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AIMS: Calcific aortic valve disease (CAVD) is the most common valve disease, which consists of a chronic interplay of inflammation, fibrosis, and calcification. In this study, sortilin (SORT1) was identified as a novel key player in the pathophysiology of CAVD, and its role in the transformation of valvular interstitial cells (VICs) into pathological phenotypes is explored. METHODS AND RESULTS: An aortic valve (AV) wire injury (AVWI) mouse model with sortilin deficiency was used to determine the effects of sortilin on AV stenosis, fibrosis, and calcification. In vitro experiments employed human primary VICs cultured in osteogenic conditions for 7, 14, and 21 days; and processed for imaging, proteomics, and transcriptomics including single-cell RNA-sequencing (scRNA-seq). The AVWI mouse model showed reduced AV fibrosis, calcification, and stenosis in sortilin-deficient mice vs. littermate controls. Protein studies identified the transition of human VICs into a myofibroblast-like phenotype mediated by sortilin. Sortilin loss-of-function decreased in vitro VIC calcification. ScRNA-seq identified 12 differentially expressed cell clusters in human VIC samples, where a novel combined inflammatory myofibroblastic-osteogenic VIC (IMO-VIC) phenotype was detected with increased expression of SORT1, COL1A1, WNT5A, IL-6, and serum amyloid A1. VICs sequenced with sortilin deficiency showed decreased IMO-VIC phenotype. CONCLUSION: Sortilin promotes CAVD by mediating valvular fibrosis and calcification, and a newly identified phenotype (IMO-VIC). This is the first study to examine the role of sortilin in valvular calcification and it may render it a therapeutic target to inhibit IMO-VIC emergence by simultaneously reducing inflammation, fibrosis, and calcification, the three key pathological processes underlying CAVD.
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Estenosis de la Válvula Aórtica , Calcinosis , Humanos , Animales , Ratones , Estenosis de la Válvula Aórtica/genética , Válvula Aórtica/patología , Calcinosis/metabolismo , Constricción Patológica , Células Cultivadas , FibrosisRESUMEN
OBJECTIVES: The study describes the evolution of optical coherence tomography (OCT) adoption and performance during percutaneous coronary intervention (PCI) following implementation of a standardized LightLab (LL) workflow. BACKGROUND: The purpose of the LL Clinical Initiative was to evaluate the impact of a standardized workflow on physician efficiency, decision making, and image quality. METHODS: The LL Clinical Initiative is a multicenter, prospective, observational clinical program. Data were collected from 48 physicians at 17 U.S. centers from 01/21/19 to 06/08/21. The study included 401 OCT-guided PCIs during the baseline phase and 1898 during the LL workflow phases. The baseline phase consisted of physicians utilizing OCT at their discretion. After completing the baseline phase, the workflow progressed through multiple phases culminating in the expansion phase, which focused on addressing greater procedural complexity. The LL workflow utilized OCT to assess plaque Morphology, lesion Length, and vessel Diameter before PCI, and optimized results by treating Medial edge dissection, stent mal-Apposition, and stent under-eXpansion (MLD MAX). High-level summary statistics were generated to elucidate trends. RESULTS: After program implementation, there was a rise in the number of PCIs where the LL workflow was utilized compared to the baseline phase (68% during the expansion phase vs. 41% at baseline; p for trend <0.0001). Adoption of the LL workflow was associated with progressively greater procedural and lesion complexity when OCT was performed pre- and post-PCI (87% vs. 52%, p < 0.0001; 55% vs. 37%, p < 0.0001, respectively). In addition, the quality of OCT imaging obtained improved after LL workflow introduction, with over 95% of pre- and post-PCI pullback quality considered usable during the expansion phase. Finally, there was a reduction in time spent on OCT interpretation, both pre-PCI (4.6 min vs. 7.5 min, p < 0.0001) and post-PCI (2.9 min vs. 5.3 min, p < 0.0001). CONCLUSIONS: After completion of the standardized OCT-guided workflow, there was greater uptake of OCT imaging, incorporation in more complex procedures, procedural efficiency, and image quality.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Angiografía Coronaria/métodos , Tomografía de Coherencia Óptica/métodos , Intervención Coronaria Percutánea/métodos , Estudios Prospectivos , Resultado del Tratamiento , Stents , Vasos Coronarios/patología , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/patologíaRESUMEN
