Risk Of Cardiac Allograft Vasculopathy Research Articles

Influence of donor age and donor-recipient age difference on intimal hyperplasia in pediatric patients with young and adult donors vs. adult patients after heart transplantation.

Optimal selection and allocation of donor hearts is a relevant aspect in transplantation medicine. Donor age and cardiac allograft vasculopathy (CAV) affect post-transplant mortality. To what extent donor age impacts intimal hyperplasia (CAVIH) in pediatric and adult patients after heart transplantation (HTx) is understudied. In a cohort of 98 HTx patients, 58 pediatric (24.1% with adult donors) and 40 adult patients, we assessed the effect of donor age and donor-recipient age difference (D-R) on the continuous parameter of maximal intima thickness (mIT) in optical coherence tomography. We evaluated their predictive value regarding higher mIT and the prevalence of CAVIH, defined as mIT > 0.3 mm, and compared it to established CAV risk factors. In the overall population, donor age correlated with mIT (p < 0.001), while in the pediatric subpopulation, both donor age and D-R correlated with mIT (p < 0.001 and p = 0.002, respectively). In the overall population, donor age was a main predictor of higher mIT and CAVIH (p = 0.001 and p = 0.01, respectively) in addition to post-transplant interval, arterial hypertension, and dyslipidemia. In the pediatric patients, dyslipidemia remained a main predictor of both higher mIT and CAVIH (p = 0.004 and p = 0.040, respectively), while donor age and D-R were not. While there was an effect of the non-modifiable parameter of donor age regarding maximal intimal thickness, a stronger association was seen between the modifiable risk factor dyslipidemia and higher maximal intimal thickness and CAVIH in both the overall population and the pediatric subpopulation.

Cardiac allograft vasculopathy in heart transplant recipients from hepatitis C viremic donors.

Recent studies suggest the transplantation of Hepatitis C (HCV) hearts from viremic donors is associated with comparable 1 year survival to nonviremic donors. Though HCV viremia is a known risk factor for accelerated atherosclerosis, data on cardiac allograft vasculopathy (CAV) outcomes are limited. We compared the incidence of CAV in heart transplant recipients from HCV viremic donors (nucleic acid amplification test positive; NAT+) compared to non-HCV infected donors (NAT-). We retrospectively reviewed annual coronary angiograms with intravascular ultrasound from April 2017 to August 2020 at two large cardiac transplant centers. CAV was graded according to ISHLT guidelines. Maximal intimal thickness (MIT) ≥ 0.5mm was considered significant for subclinical disease. Among 270 heart transplant recipients (mean age 54; 77% male), 62 patients were transplanted from NAT+ donors. CAV ≥ grade 1 was present in 8.8% of the NAT+ versus 16.8% of the NAT- group at 1 year, 20%versus 28.8% at 2 years, and 33.3%versus 41.5% at 3 years. After adjusting for donor age, donor smoking history, recipient BMI, recipient, hypertension, and recipient diabetes, NAT+ status did not confer increased risk of CAV (HR.80; 95% CI.45-1.40, p=0.43) or subclinical IVUS disease (HR.87; 95% CI.58-1.30, p=0.49). Additionally, there was no difference in the presence of rapidly progressive lesions on IVUS. Our data show that NAT+ donors conferred no increased risk for early CAV or subclinical IVUS disease following transplantation in a cohort of heart transplant patients who were treated for HCV, suggesting the short-term safety of this strategy to maximize the pool of available donor hearts.

Acetylsalicylic acid use and development of cardiac allograft vasculopathy: A national prospective study using highly automated 3-D optical coherence tomography analysis.

