Heart Transplantation Research Articles

Elevated Donor-Derived Cell-Free DNA Levels Are Associated With Reduced Myocardial Blood Flow but Not Angiographic Cardiac Allograft Vasculopathy: The EVIDENT Study.

Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA. A retrospective review was conducted on HT recipients at a high-volume center who underwent dd-cfDNA testing between September 2019 and November 2022. Inclusion criteria included undergoing CAV screening with cardiac positron emission tomography scans and coronary angiograms. Patients were grouped by the presence of angiographic CAV diagnosis and MBF reserve evaluated through cardiac positron emission tomography. The latter was subdivided into normal MBF or RMBF, with RMBF defined as an MBF reserve ≤2. Elevated dd-cfDNA was defined as ≥0.12%. Two hundred fifty-six HT recipients were included (median age, 55 years; 27.6% female; median, 8 years [interquartile range (IQR), 5-14] post-HT). Ischemic etiology of heart failure was more prevalent in the RMBF group (36%) compared with the normal MBF group (20%; P=0.02). The prevalence and magnitude of a positive dd-cfDNA test with angiographic CAV (29%; median, 0.26% [IQR, 0.15%-0.62%]) were not significantly different from those without CAV (30%; P=0.94; median, 0.31% [IQR, 0.17%-0.71%]; P=0.38). However, RMBF patients exhibited significantly higher dd-cfDNA prevalence and levels (51%; median, 0.81% [IQR, 0.48%-1.11%]) compared with normal MBF patients (27%; P<0.001; median, 0.25% [IQR, 0.15%-0.52%]; P<0.001). HT recipients with angiographic CAV had similar dd-cfDNA levels and rates as those without. Notably, dd-cfDNA levels and rates were significantly elevated in patients with RMBF assessed by positron emission tomography compared with those with normal MBF.

Patch Testing in Solid Organ Transplant Recipients: Experience From a Tertiary Medical Center Over 13 Years (2010-2022).

Background: It is generally recommended that patients not be on immunosuppressive medications for patch testing, as these medications may suppress delayed-type hypersensitivity and lead to false negative results. There is a paucity of literature describing organ transplant recipients who underwent patch testing. Objective: The aim of this study is to examine patch testing results in solid organ transplant recipients over a 13-year period at our institution. Methods: We performed a retrospective analysis of patch test data from adult transplant recipients at our institution. Transplant patients who underwent patch testing were identified from a clinical patch test database, and a chart review was conducted. Results: Eighteen patients were included in the study. Patients had received kidney, liver, or heart transplants. Seven patients (38.9%) had at least one positive reaction. The highest reaction rates were seen with methylisothiazolinone (12.5%), methyldibromo glutaronitrile (12.5%), and benzalkonium chloride (10.0%). Limitations included small sample size, data from a tertiary referral center, and retrospective analysis. Conclusions: Liver and kidney transplant recipients displayed allergic reactions during patch testing. Patients may benefit from patch testing even if receiving immunosuppressive therapy, but some reactions may be falsely negative because of immunosuppression.

Clinical Management and Transplant Considerations in Pediatric Pulmonary Hypertension Due to Left Heart Disease: A Scientific Statement From the American Heart Association.

Children with left heart disease are at risk for developing pulmonary hypertension, initially secondary to pulmonary venous hypertension that can progress to include elevated pulmonary vascular resistance, known as combined pre- and postcapillary pulmonary hypertension. Elevated pulmonary vascular resistance may pose a risk to the right ventricle of a newly transplanted heart because of increased afterload and is an important consideration for heart transplant eligibility. However, the epidemiology, pathophysiology, optimal diagnostic and treatment approaches, and thresholds for pulmonary vascular resistance in pulmonary hypertension associated with left heart disease remain unclear because of lack of evidence, particularly in pediatrics. The result is heterogeneity with respect to hemodynamic assessment, use of pulmonary vasodilator therapies, and heart transplant listing. This scientific statement aims to synthesize the available data and highlight areas of general consensus as well as important knowledge gaps.

