Maximal Intimal Thickness Research Articles

OPTICAL COHERENCE TOMOGRAPHY IN CHILDREN: DEVELOPMENT OF A PROTOCOL FOR THE STANDARDIZED QUANTITATIVE ANALYSIS OF CORONARY ARTERIES

Optical coherence tomography (OCT) is a high-resolution intravascular imaging technique that has shown promise for the early detection of intimal thickening of coronary arteries in pediatric heart transplant recipients. The potential utility of OCT as a diagnostic and/or prognostic tool is currently unclear due to a lack of a standardized approach to analyse OCT images in this population. We established the OCT Core Imaging Laboratory at BC Children’s Hospital to develop a standardized protocol for the quantitative analysis of OCT images. Our study population included n=30 pediatric cardiac transplant recipients who had OCT imaging of the coronary arteries performed as part of standard of care at BC Children’s Hospital (St Jude Medical, now Abbott). We deemed a ‘pullback’ analyzable if ≥10mm of the segment was of good image quality (defined as ≥75% of cross-section visible without artifact). We evenly selected 10-20 cross-sectional frames ≥1 mm apart, avoiding bifurcations. Using the device-manufacturer’s software, we applied digital planimetry to trace the lumen-intima border, the internal elastic lamina, and the external elastic lamina for each cross-sectional frame. Cross-sectional areas (CSA, mm2) were derived for the lumen, the intima and the media; maximal intimal thickness (mm) was defined as the widest point between the circular markers for the intima and media. We calculated the intima/media (I/M) CSA ratio. For each pullback, we derived summary values from cross-sectional frames for relevant variables as means, medians, 95th percentile (p95) and maximal values. We performed inter-rater and intra-rater reliability analyses by intra-class correlation coefficients and Bland-Atman Analyses. Overall, 82% of analyzable pullbacks met inclusion criteria for our protocol (≥10-20 frames, ≥1 mm apart), resulting in 67 pullbacks from 28 patients analysed. The right coronary artery was most frequently imaged (58%), and more often met inclusion criteria for quantitative analyses (85% vs. 82% overall). Mean vs. median and max vs. p95 summary statistics yielded very similar values for I/M CSA and maximal intimal thickness (all ICC>0.98; difference < 3%), suggesting our protocol provides robust summary values. We registered excellent inter-rater and intra-rater reliability for I/M CSA and maximal intimal thickness (all ICC>0.95; difference < 5%). We provide a systematically developed and rigorously tested protocol for the quantitative analysis of OCT images in children. The novel application of OCT to a pediatric population requires expert image analysis and has the potential to improve the care of pediatric transplant patients who are at risk of structural coronary changes.

Comparison of Segmental Versus Longitudinal Intravascular Ultrasound Analysis for Pediatric Cardiac Allograft Vasculopathy

Intravascular ultrasound (IVUS) has been routinely used in some centers to investigate cardiac allograft vasculopathy in pediatric heart transplant recipients. We present an alternative method using more sophisticated imaging software. This study presents a comparison of this method with an established standard method. All patients who had IVUS performed in 2014 were retrospectively evaluated. The standard technique consisted of analysis of 10 operator-selected segments along the vessel. Each study was re-evaluated using a longitudinal technique, taken at every third cardiac cycle, along the entire vessel. Semiautomatic edge detection software was used to detect vessel imaging planes. Measurements included outer and inner diameter, total and luminal area, maximal intimal thickness (MIT), and intimal index. Each IVUS was graded for severity using the Stanford classification. All results were given as mean ± standard deviation (SD). Groups were compared using Student t test. A P value <.05 was considered significant. There were 59 IVUS studies performed on 58 patients. There was no statistically significant difference between outer diameter, inner diameter, or total area. In the longitudinal group, there was a significantly smaller luminal area, higher MIT, and higher intimal index. Using the longitudinal technique, there was an increase in Stanford classification in 20 patients. The longitudinal technique appeared more sensitive in assessing the degree of cardiac allograft vasculopathy and may play a role in the increase in the degree of thickening seen. It may offer an alternative way of grading severity of cardiac allograft vasculopathy in pediatric heart transplant recipients.

