Background:Survival for heart transplant recipients with type 2 diabetes mellitus is reduced; however, the effect of donor diabetes in this cohort is unknown. We examined the impact of donor diabetes status on long-term outcomes among diabetic heart transplant recipients. Methods:The United Network for Organ Sharing database was queried to identify adult diabetic recipients undergoing single-organ heart transplantation between 2005 and 2025. The primary outcome was 10-year all-cause mortality, assessed after propensity score matching on 26 variables in a Cox proportional hazards model. Secondary outcomes included 30-day mortality, dialysis requirement, stroke, permanent pacemaker implantation, and length of stay. Median follow-up time was 7.05 years (95% CI 7.00-7.18). Results:Of 13,091 heart transplant recipients identified, 540 (4%) received a diabetic donor heart and 12,551 (96%) received a non-diabetic donor heart. Recipients in the diabetic donor group were older (60.0 years [IQR 54.0-65.0] vs 59.0 [52.0-64.0], p < 0.001) and had shorter waitlist times (44.5 days [IQR 14.0-185.5] vs 60.0 [17.0-213.0], p = 0.02). Donors with diabetes were older (41.0 years [IQR 34.0-48.0] vs 32.0 [23.0-41.0], p < 0.001), had a higher prevalence of hypertension (55.9% vs 15.2%, p < 0.001), and were more likely to have donor-recipient sex mismatch (26.9% vs 21.5%, p = 0.003). Propensity score matching produced 539 pairs. In the matched cohort, 10-year survival was lower among recipients of diabetic donor hearts compared with non-diabetic donor hearts (48.5% vs 57.0%, adjusted HR: 1.26, 95% CI: 1.00-1.59, p = 0.04). Secondary outcomes were similar between groups. Conclusion:Diabetic heart transplant recipients experience worse long-term survival when a diabetic donor heart is utilized.

Background Controlled hypothermic preservation of donor hearts is associated with decreased post-transplant primary graft dysfunction compared to conventional cold storage. However, mechanisms underlying this benefit in human subjects are unclear. Methods We randomized 20 heart transplant recipients at a single institution to receive donor hearts preserved with either controlled hypothermic preservation or standard cold storage. Right ventricular biopsies were obtained at donor heart recovery, immediately before implantation, and 7 days after transplantation. Protein expression profiles at each time point were evaluated using mass spectrometry, Protein Interaction Network Extractor analysis, and Ingenuity Pathway Analysis. Results Immediately before implantation, controlled hypothermic preservation was associated with increased protein expression related to fatty acid metabolism, mitochondrial intermembrane space, and contractile fiber machinery. Pathway analysis indicated increased cell viability, autophagy, and upregulation of AMP-activated protein kinase pathway with controlled hypothermic preservation. By post-transplant day 7, the protein expression profiles of the 2 groups were similar. However, controlled hypothermic preservation was associated with increased expression in the peroxisome proliferator-activated receptor signaling pathway and fatty acid oxidation. Conclusions Controlled hypothermic preservation of donor hearts shows beneficial time-dependent variability in protein expression that may confer improved organ quality at the time of transplantation.

Background:The aim of the study was to determine the prevalence of rare disease-causing variants in cardiomyopathy-associated genes in a cohort of patients with ischemic and non-ischemic dilated cardiomyopathy undergoing heart transplant. Methods:We conducted a single-center cohort study of 60 adult patients with left ventricular ejection fraction ≤50% and left ventricular end-diastolic dimension ≥95th percentile for sex/height who underwent heart transplant between January 2017 and December 2023 and consented to participate in a cardiac tissue biobank. We evaluated the prevalence of rare (minor allele frequency <0.1%) disease-causing (pathogenic or likely pathogenic by American College of Genetics and Genomics criteria) variants in cardiomyopathy-associated genes. Results:A total of 60 individuals fulfilled the inclusion criteria: 16 with ischemic dilated cardiomyopathy [88% men, median age 65 years, interquartile range (IQR) 64-68 years] and 44 with non-ischemic dilated cardiomyopathy (80% men, median age 53 years, IQR 39-65 years). We found that the prevalence of disease-causing variants was similar between patients with ischemic dilated cardiomyopathy (3/16 or 19%; 95% credible interval 6%-36%) and those with non-ischemic dilated cardiomyopathy (10/44 or 23%; 95% credible interval 12%-33%). Variants in the ischemic dilated cardiomyopathy group were found in the TTN and DMD genes. Variants in the non-ischemic dilated cardiomyopathy group were found in the TTN, FLNC, LMNA, MYH7, and RBM20 genes. Conclusions:Patients with ischemic dilated cardiomyopathy undergoing heart transplant possessed a similar burden of rare disease-causing variants as those with non-ischemic dilated cardiomyopathy. Our results suggest that genetic testing may be beneficial in patients with advanced heart failure requiring heart transplant due to ischemic dilated cardiomyopathy to detect disease-causing variants in cardiomyopathy-associated genes.

