer mitochondria membrane, where it bound, apparantly indirectly, to ATP synthase inhibitory factor subunit 1 (ATPIF1). Activated GPR35, in an ATPIF1-dependent and pertussis toxin-sensitive manner, induced ATP synthase dimerization, which prevented ATP loss upon ischemia. These findings provide a rationale for the development of specific GPR35 agonists for the treatment of ischemic diseases.

Objectives: Many centres have recently adopted pulmonary valve (PV) preservation (PVP) during tetralogy of Fallot (ToF) repair. We sought to identify the midterm functional outcomes and risk factors for pulmonary regurgitation after this procedure., Methods: All patients undergoing PVP during transatrial-transpulmonary repair for ToF with PV stenosis at our institution between January 2007 and December 2020 were reviewed., Results: Overall, 73 patients were included. At the index surgery, the body surface area was 0.31 ± 0.04 m2, the age was 4.9 ± 2.9 months and the preoperative PV z-score was -3.02 ± 1.11. At a mean follow-up of 5.3 ± 2.7 years, the fractional area change of the right ventricle (RV) was 47.1 ± 5.2%, and the tricuspid annular plane systolic excursion z-score was -3.31 ± 1.89%. The 5-year freedom from moderate/severe PV regurgitation was 61.3% [95% confidence interval (CI): 48, 73%]. There was a significant correlation between RV function and moderate/severe PR at follow-up (R2: 0.08; P = 0.03). A comparison with a group of patients undergoing a transannular patch procedure (N = 33) showed superior outcomes for patients with PVP. The preoperative PV z-score and the degree of PR at discharge were risk factors for the early development of moderate/severe PR at follow-up [hazard ratio (HR): 0.64; 95% CI: 0.48, 0.86, P = 0.01 and HR: 2.31; 95% CI: 1.00, 5.36, P = 0.04, respectively]. A preoperative PV annulus z-score ≤ -2.85 was found to be predictive for moderate/severe PR at 5 years after PVP (HR: 2.56; 95% CI: 1.31, 5.01, P = 0.002)., Conclusions: A pulmonary valve preservation strategy during tetralogy of Fallot repair should always be attempted. However, a preoperative PV annulus z-score < -2.85 and moderate/severe regurgitation upon discharge are risk factors for midterm pulmonary regurgitation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: Transcatheter aortic valve replacement (TAVR) represents a valid treatment for patients with aortic valve stenosis and high or intermediate surgical risk. However, biological transcatheter valves can also experience a structural degeneration after years, and a redo-TAVR procedure (TAVR-in-TAVR) can be a valid option. We revised the current available literature for indications, procedural and technical details and outcome on TAVR-in-TAVR procedures for degenerated TAVR valves., Methods: A systematic search was conducted in the public medical database for scientific articles on TAVR-in-TAVR procedures for degenerated transcatheter valves. Data on demographics, indications, first and second transcatheter valve type and size, mortality, complications and follow-up were extracted and analysed., Results: A total of 13 studies (1 multicentre, 3 case series, 9 case reports) were included in this review, with a total amount of 160 patients treated with TAVR-in-TAVR procedures for transcatheter valve failure. The mean age was 74.8 ± 7.8 with 84 males (52.8%). The mean elapsed time from the first TAVR procedure was 58.1 ± 23.4 months. Main indication for TAVR-in-TAVR was pure stenosis (38.4%, with mean gradient of 44.5 ± 18.5 mmHg), regurgitation (31.4%), mixed stenosis and regurgitation (29.5%) and leaflet thrombosis (8.8%). Procedural success rate was 86.8%, with second TAVR valve malposition occurred in 4 cases (2.5%). The hospital mortality rate was 1.25% (2/160). Post-procedural echocardiographic control showed moderate regurgitation in 5.6% of patients (9/160) and residual transvalvular mean gradient ≥20 mmHg in 5% of cases. Postoperative complications included major vascular complications (8.7%), new pacemaker implantation (8.7%), acute kidney failure (3.7%), stroke (0.6%) and coronary obstruction (0.6%). The mean follow-up time was 6 ± 5.6 months with 1 non-cardiovascular death reported., Conclusions: TAVR-in-TAVR represents a valid alternative to standard surgery for the treatment of degenerated transcatheter valves in high-risk patients. Despite these promising results, further studies are required to assess durability and haemodynamic performances of the second TAVR valve., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Aim of this study was to perform a systematic review a meta-analysis of the literature in order to identify predictors of acute kidney injury (AKI) in patients with mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair (TEER) and assess its effect on in-hospital outcomes and mortality. Although iodinated contrast is not typically used in TEER, these patients are still at risk for developing AKI., Methods: Studies reporting on the effect of incident AKI on mortality following TEER for MR were included. Random-effects meta-analysis was performed, comparing clinical outcomes between the