Waskulopatia w przeszczepionym sercu — nowe trendy w diagnostyce i leczeniu

Cardiac allograft vasculopathy (CAV) is one of the most significant complications in heart transplant patients. It is mentioned among three most frequent causes of death in patients over 3 years after heart transplant. It is an accelerated form of atherosclerosis with complex pathogenesis, including immunological reactions and viral infections. Classical atherosclerosis risk factors tend to influence the progress of CAV in the later stage. Due to nonspecific symptoms, diagnostic imaging is of a great value in recognizing CAV. Apart from angiography, which is the “gold standard” in diagnostics, modern imaging is increasingly gaining in importance. Intravascular ultrasound and its connection with virtual histology, as well as optical coherence tomography enable an accurate measurement of maximal intimal thickness (MIT), which is a prognostic factor of CAV progression. Moreover, these methods make it possible to assess the structure of plaques and to distinguish between CAV and atherosclerotic plaques. There are still researches conducted to find out the most favorable connections of immunosuppresive and antiproliferative drugs, which are the basis of CAV prevention and treatment. It has been observed that the effect of treatment differs depending on the used scheme. Apart from pharmacological treatment, angioplasty or coronary artery bypass graft can be profitable in some patients. The main goals of CAV researches are early diagnostics possibilities and effective suppression of this dangerous pathology progression.

Percutaneous Coronary Intervention and Coronary Artery Bypass Grafting in Heart Transplant Recipients With Transplant Coronary Arterial Vasculopathy

BackgroundTransplant coronary arterial vasculopathy (TCAV) is a major cause of death after heart transplantation (HTx). Palliative coronary revascularization has been attempted in patients with severe TCAV; however, the outcome has not been fully elucidated. MethodsNinety-six patients who were treated after HTx at our institute between 1999 and 2015 were screened for TCAV. TCAV was defined as >70% stenosis on coronary angiography (CAG) or a maximal intimal thickness of >0.5 mm in the right or left coronary arteries on intracoronary ultrasonography (IVUS). In the present study, the outcomes of patients with severe TCAV who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) were investigated. ResultsTCAV containing donor-transmitted atherosclerosis was cumulatively found in 69 patients (71.9% of the total; mean age, 34.6 ± 13.1 years; 52 men; mean follow-up duration, 83.0 ± 60.4 months). Five (7.2%) and 64 (92.8%) of the 69 patients were diagnosed as having TCAV by use of CAG and IVUS, respectively. All 5 patients diagnosed by with the use of CAG underwent coronary revascularization between 1 and 236 months after HTx. Three patients underwent PCI with drug-eluting stents, with a primary success rate of 100%. No angiographic restenosis occurred in 2 patients at 31 and 36 months after PCI, respectively. Meanwhile, 2 patients underwent CABG. No peri-operative complications occurred, and all grafts were patent as assessed by use of CAG at 34 and 5 months after CABG. ConclusionsCoronary revascularization was feasible and effective for severe TCAV with middle-term follow-up.

Donor-Transmitted Atherosclerosis Associated With Worsening Cardiac Allograft Vasculopathy After Heart Transplantation: Serial Volumetric Intravascular Ultrasound Analysis.