There is conflicting evidence on the role of acetylsalicylic acid (ASA) use in the development of cardiac allograft vasculopathy (CAV). A nationwide prospective two-center study investigated changes in the coronary artery vasculature by highly automated 3-D optical coherence tomography (OCT) analysis at 1 month and 12 months after heart transplant (HTx). The influence of ASA use on coronary artery microvascular changes was analyzed in the overall study cohort and after propensity score matching for selected clinical CAV risk factors. In total, 175 patients (mean age 52±12 years, 79% male) were recruited. During the 1-year follow-up, both intimal and media thickness progressed, with ASA having no effect on its progression. However, detailed OCT analysis revealed that ASA use was associated with a lower increase in lipid plaque (LP) burden (p=.013), while it did not affect the other observed pathologies. Propensity score matching of 120 patients (60 patient pairs) showed similar results, with ASA use associated with lower progression of LPs (p=.002), while having no impact on layered fibrotic plaque (p=.224), calcification (p=.231), macrophage infiltration (p=.197), or the absolute coronary artery risk score (p=.277). According to Kaplan-Meier analysis, ASA use was not associated with a significant difference in survival (p=.699) CONCLUSION: This study showed a benefit of early ASA use after HTx on LP progression. However, ASA use did not have any impact on the progression of other OCT-observed pathologies or long-term survival.

Early Assessment of Cardiac Allograft Vasculopathy Risk Among Recipients of Hepatitis C Virus-infected Donors in the Current Era

BackgroundTransplantation of hearts from hepatitis C virus (HCV)-positive donors has increased substantially in recent years following development of highly effective direct-acting antiviral therapies for treatment and cure of HCV. Although historical data from the pre–direct-acting antiviral era demonstrated an association between HCV-positive donors and accelerated cardiac allograft vasculopathy (CAV) in recipients, the relationship between the use of HCV nucleic acid test–positive (NAT+) donors and the development of CAV in the direct-acting antiviral era remains unclear. Methods and ResultsWe performed a retrospective, single-center observational study comparing coronary angiographic CAV outcomes during the first year after transplant in 84 heart transplant recipients of HCV NAT+ donors and 231 recipients of HCV NAT– donors. Additionally, in a subsample of 149 patients (including 55 in the NAT+ cohort and 94 in the NAT– cohort) who had serial adjunctive intravascular ultrasound examination performed, we compared development of rapidly progressive CAV, defined as an increase in maximal intimal thickening of ≥0.5 mm in matched vessel segments during the first year post-transplant. In an unadjusted analysis, recipients of HCV NAT+ hearts had reduced survival free of CAV ≥1 over the first year after heart transplant compared with recipients of HCV NAT– hearts. After adjustment for known CAV risk factors, however, there was no significant difference between cohorts in the likelihood of the primary outcome, nor was there a difference in development of rapidly progressive CAV. ConclusionsThese findings support larger, longer-term follow-up studies to better elucidate CAV outcomes in recipients of HCV NAT+ hearts and to inform post-transplant management strategies.

Heart Transplant Human Leukocyte Antigen Matching in the Modern Era

Although numerous reports have studied the consequences of human leukocyte antigen (HLA) mismatching in renal transplantation, there are limited and outdated data analyzing this association in thoracic organ transplantation. Therefore, our study reviewed the impact of HLA mismatching at both the total and the loci levels in the modern-era heart-transplant procedure on survival and chronic rejection outcomes. We performed a retrospective analysis of adult patients after heart transplant by using the United Network for Organ Sharing database from January 2005-July 2021. Total HLA and HLA-A, HLA-B and HLA-DR mismatches were analyzed. Survival and cardiac allograft vasculopathy were the outcomes of interest during a 10-year follow-up period using Kaplan-Meier curves, log-rank tests and multivariable regression models. A total of 33,060 patients were included in this study. Recipients with a high degree of HLA mismatching had increased incidences of acute organ rejection. There were no significant differences in mortality rates among any of the total or loci level groups. Similarly, there were no significant differences between total HLA mismatch groups in time to first cardiac allograft vasculopathy, though mismatching at the HLA-DR locus was associated with an increased risk of cardiac allograft vasculopathy. Our analysis suggests that HLA mismatch is not a significant predictor of survival in the modern era. Overall, the clinical implications of this study provide reassuring data for the continued use of non-HLA-matched donors in an effort to increase the donor pool. If HLA matching is to be considered for heart transplant donor-recipient selection, matching at the HLA-DR locus should take priority due to its association with cardiac allograft 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.

