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Cardiac allograft vasculopathy (CAV) causes late graft failure and mortality after heart transplantation. Donor-specific antibodies (DSAs) lead to chronic endothelial cell injury, inflammation, and arterial intimal thickening. In this study, GeoMx digital spatial profiling was used to analyze arterial areas of interest (AOIs) from CAV+DSA+ rejected cardiac allografts (N = 3; 22 AOIs total). AOIs were categorized based on CAV neointimal thickening and underwent whole transcriptome and protein profiling. By comparing our transcriptomic data with that of healthy control vessels of rapid autopsy myocardial tissue, we pinpointed specific pathways and transcripts indicative of heightened inflammatory profiles in CAV lesions. Moreover, we identified protein and transcriptomic signatures distinguishing CAV lesions exhibiting low and high neointimal lesions. AOIs with low neointima showed increased markers for activated inflammatory infiltrates, endothelial cell activation transcripts, and gene modules involved in metalloproteinase activation and TP53 regulation of caspases. Inflammatory and apoptotic proteins correlated with inflammatory modules in low neointima AOIs. High neointima AOIs exhibited elevated TGFβ-regulated transcripts and modules enriched for platelet activation/aggregation. Proteins associated with growth factors/survival correlated with modules enriched for proliferation/repair in high neointima AOIs. Our findings reveal novel insight into immunological mechanisms mediating CAV pathogenesis.

Background Methods Results Conclusions Durable biventricular support may be necessary to bridge patients with end‐stage biventricular failure to heart transplantation. This study compares waitlist and post‐transplant outcomes between patients supported with continuous flow, durable biventricular assist devices (BiVAD), and total artificial heart (TAH).Using the UNOS registry, we analyzed adult (≥18 years old), first‐time transplant candidates with TAH or BiVAD at the time of listing or transplantation from 10/1/2010–10/31/2020, with follow‐up through 3/31/2022. Multivariable proportional subdistribution hazards models and cause‐specific Cox proportional hazards models were used to compare death/deterioration or heart transplantation on the waitlist between cohorts. Kaplan–Meier and multivariable Cox proportional hazards model were used to evaluate one‐year post‐transplant survival and evaluate difference in outcomes based on annual transplant center volume.The waitlist cohort included a total of 228 patients (25% BiVAD). Waitlist outcomes between device types were similar. The transplanted cohort included a total of 352 patients (25% BiVAD). There was a trend towards worse one‐year post‐transplant survival in patients bridged with TAH versus BiVAD (log‐rank p‐value = 0.072) that persisted after adjusting for age, gender, policy, and removing dual‐organ recipients (HR 1.94 (0.94, 3.98) p‐value = 0.07). There was a difference in one‐year post‐transplant survival amongst TAH‐bridged patients when stratified by annual transplant center volume (log‐rank p‐value = 0.013). One‐year post‐transplant survival between TAH‐supported patients from high annual transplant volume centers and BiVAD‐supported patients was similar (p‐value = 0.815).BiVAD and TAH are reasonable support strategies with TAH implantation at high‐volume transplant centers (51+ transplants/year) having similar 1‐year post‐transplant survival to BiVAD‐supported patients. [ABSTRACT FROM AUTHOR]

Electrical storm (ES) is among the most fearsome events in patients in waiting list for heart transplantation (HT) and catheter ablation (CA) demonstrated to be effective in reduce the arrhythmic burden. However, selection criteria for CA suitability in this specific population have never been addressed before. We retrospectively enrolled 36 patients (mean age 51 ± 8 years; 83% men) waiting HT referred to our department for ES resistant to antiarrhythmic drugs and percutaneous stellate ganglion blockade. Twenty patients were judged suitable for VT ablation according to specific criteria including absence of increased arrhythmic burden secondary to volume overload and hemodynamic decompensation; expected CA outcome favorable due to etiology of the cardiomyopathy, no need for coronary revascularization and technical feasibility of the procedure. The pre‐emptive use of mechanical circulatory supports (MCS) were discussed integrating the PAINESD score with additional clinical and hemodynamic parameters. Acute procedural success was accounted in 85% of cases with only two major complications. The CA group reported lower length of in‐hospital stay after CA suitability evaluation (56 ± 17 vs. 131 ± 64 days, p =.004). Furthermore, at a mean follow‐up of 703 ± 145 days, this group showed reduction of ventricular arrhythmia (VA) recurrence leading to implantable cardioverter defibrillator shock (4 vs. 8, p =.051) and underwent HT with a lower level of urgency (0 vs. 6 patients needed for UNOS1 status upgrade). Respectively, one patient of the CA group and two patients of the conservative group died (p =.839). At the end of follow‐up, eight patients underwent heart transplantation (p =.964) while four patients underwent Left Ventricular Assist device (LVAD) implantation (p =.440). This pilot study should be a proof for further studies exploring CA of VAs as a possible bridge therapy to HT. [ABSTRACT FROM AUTHOR]

Background: Patients can develop de novo malignancies following orthotopic heart transplantation. However, vascular tumors are not commonly described in this population. Case presentation: We present a 69-year-old female with a history of orthotopic heart transplantation for chemotherapy-induced cardiomyopathy who developed an incidental pulmonary artery mass six years after her transplantation. Given concerns for malignancy, the patient underwent an operative excisional biopsy through a left anterior mini-thoracotomy with femoral artery and vein cannulation for cardiopulmonary bypass. The mass was determined to be a non-malignant vascular overgrowth with PIK3CA mutation. Conclusion: We present the case of an unusual pulmonary artery mass with PIK3CA mutation found in a post heart transplant patient. We were able to spare her the morbidity of a redo-sternotomy by excising the mass via a minimally invasive left anterior thoracotomy approach. [ABSTRACT FROM AUTHOR]

Purpose: Left ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy. Yet device infection represents a major lethal complication, warranting a multi-step, complex therapy approach including an urgent device exchange or heart transplantation. Still, timely diagnosis of site and extent of VAD-specific infection for a proper therapy planning poses challenges in regular clinical care. This single-center, retrospective study aimed to evaluate the impact of volumetric PET parameters with different thresholding compared to semiquantitative PET parameters for accurate diagnosis of VAD-specific infection. Procedures: Seventeen patients (1 female, 16 males; mean age 57 ± 11 years) underwent [18F]FDG imaging for suspected VAD-specific infection between April 2013 and October 2023. Various metabolic and volumetric PET parameters with different thresholding were collected for specific LVAD components including driveline entry point, subcutaneous driveline, pump pocket, inner cannula and outflow tract. Microbiology and clinical follow-up were used as the final diagnosis standard. Results: Nine of eleven patients with VAD-specific infection underwent urgent heart transplantation, and one had a surgical revision of LVAD. Two patients had non-VAD specific infections, and two had non-VAD related infections. Metabolic burden determination using a fixed absolute threshold provided the best outcome compared to relative thresholding or other metabolic SUV parameters. The total metabolic tumor volume (MTV) cutoff value was 9.3 cm3, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.43%, 82.5%, and 0.814 (95% CI 0.555–0.958), respectively. The total lesion glycolysis (TLG) was 30.6, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.4%, 82.5%, and 0.829 (95% CI 0.571–0.964), respectively. Conclusions: Volumetric PET parameters with fixed absolute thresholding appear to be a valuable auxiliary tool in the evaluation of [18F]FDG imaging to enhance the diagnostic accuracy of VAD-specific infection. [ABSTRACT FROM AUTHOR]

Background: In the setting of the COVID-19 pandemic, a rapid uptake of telehealth services was instituted with the aim of reducing the spread of disease to vulnerable patient populations including heart transplant recipients. Methods: Single-center, cohort study of all heart transplant patients seen by our institution's transplant program during the first 6 weeks of transition from in-person consultation to telehealth (23 March – 5 June 2020). Results: Face-to-face consultation allocation strongly favored patients in the early post-operative period (34 vs. 242 weeks post-transplant; p < 0.001). Telehealth consultation dramatically reduced patient travel and wait times (80 min per visit saved in telehealth patients). No apparent excess re-hospitalization or mortality was seen in telehealth patients. Conclusions: With appropriate triage, telehealth was feasible in heart transplant recipients, with videoconferencing being the preferred modality. Patients seen face-to-face were those triaged to be higher acuity based on time since transplant and overall clinical status. These patients have the expected higher rates of hospital re-admission, and therefore should continue to be seen in person. [ABSTRACT FROM AUTHOR]

