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Background: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content. Methods: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion–related MACEs and high-risk plaque characteristics. Results: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14–3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12–12.77)]) and nonculprit lesion–related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25–6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P =0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P =0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P =0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P =0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21–5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86–1.69]). Conclusions: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02171065.

Background: Hemodynamic assessment of untreated nonculprit lesions was not studied in the PROSPECT study (Providing Regional Observations to Study Predictors of Events in the Coronary Tree). We developed a virtual intravascular ultrasound–derived lesion-specific fractional flow reserve (lesion-specific IVUS-FFR) algorithm to assess individual lesion-level FFR. We sought to investigate the relation between lesion-specific IVUS-FFR and major adverse cardiovascular events (MACE) arising from untreated nonculprit lesions in the PROSPECT study. Methods: In PROSPECT, 697 patients with acute coronary syndromes underwent 3-vessel grayscale and virtual histology–IVUS to correlate untreated nonculprit plaque morphology with 3-year nonculprit related MACE (composite of cardiac death, cardiac arrest, myocardial infarction, or rehospitalization due to unstable or progressive angina). Lesion-specific IVUS-FFR was calculated from volumetric IVUS lumen area measurements at 0.4 mm intervals by applying a mathematical circulation model using basic fluid dynamics equations. Results: Lesion-specific IVUS-FFR was analyzable in 3227 nonculprit lesions in 660 patients among whom 54 nonculprit MACE events (3 myocardial infarctions) occurred at median 3.4-year follow-up. By receiver-operating characteristic analysis, the best cutoff value of lesion-specific IVUS-FFR to predict nonculprit MACE was ≤0.95. After adjusting for patient and lesion characteristics, lesion-specific IVUS-FFR (hazard ratio, 4.83 [95% CI, 2.20–10.61]; P 2 , plaque burden ≥70%, and virtual histology thin-cap fibroatheroma. Conclusions: Minor reductions in lesion-specific IVUS-FFR were independently associated with future nonculprit MACE arising from untreated angiographically mild stenoses along with previously established high-risk lesion morphological characteristics. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00180466.

Little is known about the overall diagnostic performance of computational fractional flow reserve (FFR) derived from angiography (Angio-FFR), intravascular ultrasound (IVUS-FFR), and optical coherence tomography (OCT-FFR) to detect hemodynamically significant coronary artery disease. The present study aimed to evaluate the diagnostic performance of those novel physiologic indices using conventional FFR as the gold standard.PubMed and Embase were searched in September 2021 for a systematic review and meta-analysis of studies assessing the diagnostic performance of invasive imaging-derived FFR. The primary outcomes were the summary sensitivity, specificity, correlation coefficients of each index.A total of 6572 records were initially identified and 49 studies were included in the final analysis (7010 lesions from 36 studies for Angio-FFR, 305 lesions from 5 studies for IVUS-FFR, and 667 lesions from 8 studies for OCT-FFR). Invasive imaging-derived FFR had a high diagnostic performance to detect functionally significant coronary lesions using conventional FFR as the gold standard [Angio-FFR, sensitivity 0.87 (95% CI 0.84-0.89), specificity 0.93 (95% CI 0.910.95); IVUS-FFR, sensitivity 0.90 (95% CI 0.84-0.94), specificity 0.95 (95% CI 0.90-0.98); OCT-FFR, sensitivity 0.85 (95% CI 0.78-0.91), specificity 0.93 (95% CI 0.89-0.95)]. The summary correlation coefficients of Angio-, IVUS-, and OCT-FFRs with wire-based FFR were 0.83 (95% CI 0.80-0.85), 0.85 (95% CI 0.79-0.91), and 0.80 (95% CI 0.74-0.86), respectively.This meta-analysis demonstrated that computational FFR derived from invasive coronary imaging has clinically acceptable diagnostic performances irrespective of modalities, supporting their applicability to clinical practice.

The purpose of a bioresorbable scaffold (BRS) is to provide radial support during coronary healing. In this study, coronary artery healing after optical coherence tomography (OCT)- versus angiography-guided magnesium BRS (MBRS) implantation in patients with non-ST-segment-elevation myocardial infarction (NSTEMI) is compared.75 patients were randomized 1:1 to OCT- or angiography-guided implantation of a MBRS with protocolled pre- and post-dilation. In the OCT-guided group, prespecified criteria indicating additional intervention were (1) scaffold under-expansion, (2) strut malapposition, (3) edge dissection, and (4) residual stenosis at distal or proximal reference segments. The primary endpoint was OCT-derived healing stage at 6 months.At 6 months, there was no difference in average healing stage between OCT- and angiography-guided intervention (4.6 [interquartile range (IQR): 4.5-4.7] versus 4.5 [IQR: 4.3-4.7]; p = 0.54). The MBRSs were completely resolved in 77.0% [IQR: 68.5-85.5] versus 76.5% [IQR: 67.9-85.5]; (p = 0.97). Minimal lumen area (MLA) was reduced at 6 months in both the OCT- (32.3%; p 0.01) and the angiography-guided group (21.3%; p 0.01), however OCT-guided implantation was associated with a greater reduction of total lumen volume (-27.1 ± 32.5 mmIn NSTEMI patients, OCT-guidance with protocolled pre- and post-dilation of MBRS implantation showed similar healing pattern at 6 months compared to angiography-guidance alone.The Coronary Artery Healing Process after Optical Coherence Tomography Guided Percutaneous Coronary Intervention with Magmaris Bioresorbable Scaffold in Patients with Non-ST-Segment-Elevation Myocardial Infarction: (HONEST) trial is registered with ClinicalTrials.gov, NCT03016624.

