Cardiac Allograft Vasculopathy Research Articles

Impact of co-morbidities on survival after heart transplant in females of childbearing age: analysis of the International Society for Heart and Lung Transplantation (ISHLT) Registry

Abstract Background Data on life expectancy specific to female heart transplant (HT) recipients of reproductive age are lacking, but are needed to inform shared decision making at the time of pre-conception counseling. We analyzed the ISHLT registry for post-transplant survival and studied the impact of co-morbidities in women of childbearing age. Methods Female HT recipients reported to the ISHLT registry who were aged 15–45 yrs at time of HT were included in this retrospective analysis. Primary outcome was post-transplant survival. Secondary outcomes included the impact of co-morbidities on conditional survival at 5, 10 and 15 years. Results Of 121,501 HT recipients (Jan 1992–June 2018), 30,179 (24.8%) were women. 9,229 (7.6%) were 15–45 yrs at time of HT. Overall median post-transplant survival was 15.2 yrs. Diabetes mellitus (DM) and/or severe chronic kidney disease (CKD) at HT adversely impacted long-term survival (Figure 1). Co-morbidities including cardiac allograft vasculopathy (CAV), DM and CKD negatively impacted 5yr and 10yr conditional survival, individually as well as a combination (Figure 2). 15yr conditional survival confirmed the negative impact of DM and CKD, while CAV did not reach statistical significance. Conclusion Female HT recipients of childbearing age have favorable survival post-HT. Conditional survival at 5 and 10 yrs is negatively impacted by CAV, DM and CKD. The quantification of survival outcomes after heart transplant in women of childbearing age may improve counseling as part of pre-conception informed decision making. Funding Acknowledgement Type of funding sources: None.

Characteristics, predictors and outcomes of early mTOR inhibitor use after heart transplantation: insights from the UNOS database

Abstract Background The clinical characteristics of mammalian target of rapamycin (mTOR) inhibitors use in heart transplant (HT) recipients and their outcomes have not been well described. Methods We compared patients that received mTOR inhibitors within the first 2 years after HT to patients that did not by inquiring the United Network for Organ Sharing database between 2010 and 2018. The primary endpoint was all-cause mortality with re-transplantation as a competing event. Rejection, malignancy, hospitalization for infection and renal transplantation were secondary endpoints. Results There were 1,619 (9%) and 15,686 (81%) mTORi+ and mTORi− patients respectively. Body mass index, induction, cardiac allograft vasculopathy, calculated panel reactive antibody and less days in 1A status were independently associated with mTORi+ status. Over a follow up of 10.4 years there was no difference in all cause mortality after adjusting for donor and recipient characteristics (adjusted subdistribution hazard ratio 1.03 [0.90–1.19], p=0.66) (Figure 2). mTORi+ was independently associated with increased risk for rejection (odds ratio 1.43 [1.11–1.83], p=0.005) but not for infection, malignancy or renal transplantation. Conclusion mTOR inhibitors are used in <10% patients in the first 2 years after HT and are non-inferior to contemporary immunosuppression regimens in terms of all-cause mortality, infection, malignancy or renal transplantation. They are associated with risk for rejection. Funding Acknowledgement Type of funding sources: None.

Positron emission tomography/computed tomography perfusion imaging with myocardial blood flow has diagnostic and prognostic value for cardiac allograft vasculopathy