Sex differences in clinical characteristics and outcomes in patients undergoing heart transplantation.

Whether sex affects selection for and outcomes after heart transplantation (HTx) remains unclear. We aimed to show sex differences in pre-transplant characteristics and outcomes after HTx. From 1995 to 2019, 49200 HTx recipients were prospectively enrolled in the Organ Procurement and Transplantation Network. Logistic regression models were used to evaluate clinical characteristics by sex. Multivariable Cox regression models were fitted to assess sex differences in all-cause mortality, cardiovascular mortality, graft failure, cardiac allograft vasculopathy (CAV), and malignancy. In 49200 patients (median age 55years, interquartile range 46-62; 24.6% women), 49732 events occurred during a median follow-up of 8.1years. Men were older than women, had more often ischaemic cardiomyopathy (odds ratio [OR] 3.26, 95% confidence interval [CI] 3.11-3.42; P<0.001), and a higher burden of cardiovascular risk factors, whereas women had less malignancies (OR 0.47, CI 0.44-0.51; P<0.001). Men were more often treated in intensive care unit (OR 1.24, CI 1.12-1.37; P<0.001) with a higher need for ventilatory (OR 1.24, CI 1.17-1.32; P<0.001) or VAD (OR 1.53, CI 1.45-1.63; P<0.001) support. After multivariable adjustment, men had a higher risk for CAV (hazard ratio [HR] 1.21, CI 1.13-1.29; P<0.001) and malignancy (HR 1.80, CI 1.62-2.00; P<0.001). There were no differences in all-cause mortality, cardiovascular mortality, and graft failure between sexes. In this US transplant registry, men and women differed in pre-transplant characteristics. Male sex was independently associated with incident CAV and malignancy even after multivariable adjustment. Our results underline the need for better personalized post-HTx management and care.

Clonal hematopoiesis of indeterminate potential and outcomes after heart transplantation: A multicenter study

Cardiac allograft vasculopathy (CAV) is a leading cause of late graft failure and mortality after heart transplantation (HT). Sharing some features with atherosclerosis, CAV results in diffuse narrowing of the epicardial coronaries and microvasculature, with consequent graft ischemia. Recently, clonal hematopoiesis of indeterminate potential (CHIP) has emerged as a risk factor for cardiovascular disease and mortality. We aimed to investigate the relationship between CHIP and posttransplant outcomes, including CAV. We analyzed 479 HT recipients with stored DNA samples at 2 high-volume transplant centers, Vanderbilt University Medical Center and Columbia University Irving Medical Center. We explored the association between the presence of CHIP mutations with CAV and mortality after HT. In this case-control analysis, carriers of CHIP mutations were not at increased risk of CAV or mortality after HT. In a large multicenter genomics study of the heart transplant population, the presence of CHIP mutations was not associated with an increased risk of CAV or posttransplant mortality.

The teammate trial: Study design and rationale tacrolimus and everolimus against tacrolimus and MMF in pediatric heart transplantation using the major adverse transplant event (MATE) score

Currently there are no immunosuppression regimens FDA-approved to prevent rejection in pediatric heart transplantation (HT). In recent years, everolimus (EVL) has emerged as a potential alternative to standard tacrolimus (TAC) as the primary immunosuppressant to prevent rejection that may also reduce the risk of cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD) and cytomegalovirus (CMV) infection. However, the two regimens have never been compared head-to-head in a randomized trial. The study design and rationale are reviewed in light of the challenges inherent in rare disease research. The TEAMMATE trial (NCT03386539, IND 127980) is the first multicenter randomized clinical trial (RCT) in pediatric HT. The primary purpose is to evaluate the safety and efficacy of EVL and low-dose TAC (LD-TAC) compared to standard-dose TAC and mycophenolate mofetil (MMF). Children aged <21 years at HT were randomized (1:1 ratio) at six months post-HT to either regimen, and followed for 30 months. Children with recurrent rejection, multi-organ transplant recipients, and those with an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73m2 were excluded. The primary efficacy hypothesis is that, compared to TAC/MMF, EVL/LD-TAC is more effective in preventing 3 MATEs: acute cellular rejection (ACR), CKD and CAV. The primary safety hypothesis is that EVL/LD-TAC does not have a higher cumulative burden of 6 MATEs (antibody mediated rejection [AMR], infection, and post-transplant lymphoproliferative disorder [PTLD] in addition to the 3 above). The primary endpoint is the MATE score, a composite, ordinal surrogate endpoint reflecting the frequency and severity of MATEs that is validated against graft loss. The study had a target sample size of 210 patients across 25 sites and is powered to demonstrate superior efficacy of EVL/LD-TAC. Trial enrollment is complete and participant follow-up will be completed in 2023. The TEAMMATE trial is the first multicenter RCT in pediatric HT. It is anticipated that the study will provide important information about the safety and efficacy of everolimus- vs tacrolimus-based regimens and will provide valuable lessons into the design and conduct of future trials in pediatric HT.