Gut Microbial Dysbiosis and Implications in Solid Organ Transplantation

The gut microbiome has been shown to play a significant role in solid organ transplantation, potentially influencing graft function and patient outcomes. Dysbiosis, characterized by reduced microbial diversity and an increase in pathogenic taxa, has been linked to higher incidences of allograft rejection, graft dysfunction, and post-transplant mortality. Several studies suggest that the gut microbiome might be able to serve as both a biomarker and a therapeutic target, potentially guiding personalized immunosuppressive therapies and other interventions to improve outcomes after solid organ transplantation. As summarized in this review, clinical studies have shown that specific microbial shifts correlate with adverse outcomes, including acute rejection and chronic allograft dysfunction. As research surrounding the relationship between the gut microbiome and solid organ transplant progresses, the integration of microbial analysis into clinical practice has the potential to revolutionize post-transplant care, offering new avenues to improve graft survival and patient quality of life. This review aims to provide a comprehensive overview of the relationship between gut microbial dysbiosis and transplantation outcomes, emphasizing the impact on kidney, liver, lung, and heart transplant recipients.

Insights From a 20-Year Follow-Up of the First Heart Transplant Recipient to Complete an Ironman Triathlon.

Insights From a 20-Year Follow-Up of the First Heart Transplant Recipient to Complete an Ironman Triathlon.

Early Pacemaker Dependency After Heart Transplantation Is Associated with Permanent Pacemaker Implantation, Graft Failure and Mortality

Aims: Patients after heart transplantation (HTX) often experience post-transplant bradycardia, but little is known about the outcomes of early pacemaker dependency after HTX. We compared post-transplant mortality, graft failure, and the requirement for the permanent pacemaker implantation of patients with and without early pacemaker dependency after HTX. Methods: We screened all adult patients for early pacemaker dependency after HTX (defined as immediately after surgery) who underwent HTX at Heidelberg Heart Center between 1989 and 2022. Patients were stratified by diagnosis and type of early pacemaker dependency after HTX (sinoatrial or atrioventricular conduction disturbance). Results: A total of 127 of 699 HTX recipients (18.2%) had early pacemaker dependency after HTX, including 52 patients with sinoatrial conduction disturbances (40.9%) and 75 patients with atrioventricular conduction disturbances (59.1%). Patients with early pacemaker dependency after HTX showed both increased 1-year overall mortality after HTX (55.9% vs. 15.2%, p &lt; 0.001) and higher mortality due to graft failure (25.2% vs. 4.2%, p &lt; 0.001). Multivariate analysis revealed early pacemaker dependency after HTX (HR: 5.226, 95% CI: 3.738–7.304, p &lt; 0.001) as an independent risk factor for 1-year mortality after HTX. Patients with early pacemaker dependency after HTX had a higher rate of 30-day (7.1% vs. 0.4%, p &lt; 0.001) and 1-year (11.8% vs. 0.5%, p &lt; 0.001) permanent pacemaker implantation after HTX compared to patients without early pacemaker dependency after HTX. Conclusions: Patients with early pacemaker dependency after HTX had a significantly higher rate of post-transplant mortality, graft failure, and the requirement for permanent pacemaker implantation.

MELD score predicts outcomes in patients with advanced heart failure: A longitudinal evaluation.