Abstract Background Cardiac allograft vasculopathy (CAV) is a leading cause of morbidity and mortality in patients with orthotopic heart transplantation (OHT). Invasive coronary angiography is the traditional method of screening for and diagnosing CAV. Alternative non-invasive modalities have been sought to screen for CAV. A small, single-center study utilizing Positron Emission Tomography/Computed Tomography Perfusion Imaging (PET/CT) with stress myocardial blood flow (MBF) demonstrated good diagnostic and prognostic value for CAV. Purpose The purpose of this study was to validate the proposed algorithm for diagnosing and prognosticating CAV by PET/CT with stress MBF in a large and contemporary series. Methods Patients with a history of OHT with no prior revascularization in the transplanted heart who underwent PET/CT with MBF were included in the prognostic portion of the study. For the diagnostic value of PET/CT with MBF, only patients who had a PET/CT within 12 months of coronary angiography were included. The diagnostic accuracy of PET/CT was compared to the most recent coronary angiogram. A composite outcome of death, heart failure hospitalization, acute coronary syndrome, revascularization, and re-transplantation was used to validate the prognostic ability of PET/CT with MBF. Results 450 PET/CT scans with MBF were performed and included in the prognostic portion of the study. 78 patients had PET/CT within 12 months of coronary angiography and were included in the diagnostic portion. Normal perfusion with normal myocardial blood flow had a 100% negative predictive value for moderate-severe CAV by angiography. PET/CT CAV 2/3 had a positive predictive value of 69% for moderate-severe CAV. Over 24 months, there were 20 events in the 39 patients with a PET CAV grade of 2/3 versus 21 events in the 411 patients with a PET CAV grade of 0/1 with a hazard ratio 13.3 (p<0.001). Conclusions The current proposed algorithm for diagnosing CAV by PET/CT with stress MBF has excellent negative predictive value along with good positive predictive value for detecting moderate-severe CAV by coronary angiography. A PET/CT with stress MBF with CAV classification of 2/3 is associated with a poor prognosis. Funding Acknowledgement Type of funding sources: None.

Heart Transplantation With Older Donors: Should There Be an Age Cutoff?

Heart transplantation remains limited by donor availability. Currently, only some programs accept older donors, and their use remains contentious. We compared outcomes of heart transplant recipients who received donor hearts ≥55 years with those who received donor hearts <55 years. Records of first-time adult heart transplant recipients between 2010 and 2019 were reviewed. Endpoints included 30-day and 1-, 3-, and 5-year survival; freedom from cardiac allograft vasculopathy; freedom from nonfatal major adverse cardiac events; and freedom from any rejections. The effect of donor age ≥55 years was analyzed with Cox proportional hazards modeling, 1:2 propensity score matching, and Kaplan-Meier survival analysis. Sixty-six patients received donor hearts ≥55 years and 766 received donor hearts <55 years. In the unmatched cohort, there was no significant difference in survival between the 2 groups at 30 days (93.9% vs 97.3%, P=.127), 1 year (87.9% vs 91.6%, P=.325), 3 years (86.4% vs 86.5%, P=.888), or 5 years (78.8% vs 83.8%, P=.497). The ≥55 years group had a significantly lower freedom from cardiac allograft vasculopathy and fatal major adverse cardiac events. In propensity-matched patients, recipients of donors ≥55 years had similar survival and freedom from cardiac allograft vasculopathy but significantly lower 1-year (76.7% vs 88.3%, P=.026), 3-year (68.3% vs 84.2%, P=.010), and 5-year (63.3% vs 83.3%, P=.002) freedom from nonfatal major adverse cardiac events when compared to recipients of younger donors. Carefully selected older donors can be considered for a carefully selected group of recipients with acceptable outcomes.

Eplet matching in pediatric heart transplantation: The SickKids experience.

Epitope-based tissue matching may be superior to HLA antigen matching. We compared antigen to molecular-level HLA matching on outcomes following pediatric heart transplantation (HTx). This is a retrospective, single centre cohort study (2013-2020). HLA antigen and eplet mismatch analyses were performed in HTx patients <18 years old. Primary endpoint was graft loss; secondary endpoints were rejection and cardiac allograft vasculopathy (CAV). A multivariable Cox regression analysis was used to examine associations between eplet or antigen mismatching and outcomes. A logistic regression analysis was performed to examine associations between eplet or antigen mismatching and outcomes. Seventy-seven patients (40% males) were included, with a median age at HTx 4.3 years [range 0.05-18]. Median HLA class I and II eplet mismatches were 10 (1-22) and 11 (1-23). Median class I and II antigen mismatches were 5 (1-6) and 4 (0-6). 9 patients (11.7%) died [median time 4 months (range 0.1-46)]. Eight (10.4%) patients developed AMR [median time 22 days (IQR=168)]. Twenty-one patients (27.3%) had acute cellular rejection [median time 40 days (IQR=85.5)]. In univariate analysis, patients with HLA Class II DPB eplet mismatches above the median for this cohort had an increased risk of graft loss (OR 5.3 [95%CI: 1.03-27.5], p=0.039). HLA eplet mismatching was not associated with rejection; antigen mismatching was not associated with either graft loss or rejection. In multivariable analysis, patients with HLA Class II DPB eplet mismatches above the median had an increased risk of graft loss (HR 8.14 [95% CI: 1.26-49], p=0.02). HLA eplet mismatching was not associated with rejection; antigen mismatching was not associated with graft loss or rejection. A logistic regression analysis including 'number of HLA Class II DPB eplet mismatches' correctly predicted 95.8% of the outcomes. In our cohort of pediatric heart transplant recipients, the number of HLA Class II DPB eplet mismatches was associated with graft loss. Molecular-level HLA matching is an emerging tool for graft loss risk stratification, but further study is required.