Early aspirin use and the development of cardiac allograft vasculopathy in pediatric heart transplant recipients: A pediatric heart transplant society analysis.

Cardiac allograft vasculopathy (CAV) remains a leading cause of graft loss in pediatric heart transplant (HTx) recipients. Adult literature suggests that aspirin (ASA) use in the early post-HTx period may reduce the risk of CAV. This study aimed to determine the impact of early ASA use on the development of CAV in pediatric HTx recipients. All subjects <17 years of age at time of primary HTx who survived ≥3 years without evidence of CAV were identified for inclusion from the Pediatric Heart Transplant Society database (1996-2019). Early ASA use was defined as ASA started within the first 3 years post-HTx and was classified as continuous or intermittent. Frequency of ASA use was described across centers. Kaplan-Meier method assessed freedom from CAV and overall graft survival. Multiphase parametric hazard analyses and propensity score matched analysis were used to identify independent risk factors. 3,011 patients were included with 387 (13%) receiving continuous ASA, 676 (22%) receiving intermittent ASA, and 1,948 (65%) receiving no ASA. ASA use was highly variable across centers (0%-100%). At baseline patients receiving continuous ASA therapy demonstrated inferior graft survival (p < 0.001) and worse freedom from CAV (p=0.002), but with lower CAV grades (p=0.05). In multiphase parametric hazard modeling continuous ASA use was not independently associated with CAV, but remained associated with inferior graft survival. Propensity-matched sub-analysis between continuous and no ASA groups demonstrated no difference in freedom from CAV or overall graft loss. ASA use varies widely across pediatric HTx centers. Early ASA use did not reduce the risk of CAV or graft loss in pediatric heart transplant recipients.

Role of genetics in the development of cardiac allograft vasculopathy.

The association between genetic polymorphisms and early cardiac allograft vasculopathy (CAV) development is relatively unexplored. Identification of genes involved in the CAV process may offer new insights into pathophysiology and lead to a wider range of therapeutic options. This prospective study of 109 patients investigated 44 single nucleotide polymorphisms (SNPs) within the susceptibility loci potentially related to coronary artery disease, carotid artery intima-media thickness (cIMT), and in nitric oxide synthase gene. Genotyping was done by the Fluidigm SNP Typeassays and Fluidigm 48.48 Dynamic ArrayIFC. The intima thickness progression (IT) was evaluated by coronary optical coherence tomography performed 1 month and 12 months after heart transplantation (HTx). During the first post-HTx year, the mean intima thickness (IT) increased by 24.0 ± 34.2 µm (p < 0.001) and lumen area decreased by ‒0.9 ± 1.8 mm2 (p < 0.001). The rs1570360 (A/G) SNP of the vascular endothelial growth factor A (VEGFA) gene showed the strongest association with intima thickness progression, even in the presence of the traditional CAV risk factors. SNPs previously related to carotid artery intima-media thickness rs11785239 (PRAG1), rs6584389 (PAX2), rs13225723 (LINC02577) and rs17477177 (CCDC71L), were among the five most significantly associated with IT progression but lost their significance once traditional CAV risk factors had been added. Results of this study suggest that genetic variability may play an important role in CAV development. The vascular endothelial growth factor A gene SNP rs1570360 showed the strongest association with intima thickness (IT) progression measured by OCT, even in the presence of the traditional CAV risk factors (Tab. 3, Fig. 3, Ref. 36). Text in PDF www.elis.sk Keywords: cardiac allograft vasculopathy, optical coherence tomography, vascular endothelial growth factor A, intimal thickening, genetic polymorphism.