PURPOSE OF REVIEW: The purpose of this study is to showcase advances in molecular imaging of atheroma biology in living individuals. RECENT FINDINGS: F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) continues to be the predominant molecular imaging approach for clinical applications, particularly in the large arterial beds. Recently, there has been significant progress in imaging of neovascularization and inflammation to delineate high-risk atheroma and to evaluate drug efficacy. In addition, new hardware detection technology and imaging agents are enabling in-vivo imaging of new targets on diverse imaging platforms. SUMMARY: In this review, we present recent exciting developments in molecular and structural imaging of atherosclerotic plaque inflammation and neovascularization. Building upon prior studies, these advances develop key technology that will play an important role in propelling new diagnostic and therapeutic strategies identifying high-risk plaque phenotypes and assessing new plaque stabilization therapies in clinical trials.
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Aterosclerosis/diagnóstico , Inflamación/diagnóstico , Imagen Molecular/métodos , Neovascularización Patológica/diagnóstico , Aterosclerosis/metabolismo , Humanos , Lípidos/análisis , Neovascularización Patológica/metabolismo , Reproducibilidad de los ResultadosRESUMEN
Atherosclerosis imaging strategies can delineate characteristics of plaques at risk of rupture and thrombosis. Structural plaque imaging identifies high-risk plaque features, including lipid pools, thin fibrous caps, and intraplaque hemorrhage. New molecular imaging techniques complement structural imaging approaches by illuminating important features of plaque biology, with a prominent focus on detecting inflammation as a high-risk phenotype. As we unravel the molecular and structural characteristics underlying thrombosis-prone plaques, there is significant promise for eventual early identification and prediction of atherosclerotic plaque complications before they occur. Here we focus on recent imaging insights into high-risk arterial plaques, the etiologic agent of acute myocardial infarction, stroke, and sudden cardiac death.
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Aterosclerosis/diagnóstico , Aterosclerosis/patología , Rotura/patología , Animales , Aterosclerosis/complicaciones , Hemorragia/complicaciones , Humanos , Inflamación/complicaciones , Inflamación/diagnóstico , Placa Aterosclerótica/diagnóstico , Factores de Riesgo , Rotura/complicacionesRESUMEN
BACKGROUND: While intravascular imaging guidance during percutaneous coronary intervention (PCI) improves outcomes, routine intravascular imaging usage remains low, in part due to perceived inefficiency and safety concerns. Aims: The LightLab (LL) Initiative was designed to evaluate whether implementing a standardised optical coherence tomography (OCT) workflow impacts PCI safety metrics and procedural efficiency. METHODS: In this multicentre, prospective, observational study, PCI procedural data were collected over 2 years from 45 physicians at 17 US centres. OCT-guided PCI incorporating the LL workflow (N=264), a structured algorithm using routine pre- and post-PCI OCT imaging, was compared with baseline angiography-only PCI (angio) (N=428). Propensity score analysis identified 207 matched procedures. Outcomes included procedure time, radiation exposure, contrast volume, device utilisation, and treatment strategy. RESULTS: Compared with angiography alone, LL workflow OCT-guided PCI increased the median procedural time by 9 minutes but reduced vessel preparation time (2 min LL workflow vs 3 min angio; p<0.001) and resulted in less unplanned additional treatment (4% LL workflow vs 10% angio; p=0.01). With LL workflow OCT guidance, fewer cineangiography views were needed compared to angiography guidance, leading to decreased radiation exposure (1,133 mGy LL workflow vs 1,269 mGy angio; p=0.02), with no difference in contrast utilisation between groups (p=0.28). Furthermore, LL workflow OCT guidance resulted in fewer predilatation balloons and stents being used, more direct stent placement, and greater stent post-dilatation than angiography-guided PCI. CONCLUSIONS: The incorporation of a standardised pre- and post-PCI OCT imaging workflow improves procedural efficiency and safety metrics, at a cost of a modestly longer procedure time.