IMMUNOENGINEERING APPLICATION OF MXENE FOR PREVENTION OF TRANSPLANT VASCULOPATHY

Cardiac allograft vasculopathy is an aggressive form of atherosclerosis and a major cause of mortality among patients with heart transplants. Blood vessel endothelial cells stimulate alloreactive T-lymphocytes to result in sustained inflammation. MXenes are an emerging class of nanomaterials that have significantly outperformed several existing biomaterials as anti-cancer agents, biosensors, and in anti-microbial therapies. Herein, we report the first application of titanium carbide (Ti3C2Tx) MXene nanosheets for prevention of allograft vasculopathy.

CARDIAC ALLOGRAFT VASCULOPATHY AND SURVIVAL IN PEDIATRIC HEART TRANSPLANT RECIPIENTS TRANSITIONED TO ADULT CARE

Cardiac allograft vasculopathy (CAV) is an important cause of mortality after pediatric heart transplantation (HT) but there is a paucity of data regarding its incidence and impact on survival in children once they reach adulthood. Differences in outcomes according to transplant era are also not well characterized. Our objectives were to describe the incidence of CAV overall and according to transplant era and to evaluate the impact of CAV on mortality in pediatric HT recipients transitioned to adult care.

Noninvasive Physiologic Assessment of Cardiac Allograft Vasculopathy Is Prognostic for Post-Transplant Events

BackgroundCardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial coronary arteries and the microvasculature. A leading cause of post-transplant mortality, CAV affects 50% of heart transplant recipients within 10 years of heart transplant. ObjectivesThis analysis examined the outcomes of heart transplant recipients with reduced myocardial blood flow reserve (MBFR) and microvascular CAV detected by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging. MethodsA total of 181 heart transplant recipients who underwent PET to assess for CAV were included with a median follow-up of 4.7 years. Patients were classified into 2 groups according to the total MBFR: >2.0 and ≤2.0. Microvascular CAV was defined as no epicardial CAV detected by PET and/or coronary angiography, but with an MBFR ≤2.0 by PET. ResultsIn total, 71 (39%) patients had an MBFR ≤2.0. Patients with an MBFR ≤2.0 experienced an increased risk for all outcomes: 7-fold increase in death or retransplantation (HR: 7.05; 95% CI: 3.2-15.6; P < 0.0001), 12-fold increase in cardiovascular death (HR: 12.0; 95% CI: 2.64-54.12; P = 0.001), and 10-fold increase in cardiovascular hospitalization (HR: 10.1; 95% CI: 3.43-29.9; P < 0.0001). The 5-year mean survival was 302 days less than those with an MBFR >2.0 (95% CI: 260.2-345.4 days; P < 0.0001). Microvascular CAV (adjusted HR: 3.86; 95% CI: 1.58-9.40; P = 0.003) was independently associated with an increased risk of death or retransplantation. ConclusionsAbnormal myocardial blood flow reserve, even in the absence of epicardial CAV, identifies patients at a high risk of death or retransplantation. Measures of myocardial blood flow provide prognostic information in addition to traditional CAV assessment.