Advanced heart failure (AHF) is characterized by recurrent episodes of haemodynamic instability and frequent hospitalizations, leading to a progressive decline in quality of life and high mortality rates. The objectives of this study were to evaluate the effect of the model for end-stage liver disease (MELD) score and its variations in predicting adverse outcomes [death, urgent heart transplant, and left ventricular assist device (LVAD) implant] among patients with AHF to assess the clinical associations of the MELD score in this population and to compare the efficacy of this tool with other prognostic scores in AHF. In this longitudinal prospective study, 162 patients with advanced heart failure (AHF) were enrolled; all patients included in the study were receiving the maximum tolerated medical therapy according to guidelines. The MELD score was measured at baseline and every 6months during follow-up. All patients underwent echocardiographic assessment and cardiopulmonary testing, which included the evaluation of maximal oxygen uptake (VO2max) and the minute ventilation/carbon dioxide production (VE/VCO2) slope. The mean age of the study group was 57.7±11.6years. There were 26 deaths, 5 urgent transplants, and 1 LVAD implantation during a follow-up period of 31.4±15.6months. The mean New York Heart Association (NYHA) class was 2.8±0.5, ejection fraction (EF) was 26.3±6.5%, the mean VO2max was 11.7±3.5mL/kg/min. Multiple regression analysis revealed a positive correlation between the MELD score and NT-proBNP (β=0.215; P=0.041) and furosemide dosage (β=0.187; P=0.040). Conversely, a negative correlation was observed between the MELD score and TAPSE (β=-0.204; P=0.047). Multivariate Cox regression on combined outcome shows a HR of 1.094 (95% CI 1.003-1.196) for unit increase in MELD considered as a continuous variable. The predictive role is independent by the effect of covariates considered in the analysis such as age, sex, NYHA class, EF, TAPSE, PASP, VO2max, NT-proBNP, MELD score worsening, and NT-proBNP increase. Changes in MELD score percentage, considered as a dichotomous variable (≤100% and >100%), were found to be predictors of mortality, urgent heart transplant and LVAD implant. Receiver operating characteristic (ROC) curves showed an area under the curve (AUC) of 0.887 for MELD score and composite outcome of death, urgent transplant, and need for LVAD. The predictive performance of MELD was even superior compared with MELD-Na, MELD-XI, MAGGIC risk score, and MECKI. The MELD score and its longitudinal changes are effective predictors of adverse outcomes in AHF.

Speckle-tracking echocardiography of left and right ventricle and acute cellular rejection in orthotropic heart transplantation: a systematic review and meta-analysis.

After a cardiac transplantation, the steering of immunosuppression requires an active search for acute cellular rejection (ACR). Surveillance with endomyocardial biopsy (EMB) is the gold standard. Given the costs and potential complications, there is growing interest in the use of non-invasive screening methods. Thus, we have conducted a systematic review and meta-analysis to evaluate the role of speckle-tracking echocardiography as a screening method for ACR. We searched PubMed (CENTRAL) and gray literature for studies presenting data on speckle tracking echocardiography in heart-transplant patients experiencing acute cellular rejection. The primary outcomes of the meta-analysis were left and right ventricular global longitudinal strain. We used random effects models for all our calculations. We pre-registered our meta-analysis with PROSPERO (CRD42024508654). By incorporating data from over 2000 biopsies included in 18 studies, we found that both left (LVGLS, MD -1.96, 95% CI -2.85 to -1.07, p < 0.0001), and right (RVGLS, MD -2.90, 95% CI -4.03 to -1.76, p < 0.00001) ventricular longitudinal strain were lower among patients without ACR. The change of LVGLS from baseline over time was also greater among patients experiencing ACR (MD -2.43, 95% CI -4.82 to -0.05, p = 0.045). Current data suggest that myocardial strain measured by speckle tracking echocardiography is affected in ACR and could potentially be used for early rejection detection as a rule-out strategy, leading to reduction of routine EMB in heart transplant follow-up.

Bridge to Heart Transplant With Temporary Mechanical Circulatory Support: Trends and Outcomes in the 2018 Allocation Policy Era.

The United Network for Organ Sharing (UNOS) 2018 heart allocation policy prioritizes patients receiving temporary mechanical circulatory support (tMCS) given the high waitlist mortality rate of this group. This study evaluates national trends and waitlist outcomes for patients receiving tMCS under the UNOS 2018 allocation policy. Adult patients waitlisted for isolated heart transplantation were included using the UNOS database. The prevalence of tMCS, 90 day waitlist mortality, 90 day incidence of transplantation, and posttransplant 1 year mortality were analyzed. A total of 27,343 patients were waitlisted during the study period (pre-policy change: 13,004 vs. post-policy change: 14,339). The prevalence of tMCS increased from 7.4% (n: 956) to 22.4% (n: 3,186) after the policy change (p < 0.001). The use of Impella increased proportionally among tMCS modalities. Patients on tMCS had lower adjusted odds of waitlist mortality (p < 0.001), higher adjusted incidence of transplantation (p < 0.001), and similar posttransplant mortality (p = 0.10) under the 2018 policy. Patients on extracorporeal membrane oxygenation (ECMO) support had the highest odds of 90 day waitlist mortality (p < 0.05) but also the highest incidence of transplantation in the post-policy change cohort (p < 0.05). In conclusion, the use of tMCS as bridge to heart transplantation increased threefolds and is associated with lower waitlist mortality and higher incidence of transplantation following the UNOS 2018 allocation policy change.