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Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Tomografía de Coherencia Óptica/métodos , Angiografía Coronaria/métodos , Intervención Coronaria Percutánea/métodos , Estudios Prospectivos , Flujo de Trabajo , Resultado del Tratamiento , Stents , Vasos Coronarios/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Ultrasonografía Intervencional/métodosRESUMEN
Background: Use of intravascular ultrasound (IVUS) or optical coherence tomography (OCT) during percutaneous coronary intervention (PCI) is endorsed by society guidelines, but US data on real-world outcomes are lacking. Methods: Medicare claims data were identified for inpatient PCIs performed October 2015 to March 2020, with IVUS/OCT captured by ICD-10-PCS codes. Three-way propensity score matching (angio vs IVUS vs OCT) on baseline and procedural characteristics was performed. Major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), or repeat revascularization, was evaluated through 3 years, with a 30-day blanking window after index PCI to exclude staged procedures. Results: Of the 502,821 PCI procedures, 463,201 (92%) were guided by angiography alone, with IVUS or OCT used in 37,908 (7.5%) and 1712 (0.3%), respectively. After propensity matching, compared with angiography, the risk of major adverse cardiovascular event was similar for IVUS (hazard ratio [HR], 0.97; 95% CI, 0.91-1.03; P = .285) but lower for OCT (HR, 0.85; 95% CI, 0.77-0.94; P = .001). A similar trend was observed in clinically relevant subgroups. Compared with angiography alone, the risk of MI or repeat revascularization was lower with OCT (HR, 0.86; 95% CI, 0.76-0.97; P = .015), and the risk of MI alone was lower with IVUS (HR, 0.90; 95% CI, 0.82-0.99; P = .038). Conclusions: In a real-world US cohort, IVUS and OCT were used infrequently during PCI. Compared with angiography alone, use of intracoronary imaging during index PCI was associated with lower rates of clinical events through 3 years.
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BACKGROUND New pharmacological approaches are needed to prevent stent restenosis. This study tested the hypothesis that pemafibrate, a novel clinical selective PPARα (peroxisome proliferator-activated receptor α) agonist, suppresses coronary stent-induced arterial inflammation and neointimal hyperplasia. METHODS AND RESULTS Yorkshire pigs randomly received either oral pemafibrate (30 mg/day; n=6) or control vehicle (n=7) for 7 days, followed by coronary arterial implantation of 3.5 × 12 mm bare metal stents (2-4 per animal; 44 stents total). On day 7, intracoronary molecular-structural near-infrared fluorescence and optical coherence tomography imaging was performed to assess the arterial inflammatory response, demonstrating that pemafibrate reduced stent-induced inflammatory protease activity (near-infrared fluorescence target-to-background ratio: pemafibrate, median [25th-75th percentile]: 2.8 [2.5-3.3] versus control, 4.1 [3.3-4.3], P=0.02). At day 28, animals underwent repeat near-infrared fluorescence-optical coherence tomography imaging and were euthanized, and coronary stent tissue molecular and histological analyses. Day 28 optical coherence tomography imaging showed that pemafibrate significantly reduced stent neointima volume (pemafibrate, 43.1 [33.7-54.1] mm3 versus control, 54.2 [41.2-81.1] mm3; P=0.03). In addition, pemafibrate suppressed day 28 stent-induced cellular inflammation and neointima expression of the inflammatory mediators TNF-α (tumor necrosis factor-α) and MMP-9 (matrix metalloproteinase 9) and enhanced the smooth muscle differentiation markers calponin and smoothelin. In vitro assays indicated that the STAT3 (signal transducer and activator of transcription 3)-myocardin axes mediated the inhibitory effects of pemafibrate on smooth muscle cell proliferation. CONCLUSIONS Pemafibrate reduces preclinical coronary stent inflammation and neointimal hyperplasia following bare metal stent deployment. These results motivate further trials evaluating pemafibrate as a new strategy to prevent clinical stent restenosis.