Diabetes mellitus (DM) is an important predictor of neointimal hyperplasia (NIH) and adverse clinical outcomes after percutaneous coronary intervention (PCI). LABR-312, a novel intravenous formulation of liposomal alendronate, has been shown in animal models to decrease NIH at vascular injury sites and around stent struts. The aim of the Biorest Liposomal Alendronate Administration for Diabetic Patients Undergoing Drug-Eluting Stent Percutaneous Coronary Intervention trial was to assess the safety, effectiveness, and dose response of LABR-312 administered intravenously at the time of PCI withDES in reducing NIH as measured by optical coherence tomography postprocedure in patients with DM.Patients with DM were randomized to a bolus infusion of LABR-312 vs placebo at the time of PCI. Dose escalation of LABR-312 in the study arm was given: 0.01 mg, 0.03 mg, and 0.08 mg. The primary endpoint was the in-stent %NIH volume at 9 months as measured by optical coherence tomography.From September 2016 to December 2017, 271 patients with DM undergoing PCI were enrolled; 136 patients were randomized to LABR-312 infusion and 135 patients were randomized to placebo. At 9-month follow-up, no difference was seen in the primary endpoint of %NIH between LABR-312 and placebo (13.3% ± 9.2 vs 14.6% ± 8.5, P = .35). No differences were present with the varying LABR-312 doses. Clinical outcomes at 9 months were similar between groups.Among patients with DM undergoing PCI with drug-eluting stents, a bolus of LABR-312 injected systematically at the time of intervention did not result in a lower rate in-stent %NIH volume at 9-month follow-up.

Severe coronary artery calcification has been associated with stent underexpansion, procedural complications, and increased rates of early and late adverse clinical events in patients undergoing percutaneous coronary intervention. To date, no lesion preparation strategy has been shown to definitively improve outcomes of percutaneous coronary intervention for calcified coronary artery lesions.ECLIPSE (NCT03108456) is a prospective, randomized, multicenter trial designed to evaluate two different vessel preparation strategies in severely calcified coronary artery lesions. The routine use of the Diamondback 360 Coronary Orbital Atherectomy System is compared with conventional balloon angioplasty prior to drug-eluting stent implantation. The trial aims to enroll approximately 2000 subjects with a primary clinical endpoint of target vessel failure, defined as the composite of cardiac death, target vessel-related myocardial infarction, or ischemia-driven target vessel revascularization assessed at 1 year. The co-primary endpoint is the acute post-procedural in-stent minimal cross-sectional area as assessed by optical coherence tomography in a 500-subject cohort. Enrollment is anticipated to complete in 2022 with total clinical follow-up planned for 2 years.ECLIPSE is a large-scale, prospective randomized trial powered to demonstrate whether a vessel preparation strategy of routine orbital atherectomy system is superior to conventional balloon angioplasty prior to implantation of drug-eluting stents in severely calcified coronary artery lesions.

Optical coherence tomography (OCT) has been widely adopted in research on coronary atherosclerosis and adopted clinically to optimize percutaneous coronary intervention. In this Review, Jang and colleagues summarize this rapidly progressing field, with the aim of standardizing the use of OCT in coronary atherosclerosis.Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.

The purpose of the current study was to use intravascular ultrasound (IVUS) to clarify anatomical and morphological lesion characteristics of uncrossable lesions.Uncrossable lesions are not always severely calcified. The prevalence of uncrossable lesions that are nonseverely calcified as well as other mechanisms for uncrossability has not been well clarified.A total of 252 de novo uncrossable lesions in native coronary arteries that underwent either rotational or orbital atherectomy due to inability of any balloon to cross the lesion and 38 lesions with severe calcium in which IVUS crossed preatherectomy were included. Severe calcium is defined as maximum arc of calcium ≥270°.Severe calcification was absent in 16% of uncrossable lesions, 83% of which had a significant vessel bend. Compared with crossable lesions with severe calcium, uncrossable lesions with severe calcium more often had a bend in the vessel (71% vs. 21%, p 0.001) and a longer length of continuous severe calcium (median length of calcium ≥270° 3.8 mm vs. 1.9 mm, p = 0.001). Other than severe calcium (especially long continuous calcium) or a bend in the vessel, anatomical factors associated with uncrossabilty were aorto-ostial lesion location and small vessels.Uncrossable lesions are not always severely calcified. The interaction of lesion morphology (continuous long and large arcs of calcium) and vessel geometry (bend in the vessel or ostial lesion location) affect lesion crossability.

Atherosclerotic plaque progression and rupture play an important role in cardiovascular disease development and the final drastic events such as heart attack and stroke. Medical imaging and image-based computational modeling methods advanced considerably in recent years to quantify plaque morphology and biomechanical conditions and gain a better understanding of plaque evolution and rupture process. This article first briefly reviewed clinical imaging techniques for coronary thin-cap fibroatheroma (TCFA) plaques used in image-based computational modeling. This was followed by a summary of different types of biomechanical models for coronary plaques. Plaque progression and vulnerability prediction studies based on image-based computational modeling were reviewed and compared. Much progress has been made and a reasonable high prediction accuracy has been achieved. However, there are still some inconsistencies in existing literature on the impact of biomechanical and morphological factors on future plaque behavior, and it is very difficult to perform direct comparison analysis as differences like image modality, biomechanical factors selection, predictive models, and progression/vulnerability measures exist among these studies. Encouraging data and model sharing across the research community would partially resolve these differences, and possibly lead to clearer assertive conclusions. In vivo image-based computational modeling could be used as a powerful tool for quantitative assessment of coronary plaque vulnerability for potential clinical applications.