Cardiac allograft vasculopathy in a long-term follow-up after heart transplantation: Role of remnant cholesterol in residual inflammation.

BackgroundCardiac allograft vasculopathy (CAV) is a major prognosis limiting factor in heart transplantation (HTx). Disease development and progression are influenced by multiple determinants, but the role of remnant cholesterol (RC) in CAV has not yet been investigated. Therefore, the present study aimed to assess the prevalence of CAV in a very long-term follow-up after orthotopic HTx and to examine the role of RC in residual inflammation despite secondary prevention.MethodsHerein, is a retrospective analysis of patient data collected at the last follow-up visit in an outpatient setting. Additionally, RC levels were calculated based upon cholesterol profile.ResultsThe study population consisted of 184 patients with a mean follow-up of 15.0 ± 6.8 years. More than 40% of the overall cohort had CAV at last follow-up. The mean RC was 27.1 ± 14.7 mg/dL. Patients with CAV had significantly elevated RC despite intensified statin treatment (p = 0.018). A positive correlation was observed between RC and interleukin-6 as a marker of residual inflammation. Elevated RC and prolonged follow-up emerged as significant factors related to CAV in a multivariate analysis (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.5–5.5, p = 0.001 and OR 3.3, 95% CI 1.4–7.7, p = 0.006, respectively), whereas mycophenolate mofetil was inversely associated with CAV (OR 0.4, 95% CI 0.2–0.9, p = 0.034).ConclusionsRemnant cholesterol has proinflammatory properties and is associated with CAV development in HTx. Thus, RC should be concerned as an additional tool for risk assessment.

Validation of a semi-automatic software for optical coherence tomography - analysis in heart transplanted patients.

Optical Coherence Tomography (OCT) is an intravascular imaging modality enabling detailed evaluation of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). However, its clinical application remains hampered by time-consuming manual quantitative analysis. We aimed to validate a semi-automated quantitative OCT analysis software (Iowa Coronary Wall Analyzer, ICWA-OCT) to improve OCT-analysis in HTx patients. 23 patients underwent OCT evaluation of all three major coronary arteries at 3months (3M) and 12months (12M) after HTx. We analyzed OCT recordings using the semiautomatic software and compared results with measurements from a validated manual software. For semi-automated analysis, 31,228 frames from 114 vessels were available. The validation was based on a subset of 4287 matched frames. We applied mixed model statistics to accommodate the multilevel data structure with method as a fixed effect. Lumen (minimum, mean, maximum) and media (mean, maximum) metrics showed no significant differences. Mean and maximum intima area were underestimated by the semi-automated method (β-methodmean = -0.289 mm2, p < 0.01; β-methodmax = -0.695 mm2, p < 0.01). Bland-Altman analyses showed increasing semi-automatic underestimation of intima measurements with increasing intimal extent. Comparing 3M to 12M progression between methods, mean intimal area showed minor underestimation (β-methodmean = -1.03 mm2, p = 0.04). Lumen and media metrics showed excellent agreement between the manual and semi-automated method. Intima metrics and progressions from 3M to 12M were slightly underestimated by the semi-automated OCT software with unknown clinical relevance. The semi-automated software has the future potential to provide robust and time-saving evaluation of CAV progression.

Cardiac Allograft Vasculopathy Evaluation by Optical Coherence Tomography

Cardiac allograft vasculopathy (CAV) is a rapidly progressive form of atherosclerosis and it is the common cause of late allograft dysfunction and death in patients following orthotopic heart transplantation. After heart transplantation, patients lack adequate anginal mechanisms and may present with refractory heart failure and sudden cardiac death, so regular screening is required to detect CAV. CAV narrows the coronary arteries in diffuse concentric pattern, so detection by coronary angiogram is difficult. Intravascular imaging such as optical coherence tomography (OCT) and intravascular ultrasound is most sensitive diagnostic test for the detection of CAV. Once CAV is diagnosed, patients should be on statins, adequate immunosuppressive medications such as sirolimus, everolimus in focal lesions angioplasty, and stenting can be done, but in some patients with significant burden of CAV, retransplantation is the only available option. Once CAV is diagnosed, regular surveillance of heart function is mandatory. We are reporting a case of CAV evaluation by OCT.

