Coronary Allograft Vasculopathy Research Articles

MULTIDRUG RESISTANT DYSLIPIDEMIA: A CASE REPORT

Abstract Introduction Recently introduced lipid–lowering agents (PCSK9–i, bempedoic acid) can efficiently treat statin–intolerant patients, who couldn‘t reach LDL target before. Nonetheless, there are still cases where the pharmacological management may have strong limitations. Case Report A 71 year–old woman, with multiple cardiovascular risk factors (diabetes, hypertension and familial dylipidemia, LDL–C 276) underwent heart transplantation for a hypertrophic cardiomyopathy with an evolution towards a dilated phenotype in 2005. Before the transplant, she was on low–dose statin treatment (pravastatin 10 mg/die) that was suspended years later owing to hyper–CKemia (600 U/L), despite her being totally asymptomatic. A second attempt with simvastatin/ezetimibe 40/10 mg resulted again in elevation of CK levels, associated with significant muscular pain. Thus, just ezetimibe was continued. In 2020, 15 years after the transplant, the patient underwent a coronary angiography showing a moderate coronary allograft vasculopathy (ISHLT CAV2). Specifically, a sub occlusive ostial left main coronary artery lesion was treated by percutaneous angioplasty and stent implantation. Since a lower LDL target was needed (LDL–C 55 mg/dL), Alirocumab was introduced. However, 6 months later, no significant LDL levels reduction had been observed. The shift to evolocumab led to the same result, although the patient reported full therapeutic compliance. In the suspicion of anti–drug antibodies development, we opted for Inclisiran without achieving a significant decrease in LDL–C levels. In parallel with the search for genetic mutations in the PCSK9 gene and other genes involved in cholesterol metabolism (including LDLR, APOB, and LDLRAP1 and resulting positive only for common variants in LDLR receptor), therapy with bempedoic acid was initiated, again without substantial benefit (LDL–C 118 mg/dL). Conclusion Despite cholesterol management has been simplified by the introduction of new drugs, it may still be complex in patients requiring very low LDL–C levels in some specific cases. Drugs with a LDL receptor–independent mechanism of action (e.g., evinacumab) may allow the achievement of therapeutic goals suggested by clinical guidelines.

MULTIDRUG RESISTANT DYSLIPIDEMIA: A CASE REPORT

Objective: Recently introduced lipid-lowering agents (PCSK9-i, bempedoic acid) can efficiently treat statin-intolerant patients, who couldn’t reach LDL target before. Nonetheless, there are still cases where the pharmacological management may have strong limitations. Design and method: A 71 year-old woman, with multiple cardiovascular risk factors (diabetes, hypertension and familial dylipidemia, LDL-C 276) underwent heart transplantation for a hypertrophic cardiomyopathy with an evolution towards a dilated phenotype in 2005. Before the transplant, she was on low-dose statin treatment (pravastatin 10 mg/die) that was suspended years later owing to hyper-CKemia (600 U/L), despite her being totally asymptomatic. A second attempt with simvastatin/ezetimibe 40/10 mg resulted again in elevation of CK levels, associated with significant muscular pain. Thus, just ezetimibe was continued. In 2020, 15 years after the transplant, the patient underwent a coronary angiography showing a moderate coronary allograft vasculopathy (ISHLT CAV2). Specifically, a sub occlusive ostial left main coronary artery lesion was treated by percutaneous angioplasty and stent implantation. Since a lower LDL target was needed (LDL-C 55 mg/dL), Results: Alirocumab was introduced. However, 6 months later, no significant LDL levels reduction had been observed. The shift to evolocumab led to the same result, although the patient reported full therapeutic compliance. In the suspicion of anti-drug antibodies development, we opted for Inclisiran without achieving a significant decrease in LDL-C levels. In parallel with the search for genetic mutations in the PCSK9 gene and other genes involved in cholesterol metabolism (including LDLR, APOB, and LDLRAP1 and resulting positive only for common variants in LDLR receptor), therapy with bempedoic acid was initiated, again without substantial benefit (LDL-C 118 mg/dL). Conclusions: Despite cholesterol management has been simplified by the introduction of new drugs, it may still be complex in patients requiring very low LDL-C levels in some specific cases. Drugs with a LDL receptor-independent mechanism of action (e.g., evinacumab) may allow the achievement of therapeutic goals suggested by clinical guidelines.