patients with or without incident AKI., Results: Six studies including a total of 2057 patients (377 AKI and 1680 No-AKI) were included and analyzed. AKI was significantly associated with 30-day mortality after TEER (Odds ratio (OR): 8.06; 95% CI: 3.20, 20.30, p < 0.01; I 2 = 18.4%) and all-cause mortality over a mean follow-up time of 30 months (Hazard ratio (HR): 2.48; 95% CI: 1.89, 3.24, p < 0.01; I 2 = 23.7%). AKI after TEER was associated with prolonged hospitalization (Mean difference (in days): 1.41; 95% CI: 0.52, 2.31, p < 0.01; I 2 = 82.4%). Stage 4 chronic kidney disease (CKD), device failure and history of chronic obstructive pulmonary disease (COPD) were significant predictors of AKI following TEER (CKD stage 4: OR: 2.38; 95% CI: 1.18, 4.78, p = 0.02; I 2 = 0.0%; Device failure: OR: 3.15; 95% CI: 1.94, 5.12, p < 0.01; I 2 = 0.0%; COPD: OR: 1.92; 95% CI: 1.16, 3.17; I 2 = 26.7%)., Conclusions: Our findings highlight the renal vulnerability of the TEER population to renal injury and the associated deterioration in clinical outcomes and survival., Competing Interests: Declaration of competing interest Dr. Tang is a consultant and advisory board member for Abbott and a consultant for Medtronic and W. L. Gore & Associates. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To assess the feasibility and outcomes of biventricular conversion following takedown of Fontan circulation., Methods: Retrospective analysis of patients who had takedown of Fontan circulation and conversion to biventricular circulation at a single center from September 2007 to April 2020. Failing Fontan physiology was defined as Fontan circulation pressure >15 mm Hg and/or the presence of associated complications., Results: Biventricular conversion was performed in 23 patients at a median age of 10.0 (7.5-13.0) years. Indications included failing Fontan physiology in 15 (65%) and elective takedown in 8 (35%) patients. A subset of patients (n = 6) underwent procedures for staged recruitment of the nondominant ventricle before conversion. Median z score of end-diastolic volume of borderline ventricle before takedown was -2.3 (-3.3, -1.3). Hypoplastic left heart syndrome (P < .01) and sub-/aortic stenosis (P < .01) were more common in these patients. Biventricular conversion with or without staged ventricular recruitment led to a significant increase in indexed end-diastolic volume (P < .01), indexed end-systolic volume (P < .01), and ventricular mass (P < .01) of the nondominant ventricle (14 right, 9 left ventricle). There were 5 (22%) deaths (1 [4%] early death). All who underwent elective biventricular conversion survived, whereas 2-year survival rate for patients with a failing Fontan circulation was 72.7% (95% confidence interval, 37%-90%). The overall, 3-year reoperation-free survival was 86.7% (95% confidence interval, 56%-96%). Left dominant atrioventricular canal defect (P < .01) and early era of biventricular conversion (P = .02) were significant predictors for mortality., Conclusions: A primary as well as a staged biventricular conversion is feasible in patients who have had previous Fontan procedure. Although this provides an alternative to transplantation in patients with failing Fontan, outcomes are worse in those with failing Fontan compared with elective takedown of Fontan circulation. Optimal timing needs further evaluation., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Dextro transposition of the great arteries (d-TGA) is the most common critical congenital cardiac defect surgically treated in the neonatal period by arterial switch operation (ASO). Major aortopulmonary collaterals (MAPCAs) can be present in this population and may complicate the early postoperative period. Our aim was to review our institutional data and systematically review the available literature to provide further insight on the clinical significance of MAPCAs during the early postoperative course after ASO. Methods: This is a retrospective study of patients with simple d-TGA who underwent ASO between March 1998 and September 2020 at Boston Children's Hospital. The MEDLINE, Embase, and Cochrane databases were searched from inception to June 2020. Results: Of the 671 d-TGA patients who underwent ASO at our center, 13 (1.9%) were diagnosed with MAPCAs. Five were diagnosed before ASO, while eight were diagnosed after ASO. Of these, two patients required catheterization for MAPCAs coiling during the same hospitalization on the 2nd and 11th postoperative days. The systematic review retrieved a total of 34 articles after duplicates were removed. Finally, nine studies reporting on 23 patients were deemed eligible for our analysis. The average time to MAPCAs coiling was 12 days, while the mean hospital stay was 36 days. Conclusions: MAPCAs should be included in the differential diagnosis of ASO complicated by cardiac or respiratory failure, or pulmonary hemorrhage acutely postoperatively. Once managed, recovery of these patients is predictable, and mortality is low. Further studies investigating the diagnostic value of echocardiography and the long-term outcomes of these MAPCAs are necessary.