Introduction: Despite the increased risk of sensitization in patients receiving pre-transplant durable mechanical circulatory support (D-MCS), it has been suggested that removing D-MCS at the time of transplant may lead to a drop in HLA-antibody levels. Whether this may reduce rejection rates and improve long-term outcomes in patients undergoing heart-kidney transplantation (HKTx) has not been widely investigated. Therefore, we aim to investigate the impact of pre-transplant D-MCS on 5-year clinical outcomes of patients undergoing HKTx. Methods: We included 98 patients undergoing HKTx between 2010 and 2018 at a single center. Recipient pre-transplant characteristics and clinical outcomes were compared between patients receiving D-MCS (n=24) versus non-D-MCS patients (n=74). The D-MCS cohort included those who received total artificial heart (n=13), left ventricular assist device (n=8), and biventricular assist devices (n=3). Endpoints included 1- and 5-year survival, 1-year-freedom from acute cellular rejection (defined as grade 2R or 3R), 1-year-freedom from antibody-mediated rejection (AMR, defined as pathologic AMR of grade ≥1), 5-year freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography), 5-year freedom from non-fatal major adverse cardiac events (NF-MACE including myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), and 5-year freedom from left ventricular dysfunction (LVEF ≤40). Results: At 1 year, freedom for AMR was numerically higher in the D-MCS group (100 vs. 90.2%, P=0.12). Additionally, the 5-year post-transplant survival rate was higher in the D-MCS group (95.8% vs. 80.8%), but it did not reach statistical significance (P=0.091). Comparable outcomes were noted for other outcomes, including 5-year freedom from CAV, NF-MACE, or LVD (Table 1 ). Conclusion: The current study hints at better 5-year survival in HTKx recipients receiving pre-transplant D-MCS, which could be attributed to lower rates of AMR in this population. Future larger studies are warranted to further validate these findings.

Purpose: Sensitization prior to heart transplantation (HTx) is observed in approximately 30% of transplant recipients. Given the scarcity of donor hearts, it may be necessary to cross donor specific antibodies (DSA) at the time of HTx. We assessed the impact of number and strength of DSA at the time of HTx on the development of antibody-mediated rejection (AMR) and graft dysfunction.

BACKGROUND:Primary graft dysfunction (PGD) remains the leading cause of 30-day mortality post-heart transplantation (HTx). HTx recipients experiencing severe PGD have been found to have high levels of circulating proteins associated with PGD occurrence and post-HTx survival. Whether treating these patients with therapeutic plasma exchange (TPE) can attenuate ongoing immunological and inflammatory processes and improve post-transplant outcomes has not been well-investigated. Therefore, we aim to examine the impact of treatment with TPE on 30-day and 1-year clinical outcomes of patients experiencing severe PGD post-HTx. METHODS:Between 2010 and 2022, we included 42 HTx patients who developed severe PGD. All included patients were placed on veno-arterial extracorporeal membrane oxygenation. We divided these patients into those who received TPE and those who did not (by physician choice). Endpoints included 30-day and 1-year survival, as well as 1-year-freedom from Any-treated rejection (ATR), acute cellular rejection (ACR), antibody-mediated rejection (AMR), biopsy negative rejection (BNR), cardiac allograft vasculopathy (CAV), non-fatal major adverse cardiac events (NF-MACE), and freedom from left ventricular dysfunction (LVD) at 1-year post-HTx. RESULTS:Compared to patients who did not receive TPE, those managed with TPE had increased survival rates at 30 days (78.1% vs. 40%, p = 0.007) and at 1-year post-HTx (56.25% vs. 30% p = 0.035). However, no statistically significant differences were recorded in other outcomes of interest, including 1-year freedom from CAV, ATR, ACR, AMR, BNR, NF-MACE, or LVD. CONCLUSION:TPE may serve as a promising therapeutic approach in HTx recipients experiencing severe PGD.

