Impact of myocardial bridging on coronary artery plaque formation and long-term mortality after heart transplantation.

OBJECTIVES: This study aimed to explore the impact of myocardial bridging (MB) on early development of cardiac allograft vasculopathy and long-term graft survival after heart transplantation. BACKGROUND: MB has been reported to be associated with acceleration of proximal plaque development and endothelial dysfunction in native coronary atherosclerosis. However, its clinical significance in heart transplantation remains unclear. METHODS: In 103 heart-transplant recipients, serial (baseline and 1-year post-transplant) volumetric intravascular ultrasound (IVUS) analyses were performed in the first 50 mm of the left anterior descending (LAD) artery. Standard IVUS indices were evaluated in 3 equally divided LAD segments (proximal, middle, and distal segments). MB was defined by IVUS as an echolucent muscular band lying on top of the artery. The primary endpoint was death or re-transplantation, assessed for up to 12.2 years (median follow-up: 4.7 years). RESULTS: IVUS identified MB in 62% of the study population. At baseline, MB patients had smaller intimal volume in the distal LAD than non-MB patients (p = 0.002). During the first year, vessel volume decreased diffusely irrespective of the presence of MB. Intimal growth diffusely distributed in non-MB patients, whereas MB patients demonstrated significantly augmented intimal formation in the proximal LAD. Kaplan-Meier analysis revealed significantly lower event-free survival in patients with versus without MB (log-rank p = 0.02). In multivariate analysis, the presence of MB was independently associated with late adverse events [hazard ratio 5.1 (1.6-22.2)]. CONCLUSION: MB appears to relate to accelerated proximal intimal growth and reduced long-term survival in heart-transplant recipients.

Impact of Diastolic Vessel Restriction on Quality of Life in Symptomatic Myocardial Bridging Patients Treated With Surgical Unroofing: Preoperative Assessments With Intravascular Ultrasound and Coronary Computed Tomography Angiography.

[Figure: see text].

Head-to-head comparison of quantitative measurements between intravascular imaging systems: An in vitro phantom study.

INTRODUCTION: The present study aimed to compare the accuracy of quantitative measurements by contemporary intravascular imaging systems including optical frequency domain imaging (OFDI), frequency domain optical coherence tomography (FD-OCT), and 6 intravascular ultrasound (IVUS) systems. METHODS: We imaged five cylindrical phantom models made from an acrylic resin with known lumen diameters (1.51, 2.03, 3.04, 4.04, and 5.04 mm, respectively) using OFDI (FastView and LUNAWAVE, Terumo), FD-OCT (Dragonfly JP and ILUMIEN OPTIS, Abbott Vascular), and 6 mechanically rotating IVUS systems including a system, two 40-MHz, one 45-MHz, two 60-Mhz and one broad-band frequency IVUS systems. The OFDI, FD-OCT, and IVUS images were obtained using automated motorized pullback in a tank filled with 37-degree Celsius saline and, in cases of OFDI and FD-OCT, contrast-saline mixture (1:1 ratio) and contrast under the system setting of the refractive index for the corresponding flush medium. RESULTS: All the imaging systems showed good accuracy and excellent precision of lumen measurement with the relative differences between the measured diameter and actual phantom diameter being ranging from -2.9% to 8.0% and minimum standard deviations of the measured diameters (≤0.02 mm). CONCLUSION: The present study demonstrated that contemporary intravascular imaging systems including OFDI, FD-OCT, and IVUS provided clinically acceptable accuracy and excellent precision of quantitative lumen measurement in phantom models in vitro across a wide range of dimensions. Future research to confirm these findings in vivo are warranted.

Intravascular ultrasound predictors of long-term outcomes following ABSORB bioresorbable scaffold implantation: A pooled analysis of the ABSORB III and ABSORB Japan trials.