Is Donor/Recipient Cytomegalovirus Mismatch Truly Associated with Increased Risk for Cardiac Allograft Vasculopathy in the Current Era?

<h3>Purpose</h3> Cytomegalovirus (CMV) infections have been associated with the subsequent development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). This is most prominent with patients receiving a donor with positive CMV serology when the patient is CMV serology negative. This mismatched patient cohort was subsequently reviewed for the development of CMV serology positivity, CMV syndrome, and CMV disease (specific organ involvement). <h3>Methods</h3> Between 2010 and 2016, we assessed 138 HTx patients who had CMV mismatch (donor positive/recipient negative). Patients were treated with CMV prophylaxis with Valcyte for 1 year. CMV patients were then divided (data at 1-year) into those that developed serology positive CMV on IgG, CMV syndrome (who presented with fever, chills, and sweats), CMV disease (organ specific disease, such as retinitis, peritonitis, gastroenteritis). All groups were then assessed for 5-year survival and the development of CAV by angiography. <h3>Results</h3> In CMV mismatched patients, there was no significant difference in 5-year survival or freedom from angiographic CAV in those patients with clinical CMV (asymptomatic IgG positive, CMV syndrome, CMV disease groups) compared to the asymptomatic IgG negative group. <h3>Conclusion</h3> In the current era, CMV mismatch patients (donor positive/recipient negative CMV serology) do not appear to be at increased risk for poor outcome. Valcyte prophylaxis for 1 year may be beneficial.

Cardiac Allograft Vasculopathy in Heart Transplant Recipients from Hepatitis C Viremic Donors, Data from Two Large Academic Transplant Centers

<h3>Purpose</h3> Heart transplantation from Hepatitis C (HCV) viremic donors is an increasingly utilized strategy, though long-term outcomes with respect to cardiac allograft vasculopathy (CAV) are unknown. HCV is implicated as a potent trigger of the inflammatory cascade and may be associated with CAV. We report the incidence of CAV and subclinical disease in recipients of HCV-viremic donors (nucleic amplification test positive: NAT+) vs non-viremic donors (nucleic amplification test negative: NAT-) <h3>Methods</h3> We retrospectively reviewed coronary angiograms with intravascular ultrasound (IVUS) of patients who received NAT+ and NAT- hearts between January 2014 and July 2020 at two large academic institutions. Donor-derived acute HCV infection was treated with a direct-acting antiviral agent per site protocol. CAV was graded according to ISHLT guidelines. Maximal intimal thickness (MIT) of the left main and left anterior descending artery was measured by IVUS. MIT ≥ 0.5mm was considered significant subclinical disease. Two-sample t tests were performed for continuous variables. Chi-square or Fisher's exact test were used for categorical variables. <h3>Results</h3> Among 178 patients, 65 received NAT+ donor hearts. Average recipient age was 58 and 55 years in the NAT+ and NAT- groups respectively and 15% vs 27% were female. NAT- donors were older (42 vs 36 years), but with no significant difference in cardiac risk factors including tobacco use, hypertension, and diabetes. CAV ≥ grade 1 was present in 9.1% of the NAT+ vs 18.8% of the NAT- group at 1 year (p=0.16), and 19.4% vs 21.0% at 2 years (p=1). Rates of significant IVUS disease were 53.7% in NAT+ vs 70.5% in NAT- at 1 year (p=0.068), and 72.2% vs 78.3% at 2 years (p=0.3). <h3>Conclusion</h3> Among heart transplant recipients from HCV viremic donors our data show no difference in rates of angiographic CAV or subclinical disease by IVUS at 1 or 2 years. While these results are encouraging, longer follow up is needed to assess CAV risk in this population.