Purpose: Heart failure (HF) is a complex clinical syndrome associated with morbidity and mortality. Identification of independent predictors of risk in HF patients is crucial for guiding proper management strategies. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a validated tool that assesses the quality of life and functional status in HF patients. Therefore, we aimed to assess the KCCQ's Overall Summary Score (KCCQ-OSS) and independent parameters such as demographics, ejection fraction (EF), and other KCCQ-related variables as predictors of outcome in the study population.

Purpose: Heart-kidney (HKTx) transplants are becoming more prevalent. Data from the ISHLT registry supports that combined HKTx have less cardiac rejection than heart transplant alone. It is not known whether this protection is equally observed in both Black and White HKTx patients. We explored 1 year freedom from any-treated rejection (ATR) in HKTx between Black and White patients.

Purpose: While tacrolimus is the cornerstone of contemporary heart transplant immunosuppression, optimal target trough levels have not been established. In the Tacrolimus Alone or Tacrolimus in Combination Compared (TICTAC) Trial, patients randomized to standard of care had tacrolimus targets of 8-10 ng/mL during the first year. In our heart transplant program, the target tacrolimus trough level is between 10-15 ng/ml for the first month, 8-12 ng/ml for months 2-3, and 5-10 ng/ml thereafter. We sought to determine the impact of lower tacrolimus targets.

BACKGROUND:Appropriate anticoagulation is crucial for the success of left ventricular assist device patients. Currently, there is no consensus on the optimal management of their subtherapeutic INR in ambulatory setting. Our goal is to evaluate both the short-term adverse events and long-term outcomes of enoxaparin bridging at a major transplant center, following the implementation of bridging safety criteria. METHODS:In total, 85 patients' medical records were reviewed between 7/2019 and 5/2022, with 51 patients meeting safety criteria were bridged with enoxaparin and 34 non-bridged. The primary endpoint was the occurrence of major bleeding/thrombosis events within 30 days of bridging. The secondary endpoint was freedom from events 30 days after enoxaparin initiation and overall patient survivability until the last follow-up. RESULTS:Within 30 days, no major bleeding/thrombotic events were noted. After 30 days, the major bleeding rate was 5.8% in bridged vs. 11.8% in non-bridged patients (p = 0.02). Overall, 3-year survival was 78% in the bridged vs. 49% in non-bridged patients (p < 0.001). In patients with no events, 3-year survival was 80% in bridged vs. 58% in non-bridged (p < 0.001). In the patients with bleeding events, 3-year survival was 55% in bridged vs. 51% in non-bridged (p = 0.11). At 1 year, freedom from bleeding in the bridged patients was 81% in patients with no events vs. 0% in those with an event (p < 0.0001). CONCLUSION:When eligibility criteria for safe bridging were applied, the use of enoxaparin bridging was associated with no major bleeding/thrombotic events during bridging and improved 3-year survival in LVAD patients. Economically, using outpatient enoxaparin resulted in substantial healthcare savings, fewer readmissions, and improved quality of life.

Introduction: Ischemic dilated cardiomyopathy (IDCM) is defined as DCM caused by severe stenosis of one or more coronary arteries. Patients with non-ischemic dilated cardiomyopathy (NIDCM) have normal coronary arteries and may possess rare disease-causing variants in cardiac proteins such as TTN . However, IDCM and NIDCM share echocardiographic and pathologic features, possibly suggesting a shared etiology. Hypothesis: There is a similar prevalence of pathogenic (P)/likely pathogenic (LP) variants in patients with IDCM compared to patients with NIDCM. Aims: We compared the prevalence of P/LP genetic variants in DCM-associated genes in a cohort of patients with NIDCM or IDCM who received a heart transplant. Methods: We conducted a retrospective cohort study of patients who received a heart transplant between May 2017 and October 2023 at Cedars Sinai Medical Center in Los Angeles, CA. All subjects had LVEF ≤ 50% and LVEDD ≥ 95 th percentile for sex and height. Whole exome sequencing was performed on explanted heart tissue. We assessed for rare variants (minor allele frequency <0.1%) in genes with a definite, strong, or moderate rating in the ClinGen DCM Gene Curation Expert Panel. Variant pathogenicity was interpreted using the American College of Genetics and Genomics criteria for DCM. Ischemic cardiomyopathy was defined by the Felker criteria (Felker et al., JACC 2002). Results: We included 60 subjects: 16 with IDCM and 44 with NIDCM. There was no difference in LVEF or LVEDD between groups (TABLE). 2/16 (12.5%) patients with IDCM carried a P/LP variant, both of which were in TTN . 11/44 (25.0%) patients with NIDCM carried a P/LP variant: 6 in TTN and 1 each in FLNC, ILK, LMNA, MYH7 , and RBM20 . The prevalence of TTN variants in each group was similar (12.5% in IDCM vs. 13.6% in NIDCM) and higher than the expected frequency in the general population (0.2%). There was no significant difference in the prevalence of P/LP variants between the groups (chi-squared p-value 0.493, Bayes factor 0.45). Conclusion: Patients with IDCM exhibited a similar prevalence of P/LP variants to NIDCM patients, which suggests a shared genetic burden. If further studies confirm our findings, genetic testing for individuals with IDCM may be warranted.