BACKGROUND: The long-term prognostic impact of IVUS findings following Absorb BVS implantation remains uncertain. This study aimed to identify the IVUS predictors of long-term clinical outcomes following ABSORB bioresorbable vascular scaffold (BVS) implantation from the pooled IVUS substudy cohorts of the ABSORB III and Japan trials. METHODS: A total of 298 lesions in 286 patients were enrolled with 2:1 randomization to ABSORB BVS vs. cobalt-chromium everolimus-eluting stents. This sub-analysis included 168 lesions of 160 patients in the Absorb arm whose post-procedural quantitative IVUS were available. The primary endpoint of this analysis was device-oriented composite endpoint (DOCE) of target lesion failure, including cardiac death, target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization. The median follow-up duration was 4.9 [3.1-5.0] years. RESULTS: During follow-up, DOCE occurred in 10.1% of lesions treated with Absorb BVS. Among several post-procedural IVUS indices associated with DOCE, non-uniform device expansion (defined as uniformity index = minimum / maximum device area) (hazard ratio 0.47 per 0.1 increase [95%CI 0.28 to 0.77]; p = 0.003) and residual reference plaque burden (hazard ratio 4.01 per 10% increase [95%CI 1.50 to 10.77]; p = 0.006) were identified as independent predictors of DOCE by Cox multivariable analysis. CONCLUSIONS: Nonuniform device expansion and substantial untreated residual plaque in reference segments were associated with long-term adverse events following BVS implantation. Baseline imaging to identify the appropriate device landing zone and procedural imaging to achieve uniform device expansion if possible (e.g. through post-dilatation) may improve clinical outcomes of BVS implantation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01751906 (ABSORB III); NCT01844284 (ABSORB Japan).

Deep learning-based intravascular ultrasound segmentation for the assessment of coronary artery disease.

BACKGROUND: Accurate segmentation of the coronary arteries with intravascular ultrasound (IVUS) is important to optimize coronary stent implantation. Recently, deep learning (DL) methods have been proposed to develop automatic IVUS segmentation. However, most of those have been limited to segmenting the lumen and vessel (i.e. lumen-intima and media-adventitia borders), not applied to segmenting stent dimension. Hence, this study aimed to develop a DL method for automatic IVUS segmentation of stent area in addition to lumen and vessel area. METHODS: This study included a total of 45,449 images from 1576 IVUS pullback runs. The datasets were randomly split into training, validation, and test datasets (0.7:0.15:0.15). After developing the DL-based system to segment IVUS images using the training and validation datasets, we evaluated the performance through the independent test dataset. RESULTS: The DL-based segmentation correlated well with the expert-analyzed segmentation with a mean intersection over union (± standard deviation) of 0.80 ± 0.20, correlation coefficient of 0.98 (95% confidence intervals: 0.98 to 0.98), 0.96 (0.95 to 0.96), and 0.96 (0.96 to 0.96) for lumen, vessel, and stent area, and the mean difference (± standard deviation) of 0.02 ± 0.57, -0.44 ± 1.56 and - 0.17 ± 0.74 mm2 for lumen, vessel and stent area, respectively. CONCLUSION: This automated DL-based IVUS segmentation of lumen, vessel and stent area showed an excellent agreement with manual segmentation by experts, supporting the feasibility of artificial intelligence-assisted IVUS assessment in patients undergoing coronary stent implantation.

Scaffold underexpansion and late lumen loss after bioresorbable scaffold implantation: Insights from ABSORB JAPAN trial.

BACKGROUND: Device underexpansion is associated with late adverse outcomes after bioresorbable vascular scaffold (BVS) implantation. This study, representing official IVUS results of the ABSORB Japan trial, aimed to characterize IVUS findings, focusing specifically on acute device expansion, and to investigate its impact on late lumen loss (LLL) with Absorb-BVS compared with cobalt-chromium everolimus-eluting stents (CoCr-EES). METHODS: ABSORB Japan enrolled 148 patients (2:1 randomization) in the IVUS cohort. Serial IVUS was prescheduled at post-procedure and 3 years. Acute device expansion was evaluated with respect to the degree and uniformity of the implanted device. RESULTS: Overall, Absorb-BVS showed smaller and more nonuniform device expansion at post-procedure, compared with CoCr-EES, which was particularly prominent in small-vessel lesions. In serial analysis, Absorb-BVS showed unique associations of smaller device expansion (r = 0.40, p = 0.001) and more nonuniformity (r = 0.29, p = 0.007) at post-procedure with greater LLL at 3 years, primarily attributable to greater negative remodeling (r = 0.39, p = 0.006). In contrast, acute device expansion showed no relation with subsequent lumen change in CoCr-EES. In Absorb-BVS, ischemic-driven target lesion or vessel revascularization (ID-TLR or ID-TVR) at 3 years occurred more frequently in small- versus large-vessel lesions (12.5% vs. 0%, p = 0.04 for ID-TLR and 15.6% vs. 2.3%, p = 0.08 for ID-TVR). Conversely, Absorb BVS had no target lesion nor vessel failure, even in small-vessel lesions, when adequate device expansion was achieved at post-procedure. CONCLUSIONS: Unlike CoCr-EES, underexpansion was associated with greater negative remodeling and LLL in Absorb-BVS. This may in part account for the poorer outcomes of Absorb-BVS than CoCr-EES when under-expanded.

