Cardiac Allograft Vasculopathy Research Articles

Role of HLA matching and donor specific antibody development in long-term survival, acute rejection and cardiac allograft vasculopathy

Although there are different data supporting benefits of HLA matching in kidney transplantation, its role in heart transplantation is still unclear. HLA mismatch (MM) between donor and recipient can lead to the development of donor-specific antibodies (DSA) which produces negative events on the outcome of heart transplantation. Moreover, DSAs are involved in the development of antibody-mediated rejection (AMR) and are associated with an increase in cardiac allograft vasculopathy (CAV). In this study it is analyzed retrospectively the influence of HLA matching and anti-HLA antibodies on overall survival, AMR and CAV in heart transplantation. For this retrospective study are recruited heart transplanted patients at the Cardiac Transplantation Centre of Naples between 2000 and 2019. Among the 155 heart transplant patients, the mean number of HLA-A, B, -DR MM (0 to 6) between donor and recipient was 4.5 ± 1.1. The results show a negative association between MM HLA-DR and survival (p = 0.01). Comparison of patients with 0–1 MM at each locus to all others with 2 MM, for both HLA class I and class II, has not showed significant differences in the development of CAV. Our analysis detected DSA in 38.1% of patients. The production of de novo DSA reveals that there is not an influence on survival (p = 0.72) and/or AMR (p = 0.39). Instead, there is an association between the production of DSA class II and the probability of CAV development (p = 0.03). Mean fluorescence intensity (MFI) values were significantly higher in CAV-positive patients that CAV-negative patients (p = 0.02). Prospective studies are needed to evaluate HLA class II matching as an additional parameter for heart allocation, especially considering the increment of waiting list time.

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.

Three-year outcomes of de novo tacrolimus extended-release tablets (LCPT) compared to twice-daily tacrolimus in adult heart transplantation

BackgroundExtended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. Methods25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. ResultsLCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, −37%, −1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. ConclusionLCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients.

Cardiac allograft vasculopathy outcomes among donation after circulatory death heart transplant recipients

Cardiac allograft vasculopathy accounts for significant long-term morbidity and mortality in heart transplant recipients; limited data exists for donation after circulatory death. Intravascular ultrasound assessment is a gold standard for early diagnosis of CAV and has strong prognostic power. We evaluated all consecutive circulatory and brain death heart transplant recipients from January 2020 to March 2022. Patients were followed for need for percutaneous coronary intervention, development of severe allograft vasculopathy or death. Among 143 heart transplant recipients, 39 received circulatory death and 104 received brain death hearts. Baseline characteristics were similar between groups: median age (56.3 vs 53.7 years, p = 0.290), female sex (15% vs 26%, p = 0.265) and sirolimus use (69% vs 53%, p = 0.116). At 1 year, there were no significant differences in maximal intimal thickness (0.49 vs. 0.46 mm, p = 0.861) or Stanford classification. During a median follow-up of 793 days [IQR 618, 1003], there was no difference in the unadjusted or adjusted primary composite outcome of death, PCI, or ISHLT cardiac allograft vasculopathy MIT > 0.6mm (unadjusted HR 0.42, 95% CI: 0.05, 3.48, p = 0.42), event rate 9.6% vs 2.6%, p= 0.29, nor was there a difference in death, PCI or severe IVUS disease (HR 1.44, 95% CI 0.81, 2.56, p = 0.21). In DCD heart transplant recipients, circulatory death donors did not have a significantly higher risk for coronary allograft vasculopathy by IVUS or related complications at one year following transplantation.

Enhancing the Prediction of Cardiac Allograft Vasculopathy Using Intravascular Ultrasound and Machine Learning: A Proof of Concept.

Cardiac allograft vasculopathy (CAV) is the leading cause of late graft dysfunction in heart transplantation. Building on previous unsupervised learning models, we sought to identify CAV clusters using serial maximal intimal thickness and baseline clinical risk factors to predict the development of early CAV. This is a single-center retrospective study including adult heart transplantation recipients. A latent class mixed-effects model was used to identify patient clusters with similar trajectories of maximal intimal thickness posttransplant and pretransplant covariates associated with each cluster. Among 186 heart transplantation recipients, we identified 4 patient phenotypes: very low, low, moderate, and high risk. The 5-year risk (95% CI) of the International Society for Heart and Lung Transplantation-defined CAV in the high, moderate, low, and very low risk groups was 49.1% (35.2%-68.5%), 23.4% (13.3%-41.2%), 5.0% (1.3%-19.6%), and 0%, respectively. Only patients in the moderate to high risk cluster developed the International Society for Heart and Lung Transplantation CAV 2-3 at 5 years (P=0.02). Of the 4 groups, the low risk group had significantly younger female recipients, shorter ischemic time, and younger female donors compared with the high risk group. We identified 4 clusters characterized by distinct maximal intimal thickness trajectories. These clusters were shown to discriminate against the development of angiographic CAV. This approach allows for the personalization of surveillance and CAV-directed treatment before the development of angiographically apparent disease.