Donor-derived cell-free DNA, gene expression profile, and acute rejection in donation after circulatory death (DCD) heart transplant recipients

BackgroundAcute rejection (AR) is a leading cause of early morbidity and mortality in heart transplant (HTx) recipients. There is limited data in donor after circulatory death (DCD) HTx recipients where ischemia reperfusion injury may contribute to development of AR and may be detected early with non-invasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA) and gene expression profile (GEP). The goal of this study is to compare dd-cfDNA, GEP and rejection outcomes in DCD and donor after brain death (DBD) HTx recipients. MethodsThis single-center, retrospective study included DCD and DBD HTx recipients from January 2020 to September 2022. Patients were excluded from the study if dd-cfDNA and GEP were not available. The CareDx HeartCare platform was used to obtain dd-cfDNA (AlloSure-Heart) and GEP (AlloMap) with the highest values for each patient recorded at 6 and 12 months. The mean values for these non-invasive markers were compared between DCD and DBD groups. Patients were followed for clinical outcomes, including treated AR, coronary allograft vasculopathy (CAV) and death, through September 2023. ResultsA total of 156 HTx patients were included with 50 DCD and 106 DBD recipients. Baseline characteristics were similar between DCD and DBD recipients including mean age (58.5 years vs 56.9 years, p = 0.48), male sex (82% vs 76%, p = 0.56) and Caucasian race (46% vs 43%, p = 0.78). There were no significant differences in mean AlloSure-Heart at 6 and 12 months between DCD and DBD recipients. AlloMap was significantly lower at 6 months (p = 0.04), but not at 12 months between DCD and DBD recipients. With respect to clinical outcomes at 1 year, there were no significant differences in treated AR (22% vs 14%, p = 0.32), ISHLT grade ≥ 2 CAV (0 vs 4%, p = 0.44) or mortality (2% vs 0%, p = 0.69) between DCD and DBD recipients. ConclusionsIn this single center study, there were no significant differences in mean dd-cfDNA and treated AR at 1 year between DCD and DBD HTx recipients. There was a significant increase in mean GEP at 6 months, but not at 12 months in the DBD cohort. Overall, there does not appear to be clinically significant cardiac allograft injury related to DCD as measured by non-invasive markers. Further work is needed to confirm these findings.

A discrete approximation method for modeling interval-censored multistate data.

Many longitudinal studies are designed to monitor participants for major events related to the progression of diseases. Data arising from such longitudinal studies are usually subject to interval censoring since the events are only known to occur between two monitoring visits. In this work, we propose a new method to handle interval-censored multistate data within a proportional hazards model framework where the hazard rate of events is modeled by a nonparametric function of time and the covariates affect the hazard rate proportionally. The main idea of this method is to simplify the likelihood functions of a discrete-time multistate model through an approximation and the application of data augmentation techniques, where the assumed presence of censored information facilitates a simpler parameterization. Then the expectation-maximization algorithm is used to estimate the parameters in the model. The performance of the proposed method is evaluated by numerical studies. Finally, the method is employed to analyze a dataset on tracking the advancement of coronary allograft vasculopathy following heart transplantation.

(506) - Thymectomy Duration in Congenital Heart Disease Patients Correlates with Early Coronary Allograft Vasculopathy Development in Pediatric Heart Transplant

(506) - Thymectomy Duration in Congenital Heart Disease Patients Correlates with Early Coronary Allograft Vasculopathy Development in Pediatric Heart Transplant

CT pericoronary adipose tissue density predicts coronary allograft vasculopathy and adverse clinical outcomes after cardiac transplantation.