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Enfermedad de la Arteria Coronaria , PPAR alfa , Animales , Benzoxazoles , Butiratos , Constricción Patológica , Hiperplasia , Inflamación/prevención & control , Neointima , Stents , PorcinosRESUMEN
PURPOSE OF REVIEW: Physiological assessment of coronary artery disease (CAD) is an essential component of the interventional cardiology toolbox. However, despite long-term data demonstrating improved outcomes, physiology-guided percutaneous coronary intervention (PCI) remains underutilized in current practice. This review outlines the indications and technical aspects involved in evaluating coronary stenosis physiology, focusing on the latest developments in the field. RECENT FINDINGS: Beyond fractional flow reserve (FFR), non-hyperemic pressure ratios (NHPR) that assess coronary physiology at rest without hyperemia now abound. Additional advances in other alternative FFR approaches, including non-invasive coronary CT (FFRCT), invasive angiography (FFRangio), and optical coherence tomography (FFROCT), are being realized. Artificial intelligence algorithms and robust tools that enable detailed pre-procedure "virtual" intervention are also emerging. The benefits of coronary physiological assessment to determine lesion functional significance are well established. In addition to stable CAD, coronary physiology can be especially helpful in clinical scenarios such as left main and multivessel CAD, serial lesions, non-infarct-related arteries in acute coronary syndromes, and residual ischemia post-PCI. Today, coronary physiological assessment remains an indispensable tool in the catheterization laboratory, with an exciting technological future that will further refine clinical practice and improve patient care.
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Background Intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) offers tomographic images of the coronary vessels, allowing optimization of stent implantation at the time of PCI. However, the long-term beneficial effect of IVUS over PCI guided by coronary angiography (CA) alone remains under question. We sought to investigate the outcomes of IVUS-guided compared with CA-guided PCI. Methods and Results We performed a comprehensive search of PubMed, Medline, and Cochrane Central Register, looking for randomized controlled trials and observational studies that compared PCI outcomes of IVUS with CA. Data were aggregated for the primary outcome measure using the random-effects model as pooled risk ratio (RR). The primary outcomes were the rate of cardiovascular death, need for target lesion revascularization, occurrence of myocardial infarction, and rate of stent thrombosis. A total of 19 studies met the inclusion criteria, comprising 27 610 patients divided into IVUS (n=11 513) and CA (n=16 097). Compared with standard CA-guided PCI, we found that the risks of cardiovascular death (RR, 0.63; 95% CI, 0.54-0.73), myocardial infarction (RR, 0.71; 95% CI, 0.58-0.86), target lesion revascularization (RR, 0.81; 95% CI, 0.70-0.94), and stent thrombosis (RR, 0.57; 95% CI, 0.41-0.79) were all significantly lower using IVUS guidance. Conclusions Compared with standard CA-guided PCI, the use of IVUS imaging guidance to optimize stent implantation is associated with a reduced risk of cardiovascular death and major adverse events, such as myocardial infarction, target lesion revascularization, and stent thrombosis.
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Angiografía Coronaria , Enfermedad de la Arteria Coronaria/terapia , Intervención Coronaria Percutánea , Ultrasonografía Intervencional , Anciano , Angiografía Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/mortalidad , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Stents , Resultado del Tratamiento , Ultrasonografía Intervencional/efectos adversosRESUMEN
Paclitaxel drug-coated balloons (DCBs) reduce restenosis, but their overall safety has recently raised concerns. This study hypothesized that DCBs could lessen inflammation and reduce plaque progression. Using 25 rabbits with cholesterol feeding- and balloon injury-induced lesions, DCB-percutaneous transluminal angioplasty (PTA), plain PTA, or sham-PTA (balloon insertion without inflation) was investigated using serial intravascular near-infrared fluorescence-optical coherence tomography and serial intravascular ultrasound. In these experiments, DCB-PTA reduced inflammation and plaque burden in nonobstructive lesions compared with PTA or sham-PTA. These findings indicated the potential for DCBs to serve safely as regional anti-atherosclerosis therapy.
