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Background: Patients with complex coronary artery disease, as defined by high SYNTAX scores, undergoing percutaneous coronary intervention (PCI) have poorer outcomes when compared with patients with lower SYNTAX I scores. This study aimed to assess if mechanical circulatory support using Impella mitigates the effect of the SYNTAX I score on outcomes after high-risk percutaneous coronary intervention (HRPCI)., Methods: Using data from the PROTECT III study, patients undergoing Impella-assisted HRPCI between March 2017 and March 2020 were divided into 3 cohorts based on SYNTAX I score-low (≤22), intermediate (23-32), and high (≥33). Procedural and clinical outcomes out to 90 days were compared between groups. Multivariable regression analysis was used to assess the impact of SYNTAX I score on major adverse cardiovascular and cerebrovascular events (MACCE) at 90 days., Results: A total of 850 subjects with core laboratory-adjudicated SYNTAX I scores were identified (low: n = 310; intermediate: n = 256; high: n = 284). Patients with high SYNTAX I scores were older than those with low or intermediate SYNTAX I scores (72.7 vs 69.7 vs 70.1 years, respectively; P < .01). After adjustment for covariates, high SYNTAX I score remained a significant predictor of 90-day MACCE (hazard ratio [HR], 2.14; 95% CI, 1.42-3.69; P < .01 vs low), whereas intermediate SYNTAX I score was not (HR, 0.92; 95% CI, 0.47-1.77; P = .80 vs low). These findings persisted after adjustment for post-PCI SYNTAX I score., Conclusions: A high SYNTAX I score was associated with higher rates of 90-day MACCE in patients who underwent Impella-assisted HRPCI. Further research is needed to understand the patient and procedural factors driving this finding., (© 2024 The Author(s).)

Competing Interests: Dr Strom additionally reports research grants from Anumana, HeartSciences, Ultromics, and Philips Healthcare; consulting for Edwards Lifesciences, Bracco Diagnostics, Philips Healthcare, General Electric Healthcare, and EVERSANA Lifesciences and is a member of the scientific advisory boards for Ultromics, EchoIQ, and HeartSciences, and serves on a data safety monitoring board for Pfizer. Dr Osborn reports research grants from the National Heart, Lung, and Blood Institute (R43HL167290), Philips Healthcare, and Zoll Circulation; consulting for Gentuity,NuPulse CV, and OpSens, and is a member of the scientific advisory board for Dyad Medical and holds equity in this company. Ms. Stout reports consulting for Bracco Diagnostics. All other authors report no conflicts.

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., Competing Interests: Conflict of interest: E.A. has participated in advisory board for Elastrin Therapeutics; G.T. has received consulting fees from Ionis Pharmaceuticals and has participated in advisory boards for Amgen and Sanofi., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

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.

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., Competing Interests: Dr Bergmark receives grant support through institution from Pfizer, Ionis, AstraZeneca, Abbott Vascular, Philips; receives consulting/personal fees from Abiomed, SpectraWAVE, Endovascular Engineering, CSI, Philips, Abbott Vascular, Servier, Daiichi-Sankyo, Janssen, and Quark; and is a member of the TIMI Study Group, which has received institutional grant support through the Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, Daiichi-Sankyo, Eisai, Intarcia, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, The Medicines Company, and Zora Biosciences. Dr Osborn receives research grant support from NIH/NHLBI (K08 HL130465); sponsored research from Dyad Medical, NuPulseCV, and Opsens; and consulting/personal fees from Abbott Vascular, Canon, Opsens, and Philips; is a scientific advisory board member of Dyad Medical; and holds equity in this company. Dr Ali receives grants from NIH/NHLBI, Abbott, Philips, Boston Scientific, Abiomed, Opsens, Acist Medical, Medtronic, Cardiovascular Systems; personal from Boston Scientific, Abiomed, Amgen, and Astra Zeneca; and equity from Shockwave Medical. Dr Gupta receives payment from the Arnold & Porter Law Firm for work related to the Sanofi clopidogrel litigation and from the Ben C. Martin Law Firm for work related to the Cook Celect IVC filter litigation; receives consulting fees from Edwards LifeSciences; and holds equity in Heartbeat Health, a telecardiology healthcare platform. Drs Koli, Prillinger, West, and Hasegawa are employees of and holds stock in Abbott. Dr Croce receives grant support from Abbott, Takeda, Teleflex, and CSI; receives honoraria from Abbott, Biotronik, Philips, Abiomed, CSI, Takeda, and Cordis; and is a major stock shareholder in Dyad Medical. Dr Secemsky receives research grants to BIDMC: NIH/NHLBI K23HL150290, Food and Drug Administration, Harvard Medical School’s Shore Faculty Development Award, AstraZeneca, BD, Boston Scientific, Cook, CSI, Laminate Medical, Medtronic and Philips and consulting/speaking fees from Abbott, Bayer, BD, Boston Scientific, Cook, CSI, Endovascular Engineering, Inari, Janssen, Medtronic, Philips, and VentureMed., (© 2022 The Authors.)

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., (© 2022 Wiley Periodicals LLC.)

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] mm 3 versus control, 54.2 [41.2-81.1] mm 3 ; 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.

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., (© 2020 The Authors.)

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.

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 (FFR CT ), invasive angiography (FFR angio ), and optical coherence tomography (FFR OCT ), 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.