BackgroundThe influence of preexisting donor-transmitted atherosclerosis (DA) on cardiac allograft vasculopathy (CAV) development remains unclear.MethodsWe performed 3-dimensional intravascular ultrasound (3D-IVUS) analysis in 42 heart transplantation (HTx) recipients at 2.1 ± 0.9 months (baseline) and 12.2 ± 0.4 months post-HTx, as well as consecutive 3D-IVUS analyses up to 3 years post-HTx in 35 of the 42 recipients. Donor-transmitted atherosclerosis was defined as a maximal intimal thickness of 0.5 mm or greater at baseline. Changes in volumetric IVUS parameters were compared in recipients with (DA group) and without DA (DA-free group) at baseline, 1 year, and 3 years post-HTx.ResultsDonor-transmitted atherosclerosis was observed in 57.1% of 42 recipients. The DA group exhibited a significantly greater increase in plaque volume at 1 year post-HTx (P < 0.001), leading to increased percent plaque volume (plaque volume/vessel volume, [%]) (P < 0.001) and decreased luminal volume (P = 0.021). Donor-transmitted atherosclerosis was independently associated with a greater increase in percent plaque volume during the first post-HTx year (P = 0.011). From 1 to 3 years post-HTx, the DA group underwent continuous reduction in luminal volume (P = 0.022). These changes resulted in a higher incidence of angiographic CAV at 3 years post-HTx in the DA group (58.8% vs 5.6%, P = 0.002).ConclusionsThis volumetric IVUS study suggests that DA correlates with the worsening change in CAV several years post-HTx. Donor-transmitted atherosclerosis recipients may require more aggressive treatment to prevent subsequent CAV progression.

Cholesterol efflux capacity of high-density lipoprotein correlates with survival and allograft vasculopathy in cardiac transplant recipients

Cardiac allograft vasculopathy (CAV) is a major cause of mortality after cardiac transplantation. High-density lipoprotein (HDL) cholesterol efflux capacity (CEC) is inversely associated with coronary artery disease. In 2 independent studies, we tested the hypothesis that reduced CEC is associated with mortality and disease progression in CAV. We tested the relationship between CEC and survival in a cohort of patients with CAV (n = 35). To determine whether reduced CEC is associated with CAV progression, we utilized samples from the Clinical Trials in Organ Transplantation 05 (CTOT05) study to determine the association between CEC and CAV progression and status at 1 year (n = 81), as assessed by average change in maximal intimal thickness (MIT) on intravascular ultrasound. Multivariable Cox proportional hazard models demonstrated that higher levels of CEC were associated with improved survival (hazard ratio 0.26, 95% confidence interval 0.11 to 0.63) per standard deviation CEC, p = 0.002). Patients who developed CAV had reduced CEC at baseline and 1-year post-transplant. We observed a significant association between pre-transplant CEC and the average change in MIT, particularly among patients who developed CAV at 1 year (β = -0.59, p = 0.02, R2 = 0.35). Reduced CEC is associated with disease progression and mortality in CAV patients. These findings suggest the hypothesis that interventions to increase CEC may be useful in cardiac transplant patients for prevention or treatment of CAV.

Attenuated-Signal Plaque Progression Predicts Long-Term Mortality After Heart Transplantation: IVUS Assessment of Cardiac Allograft Vasculopathy

BackgroundAlthough cardiac allograft vasculopathy (CAV) is typically characterized by diffuse coronary intimal thickening with pathological vessel remodeling, plaque instability may also play an important role in CAV. Previous studies of native coronary atherosclerosis have demonstrated associations between attenuated-signal plaque (ASP), plaque instability, and adverse clinical events. ObjectivesThis study’s aim was to characterize the association between ASP and long-term mortality post-heart transplantation. MethodsIn 105 heart transplant recipients, serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in the first 50 mm of the left anterior descending artery. The ASP score was calculated by grading the measured angle of attenuation from grades 0 to 4 (specifically, 0°, 1° to 90°, 91° to 180°, 181° to 270°, and >270°) at 1-mm intervals. The primary endpoint was all-cause death or retransplantation. ResultsAt 1-year post-transplant, 10.5% of patients demonstrated ASP progression (newly developed or increased ASP). Patients with ASP progression had a higher incidence of acute cellular rejection during the first year (63.6% vs. 22.3%; p = 0.006) and tendency for greater intimal growth (percent intimal volume: 9.2 ± 9.3% vs. 4.4 ± 5.3%; p = 0.07) than those without. Over a median follow-up of 4.6 years, there was a significantly lower event-free survival rate in patients with ASP progression at 1-year post-transplant compared with those without. In contrast, maximum intimal thickness did not predict long-term mortality. ConclusionsASP progression appears to reflect chronic inflammation related to acute cellular rejection and is an independent predictor of long-term mortality after heart transplantation. Serial assessments of plaque instability may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

Perfusion Cardiac Magnetic Resonance Imaging as a Rule-Out Test for Cardiac Allograft Vasculopathy.