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PURPOSE: To examine the impact of cardiovascular magnetic resonance (CMR) partitioning methods on volumetric analysis in hypertrophic cardiomyopathy (HCM) patients. The standard CMR method for partitioning ventricular myocardium from ventricular cavity includes the myocardial papillary and trabecular muscles in the cavity volume. This approach may misrepresent ventricular mass and volume in patients with HCM due to large papillary muscles and extensive trabeculations. MATERIALS AND METHODS: Ventricular volume and mass analyses were performed in 30 patients with HCM using the standard method and a detailed method that excluded papillary and trabecular muscles from the left ventricular (LV) volume while including them in LV mass. We also analyzed the degree of mitral regurgitation and compared the results with Doppler echocardiography in a subgroup of 12 patients. Interobserver variability was assessed. RESULTS: The detailed method yielded 17% higher indexed LV mass, 20% lower indexed LV diastolic volume, 13% higher LV ejection fraction (EF) (all P < 0.0001). The resultant mitral regurgitant volumes using the detailed method had less discrepancy with Doppler echocardiography results compared with the results from the standard methods. Interobserver variability was similar by both methods. CONCLUSION: For patients with HCM, a detailed analysis in which the ventricular papillary and trabecular muscles are excluded from LV volume is preferred.
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Cardiomiopatía Hipertrófica/patología , Corazón/fisiología , Músculos/patología , Músculos Papilares/patología , Adulto , Ecocardiografía/métodos , Femenino , Corazón/anatomía & histología , Ventrículos Cardíacos/patología , Humanos , Masculino , Persona de Mediana Edad , Válvula Mitral/patología , Insuficiencia de la Válvula Mitral , Ultrasonografía Doppler/métodos , Función Ventricular IzquierdaRESUMEN
PURPOSE OF REVIEW: Molecular imaging aims to illuminate vital molecular and cellular aspects of disease in vivo, and is rapidly translating into the clinical arena. Advantages of this field include enabling serial biological studies in living subjects, assessment of pharmaceutical efficacy, and in-vivo characterization of clinical diseases. Here we present recent exciting advances in molecular imaging of atherosclerotic vascular disease. RECENT FINDINGS: Atherosclerosis molecular imaging approaches are now available for magnetic resonance, nuclear, computed tomography, ultrasound, and near-infrared fluorescence imaging. Advances in agent synthesis and detection technology are now enabling in-vivo imaging of endothelial cell activation, macrophages, cellular metabolism, protease activity, apoptosis, and osteogenic activity. Several agents show clinical utility for the detection of high-risk plaques. SUMMARY: Molecular imaging is actively unraveling the biological basis of atherosclerosis in living subjects. In the near-term, molecular imaging will play an important role in assessing novel atherosclerosis pharmacotherapies in clinical trials. Longer term, molecular imaging should enable accurate identification of high-risk plaques responsible for myocardial infarction, stroke, and ischemic limbs.
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Aterosclerosis/diagnóstico , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/patología , Humanos , Imagen por Resonancia Magnética , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/fisiopatología , Espectrometría de Fluorescencia , Espectroscopía Infrarroja Corta , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/fisiopatología , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
A cancer patient presented with acute chest pain at rest 40 hours after IV fluorouracil infusion. Angiography showed evidence of myocardial bridging.