Despite recent advances, hypoplastic left heart syndrome (HLHS) patients subsequent to the Fontan still have significant morbidity and mortality. Some require heart transplant due to systemic ventricular dysfunction. Limited data exist on timing for transplant referral. This study aims to correlate systemic ventricular strain by echocardiography to transplant-free survival. HLHS patients who had Fontan palliation at our institution were included. Patients were divided into: 1) Required transplant or experienced mortality (composite end point); 2) Did not require transplant or survived. For those who experienced the composite endpoint, the last echocardiogram prior to the composite outcome was used, while for those who did not experience the composite endpoint the last echocardiogram obtained was used. Several qualitative and quantitative parameters were analyzed with focus on strain parameters. Ninety-five patients with HLHS Fontan palliation were identified. Sixty-six had adequate images and eight (12%) experienced transplant or mortality. These patients had greater myocardial performance index by flow Doppler (0.72 versus 0.53, p = 0.01), higher systolic/diastolic duration ratio (1.51 versus 1.13, p = 0.02), lower fractional area change (17.65 versus 33.99, p < 0.01), lower global longitudinal strain (GLS) (-8.63 versus − 17.99, p < 0.01), lower global longitudinal strain rate (GLSR) (− 0.51 versus − 0.93, p < 0.01), lower global circumferential strain (GCS) (-6.68 versus -18.25, p < 0.01), and lower (GCSR) global circumferential strain rate (-0.45 versus -1.01, p < 0.01). ROC analysis demonstrated predictive value for GLS − 7.6 (71% sensitive, 97% specific, AUC 81%), GLSR -0.58 (71% sensitive, 88% specific, AUC 82%), GCS − 10.0 (86% sensitive, 91% specific, AUC 82%), and GCSR -0.85 (100% sensitive, 71% specific, AUC 90%). GLS and GCS can help predict transplant-free survival in patients with hypoplastic left heart syndrome having undergone Fontan palliation. Higher strain values (closer to zero) may be a helpful tool in determining when transplant evaluation is warranted in these patients. [ABSTRACT FROM AUTHOR]

Prior studies have shown reduced development of cardiac allograft vasculopathy (CAV) in multiorgan transplant recipients. The aim of this study was to compare the incidence of CAV between isolated heart transplants and simultaneous multiorgan heart transplants in the contemporary era. We utilized the Scientific Registry of Transplant Recipients to perform a retrospective analysis of first-time adult heart transplant recipients between January 1, 2010 and December 31, 2019 in the United States. The primary end-point was the development of angiographic CAV within 5 years of follow-up. Among 20,591 patients included in the analysis, 1,279 (6%) underwent multiorgan heart transplantation (70% heart-kidney, 16% heart-liver, 13% heart-lung, and 1% triple-organ), and 19,312 (94%) were isolated heart transplant recipients. The average age was 53 years, and 74% were male. There were no significant between-group differences in cold ischemic time. The incidence of acute rejection during the first year after transplant was significantly lower in the multiorgan group (18% vs 33%, p < 0.01). The 5-year incidence of CAV was 33% in the isolated heart group and 27% in the multiorgan group (p < 0.0001); differences in CAV incidence were seen as early as 1 year after transplant and persisted over time. In multivariable analysis, multiorgan heart transplant recipients had a significantly lower likelihood of CAV at 5 years (hazard ratio = 0.76, 95% confidence interval: 0.66-0.88, p < 0.01). Simultaneous multiorgan heart transplantation is associated with a significantly lower long-term risk of angiographic CAV compared with isolated heart transplantation in the contemporary era. [ABSTRACT FROM AUTHOR]

Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools. Consecutive incident PAH patients aged ≥18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n = 152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n = 143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n = 201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n = 519 patients). Risk stratification was based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) 3-strata model and Registry to Evaluate Early and Long-Term PAH disease Management (REVEAL) 2.0 score. These phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% CI 1.6–2.8, p < 0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% CI 0.18–0.47, p < 0.001). Echocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients. [ABSTRACT FROM AUTHOR]

Use of donation after circulatory death (DCD) and hepatitis C virus (HCV) positive donors in heart transplantation have increased the donor pool. Given poor waitlist outcomes in the adult congenital heart disease (ACHD) population, we investigated waitlist outcomes associated with willingness to consider DCD and HCV+ offers and post-transplant outcomes following HCV+ and DCD transplantation for these candidates. Using the United Network for Organ Sharing database, we identified adult ACHD candidates and recipients listed or transplanted, respectively, between 01/01/2016 and 09/30/2023 for the HCV analysis and between 12/01/2019 and 09/30/2023 for the DCD analysis. Among candidates, we compared the cumulative incidence of transplant, with waitlist death/deterioration as a competing risk, by willingness to consider HCV+ and DCD offers. Among recipients of HCV+ (vs HCV-) and DCD (vs brain death [DBD]) transplants, we compared perioperative outcomes and post-transplant survival. Of 1,436 ACHD candidates from 01/01/2016 to 09/30/2023, 37.0% were willing to consider HCV+ heart offers. Of 886 ACHD candidates from 12/01/2019 to 09/30/2023, 15.5% were willing to consider DCD offers. On adjusted analysis, willingness to consider HCV+ offers was associated with 84% increased likelihood of transplant, and willingness to consider DCD offers was associated with 56% increased likelihood of transplant. Of 904 transplants between 01/01/2016 and 09/30/2023, 6.4% utilized HCV+ donors, and of 540 transplants between 12/01/2019 and 09/30/2023, 6.9% utilized DCD donors. Recipients of HCV+ (vs HCV-) and DCD (vs DBD) heart transplants had similar likelihood of perioperative outcomes and 1-year survival. ACHD candidates who were willing to consider HCV+ and DCD offers were more likely to be transplanted and had similar post-transplant outcomes compared to recipients of HCV- and DBD organs. [ABSTRACT FROM AUTHOR]

Vascular endothelial growth factor (VEGF)-A is an angiogenic and proinflammatory cytokine with profound effects on microvascular permeability and vasodilation. Several processes may induce VEGF-A expression in brain-dead organ donors. However, it remains unclear whether donor VEGF-A is linked to adverse outcomes after heart transplantation. We examined plasma VEGF-A levels from 83 heart transplant donors as well as the clinical data of these donors and their respective recipients operated between 2010 and 2016. The donor plasma was analyzed using Luminex-based Multiplex and confirmed with a single-target ELISA. Based on donor VEGF-A plasma levels, the recipients were divided into 3 equal-sized groups (low VEGF <500 ng/liter, n = 28; moderate VEGF 500–3000 ng/liter, n = 28; and high VEGF >3000 ng/liter, n = 27). Biochemical and clinical parameters of myocardial injury as well as heart transplant and kidney function were followed-up for one year, while rejection episodes, development of cardiac allograft vasculopathy, and mortality were monitored for 5 years. Baseline parameters were comparable between the donor groups, except for age, where median ages of 40, 45, and 50 were observed for low, moderate, and high donor plasma VEGF levels groups, respectively, and therefore donor age was included as a confounding factor. High donor plasma VEGF-A levels were associated with pronounced myocardial injury (TnT and TnI), a higher inotrope score, and a higher incidence of primary graft dysfunction in the recipient after heart transplantation. Furthermore, recipients with allografts from donors with high plasma VEGF-A levels had a longer length of stay in the intensive care unit and the hospital, and an increased likelihood for prolonged renal replacement therapy. Our findings suggest that elevated donor plasma VEGF-A levels were associated with adverse outcomes in heart transplant recipients, particularly in terms of myocardial injury, primary graft dysfunction, and long-term renal complications. Donor VEGF-A may serve as a potential biomarker for predicting these adverse outcomes and identifying extended donor criteria. [ABSTRACT FROM AUTHOR]

T cells drive acute cellular rejection (ACR) and its progression to chronic lung allograft dysfunction (CLAD) following lung transplantation. International Society for Heart and Lung Transplantation grade A1 ACR without associated allograft dysfunction is often untreated, yet some patients develop progressive graft dysfunction. T-cell composition of A1 ACR lesions may have prognostic value; therefore, protein-level and epigenetic techniques were applied to transbronchial biopsy tissue to determine whether differential T-cell infiltration in recipients experiencing a first episode of stable grade A1 ACR (StA1R) is associated with early CLAD. Sixty-two patients experiencing a first episode of StA1R were divided into those experiencing CLAD within 2 years (n = 13) and those remaining CLAD-free for 5 or more years (n = 49). Imaging mass cytometry (IMC) was used to profile the spectrum and distribution of intragraft T cell phenotypes on a subcohort (n = 16; 8 early-CLAD and 8 no early-CLAD). Immunofluorescence was used to quantify CD4+, CD8+, and FOXP3+ cells. Separately, CD3+ cells were fluorescently labeled, micro-dissected, and the degree of Treg-specific demethylated region methylation was determined. PhenoGraph unsupervised clustering on IMC revealed 50 unique immune cell subpopulations. Methylation and immunofluorescence analyses demonstrated no significant differences in Tregs between early-CLAD and no early-CLAD groups. Immunofluorescence revealed that patients who developed CLAD within 2 years of lung transplantation showed greater CD8+ T cell infiltration compared to those who remained CLAD-free for 5 or more years. In asymptomatic patients with a first episode of A1 rejection, greater CD8+ T cell content may be indicative of worse long-term outlook. [ABSTRACT FROM AUTHOR]