Long-term post-transplantation outcomes in patients with hypertrophic cardiomyopathy: Single-center 35-year experience.

Heart transplantation (HT) is the only option for most patients with end-stage heart failure and hypertrophic cardiomyopathy (HCM) who fail medical therapy. Data on the long-term outcomes post-transplant in HCM individuals remain scarce. We analyzed data of 319 adult patients who underwent HT between 1984 and 2019. Patients were followed for cardiac allograft rejection, cardiac allograft vasculopathy (CAV), death, or re-transplantation. Outcomes of 24 patients with HCM, 160 with ischemic, and 135 with dilated cardiomyopathy were compared. During a mean follow-up of 11.6±7.2 (max 27.8), 16.7±8.2 (max 32.7), and 16.1±9.7 (max 34.6) years after HT in hypertrophic, ischemic, and dilated cardiomyopathy groups, respectively: 10-year survival rate was 67%, 62%, 69%, respectively (p=.04). Post-transplantation, HCM individuals more often than the other two studied groups required prolonged inotropic support (37%, 12%, 17%, respectively, p=.02), temporary mechanical circulatory support (45%, 13%, 14%, respectively, p<.01), and renal replacement therapy immediately post-HT (55%, 19%, 24%, respectively, p<.01). No significant inter-group differences were noted in the 10-year freedom from acute allograft rejection (38%, 46%, 43%, respectively, p=.38) or 10-year freedom from CAV (88%, 78%, 81%, respectively, p=.57). The long-term post-transplant prognosis of adult patients with hypertrophic cardiomyopathy is favorable despite more challenging immediate post-HT course.

Heart transplantation and biomarkers: a review about their usefulness in clinical practice.

Advanced heart failure (AdvHF) can only be treated definitively by heart transplantation (HTx), yet problems such right ventricle dysfunction (RVD), rejection, cardiac allograft vasculopathy (CAV), and primary graft dysfunction (PGD) are linked to a poor prognosis. As a result, numerous biomarkers have been investigated in an effort to identify and prevent certain diseases sooner. We looked at both established biomarkers, such as NT-proBNP, hs-troponins, and pro-inflammatory cytokines, and newer ones, such as extracellular vesicles (EVs), donor specific antibodies (DSA), gene expression profile (GEP), donor-derived cell free DNA (dd-cfDNA), microRNA (miRNA), and soluble suppression of tumorigenicity 2 (sST2). These biomarkers are typically linked to complications from HTX. We also highlight the relationships between each biomarker and one or more problems, as well as their applicability in routine clinical practice.

Paediatric heart transplantation: life-saving but not yet a cure.

In the 1980s, heart transplantation was the first successful treatment for infants born with hypoplastic left heart syndrome. Infants who have required heart transplantation benefit from immunologic "advantages," including long-term survival free from cardiac allograft vasculopathy. Currently ∼ 90% of children undergoing a heart transplant are reaching their first-year anniversary and the clinical practices of paediatric heart transplantation have dramatically improved. These successes are largely attributed to research sponsored by the Pediatric Heart Transplant Study Group, the International Society of Heart and Lung Transplantation and, more recently, the Non-profits Enduring Hearts and Additional Ventures. Despite these successes, the field is challenged to increase progress to achieve long-term survival into adulthood. The wait-list mortality, especially among infants, is unacceptably high often leading to palliative measures that can increase post-transplant mortality. Cardiac allograft vasculopathy remains a major cause for progressive graft loss of function and sudden death. The relative tolerance seen in immature recipients has not been translated to modifying older recipients' post-transplant outcomes. The modifiable cause(s) for the increased risks of transplantation in children of different ethnicities and races require definition. Addressing these challenges faces the reality that for-profit research favours funding adult recipients, with ∼ 10-fold greater numbers, and their more modest longevity goals. Advocacy for funding "incentives" such as the Orphan Drug rules in the United States and upholding principles of equity and inclusion are critical to addressing the challenges of paediatric heart transplant recipients worldwide.