315.14: The Stem Cell Mobilizator Plerixafor Reduces Transplant Vasculopathy in a Murine Aortic Allograft Model

Purpose: Effector and regulatory T cells (Tregs) are main cell populations in the context of cardiac allograft vasculopathy (CAV). The immunostimulant plerixafor mobilizes hematopoietic stem cells and may boost T cell. Therefore, the aim of this study was to evaluate if a single or repeated application as well as continuous treatment with plerixafor increases peripheral bone marrow derived stem cells including Tregs leading to tolerance induction and thus reducing chronic rejection in a mouse allograft transplant model. Methods: Fully allogeneic mouse aortas from C57BL/6 mice (H2b) were abdominally transplanted into CBA mice (H2k). The continuous plerixafor application [1mg/kg/d] was carried out for 14 days using implanted small osmotic pumps. Single dose (s.c.) injection of 1mg/kg/d or 5mg/kg/d were done at day 1 after transplantation (Tx.) and pulsed injections [1mg/kg/d] were conducted on days 1, 7, 14, and 21 after Tx. The control allograft group received vehicle loaded osmotic pumps. Stem cell mobilization was monitored by FACS. Recipients were sacrificed on day 14 for intragraft gene expression analysis or on day 30 for histological measurements. Results: Murine aortic grafts with pulsed plerixafor injections showed significantly reduced neointima proliferation compared to control allografts (33.65%±8.84% vs.53.13% ±12.41%; p<0.05). The single shot and continuous treatment groups exhibited no improvement concerning neointima formation vs. the untreated group. First FACS analysis revealed significantly less hematopoietic stem cells (HSC) in the bone marrow of plerixafor treated mice vs. the control at day 14 after Tx. Though, there were significantly more HSCs in the peripheral blood on day 30 after Tx, with the pulsed injection even doubling HSCs [0.0152%±0.008; p < 0.005 (pulsed); 0.0046%±0.002%; p < 0.01 (pump); 0.0076%±0.001%; p < 0.01 (single dose of 1mg/kg); 0.0039%±0.0017%; p < 0.1 (single dose of 5mg/kg) vs. 0.0018%±0.0016% (control)]. Intragraft gene expression results showed clearly reduced IFNγ expression and a significantly increase of IL-4, IL-10 and TGFβ. Conclusion: The data suggests that pulsed, continued and single dose application of plerixafor leads to potent stem cell mobilization and hereby the repeated treatment with plerixafor reduces neointima formation in a mouse aortic transplant model. Manfred-Roth Stiftung. Forschungsstiftung Medizin, FAU Erlangen-Nürnberg.

Characteristics, Predictors, and Outcomes of Early mTOR Inhibitor Use After Heart Transplantation: Insights From the UNOS Database.

BackgroundThe clinical characteristics of mTOR (mammalian target of rapamycin) inhibitors use in heart transplant recipients and their outcomes have not been well described.Methods and ResultsWe compared patients who received mTOR inhibitors within the first 2 years after heart transplantation to patients who did not by inquiring the United Network for Organ Sharing (UNOS) database between 2010 and 2018. The primary end point was all‐cause mortality with retransplantation as a competing event. Rejection, malignancy, hospitalization for infection, and renal transplantation were secondary end points. There were 1619 (9%) and 15 686 (81%) mTOR inhibitors+ and mTOR inhibitors− patients, respectively. Body mass index, induction, cardiac allograft vasculopathy, calculated panel reactive antibody, and fewer days in 1A status were independently associated with mTOR inhibitors+ status. Over a follow‐up of 10.4 years, there was no difference in all‐cause mortality after adjusting for donor and recipient characteristics (adjusted subdistribution hazard ratio, 1.03 [0.90–1.19]; P=0.66). mTOR inhibitors+ were independently associated with increased risk for rejection (odds ratio [OR], 1.43 [1.11–1.83]; P=0.005) and basal skin cancer (OR, 1.35 [1.19–1.51]; P=0.012) but not for infection or renal transplantation.ConclusionsmTOR inhibitors are used in <10% patients in the first 2 years after heart transplantation and are noninferior to contemporary immunosuppression regimens in terms of all‐cause mortality, infection, malignancy, or renal transplantation. They are associated with risk for rejection.