What Genetic Modifications of Source Pigs Are Essential and Sufficient for Cell, Tissue, and Organ Xenotransplantation?

Xenotransplantation of porcine organs has made remarkable progress towards clinical application. A key factor has been the generation of genetically multi-modified source pigs for xenotransplants, protected against immune rejection and coagulation dysregulation. While efficient gene editing tools and multi-cistronic expression cassettes facilitate sophisticated and complex genetic modifications with multiple gene knockouts and protective transgenes, an increasing number of independently segregating genetic units complicates the breeding of the source pigs. Therefore, an optimal combination of essential genetic modifications may be preferable to extensive editing of the source pigs. Here, we discuss the prioritization of genetic modifications to achieve long-term survival and function of xenotransplants and summarise the genotypes that have been most successful for xenogeneic heart, kidney, and islet transplantation. Specific emphasis is given to the choice of the breed/genetic background of the source pigs. Moreover, multimodal deep phenotyping of porcine organs after xenotransplantation into human decedents will be discussed as a strategy for selecting essential genetic modifications of the source pigs. In addition to germ-line gene editing, some of these modifications may also be induced during organ preservation/perfusion, as demonstrated recently by the successful knockdown of swine leukocyte antigens in porcine lungs during ex vivo perfusion.

Atypical presentation of Andersen-Tawil syndrome: heart failure with reduced ejection without periodic paralysis or dysmorphic features

Background: Andersen-Tawil syndrome (ATS) is a rare autosomal dominant disorder caused by variants in the KCNJ2 gene. It is associated with periodic paralysis, dysmorphic features and cardiac arrhythmias. The syndrome exhibits incomplete penetrance, leading to a broad spectrum of clinical manifestations, making diagnosis challenging. Case description: A male in his mid-20s with class 3 obesity presented to the emergency department with a week-long history of worsening chest pain, orthopnoea and fatigue. His family history was significant for sudden cardiac death affecting both his mother and brother, with his father having died from complications of Wolff-Parkinson-White syndrome. Cardiovascular examination revealed an S3 heart sound and elevated brain natriuretic peptide levels at 875 pg/ml, with undetectable troponins; potassium level on admission was 3.6 mEq/l. An electrocardiogram showed normal sinus rhythm, first-degree heart block, left atrial enlargement, left bundle branch block and a prolonged QTc of 486 ms. A transthoracic echocardiogram demonstrated a 15-20% reduction in ejection fraction with global left ventricular hypokinesis and left atrial enlargement. Ultimately, he was diagnosed with non-ischaemic dilated cardiomyopathy and referred for genetic testing, which revealed a KCNJ2 variant. Shortly after discharge, he experienced a 55-second run of ventricular tachycardia, necessitating the placement of a single-chamber ICD. Currently, the patient remains on guideline-directed medical therapy and is listed for a heart transplant. Conclusions: Dilated cardiomyopathy, although a rare manifestation in ATS, can profoundly increase the risk of fatal arrythmias, necessitating the need for a low threshold of suspicion, to ensure timely diagnosis and management.