BACKGROUND Connecting the antegrade wire (AW) and the retrograde wire (RW) is a goal of chronic total occlusion (CTO) treatment, but angiographic guidewire location is sometimes misleading. AIMS The aim of this study was to evaluate the association between intravascular ultrasound (IVUS)-defined AW and RW position and procedural outcomes when treating CTO lesions using the retrograde approach. METHODS Overall, 191 CTO lesions treated using an IVUS-guided retrograde approach at three centres in Japan, China, and the USA were included. RESULTS When the AW and RW angiographically overlapped, four wire positions were seen on IVUS: (i) AW within the plaque (AW-intraplaque) and RW-intraplaque in 34%; (ii) AW-intraplaque and RW in the subintimal space (RW-subintima) in 28%; (iii) AW-subintima and RW-subintima in 22%; or (iv) AW-subintima and RW-intraplaque in 16%. The procedure succeeded without repositioning the wire in 89% of AW-intraplaque/RW-intraplaque, 61% of AW-intraplaque/RW-subintima and 57% of AW-subintima/RW-subintima, but only one (3%) AW-subintima/RW-intraplaque. Lesion and procedure complexity and failure/complications were greatest in AW-subintima/RW-intraplaque. CONCLUSIONS IVUS-identified vascular compartment concordance versus IVUS-identified vascular compartment mismatch leads to higher success rates irrespective of intraplaque or subintimal passage. AW-subintima/RW-intraplaque was associated with the most complex CTO morphology and procedure, and repositioning the wire was almost always necessary. Visual summary. When the antegrade wire is in the subintimal space and the retrograde wire is in the intraplaque, re-wiring is almost always necessary.

OBJECTIVES Incidence and prognosis of ST-segment elevation myocardial infarction (STEMI) vary according to ambient temperature and season. We sought to assess whether season and temperature on the day of STEMI are associated with infarct size, microvascular obstruction (MVO), left ventricular ejection fraction (LVEF) and clinical outcomes after primary percutaneous coronary intervention (PCI). METHODS Individual patient data from 1598 patients undergoing primary PCI in six randomized clinical trials were pooled. Infarct size was evaluated by cardiac magnetic resonance within 30 days in all trials. Patients were categorized either by whether they presented on a day of temperature extremes (minimum temperature 25 °C) or according to season. RESULTS A total of 558/1598 (34.9%) patients presented with STEMI on a day of temperature extremes, and 395 (24.7%), 374 (23.4%), 481 (30.1%) and 348 (21.8%) presented in the spring, summer, fall and winter. After multivariable adjustment, temperature extremes were independently associated with larger infarct size (adjusted difference 2.8%; 95% CI, 1.3-4.3; P

Objectives We investigated clinical determinants of disease burden and vulnerability using optical coherence tomography (OCT) co-registered with intravascular ultrasound (IVUS) in a large cohort of patients. Methods A total of 704 patients [44.5% with acute coronary syndromes (ACS)] underwent coronary intervention. IVUS plaque burden and OCT lipid, macrophage and calcium indices and the presence of thrombus, plaque rupture and thin-cap fibroatheroma (TCFA) were analyzed. Results Median patient age was 66 years with 81.8% men, 34.4% with diabetes mellitus and 15.5% with preadmission statins. Median lesion length was 25.7 mm, and 33.0% had a TCFA. Adjusted models indicated (1) older patient age was related to more calcium, but fewer macrophages; (2) men were related to more thrombus with plaque rupture while women had more thrombus without plaque rupture; (3) ACS presentation was related to morphological acute thrombotic events (more thrombus with/without rupture) and plaque vulnerability (more TCFA, more lipid and macrophages and larger plaque burden); (4) diabetes mellitus was related to a greater atherosclerotic disease burden (more lipid and calcium and larger plaque burden) and more thrombus without rupture; (5) hypertension was related to more macrophages; (6) current smoking was related to less calcium; and (7) renal insufficiency and preadmission statin therapy were not independently associated with IVUS or OCT plaque morphology. Conclusion Patient characteristics, especially diabetes mellitus and aging, affect underlying atherosclerotic burden, among which a greater lipidic burden along with sex differences influence local thrombotic morphology that affects clinical presentation.

Objectives The aim of this study was to evaluate various stent expansion indexes to determine the best predictor of clinical outcomes. Background Numerous intravascular ultrasound (IVUS) studies have shown minimum stent area (MSA) to be the most powerful predictor of future events. Methods ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective, multicenter registry of 8,582 patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents. Native coronary artery lesions treated with IVUS-guided PCI with final analyzable IVUS were included. Ten stent expansion indexes (MSA, MSA/vessel area at MSA site, conventional stent expansion [MSA/average of proximal and distal reference luminal area], minimum stent expansion using Huo-Kassab or linear model accounting for vessel tapering, stent asymmetry [minimum/maximum stent diameter within the entire stent], stent eccentricity [smallest minimum/maximum stent diameter at a single slice within the stent], IVUS-XPL [Impact of intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions] criteria, ULTIMATE [Intravascular Ultrasound Guided Drug Eluting Stents Implantation in “All-Comers” Coronary Lesions] criteria, and ILUMIEN IV criteria) were evaluated for their associations with lesion-specific 2-year clinically driven target lesion revascularization (TLR) or definite stent thrombosis. Results Overall, 2,140 lesions in 1,831 patients were included; final MSA measured 6.2 ± 2.4 mm2. Among the 10 stent expansion indexes, only MSA/vessel area at the MSA site was independently associated with 2-year clinically driven TLR or definite stent thrombosis (hazard ratio: 0.77; 95% confidence interval: 0.59-0.99; P = 0.04) after adjusting for morphologic and procedural parameters. Conclusions In this IVUS-guided PCI cohort with excellent final MSA overall, stent/vessel area at the MSA site, an index of relative stent expansion, was superior to absolute MSA and other expansion indexes in predicting 2-year clinically driven TLR or definite stent thrombosis.