Comparison of mid-term clinical outcome in heart transplantation patients using mycophenolate mofetil vs. enteric-coated mycophenolate sodium.

BackgroundMycophenolate mofetil (MMF) is a prodrug of mycophenolic acid (MPA) and a key immunosuppressant for improving graft survival in patients with heart transplantation (HTx). However, dose reduction or interruption is occasionally needed due to gastrointestinal (GI) side effects. Enteric-coated mycophenolate sodium (EC-MPS) is an alternative form of MPA delivery to improve GI tolerability. In the present study, the efficacy of EC-MPS compared with MMF in HTx patients was investigated.MethodsIn this retrospective study, the Korean Organ Transplant Registry (KOTRY) data were used to analyze the efficacy and rejection rate of MMF and EC-MPS. A total of 611 patients was enrolled from 2014 to February of 2021. Patients were divided based on the use of MMF or EC-MPS at 6 months post-HTx. Patients who were not prescribed MMF or EC-MPS were excluded. Graft survival, all-cause mortality, and treated rejection were compared between the two groups. All statistical analyses were performed using SPSS; characteristics were compared using Pearson chi-square test and survival rate with Kaplan-Meier plot and log-rank test.ResultsA total of 510 HTx patients was analyzed (mean age: 51.74 ± 13.16 years, males: 68.2%). At 6 months after HTx, 78 patients were taking EC-MPA (12.8%) and 432 patients were taking MMF (70.7%). The median follow-up was 42.0 months (IQR: 21.7–61.0 months). Post-HTx outcomes including overall survival, all cause mortality, acute cell mediated rejection (ACR), acute antibody mediated rejection (AMR), treated rejection, and cardiac allograft vasculopathy (CAV) were comparable between the two groups during follow-up.ConclusionNotable differences were not observed in overall survival, all cause mortality, ACR, AMR, treated rejection, and CAV between MMF and EC-MPS groups. Efficacy of EC-MPS was similar to that of MMF in HTx patients during mid-term follow up after HTx.

Humoral response to heterologous prime-booster vaccination in heart transplant recipients aged 18-70 years primed with a viral vector SARS-CoV-2 vaccine.

Solid organ transplant recipients have demonstrated a blunted immune response to standard 2‐dose vaccination against SARS‐CoV‐2. This study sought to determine the humoral response to heterologous booster vaccination (viral vector vaccine dose 1 and 2 + mRNA booster). Heart transplant recipients, aged 18 to 70 years of age who initially received two doses of the viral vector ChAdOx1 nCoV‐19 vaccine followed by a BNT162b2 mRNA booster were recruited. A detectable antibody response in the absence of prior SARS‐CoV‐2 was the primary outcome measured. This was defined as an anti‐spike titre of ≥0.8 U/mL on the Elecsys anti‐SARS‐CoV‐2 S immunoassay. A total of 80 heart transplant patients (mean age 49 ± 13 years, 28% female) were included. Blood samples were drawn at a median of 30 (IQR 28‐33) days after the BNT162b2 mRNA booster. The frequency of a detectable antibody response increased from 37.5% (n = 30) after dose 2 to 56% (n = 45) post dose 3 (p < 0.001). A non‐detectable antibody response was significantly more common in recipients with a shorter time interval from transplantation (p < 0.001), lower likelihood of cardiac allograft vasculopathy (p = 0.003) and in those prescribed a triple versus dual immunosuppressant regime (p = 0.009) and a tacrolimus versus cyclosporine basedregimen (p = 0.007). Despite heterologous prime‐booster vaccination 44% of this vulnerable population ultimately continue to have no detectable antibodies.