Cardiac allograft vasculopathy (CAV) is a leading cause of mortality after heart transplantation. Noninvasive imaging techniques used in CAV evaluation have important limitations. In a cross-sectional study, we investigated perfusion cardiac magnetic resonance (CMR) imaging to determine an optimal myocardial perfusion reserve index (MPR) cutoff for detecting CAV using receiver operating characteristic curve analysis. We evaluated CMR performance using sensitivity, specificity and likelihood ratio analysis. We included 29 patients (mean 5 ± 4 years after transplant) scheduled for coronary angiography with intravascular ultrasound (IVUS) who completed CMR. CAV was defined as maximal intimal thickness (MIT) >0.5 mm by IVUS of the left anterior descending artery. CAV was evident in 19 patients (70%) on IVUS (mean MIT 0.82 ± 0.42 mm). MPR was significantly lower in patients with MIT ≥0.50 mm (1.35 ± 0.23 vs. 1.71 ± 0.45, p = 0.013). There was moderate inverse correlation between MPR and MIT (r = -0.36, p = 0.075). The optimal MPR cutoff ≤1.68 for predicting CAV showed sensitivity of 100%, specificity of 63%, a negative predictive value of 100%, a positive predictive value of 86% and a positive likelihood ratio of 2.7. An MPR ≤1.68 has high negative predictive value, suggesting its potential as a test to rule out CAV.

Pre-existing and Postoperative Intimal Hyperplasia and Arteriovenous Fistula Outcomes

The contribution of intimal hyperplasia (IH) to arteriovenous fistula (AVF) failure is uncertain. This observational study assessed the relationship between pre-existing, postoperative, and change in IH over time and AVF outcomes. Prospective cohort study with longitudinal assessment of IH at the time of AVF creation (pre-existing) and transposition (postoperative). Patients were followed up for up to 3.3 years. 96 patients from a single center who underwent AVF surgery initially planned as a 2-stage procedure. Veins and AVF samples were collected from 66 and 86 patients, respectively. Matched-pair tissues were available from 56 of these patients. Pre-existing, postoperative, and change in IH over time. Anatomic maturation failure was defined as an AVF that never reached a diameter > 6mm. Primary unassisted patency was defined as the time elapsed from the second-stage surgery to the first intervention. Maximal intimal thickness in veins and AVFs and change in intimal thickness over time. Pre-existing IH (>0.05mm) was present in 98% of patients. In this group, the median intimal thickness increased 4.40-fold (IQR, 2.17- to 4.94-fold) between AVF creation and transposition. However, this change was not associated with pre-existing thickness (r(2)=0.002; P=0.7). Ten of 96 (10%) AVFs never achieved maturation, whereas 70% of vascular accesses remained patent at the end of the observational period. Postoperative IH was not associated with anatomic maturation failure using univariate logistic regression. Pre-existing, postoperative, and change in IH over time had no effects on primary unassisted patency. The small number of patients from whom longitudinal tissue samples were available and low incidence of anatomic maturation failure, which decreased the statistical power to find associations between end points and IH. Pre-existing, postoperative, and change in IH over time were not associated with 2-stage AVF outcomes.

Index of microvascular resistance after early conversion from calcineurin inhibitor to everolimus in heart transplantation: A sub-study to a 1-year randomized trial