BACKGROUND A large, prospective, multicentre trial recently showed that fractional flow reserve (FFR) derived from coronary angiography (FFRangio) has an accuracy of 92% compared with conventional guidewire-based FFR (FFRwire); however, little is known about whether specific patient/lesion characteristics affect the diagnostic performance. AIMS The primary goal of the present study was to investigate whether specific patient or lesion characteristics such as high body mass index (BMI), presentation with an acute coronary syndrome, or lesion location affect the diagnostic performance of FFRangio in patients enrolled in the FAST-FFR study. METHODS FFRangio was measured in a blinded fashion in 301 patients (319 vessels) who were undergoing FFRwire assessment. Using an FFRwire ≤0.80 as a reference, the diagnostic performance of FFRangio was compared in pre-specified subgroups. RESULTS The mean FFRwire and FFRangio were 0.81±0.13 and 0.80±0.12. Overall, FFRangio had a sensitivity of 93.5% and specificity of 91.2% for predicting FFRwire. Patient characteristics including age, sex, clinical presentation, body mass index, and diabetes did not affect sensitivity or specificity (p>0.05 for all). Similarly, lesion characteristics including calcification and tortuosity did not affect sensitivity or specificity (p>0.05 for all), nor did lesion location (proximal, middle, versus distal). Sensitivity was equally high across all target vessels, while specificity was highest in the LAD and lower (~85%) in the RCA and LCx (p

Advances in intravascular imaging have enabled assessment of the underlying plaque morphology in acute coronary syndromes, which allows for the initiation of individualized therapy. The atherothrombotic substrates for acute coronary syndromes consist of plaque rupture, erosion, and calcified nodule, whereas spontaneous coronary artery dissection, coronary artery spasm, and coronary embolism constitute rarer nonatherothrombotic etiologies. This review provides a brief overview of the data from clinical studies that have used intravascular optical coherence tomography to assess the culprit plaque morphology. We discuss the usefulness of intravascular imaging for effective treatment of patients presenting with acute coronary syndromes by percutaneous coronary intervention.

Coronary vessel layer structure may have a considerable impact on plaque stress/strain calculations. Most current plaque models use single-layer vessel structures due to the lack of available multilayer segmentation techniques. In this paper, an automatic multilayer segmentation and repair method was developed to segment coronary optical coherence tomography (OCT) images to obtain multilayer vessel geometries for biomechanical model construction. Intravascular OCT data were acquired from six patients (one male; mean age: 70.0) using a protocol approved by the local institutional review board with informed consent obtained. A total of 436 OCT slices were selected in this study. Manually segmented data were used as the gold standard for method development and validation. The edge detection method and cubic spline surface fitting were applied to detect and repair the internal elastic membrane (IEM), external elastic membrane (EEM) and adventitia–periadventitia interface (ADV). The mean errors of automatic contours compared to manually segmented contours were 1.40%, 4.34% and 6.97%, respectively. The single-layer mean plaque stress value from lumen was 117.91 kPa, 10.79% lower than that from three-layer models (132.33 kPa). On the adventitia, the single-layer mean plaque stress value was 50.46 kPa, 156.28% higher than that from three-layer models (19.74 kPa). The proposed segmentation technique may have wide applications in vulnerable plaque research.

Background: Clinical and morphological factors associated with lipidic versus calcified neoatherosclerosis within second-generation drug-eluting stents and the impact of lipidic versus calcified neoatherosclerosis on long-term outcomes after repeat intervention have not been well studied. Methods: A total of 512 patients undergoing optical coherence tomography before percutaneous coronary intervention for second-generation drug-eluting stents in-stent restenosis were included. Neoatherosclerosis was defined as lipidic or calcified neointimal hyperplasia in ≥3 consecutive frames or ruptured lipidic neointimal hyperplasia. The primary outcome was target lesion failure (cardiac death, target vessel myocardial infarction, definite stent thrombosis, or clinically driven target lesion revascularization). Results: The overall prevalence of neoatherosclerosis was 28.5% (146/512): 56.8% lipidic, 30.8% calcified, and 12.3% both lipidic and calcific. The prevalence increased as a function of time from stent implantation: 20% at 1 to 3 years, 30% at 3 to 7 years, and 75% >7 years. Renal insufficiency, poor lipid profile, and time from stent implantation were associated with lipidic neoatherosclerosis, whereas severe renal insufficiency, female sex, and time from stent implantation were associated with calcified neoatherosclerosis. Multivariable Cox regression revealed that female sex and lipidic neoatherosclerosis were associated with more target lesion failure, whereas stent age and final minimum lumen diameter after reintervention were related to lower target lesion failure. Calcified neoatherosclerosis was not related to adverse events after reintervention for in-stent restenosis given a large enough minimum lumen diameter was achieved. Conclusions: Lipidic but not calcified neoatherosclerosis was associated with poor subsequent outcomes after repeat revascularization if optimal stent expansion was achieved in lesions with calcified neoatherosclerosis.

