Coronary Allograft Vasculopathy Research Articles

The outcome of restrictive cardiac allograft physiology in severe coronary allograft vasculopathy

BackgroundMicrovascular dysfunction after heart transplantation leads to restrictive cardiac allograft physiology (RCP), which is classified as severe coronary allograft vasculopathy (CAV); however, the prognosis of RCP remains unclear. Therefore, in this study, we aimed to elucidate the prognosis of RCP in comparison with that of severe angiographic CAV. MethodsWe assessed 116 patients with severe CAV who underwent heart transplantation between 2004 and 2023. RCP was defined as symptomatic heart failure with restrictive hemodynamic values (mean right atrial pressure >12 mmHg, pulmonary capillary wedge pressure >25 mmHg, and cardiac index <2.0 L/min/m2). The primary outcome was death or re-transplantation. ResultsOf the 116 patients with severe CAV, 42 had RCP (RCP-CAV group) and 74 had severe angiographic CAV without RCP (Angio-CAV group). A significantly shorter time from heart transplantation to diagnosis and lower subsequent percutaneous catheter intervention after diagnosis were seen in the RCP-CAV group than in the Angio-CAV group (both p<0.001). Freedom from death or re-transplantation at 5 years was significantly worse in the RCP-CAV group compared to the Angio-CAV group (18.4% vs 35.4%, p=0.001). In the Cox proportional hazard model, RCP was independently associated with an increased risk of death or re-transplantation (hazard ratio 2.08, 95% confidence intervals 1.26–3.44, p=0.004). ConclusionsThe prognosis of patients with RCP was significantly worse than that of patients with severe angiographic CAV. The early detection of microvascular dysfunction and re-transplantation listing may improve the prognosis of patients with RCP.

Optimization of Hypercholesterolemia Treatment after Heart Transplant: The Role of PCSK9 Inhibitors.

Previous studies have reported the benefit of statins after heart transplant (HT). However, the use of high-dose statins might be limited in some HT patients due to intolerance and interactions with immunosuppression or might not be enough to achieve low-density lipoprotein (LDL) cholesterol goals. Hyperlipidemia has been associated with coronary allograft vasculopathy. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors might be a safe and effective option in HT patients with suboptimal lipid control. In a retrospective study, we identified HT patients in our center with LDL cholesterol >100 mg/dL, after diet modifications and up-titration of statins to maximum tolerated dose, treated with PCSK9i. The primary endpoint was LDL reduction one month after, and secondary endpoints were the development of donorspecific HLA antibodies (DSA) and the presence of coronary allograft vasculopathy or rejection. From January, 2018, to January, 2024, we identified five HT patients treated with PCSK9 inhibitors. In all cases, evolocumab was used. A significant reduction in LDL cholesterol was observed (151.6 ± 13.5 mg/dl to 72.4 ± 14.6 mg/dl; p = 0.04, mean reduction 75.7 ± 14.1 mg/dl), as well as in total cholesterol (231 ± 34.6 mg/dl to 152.2 ± 38.9 mg/dl; p < 0.01, mean reduction 78.8 ± 22.2 mg/dl). A significant increase in HDL cholesterol was not observed (45.4 ± 10.9 mg/dl to 46.2 ± 11.1 mg/dl; p = 0.60). One patient developed DSA five years after treatment onset. Rejection and coronary allograft vasculopathy were not observed. PCSK9 inhibitors are safe and effective in reducing LDL in HT patients. However, larger studies are needed to clarify if they can reduce the development of coronary allograft vasculopathy.

Myocardial Work by Speckle-Tracking Echocardiography in Heart Transplant Recipients: Association Between Global Work Efficiency and Coronary Allograft Vasculopathy

Coronary allograft vasculopathy (CAV) is a leading cause of morbidity and mortality following heart transplantation. CAV is often diagnosed in later stages or during routine screening in asymptomatic subjects. Myocardial work (MW), calculated using left-ventricular global longitudinal strain (LV-GLS) and systemic blood pressure, may be associated with the presence of CAV and outperform conventional echocardiographic parameters. In this retrospective observational study, heart transplant recipients undergoing regular follow-up at our Institution between May 2022 and September 2023 were enrolled. All included patients underwent speckle tracking echocardiography, including MW indices. CAV was classified according to invasive coronary angiography or computed tomography performed within 12 months of index echocardiography. We collected all available clinical and echocardiographic parameters and evaluated potential association with CAV. CAV was detected in 29/93 (31%) patients (CAV+). Of the MW indices, mean global work efficiency (GWE) was 90±6%, and was significantly lower in CAV+ than CAV- subjects (86±7% vs 91±4%, p<0,001). GWE (OR 0.86; CI 0.77-0.94, p=0.002), E/e’ ratio (OR 1.27; CI 1.08-1.52, p=0.006) and LVEF (OR 0.90; CI 0.81-0.98, p=0.017) were independently associated with the presence of CAV. GWE (GWE vs LV-GLS, delta AUC 0.154, p=0.047) and the proposed model (GWE+E/e’ vs LV-GLS, delta AUC 0.198, p=0.004) were significantly superior in stratifying incremental risk for CAV compared to LV-GLS. In conclusion GWE was observed to be independently associated with the presence of CAV. MW could represent a novel non-invasive screening method for CAV in heart transplant recipients. Larger and prospective studies are needed to confirm this hypothesis.