Background: Heart transplant recipients frequently require kidney transplantation for concomitant advanced chronic kidney disease. Data on simultaneous (heart and kidney transplants performed simultaneously) versus sequential (heart transplant performed before kidney) heart–kidney transplants in children are limited. Herein, we compare kidney transplant outcomes between the two groups. Method: We used the Scientific Registry of Transplant Recipients to identify all pediatric (age <21 years) heart transplant recipients who also received a kidney transplant within 10 years of the heart transplant. We divided the study cohort into simultaneous heart–kidney and sequential heart–kidney recipients. We compared patient and death-censored graft survival using the Cox regression, adjusting for age at kidney transplant, sex, race, pre-transplant dialysis, donor type, and prior kidney transplant. We evaluated delayed graft function (defined as dialysis within the first week posttransplant) using logistic regression. Results: Our analysis cohort included 165 recipients (86 simultaneous and 79 sequential). The incidence of delayed graft function was higher in simultaneous recipients (22.4 vs. 7.7%, p=0.017), but the difference lost statistical significance on multivariable analysis. We found no difference in patient survival (aHR 0.97; 95% CI 0.39, 2.41; p=0.95) after kidney transplant but higher death-censored kidney graft survival in sequential heart–kidney recipients compared with simultaneous heart–kidney recipients (aHR 4.26; 95% CI 1.21, 14.9; p=0.02). Conclusion: Sequential heart–kidney transplants are associated with higher death-censored kidney allograft survival in children compared with simultaneous heart–kidney transplants. [ABSTRACT FROM AUTHOR]

Multi-organ transplantation involves the transplant of two or more organs from a single donor into a single recipient; in most cases, one of these organs is a kidney. Multi-organ transplantation is uncommon in pediatric transplantation but can be life-saving or significantly life-improving for children with rare diseases, including primary heart, liver, pancreas, or intestinal failure with secondary kidney failure, metabolic disorders, and genetic conditions causing multi-organ dysfunction. This manuscript reviews the current state of pediatric multi-organ transplantation that includes a kidney, with a focus on indications, evaluation, and key differences in management compared to kidney-alone transplantation. Guidelines and consensus statements for pediatric multi-organ transplantation are nonexistent; this review condenses reported statistics and peer-reviewed expert opinion while highlighting areas in need of further research. [ABSTRACT FROM AUTHOR]

The article discusses the need for a robust and scientific training program for cardiothoracic transplantation surgeons in the 21st century. It highlights the importance of training surgeons not only in surgical skills but also in transplantation at a molecular level. The article mentions the establishment of a national fellowship in the UK to deliver transplant-specific surgical training and the need for improvements in the quality of training. It also emphasizes the importance of early engagement and mentorship, an international approach, certification, formal training courses, research in education, mentorship programs, surgical research, funding, and reaching out to societies with lacking transplant infrastructure. Overall, the article emphasizes the need for investment in a structured and multifaceted training program to train competent and innovative transplant surgeons. [Extracted from the article]

Aims: Risk stratification of patients with new‐onset acute heart failure (AHF) is important but remains challenging. In the present study, we evaluated the prognostic value of a new multiparameter right ventricular dysfunction (RVD) score. Methods and results: Patients (n = 210) hospitalized due to new‐onset AHF between 2015 and 2018 were retrospectively included. Mean age was 56 ± 10 years, 24% were female and median left ventricular ejection fraction was 28% (interquartile range 20; 34%). The RVD score, tricuspid annular plane systolic excursion (TAPSE), and fractional area change (FAC) were determined at index hospitalization and after therapy titration. The 4‐point RVD score included reduced TAPSE, right ventricular enlargement, moderate or severe tricuspid regurgitation and increased central venous pressure. The study endpoint was a composite of all‐cause mortality, left ventricular assist device implantation, and heart transplantation. After 60 months median follow‐up time, 53 (25%) patients met the endpoint. At index hospitalization, there were no significant differences in any echocardiographic parameter between patients with and without the endpoint. After therapy titration, there were differences in TAPSE (16 vs. 19 mm, P = 0.001), FAC (33 vs. 40%, P < 0.001) and the proportion of patients with RVD score ≥2 (36 vs. 4%, P < 0.001). The presence of RVD despite therapy titration had different impact on survival depending on the parameter considered: the proportion of patients free from events after 1 year was 87% in patients with TAPSE <17 mm, 89% in patients with FAC <35% and 65% in patients with RVD score ≥2. In a multivariable analysis, RVD score ≥2 after therapy titration, but not TAPSE <17 mm or FAC < 35%, remained associated with a higher risk of the composite endpoint (hazard ratio 3.11, 95% confidence interval 1.44–6.74). Conclusions: A novel multiparametric RVD score might improve prognostic stratification in patients with new‐onset AHF. RVD after therapy titration, but not at index hospitalization is associated with a higher risk of the composite endpoint. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to investigate the association of soluble suppression of tumorigenicity‐2 (sST2) measured by point‐of‐care testing assay with clinical outcomes in patients hospitalized with heart failure after adjusting for other predictors including N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and high‐sensitivity cardiac troponin T (hs‐cTnT). Methods: A total of 1726 consecutive patients hospitalized with heart failure from July 2015 to December 2021 were enrolled. Baseline serum sST2 concentrations were measured by immunofluorescence assay. Primary endpoint event was the composite of all‐cause death, heart transplantation, or left ventricular assist device. Results: During the median follow‐up duration of 682 days, 434 patients (25.1%) suffered from primary endpoint events. Baseline sST2 remained an independent predictor of the primary endpoint event in patients hospitalized with heart failure after adjusting for other predictors including NT‐proBNP and hs‐cTnT [per log (unit) increase, adjusted hazard ratio (HR) (95% confidence interval) (CI): 1.20 (1.09, 1.32), P < 0.001]. And baseline sST2 had a better prognostic value for patients with chronic decompensated heart failure [per log (unit) increase, adjusted HR (95% CI): 1.19 (1.07, 1.31)] than for those with acute new onset heart failure [per log (unit) increase, adjusted HR (95% CI): 1.28 (0.94, 1.75), P value for interaction <0.001], as well as a better prognostic value for patients with New York Heart Association (NYHA) functional class I–II [per log (unit) increase, adjusted HR (95% CI): 1.67 (1.11, 2.52)] than for those with NYHA functional class III‐IV [per log (unit) increase, adjusted HR (95% CI): 1.18 (1.07, 1.31), P value for interaction <0.001]. Baseline sST2 was also a good predictor of the primary endpoint event in patients hospitalized with heart failure at 1 month, 3 months, 1 year and 2 years (area under the curve: 0.789, 0.775, 0.736 and 0.733, respectively), and the best cut‐off values were 27.2 ng/ml, 27.1 ng/ml, 27.1 ng/ml and 25.1 ng/ml, respectively. Furthermore, baseline sST2 could provide additional prognostic value when added to baseline NT‐proBNP and hs‐cTnT (all P values <0.05). According to the category of elevated biomarkers (including NT‐proBNP, hs‐cTnT, and sST2), patients with three elevated biomarkers had a higher risk of the primary endpoint event compared with those with one or two elevated biomarkers (all P values <0.05). Conclusions: Baseline sST2 remained an independent predictor of adverse events after adjusting for other predictors including NT‐proBNP and hs‐cTnT, particularly in patients with chronic decompensated heart failure and NYHA functional class I–II. And in the basis of baseline NT‐proBNP and hs‐cTnT, adding baseline sST2 could provide additional prognostic value for patients hospitalized with heart failure. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion Early post‐transplant hyperglycaemia (EPTH) and post‐transplant diabetes mellitus (PTDM) are common following solid organ transplantation and may be associated with adverse outcomes. We studied the prevalence of EPTH and cumulative 5‐year prevalence of PTDM in a modern cohort of heart transplant recipients who were free from diabetes at baseline as well as the association of EPTH, PTDM and pre‐transplant T2DM with adverse transplant‐related outcomes.Retrospective cohort study of heart transplant recipients followed for 5 years at a single centre in Sydney, Australia.A total of 141 patients were included, of whom 25 had pre‐existing type 2 diabetes mellitus (T2DM) and 116 were free from diabetes at baseline. In patients without pre‐existing T2DM, 88 of 116 (76%) experienced EPTH, which was associated with higher rates of acute rejection and hospitalizations, and lower 5‐year survival. PTDM developed in 45 of 116 (39%) patients, all of whom had experienced EPTH. Both PTDM and pre‐existing T2DM were associated with increased rates of graft rejection and hospitalization, and greater than three‐fold increased likelihood of death compared to patients that remained free from diabetes.EPTH and PTDM are highly prevalent following cardiac transplantation. EPTH develops within days of transplant and is strongly associated with progression to PTDM. Pre‐existing T2DM, PTDM and EPTH are associated with greater hospitalization, increased episodes of rejection and worse 5‐year survival compared to patients who remained free from diabetes during follow‐up. [ABSTRACT FROM AUTHOR]