Mechanical properties of the arterial walls could provide meaningful information for the diagnosis, management and treatment of cardiovascular diseases. Classically, various experimental approaches were conducted on dissected arterial tissues to obtain their stress–stretch relationship, which has limited value clinically. Therefore, there is a pressing need to obtain biomechanical behaviors of these vascular tissues in vivo for personalized treatment. This paper reviews the methods to quantify arterial mechanical properties in vivo. Among these methods, we emphasize a novel approach using image-based finite element models to iteratively determine the material properties of the arterial tissues. This approach has been successfully applied to arterial walls in various vascular beds. The mechanical properties obtained from the in vivo approach were compared to those from ex vivo experimental studies to investigate whether any discrepancy in material properties exists for both approaches. Arterial tissue stiffness values from in vivo studies generally were in the same magnitude as those from ex vivo studies, but with lower average values. Some methodological issues, including solution uniqueness and robustness; method validation; and model assumptions and limitations were discussed. Clinical applications of this approach were also addressed to highlight their potential in translation from research tools to cardiovascular disease management.

Aims We aimed to use optical coherence tomography (OCT) to identify differences in atherosclerotic culprit lesion morphology in women with myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) compared with MI with obstructive coronary artery disease (MI-CAD). Methods and results Women with an OCT-determined atherosclerotic aetiology of non-ST segment elevation (NSTE)-MINOCA (angiographic diameter stenosis We analysed 58 women with NSTE-MINOCA and 52 women with NSTE-MI-CAD. Optical coherence tomography features of underlying vulnerable plaque (thin-cap fibroatheroma) were less common in MINOCA (3 vs. 35%) than in MI-CAD. Intraplaque haemorrhage (47 vs. 2%) and layered plaque (31 vs. 12%) were more common in MINOCA than MI-CAD, whereas plaque rupture (14 vs. 67%), plaque erosion (8 vs. 14%), and calcified nodule (0 vs. 6%) were less common in MINOCA. The angle of ruptured cavity was smaller and thrombus burden was lower in MINOCA. Conclusion The prevalence of atherothrombotic culprit lesion subtype varied substantially between MINOCA and MI-CAD. A majority of culprit lesions in MINOCA had the appearance of IPH or layered plaque. Clinical Trial Registration Information Clinical Trial Name: Heart Attack Research Program- Imaging Study (HARP); ClinicalTrial.gov Identifier: NCT02905357; URL: https://clinicaltrials.gov/ct2/show/NCT02905357

BACKGROUND: Intravascular optical coherence tomography (IVOCT) enables detailed plaque characterisation in-vivo, but visual assessment is time-consuming and subjective.AIMS: This study aims to develop and validate an automatic framework for IVOCT plaque characterisation using artificial intelligence (AI).METHODS: IVOCT pullbacks from 5 international centres were analysed in a corelab, annotating basic plaque components, inflammatory markers and other structures. A deep convolutional network with encoding-decoding architecture and pseudo-3D input was developed and trained using hybrid loss. The proposed network was integrated into commercial software to be externally validated on additional IVOCT pullbacks from three international corelabs, taking the consensus among corelabs as reference.RESULTS: Annotated images from 509 pullbacks (391 patients) were divided into 10,517 and 1,156 cross-sections for the training and testing datasets, respectively. Dice coefficient of the model was 0.906 for fibrous plaque, 0.848 for calcium and 0.772 for lipid in the testing dataset. Excellent agreement in plaque burden quantification was observed between the model and manual measurements (R2=0.98). In the external validation, the software correctly identified 518 out of 598 plaque regions from 300 IVOCT cross-sections, with a diagnostic accuracy of 97.6%[95%CI:93.4%-99.3%] in fibrous plaque, 90.5%[95%CI:85.2%-94.1%] in lipid and 88.5%[95%CI:82.4%-92.7%] in calcium. The median time required for analysis was 21.4 (18.6-25.0) seconds per pullback.CONCLUSIONS: A novel AI framework for automatic plaque characterisation in IVOCT was developed, providing excellent diagnostic accuracy in both internal and external validation. This model might reduce subjectivity in image interpretation and facilitate IVOCT quantification of plaque composition, with potential applications in research and IVOCT-guided PCI.

Aims In the ILUMIEN III trial, among 450 randomised patients with non-complex lesions undergoing percutaneous coronary intervention (PCI), optical coherence tomography (OCT) guidance led to greater stent expansion than angiography guidance, similar minimal stent area compared to both intravascular ultrasound (IVUS) guidance and angiography guidance, and lower rates of uncorrected dissection and malapposition than both IVUS guidance and angiography guidance. Whether these differences impact on clinical outcomes is unknown. The aim of the present study was to report the 12-month clinical follow-up data from the ILUMIEN III study. Methods and results OCT-guided PCI, using an external elastic lamina-based protocol, was compared to operator-directed IVUS-guided or angiography-guided PCI. Target lesion failure (TLF) and major adverse cardiovascular events (MACE) at 12 months were adjudicated by a blinded clinical events committee. There were no significant differences in the rates of TLF (2.0% OCT, 3.7% IVUS, 1.4% angiography), MACE (9.8% OCT, 9.1% IVUS, 7.9% angiography), or any of the individual components of these outcomes among the groups. No independent predictors of 12-month stent-related clinical events were identified from final OCT. Conclusions In this underpowered study, OCT-guided PCI of non-complex lesions did not show a statistical difference in clinical outcomes at 12 months compared with IVUS or angiography guidance. An appropriately powered trial, including only complex patients and lesions, is underway to substantiate the potential clinical benefit of OCT-guided PCI. Trial registration NCT02471586.