Early Use of Aspirin for Coronary Allograft Prophylaxis in Heart Transplant Recipients.

Coronary allograft vasculopathy (CAV) remains a significant cause of morbidity and mortality after heart transplantation. The use of aspirin for CAV prophylaxis has recently garnered interest as a possible therapeutic adjunct in this setting. This 2-center retrospective cohort study included 372 patients who underwent heart transplantation between January 2009 and March 2018 and were stratified according to the commencement of aspirin during their index transplant admission. The primary outcome was the development of moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) at surveillance coronary angiography. Secondary endpoints included mortality at follow-up. There were no differences in age, sex, and cause of heart failure. In the early aspirin group, the preponderant risk factors included use of ventricular assist devices, pretransplant smoking, and mild or moderate rejection. Multivariable analyses to assess for independent predictors of CAV development and mortality demonstrated that aspirin was associated with reduced mortality (adjusted hazard ratio = 0.19; 95% confidence interval, 0.08-0.47, P < 0.01) and a trend toward a protective effect against the development of moderate or severe CAV (adjusted hazard ratio = 0.24; 95% confidence interval, 0.54-1.19; P = 0.08). In this retrospective risk-adjusted 2-center cohort study, early aspirin administration was associated with reduced risk of death and a trend toward a protective effect against CAV development. These findings warrant validation in prospective randomized trials.

Adult Congenital Heart Disease Transplantation: Does Univentricle Physiology Impact Early Mortality?

BackgroundWith patients with congenital heart disease increasingly living into adulthood, there is a growing population of patients with adult congenital heart disease (ACHD) who have heart failure. Limited data exist on evaluating heart transplantation in this population. MethodsA retrospective review was performed of patients with ACHD who underwent heart transplantation from November 1990 to January 2023. Kaplan-Meier, cumulative incidence accounting for competing risk of death, and subgroup analyses comparing those patients with biventricular (BiV) and univentricular (UniV) physiology were performed. Data are presented as median (interquartile range [IQR]) or counts (%). ResultsA total of 77 patients with a median age of 36 years (IQR, 27-45 years) were identified, including 57 (74%) BiV and 20 (26%) UniV patients. Preoperatively, UniV patients were more likely to have cirrhosis (9 of 20 [45.0%] vs 4 of 57 [7.0%]; P < .001) and protein losing enteropathy (4 of 20 [20.0%] vs 1 of 57 [1.8%]; P = .015). Multiorgan transplantation was performed in 23 patients (30%) and more frequently in UniV patients (10 [50%] vs 13 [23%]; P = .04). Operative mortality was 6.5%, 2 of 20 (10%) among UniV patients and 2 of 57 (4%) among BiV patients (P = .276). Median clinical follow-up was 6.0 years (IQR, 1.4-13.1 years). Survival tended to be lower among UniV patients compared with BiV patients, particularly within the first year (P = .09), but it was similar for survivors beyond 1 year. At 5 years, the incidence of rejection was 28% (IQR, 17%-38%) and that of coronary allograft vasculopathy was 16% (IQR, 7%-24%). ConclusionsUnderlying liver disease and the need for heart-liver transplantation were significantly higher among UniV patients. Survival tended to be lower among UniV patients, particularly within the first year, but it was similar for survivors beyond 1 year.

A Comprehensive Excursus of the Roles of Echocardiography in Heart Transplantation Follow-Up.

Current guidelines for the care of heart transplantation recipients recommend routine endomyocardial biopsy and invasive coronary angiography as the cornerstones in the surveillance for acute rejection (AR) and coronary allograft vasculopathy (CAV). Non-invasive tools, including coronary computed tomography angiography and cardiac magnetic resonance, have been introduced into guidelines without roles of their own as gold standards. These techniques also carry the risk of contrast-related kidney injury. There is a need to explore non-invasive approaches providing valuable information while minimizing risks and allowing their application independently of patient comorbidities. Echocardiographic examination can be performed at bedside, serially repeated, and does not carry the burden of contrast-related kidney injury and procedure-related risk. It provides comprehensive assessment of cardiac morphology and function. Advanced echocardiography techniques, including Doppler tissue imaging and strain imaging, may be sensitive tools for the detection of minor myocardial dysfunction, thus providing insight into early detection of AR and CAV. Stress echocardiography may offer a valuable tool in the detection of CAV, while the assessment of coronary flow reserve can unravel coronary microvascular impairment and add prognostic value to conventional stress echocardiography. The review highlights the role of Doppler echocardiography in heart transplantation follow-up, weighting advantages and limitations of the different techniques.

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