Frequency of screening for cardiac allograft vasculopathy: warranty period of initial low risk positron emission tomography.

The short-term risk of moderate-severe cardiac allograft vasculopathy (CAV) after a low-risk positron emission tomography/computed tomography (PET/CT) is unknown, and therefore, there is no guidance on how frequently to perform screening. The aim of this study was to assess the rate of progression to moderate-severe CAV as part of an annual screening programme. Patients with no history of CAV 2/3 and a low-risk result on initial screening PET/CT (CAV 0/1) were enrolled in the study. The primary outcome was the progression to CAV 2/3 as part of an annual screening programme (within 6-18 months of initial scan). PET CAV results were graded according to a published and externally validated diagnostic criterion for CAV. Over the study period, 231 patients underwent an initial PET/CT and had a subsequent evaluation for CAV. In this cohort, 4.3% of patients progressed to CAV 2/3 at a median of 374 days (interquartile range 363-433). Initial PET CAV grade was the most significant patient characteristic associated with the progression of CAV, with 17% of patients with PET CAV 1 progressing to CAV 2/3 compared with 1.6% with PET CAV 0 (odds ratio 12.4, 95% confidence interval 3.06-50.3). The rate of progression to moderate-severe CAV at 1 year after the lowest-risk PET/CT is low, but approximately 1/6 patients with PET CAV 1 progress to CAV 2/3. Annual screening with PET/CT for select patients with PET CAV 0 may not be warranted. The optimal screening interval awaits confirmation of our findings in multi-centre registries.

Spatial multiomics of arterial regions from cardiac allograft vasculopathy rejected grafts reveal novel insights into the pathogenesis of chronic antibody-mediated rejection

Cardiac allograft vasculopathy (CAV) causes late graft failure and mortality after heart transplantation. Donor-specific antibodies (DSAs) lead to chronic endothelial cell injury, inflammation, and arterial intimal thickening. In this study, GeoMx digital spatial profiling was used to analyze arterial areas of interest (AOIs) from CAV+DSA+ rejected cardiac allografts (N = 3; 22 AOIs total). AOIs were categorized based on CAV neointimal thickening and underwent whole transcriptome and protein profiling. By comparing our transcriptomic data with that of healthy control vessels of rapid autopsy myocardial tissue, we pinpointed specific pathways and transcripts indicative of heightened inflammatory profiles in CAV lesions. Moreover, we identified protein and transcriptomic signatures distinguishing CAV lesions exhibiting low and high neointimal lesions. AOIs with low neointima showed increased markers for activated inflammatory infiltrates, endothelial cell activation transcripts, and gene modules involved in metalloproteinase activation and TP53 regulation of caspases. Inflammatory and apoptotic proteins correlated with inflammatory modules in low neointima AOIs. High neointima AOIs exhibited elevated TGFβ-regulated transcripts and modules enriched for platelet activation/aggregation. Proteins associated with growth factors/survival correlated with modules enriched for proliferation/repair in high neointima AOIs. Our findings reveal novel insight into immunological mechanisms mediating CAV pathogenesis.

Safety and efficacy of everolimus-eluting bioresorbable vascular scaffold for cardiac allograft vasculopathy (CART).

Cardiac allograft vasculopathy (CAV) is still the main drawback of heart transplantation (HTx) and percutaneous coronary intervention (PCI) is a palliative measure because of the high incidence of failure. This study aimed to investigate the safety and efficacy of bioresorbable scaffolds (BRSs) as potential novel therapeutic tool for the treatment of coronary stenoses in CAV. This is a multicenter, single-arm, prospective, open-label study (CART, NCT02377648), that included patients affected by advanced CAV treated with PCI and second-generation ABSORB BRS (Abbott Vascular). The primary endpoint was the incidence of 12-month angiographic in-segment scaffold restenosis (ISSR). Secondary endpoints were the incidence of major adverse cardiac events (MACEs) at 12- and 36-month follow-up and the incidence of ISSR at 36months. A paired intracoronary imaging analysis at baseline and follow-up was also performed. Between 2015 and 2017 35 HTx patients were enrolled and treated for 44 coronary lesions with 51 BRSs. The primary endpoint occurred in 13.5% of the lesions (5/37), with a cumulative ISSR rate up to 3years of 16.2% (6/37). Angiographic lumen loss was 0.40 ± 0.62mm at 12months and 0.53 ± 0.57mm at 36months. Overall survival rate was 91.4% and 74.3%, and MACEs incidence 14.2% and 31.4% at 12 and 36months, respectively. At the paired intracoronary imaging analysis, a significant increase of the vessel external elastic membrane area in the treated segment and some progression of CAV proximally to the BRS were detected. BRS-based PCI for the treatment of CAV is feasible and safe, with an ISSR incidence similar to what reported in retrospective studies with drug-eluting stents.