Aims Randomised trials have demonstrated improvement in clinical outcomes with intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) compared with angiography-guided PCI. The ILUMIEN III trial demonstrated non-inferiority of an optical coherence tomography (OCT)- versus IVUS-guided PCI strategy in achieving similar post-PCI lumen dimensions. ILUMIEN IV is a large-scale, multicentre, randomised trial designed to demonstrate the superiority of OCT- versus angiography-guided stent implantation in patients with high-risk clinical characteristics (diabetes) and/or complex angiographic lesions in achieving larger post-PCI lumen dimensions and improving clinical outcomes. Methods and results ILUMIEN IV is a prospective, single-blind clinical investigation that will randomise between 2,490 and 3,656 patients using an adaptive design to OCT-guided versus angiography-guided coronary stent implantation in a 1:1 ratio. The primary endpoints are: (1) post-PCI minimal stent area assessed by OCT in each randomised arm, and (2) target vessel failure, the composite of cardiac death, target vessel myocardial infarction, or ischaemia-driven target vessel revascularisation. Clinical follow-up will continue for up to two years. The trial is currently enrolling, and the principal results are expected in 2022. Conclusions The large-scale ILUMIEN IV randomised controlled trial will evaluate the effectiveness of OCT-guided versus angiography-guided PCI in improving post-PCI lumen dimensions and clinical outcomes in patients with diabetes and/or with complex coronary lesions. Trial registration NCT03507777.

Chronic total occlusions remain among the most technically challenging lesions to treat percutaneously. Limitations of 2-dimensional angiography may further hinder successful treatment of these lesions. Intrasvascular ultrasound has a key role in percutaneous recanalization for a chronic total occlusion by providing key lesion characteristics, facilitating guidewire crossing, elucidating the intraplaque or extralaque path of the guidewire, optimizing lesion preparation, guiding stenting and identifying suboptimal results. Live visualization of the guidewire during crossing may reduce extraplaque wire tracking. This review describes the practical uses of intravascular imaging for commonly encountered scenarios when treating chronic total occlusions.

Introduction: Coronary stenosis due to atherosclerosis restricts blood flow. Stenosis progression would lead to increased clinical risk such as heart attack. Although many risk factors were found to contribute to atherosclerosis progression, factors associated with fatigue is underemphasized. Our goal is to investigate the relationship between fatigue and stenosis progression based on in vivo intravascular ultrasound (IVUS) images and finite element models.Methods: Baseline and follow-up in vivo IVUS and angiography data were acquired from seven patients using Institutional Review Board approved protocols with informed consent obtained. Three hundred and five paired slices at baseline and follow-up were matched and used for plaque modeling and analysis. IVUS-based thin-slice models were constructed to obtain the coronary biomechanics and stress/strain amplitudes (stress/strain variations in one cardiac cycle) were used as the measurement of fatigue. The change of lumen area (DLA) from baseline to follow-up were calculated to measure stenosis progression. Nineteen morphological and biomechanical factors were extracted from 305 slices at baseline. Correlation analyses of these factors with DLA were performed. Random forest (RF) method was used to fit morphological and biomechanical factors at baseline to predict stenosis progression during follow-up.Results: Significant correlations were found between stenosis progression and maximum stress amplitude, average stress amplitude and average strain amplitude (p < 0.05). After factors selection implemented by random forest (RF) method, eight morphological and biomechanical factors were selected for classification prediction of stenosis progression. Using eight factors including fatigue, the overall classification accuracy, sensitivity and specificity of stenosis progression prediction with RF method were 83.61%, 86.25% and 80.69%, respectively.Conclusion: Fatigue correlated positively with stenosis progression. Factors associated with fatigue could contribute to better prediction for atherosclerosis progression.

The aim of this study was to compare the ability of two different atherectomy modalities, the directional atherectomy system (DAS) and the orbital atherectomy system (OAS), to modify plaque and augment luminal gain as evaluated by angiography and intravascular ultrasound (IVUS) in patients with symptomatic femoro-popliteal peripheral arterial disease (PAD).Atherectomy is frequently utilized in the treatment of complex PAD. To date, there are no head-to-head comparisons of existing devices and their selection is based mostly on operator preference rather than on supportive data.This was a single-center, prospective, randomized trial designed to assess the impact of DAS in comparison to OAS on atherosclerotic plaque. Pre- and postatherectomy lesion characterization was performed by angiography and IVUS. Drug-coated balloon (DCB) angioplasty was performed after atherectomy with similar analysis repeated.Sixty patients were randomized to undergo either DAS or OAS. Pretreatment angiographic and IVUS characteristics were similar in the DAS and OAS groups. DAS led to a greater reduction in plaque volume throughout the entire lesion (5.9% vs. 1.1%, p = 0.003). This corresponded to a greater increase in total vessel and lumen volume by IVUS (161.5 mmCompared to OAS, DAS demonstrated a greater plaque volume reduction and luminal gain with significantly fewer stents needed post-DCB.