Obesity and dyslipidemia predict cardiac allograft vasculopathy and graft loss in children and adolescents post-heart transplant: A PHTS multi-institutional analysis.

Obesity and dyslipidemia afflict children of all ages. We explored the prevalence of obesity and dyslipidemia in pediatric heart transplant (HT) recipients and its effects on cardiac allograft vasculopathy (CAV) and survival. This study included primary HT recipients (≤18years) transplanted between 01/1996 and 12/2018 included in the Pediatric Heart Transplant Society database. Obesity was categorized according to WHO/CDC guidelines and dyslipidemia according to the National Cholesterol Education Program. Kaplan-Meier analyses for CAV and graft loss stratified for BMI and lipid panels were generated and risk factors identified using multivariate analyses. Among 6291 HT patients (median age [range] at HT=4.3 [0.6-12.8]years; 45% Female; 68% White), 56% had a normal BMI at HT. Obese patients at HT had an increased risk for graft loss (HR 1.19, 95% CI 1.01-1.4, p=.04). Poor total cholesterol (TC), LDL-C, and TG were associated with the risk of both CAV (HR 1.79, p<.0001; HR 1.65, p=.0015; HR 1.53, p<.0001, respectively) and graft loss (HR 1.58, p=.0008; HR 1.22, p=.04; HR 1.43, p=.0007, respectively). Pediatric patients who are obese at the time of HT and dyslipidemic at 1year post-HT are at an increased risk for CAV and graft loss. Preventative interventions may reduce morbidity and mortality among this cohort.

Low-Density Lipoprotein Cholesterol Level Trends and the Development of Cardiac Allograft Vasculopathy After Heart Transplantation

BackgroundUnlike the relationship with atherosclerotic coronary artery disease, that between low-density lipoprotein cholesterol (LDL-C) and cardiac allograft vasculopathy (CAV) is unclear. Our objectives were to characterize lipid profiles early after heart transplantation (HT) and evaluate the relationship between early LDL-C and the development of CAV. MethodsWe retrospectively reviewed consecutive adults who underwent HT at 2 centres during the time period 2010-2018. The primary outcome was the incidence of angiographic CAV. The relationship between LDL-C and CAV was assessed using Cox proportional hazards and logistic regression models adjusted a priori for clinically important covariates, including recipient and donor age, recipient sex, ischemic time, and pre-HT diabetes. ResultsA total of 386 patients followed for a median (range) of 4.4 (2.8-6.8) years were included. LDL-C at baseline (2.11 ± 0.86 mmol/L) and 1 year after HT (2.20 ± 0.88 mmol/L) was similar (P = 0.21), but it was lower at the end of follow-up (1.89 ± 0.74 mmol/L, P < 0.01). Of 309 patients who underwent angiography, 54% had CAV. The risk of CAV did not vary according to baseline, 1-year, or change from baseline to 1-year LDL-C. The odds of CAV at 1 year were equally likely across LDL-C values (adjusted odds ratio 1.00, 95% confidence interval: 0.61-1.63 for baseline, and adjusted odds ratio 1.25, 95% confidence interval: 0.74-2.10 for 1-year LDL-C). ConclusionsNo association was identified between early LDL-C and the development of CAV. Our findings do not support targeting a specific LDL-C for patients who do not otherwise meet criteria for guideline-recommended LDL-C target levels. Randomized studies are warranted to determine if lipid-lowering to a specific LDL-C target level modifies the risk of CAV.