To assess pericoronary adipose tissue (PCAT) density on Coronary Computed Tomography Angiography (CCTA) as a marker of inflammatory disease activity in coronary allograft vasculopathy (CAV). PCAT density, lesion volumes, and total vessel volume-to-myocardial mass ratio (V/M) were retrospectively measured in 126 CCTAs from 94 heart transplant patients (mean age 49 [SD 14.5] years, 40% female) who underwent imaging between 2010 to 2021; age and sex-matched controls; and patients with atherosclerosis. PCAT density was higher in transplant patients with CAV (n = 40; -73.0 HU [SD 9.3]) than without CAV (n = 86; -77.9 HU [SD 8.2]), and controls (n = 12; -86.2 HU [SD 5.4]), p < 0.01 for both. Unlike patients with atherosclerotic coronary artery disease (n = 32), CAV lesions were predominantly non-calcified, comprised of mostly fibrous or fibrofatty tissue. V/M was lower in patients with CAV than without (32.4 mm3/g [SD 9.7] vs. 41.4 mm3/g [SD 12.3], p < 0.0001). PCAT density and V/M improved the ability to predict CAV from AUC 0.75 to 0.85 when added to donor age and donor hypertension status (p < 0.0001). PCAT density above -66 HU was associated with a greater incidence of all-cause mortality (OR 18.0 [95%CI 3.25-99.6], p < 0.01) and the composite endpoint of death, CAV progression, acute rejection, and coronary revascularization (OR 7.47 [95%CI 1.8-31.6], p = 0.01) over 5.3 (SD 2.1) years. Heart transplant patients with CAV have higher PCAT density and lower V/M than those without. Increased PCAT density is associated with adverse clinical outcomes. These CCTA metrics could be useful for diagnosis and monitoring of CAV severity.

Metabolic Syndrome and Heart Transplantation: An Underestimated Risk Factor?

Metabolic Syndrome (MetS), a multifactorial condition that increases the risk of cardio-vascular events, is frequent in Heart-transplant (HTx) candidates and worsens with immunosuppressive therapy. The aim of the study was to analyze the impact of MetS on long-term outcome of HTx patients. Since 2007, 349 HTx patients were enrolled. MetS was diagnosed if patients met revised NCEP-ATP III criteria before HTx, at 1, 5 and 10years of follow-up. MetS was present in 35% of patients pre-HTx and 47% at 1year follow-up. Five-year survival in patients with both pre-HTx (65% vs. 78%, p < 0.01) and 1year follow-up MetS (78% vs 89%, p < 0.01) was worst. At the univariate analysis, risk factors for mortality were pre-HTx MetS (HR 1.86, p < 0.01), hypertension (HR 2.46, p < 0.01), hypertriglyceridemia (HR 1.50, p=0.03), chronic renal failure (HR 2.95, p < 0.01), MetS and diabetes at 1year follow-up (HR 2.00, p < 0.01; HR 2.02, p < 0.01, respectively). MetS at 1year follow-up determined a higher risk to develop Coronary allograft vasculopathy at 5 and 10year follow-up (25% vs 14% and 44% vs 25%, p < 0.01). MetS is an important risk factor for both mortality and morbidity post-HTx, suggesting the need for a strict monitoring of metabolic disorders with a careful nutritional follow-up in HTx patients.

HTK vs. HTK-N for Coronary Endothelial Protection during Hypothermic, Oxygenated Perfusion of Hearts Donated after Circulatory Death.

Protection of the coronary arteries during donor heart maintenance is pivotal to improve results and prevent the development of coronary allograft vasculopathy. The effect of hypothermic, oxygenated perfusion (HOP) with the traditional HTK and the novel HTK-N solution on the coronary microvasculature of donation-after-circulatory-death (DCD) hearts is known. However, the effect on the coronary macrovasculature is unknown. Thus, we maintained porcine DCD hearts by HOP with HTK or HTK-N for 4 h, followed by transplantation-equivalent reperfusion with blood for 2 h. Then, we removed the left anterior descending coronary artery (LAD) and compared the endothelial-dependent and -independent vasomotor function of both groups using bradykinin and sodium-nitroprusside (SNP). We also determined the transcriptome of LAD samples using microarrays. The endothelial-dependent relaxation was significantly better after HOP with HTK-N. The endothelial-independent relaxation was comparable between both groups. In total, 257 genes were expressed higher, and 668 genes were expressed lower in the HTK-N group. Upregulated genes/pathways were involved in endothelial and vascular smooth muscle cell preservation and heart development. Downregulated genes were related to ischemia/reperfusion injury, oxidative stress, mitochondrion organization, and immune reaction. The novel HTK-N solution preserves the endothelial function of DCD heart coronary arteries more effectively than traditional HTK.

Screening of cardiac allograft vasculopathy in heart transplant patients with coronary computed tomography angiography.