Epidemiological and Clinical Characteristics of the Course of COVID-19 Among Vaccinated and Unvaccinated Heart Transplant Recipients in Slovenia

Background: Patients receiving heart transplantation require lifelong immunosuppression and compared to the general population, they have a more than five times higher chance of acquiring COVID-19, and their mortality rates are higher. The aim of the present study was to estimate the epidemiological and clinical characteristics of COVID-19 in heart transplant recipients (HTRs) in Slovenia to estimate the vaccination rate and evaluate possible vaccination-hesitant subgroups. Methods: All SARS-CoV-2-positive HTRs (N = 79) between 1 March 2020 and 31 December 2023 at the Infectious Diseases Department, University Medical Centre Ljubljana, Slovenia, were included retrospectively. Demographic, clinical and vaccination data were extracted from medical documentation and a statistical evaluation was performed. Results: The observed vaccination rate was 63.3%, but among patients who received transplants before the pandemic, it was statistically significantly higher (p = 0.027). Vaccinated HTRs were statistically significantly older (p = 0.004) and had a significantly higher Charlson Comorbidity Index (p = 0.018). Our results indicate no significant differences between vaccinated and unvaccinated HTRs regarding acute respiratory insufficiency (p = 0.135), length of hospital stay (p = 0.106), intensive care unit admission (0.414) and in-hospital mortality (p = 0.317), but we observed statistically more frequently an asymptomatic course in those vaccinated (p = 0.050), and a longer length of stay in vector vaccine recipients (p = 0.011) and in those not re-vaccinated (p = 0.030). There was a significantly higher re-vaccination rate in males (p = 0.005). Conclusions: An asymptomatic course of COVID-19 was more often observed in vaccinated HTRs. Our findings suggest statistically significant differences in COVID-19 vaccine acceptance rates; younger HTRs and those transplanted after the pandemic are more hesitant to vaccinate, while females accept booster doses less frequently.

Proteomics in Acute Heart Transplant Rejection, On Behalf of the GRAfT Investigators.

Proteomic phenotyping can provide insights into rejection pathophysiology, novel biomarkers, and therapeutic targets. Within the prospective, multicenter Genomic Research Alliance for Transplantation study, 181 proteins were evaluated from blood drawn at the time of endomyocardial biopsy; protein fold change, logistic regression, and pathway analyses were conducted, with protein discovery adjusted for a 5% false discovery rate. Among 104 adult heart transplant patients (31% female sex, 53% Black race, median age 52 y), 74 had no rejection, 18 developed acute cellular rejection (ACR), and 12 developed antibody-mediated rejection (AMR). Differential expression was found in 2 proteins during ACR (inflammatory proteins CXCL10 and CD5) and 73 proteins during AMR. The most abundant AMR proteins were the heart failure biomarkers N-terminal pro-B-type natriuretic peptide and suppression of tumorigenicity 2. In univariate logistic regression, odds of identifying ACR on endomyocardial biopsy increased with doubling of CXCL10 (odds ratio [OR] 2.2 [95% confidence interval (CI), 1.3-3.6]) and CD5 (OR 4.7 [95% CI, 1.7-12.9]) concentrations, and odds of AMR increased with doubling of N-terminal pro-B-type natriuretic peptide (OR 13.0 [95% CI, 2.7-62.7) and suppression of tumorigenicity 2 (OR 4.8 [95% CI, 2.1-10.7]) concentrations. After multivariable analysis with clinical covariates, these proteins showed similar odds of ACR or AMR on biopsy. Pathway analysis identified T cell-receptor signaling and cell differentiation as key pathways in ACR and cardiovascular disease and cell turnover in AMR. Proteomic analysis reveals unique biomarkers and biological pathway expression in ACR and AMR. Cardiac injury-associated biomarkers were more pronounced in AMR, whereas inflammatory biomarkers were more pronounced in ACR. Proteomic analysis may provide insights into rejection pathophysiology, detection, and therapy.

Successful Orthotopic Heart Transplantation After the Longest Duration of EXCOR® Pediatric Support in the World

Successful Orthotopic Heart Transplantation After the Longest Duration of EXCOR® Pediatric Support in the World

Dysregulated Treg repair responses lead to chronic rejection after heart transplantation.