Microvascular function in transplanted hearts can be evaluated by methods used in routine left heart catheterization follow-up after heart transplantation (HTx). This sub-study of a randomized study compared the effects of everolimus (EVR) and calcineurin inhibitor (CNI) treatment on microvascular function as expressed by the index of microvascular resistance (IMR) at 1 year after HTx. A secondary objective was to compare the change in IMR from 7-11 weeks to 1 year after HTx between randomized groups. There were 70 HTx recipients included and randomly assigned to combination therapy (EVR and CNI with early CNI withdrawal) vs conventional CNI treatment. Coronary physiologic assessment was performed 7-11 weeks and 1 year after HTx. A linear mixed model was used to assess the group difference at 1 year and the difference in IMR change between 7-11 weeks and 1 year after HTx. At 1 year, there was no significant difference in IMR between the EVR group (17.5 mm Hg∙sec ± 8.9) (mean ± SD) and the CNI group (14.9 mm Hg∙sec ± 6.6, p = 0.17). The difference in IMR change between the 2 treatment arms was 1.6 mm Hg∙sec (95% confidence interval, -2.8 to 5.9; p = 0.49). Spearman's rank correlation coefficient at 1 year after HTx between IMR and maximal intimal thickness as assessed with intravascular ultrasound in the left anterior descending artery was -0.13 (p = 0.28). In this prospective, open, randomized study comparing early CNI withdrawal with mammalian target of rapamycin inhibitors immunosuppression during the first year after HTx, early transition from CNI-based immunosuppression to EVR-based treatment did not result in differences in microvascular function as assessed by the IMR.

Association of periarterial neovascularization with progression of cardiac allograft vasculopathy and long-term clinical outcomes in heart transplant recipients

This study investigated the relationship between periarterial neovascularization, development of cardiac allograft vasculopathy (CAV), and long-term clinical outcomes after heart transplantation. Proliferation of the vasa vasorum is associated with arterial inflammation. The contribution of angiogenesis to the development of CAV has been suggested. Serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in 102 heart transplant recipients. Periarterial small vessels (PSV) were defined as echolucent luminal structures <1 mm in diameter, located ≤2 mm outside of the external elastic membrane. The signal void structures were excluded when they connected to the coronary lumen (considered as side branches) or could not be followed in ≥3 contiguous frames. The number of PSV was counted at 1-mm intervals throughout the first 50 mm of the left anterior descending artery, and the PSV score was calculated as the sum of cross-sectional values. Patients with a PSV score increase of ≥ 4 between baseline and 1-year post-transplant were classified as the "proliferative" group. Maximum intimal thickness was measured for the entire analysis segment. During the first year post-transplant, the proliferative group showed a greater increase in maximum intimal thickness (0.33 ± 0.36 mm vs 0.10 ± 0.28 mm, p < 0.001) and had a higher incidence of acute cellular rejection (50.0% vs 23.9%, p = 0.025) than the non-proliferative group. On Kaplan-Meier analysis, cardiac death-free survival rate over a median of 4.7 years was significantly lower in the proliferative group than in the non-proliferative group (hazard ratio, 3.10; p = 0.036). The increase in PSV, potentially representing an angioproliferative response around the coronary arteries, was associated with early CAV progression and reduced survival after heart transplantation.

Induction Therapy With Antithymocyte Globulin in Patients Undergoing Cardiac Transplantation Is Associated With Decreased Coronary Plaque Progression as Assessed by Intravascular Ultrasound.

Antithymocyte globulin (ATG) is used as induction therapy after cardiac transplant for enhancing immunosuppression and delaying the initiation of nephrotoxic drugs. It is unknown if ATG induction is associated with decreased coronary plaque progression by intravascular ultrasound (IVUS). Patients transplanted between March 2010 and December 2012 with baseline and 1-year IVUS were included. All patients transplanted were included in a secondary analysis. Change in plaque progression was measured in a blinded fashion on matched coronary segments and contrasted between patients induced with ATG and those who were not. One hundred and three patients were included in IVUS arms. Mean age at transplant was 55.8 ± 12.6 years, and 33.0% were female. Patients induced with ATG were more sensitized (54.3% versus 14.3%). Plaque progression was attenuated in patients who received ATG by changes in maximal intimal area (1.0 ± 1.2 versus 2.3 ± 2.6 mm(2); P = 0.001), maximal percent stenosis (6.3 ± 7.9 versus 12.8 ± 12.3%; = 0.003), maximal intimal thickness (0.2 ± 0.2 versus 0.3 ± 0.3 mm; P = 0.035), and plaque volume (0.5 ± 0.7 versus 1.0 ± 1.3 mm(3)/mm; P = 0.016). Rapid plaque progression by maximal percent stenosis (≥ 20%) occurred less frequently in the ATG arm (4.3% versus 26.3; P = 0.003). Survival (P = 0.242) and any treated rejection (P = 0.166) were not statistically different between groups. Patients receiving ATG had a higher rate of first-year infection (P = 0.003), perhaps related to increased intravenous antibiotic use immediately postoperatively, and a trend toward more biopsy-proven rejection (P = 0.073). Induction therapy with ATG is associated with reduced first-year coronary plaque progression as assessed by IVUS, despite an increased prevalence of sensitized patients with a trend toward more rejection.