Although coronary angiography (CA) is the gold standard for coronary allograft vasculopathy (CAV) screening, non-invasive modalities have arisen as potential alternatives, such as coronary computed tomography angiography (CCTA). CCTA also quantifies plaque burden, which may influence medical treatment. From January 2021 to April 2022, we prospectively included heart transplant recipients who performed CCTA as a first-line method for CAV detection in a single center. Clinical, CCTA, and CA data were collected. 38 patients were included, 60.5% men, aged 58±14 years. The most frequent cause of transplantation was dilated cardiomyopathy (42.1%), and the median graft duration was 10 years [interquartile range (IQR) 9]. The median left ventricle ejection fraction was 61.5% (IQR 6). The median calcium score was 17 (IQR 231) and 32 patients (84.2%) proceeded to CCTA: 7, 24, and 1 patients had a graded CAV of 0, 1, and 2, respectively. Most patients (37.5%) had both calcified and non-calcified plaques, and the median number of affected segments was 2 (IQR 3). The remaining six patients had extensive coronary calcification, so CA was performed: 4 had CAV1, 1 had CAV2, and 1 had CAV3. During follow-up (12.2±4.2 months), there were neither deaths nor acute coronary syndromes. After CCTA, therapeutic changes occurred in about 10 (26.3%) of patients, mainly related to anti-lipid intensification; such changes were more frequent in patients with diabetes after heart transplant. In this cohort, CCTA led to therapeutic changes in about one-quarter of patients; more studies are needed to assess how CCT may guide therapy according to plaque burden.

Impacts of Pre-transplant Panel-Reactive Antibody on Post-transplantation Outcomes: A Study of Nationwide Heart Transplant Registry Data.

The number of sensitized heart failure patients on waiting lists for heart transplantation (HTx) is increasing. Using the Korean Organ Transplantation Registry (KOTRY), a nationwide multicenter database, we investigated the prevalence and clinical impact of calculated panel-reactive antibody (cPRA) in patients undergoing HTx. We retrospectively reviewed 813 patients who underwent HTx between 2014 and 2021. Patients were grouped according to peak PRA level as group A: patients with cPRA ≤10% (n= 492); group B: patients with cPRA >10%, <50% (n=160); group C patients with cPRA ≥50% (n=161). Post-HTx outcomes were freedom from antibody-mediated rejection (AMR), acute cellular rejection, coronary allograft vasculopathy, and all-cause mortality. The median follow-up duration was 44 (19-72) months. Female sex, re-transplantation, and pre-HTx renal replacement therapy were independently associated with an increased risk of sensitization (cPRA ≥50%). Group C patients were more likely to have longer hospital stays and to use anti-thymocyte globulin as an induction agent compared to groups A and B. Significantly more patients in group C had positive flow cytometric crossmatch and had a higher incidence of preformed donor-specific antibody (DSA) compared to groups A and B. During follow-up, group C had a significantly higher rate of AMR, but the overall survival rate was comparable to that of groups A and B. In a subgroup analysis of group C, post-transplant survival was comparable despite higher preformed DSA in a desensitized group compared to the non-desensitized group. Patients with cPRA ≥50% had significantly higher incidence of preformed DSA and lower freedom from AMR, but post-HTx survival rates were similar to those with cPRA <50%. Our findings suggest that sensitized patients can attain comparable post-transplant survival to non-sensitized patients when treated with optimal desensitization treatment and therapeutic intervention.

CT Pericoronary Adipose Tissue Density Predicts Coronary Allograft Vasculopathy And Adverse Clinical Outcomes After Cardiac Transplantation

CT Pericoronary Adipose Tissue Density Predicts Coronary Allograft Vasculopathy And Adverse Clinical Outcomes After Cardiac Transplantation

Stabilization of Rapidly Progressive Cardiac Allograft Vasculopathy Using mTOR Inhibition After Heart Transplantation