Kiosk 9R-FB-07 - Safety and Feasibility of Adenosine Stress CMR in Heart Transplant Recipients with Suspected Cardiac Allograft Vasculopathy

Kiosk 9R-FB-07 - Safety and Feasibility of Adenosine Stress CMR in Heart Transplant Recipients with Suspected Cardiac Allograft Vasculopathy

Cardiac magnetic resonance assessment of acute rejection and cardiac allograft vasculopathy in pediatric heart transplant

In pediatric heart transplant (PHT), cardiac catheterization with endomyocardial biopsy (EMB) is standard for diagnosing acute rejection (AR) and cardiac allograft vasculopathy (CAV) but is costly and invasive. To evaluate the ability of cardiac magnetic resonance (CMR) to noninvasively identify differences in PHT patients with AR and CAV. Patients were enrolled at three children's hospitals. Data were collected from surveillance EMB or EMB for-cause AR. Patients were excluded if they had concurrent diagnoses of AR and CAV, CMR obtained >7days from AR diagnosis, they had EMB negative AR, or could not undergo contrasted, unsedated CMR. Kruskal-Wallis test was used to compare groups: (1) No AR or CAV (Healthy), (2) AR, (3) CAV. Wilcoxon rank-sum test was used for pairwise comparisons. Fifty-nine patients met inclusion criteria (median age 17years [IQR 15-19]) 10 (17%) with AR, and 11 (19%) with CAV. AR subjects had worse left ventricular ejection fraction compared to Healthy patients (p=0.001). Global circumferential strain (GCS) was worse in AR (p=0.054) and CAV (p=0.019), compared to Healthy patients. ECV, native T1, and T2 z-scores were elevated in patients with AR. CMR was able to identify differences between CAV and AR. CAV subjects had normal global function but abnormal GCS which may suggest subclinical dysfunction. AR patients have abnormal function and tissue characteristics consistent with edema (elevated ECV, native T1 and T2 z-scores). Characterization of CMR patterns is critical for the development of noninvasive biomarkers for PHT and may decrease dependence on EMB.

Quantitative flow ratio computed from invasive coronary angiography as a predictor for cardiac allograft vasculopathy after cardiac transplant.

Cardiac allograft vasculopathy (CAV) is a significant determinant of long-term survival in heart transplant recipients. Standard CAV screening typically utilizes invasive coronary angiography (ICA). Quantitative flow ratio (QFR) is a computational method for functional testing of coronary stenosis, and may add diagnostic value to ICA in assessing CAV. Consecutive subjects who received heart transplantation and underwent two separate routine coronary angiograms between January 2013 and April 2016 were enrolled. Coronary angiograms and IVUS were performed per local protocol at 1, 2, 3 and 5years post-transplant. QFR was calculated offline. CAV was assessed semi-quantitively based on coronary angiogram results. Twenty-two patients were enrolled. Mean time from transplant to first included ICA was 2.1years. QFR in at least 1 coronary vessel was interpretable in 19/22 (86%) of initial ICA (QFR1). QFR1 correlated well with the CAV score derived from the second ICA (CAV2) with a clustering of CAV at lower QFR values. In a receiver-operating characteristic (ROC) analysis, an optimal QFR threshold of 0.88 yielded 0.94 sensitivity and 0.67 specificity (AUC of 0.79) for at least non-obstructive subsequent CAV. Initial angiographically and intravascular ultrasound derived CAV severity poorly predicted subsequent CAV severity. QFR derived from invasive coronary angiography predicts subsequent development of CAV more accurately than angiography and intravascular ultrasound. This novel method of coronary flow assessment in recipients of heart transplantation may be useful to diagnose and predict subsequent CAV development.