Chronic rejection (CR) after organ transplantation is alloimmune injury manifested by graft vascular remodeling and fibrosis that is resistant to immunosuppression. Single-cell RNA-Seq analysis of MHC class II-mismatched (MHCII-mismatched) heart transplants developing chronic rejection identified graft IL-33 as a stimulator of tissue repair pathways in infiltrating macrophages and Tregs. Using IL-33-deficient donor mice, we show that graft fibroblast-derived IL-33 potently induced amphiregulin (Areg) expression by recipient Tregs. The assessment of clinical samples also confirmed increased expression of Areg by intragraft Tregs also during rejection. Areg is an EGF secreted by multiple immune cells to shape immunomodulation and tissue repair. In particular, Areg is proposed to play a major role in Treg-mediated muscle, epithelium, and nerve repair. Assessment of recipient mice with Treg-specific deletion of Areg surprisingly uncovered that Treg secretion of Areg contributed to CR. Specifically, heart transplants from recipients with Areg-deficient Tregs showed less fibrosis, vasculopathy, and vessel-associated fibrotic niches populated by recipient T cells. Mechanistically, we show that Treg-secreted Areg functioned to increase fibroblast proliferation. In total, these studies identify how a dysregulated repair response involving interactions between IL-33+ fibroblasts in the allograft and recipient Tregs contributed to the progression of CR.

Treatment With mTOR Inhibitors as Primary Immunosuppression After Combined Heart and Kidney Transplantation.

Sirolimus (SRL) mitigates cardiac allograft vasculopathy (CAV) progression and confers renal protection after heart transplantation (HT). However, its safety and efficacy in patients undergoing combined heart and kidney transplantation (HKT) are unclear. This study aimed to investigate the impact of conversion from calcineurin inhibitors (CNI) to SRL on CAV progression, renal function, and outcomes in HKT compared to isolated HT. A cohort of 302 patients who underwent either HT only (n=262) or HKT (n=40) was analyzed. CAV progression was assessed by measuring the delta (Δ) annual change in plaque volume (PV) and plaque index (PI) using coronary intravenous ultrasound (IVUS). Clinical adverse outcomes included all-cause death and CAV-associated events. Overall, 217 (72%) patients were converted from CNI to SRL as primary immunosuppression. HT recipients were more likely to be converted to SRL than HKT recipients (74% vs. 55%, P=0.01). HKT was associated with higher ΔPV (P=0.01) and a trend toward higher ΔPI (P=0.06) than HT-only, but this association was attenuated after adjustment to SRL conversion. HKT was associated with similar risk of death (HR 0.98, 95%CI: 0.39-2.5, P=0.97) and CAV-related events (HR 1.6, 95%CI: 0.91-2.8, P=0.10). Conversion to SRL was associated with decreased risk of death and CAV-related events in the overall cohort. This association was not modified by the type of organ transplantation and without a significant effect on estimated glomerular filtration rate or proteinuria. Conversion to sirolimus as a primary immunosuppressant could be effective for either HT-only or HKT recipients.

Emerging role of circulating piRNAs in the diagnosis of heart transplant rejection.

Liquid biopsy offers a potential alternative to decrease or eliminate endomyocardial biopsy (EMB) for diagnosing allograft rejection. piRNAs are novel and promising disease biomarkers for their intrinsic characteristics such as stability in body fluids; however, their role in allograft rejection remains unexplored. A training set based on small RNA sequencing technology was performed to identify piRNAs in endomyocardial tissue (n=8) and serum samples (n=40) from patients following heart transplantation. A validation set of the potential piRNAs identified in the training study was conducted in an independent larger cohort for the detection of acute cellular rejection (ACR, n=105) and antibody-mediated rejection (AMR, n=61). We identified 20292 piRNAs in endomyocardial tissue and 24602 piRNAs in serum samples from patients following heart transplantation. We identified seven piRNAs with a coincident expression profile in both types of samples and potential capacity for the non-invasive detection of cardiac rejection. Validation in a large independent cohort demonstrated that a panel of these piRNAs showed excellent performance for detecting grade ≥2R ACR (AUC=0.819; p<0.0001) and grade 1R ACR (AUC=0.721; p=0.001). Furthermore, our piRNA panel showed a potential discrimination ability of pAMR2 (AUC=0.967; p<0.0001). To the best of knowledge, this study is the first to report the presence of piRNAs in both endomyocardial tissue and serum samples of patients after heart transplant, including their association with allograft rejection events. We propose a novel piRNA panel for the detection of cardiac allograft rejection.