Inhibition of the mammalian target of rapamycin (mTor) pathway after heart transplantation has been associated with reduced progression of coronary allograft vasculopathy (CAV). The application of low-dose mTOR inhibition in the setting of modern immunosuppression, including tacrolimus, remains an area of limited exploration. This retrospective study included patients who received heart transplantation between January 2009 and January 2019 and had baseline, 1-year and 2-3-year coronary angiography with intravascular ultrasound (IVUS). Intimal thickness in 5 segments along the left anterior descending artery was compared across imaging time points in patients who were transitioned to low-dose mTOR inhibitor (sirolimus) vs standard treatment with mycophenolate on a background of tacrolimus. Long-term adverse cardiovascular outcomes (revascularization, severe CAV, retransplant, and cardiovascular death) were also assessed. Among 216 patients (mean age 51.5 ± 11.9 years, 77.8% men, 80.1% white), 81 individuals (37.5%) were switched to mTOR inhibition. mTOR inhibition was associated with a reduction in intimal thickness by 0.05 mm (95% CI 0.02-0.07; P < 0.001). This reduction was driven by patients who met the criteria for rapidly progressive CAV 1-year post-transplant (0.12 mm; P = 0.016 for interaction). After a median follow-up of 8.6 (IQR 6.6-11) years, 40 patients had major adverse cardiovascular outcomes. The use of mTOR inhibitors was not significantly associated with cardiovascular outcomes (P = 0.669). Transitioning patients after heart transplantation to an immunosuppression regimen composed of low-dose mTOR inhibition and tacrolimus was associated with a lack of progression of CAV, particularly in those with rapidly progressive CAV at 1 year, but not with long-term cardiovascular outcomes.

Incidence and determinants of non-radial vascular approach for coronary angiography among heart transplant recipients

Abstract Background Repeated coronary angiograms may be required among heart transplant (HT) recipients to detect coronary allograft vasculopathy (CAV), exposing to higher risk of non-radial vascular approach over time. Objective To describe the incidence and determinants of non-radial vascular approach in this specific population in a large HT center. Methods Consecutive HT recipients undergoing coronary angiography between October 2020 to November 2022 at our Hospital, the largest French HT center, were included and all previous coronary angiograms performed after heart transplantation were retrospectively reviewed. A radial vascular approach has systematically been the first-line approach for coronary angiography in the last two decades. Coronary angiography is routinely performed one year after heart transplantation and every couple of years thereafter or more frequently in case of CAV progression or clinical indication. Determinants of non-radial vascular approach were assessed using multivariate logistic regression analyses, which included the individual mean number of coronary angiographies per year after heart transplantation to account for disparities in follow-up between the two groups. Results A total of 326 patients were included during the period of interest, with a median number of 4 (1-7) coronary angiographies performed over a median duration of 7.0 (1.8-13.1) years (Table 1). A non-radial approach was used in 108 (33.1%) patients, after a median delay from HT of 3.0 (1.0 - 8.4) years (Figure 1). Independent determinants of non-radial approach were female sex (Odds Ratio [OR] 2.18, 95% confidence interval [CI] 1.06 – 4.50), older age at the time of HT (OR 0.98 95%CI 0.96-0.99), post-transplantation dialysis (OR 7.34, 95%CI 2.41 – 22.30) and the development of type 3 CAV according to the International Society Heart and Lung Transplantation (ISHLT) classification (OR 2.01, 95%CI 1.20 – 3.35. Severe complications related to the vascular approach remained rare. Conclusions Non-radial vascular approach remains frequent among HT recipients. In a center of high HT volume and high radial access volume, non-radial vascular approach is used in one out of three HT recipients with multifactorial reasons.

CT pericoronary adipose tissue density predicts coronary allograft vasculopathy and adverse clinical outcomes after cardiac transplantation