Capabilities of intravascular imaging techniques in the diagnosis of cardiac allograft vasculopathy: Literature review

Cardiac allograft vasculopathy (CAV) is a coronary heart disease (CHD), arising after an orthotopic heart transplant (OHT), and it is one of the leading causes of death in heart recipients. The probability of death is 10%. CAV can manifest as early as 1 year after OHT. Patients do not have pain syndrome that is typical for CHD due to cardiac denervation. The first clinical manifestations may be congestive heart failure, ventricular arrhythmias or even sudden cardiac death. Coronary angiography is the routine technique for CAV detection. However, it is not sensitive enough (about 44%) for CAV detection at an early stage of the disease. Today, intravascular imaging methods (intravascular ultrasound, optical coherence tomography), which allow the evaluation of the morphology of coronary artery lesions, including CAV, have become widespread. This article is devoted to the modern capabilities of intravascular imaging methods in the diagnosis of CAV. CAV is the main cause of myocardial infarction and chronic heart failure in patients after OHT. Intravascular imaging techniques allow early detection of this condition and prevention of unfavorable outcomes in a complex category of heart recipients. Given the advantages of optical coherence tomography (OCT) and disadvantages of intravascular ultrasound (IVUS), OCT appears to be a more informative method of CAV detection.

Informing preconception counseling: Outcomes among female heart transplant recipients in the ISHLT registry

The numbers of women of child-bearing age undergoing heart transplantation (HT) and female pediatric HT recipients surviving to child-bearing age have increased, along with improvements in post-transplant survival. Data regarding life expectancy and comorbidities in reproductive-aged female HT recipients are needed to inform shared decision-making at the time of preconception counseling. The International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry was investigated for HT recipients between January 1, 2000 and June 30, 2017. Women of childbearing age were defined as those aged 15-45 years, either at transplant, or at the respective post-transplant follow-up. Characteristics and outcomes of female recipients of childbearing age at transplant, 5-, 10-, and 15-year follow-up were compared to females>45 years of age, males 15-45 years and males>45 years of age at the corresponding time intervals. Outcomes included survival, development of diabetes (DM), severe renal dysfunction (CKD), and cardiac allograft vasculopathy (CAV). During the study period, 71,585 HT recipients were included: 24% (n=17,194) were female and 9.2% (n=6602) were of childbearing age at HT. A pre-transplant diagnosis of peripartum cardiomyopathy was associated with significantly worse post-transplant survival, a finding that remained independent of panel reactive antibody levels. The presence of pre-transplant DM and/or severe CKD was significantly associated with lower survival as were the presence of CAV, DM, and CKD post-HT. Knowledge of the impact of pre-existing comorbidities and complications post-HT on survival are important for risk stratification for preconception counseling post-HT.

Multimodality Imaging in Advanced Heart Failure for Diagnosis, Management and Follow-Up: A Comprehensive Review.

Advanced heart failure (AHF) presents a complex landscape with challenges spanning diagnosis, management, and patient outcomes. In response, the integration of multimodality imaging techniques has emerged as a pivotal approach. This comprehensive review delves into the profound significance of these imaging strategies within AHF scenarios. Multimodality imaging, encompassing echocardiography, cardiac magnetic resonance imaging (CMR), nuclear imaging and cardiac computed tomography (CCT), stands as a cornerstone in the care of patients with both short- and long-term mechanical support devices. These techniques facilitate precise device selection, placement, and vigilant monitoring, ensuring patient safety and optimal device functionality. In the context of orthotopic cardiac transplant (OTC), the role of multimodality imaging remains indispensable. Echocardiography offers invaluable insights into allograft function and potential complications. Advanced methods, like speckle tracking echocardiography (STE), empower the detection of acute cell rejection. Nuclear imaging, CMR and CCT further enhance diagnostic precision, especially concerning allograft rejection and cardiac allograft vasculopathy. This comprehensive imaging approach goes beyond diagnosis, shaping treatment strategies and risk assessment. By harmonizing diverse imaging modalities, clinicians gain a panoramic understanding of each patient's unique condition, facilitating well-informed decisions. The aim is to highlight the novelty and unique aspects of recently published papers in the field. Thus, this review underscores the irreplaceable role of multimodality imaging in elevating patient outcomes, refining treatment precision, and propelling advancements in the evolving landscape of advanced heart failure management.

Cardiac magnetic resonance imaging in detection of progressive graft dysfunction in pediatric heart transplantation.