Depressive symptoms at 1 year after surgery increase the risk of cardiac allograft vasculopathy and mortality in heart transplant recipients: A prospective cohort study

ObjectiveTo investigate the impact of depressive symptoms at 1-year post-heart transplant (HTx) on cardiac allograft vasculopathy (CAV) and mortality. MethodsWe performed a single-center prospective cohort study of patients 1-year post-HTx consecutively enrolled between January 2001 and September 2015, and followed-up until November 2020. Kaplan-Meier and uni- and multivariate cox proportional hazards models were used to investigate the impact of depressive symptoms (Beck Depression Inventory) on all-cause mortality and clustered CAV events, i.e. time to angiographically detected CAV, revascularizations, retransplantation/CAV-mortality. Results23.7% (45/190) (median age 53.5 [IQR 19.3], 77% men) had mild to severe depressive symptoms (BDI 10–63). Forty-four patients (23.2%) died during a 10.4 years median follow-up. Depressive symptoms (BDI ≥ 10) increased all-cause mortality risk (HR = 2.52 [1.35–4.71], p = .004), even after adjusting for confounders (HR = 2.95 [1.50–5.80], p = .002). CAV data were available for 156 patients. During a 9.9 years median follow-up, 51 patients (32.7%) developed CAV or revascularization of which 8 received at least a second revascularization, 3 were re-transplanted, and 9 died from CAV-related causes. Analysis showed a significant increased CAV-risk among depressed patients (HR = 2.27 [1.10–4.69], p = .026), even in adjusted models (HR = 2.25 [1.01–4.98, p = .047). ConclusionDepressive symptoms at 1-year post-HTx unfavorably impact mortality and CAV, highlighting the need for interventions.

Low-Density Lipoprotein Cholesterol Trends and the Development of Cardiac Allograft Vasculopathy after Heart Transplantation

<h3>Purpose</h3> The relationship between low-density lipoprotein cholesterol (LDL-C) and cardiac allograft vasculopathy (CAV) is unclear. The objectives of this study were to characterize lipid profiles early after heart transplant (HT), and to evaluate the relationship between early serum LDL-C and the development of CAV. <h3>Methods</h3> We retrospectively reviewed consecutive adults who underwent HT at the University of Ottawa Heart Institute (Ottawa, Canada) and Toronto General Hospital (Toronto, Canada) from 2010-2018. The primary outcome was the incidence of CAV (ISHLT grade 1-3). The relationship between LDL-C and CAV was assessed using Cox proportional hazards and logistic regression models adjusted <i>a priori</i> for clinically important covariates including recipient and donor age, recipient sex, ischemic time and pre-HT diabetes. <h3>Results</h3> 386 patients followed for 4.4 (2.8-6.8) years were included. LDL-C at baseline (2.11±0.86 mmol/L) and at 1-year after HT (2.20±0.88 mmol/L) was similar (p=0.21) but was significantly lower at the end of study follow-up (1.89±0.74 mmol/L) (p<0.01). Of 309 patients who underwent angiography, 54% developed CAV. The risk of CAV did not vary according to baseline, 1-year or change from baseline to 1-year pre-specified LDL-C thresholds (Figure). The odds of CAV at 1-year was equally likely across LDL-C values (adjusted OR 1.00, 95% CI: 0.61-1.63 for baseline and adjusted OR 1.25, 95% CI: 0.74-2.10 for 1-year LDL-C). <h3>Conclusion</h3> There was no relationship between early LDL-C and the development of CAV after HT. Our findings do not support targeting a specific LDL-C for patients who do not otherwise meet criteria for non-HT guideline recommended LDL-C targets. Randomized studies are warranted to determine if lipid-lowering to a specific LDL-C target decreases the development and progression of CAV.

Aspirin Use and the Development of Cardiac Allograft Vasculopathy in Pediatric Heart Transplant Recipients