Background: Epicardial Adipose Tissue (EAT) surrounds the epicardium and can mediate harmful effects related to Coronary Artery Disease (CAD)., Objective: We explored the regional differences between adipose stores surrounding diseased and non-diseased segments of coronary arteries in patients with advanced CAD., Methods: We enrolled 32 patients with known CAD who underwent coronary artery bypass graft (CABG) surgery. Inflammatory mediators were measured in EAT biopsies collected from a region of the Left Anterior Descending Artery (LAD) with severe stenosis (diseased segment) and without stenosis (non-diseased segment)., Results: Mean age was 64.3±11.1 years, and mean EAT thickness was 7.4±1.9 mm. Dyslipidemia was the most prevalent comorbidity (81% of the patients). Out of a total of 11 cytokines, resistin (p=0.039), matrix metallopeptidase 9 (MMP-9) (p=0.020), C-C motif chemokine ligand 5 (CCL-5) (p=0.021), and follistatin (p=0.038) were significantly increased in the diseased compared with the non-diseased EAT segments. Indexed tumor necrosis factor-alpha (TNF-α), defined as the diseased to non-diseased cytokine levels ratio, was significantly correlated with increased EAT thickness both in the whole cohort (p=0.043) and in a subpopulation of patients with dyslipidemia (p=0.009). Treatment with lipid-lowering agents significantly decreased indexed TNF-α levels (p=0.015). No significant alterations were observed in the circulating levels of these cytokines with respect to CAD-associated comorbidities., Conclusion: Perivascular EAT is a source of cytokine secretion in distinct areas surrounding the coronary arteries in patients with advanced CAD. Adipocyte-derived TNF-α is a prominent mediator of local inflammation., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The optimal revascularization strategy for patients with left main coronary artery disease is still controversial. This is systematic review and meta-analysis aims to evaluate the outcomes of percutaneous coronary intervention (PCI) with drug-eluting stents compared with coronary artery bypass graft (CABG) for LM disease., Methods: Online electronic databases were systematically reviewed until January 2020 for randomized trials comparing PCI with drug-eluting stents and CABG. Primary outcomes were: all-cause mortality, myocardial infarction (MI), stroke, and repeated revascularization. Secondary outcomes included periprocedural and nonperiprocedural MI. The period of follow-up included 30 days, 1 year, and 5 years. Odds ratio and 95% confidence interval were calculated with a fixed-effects model., Results: A total of 4595 patients (5 randomized trials) with left main coronary artery disease were included. At 30 days and 1 year, PCI was associated with lower incidence of stroke, higher repeated revascularization, and similar odds of mortality and MI compared with CABG. At 5 years, PCI was associated with higher rates of MI (odds ratio, 1.43; 95% confidence interval, 1.13-1.79; P = .003) and repeat revascularization (odds ratio, 1.89; 95% CI, 1.58-2.26; P < .001) than CABG. PCI was associated with lower periprocedural MI at 30 days, whereas at 5 years PCI was associated with higher nonperiprocedural MI (odds ratio, 2.32; 95% confidence interval, 1.62-3.31; P < .001). Mortality and stroke rate did not differ at 5-year follow-up., Conclusions: Patients with left main coronary artery disease treated with either PCI or CABG do not show significant difference in early or 5-year mortality. Although CABG was associated with higher stroke rates at 30 days and 1 year, PCI was associated with an increase in MI and need for repeat revascularization at 5 years., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: In this study, we sought to identify independent risk factors for mortality and reintervention after early surgical correction of truncus arteriosus using a novel statistical method., Methods: Patients undergoing neonatal/infant truncus arteriosus repair between January 1984 and December 2018 were reviewed retrospectively. An innovative statistical strategy was applied integrating competing risks analysis with modulated renewal for time-to-event modeling., Results: A total of 204 patients were included in the study. Mortality occurred in 32 patients (15%). Smaller right ventricle to pulmonary artery conduit size and truncal valve insufficiency at birth were significantly associated with overall mortality (right ventricle to pulmonary artery conduit size: hazard ratio, 1.34; 95% confidence interval, 1.08-1.66, P = .008; truncal valve insufficiency: hazard ratio, 2.5; 95% confidence interval, 1.13-5.53, P = .024). truncal valve insufficiency at birth, truncal valve intervention at index repair, and number of cusps (4 vs 3) were associated with truncal valve