Validated model of platelet slip at stenosis and device surfaces.

Platelets are central to thrombosis. However, it is unknown whether platelets slip at vascular or device surfaces. The presence of platelet slip at a surface would interrupt physical contact between the platelet and that surface, and therefore diminish adhesion and thrombosis. Unfortunately, no existing technology can directly measure platelet slip in a biological environment. The objective of this study was to explore whether microspheres-modeling platelets-slip at different vascular and device surfaces in an acrylic scaled-up model coronary artery. The microspheres (3.12 µm diameter) were suspended in a transparent glycerol/water experimental fluid, which flowed continuously at Reynolds numbers typical of coronary flow (200-400) through the model artery. We placed a series of axisymmetric acrylic stenoses (cross-sectional area reduction [CSAr], 20-90%) into the model artery, both without and with a central cylinder present (modeling a percutaneous interventional guide wire, and with a scaled-up Doppler catheter mounted upstream). We used laser Doppler velocimetry (LDV) to measure microsphere velocities within, proximal and distal to each stenosis, and compared to computer simulations of fluid flow with no-slip. For validation, we replaced the acrylic with paraffin stenoses (more biologically relevant from a surface roughness perspective) and then analyzed the signal recorded by the scaled-up Doppler catheter. Using the LDV, we identified progressive microsphere slip proportional to CSAr inside entrances for stenoses ≥60% and ≥40% without and with cylinder present, respectively. Additionally, microsphere slip occurred universally along the cylinder surface. Computer simulations indicated increased fluid shear rates (velocity gradients) at these particular locations, and logistic regression analysis comparing microsphere slip with fluid shear rate resulted in a c-index of 0.989 at a cut-point fluid shear rate of (10.61 [cm-1]×mean velocity [cm×sec-1]). Moreover, the presence of the cylinder caused disordering of microsphere shear rates distal to higher grade stenoses, indicating a disturbance in their flow. Finally, despite lower precision, the signal recorded by the scaled-up Doppler catheter nonetheless indicated slip at the entry into and at most locations distal to the 90% stenosis. Our validated model establishes proof of concept for platelet slip, and platelet slip explains several important basic and clinical observations. If technological advances allow confirmation in a true biologic environment, then our results will likely influence the development of shear-dependent antiplatelet drugs. Also, adding shear rate information, our results provide a direct experimental fluid dynamic foundation for antiplatelet-focused antithrombotic therapy during coronary interventions directed towards higher grade atherosclerotic stenoses.

Early invasive assessment of the coronary microcirculation predicts subsequent acute rejection after heart transplantation.

BACKGROUND: Acute allograft rejection (AAR) plays an important role in patient and graft survival; therefore, more emphasis should be placed on its prediction. This study aimed to investigate baseline clinical and diagnostic variables associated with subsequent AAR during the first year post-transplant, especially focusing on early physiologic and anatomic measures. METHODS: This study enrolled 88 heart transplant patients who underwent fractional flow reserve (FFR), coronary flow reserve (CFR), the index of microcirculatory resistance (IMR) and intravascular ultrasound (IVUS) in the left anterior descending artery at baseline (within 8 weeks post-transplant). Cardiac index (CI), pulmonary capillary wedge pressure (PCWP), mean pulmonary artery pressure (mPAP), right atrial pressure and left ventricular ejection fraction were also evaluated. AAR was defined as acute cellular rejection of grade ≥2R and/or pathological antibody-mediated rejection of grade ≥pAMR2. RESULTS: During the first year post-transplant, 25.0% of patients experienced AAR. Patients with AAR during the first year showed higher rates of recipient obesity, lower rates of recipient-donor sex mismatch and rATG and tacrolimus uses, higher PCWP, mPAP and IMR, and lower CFR at baseline, compared with those without. In the multivariate analysis, only baseline IMR ≥ 16.0 was independently associated with AAR during the first year, demonstrating high negative predictive value (96.7%). CONCLUSIONS: Invasively assessing microvascular resistance (baseline IMR ≥ 16.0) in the early post-transplant period was an independent determinant of subsequent acute allograft rejection during the first year post-transplant, suggesting that early assessment of IMR may enhance patient risk stratification and target medical therapies to improve patient outcome.