Introduction: Post-heart Transplant (HTx) ischemia-reperfusion injury (IRI) is not uncommon and has been associated with an increased risk of rejection and cardiac allograft vasculopathy. IRI may occur due to long ischemia time, high dose inotropes, and technical surgical reasons. Identifying other recipient and donor characteristics that might set patients at higher risk for developing IRI might help inform decision-making and improve patient outcomes. Therefore, we aim to investigate predictors of developing IRI immediately after HTx. Methods: Between 2010 and 2020, we assessed 893 patients undergoing HTx at our center. Recipient and donor characteristics were collected and compared between patients who were noted to have immediate post-HTx (within 30 days) IRI on their endomyocardial biopsy (n=241) vs. those who did not (n=652). Multivariable logistic regression was used to determine predictors of IRI development and included all univariate significant variables with (P<0.1). Outcomes were represented as odds ratios with corresponding 95% confidence intervals. Results: Among 893 patients undergoing HTx, 241 (27%) had IRI within 30 days post-HTx (time to IRI was 14.4 ± 7.3 days). Compared to patients without IRI, those who developed IRI trended towards being older (57 ± 12 vs. 55 ±13 years, P=0.07), were less likely to receive induction therapy with anti-thymocyte globulin (ATG) (43.6 vs. 52.9%, P=0.01), and less likely to be listed with an urgent status at the time of HTx (62.7% vs. 71.9%, P=0.008). Patients listed with an urgent status were on optimal hemodynamic support. No other significant differences were recorded in other pre-transplant or peri-operative recipient characteristics among patients who developed IRI vs. those who did not. In regard to donor characteristics, those who developed IRI received hearts from older donors (37 ± 13.5 vs. 34.9 ± 12.2, P=0.03) and showed a trend toward a higher likelihood of donor-recipient sex mismatch (29.9% vs. 23.6%, P=0.059), regardless of recipient sex. On multivariable logistic regression, only ATG-induction [OR:0.69, 95%CI [0.51-0.93], P=0.015) therapy and urgent status at transplantation [OR:07, 95%CI [0.51-0.96], P=0.028) were significant predictors of IRI development Conclusion: Optimal prioritization of HTx candidates on the waitlist and use of ATG induction therapy seem to protect against immediate IRI post-HTx.

Purpose: Approximately 10% of heart transplant (HTx) recipients develop cancer within 1-5 years after HTx, and malignancy remain an impediment to long-term survival. We examined the prevalence and factors contributing to malignancies within the first-year after heart transplantation in at a large HTx program.

Introduction: Post-heart Transplant (HTx) ischemia-reperfusion injury (IRI) is associated with an increased risk of rejection and cardiac allograft vasculopathy (CAV). It has been suggested that induction therapy with anti-thymocyte globulin (ATG) may protect against immediate (in the first 30 days) IRI post-HTx. Additionally, ATG has been associated with reduced first-year coronary plaque progression as assessed by intravascular ultrasound (IVUS) among HTx recipients. Whether ATG can decrease first-year intimal thickening in patients experiencing IRI has not been investigated. Therefore, we aim to examine the clinical outcomes of patients who received ATG induction therapy and experienced immediate IRI post-HTx. Methods: Between 2010 and 2020, we assessed 241 patients undergoing HTx and were noted to have immediate post-HTx IRI on their endomyocardial biopsy. Patients were divided into those who received ATG (n=105) induction therapy vs. non-receivers (n=136). In our program, ATG is given to sensitized patients or those with baseline serum creatinine >2.0 mg/dL to delay the initiation of tacrolimus, which may introduce bias to this study. Endpoints included 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR, grade 2R or 3R), and antibody-mediated rejection (AMR, pAMR grade ≥1, 3-year survival, and 3-year freedom from non-fatal major adverse cardiac events (NF-MACE, including myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, and stroke). IVUS was performed at 4-8 weeks (baseline) and at 1 year post-HTx. Studied IVUS parameters included first-year average change in maximum initial thickness (MIT) and change in MIT ≥0.5mm. Results: Among patients with immediate post-HTx IRI, patients who received ATG induction therapy (57% were sensitized pre-HTx) remained at high immunological risk at 1 year with significantly lower freedom from ATR and AMR but had similar 3-year survival as compared to those who did not receive ATG (Table 1). No between-group differences were observed in the average 1-year change in MIT or the percentage of patients with ≥0.5mm change in MIT. Conclusion: Induction therapy with ATG did not appear to decrease first-year intimal thickening in patients experiencing IRI immediately post-HTx. Future studies are warranted to mitigate immunological complications and reduce coronary plaque progression in high-risk HTx patients.