Epicardial fat volume is related to the degree of cardiac allograft vasculopathy

ObjectivesIncreasing evidence suggests a role for epicardial fat in the development of coronary artery disease in the general population. Heart transplantation patients are at increased risk of developing a specific form of coronary artery disease, cardiac allograft vasculopathy (CAV), which has far-reaching consequences in terms of morbidity and mortality. Until now, the role of epicardial fat volume (EFV) in the development of CAV remains unknown. Hence, we investigated the relationship between EFV and CAV as well as the influence of donor/recipient sex on EFV.MethodsAdult heart transplant patients who underwent coronary computed tomography angiography (CCTA) for CAV screening who were four or more years post-HT were included. Using the CT examinations, we quantified the EFV and the degree of CAV. Ordinal and linear regression models were used to assess the association of EFV with CAV.ResultsIn total, 149 (median age 44.5 years, 36% women) patients were included. The median time between HT and the CT scan was 11.0 (7.3–16.1) years. CAV grade 0, 1, 2 and 3 were seen in 85 (57%), 32 (22%), 14 (9%), and 18 (12%) patients, respectively. The median EFV was 208.4 (128.9–276.0) mL. Larger EFV were related to higher degrees of CAV (median of 164.7 to 290.6 mL for CAV grade 0 and 3, respectively, OR 5.23 (2.47–11.06), p < 0.001). Male recipients had significantly more EFV than female recipients irrespective of the donor sex (232.7 mL vs. 147.2 mL respectively, p < 0.001). Determinants for EFV were recipient sex, number of rejections, donor age, time between HT and CT scan, recipient BMI, and diabetes mellitus.ConclusionsEFV was associated with higher degrees of CAV. The recipient sex influenced the EFV more than the donor sex.Key Points• Patients after heart transplantation have a high amount of epicardial fat while larger amounts of epicardial fat are related to higher grades of cardiac allograft vasculopathy.• Determinants of higher epicardial fat volume included recipient sex, number of rejections, donor age, time between HT and CT scan, recipient BMI, and diabetes mellitus.• Longitudinal studies are needed to further disentangle the role of epicardial fat in the development and progression of cardiac allograft vasculopathy.Graphical abstractDemonstration of four patients (from CAV grade 0 to CAV grade 3) in whom epicardial fat volume was determined. In red, the voxels identified as epicardial fat.

Early trends in cardiac allograft vasculopathy after implementation of the 2018 donor heart allocation policy in the United States

Study ObjectiveTo evaluate the impact of the new donor heart allocation system implemented in the United States in October 2018 on development of early cardiac allograft vasculopathy (CAV). DesignRetrospective cohort study. ParticipantsAdult (≥ 18 years) heart transplant recipients registered in the United Network for Organ Sharing database between October 18, 2015 and October 17, 2018 (old system) and October 18, 2018 and May 31, 2020 (new system). Main Outcome MeasureIncidence of angiographic CAV at 1 year (accelerated CAV) in the overall transplant population and among the highest acuity subgroup—Status 1A (old) and Status 1 or 2 (new). We included recipient and donor demographic, cardiovascular, and transplant factors in multivariable logistic regression models to identify predictors of accelerated CAV. ResultsOf 10,375 transplant recipients, 6,660 (64%) and 3,715 (36%) were listed in the old and new allocation cohorts, respectively. The incidence of accelerated CAV was 521 (8%) in the old period compared with 272 (7%) in the new period (P = .36). Similar incidence rates were observed in the highest acuity subgroup—363 (8%) compared with 143 (7%), respectively (P = .13). In adjusted analyses of the high-acuity cohort, the new allocation system was not associated with a higher likelihood of accelerated CAV (odds ratio = 0.87, 95% confidence interval: 0.70-1.08, P = .20). ConclusionsThe new donor heart allocation system is not associated with development of accelerated angiographic CAV at 1 year, including among recipients requiring the most urgent transplants.