Clinical Characteristics of In-stent Neoatherosclerosis Causing Late Stent Failure

Background: In-stent neoatherosclerosis (NA) is a cause of late stent failure. Late stent failure remains a challenging issue after stenting, and its causal mechanism has not been elucidated. Objectives: The aim of this study was to investigate the clinical characteristics of late stent failure with or without NA by optical coherence tomography (OCT). Methods and results: Among 179 patients who had undergone coronary stent implantation (bare metal stent and drug-eluting stent), 22 patients experienced late stent failure with and without NA identified by OCT. The presence of lipid-laden plaque or calcification inside the stent was defined as NA. The 22 patients were divided into two groups according to OCT images: 13 patients with NA (NA group) and 9 patients without NA (non-NA group). OCT analysis also showed that thrombus was more frequently observed and maximum intimal thickness was significantly larger in the NA than in the non-NA group (35.7 % vs 0.0 % and 1.26 mm vs 0.98 mm, p<0.05, respectively). In terms of characteristics, in-stent restenosis lesions and use of oral anticoagulants occurred at a lower frequency, and the minimal lumen diameter was significantly smaller in the NA group than in the non-NA group (7.7 % vs 44.4 %, 0.0 % vs 66.7 %, and 0.33 mm vs 0.83 mm, p<0.05, respectively). Conclusion: In-stent restenosis and use of anticoagulants may be associated with the mechanism of in-stent neoatherosclerosis.

Abstract 16838: Circulating miRNAs Can Predict Cardiac Allograft Vasculopathy in Pediatric Heart Transplant Recipients in a Sex-dependent Manner

Introduction: MicroRNAs (miRs) are small noncoding ~22 nucleotide RNAs capable of modulating the expression of many genes. Our hypothesis was that circulating miRs are useful biomarkers of cardiac allograft vasculopathy (CAV) in pediatric heart transplant recipients (PHTR). Methods: An array for 765 miRs was performed using the Applied Biosystems technology normalized by a global normalization method as determined by the Expression Suite Software. Serum was obtained from 132 PHTR at the time of routine surveillance catheterization with coronary evaluation (intravascular ultrasound [IVUS] performed if ≥ 25 kg). Rejection free CAV+ patients were matched by age at transplant and time since transplant to CAV- controls. Statistical analysis was performed using the Wilcoxon test. Results: Samples were analyzed from 32 CAV+ PHTR matched to 17 CAV-controls. There were no significant differences between expression of miRs between CAV+ and CAV- PHTR alone, but differences in expression were found when PHTR were separated by sex. miRs significantly upregulated in females (F) included miRs-636 (F with both IVUS and angiographic CAV; p=0.008), -636 and -523 (F with a maximal intimal thickness [MIT] of ≥ 0.5mm; p=0.008 and 0.01, respectively), and -509 and -636 (F with any diagnosis of CAV; p=0.01 and p=0.01, respectively). miRs significantly upregulated in males (M) included miRs-422a (M with both IVUS and angiographic CAV; p=0.007), -422a and let-7e (M with a MIT of ≥ 0.5mm; p=0.003 and p=0.01, respectively), and -422a (M with any diagnosis of CAV; p=0.002). miR-19a was significantly downregulated in in M with any diagnosis of CAV (p=0.04). Boxplots highlighting differential expression of miRs by sex in CAV are shown in Figure 1. Conclusions: miRs are differentially expressed between PHTR with CAV on the basis of sex. A unique biomarker signature of miRs that are specific to PHTR with CAV would be valuable in the risk stratification of this challenging patient population.