BACKGROUND: Acute coronary syndromes most commonly arise from thrombosis of lipid-rich coronary atheromas that have large plaque burden despite angiographically appearing mild.OBJECTIVES: We sought to examine the outcomes of percutaneous coronary intervention (PCI) of non-flow-limiting vulnerable plaques.METHODS: Three-vessel imaging was performed with a combination intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) catheter after successful PCI of all flow-limiting coronary lesions in 898 patients presenting with myocardial infarction (MI). Patients with an angiographically non-obstructive stenosis not intended for PCI but with IVUS plaque burden ≥65% were randomized to treatment of the lesion with a bioresorbable vascular scaffold (BVS) plus guideline-directed medical therapy (GDMT) vs. GDMT alone. The primary powered effectiveness endpoint was the IVUS-derived minimum lumen area (MLA) at protocol-driven 25-month follow-up. The primary (non-powered) safety endpoint was randomized target lesion failure (TLF; cardiac death, target vessel-related MI or clinically-driven target lesion revascularization) at 24 months. The secondary (non-powered) clinical effectiveness endpoint was randomized lesion-related major adverse cardiac events (MACE; cardiac death, MI, unstable angina, or progressive angina) at latest follow-up.RESULTS: A total of 182 patients were randomized (93 BVS, 89 GDMT alone) at 15 centers. The median angiographic diameter stenosis of the randomized lesions was 41.6%; by NIRS-IVUS median plaque burden was 73.7%, median MLA was 2.9 mm2, and median maximum lipid plaque content was 33.4%. Angiographic follow-up at 25 months was completed in 167 patients (91.8%), and median clinical follow-up was 4.1 years. The follow-up MLA in BVS-treated lesions was 6.9±2.6 mm2 compared with 3.0±1.0 mm2 in GDMT alone-treated lesions (least square means difference 3.9 mm2, 95% CI 3.3-4.5, PCONCLUSIONS: PCI of angiographically mild lesions with large plaque burden was safe, substantially enlarged the follow-up MLA and was associated with favorable long-term clinical outcomes, warranting the performance of an adequately powered randomized trial.

Aims: The aim of the trial was to examine the influence of ezetimibe on plaque morphology in patients with ST-segment Elevation Myocardial Infarction (STEMI)with respect to fibrous cap thickness (FCT)and arcs of lipid plaque, calcific plaque, and macrophages using Optical Coherence Tomography (OCT). Methods and results: In 87 statin naïve patients with STEMI treated with primary percutaneous intervention, a non-culprit study plaque in a non-infarct related coronary artery was assessed with OCT at baseline and after 12 months. Patients were treated with atorvastatin 80 mg and randomized (1:1)to ezetimibe 10 mg (n = 43)or placebo (n = 44). An increase in median FCT (ezetimibe 200 (140–260)μm to 240 (190–305)μm (p = 0.002)vs. placebo 205 (135–260)μm to 230 (180–270)μm (p < 0.001), between groups p = ns), a reduction in lipid arc (ezetimibe 1728.5 (1022.5–3904.7)° to 1164.5 (736.6–2580.1)° (p = 0.001)vs. placebo 1671.6 (978.3–2868.7)° to 1373.7 (791.2–2267.3)° (p = 0.019), between groups p = ns), and macrophage arc (ezetimibe 1730.3 (965.7–2984.4)° to 1324.8 (819.0–2819.7)° (p < 0.05)vs. placebo 1570.5 (794.7–3016.8)° to 1418.9 (584.1–2501.1)° (p < 0.01), between groups p = ns)were observed. Conclusion: Aggressive LDL-lowering resulted in changes in OCT assessed plaque composition by increased FCT thickness and a reduction in lipid content and macrophage infiltration. Addition of ezetimibe 10 mg to atorvastatin 80 mg resulted in further LDL reduction, but no additional change in plaque composition was found.

Although coronary artery calcium (CAC) density has been associated with plaque stability, pathological evidence is lacking. We investigated the relationship between coronary computed tomography (CCT)-derived CAC density and multiple calcified and high-risk plaque (HRP) characteristics using optical coherence tomography (OCT).We analyzed 83 plaques from 33 stable angina patients who underwent both CCT and OCT. CAC density was measured at calcium plaques with ≥90 Hounsfield units (HU) and ≥130 HU using custom CT software. The correlation between median CAC density and OCT-derived calcium size (thickness and area) was assessed. To investigate whether median CAC densities measured at the 90 HU threshold were associated with plaque vulnerability, OCT-derived plaque characteristics and HRP characteristics were compared between the low (90-129 HU), intermediate (130-199 HU) and high (≥200 HU) CAC HU groups.Median CAC densities at 130 HU were moderately associated with calcium thickness (R = 0.573, p 0.001) and area (R = 0.560, p 0.001). Similar results were observed at 90 HU (thickness, R = 0.615, p 0.001; area, R = 0.612, p 0.001). Among groups with low, intermediate and high HU levels, calcium thickness (0.42 ± 0.14 mm, 0.60 ± 0.17 mm and 0.77 ± 0.19 mm, respectively; p 0.001) and area (0.55 ± 0.29 mmOCT-derived calcium size, but not HRP characteristics, were associated with CAC density, suggesting that CAC density is driven mainly by calcified plaque size but not local plaque vulnerability.