A cancer patient presented with acute chest pain at rest 40 hours after IV fluorouracil infusion. Angiography showed evidence of myocardial bridging.

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions, please email: journals.permissions@oup.com.)

Metabolic and molecular imaging continues to advance our understanding of vascular disease pathophysiology. At present, 18 F-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., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

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)., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

Molecular imaging seeks to unravel critical molecular and cellular events in living subjects by providing complementary biological information to current structural clinical imaging modalities. In recent years, molecular imaging efforts have marched forward into the clinical cardiovascular arena, and are now actively illuminating new biology in a broad range of conditions, including atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm, cardiomyopathy, and valvular disease. Development of novel molecular imaging reporters is occurring for many clinical cardiovascular imaging modalities (positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging), as well as in translational platforms such as intravascular fluorescence imaging. The ability to image, track, and quantify molecular biomarkers in organs not routinely amenable to biopsy (e.g., the heart and vasculature) open new clinical opportunities to tailor therapeutics based on a cardiovascular disease molecular profile. In addition, molecular imaging is playing an increasing role in atherosclerosis drug development in phase II clinical trials. Here, we present state-of-the-art clinical cardiovascular molecular imaging strategies, and explore promising translational approaches positioned for clinical testing in the near term., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

Molecular imaging aims to enable personalized medicine via imaging-specific molecular and cellular targets that are relevant to the diagnosis and treatment of disease. By providing in vivo readouts of biological detail, molecular imaging complements traditional anatomical imaging modalities to allow: 1) visualization of important disease-modulating molecules and cells in vivo; 2) serial investigations to image evolutionary changes in disease attributes; and 3) evaluation of the in vivo molecular effects of biotherapeutics. The added information garnered by molecular imaging can improve risk assessment and prognosticative studies, this is of particular benefit in the management of cardiovascular disease (CVD)., (Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

Fluid shear stress stimulation induces endothelial cells to elongate and align in the direction of applied flow. Using the complementary techniques of photoactivation of fluorescence and fluorescence recovery after photobleaching, we have characterized endothelial actin cytoskeleton dynamics during the alignment process in response to steady laminar fluid flow and have correlated these results to motility. Alignment requires 24 h of exposure to fluid flow, but the cells respond within minutes to flow and diminish their movement by 50%. Although movement slows, the actin filament turnover rate increases threefold and the percentage of total actin in the polymerized state decreases by 34%, accelerating actin filament remodeling in individual cells within a confluent endothelial monolayer subjected to flow to levels used by dispersed nonconfluent cells under static conditions for rapid movement. Temporally, the rapid decrease in filamentous actin shortly after flow stimulation is preceded by an increase in actin filament turnover, revealing that the earliest phase of the actin cytoskeletal response to shear stress is net cytoskeletal depolymerization. However, unlike static cells, in which cell motility correlates positively with the rate of filament turnover and negatively with the amount polymerized actin, the decoupling of enhanced motility from enhanced actin dynamics after shear stress stimulation supports the notion that actin remodeling under these conditions favors cytoskeletal remodeling for shape change over locomotion. Hours later, motility returned to pre-shear stress levels but actin remodeling remained highly dynamic in many cells after alignment, suggesting continual cell shape optimization. We conclude that shear stress initiates a cytoplasmic actin-remodeling response that is used for endothelial cell shape change instead of bulk cell translocation.

We have derived a broad, deterministic model of the steady-state actin cycle that includes its major regulatory mechanisms. Ours is the first model to solve the complete nucleotide profile within filaments, a feature that determines the dynamics and geometry of actin networks at the leading edges of motile cells, and one that has challenged investigators developing models to interpret steady-state experiments. We arrived at the nucleotide profile through analytic and numerical approaches that completely agree. Our model reproduces behaviors seen in numerous experiments with purified proteins, but allows a detailed inspection of the concentrations and fluxes that might exist in these experiments. These inspections provide new insight into the mechanisms that determine the rate of actin filament treadmilling. Specifically, we find that mechanisms for enhancing Pi release from the ADP.Pi intermediate on filaments, for increasing the off rate of ADP-bound subunits at pointed ends, and the multiple, simultaneous functions of profilin, make unique and essential contributions to increased treadmilling. In combination, these mechanisms have a theoretical capacity to increase treadmilling to levels limited only by the amount of available actin. This limitation arises because as the cycle becomes more dynamic, it tends toward the unpolymerized state.

Cycling of actin subunits between monomeric and filamentous phases is essential for cell crawling behavior. We investigated actin filament turnover rates, length, number, barbed end exposure, and binding of cofilin in bovine arterial endothelial cells moving at different speeds depending on their position in a confluent monolayer. Fast-translocating cells near the wound edge have short filament lifetimes compared with turnover values that proportionately increase in slower moving cells situated at increasing distances from the wound border. Contrasted with slow cells exhibiting slow actin filament turnover speeds, fast cells have less polymerized actin, shorter actin filaments, more free barbed ends, and less actin-associated cofilin. Cultured primary fibroblasts manifest identical relationships between speed and actin turnover as the endothelial cells, and fast fibroblasts expressing gelsolin have higher actin turnover rates than slow fibroblasts that lack this actin-severing protein. These results implicate actin filament severing as an important control mechanism for actin cycling in cells.