Optical coherence tomography for characterization of cardiac allograft vasculopathy in late survivors of pediatric heart transplantation

Optical coherence tomography (OCT) has been shown to reliably detect cardiac allograft vasculopathy (CAV). In recent studies performed in adult heart transplant (HTx) recipients, OCT revealed the presence of vulnerable plaques and complicated coronary artery lesions, thus challenging the current concept that CAV disease is a diffuse concentric and fibrosing vasculopathy. The aim of our study was to characterize CAV by OCT in a young population of HTx recipients. We prospectively enrolled 21 young HTx recipients (mean age 27 years, range 22 to 38 years) to undergo OCT of the left anterior descending coronary artery (LAD) in addition to annual CAV screening by coronary angiography and virtual histology intravascular ultrasound (VH-IVUS). Quantitative OCT analysis was performed at the site of maximal intimal thickness (MIT) for each LAD segment. Patients were 27 years old with a mean time from cardiac transplantation of 14.7 ± 6.8 years. All patients exhibited intimal hyperplasia with an abnormal (>1) intima-to-media ratio. The median (interquartile range) MIT values by OCT were 0.37 (0.22 to 0.54) mm, 0.46 (0.29 to 0.54) mm and 0.34 (0.25 to 0.49) mm in the distal, middle and proximal LAD segments, respectively. Qualitative OCT analysis rarely showed features of vulnerable plaque or complicated lesions. Consistently, at VH-IVUS, the prevalent component at the site of MIT per vessel assessed by OCT was fibrous tissue. Unlike recent evidence in adult HTx recipients, OCT findings of vulnerable plaque and complicated coronary lesions were found to be rare among late survivors of pediatric HTx.

(924) - Cardiac Allograft Vasculopathy in Young Adults Who Underwent Heart Transplant in Childhood - A Serial Intravascular Ultrasound Study

(924) - Cardiac Allograft Vasculopathy in Young Adults Who Underwent Heart Transplant in Childhood - A Serial Intravascular Ultrasound Study

Morphometric and histological parameters in veins of diabetic patients undergoing brachiocephalic fistula placement.

Diabetic patients with end-stage renal failure have higher rates of arteriovenous failures when compared with nondiabetics. The aim was to compare differences in indicators of vascular remodeling and endothelial dysfunction in veins of patients with or without diabetes at the time of surgical placement. In this prospective observational trial, vein samples were collected from patients when a brachiocephalic fistula was created. Morphometric measurements and extent of fibrosis were determined using Image J software. Histological analysis, for the presence of myofibroblasts and level of endothelial nitric oxide synthase, was performed by immunohistochemical staining and scored in semi-quantitative manner. Asymmetric dimethylarginine was determined at the time of access placement. Comparison of diabetics and nondiabetics was performed using Wilcoxon rank sum and Fisher's exact tests. Eighteen patients were included; 10 were diabetics. There was a significant difference in the measurement of vein area between groups, with diabetic vein samples having larger luminal area of average 832,001.18 μm(2) (317,582.17-3,695,670.36, P = 0.04). The maximal intimal to medial thickness ratio was higher in diabetic vein samples (0.71 vs. 0.24, P = 0.03) along with statistically significant higher maximal intimal thickness (312.12 vs. 115.14 μm, P = 0.03). There is a significant difference in vascular wall remodeling between diabetics and nondiabetics at the level of the cephalic vein at the time of brachiocephalic placement. The unexpected finding of significantly larger luminal area in diabetic veins could be a major factor positively affecting brachiocephalic outcomes in otherwise impaired remodeling in this patient population.