reoperations (truncal valve insufficiency: hazard ratio, 2.38; 95%, confidence interval, 1.13-5.01, P = .02; cusp number: hazard ratio, 6.62; 95% confidence interval, 2.54-17.3, P < .001). Right ventricle to pulmonary artery conduit size 11 mm or less was associated with a higher risk of early catheter-based reintervention (hazard ratio, 1.54; 95% confidence interval, 1.04-2.28, P = .03) and reoperation (hazard ratio, 1.96; 95% confidence interval, 1.33-2.89, P = .001) on the right ventricle to pulmonary artery conduit., Conclusions: Smaller right ventricle to pulmonary artery conduit size and truncal valve insufficiency at birth were associated with overall mortality after truncus arteriosus repair. Quadricuspid truncal valve, the presence of truncal valve insufficiency at the time of diagnosis, and truncal valve intervention at index repair were associated with an increased risk of reoperation. The size of the right ventricle to pulmonary artery conduit at index surgery is the single most important factor for early reoperation and catheter-based reintervention on the conduit., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Endocardial fibroelastosis (EFE) is defined by fibrotic tissue on the endocardium and forms partly through aberrant endothelial-to-mesenchymal transition. However, the pathologic triggers are still unknown. In this study, we showed that abnormal flow induces EFE partly through endothelial-to-mesenchymal transition in a rodent model, and that losartan can abrogate EFE development. Furthermore, we translated our findings to human endocardial endothelial cells, and showed that laminar flow promotes the suppression of genes associated with mesenchymal differentiation. These findings emphasize the role of flow in promoting EFE in endocardial endothelial cells and provide a novel potential therapy to treat this highly morbid condition., Competing Interests: This work has been supported by Boston Children’s Hospital, Department of Cardiovascular Surgery, Internal Funding Boston Children’s Hospital, Kaplan Fellowship. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

Objective: Atherosclerosis is a chronic inflammatory disease promoted by pro-inflammatory cytokines produced by NOD-, LRR- and pyrin domain-containing protein 3 (NLRP 3) inflammasome. Colchicine is an anti-inflammatory agent that inhibits inflammasome's action and stabilizes atherosclerotic lesions. N-acetylcysteine (NAC) reduces low-density lipoprotein (LDL) oxidation, metalloproteinase levels, and foam cell count and volume. Fenofibrate also has antioxidant, anti-inflammatory, and anticoagulant properties while also having a beneficial effect on the vasomotor function of the endothelium. The purpose of this study is to investigate the effect of per os colchicine administration in combination with fenofibrate and NAC on triglyceride levels and the development of atherosclerotic lesions in cholesterol-fed rabbits., Materials and Methods: Twenty-eight male, 2 months old New Zealand White rabbits were separated into four groups and were fed with different types of diet for 7 weeks: standard, cholesterol 1% w/w, cholesterol 1% w/w plus colchicine 2 mg/kg body weight plus 250 mg/kg body weight/day fenofibrate, and cholesterol 1% w/w plus colchicine 2 mg/kg body weight plus 15 mg/kg body weight/day NAC. Blood samples were drawn from all animals. Lipid profiles were assessed, and interleukin 6 (IL-6) measurements were performed using an enzyme-linked immunosorbent assay (ELISA) kit. Histologic examination was performed on aorta specimens stained with eosin and hematoxylin. Aortic intimal thickness was evaluated using image analysis., Results: Colchicine administration in combination with fenofibrate or NAC statistically significantly reduced the extent of atherosclerotic lesions in aortic preparations. Co-administration of colchicine with NAC has a stronger anti-atherogenic effect than the colchicine plus fenofibrate regimen. Triglerycide levels were decreased in the colchicine plus fenofibrate group and the colchicine plus NAC group at the end of the experiment (p < 0.05), whereas the Cholesterol group had increased levels. A favorable significant lower concentration of IL-6 was detected in the colchicine plus NAC group vs. the other groups., Conclusions: In an experimental rabbit model, it appears that colchicine statistically significantly reduces the development of atherosclerosis of the aorta, especially in combination with NAC. Colchicine, as an NLRP3 inflammasome inhibitor, and NAC, as an agent that directly targets IL-6 signaling, can reduce the inflammatory risk. Fenofibrate enhances the attenuating role of colchicine on triglyceride levels. Clinical studies should investigate whether similar effects can be observed in humans.