Background: The outcome of heart transplantation is significantly affected by perioperative infections. Individualised immunosuppression strategies are essential to reduce the risk of such infections. Case presentation: We report the successful management of a 56-year-old male patient diagnosed with dilated cardiomyopathy who underwent heart transplantation. During the perioperative period, the patient was prescribed cefoperazone sodium and sulbactam sodium, which induced a severe skin reaction: toxic epidermal necrolysis (TEN). The patient was treated with prednisone, immunoglobulins, etanercept, and other active immunomodulatory measures, together with an individualised anti-rejection regimen and physical therapy. The systemic rash resolved within a month, and the patient was successfully discharged after surgery. Conclusion: Effective management of heart transplantation necessitates balancing immunosuppression and infection prevention. Individualised immunosuppressive strategies are critical for optimal clinical outcomes. [ABSTRACT FROM AUTHOR]

Lung transplantation (LTx) is a well-known treatment for end-stage lung disease. This study aimed to report the incidence of cancer after LTx and long-term outcome among lung transplant recipients with a pretransplant diagnosis of cancer. Patients who underwent LTx between 1990–2016 were included in the study. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer Registry and the Cause-of-Death registry. A total of 614 patients were followed for a median of 5.1 years. In all, 159 malignancies were diagnosed. The excess risk of cancer or standardized incidence ratio (SIR) following LTx was 5.6-fold compared to the general Swedish population. The most common malignancies were non-melanoma skin cancer (NMSC) (SIR 76.5 (95%CI 61.7–94.8); non-Hodgkin lymphoma (SIR 23.5, 95%CI 14.8–37.2); and lung cancer (SIR 8.89, 95%CI 5.67–13.9). There was no significant difference in overall survival between those with and without a history of cancer before LTx (p = 0.56). In total, 159 malignancies were identified after LTx, which was a 5.6-fold higher relative to the general population. A history of previous cancer yields similar survival in selected recipients, compared to those without cancer prior to LTx. [ABSTRACT FROM AUTHOR]

Heart transplant patients have an increased risk of developing cancer. Patients who underwent HTx between 1985 and 2017 were included. Detection of cancer was obtained by cross-checking the study population with the Swedish Cancer-Registry and the Causeof-Death-Registry. A total of 664 patients were followed for a median of 7.7 years. In all, 231 malignancies were diagnosed in 138 patients. Compared to the general population the excess risk of cancer following HTx was 6.2-fold calculated as the standardized incidence ratio (SIR) and 2.9-fold after exclusion of non-melanoma skin cancer (NMSC). The most common malignancies were NMSC, non-Hodgins lymphoma, and lung cancer. There was no significant difference in overall survival between those with and without a history of cancer before HTx (p = 0.53). During a median follow-up of 7.7 years, 19% of HTx recipients developed cancer, 6.2-fold higher relative to the general population, and 2.9-fold higher when excluding NMSC. Risk factors for malignancies (excluding NMSC) included previous smoking, hypertension and prolonged ischemic time; and for NMSC, increasing age, seronegative CMV-donors, and azathioprine. A previous cancer in selected recipients results in similar survival compared to those without cancer prior to HTx. [ABSTRACT FROM AUTHOR]

Paediatric heart transplant is an established treatment for end stage heart failure in children, however patients have to commit to lifelong medical surveillance and adhere to daily immunosuppressants to minimise the risk of rejection. Compliance with immunosuppressants can be burdensome with their toxic side effects and need for frequent blood monitoring especially in children. Though the incidence of early rejection episodes has significantly improved overtime, the long-term allograft health and survival is determined by Cardiac Allograft Vasculopathy (CAV) which affects a vast number of post-transplant patients. Once CAV has set in, there is no medical or surgical treatment to reverse it and graft survival is significantly compromised across all age groups. Current treatment strategies include novel immunosuppressant agents and drugs to lower blood lipid levels to address the underlying immunological pathophysiology and to manage traditional cardiac risk factors. Translational researchers are seeking novel immunological approaches that can lead to permanent acceptance of the allograft such as using regulatory T cell (Tregs) immunotherapy. Clinical trials in the setting of graft versus host disease, autoimmunity and kidney and liver transplantation using Tregs have shown the feasibility and safety of this strategy. This review will summarise current knowledge of the latest clinical therapies for CAV and pre-clinical evidence in support of Treg therapy for CAV. We will also discuss the different Treg sources and the considerations of translating this into a feasible immunotherapy in clinical practice in the paediatric population. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the diagnostic value of pre-existing computed tomography (CT) examinations for the detection of dental pathologies compared with clinical dental examination in patients with end-stage heart failure. Methods: For this purpose, 59 patients with end-stage heart failure and pre-existing non-dental CT images of the craniofacial region were included. Virtual orthopantomograms (vOPG) were reconstructed. Dental pathologies were analyzed in vOPG and source-CT images. Imaging and clinical findings less than 6 months apart were compared (n = 24). Results: The subjective image quality of vOPG was more often rated as insufficient than CT (66%; 20%; p < 0.01). Depending on examination (CT, vOPG or clinic), between 33% and 92% of the patients could require dental intervention such as treatment of caries and periodontitis or tooth extraction. vOPG led to a higher (80%) prevalence of teeth requiring treatment than CT (39%; p < 0.01). The prevalence of teeth requiring treatment was similar in CT (29%) and clinic (29%; p = 1.00) but higher in vOPG (63%; p < 0.01). CT (stage 3 or 4: 42%) and vOPG (38%) underestimated the stage of periodontitis (clinic: 75%; p < 0.01). Conclusions: In conclusion, available CT images including the craniofacial region from patients with end-stage heart failure may contain valuable information regarding oral health status. The assessability of vOPGs might be insufficient and must be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions The SynCardia® temporary total artificial heart (TAH) serves as a mechanical circulatory support device for patients suffering from irreversible biventricular failure.This retrospective study analyzed 196 consecutive patients who underwent TAH implantation at our center from 2001 to 2021. We assessed survival rates and all‐cause mortality during TAH support, including survival post‐heart transplantation.The median age of patients was 55 years, with 88% being male. The primary diagnoses included cardiomyopathy (43.9%), acute myocardial infarction (26.5%), and postcardiotomy heart failure (15.5%). At implantation, 87.2% of patients were classified as INTERMACS Profile 1. The median duration of support was 96 days (IQR: 23–227). Survival rates at 1, 6, and 12 months were 72%, 41%, and 34%, respectively. Postoperative rethoracotomy was necessary in 44.4% of patients; 39.3% experienced neurological events and 24.6% developed gastrointestinal bleeding. Overall, 64.8% of patients died while on support, primarily due to multiple organ failure (55.9%). Factors such as older age, higher bilirubin levels, postcardiotomy and specific underlying diagnoses were independent predictors of mortality during TAH support. On a positive note, 35.2% of patients underwent successful heart transplants, with 1‐, 5‐, and 10‐year posttransplant survival rates of 65%, 58%, and 51%, respectively.While high mortality rates persist among patients with biventricular failure, the SynCardia® TAH offers a viable interim solution for critically ill patients, particularly those who can be successfully bridged to heart transplantation. [ABSTRACT FROM AUTHOR]

This study's goals were to determine the health status of a group of heart transplant recipients (HTRs) and their level of physical activity and to compare the health status among them and with a group of healthy sedentary individuals. Fifty-four HTRs and eighteen sedentary individuals (S) were assigned to four groups, according to their level of physical activity (determined with the International Physical Activity Questionnaire); patients with a low, moderate, and high level of physical activity (HTRL, HTRM, and HTRH, respectively) and S participants underwent a basic blood analysis and several tests to assess their cardiovascular, neuromuscular, and functional mobility condition and their quality of life. The S and HTRH were very similar in terms of BP, HR, and blood analysis while HTRM and HTRL differed from both S and HTRH in these parameters. Regarding the cardiovascular, neuromuscular, functional mobility, and quality of life variables assessed in this study, HTRH showed the best results across all of them, followed by S, HTRM, and HTRL. It is suggested that the weekly level of physical activity of HTRs should be high, which might help them to enhance their health and quality of life. [ABSTRACT FROM AUTHOR]

Non-adherence to immunosuppressive medication among transplant patients is associated with poor clinical outcomes and higher economic costs. Barriers to immunosuppressives are a proximal determinant of non-adherence. So far, international variability of barriers to adherence in transplantation has not been studied. As part of the cross-sectional multi-country and multi-center BRIGHT study, barriers to adherence were measured in 1,382 adult heart transplant recipients of 11 countries using the 28-item self-report questionnaire "Identifying Medication Adherence Barriers" (IMAB). Barriers were ranked by their frequency of occurrence for the total sample and by country. Countries were also ranked the by recipients' total number of barriers. Intra-class correlations were calculated at country and center level. The five most frequently mentioned barriers were sleepiness (27.1%), being away from home (25.2%), forgetfulness (24.5%), interruptions to daily routine (23.6%) and being busy (22.8%), fairly consistently across countries. The participants reported on average three barriers, ranging from zero up to 22 barriers. The majority of the variability among reported barriers frequency was situated at the recipient level (94.8%). We found limited international variability in primarily person-level barriers in our study. Understanding of barriers in variable contexts guides intervention development to support adherence to the immunosuppressive regimen in real-world settings. [ABSTRACT FROM AUTHOR]