Abstract Background Coronary allograft vasculopathy (CAV) is a common cause of heart transplant failure. Coronary Computed Tomography Angiography (CCTA) is used to assess for luminal stenoses in patients with suspected CAV, but additional non-invasive markers are needed to detect early disease and guide the use of treatments that can prevent or slow CAV progression. Purpose We tested the hypotheses that: 1) coronary artery inflammation assessed by pericoronary adipose tissue (PCAT) density and/or total vessel volume-to-myocardial mass ratio (V/M) measured by CCTA could improve the ability to detect CAV in heart transplant patients; and 2) these semi-automated quantitative CCTA metrics would be associated with adverse clinical outcomes. Methods In this retrospective observational cohort study, PCAT density, V/M, and lesion composition were measured in consecutive CCTAs from patients who underwent heart transplantation at a single site between 2010 to 2021. These parameters were incorporated into predictive models for CAV as defined by International Society for Heart &amp; Lung Transplant criteria, and evaluated against long-term clinical outcomes. Results A total of 126 CCTAs were analysed from 94 patients after heart transplant (mean age 49 [SD 14.5] years, 40% female) without CAV (n=86) and with CAV (n=40). PCAT density was higher in transplant patients with CAV (-73.0 HU [SD 9.26]) than without CAV (-77.9 HU [SD 8.23]), and age and sex-matched controls (n=12; -86.19 HU, [SD 5.38]), p&amp;lt;0.001 for both. Unlike patients with atherosclerotic coronary artery disease (n=32), CAV lesions were predominately non-calcified, comprised of mostly fibrous or fibrofatty tissue. V/M was lower in patients with CAV than without (32.4 mm3/g vs. 44.4 mm3/g, p&amp;lt;0.001). PCAT density and V/M improved the ability to predict CAV from AUC 0.78 to 0.87 on receiver operating characteristic analysis (Figure A) when added to donor age and donor/recipient hypertension status (p&amp;lt;0.0001). PCAT density above -66 HU was associated with a greater incidence of all-cause mortality (OR 16.6 95%CI 2.88-109.98, p&amp;lt;0.01; Figure B, box-plot) and the composite endpoint of death, CAV progression, acute rejection, and coronary revascularisation (OR 6.3 95%CI 1.6-32.9, p=0.01) over 5.25 (SD 2.1) years. Conclusions Heart transplant patients with CAV have higher PCAT density and lower V/M than those without. Patients with very high PCAT density on CT had markedly increased incidence of all-cause mortality and major adverse clinical events. These semi-automated metrics could be a useful addition to standard clinical CCTA reporting for diagnosis and monitoring of CAV.Diagnostic Benefit of CTCA MetricsPCAT is predictor of Future Mortality

Abstract 14448: Graft Loss and Rejection Following COVID in Pediatric Heart Transplantation - A Pediatric Heart Transplant Society (PHTS) Propensity Matched Analysis

Introduction: While short-term outcomes following COVID among pediatric heart transplant (HT) recipients have been described, graft outcomes including the risks of subsequent graft loss and rejection following COVID are unknown. Hypothesis: We sought to determine the overall trends of post-HT survival during the COVID pandemic and determine if there was an increased risk for subsequent graft loss and/or rejection following post-HT COVID. Methods: All pediatric recipients of first HT between 1/2003-6/2022 in the Pediatric Heart Transplant Society ( PHTS) database were included. To assess if early post-HT survival changed during the COVID pandemic, 2-year HT survival was compared among those who underwent HT in 2014-2016, 2017-2019, and 2020-2022. To compare the risks of graft loss and rejection (acute cellular and/or antibody-mediated) between those with vs without post-HT COVID, a 1:2 (COVID vs non-COVID) propensity-score matched analysis using multiple pre-HT and post-HT factors (including exact matches for HT year and time post-HT) and Kaplan Meir analysis were performed. Patients with COVID within 3 months post-HT were excluded. Results: The 2-year post-HT survival was similar among patients who underwent HT across the 3 eras (Fig 1A). Among the overall 6634 patients (n = 888 [13%] with post-HT COVID), 861 patients with post-HT COVID and 1716 without post-HT COVID were included in propensity-score matching. There was no difference in the risk of subsequent graft loss (Fig 1B) or rejection (Fig 1C) among those with vs those without post-HT COVID. Conclusions: No differences were observed in early pediatric post-HT survival during the COVID pandemic compared to the immediately prior era. Post-HT COVID did not increase the risks of subsequent graft loss or rejection. Longer-term follow up is necessary to look at other potential post-HT COVID outcomes, such as coronary allograft vasculopathy.