Influence of Donor Transfusion on Heart Transplantation Outcomes: A United Network for Organ Sharing Registry Analysis.

There is a lack of evidence regarding the impact of donor blood transfusion on heart transplant (HT) outcomes. We sought to elucidate the influence of donor transfusion on HT outcomes using the national database. From January 2004 to March 2023, donor transfusion information was available for 40538 recipients for HT in the United Network for Organ Sharing (UNOS) database. We used the UNOS 4-level designation of transfusion (no blood [N = 18575], 1-5 units [N = 14098], 6-10 units [N = 4766], and massive transfusion of > 10 units [N = 3099]). Among this cohort, 53.2% of donors (N = 20220) received a blood transfusion during the same admission. Donors who required blood transfusion commonly had head trauma as a cause of death (no-blood, 22%vs. 1-5 units, 61%, 6-10 units, 88%, massive, 89%, p < 0.001). An increased amount of donor blood transfusion did not affect rates of acute rejection (no-blood, 18%vs. 1-5 units, 19%, 6-10 units, 17%, massive, 19%, p = 0.13). The number of units transfused also did not affect 1-year survival rates. The Cox hazard model showed no effect of massive transfusion on mortality following transplant (no-blood, reference vs. 1-5 units; HR, 1.02 [p = 0.35], 6-10 units; HR, 1.10 [p = 0.01], massive transfusion; HR 1.04 [p = 0.3]). Massive transfusion in donors was not associated with increased recipient mortality. Additionally, the amount of donor blood transfusion did not affect rejection rates following HT. The present study suggests that a history of donor blood transfusion, as well as the amount of transfusion, should not preclude donor heart utilization.

A gift of life, not immortality: Evaluation of a strategy of heart transplant listing in the older patient with advanced heart failure

Patients 65 years of age or older represent the fastest-growing demographic group added to the U.S. heart transplant (HT) list. While post-HT outcomes appear acceptable, immortal time bias is introduced if adverse outcomes that occur while waiting for HT are not considered. Recent durable left ventricular assist device (dLVAD) technological innovations have engendered the question of whether this patient subgroup would achieve equivalent survival from a strategy of primary dLVAD implant as opposed to HT listing. We identified adults ≥65 years of age listed for HT between 2018-2021, excluding persons with dLVAD support and/or multi-organ listing. Among 1176 patients, 2-year survival from HT listing was 78.4 ± 1.2%, similar to the 71% to 75% reported in The Society of Thoracic Surgeons (STS) Intermacs National Database for older adults. Linkage of the Scientific Registry of Transplant Recipients with STS Intermacs would enable comparative effectiveness analyses of surgical heart failure therapeutic strategies in high-risk patient cohorts.

Optimizing Outcomes in Heart Transplantation: The Role of High-Intensity Statin Therapy.

Heart transplantation is a vital procedure for patients with end-stage heart failure, but it faces significant challenges, including graft dysfunction, rejection, and cardiac allograft vasculopathy (CAV), which can compromise long-term graft success. Research suggests that statin therapy may offer significant benefits to heart transplant recipients, such as improved long-term survival and reduced rates of graft rejection and mortality. The aim of this review is to thoroughly examine the recent literature on this topic since 2005. Early use of high-dose statins appears to be particularly effective in preventing vasculopathy and improving outcomes, although a titrated approach may help to reduce side effects. High-dose statins may provide superior cardiovascular benefits, including lower rates of CVD, slower progression of CVD and improved long-term graft survival. Despite potential concerns about adverse effects, evidence suggests that high-intensity statins improve cholesterol levels without increasing serious adverse events after transplantation. The goal of statin therapy in heart transplant recipients is to balance the well-established benefits seen in the general population with the specific needs of this group, with the ultimate goal of improving both longevity and quality of life.