Conventional diastolic dysfunction parameters seem to be imperfect when applied to the pediatric cardiomyopathy population. The aim of this pilot study was to search for novel echocardiographic parameters associated with adverse outcomes in children with the most common cardiomyopathies. Fifty-six patients with pediatric cardiomyopathies (28 with dilated, 21 with hypertrophic, 7 with left ventricular non-compaction cardiomyopathy) and 28 healthy subjects were included in the study. Left atrial reservoir (LASr), conduit (LAScd) and contraction (LASct) strain, left atrial stiffness index (LASI), as well as conventional diastolic dysfunction parameters were measured using echocardiography. Adverse outcomes were defined as heart failure (including heart transplant) and arrhythmic endpoints. Patients with adverse outcomes presented with significantly lower LASr (16.68% ± 8.64% vs. 33.97% ± 9.99%, p-value < 0.001), lower LAScd (− 10.37% ± 5.83% vs. − 25.50% ± 9.24%, p-value < 0.001) and higher values of LASI (0.69 [IQR 0.34; 1.11] vs. 0.21 [IQR 0.16; 0.31], p-value < 0.001). LASr < 20%, LAScd ≥ − 12%, and LASI ≥ 0.26 were all associated with reduced survival. LASr, LAScd and LASI seem to be promising parameters in predicting adverse outcomes in the most common pediatric cardiomyopathies. Left atrial strain parameters and LASI are helpful in differentiating healthy control subjects from children with hypertrophic and dilated cardiomyopathies. [ABSTRACT FROM AUTHOR]

Background: Cardiac fibromas are extremely rare in adults. The preferred treatment is surgical resection, but antiarrhythmic medications or heart transplantation have also been used previously. The cardiac imaging, particularly MRI, can be useful to help delineate between primary cardiac tumors, and surgical factors such as the extent/size of the fibroma, involvement of the coronary arteries or mitral apparatus and amount of residual myocardium influence whether surgical resection is feasible. Case presentation: A 42-year-old male presented with a wide-complex tachycardia, unresponsive to amiodarone. An echocardiogram was performed which showed a possible posterior wall mass. A cardiac MRI showed a well circumscribed lateral wall intracardiac fibroma, measuring 5.2 × 5.1 × 3.8 cm with preserved function. Surgical resection was successful, and he was discharged without a defibrillator. Conclusions: Cardiac fibromas are encapsulated tumors which do not infiltrate myocardium and should be surgically resected if possible. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion The Organ Care System (OCS) (Transmedics, Andover, MA) reduces cold ischemic time of donor hearts by producing a normothermic beating state during ex vivo perfusion, enabling extended ex situ intervals, which potentially increases donor pool. We aimed to compare outcomes in utilization of OCS and conventional cold storage technique.Consecutive heart transplants following brain death at our institution between May 2022 and July 2023 were analyzed. Recipients were divided into those receiving hearts preserved with OCS [N = 15] and those with conventional cold storage (Control, N = 27), with OCS utilization when anticipated ischemic time was more than 4 h. Pre‐transplant characteristics and transplant outcomes were compared.OCS utilization allowed a significant increase in distance traveled for heart retrieval (OCS, 624 ± 269 vs. Control, 153 ± 128 miles, p < 0.001), with longer mean total preservation times (6.2 ± 1.1 vs 2.6 ± 0.6 h, p < 0.001). All but one patient displayed a general decrease or plateau in lactate throughout perfusion time by OCS. Both groups experienced similar rates of severe primary graft dysfunction (OCS, 6.7% [N = 1] vs. Control, 11.1% [N = 3], p = 0.63), with 100% in‐hospital survival in the OCS group compared to 96.3% in the Control group (p = 0.34). Kaplan–Meier survival analysis showed that estimated one‐year survival were comparable (OCS, 93.3 ± 6.4% vs. Control, 88.9 ± 6.0%, p = 0.61).With a mean preservation time of around 6 h and distance covered of over 600 miles, our results using OCS indicate a potential to safely increase the quantity and viability of accessible organs, thus broadening the donor pool without negatively affecting outcomes. [ABSTRACT FROM AUTHOR]

Physical therapy students must learn about heart transplantation. They need to know how to care for these patients' emotions and needs. The study aimed to compare the effectiveness of a narrative photography (NP) program and a traditional learning (TL) program in physical therapy students' knowledge, satisfaction, empathy, and moral sensitivity. A two‐armed assessor‐blinded randomized controlled trial was carried out. One hundred and seventeen physical therapy students participated in the study. They were divided into two groups: (i) NP group (n = 56) and (ii) TL group (n = 61). At the end of the program, NP group's knowledge increased when compared with the TL group (p = 0.02). 90.57% of the sample was very satisfied/satisfied with the NP method, and 88.68% felt that NP helped them to understand the importance of considering subjective realities. In conclusion, NP improved knowledge and satisfaction compared with the TL group. These results suggest that NP may be a useful method to improve the academic outcomes of physical therapy students in the heart transplantation field; thus, NP may be considered a teaching–learning methodology of choice in physical therapy students. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis B virus (HBV) vaccination is recommended for solid organ transplant (SOT) candidates. However, there is a lack of data on the HBV vaccine compliance, serologic response, and durability of HBV seroprotection in thoracic organ transplantation recipients. Methods: We conducted a retrospective study of adult thoracic organ (heart and lung) transplant candidates who received HBV vaccination at Mayo Clinic sites in Minnesota, Arizona, and Florida between January 2018 and August 2023. Conventional recombinant hepatitis B vaccine (Recombivax HB) was used before 2020, and Heplisav‐B was preferred after 2020. HBV seroprotection was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L. Furthermore, we compared characteristics between recipients who maintained HBV seroprotection and those who lost HBV seroprotection (HBsAb < 10 IU/L) at 30 days posttransplantation (D30). Results: Among 922 candidates who were eligible for HBV vaccination, 430 (47%) completed the HBV vaccine series. Patients receiving Heplisav‐B were more likely to complete the series than Recombivax HB (81% vs. 60%, p < 0.001) and Heplisav‐B had a higher seroprotection rate than Recombivax HB (75% vs. 64%, p = 0.023). Multivariate logistic regression analysis identified receiving Heplisav‐B as an independent predictor for HBV seroprotection (adjusted odds ratio [aOR] 1.723; 95% confidence interval [CI] 1.056–2.810; p = 0.029). A total of 145 thoracic organ transplant recipients achieved HBV seroprotection at the date of transplantation. Loss of HBV seroprotection occurred in 38 (26%) patients at D30. Multivariate logistic regression analysis identified two predictors for HBV seroprotection loss at D30: age ≥ 60 years (aOR, 2.503; 95% CI 1.026–6.107; p = 0.044), and pretransplant HBsAb level between 10 and 100 IU/L (aOR, 18.575; 95% CI 5.211–66.209; p < 0.001). Conclusions: Although less than half of thoracic organ transplant candidates completed HBV vaccine series pretransplant, Heplisav‐B provided a higher vaccine completion rate and seroprotection than the 3‐dose Recombivax HB. Clinicians should also be aware of the increased loss of HBV seroprotection in thoracic organ transplant recipients with age ≥ 60 years and pretransplant HBsAb between 10 and 100 IU/L. Assessment of seroprotection after HBV vaccination should be prioritized during the pretransplant period. [ABSTRACT FROM AUTHOR]

Background: The 2018 UNOS allocation policy change deprioritized geographic boundaries to organ distribution, and the effects of this change have been widespread. The aim of this investigation was to analyze changes in donor transplant center distance for organ travel and corresponding outcomes before and after the allocation policy change. Methods: The UNOS database was utilized to identify all adult patients waitlisted for heart transplants from 2016 to 2021. Transplant centers were grouped by average donor heart travel distance based on whether they received more or less than 50% of organs from >250 miles away. Descriptive statistics were provided for waitlisted and transplanted patients. Regression analyses modeled waitlist mortality, incidence of transplant, overall survival, and graft survival. Results: Centers with a longer average travel distance had a higher mean annual transplant volume with a reduction in total days on a waitlist (86.6 vs. 149.2 days), an increased cold ischemic time (3.6 vs. 3.2 h), with no significant difference in post‐transplant overall survival or graft survival. Conclusions: The benefits of reducing waitlist time while preserving post‐transplant outcomes extend broadly. The trends observed in this investigation will be useful as we revise organ transplant policy in the era of new organ procurement and preservation techniques. [ABSTRACT FROM AUTHOR]