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Vasoespasmo Coronario , Fluorouracilo , Puente Miocárdico , Nitroglicerina/administración & dosificación , Neoplasias Pancreáticas/tratamiento farmacológico , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Angiografía Coronaria/métodos , Vasoespasmo Coronario/diagnóstico , Vasoespasmo Coronario/tratamiento farmacológico , Vasoespasmo Coronario/etiología , Sustitución de Medicamentos/métodos , Electrocardiografía/métodos , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Persona de Mediana Edad , Puente Miocárdico/diagnóstico , Puente Miocárdico/fisiopatología , Puente Miocárdico/terapia , Resultado del Tratamiento , Vasodilatadores/administración & dosificaciónRESUMEN
Metabolic and molecular imaging continues to advance our understanding of vascular disease pathophysiology. At present, 18F-FDG PET imaging is the most widely used clinical tool for metabolic and molecular imaging of atherosclerosis. However, novel nuclear tracers and intravascular optical near-infrared fluorescence imaging catheters are emerging to assess new biologic targets in vivo and in coronary arteries. This review highlights current metabolic and molecular imaging clinical and near-clinical applications within atherosclerosis and venous thromboembolism, and explores the potential for metabolic and molecular imaging to affect patient-level risk prediction and disease treatment.
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Aterosclerosis/diagnóstico por imagen , Aterosclerosis/metabolismo , Imagen Molecular/métodos , Tomografía de Emisión de Positrones/métodos , Tromboembolia Venosa/diagnóstico por imagen , Tromboembolia Venosa/metabolismo , Aterosclerosis/patología , Biomarcadores/metabolismo , Humanos , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tromboembolia Venosa/patologíaRESUMEN
AIMS: (i) to evaluate a novel hybrid near-infrared fluorescence-intravascular ultrasound (NIRF-IVUS) system in coronary and peripheral swine arteries in vivo; (ii) to assess simultaneous quantitative biological and morphological aspects of arterial disease. METHODS AND RESULTS: Two 9F/15MHz peripheral and 4.5F/40MHz coronary near-infrared fluorescence (NIRF)-IVUS catheters were engineered to enable accurate co-registrtation of biological and morphological readings simultaneously in vivo. A correction algorithm utilizing IVUS information was developed to account for the distance-related fluorescence attenuation due to through-blood imaging. Corrected NIRF (cNIRF)-IVUS was applied for in vivo imaging of angioplasty-induced vascular injury in swine peripheral arteries and experimental fibrin deposition on coronary artery stents, and of atheroma in a rabbit aorta, revealing feasibility to intravascularly assay plaque structure and inflammation. The addition of ICG-enhanced NIRF assessment improved the detection of angioplasty-induced endothelial damage compared to standalone IVUS. In addition, NIRF detection of coronary stent fibrin by in vivo cNIRF-IVUS imaging illuminated stent pathobiology that was concealed on standalone IVUS. Fluorescence reflectance imaging and microscopy of resected tissues corroborated the in vivo findings. CONCLUSIONS: Integrated cNIRF-IVUS enables simultaneous co-registered through-blood imaging of disease related morphological and biological alterations in coronary and peripheral arteries in vivo. Clinical translation of cNIRF-IVUS may significantly enhance knowledge of arterial pathobiology, leading to improvements in clinical diagnosis and prognosis, and helps to guide the development of new therapeutic approaches for arterial diseases.
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Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Enfermedades Vasculares Periféricas/diagnóstico por imagen , Espectrometría de Fluorescencia/métodos , Espectroscopía Infrarroja Corta/métodos , Ultrasonografía Intervencional/métodos , Algoritmos , Animales , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/patología , Enfermedades Vasculares Periféricas/patología , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Conejos , Stents , PorcinosRESUMEN
OBJECTIVES: This study sought to determine whether indocyanine green (ICG)-enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. BACKGROUND: New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration-approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. METHODS: Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. RESULTS: ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound-identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and lipid, and, notably, intraplaque hemorrhage. CONCLUSIONS: This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities and provides new insights into its targeting mechanisms in clinical and experimental atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically translatable approach to image pathobiological aspects of coronary atherosclerosis. (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque [BRIGHT-CEA]; NCT01873716).