Background Outcome differences of young versus old age recipients according to the pre-heart transplantation body mass index (BMI) have not well been investigated. Methods Between Sep 1990 and June 2022, patients over 18 years old who underwent heart transplantation with available pre-transplant BMI data retrospectively enrolled in this study. Patients were grouped in older (≥ 60 years old) and younger age (< 60 years old) at the time of the transplantation. Patients were further divided into underweight (BMI <18.5 kg/m2), normal weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obesity (30 ≤ BMI kg/m2). A composite of all cause death or retransplantation were evaluated for the clinical outcome. Results A total of 1,995 patients were analyzed. There were 1,113 patients (55.8%) in the younger age group and 882 patients (44.2%) in the older age group. In the younger age group, there were 68 (6.1%) underweight, 476 (42.8%) normal weight, 358 (32.2%) overweight, and 211 (19.0%) obesity patients. In the older age group, there were 26 (2.9%) underweight, 455 (51.6%) normal weight, 296 (33.6%) overweight, and 105 (11.9%) obesity patients. In the younger age group, there was a stepwise increase of the risk of death or retransplantation as the BMI increased (26.5%, 33.2%, 38.8%, 44.5% respectively). In the older age group, there was no significant difference in outcome between BMI groups (46.2%, 44.8%, 44.3%, 47.6%, respectively). During the median follow-up of 2,181 days (interquartile range 799, 3796), Kaplan-Meier survival curve revealed significantly lower survival according to the increase of BMI (Breslow = 0.028), but no significant differences between groups with lower tendency of survival in in obesity patients followed by underweight patients (Breslow = 0.051). In multivariate analysis, high BMI was the independent predictor for death or retransplantation (p=0.005). Conclusions Younger patients tend to proceed heart transplantation more with suboptimal BMI status compared to the older patients. The outcome differences according to BMI were more prominent in younger age group. More aggressive treatment for the weight reduction such as sleeve gastrectomy need to be more focused on younger candidates who are waiting for heart transplantation.

Purpose: Diabetes is a well-known risk factor for the development of atherosclerosis in non-transplant patients. However, the outcomes of donor hearts from diabetics is not clear. Therefore, we assessed the impact of donor diabetes on post-HTx outcomes.

Purpose: The CAV trajectory score provides 4 trajectories to the development of CAV with increasing probabilities of developing CAV in the subsequent 10 years. In our program, those with a low-risk trajectory have angiograms at 5-year instead of 1-year intervals. The purpose of this study was to assess the real-world application of this CAV trajectory score to minimize frequency of surveillance angiograms.

Purpose: Most heart transplant programs do not cross donor-specific antibodies (DSA) at the time of transplant due to risk of hyperacute rejection or delayed hyperacute rejection as well as increased risk of antibody-mediated rejection (AMR) in the first year after heart transplant. Other programs have been crossing DSA if they are at low level (less than 5000 MFI). Post-transplant therapy such as anti-thymocyte globulin and intravenous immune globulin have been reported to be helpful to prevent AMR.

Purpose: The development of de novo donor specific antibody (DSA) after heart transplant has been reported to be associated with lower survival, development of cardiac allograft vasculopathy and graft dysfunction. More specifically, those patients with DSA that have the ability to bind complement (C1q+), are reported to have even worse outcome after heart transplant. It is not known whether the treatment of asymptomatic DSA C1q+ is efficacious. In our program, asymptomatic DSA C1q+ have been treated with combinations of IVIG and rituximab per physicians' choice.