Bioresorbable Scaffold for Treatment of Coronary Artery Lesions: Intravascular Ultrasound Results From the ABSORB Japan Trial.

OBJECTIVES: The aim of this study was to characterize post-procedural intravascular ultrasound (IVUS) findings in the ABSORB Japan trial, specifically stratified by the size of target coronary arteries. BACKGROUND: Despite overall noninferiority confirmed in recent randomized trials comparing bioresorbable vascular scaffolds (BVS) (Absorb BVS) and cobalt-chromium everolimus-eluting metallic stents (CoCr-EES), higher event rates of Absorb BVS have been reported with suboptimal deployment, especially in small coronary arteries. METHODS: In the ABSORB Japan trial, 150 patients (2:1 randomization) were scheduled in the IVUS cohort. Small vessel was defined as mean reference lumen diameter <2.75 mm. Tapered-vessel lesions were defined as tapering index (proximal/distal reference lumen diameter) ≥1.2. RESULTS: Overall, IVUS revealed that the Absorb BVS arm had smaller device expansion than the CoCr-EES arm did, which was particularly prominent in small- and tapered-vessel lesions. Higher tapering index was also associated with higher rates of incomplete strut apposition in Absorb BVS, but not in CoCr-EES. With respect to procedural techniques, small-vessel lesions were treated more frequently with noncompliant balloons at post-dilatation but using significantly lower pressure in the Absorb BVS arm. In contrast, tapered-vessel lesions were post-dilated at equivalent pressure but with significantly smaller balloon catheters in the Absorb BVS arm, compared with the CoCr-EES arm. CONCLUSIONS: The significantly smaller device expansion especially in small vessels may account for the poorer outcomes of Absorb BVS in this lesion type. Appropriate optimization strategy, possibly different between polymeric and metallic devices, needs to be established for bioresorbable scaffold technology. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 Absorb™ BVS) in Japanese Population [ABSORB JAPAN]; NCT01844284).

Assessment of bioresorbable scaffold with a novel high-definition 60 MHz IVUS imaging system: Comparison with 40-MHz IVUS referenced to optical coherence tomography.

BACKGROUND: In vivo assessment of bioresorbable scaffold (BRS) is of growing clinical interest. The novel 60MHz high-definition intravascular ultrasound (HD-IVUS) has been developed to overcome the limitations of conventional 40 MHz IVUS. This study aimed to evaluate the performance and limitations of 60 MHz HD-IVUS compared with 40 MHz IVUS with respect to polymeric-strut visualization, quantitative and qualitative analysis, and feasibility of high-speed pullback in the assessment of BRS. METHODS AND RESULTS: In a bench-test model, 361 struts were analyzed to evaluate the influence of ultrasound-beam angles and proximity of adjacent struts on IVUS visualization of BRS struts. Various settings were created by deforming the BRS and positioning the transducer offcenter. In an in vivo swine coronary model, scaffold and lumen areas, degree of visible external elastic membrane, incomplete strut apposition, and strut fracture were evaluated in 59 matched cross-sections obtained at conventional (0.5 mm/sec) and high speed (10 mm/sec) pullbacks. Both studies utilized optical coherence tomography (OCT) as reference. Overall, 60 MHz HD-IVUS demonstrated significantly improved visualization of polymeric struts compared with 40 MHz IVUS (well-visualized: 84.5% vs 62.3%, not visible: 4.4% vs 13.9%, respectively. P < 0.001), which was less affected by the beam angle and adjacent strut proximity. In the in vivo model, 60-MHz HD-IVUS showed better agreement of area measurements and strut abnormalities with OCT than 40 MHz IVUS. These findings were also confirmed on high-speed pullback images of 60 MHz HD-IVUS. CONCLUSION: As referenced to OCT, this study showed superiority of 60 MHz HD-IVUS over 40 MHz IVUS in the assessment of BRS with feasibility of high-speed pullback imaging.

Impact of Stent Size Selection on Acute and Long-Term Outcomes After Drug-Eluting Stent Implantation in De Novo Coronary Lesions.