Abstract 12489: Sex Differences in Incidence and Outcomes of Patients With New-Onset Post-Transplant Diabetes Mellitus After Heart Transplantation

Introduction: Post-transplant diabetes mellitus (PTDM) is a common complication following heart transplantation (HT), mostly commonly occurring in the first year after transplant. A few risk factors for the development of PTDM have been identified, including immunosuppressive medications such as calcineurin inhibitors and glucocorticoids. Some studies have suggested that among HT recipients, women have higher rates of acute rejection which may necessitate higher doses of steroids and further hyperglycemia. However, differences between sexes in the incidence of PTDM after HT have not been established. Methods: A retrospective review of patients who underwent HT at a large-volume center between January 1, 2010 and December 31, 2019 was performed. Patients undergoing re-transplantation or dual-organ transplantation were excluded. PTDM was defined as hemoglobin A1C≥6.5% or a random glucose &gt;200 after HT among patients with no prior history of DM. Predictors of PTDM by sex were analyzed with logistic regression, and post-transplant outcomes were analyzed with Chi-Square analysis. Results: Among 317 transplant patients without pre-transplant DM, 71 (22.4%) patients were identified who had PTDM: 24 females (33.7%), 47 males (66.2%). There were no statistically significant differences in baseline characteristics between males and females who developed PTDM including age, race, pre-transplant HTN, calcineurin or steroid dosing at 1 month and 1 year post-transplant. Baseline HTN (OR 2.9, [1.3, 6.7], p=0.009) and mean steroid dose over the first 2 years post-transplant (OR 1.2, [1.0, 1.3], p=0.006) were predictors of PTDM in females but not in males, and mean tacrolimus dose was a predictor in males (OR 1.1, [1.0, 1.2], p=0.001) but not in females. Time to PTDM diagnosis did not differ by sex (log-rank p=0.56). Additionally, post-transplant outcomes in patients with PTDM including acute cellular rejection, antibody-mediated rejection, coronary allograft vasculopathy and death did not differ by sex. Conclusion: PTDM is a common complication of HT. Our study suggests that risk factors for PTDM among HT recipients differ by sex. Future studies should investigate the mechanisms underlying these differences to further guide sex-specific post-HT care.

Contemporary outcomes of pediatric cardiac transplantation with a positive retrospective crossmatch.

A positive crossmatch (+ XM) has traditionally been associated with adverse outcomes following pediatric heart transplantation. However, more recent studies suggest that favorable intermediate-term outcomes may be achieved despite a + XM. This study's hypothesis is that children with a + XM have similar long-term survival, but higher rate of complications such as rejection, coronary allograft vasculopathy (CAV), and infection, compared to patients with a negative (-) XM. The Pediatric Heart Transplant Society Registry (PHTS) database was queried from 2010-2021 for all patients <18 years of age with a known XM. Baseline demographics were compared between + XM and - XM groups using appropriate parametric and non-parametric group comparisons. Cox Proportional Hazards Modeling was used to identify risk factors for post-transplant graft loss, rejection, and CAV. Of 4599 pediatric heart transplants during the study period, XM results were available for 3914 (85%), of which 373 (9.5%) had a + XM. Univariate analysis showed lower 10-year survival for patients with + XM (HR = 1.3, p = .04). Multivariate analyses revealed no significant difference in 10-year survival in the 2 groups; however, time to first rejection (p = .0001) remained significantly shorter in the + XM group. Pediatric patients transplanted across a + XM experience earlier rejection; however, after multivariate adjustment, + XM is not independently associated with intermediate-term graft loss. The risk of heart transplantation against a + XM must be balanced with the ongoing risk of waitlist mortality.

Elevated Aortic Stiffness after Pediatric Heart Transplantation.

In adults, arterial stiffness has been linked to the development of target end-organ damage, thought to be related to abnormal transmission of pulse pressure. Increased arterial stiffness and endothelial dysfunction have been hypothesized to contribute to the development of microvascular dysfunction and coronary allograft vasculopathy (CAV), an important comorbidity after heart transplantation. However, little data exists regarding arterial stiffness in pediatric heart transplantation and its influence on development of coronary allograft vasculopathy is not well understood. We sought to assess aortic stiffness and distensibility in pediatric post-heart transplant patients. A prospective, observational study analyzing the ascending (donor tissue) and descending aorta (recipient tissue) using transthoracic echocardiographic M-mode measurements in patients aged < 21 years was conducted. Descending and ascending aorta M-modes were obtained from the subcostal long axis view, and the parasternal long axis view 3-5mm above the sinotubular junction, respectively. Two independent reviewers averaged measurements over 2-3 cardiac cycles, and Aortic Distensibility (AD) and Aortic Stiffness Index (ASI) were calculated using previously validated methods. We recruited 39 heart transplant (HT) patients and 47 healthy controls. Median end diastolic dimension of the ascending aorta (donor tissue) was significantly larger in the transplant group than the control group (1.92cm vs. 1.74cm, p = 0.01). Ascending aortic distensibility in post-transplant patients was significantly lower than in the control group (4.87 vs. 10.53, p < 0.001). Ascending aortic stiffness index was higher in the transplant patients compared to the controls (4.63 vs. 2.21, p < 0.001). There is evidence of altered ascending aortic distensibility and stiffness parameters in post-heart transplant patients. Further studies are required to assess its influence on complications like development of coronary artery vasculopathy.