Background: There are diverse indications for heart transplantation (HTx), often categorized into ischemic (ICM) and nonischemic (NICM) cardiomyopathy. Although there is extensive research comparing the outcomes for these disease processes following certain therapeutic interventions, there are limited data on how recipient etiology impacts post‐HTx survival. Our investigation seeks to identify this relationship. Methods: We conducted a retrospective analysis using adult HTx patients from the United Network for Organ Sharing database between 2000 and 2021. Patients with a combined heart–lung transplant or previous HTx were excluded. ICM included coronary artery disease (CAD) and ischemic dilated cardiomyopathy. NICM included nonischemic dilated (NIDCM), hypertrophic (HCM), and restrictive (RCM) cardiomyopathy. Overall survival was analyzed using Kaplan–Meier curves, log‐rank tests, and multivariable Cox regression models. Results: A total of 42 268 patients were included in our study. Recipients with ICM were older and more likely to be males, obese, diabetics, and smokers. We found that patients with ICM had an increased incidence of transplant CAD (OR = 1.23, p < 0.001) and risk of mortality (hazard ratio [HR] = 1.22, p < 0.001) compared to NICM. When NICM was expanded, RCM had a similar hazard risk compared to ICM (HR = 1.03, p = 0.650), whereas both NIDCM (HR = 0.81, p < 0.001) and HCM (HR = 0.70, p < 0.001) had improved survival. Conclusion: Our study provides evidence to suggest that ICM has decreased survival when compared to NICM. When NICM was expanded, RCM was found to have an increased mortality risk similar to ICM, whereas NIDCM and HCM both had superior outcomes. The clinical implication of this investigation will allow clinicians to better understand the prognosis of certain patient groups. [ABSTRACT FROM AUTHOR]

Persistent acute kidney injury (pAKI), compared with acute kidney injury (AKI) that resolves in <72 h, is associated with worse prognosis in critically ill patients. Definitions and prognosis of pAKI are not well characterized in solid organ transplant patients. Our aims were to investigate (a) definitions and incidence of pAKI; (b) association with clinical outcomes; and (c) risk factors for pAKI among heart, lung, and liver transplant recipients. We systematically reviewed the literature including PubMed, Embase, Web of Science, and Cochrane from inception to 8/1/2023 for human prospective and retrospective studies reporting on the development of pAKI in heart, lung, or liver transplant recipients. We assessed heterogeneity using Cochran's Q and I2. We identified 25 studies including 6330 patients. AKI (8%–71.6%) and pAKI (2.7%–55.1%) varied widely. Definitions of pAKI included 48–72 h (six studies), 7 days (three studies), 14 days (four studies), or more (12 studies). Risk factors included age, body mass index (BMI), diabetes, preoperative chronic kidney disease (CKD), intraoperative vasopressor use, and intraoperative circulatory support. pAKI was associated with new onset of CKD (odds ratio [OR] 1.41–11.2), graft dysfunction (OR 1.81–8.51), and long‐term mortality (OR 3.01–13.96), although significant heterogeneity limited certainty of CKD and graft dysfunction outcome analyses. pAKI is common and is associated with worse mortality among liver and lung transplant recipients. Standardization of the nomenclature of AKI will be important in future studies (PROSPERO CRD42022371952). [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to determine outcomes after heart transplantation for cytomegalovirus (CMV) mismatched patients (D+/R−) who underwent a surveillance and preemptive therapy protocol, compared to nonmismatch patients. Methods: A review of patient records from January 2010 to December 2020 with follow‐up to October 2023 was done. The protocol consisted weekly surveillance with CMV PCR starting 4 weeks after transplant continuing up until the patient seroconverts or up to 3 months posttransplant if the patient does not seroconvert. Valganciclovir was given for 2 weeks to those who seroconverted. Results: Two hundred and twenty‐one patients were included, and 23% were mismatched patients. Overall survival was not different between CMV groups (p = NS). Causes of death and morbidities were also not significantly different (p = NS). Sixty‐six percent of mismatch patients seroconverted, and there was also a significantly older donor age in the seroconverted patients compared to nonseroconverted patients (41 ± 11 vs. 29 ± 12 years, p < 0.005), indicating a higher risk donor profile. A multivariate Cox regression including donor age showed that there was no increase in mortality in the seroconverted mismatches compared to nonmismatch patients (p = NS). Conclusions: There is no significant increased mortality or morbidity using a CMV surveillance and preemptive therapy protocol. The effect of donor age on seroconversion of mismatches requires further validation. [ABSTRACT FROM AUTHOR]

(1) Background: Cardiac donation after circulatory death (DCD) is an emerging paradigm in organ transplantation. However, this technique is recent and has only been implemented by highly experienced centers. This study compares the characteristics and outcomes of thoraco-abdominal normothermic regional perfusion (TANRP) and static cold-storage DCD and traditional donation after brain death (DBD) cardiac transplants (CT) in a newly stablished transplant program with restricted donor availability. (2) Method: We performed a retrospective, single-center study of all adult patients who underwent a CT between November 2019 and December 2023, with a follow-up conducted until August 2024. Data were retrieved from medical records. A review of the current literature on DCD CT was conducted to provide a broader context for our findings. The primary outcome was survival at 6 months after transplantation. (3) Results: During the study period, 76 adults (median age 56 years [IQR: 50–63 years]) underwent CT, and 12 (16%) were DCD donors. DCD donors had a similar age (46 vs. 47 years, p = 0.727), were mostly male (92%), and one patient had left ventricular dysfunction during the intraoperative DCD process. There were no significant differences in recipients' characteristics. Survival was similar in the DCD group compared to DBD at 6 months (100 vs. 94%) and 12 months post-CT survival (92% vs. 94%), p = 0.82. There was no primary graft dysfunction in the DCD group (9% in DBD, p = 0.581). The median total hospital stay was longer in the DCD group (46 vs. 21 days, p = 0.021). An increase of 150% in transplantation activity due to DCD was estimated. (4) Conclusions: In a new CT program that utilized older donors and included recipients with similar illnesses and comorbidities, comparable outcomes between DCD and DBD hearts were observed. DCD was rapidly incorporated into the transplant activity, demonstrating an expedited learning curve and significantly increasing the availability of donor hearts. [ABSTRACT FROM AUTHOR]

Purpose: Pediatric Cardiac Quality of Life Inventory (PCQLI) is a disease-specific pediatric cardiac health-related quality of life (HRQOL) instrument that is reliable, valid, and generalizable. We aim to demonstrate PCQLI responsiveness in children undergoing arrhythmia ablation, heart transplantation, and valve surgery before and after cardiac intervention. Methods: Pediatric cardiac patients 8–18 years of age from 11 centers undergoing arrhythmia ablation, heart transplantation, or valve surgery were enrolled. Patient and parent-proxy PCQLI Total, Disease Impact and Psychosocial Impact subscale scores were assessed pre- and 3–12 months follow-up. Patient clinical status was assessed by a clinician post-procedure and dichotomized into markedly improved/improved and no change/worse/much worse. Paired t-tests examined change over time. Results: We included 195 patient/parent-proxies: 12.6 ± 3.0 years of age; median follow-up time 6.7 (IQR = 5.3–8.2) months; procedural groups − 79 (41%) ablation, 28 (14%) heart transplantation, 88 (45%) valve surgery; clinical status − 164 (84%) markedly improved/improved, 31 (16%) no change/worse/much worse. PCQLI patient and parent-proxies Total scores increased (p ≤ 0.013) in each intervention group. All PCQLI scores were higher (p < 0.001) in the markedly improved/improved group and there were no clinically significant differences in the PCQLI scores in the no difference/worse/much worse group. Conclusion: The PCQLI is responsive in the pediatric cardiac population. Patients with improved clinical status and their parent-proxies reported increased HRQOL after the procedure. Patients with no improvement in clinical status and their parent-proxies reported no change in HRQOL. PCQLI may be used as a patient-reported outcome measure for longitudinal follow-up and interventional trials to assess HRQOL impact from patient and parent-proxy perspectives. [ABSTRACT FROM AUTHOR]

Objective To investigate the antigen presentation characteristics of dendritic cells (DC) and B cells in cardiac grafts. Methods The heart of BALB/c mice was transplanted into the abdominal cavity of C57BL/6J mice. CD45+ cells in the heart graft were extracted and sorted by flow cytometry at postoperative 5 d, and single cell RNA sequencing was performed. Taking DC and B cell subsets in cardiac grafts as the main study cells, the changing trend, antigen presenting ability and intercellular communication with T cells after heart transplantation were analyzed by bioinformatics analysis and flow cytometry. Gene ontology (GO) function enrichment difference analysis was adopted to prove the specific function and the reliability annotation of cell subsets. Results Germinal center-like B cell (GC-L B) was the B cell subset with the largest increase in quantity during the acute rejection phase, accounting for 87%. Classical DC (cDC) 2 was the only DC subset with a significant increase in quantity during acute rejection of heart transplantation, accounting for 44% of DC subset, and it occupied the highest communication intensity with T cells after heart transplantation. Mononucleated DC (moDC) and memory B cell (MBC) were the main transmitters of T cell input signals in nontransplanted hearts, whereas transformed into cDC2 and GC-L B during the acute rejection phase. Among them, MBC and GC-L B were the main sources of T cell input signals in non-transplanted hearts and heart grafts. Conclusions Compared with DC, B cells occupy a higher number and weight in the intercellular communication with T cells in non-transplanted hearts and heart grafts, prompting that the antigen presenting activity of B cells is more active and stronger than DC in the early stage of acute rejection of heart transplantation. [ABSTRACT FROM AUTHOR]