<h3>Purpose</h3> Cardiac allograft vasculopathy (CAV) has limited treatment options and results in significant mortality. Data in adult heart transplant (HTx) recipients suggests that aspirin (ASA) use may reduce the risk of CAV. However, there are limited pediatric data on this topic. This study aimed to assess the use of ASA in pediatric HTx recipients and its association with CAV. <h3>Methods</h3> All patients in the Pediatric Heart Transplant Society database < 17 years of age who underwent primary HTx and had > 3 years of follow up were included. ASA use during the first 3 years post-transplant was defined as continuous, intermittent, or no ASA use. Time to CAV and graft loss was compared across groups using the Kaplan Meier method. A multivariable survival model was constructed for each outcome to assess the impact of early post-HTx ASA use. <h3>Results</h3> A total of 3,011 patients were identified for inclusion with 387 (13%) continuous, 676 (22%) intermittent, and 1948 (65%) with no ASA use. ASA use was more common in older patients (p<0.001). Patients receiving continuous ASA were less likely to receive induction therapy at HTx compared to other groups (p<0.001). ASA use was highly variable across centers, ranging from 0% to 100% (Figure 1a). Patients receiving continuous ASA therapy demonstrated worse freedom from CAV (p= 0.002) and inferior graft survival (p<0.001) (Figures 1b-c). In multivariable analyses, early ASA use was not associated with improvements in freedom from CAV or graft survival. <h3>Conclusion</h3> ASA use varies widely across pediatric HTx centers. Early ASA use did not reduce the risk of CAV or graft loss.

Triglyceride Glucose Index is an Independent Predictor for Cardiac Allograft Vasculopathy and Cardiovascular Mortality Following Heart Transplantation

<h3>Purpose</h3> Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). The triglyceride glucose (TyG) index, the product of plasma glucose and triglycerides, a surrogate of insulin resistance, has been demonstrated to predict cardiovascular morbidity and mortality in the non-transplant population. We investigated the association between TyG index and cardiovascular outcomes following HT. <h3>Methods</h3> A total of 215 HT patients were assessed for TyG index using the formula ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Patients were divided into high and low TyG index groups according to the median value (8.91) at 3-month post HT. Endpoints included CAV, cardiovascular (CV) mortality, treated rejection (TR), and non-fatal major adverse cardiac events (NF-MACE). <h3>Results</h3> Baseline patient and donor clinical and demographic characteristics were similar for the two groups. Kaplan-Meier analyses showed that at 8 years after HT (median follow-up time), high TyG index was associated with lower freedom from CAV (69 vs. 87%, log-rank p = 0.003, Figure), lower freedom from the combined endpoint of CAV/CV mortality (64 vs. 82%, log-rank p=0.004), and lower freedom from NF-MACE (79 vs. 92%, log-rank p=0.009). There were no significant differences in freedom from TR. Multivariable analyses consistently demonstrated that a high TyG index was independently associated with a significant 3.2-fold increased risk of CAV and 2.40-fold increased risk of CAV/CV mortality (95%CI 1.51 to 6.88, p = 0.003, Figure; 95%CI 1.21 to 4.75, p = 0.02, respectively). <h3>Conclusion</h3> The study supports the strong association between the TyG index and HT outcomes. A high TyG index was an independent predictor of CAV and CV mortality. Further studies are needed to determine whether interventions for the TyG index have a positive impact on improving CAV outcomes.

Weight gain post-heart transplantation is associated with an increased risk for allograft vasculopathy and rejection.

Obesity and overweight are associated with an increased risk for cardiovascular disease. Since fat mass (FM) and fat-free mass (FFM) both contribute to total body weight (TBW), we characterized the post-heart transplantation (HT) change in TBW and its implications for outcomes. Post-HT changes in TBW, FM, and FFM were reviewed for 211 HT patients assessed during 1997-2017. Endpoints included cardiac allograft vasculopathy (CAV) and rejection. Median TBW increased by 7.3% at 1year, with a significant rise in the obese category (28% vs. 13%, p<0.001) and with FM versus FFM making the main contribution (23% vs. 3%, p<0.001). When patients were divided according to median TBW change ("high" vs. "low"), Kaplan-Meier analysis showed that 10-year freedom from CAV (log-rank p<0.005) and rejection (log-rank p<0.01) was significantly higher for the "low" TBW change group. Consistently, multivariable analyses showed that the "high" group was independently associated with significant 3.5-fold and 4.2-fold increased risks for CAV (95% CI 1.4-8.7, p=0.01) and rejection (95% CI 1.2-15.4, p=0.03), respectively. Weight gain, contributed mostly by FM, is independently associated with an increased risk for CAV and rejection. Follow-up emphasis should be placed on weight gain and preventative measures.