Long-term efficacy of everolimus as de novo immunosuppressant on the cardiac allograft vasculopathy in heart transplant recipients

Background and aimsData on the long-term effects of everolimus (EVL) on the de novo immunosuppression of heart transplant (HT) recipients with progressive cardiac allograft vasculopathy (CAV) and vascular remodeling are lacking. Hence, in this study, we aimed to determine the long-term safety and efficacy of EVL as a de novo immunosuppressant therapy for CAV progression and the clinical outcomes after HT. MethodsWe retrospectively reviewed the medical records of 144 HT recipients who survived for at least one year after HT. CAV progression was assessed via serial coronary intravascular ultrasonography (IVUS) in recipients who underwent at least two IVUS studies. ResultsA significant attenuation in the percentage of the atheroma volume progression was observed in those who took EVL (1.2%) compared with those who took cyclosporin (CSA; 7.3%; p = 0.005 vs. EVL) or tacrolimus (TAC; 6.6%; p = 0.0052 vs. EVL) at 1 year after HT. This trend persisted for the next 3 and 5 years after HT. Moreover, the remodeling index was greater in the EVL (1.08) group than in the CSA (0.23) or TAC (−0.25) groups 1 year after HT. The results of the Kaplan–Meier analysis over a median follow-up period of 8 years revealed that there was no statistical difference in the primary endpoint between the three groups. ConclusionsDe novo immunosuppression with EVL is associated with attenuated CAV progression for the first 5 years of follow-up via IVUS. Moreover, EVL has comparable long-term clinical outcomes to those of CSA- or TAC-based protocols.

Non-invasive Imaging in the Evaluation of Cardiac Allograft Vasculopathy in Heart Transplantation: A Systematic Review.

Cardiac allograft vasculopathy (CAV) is the leading cause of long-term graft dysfunction in patients with heart transplantation and is linked with significant morbidity and mortality. Currently, the gold standard for diagnosing CAV is coronary imaging with intravascular ultrasound during traditional invasive coronary angiography. Invasive imaging, however, carries increased procedural risk and expense to patients in addition to requiring an experienced interventionalist. With the improvements in non-invasive cardiac imaging modalities such as transthoracic echocardiography, computed tomography, magnetic resonance imaging and positron emission tomography, an alternative non-invasive imaging approach for the early detection of CAV may be feasible. In this systematic review, we explored the literature to investigate the utility of non-invasive imaging in diagnosis of CAV in >3000 patients across 49 studies. We also discuss the strengths and weaknesses for each imaging modality. Overall, all 4 imaging modalities show good to excellent accuracy for identifying CAV with significant variations across studies. Majority of the studies compared non-invasive imaging with invasive coronary angiography without intravascular imaging. In summary, non-invasive imaging modalities offer an alternative approach to invasive coronary imaging for CAV. Future studies should investigate longitudinal non-invasive protocols in low-risk patients after heart transplantation.

Feasibility and Safety of Coronary Angiography via Radial Approach in Cardiac Transplant Recipients: A Single Center Experience.

Coronary angiography remains the gold standard post-transplant screening test for cardiac allograft vasculopathy. This procedure has traditionally been performed via femoral approach. Data on safety and efficacy of radial approach in cardiac transplant patients remains scarce. Single center retrospective study including all cardiac transplant patients who underwent coronary angiography via transradial approach (TRA) or transfemoral approach (TFA). Safety and efficacy outcomes were compared between the 2 groups. Primary end points included major bleeding, vascular complications, crossover to femoral approach, contrast use and radiation exposure. A total of 201 patients were included. 96 patients (47.8%) underwent angiography via TRA. At baseline, no significant differences with regards to age, gender, or traditional risk factors such as HTN, DM, hyperlipidemia were noted between the 2 groups. Most patients underwent intravascular ultrasound (n = 179, 89%) with no statistically significant differences between the 2 groups (TRA: 90.6% vs TFA: 87.6%, P = 0.5). Additionally, there were no statistically significant differences in radiation exposure, amount of contrast use and fluoroscopy time between the 2 groups. Although there were trends toward increased bleeding among TFA group, these were not statistically significant and were mostly driven by access site hematomas. Use of TRA increased over time and Conversion from TRA to TFA was low (n = 4, 4.2%). Coronary angiography via the radial approach in cardiac transplant recipients is feasible, safe and is associated with low a risk of bleeding with no significant increase in radiation exposure when compared to the traditional femoral approach.