Το perform a systematic review and meta-analysis of the available literature comparing safety and efficacy outcomes between percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and coronary artery bypass grafting (CABG) in patients with chronic kidney disease (CKD). Eligible studies included patients with eGFR < 60 mL/min/1.73 m 2 that underwent revascularization. Subgroup analyses according to DES generation and dialysis status were performed. A total of 7157 and 8156 patients were included in the CABG and PCI arms respectively across 16 studies eligible studies. Weighted mean age was 68.6 and 63.8 years for the CABG and PCI arms, respectively. Mean follow-up time was 3.2 and 2.9 years respectively. Compared to CABG, PCI was associated with increased risk for all-cause mortality (hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.13, 1.46; P < 0.01), cardiac mortality (HR: 1.59, 95% CI: 1.13, 2.23; P = 0.01), myocardial infarction (MI) (HR: 1.89, 95% CI: 1.43, 2.49; P < 0.01), and repeat revascularization (HR: 2.97, 95% CI: 2.20, 3.97; P < 0.01). Risk for stroke was lower (HR: 0.64, 95% CI: 0.50, 0,81; P < 0.01) in the PCI group. These results were unchanged when 1st or 2nd DES were used. A subgroup analysis showed no difference in all-cause mortality for DES PCI vs CABG in dialysis patients (HR: 1.11, 95% CI: 0.71, 1.73; P = 0.65). In patients with CKD, PCI is associated with higher risk of mortality, MI, and repeat revascularization compared with CABG and regardless of DES generation. Risk of stroke is higher with CABG. Type of revascularization had no impact on survival of dialysis patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Approximately 50% of heart transplant (HT) programs utilize induction therapy (IT) with interleukin-2 receptor antagonists (IL2RA) or polyclonal anti-thymocyte antibodies (ATG)., Methods: Adult HT recipients were identified in the UNOS Registry between 2010 and 2020. We compared mortality between IT strategies with competing risk analysis., Results: A total of 28 634 HT recipients were included in the study (50.1% no IT, 21.3% ATG, 27.9% IL2RA, .7% alemtuzumab, .01% OKT3). Adjusted all-cause, 30 day and 1 year mortality were lower among those treated with IT than no IT (sub-hazard ratio [SHR] .87, 95% CI .79-.96, SHR .86, .76-.97, SHR .76, .63-.93, P = .007, respectively). In propensity score matching analysis IT was associated with lower 30-day and 1-year mortality. IL2RA had higher all-cause and 1-year mortality than ATG (SHR 1.41, 95% CI 1.23-1.69 and 1.55, 95% CI 1.29-1.88, respectively). Utilization of IT was associated with significantly lower risk of treated rejection at 1 year after HT compared with no IT (relative risk ratio [RRR] .79) and similarly ATG compared with IL2RA (RRR .51)., Conclusion: IT was associated with lower mortality and treated rejection episodes than no IT. IL2RA is the most used IT approach but ATG has lower risk of treated rejection and mortality., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: To report outcomes in a pilot study of autologous mitochondrial transplantation (MT) in pediatric patients requiring postcardiotomy extracorporeal membrane oxygenation (ECMO) for severe refractory cardiogenic shock after ischemia-reperfusion injury (IRI)., Methods: A single-center retrospective study of patients requiring ECMO for postcardiotomy cardiogenic shock following IRI between May 2002 and December 2018 was performed. Postcardiotomy IRI was defined as coronary artery compromise followed by successful revascularization. Patients undergoing revascularization and subsequent MT were compared with those undergoing revascularization alone (Control)., Results: Twenty-four patients were included (MT, n = 10; Control, n = 14). Markers of systemic inflammatory response and organ function measured 1 day before and 7 days following revascularization did not differ between groups. Successful separation from ECMO-defined as freedom from ECMO reinstitution within 1 week after initial separation-was possible for 8 patients in the MT group (80%) and 4 in the Control group (29%) (P = .02). Median circumferential strain immediately following IRI but before therapy was not significantly different between groups. Immediately following separation from