Coronary allograft vasculopathy in post-heart transplant patients: pathogenesis and role of cardiac computed tomography in diagnosis-a comprehensive review.

Coronary allograft vasculopathy, often known as cardiac allograft vasculopathy (CAV), is a substantial source of morbidity and mortality in people who have had heart transplants. Early detection and monitoring of CAV are crucial for improving outcomes in this population. Although cardiac computed tomography (CT) has emerged as a possible method for finding and evaluating CAV, invasive coronary angiography has long been thought of as the gold standard for recognizing CAV. This study focuses on the utility of cardiac CT for CAV diagnosis and treatment in the post-heart transplant population. It provides an overview of recent studies on the application of cardiac CT in CAV and highlights the advantages and disadvantages of this imaging modality. The potential application of cardiac CT for CAV risk assessment and care is also examined in the study. Overall, the data point to a potential role for cardiac CT in the detection and treatment of CAV in post-heart transplant patients. It enables evaluation of the whole coronary tree and low-radiation, high-resolution imaging of the coronary arteries. Hence, further study is required to determine how best to employ cardiac CT in treating CAV in this group.

P475 RECURRENT CORONARY ARTERY VASOSPASM COMPLICATED BY CARDIAC ARRESTS IN HEART TRANSPLANT RECIPIENT: AN UNUSUAL ENEMY

Abstract Even if coronary vasospasm (CV) is considered a rare phenomenon in heart transplant (HT) recipients, during routine coronary angiography asymptomatic CV may be observed. We report the case of a 30–year–old male who underwent HT in 2007 for dilatative cardiomyopathy. He was maintained on tacrolimus and mycophenolate mofetil and had no significant rejection or coronary allograft vasculopathy (CAV) demonstration. In December 2020 patient presented with cardiac arrest preceded by angina. Coronary angiography demonstrated diffuse spasm of the right coronary artery (RCA) with resolution after intracoronary nitrate administration. An endomyocardial biopsy (EBM) revealed no signs of cellular rejection whilst cardiac magnetic resonance showed signs of acute rejection (Fig.1). Moreover, two major histocompatibility complex (MHC) Class 2 donor–specific antibodies (DSAs) were positive with a high title. Treatment for antibody–mediated rejection (AMR) was initiated with steroids and plasmapheresis, followed by immunoglobulin infusion. Cardiac defibrillator was implanted before discharge. In August 2021, patient experienced a second cardiac arrest. Left heart catheterization found diffuse CV and after nitrates administration, proximal critical stenosis of RCA was pointed out and treated with stent insertion (Fig. 2–3). EMB and DSAs assessment were both negative. The patient was discharged after medical therapy optimization for CV prevention including the switch from mycophenolate to everolimus. After two more episodes of ACS with angiography finding of CV we decided to empirically treat the patient with weekly photopheresis sessions. Despite aggressive AMR management, a third ACC occurred in March 2022. The patient was finally reintroduced to the HT waiting list. Most CV episodes run without any symptoms due to the denervated heart post–transplant so probably re–innervation occurred in our patient. Calcium channel blockers, nitrates, and beta–blockers failed in CV prevention, suggesting ineffectiveness in HT recipients because of a different pathogenetic mechanism when compared to healthy subjects. Furthermore, documentation of coronary disease progression after the second ACC supports the hypothesis that CV could be the first manifestation of CAV. An intriguing hypothesis would be the presence of pathological vasoreactivity in the donor‘s heart, ascribable to an “inherited” endothelial dysfunction that could last be exacerbated by multiple factors, including AMR.