Objective To investigate the regulatory effect of Xuebijing injection on inflammatory reaction during the preservation of isolated empty beating pig hearts with extracorporeal membrane oxygenation. Methods Twelve healthy Guangxi Bama miniature pigs were randomly divided into the Xuebijing group (n=6) and normal saline group (n=6). After the models were established in the Xuebijing group, Xuebijing injection was given at a dose of 5 mL/h through micropump in membrane oxygenator. In the normal saline group, an equivalent amount of 0.9% sodium chloride injection was pumped. Continuous pumping was performed for 8 h in both groups. The time of cardiac resuscitation and perfusion pressure, heart rate, perfusion flow rate after 8 h preservation were recorded in two groups. Pathological and ultrastructural changes of myocardial tissues in the left ventricular wall of hearts with cardiac arrest were observed after 8 h preservation. Serum levels of myocardial injury markers and inflammatory cytokines were detected in two groups at the beginning (T0), 2 h (T2), 4 h (T4), 6 h (T6) and 8 h (T8) after model establishment, respectively. The expression levels of NOD-like receptor protein 3(NLRP3), cysteinyl aspartate specific proteinase-1(Caspase-1), apoptosis-associated speck-like protein containing a CARD(ASC) messenger RNA (mRNA) in myocardial tissues were measured at T0, T2, T4, T6 and T8, respectively. Results There were no significant differences in the time of cardiac resuscitation and perfusion pressure, heart rate, perfusion flow rate after 8 h preservation between two groups (all P>0.05). Compared with the normal saline group, the levels of lactate dehydrogenase (LDH) at T4, creatine kinase (CK), LDH and α-hydroxybutyrate dehydrogenase (α-HBDH) at T6 and T8, tumor necrosis factor (TNF)-α at T4, T6 and T8, and interleukin (IL)-6, IL-18 and IL-1β at T0, T2, T4, T6 and T8 were lower, and the mRNA relative expression levels of NLRP3 and Caspase-1 at T2, T4 and T6, and Caspase-1 and ASC at T8 were lower in the Xuebijing group, respectively (all P<0.05). Hematoxylin-eosin staining and transmission electron microscopy showed that the degree of myocardial injury in the Xuebijing group was slighter than that in the normal saline group. Conclusions Xuebijing injection may effectively mitigate inflammatory response and exert certain myocardial protection effect during the ECMO preservation of isolated empty beating pig hearts. [ABSTRACT FROM AUTHOR]

The quality-adjusted life year (QALY) measures disease burden and treatment, combining overall survival and health-related quality of life (HRQOL). We estimated QALYs in 3 groups of older patients (60-80 years) with heart failure (HF) who underwent heart transplantation (HT, with pre-transplant mechanical circulatory support [HT MCS] or HT without pre-transplant MCS [HT Non-MCS]) or long-term MCS (destination therapy). We also identified factors associated with gains in QALYs through 24 months follow-up. Of 393 eligible patients enrolled (10/1/15-12/31/18) at 13 U.S. sites, 161 underwent HT (n = 68 HT MCS, n = 93 HT Non-MCS) and 144 underwent long-term MCS. Survival and HRQOL data were collected through 24 months. QALY health utilities were based on patient self-report of EQ-5D-3L dimensions. Mean-restricted QALYs were compared among groups using generalized linear models. For the entire cohort, mean age in years closest to surgery was 67 (standard deviation, SD: 4.7), 78% were male, and 83% were White. By 18 months post-surgery, sustained significant differences in adjusted average ± SD QALYs emerged across groups, with the HT Non-MCS group having the highest average QALYs (24-month window: HT Non-MCS = 22.58 ± 1.1, HT MCS = 19.53 ± 1.33, Long-term MCS = 19.49 ± 1.3, p = 0.003). At 24 months post-operatively, a lower gain in QALYs was associated with HT MCS, long-term MCS, a lower pre-operative LVEF, NYHA class III or IV before surgery, and an ischemic or other etiology of HF. Determination of QALYs may provide important information for policy makers and clinicians to consider regarding benefits of HT and long-term MCS as treatment options for older patients with HF. [ABSTRACT FROM AUTHOR]

It is unknown whether racial disparities in access to heart transplantation (HT) are amplified when coupled with substance use. We examined patients evaluated for HT over 8 years at an urban transplant center. We evaluated substance use and race/ethnicity as independent and interactive predictors of HT and left ventricular assist device (LVAD) implantation. Of 1,148 patients evaluated for HT, substance use was cited as an ineligibility factor in 151 (13%) patients, 16 (11%) of whom ultimately received HT. Significantly more non-Hispanic Black (NHB) patients were deemed ineligible due to substance use (n = 59, 19%) compared to other races/ethnicities (non-Hispanic white: n = 68, 12%; other race/ethnicity: n = 24, p = 0.002). No racial differences were observed in the likelihood of HT among patients initially excluded for substances, but more NHB patients ultimately received LVAD than the other racial groups. This study encourages greater awareness of the role of substance use and race in the HT evaluation. [ABSTRACT FROM AUTHOR]

Current monitoring after heart transplantation (HT) employs repeated invasive endomyocardial biopsies (EMB). Although positive EMB confirms rejection, EMB fails to predict impending, subclinical, or EMB-negative rejection events. While non-human leukocyte antigen (non-HLA) antibodies have emerged as important risk factors for antibody-mediated rejection after HT, their use in clinical risk stratification has been limited. A systematic review of the role of non-HLA antibodies in rejection pathologies has the potential to guide efforts to overcome deficiencies of EMB in rejection monitoring. Databases were searched to include studies on non-HLA antibodies in HT recipients. Data collected included the number of patients, type of rejection, non-HLA antigen studied, association of non-HLA antibodies with rejection, and evidence for synergistic interaction between non-HLA antibodies and donor-specific anti-human leukocyte antigen antibody (HLA-DSA) responses. A total of 56 studies met the inclusion criteria. Strength of evidence for each non-HLA antibody was evaluated based on the number of articles and patients in support versus against their role in mediating rejection. Importantly, despite previous intense focus on the role of anti-major histocompatibility complex class I chain-related gene A (MICA) and anti-angiotensin II type I receptor antibodies (AT1R) in HT rejection, evidence for their involvement was equivocal. Conversely, the strength of evidence for other non-HLA antibodies supports that differing rejection pathologies are driven by differing non-HLA antibodies. This systematic review underscores the importance of identifying peri-HT non-HLA antibodies. Current evidence supports the role of non-HLA antibodies in all forms of HT rejection. Further investigations are required to define the mechanisms of action of non-HLA antibodies in HT rejection. [ABSTRACT FROM AUTHOR]

Sarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and predicts poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate for skeletal muscle mass, in HF, left ventricular assist device (LVAD), and heart transplant (HT), and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota. We enrolled 460 HF, LVAD, and HT patients. Repeated measures pre/post-procedures were obtained prospectively in a subset of LVAD and HT patients. SI (serum creatinine/cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S ribosomal ribonucleic acid sequencing among 335 stool and 341 saliva samples. Multivariable regression assessed the relationship between SI and (1) New York Heart Association class; (2) pre- versus post-LVAD or HT; and (3) biomarkers of inflammation and microbial diversity. Median (interquartile range) natural logarithm (ln)-SI was −0.13 (−0.32, 0.05). Ln-SI decreased across worsening HF class, further declined at 1 month after LVAD and HT, and rebounded over time. Ln-SI was correlated with inflammation (r = −0.28, p < 0.01), gut (r = 0.28, p < 0.01), and oral microbial diversity (r = 0.24, p < 0.01). These associations remained significant after multivariable adjustment in the combined cohort but not for all individual cohorts. The presence of the gut taxa Roseburia inulinivorans was associated with increased SI. SI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. In the combined cohort, SI levels covaried with inflammation in a similar fashion and were significantly related to overall microbial (gut and oral) diversity, including specific taxa compositional changes. [ABSTRACT FROM AUTHOR]