ECMO, ventricular strain was significantly better in the MT group (-23.0%; range, -20.0% to -28.8%) compared with the Control group (-16.8%; range, -13.0% to -18.4%) (P = .03). Median time to functional recovery after revascularization was significantly shorter in the MT group (2 days vs 9 days; P = .02). Cardiovascular events were lower in the MT group (20% vs 79%; P < .01). Cox regression analysis showed higher composite estimated risk of cardiovascular events in the Control group (hazard ratio, 4.6; 95% confidence interval, 1.0 to 20.9; P = .04) CONCLUSIONS: In this pilot study, MT was associated with successful separation from ECMO and enhanced ventricular strain in patients requiring postcardiotomy ECMO for severe refractory cardiogenic shock after IRI., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Redo coronary artery bypass grafting (CABG) can be performed with either the off-pump (OPCAB) or the on-pump (ONCAB) technique., Method: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this meta-analysis compared the safety and efficacy of OPCAB versus ONCAB redo CABG., Results: Twenty-three (23) eligible studies were included (OPCAB, n=2,085; ONCAB, n=3,245). Off-pump CABG significantly reduced the risk of perioperative death (defined as in-hospital or 30-day death rate), myocardial infarction, atrial fibrillation, and acute kidney injury. The two treatment approaches were comparable regarding 30-day stroke and late all-cause mortality., Conclusions: Off-pump redo CABG resulted in lower perioperative death and periprocedural complication rates. No difference was observed in perioperative stroke rates and long-term survival between the two techniques., (Copyright © 2021 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Purpose: We sought to develop and validate machine learning (ML) models to increase the predictive accuracy of mortality after heart transplantation (HT)., Methods and Results: We included adult HT recipients from the United Network for Organ Sharing (UNOS) database between 2010 and 2018 using solely pre-transplant variables. The study cohort comprised 18 625 patients (53 ± 13 years, 73% males) and was randomly split into a derivation and a validation cohort with a 3:1 ratio. At 1-year after HT, there were 2334 (12.5%) deaths. Out of a total of 134 pre-transplant variables, 39 were selected as highly predictive of 1-year mortality via feature selection algorithm and were used to train five ML models. AUC for the prediction of 1-year survival was .689, .642, .649, .637, .526 for the Adaboost, Logistic Regression, Decision Tree, Support Vector Machine, and K-nearest neighbor models, respectively, whereas the Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score had an AUC of .569. Local interpretable model-agnostic explanations (LIME) analysis was used in the best performing model to identify the relative impact of key predictors. ML models for 3- and 5-year survival as well as acute rejection were also developed in a secondary analysis and yielded AUCs of .629, .609, and .610 using 27, 31, and 91 selected variables respectively., Conclusion: Machine learning models showed good predictive accuracy of outcomes after heart transplantation., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction : Aortic and mitral bioprosthesis are the gold standard treatment to replace a pathological native valve. However, bioprostheses are prone to structural valve degeneration, resulting in limited long-term durability. During the past decade, the implantation of transcatheter stent-valves within degenerated aortic and mitral bioprostheses, (the so-called 'valve-in-valve' procedure), represents a valid alternative to redo surgery in patients with high-risk surgical profiles. Areas covered : We reviewed the clinical outcomes and the procedural details of transcatheter aortic and mitral valve-in-valve series according to current published literature and include a practical guide for valve sizing and stent-valve positioning and strategies to prevent complications. Expert opinion : In both aortic and mitral positions meticulous planning is fundamental in these procedures to avoid serious complications including patient prosthesis mismatch, coronary obstruction and left ventricular outflow tract obstruction.