BACKGROUND: Although significant undersizing often results in incomplete stent apposition or underexpansion, the possible impact of oversized stent implantation on arterial wall injury has not been systematically investigated with drug-eluting stents. The aim of this study was to investigate the impact of stent oversizing on acute and long-term outcomes after drug-eluting stents implantation in de novo coronary lesions. METHODS AND RESULTS: Serial (baseline and 6-12 months) coronary angiography and intravascular ultrasound were performed in 2931 lesions treated with drug-eluting stents (355 sirolimus, 846 paclitaxel, 1387 zotarolimus, and 343 everolimus). The percentage of stent oversizing to angiographic reference vessel diameter (RVD) was calculated as (nominal stent diameter-RVD)/RVD×100 (%). Clinical outcomes, including target lesion revascularization and stent thrombosis, were followed for 1 year. Overall, smaller preintervention RVD was associated with higher percentage of stent oversizing (P<0.001). The significant oversizing group underwent less post-dilatation (P=0.002) but achieved greater stent expansion (P<0.001) and less incomplete stent apposition (P<0.001) without increase of edge dissection after procedure. When stratified by vessel size and stent oversizing, progressive decreases of restenosis (P=0.002) and target lesion revascularization rates (P=0.007) were found in favor of larger vessel size and oversized stents. Stent thrombosis was observed the most in small RVD with low percentage of stent oversizing group among the subgroups (P=0.040). CONCLUSIONS: The positive impact of stent oversizing was documented on procedural and clinical outcomes. In particular, small vessels treated with smaller stents were associated with greater adverse events, suggesting that aggressive selection of larger stents, with appropriate attention to edge effects, may optimize long-term outcomes, even in drug-eluting stents implantation.

Needs-Based Innovation in Interventional Radiology: The Biodesign Process.

There are many possible mechanisms for innovation and bringing new technology into the marketplace. The Stanford Biodesign innovation process is based in a deep understanding of clinical unmet needs as the basis for focused ideation and development. By identifying and vetting a compelling unmet need, the aspiring innovator can "derisk" a project and maximize chances for successful development in an increasingly challenging regulatory and economic environment. As a specialty founded by tinkerers, with a history of disruptive innovation that has yielded countless new ways of delivering care with minimal invasiveness, lower morbidity, and lower cost, interventional radiologists are uniquely well positioned to identify unmet needs and develop novel solutions free of dogmatic convention.

The effect of negative remodeling on fractional flow reserve after cardiac transplantation.

BACKGROUND: Negative remodeling is a common occurrence early after cardiac transplantation. Its impact on the development of myocardial ischemia is not well documented. The aim of this study is to investigate the impact of negative remodeling on fractional flow reserve after cardiac transplantation. METHODS: Thirty-four cardiac transplant recipients underwent intravascular ultrasound (IVUS) and fractional flow reserve (FFR) assessment soon after transplantation and one year later. Patients were divided into those with and without negative remodeling based on IVUS, and the impact on FFR was assessed. In the 19 patients with negative remodeling, there was no significant change in plaque volume (119.3±82.0 to 131.3±91.2mm3, p=0.21), but vessel volume (775.6±212.0 to 621.9±144.1mm3, p<0.0001) and lumen volume (656.3±169.1 to 490.7±132.0mm3, p<0.0001) decreased significantly and FFR likewise decreased significantly (0.88±0.06 to 0.84±0.07, p=0.04). In the 15 patients without negative remodeling, vessel volume did not change (711.7±217.6 to 745.7±198.5, p=0.28), but there was a significant increase in plaque volume (126.8±88.3 to 194.4±92.7, p<0.001) and a resultant significant decrease in FFR (0.89±0.05 to 0.85±0.05, p=0.01). CONCLUSION: Negative remodeling itself, without any change in plaque volume can cause a significant decrease in fractional flow reserve after cardiac transplantation and appears to be another possible mechanism for myocardial ischemia.

Impact of attenuated-signal plaque observed by intravascular ultrasound on vessel response after drug-eluting stent implantation.

BACKGROUND AND AIMS: The aim of this study was to investigate the impact of attenuated-signal plaque (ASP) observed by intravascular ultrasound (IVUS) on vessel response after drug-eluting stent implantation. METHODS: Data were derived from the IVUS cohort of the J-DESsERT trial comparing paclitaxel- and sirolimus-eluting stents. Serial IVUS analysis (pre- and post-intervention, and 8-month follow-up) was performed in 136 non-AMI lesions. ASP was defined as hypoechoic plaque with ultrasound attenuation without calcification. Calcified plaque (CP) was defined as brightly echoreflective plaque with acoustic shadowing. ASP and CP scores were calculated by grading their measured angle as 0 to 4 for 0°, <90°, 90-180°, 180-270° and >270°, respectively. The entire stented segment was analyzed at 1-mm intervals. RESULTS: At pre-intervention, ASP was observed in 40.4% of lesions, and this group had greater % neointimal volume (%NIV) at follow-up than the no-ASP group (p = 0.011). ASP score at pre-intervention positively correlated with %NIV (p = 0.023). During the follow-up, ASP score significantly decreased (p < 0.001), and CP score significantly increased (p < 0.001), with a negative correlation between them (p < 0.001). A decrease in the ASP score was associated with less %NIV in PES (p = 0.031), but not in SES (p = 0.229). CONCLUSIONS: The greater extent of plaque with IVUS-signal attenuation at pre-intervention and its persistence during follow-up were associated with neointimal proliferation, possibly representing sustained inflammatory status, depending on the type of DES used.