Chronic graft failure (CGF) in pediatric heart transplant (PHT) is multifactorial and may present with findings of fibrosis and microvessel disease (MVD) on endomyocardial biopsy (EMB). There is no optimal CGF surveillance method. We evaluated associations between cardiac magnetic resonance imaging (CMR) and historical/EMB correlates of CGF to assess CMR's utility as a surveillance method. Retrospective analysis of PHT undergoing comprehensive CMR between September 2015 and January 2022 was performed. EMB within 6 months was graded for fibrosis (scale 0-5) and MVD (number of capillaries with stenotic wall thickening per field of view). Correlation analysis and logistic regression were performed. Forty-seven PHT with median age at CMR of 15.7 years (11.6, 19.3) and time from transplant of 6.4 years (4.1, 11.0) were studied. Cardiac allograft vasculopathy (CAV) was present in 11/44 (22.0%) and historical rejection in 14/41 (34.2%). CAV was associated with higher global T2 (49.0 vs. 47.0 ms; p = 0.038) and peak T2 (57.0 vs. 53.0 ms; p = 0.013) on CMR. Historical rejection was associated with higher global T2 (49.0 vs. 47.0 ms; p = 0.007) and peak T2 (57.0 vs. 53.0 ms; p = 0.03) as well as global extracellular volume (31.0 vs. 26.3%; p = 0.03). Higher fibrosis score on EMB correlated with smaller indexed left ventricular mass (rho = -0.34; p = 0.019) and greater degree of MVD with lower indexed left ventricular end-diastolic volume (rho = -0.35; p = 0.017). Adverse ventricular remodeling and abnormal myocardial characteristics on CMR are present in PHT with CAV, historical rejection, as well as greater fibrosis and MVD on EMB. CMR has the potential use for screening of CGF.

Cardiac allograft vasculopathy in heart transplanted recipients: The multivessel study

BackgroundCardiac Allograft Vasculopathy (CAV) is a prevailing complication following heart transplantation. We aimed to investigate if CAV causes equal vascular remodeling in the major coronary arteries using quantitative Optical Coherence Tomography (OCT) and to explore the prognostic potential of OCT derived measurements from each coronary artery. Methods64 heart transplanted patients had a combined total of 114 full three-vessel OCTs and coronary angiographies performed between 2013 and 2019. OCT pullbacks were categorized by angiographic CAV classification. Registration of disease progression was censored on July 1, 2022. ResultsOCT recordings were classified as follows: No significant CAV, n = 73; mild CAV, n = 18; moderate CAV, n = 13 and severe CAV, n = 10. From inter-coronary comparison of severe CAV, we found significant differences by both average lumen/intima ratio (p<0.0001) and average intima/media ratio (p<0.0001). The left descending artery (LAD) showed increasingly smaller luminal areas and larger intimal areas within CAV groups compared with the remaining coronary arteries. No differences were seen between major coronary arteries without significant CAV.LAD derived average intima/media ratio (HR: 3.39; 95% CI: 1.33 to 8.63; p = 0.01) and average lumen/intima ratio (HR: 2.77; 95% CI: 1.09 to 7.05; p = 0.03) were the strongest predictors of CAV progression. LAD predictions were superior to predictions based on all three coronary arteries. ConclusionsLAD derived OCT measurements were increasingly affected by CAV compared with the circumflex and right coronary artery. Average lumen/intima and intima/media ratios were the strongest predictors of CAV progression.

Functional Assessment of Long-Term Microvascular Cardiac Allograft Vasculopathy.

Cardiac allograft vasculopathy (CAV) is a leading cause of death and retransplantation following heart transplantation (HTX). Surveillance angiography performed yearly is indicated for the early detection of the disease, but it remains of limited sensitivity. We performed bolus thermodilution-based coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) and fractional flow reserve (FFR) measurements in HTX patients undergoing yearly surveillance coronary angiography without overt CAV. In total, 27 HTX patients were included who had 52 CFR, IMR, and FFR measurements at a mean of 43 months after HTX. Only five measurements were performed in the first year. CFR decreased significantly by 0.13 every year (p = 0.04) and IMR tended to increase by 0.98 every year (p = 0.051), whereas FFR did not change (p = 0.161) and remained well above 0.80 over time. After one year, CFR decreased significantly (p = 0.022) and IMR increased significantly (p = 0.015), whereas FFR remained unchanged (p = 0.72). The functional status of the epicardial coronary arteries of transplanted hearts did not deteriorate over time. On the contrary, a significant decrease in CFR was noted. In view of the increasing IMR, this is caused by the deterioration of the function of microvasculature. CFR and IMR measurements may provide an early opportunity to diagnose CAV.