Molecular testing with gene-expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) is increasingly used in the surveillance for acute cellular rejection (ACR) after heart transplant. However, the performance of dual testing over each test individually has not been established. Further, the impact of dual noninvasive surveillance on clinical decision-making has not been widely investigated. We evaluated 2,077 subjects from the Surveillance HeartCare Outcomes Registry registry who were enrolled between 2018 and 2021 and had verified biopsy data and were categorized as dual negative, GEP positive/dd-cfDNA negative, GEP negative/dd-cfDNA positive, or dual positive. The incidence of ACR and follow-up testing rates for each group were evaluated. Positive likelihood ratios (LRs+) were calculated, and biopsy rates over time were analyzed. The incidence of ACR was 1.5% for dual negative, 1.9% for GEP positive/dd-cfDNA negative, 4.3% for GEP negative/dd-cfDNA positive, and 9.2% for dual-positive groups. Follow-up biopsies were performed after 8.8% for dual negative, 14.2% for GEP positive/dd-cfDNA negative, 22.8% for GEP negative/dd-cfDNA positive, and 35.4% for dual-positive results. The LR+ for ACR was 1.37, 2.91, and 3.90 for GEP positive, dd-cfDNA positive, and dual-positive testing, respectively. From 2018 to 2021, biopsies performed between 2 and 12-months post-transplant declined from 5.9 to 5.3 biopsies/patient, and second-year biopsy rates declined from 1.5 to 0.9 biopsies/patient. At 2 years, survival was 94.9%, and only 2.7% had graft dysfunction. Dual molecular testing demonstrated improved performance for ACR surveillance compared to single molecular testing. The use of dual noninvasive testing was associated with lower biopsy rates over time, excellent survival, and low incidence of graft dysfunction. [Display omitted] [ABSTRACT FROM AUTHOR]

In the 1990s, neonates born with severe congenital heart disease faced more than 50% mortality awaiting an ABO-compatible (ABOc) transplant donor. This desperate situation, together with knowledge of gaps in the adaptive immune system in early childhood, led to the clinical exploration of intentional ABO-incompatible (ABOi) heart transplantation. In 2001, West et al. reported the first series of 10 infants in Canada. Since then, consideration of ABOi heart donors has become the standard of care for children awaiting transplantation in the first few years of life, resulting in reduced wait times and better organ utilization with noninferior post-transplant outcomes compared to ABOc recipients. This state-of-the-art review discusses the clinical development and evolution, underlying and resulting immunological aspects, current challenges, and future directions of ABOi heart transplantation. [ABSTRACT FROM AUTHOR]

In 1984, 21 years after the first liver transplantation, Thomas Starzl achieved a milestone by performing the world's first combined heart-liver transplantation. While still uncommon, the practice of combined heart-liver transplants is on the rise globally. In this review, the authors delve into the current literature on this procedure, highlighting the evolving landscape and key considerations for anesthesiologists. Over the years, there has been a remarkable increase in the number of combined heart-liver transplantations conducted worldwide. This surge is largely attributed to the growing population of adult survivors with single-ventricle physiology, palliated with a Fontan procedure, who later present with late Fontan failure and Fontan-associated liver disease. Research indicates that combined heart-liver transplantation is an effective treatment option, with reported outcomes comparable with isolated heart or liver transplants. Managing anesthesia during a combined heart-liver transplant procedure is challenging, especially in the context of underlying Fontan physiology. International experience in this field remains somewhat limited, with most techniques derived from expert opinions or experiences with single-organ heart and liver transplants. These procedures are highly complex and performed infrequently. As the number of combined heart-liver transplants continues to rise globally, there is a growing need for clear guidance on periprocedural surgical and anesthetic management. Anesthesiologists overseeing these patients must consider multiple factors, balancing various comorbidities with significant hemodynamic and metabolic shifts. An increase in (multicenter) studies focusing on specific interventions to enhance patient and organ outcomes is anticipated in the coming years. [ABSTRACT FROM AUTHOR]

Purpose of Review: This review aims to evaluate the current diagnostic standards for cardiac allograft vasculopathy (CAV) in heart transplant recipients, with a focus on the role of positron emission tomography (PET) myocardial perfusion imaging (MPI). The review addresses the efficacy of PET as a non-invasive alternative to invasive coronary angiography (ICA) and discusses recent guidelines and advancements in the detection and management of CAV. Recent Findings: Recent research underscores the potential role of PET imaging in detecting CAV, particularly by assessing myocardial blood flow (MBF) and myocardial flow reserve (MFR). PET has emerged as a highly effective tool, offering potential advantages in diagnostic accuracy, cost-effectiveness, and reduced radiation exposure compared to ICA. The 2023 International Society for Heart and Lung Transplantation guidelines list PET MPI as a Class IIa indication for non-invasive CAV screening, highlighting its superior prognostic value. Studies demonstrate that PET-derived MBF and MFR correlate well with invasive measures and predict adverse outcomes, emphasizing the role of PET MPI in the early detection and management of CAV. Additionally, PET MPI can potentially reduce the need for frequent invasive procedures, thereby lowering healthcare costs. Summary: PET MPI significantly enhances the detection and prognostication of CAV in heart transplant recipients, providing a non-invasive, accurate, and cost-effective alternative to ICA. Integrating PET into routine surveillance protocols can improve early diagnosis and management of CAV, ultimately enhancing patient outcomes. Large multicenter studies are needed to optimize surveillance strategies and to further validate the role of PET in CAV detection and management. [ABSTRACT FROM AUTHOR]

Combined heart-liver transplantation (CHLT) is a viable option for concurrent heart and liver failure, yet its indications are unclear. This preliminary study aimed to describe pre-transplant characteristics and outcomes of patients with liver fibrosis undergoing HT and CHLT, while exploring decompensated liver dysfunction following HT. A total of 52 patients (HT = 42; CHLT = 10) were included. In HT patients, F1 fibrosis was more common (52%), with 43% exhibiting F3 or F4 fibrosis. F4 fibrosis was predominant in the CHLT patients (80%). Post-hepatic portal hypertension was present in 62% of HT and 90% of CHLT patients. None progressed to liver decompensation (i.e., new ascites, variceal bleed, jaundice, hepatic hydrothorax, or hepatic encephalopathy) after HT. Over a median follow-up period of 3.7 [IQR 1.2–9.1] years, the two groups did not differ statistically in survival (p = 0.60). Altogether, HT and CHLT may have similar survival outcomes, and HT patients may not progress to decompensation postoperatively despite advanced fibrosis. Decompensated cirrhosis could serve as a factor for identifying CHLT candidates, but it is crucial to differentiate it from post-hepatic portal hypertension, which does not necessitate liver transplant. Further research is needed to determine selection criteria for CHLT, ensuring efficient utility of organs. [ABSTRACT FROM AUTHOR]

The hallmark of aluminum phosphide (AlP) poisoning is heart failure in victims which is associated with reactive oxygen species (ROS), mitochondrial dysfunction, oxidative stress, alteration in antioxidant defense system and depletion of ATP in cardiomyocytes. In the present study, we hypothesized that the injection of isolated mitochondria into blood or mitochondrial transplantation can likely create a primary target for phosphine released from AlP and inhibit AlP-induced mortality and cardiotoxicity in rat. Male, Wistar, healthy and adult rats were randomly divided into 5 groups as control, AlP (12.5 mg/kg, orally), AlP + mitochondria (125 µg/kg), AlP + mitochondria (250 µg/kg) and mitochondria (250 µg/kg) alone. Functional and intact mitochondria isolated from rat heart and transplantation was carried out via tail vein, 30 min after exposure to AlP. Survival rate, histopathological alterations, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters were monitored and analyzed during 30 days. We found that injection of healthy mitochondria into blood at concentrations of 125 and 250 125 µg/ml significantly increased the survival of rats up to 40% and 56.25% respectively, during 30 days. Moreover, we observed that mitochondria injection into blood decreased histopathological damages, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters. To our knowledge, the current study is the first report in the literature that demonstrated good therapeutic effects of mitochondrial transplantation in AlP-induced mortality and cardiotoxicity. The findings of the present study suggests that injection of exogenous mitochondria into blood could be an effective therapeutic strategy in treating AlP poisoning. [ABSTRACT FROM AUTHOR]

Heart transplantation is the gold-standard treatment for terminal heart failure. Despite being successful, pre- and post-transplant limitations interfere with patients' functional capacity, self-care, and quality of life post-surgery. Rehabilitation is necessary to address these limitations, prevent complications, and promote a safe return home. This study analyzes the safety of a phase 1 cardiac rehabilitation protocol (RN4HTx) in heart transplant patients and its effects on self-care capacity. A quantitative, descriptive study was conducted with 19 heart transplant recipients. The protocol was implemented in collaboration with a rehabilitation professional, who monitored adverse events, hemodynamic variables, self-care capacity (Barthel) pre- and post-transplant, and functional capacity at discharge (6 min walk test). The results showed that 68.42% of recipients were men, with an average age of 50.21 years and 15 days of hospitalization post-transplant. Approximately 73.68% of recipients were transferred from other wards with changes in functional capacity. All patients progressed to the final stage of the program without adverse events. There was a notable improvement in self-care capacity before and after transplantation, with a measure of functional status of 310.035 m (6MWT). The study found that RN4HTx is a feasible cardiac rehabilitation program without adverse events in the immediate postoperative period following heart transplantation, positively impacting functional recovery and therapeutic self-care capacity, thus increasing the safety of returning home. This study was retrospectively registered on Clinical Trials—NCT06552390. [ABSTRACT FROM AUTHOR]