The Impact of Postgraduate Health Technology Innovation Training: Outcomes of the Stanford Biodesign Fellowship.

Stanford Biodesign launched its Innovation Fellowship in 2001 as a first-of-its kind postgraduate training experience for teaching biomedical technology innovators a need-driven process for developing medical technologies and delivering them to patients. Since then, many design-oriented educational programs have been initiated, yet the impact of this type of training remains poorly understood. This study measures the career focus, leadership trajectory, and productivity of 114 Biodesign Innovation Fellowship alumni based on survey data and public career information. It also compares alumni on certain publicly available metrics to finalists interviewed but not selected. Overall, 60% of alumni are employed in health technology in contrast to 35% of finalists interviewed but not selected. On leadership, 72% of alumni hold managerial or higher positions compared to 48% of the finalist group. A total of 67% of alumni reported that the fellowship had been "extremely beneficial" on their careers. As a measure of technology translation, more than 440,000 patients have been reached with technologies developed directly out of the Biodesign Innovation Fellowship, with another 1,000,000+ aided by solutions initiated by alumni after their training. This study suggests a positive impact of the fellowship program on the career focus, leadership, and productivity of its alumni.

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

BACKGROUND: Although 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. OBJECTIVES: This study's aim was to characterize the association between ASP and long-term mortality post-heart transplantation. METHODS: In 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. RESULTS: At 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. CONCLUSIONS: ASP 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.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part II. In Vivo Imaging of Bone Marrow Stromal Cells in Swine with PET/CT and MR Imaging.

Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone. Clinical MR imaging and PET reporter gene molecular imaging were performed after intravenous injection of the radiotracer fluorine 18-radiolabeled 9-[4-fluoro-3-(hydroxyl methyl) butyl] guanine ((18)F-FHBG). Linear regression analysis of both MR imaging and PET data and nonlinear regression analysis of PET data were performed, accounting for multiple injections per animal. Results MR imaging showed a positive correlation between MSC-TF-NP cell number and dephasing (dark) signal (R(2) = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 × 10(7) cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R(2) = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R(2) = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 × 10(8) cells. Conclusion The authors quantitatively determined the limit of detection of MSC after CCT in swine by using clinical PET reporter gene imaging and clinical MR imaging with cell prelabeling. (©) RSNA, 2016 Online supplemental material is available for this article.

Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction.

Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.

Acute stent recoil and optimal balloon inflation strategy: an experimental study using real-time optical coherence tomography.

AIMS: Our aim was to evaluate stent expansion and acute recoil at deployment and post-dilatation, and the impact of post-dilatation strategies on final stent dimensions. METHODS AND RESULTS: Optical coherence tomography (OCT) was performed on eight bare metal platforms of drug-eluting stents (3.0 mm diameter, n=6 for each) during and after balloon inflation in a silicone mock vessel. After nominal-pressure deployment, a single long (30 sec) vs. multiple short (10 sec x3) post-dilatations were performed using a non-compliant balloon (3.25 mm, 20 atm). Stent areas during deployment with original delivery systems were smaller in stainless steel stents than in cobalt-chromium and platinum-chromium stents (p<0.001), whereas subsequent acute recoil was comparable among the three materials. At post-dilatation, acute recoil was greater in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001), resulting in smaller final stent areas in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001). In comparison between conventional and latest-generation cobalt-chromium stents, stent areas were not significantly different after both deployment and post-dilatation. With multiple short post-dilatations, acute recoil was significantly improved from first to third short inflation (p<0.001), achieving larger final area than a single long inflation, despite stent materials/designs (p<0.001). CONCLUSIONS: Real-time OCT revealed significant acute recoil in all stent types. Both stent materials/designs and post-dilatation strategies showed a significant impact on final stent expansion.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.