Interplay of coronary angiography and intravascular ultrasound in predicting long-term outcomes after heart transplantation

Cardiac allograft vasculopathy (CAV) remains the major cause of late graft-related death after heart transplantation (HT). Identification of patients at risk of cardiovascular events has relevant implications in appropriately guiding resources and intensity of follow-up. In this context, the prognostic relevance of serial coronary imaging long-term after HT is unexplored. Recipients with intravascular ultrasound (IVUS) and coronary angiography performed 1 and 5 years after HT were monitored for subsequent 1 to 10 years to analyze the association of serial coronary imaging with cardiovascular death and major cardiovascular events (MACEs). Included were 131 patients. The MACE incidence was 31.8 per 1,000 patient-years, and cardiovascular mortality was 17.4 per 1,000 patient-years. Progression of coronary lesions detected by angiography and changes in IVUS-defined parameters, including an increase in maximal intimal thickness (MIT) ≥0.35 mm and vascular remodeling, predicted MACE occurrence. However, only MIT change ≥0.35 mm also predicted cardiovascular mortality. Among patients with normal or stable angiography, an MIT change ≥0.35 mm identified those with a significantly higher MACE rate (80 vs 13 events/1,000 patient-years). Worsening metabolic parameters appeared associated with the increasing severity of CAV development. Combined imaging analysis of progression of angiographic lesions and IVUS-detected MIT between 1 and 5 years post-HT allows discriminating patients at high, intermediate, and low risk for adverse long-term cardiovascular outcomes. The metabolic syndrome milieu is confirmed as a key risk factor for long-term CAV progression and adverse prognosis.

Elevated immune monitoring early after cardiac transplantation is associated with increased plaque progression by intravascular ultrasound.

Immune monitoring (IM) has not been shown to be associated with cardiac allograft vasculopathy (CAV). Maximal intimal area, average percent stenosis, plaque volume, and maximal intimal thickness (MIT) were measured for matched baseline and one-yr IVUS segments in a blinded fashion. Patients were divided into quartiles by IM scores and outcomes compared. Optimal IM cutoff was determined. IM assays were measured at 63.7 ± 16.4 d after transplantation in fifty patients. Progression of maximal intimal area (p = 0.005), average percent stenosis (p < 0.001), plaque volume (p = 0.005), and MIT (p = 0.001) were increased across the quartiles. An optimal IM assay cutoff of 406.0 ng ATP/mL demonstrated a sensitivity of 66.7% and specificity of 94.3% for predicting rapid progression of MIT ≥ 0.5 mm. Mean IM scores for Group 1 vs. Group 2 were 176.4 ± 102.2 and 616.3 ± 239.5 ngATP/mL, respectively. Rapid progression of MIT ≥ 0.5 mm occurred in 5/38 patients (13.2%) in Group 1 vs. 10/12 patients (83.3%) in Group 2 (p < 0.001). The risk ratio for rapid progression with elevated IM was 11.7 (p < 0.001). Elevated early IM scores are associated with progression of CAV by IVUS. These findings suggest the potential of IM for tailoring of immunosuppressive regimens to minimize the progression of CAV in high-risk patients.

Abstract 14927: Everolimus versus Mycophenolate for Cardiac Transplantation

The role of everolimus in cardiac transplantation is being increasingly recognized.Multiple studies have been published comparing the use of everolimus and mycophenolate with varying results. We aimed to perform a meta-analysis of the published literature. We searched Pubmed, EBSCO and Cochrane databases for terms “everolimus”, “mycophenolate”, “heart transplantation”, “cardiac transplantation” and their combinations. All studies in which everolimus was compared to mycophenolate were included. Studies in language other than English were excluded. Rates of biopsy proven acute rejection (OR 0.82 CI 0.67 to 1.00, p = 0.05), hemodynamically significant rejection (OR 0.76, CI 0.39 to 1.50, p = 0.43)or change in glomerular filtration rate (GFR) (mean difference -1.91, CI -6.90 to 3.08, p = 0.45) were similar between everolimus and mycophenolate groups. Everolimus use was associated with significant reduction in average maximal intimal thickness (mean difference -0.04 CI -0.06 to -0.02, p = 0.001) and cytomegalovirus antigenemia (OR 0.38, CI 0.28 to 0.53, p &lt; 0.00001). There was no significant heterogeneity for any endpoint except change in GFR. As compared to mycophenolate, everolimus use is associated with similar antirejection outcomes after cardiac transplantation but with reduced maximal intimal thickness and cytomegalovirus antigenemia.