Background: We sought to identify predictive factors for aortic valve (AoV) surgery after neonatal balloon aortic valvuloplasty (BAV) and characterize clinical outcomes of AoV surgery after neonatal BAV., Methods: Time-to-event analysis identified predictors for AoV surgery after neonatal BAV. Clinical outcomes of AoV surgery following neonatal BAV were examined., Results: This study included 96 consecutive patients who underwent neonatal BAV for congenital aortic stenosis between 1998 and 2018, in 26 of whom a fetal BAV had been performed. Fifty-six patients underwent AoV surgery at a median age of 2.0 years. Significant risk factors for AoV surgery in univariate Cox regression (result presented as hazard ratio [HR], [95% CI]; P value) were a history of fetal BAV (HR, 4.05 [95% CI, 2.19–7.40]; P<0.001), AoV annulus diameter Z score (HR, 0.56 [95% CI, 0.43–0.75]; P=0.001), the presence of endocardial fibroelastosis (HR, 2.61 [95% CI, 1.48–4.51]; P=0.001), severe left ventricular dysfunction before neonatal BAV (HR, 1.75 [95% CI, 1.03–2.97]; P=0.04), and recent era (HR, 3.08 [95% CI, 1.68–5.91]; P=0.0002) in the entire cohort. Area under the receiver operating characteristic curve and Youden J index analysis identified a cutoff value for AoV annulus diameter Z score of −2.6 in patients without fetal BAV. In 24 patients with midterm cardiac catheterization data, univariate linear regression analysis (result presented as B coefficient [95% CI]; P) showed that the presence of greater-than-moderate aortic regurgitation immediately after BAV (B coefficient, 4.8 [95% CI, 1.0–8.6]; P=0.018) and before AoV surgery (B coefficient, 6.1 [95% CI, 2.2–10.0]; P=0.004) were significant risk factors for elevated left ventricular end-diastolic pressure after AoV surgery, while concomitant endocardial fibroelastosis resection at AoV surgery had a protective effect (B coefficient, −3.8 [95% CI, −7.6 to −0.06]; P=0.05)., Conclusions: A small AoV annulus diameter Z score with a cutoff value of −2.6 and a history of fetal BAV were significantly associated with AoV surgery after neonatal BAV. Concomitant endocardial fibroelastosis resection is recommended at AoV surgery following neonatal BAV to improve left ventricular diastolic function.

We sought to systematically describe the epidemiology, etiology, clinical and operative characteristics as well as outcomes of patients who underwent pericardiectomy for constrictive pericarditis in the contemporary era. We conducted a systematic search of the MEDLINE, Embase, and Cochrane databases from their inception to April 1, 2020 for studies assessing the outcomes of pericardiectomy in patients with constrictive pericarditis. Studies with patients enrolled before 1985, pediatric patients or studies including >10% tuberculous pericarditis were excluded. The impact of pericarditis etiology on outcomes was evaluated with a meta-analysis. We analyzed 27 eligible studies and 2,114 patients. Etiology was most commonly idiopathic (50.2%), followed by after-cardiac surgery (26.2%) and radiation (6.9%). Patients were mostly men (76%), mean age 58 and with advanced symptoms (NYHA III/IV 70.1%). Total pericardiectomy was preferred (85.8%) and concomitant cardiac surgery was relatively common (23.8%). Operative mortality was 6.9% and 5-year mortality was 32.7%. Radiation and after-cardiac surgery patients had 3 and 2 times higher long-term risk for mortality respectively compared with idiopathic. A sensitivity analysis did not result in changes in the results. Thirty percent of included studies had more than low bias primarily originating from follow up and selection. Pericardiectomy is therefore performed mostly in middle-aged men with advanced symptoms and low co-morbidity burden and still caries significant operative mortality. Radiation and after-cardiac surgery patients have a significantly higher mortality risk compared with idiopathic. Several methodological issues and significant heterogeneity limit the generalization of these data and randomized controlled trials may have to be considered., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)