OBJECTIVES We sought to assess in-hospital and long-term outcomes of retrograde compared with antegrade-only percutaneous coronary intervention for chronic total occlusion (CTO PCI). BACKGROUND Procedural and clinical outcomes following retrograde compared with antegrade-only CTO PCI remain unknown. METHODS Using the core-lab adjudicated OPEN-CTO registry, we compared the outcomes of retrograde to antegrade-only CTO PCI. Primary endpoints included were in-hospital major adverse cardiac and cerebrovascular events (MACCE) (all-cause death, stroke, myocardial infarction [MI], emergency cardiac surgery, or clinically significant perforation) and MACCE at 1-year (all-cause death, MI, stroke, target lesion revascularization, or target vessel reocclusion). RESULTS Among 885 single CTO procedures from the OPEN-CTO registry, 454 were retrograde and 431 were antegrade-only. Lesion complexity was higher (J-CTO score: 2.7 vs. 1.9; p

We sought to investigate the characteristics and prognostic impact of healed plaque (HP) detected by optical coherence tomography (OCT) in non-culprit segments in treated vessels.OCT analysis included HP having a different optical intensity with clear demarcation from underlying plaque, thin-cap fibroatheroma (TCFA), and minimal lumen area. Non-culprit lesion (NCL) was defined as a plaque with90° arc of disease (≥0.5 mm intimal thickness), length ≥2 mm, and location5 mm from the stent edges. Major adverse cardiac event (MACE) included cardiac death, myocardial infarction (MI), or ischemia-driven revascularization (IDR).We studied a total of 726 NCLs in 538 patients who underwent percutaneous coronary intervention with evaluable non-culprit segments by OCT. The prevalence of an HP was 17.8% (129/726) per lesion and 21.9% (118/538) per patient. At median follow-up of 2.2 years, there were 65 NCL-related MACE events, including 6 MIs and 65 IDRs of which 87.7% had a stable presentation. The presence of untreated HP was positively correlated with subsequent NCL-related MACE (hazard ratio [HR] 2.01, 95% confidence interval [CI], 1.20-3.37, p 0.01). There were 16 IDRs with stable angina occurring at a specific OCT-imaged NCL where an untreated HP was positively associated with subsequent NCL-related MACE (HR 3.72, 95% CI 1.35-10.30, p = 0.01) along with TCFA (HR 10.0, 95% CI 3.20-31.40, p 0.01) and minimal lumen area3.5 mmAn OCT-detected HP in an NCL is a marker for future (mostly) stable non-culprit-related MACE at both a patient- and lesion-level.

Plaque vulnerability prediction is of great importance in cardiovascular research. In vivo follow-up intravascular ultrasound (IVUS) coronary plaque data were acquired from nine patients to construct fluid-structure interaction models to obtain plaque biomechanical conditions. Morphological plaque vulnerability index (MPVI) was defined to measure plaque vulnerability. The generalized linear mixed regression model (GLMM), support vector machine (SVM) and random forest (RF) were introduced to predict MPVI change (ΔMPVI = MPVI

Background Supersaturated oxygen (SSO2 ) has recently been approved by the U.S. Food and Drug Administration for administration after primary percutaneous coronary intervention (pPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) based on its demonstration of infarct size reduction in the IC-HOT study. Objectives To describe the 1-year clinical outcomes of intracoronary SSO2 treatment after pPCI in patients with anterior STEMI. Methods IC-HOT was a prospective, open-label, single-arm study in which 100 patients without cardiogenic shock undergoing successful pPCI of an occluded left anterior descending coronary artery were treated with a 60-min SSO2 infusion. One-year clinical outcomes were compared with a propensity-matched control group of similar patients with anterior STEMI enrolled in the INFUSE-AMI trial. Results Baseline and postprocedural characteristics were similar in the two groups except for pre-PCI thrombolysis in myocardial infarction 3 flow, which was less prevalent in patients treated with SSO2 (9.6% vs. 22.9%, p = .02). Treatment with SSO2 was associated with a lower 1-year rate of the composite endpoint of all-cause death or new-onset heart failure (HF) or hospitalization for HF (0.0% vs. 12.3%, p = .001). All-cause mortality, driven by cardiovascular mortality, and new-onset HF or HF hospitalization were each individually lower in SSO2 -treated patients. There were no significant differences between groups in the 1-year rates of reinfarction or clinically driven target vessel revascularization. Conclusions Infusion of SSO2 following pPCI in patients with anterior STEMI was associated with improved 1-year clinical outcomes including lower rates of death and new-onset HF or HF hospitalizations.

The aim of this study was to use optical coherence tomography (OCT) to predict newly implanted stent expansion for treatment of in-stent restenosis (ISR).With OCT guidance, 143 ISR lesions were treated with a new stent. Stent underexpansion was defined as minimum stent area (MSA)4.5 mm2 and MSA/average of reference lumen area70%. New stent underexpansion was found in 33 lesions (23%). These had a smaller old stent MSA (4.13 [3.32-4.62] versus 5.18 [4.01-6.38] mm2, p=0.001), and had a higher prevalence of multiple old stent layers (51.5% versus 10.9%, p0.001) and neointimal or peri-stent calcium (69.7% versus 37.3%, p=0.001) compared to those without new stent underexpansion. Old stent underexpansion, multiple layers of old stent, maximum calcium angle180°, and maximum calcium thickness0.5 mm were independently associated with new stent underexpansion. Patients with new stent underexpansion had a higher prevalence of major adverse cardiac events (35.5% vs 14.3%, p=0.009), mainly driven by a higher rate of myocardial infarction and target vessel revascularisation at two years.When re-stenting an ISR lesion, old stent underexpansion, the amount of neointimal or peri-stent calcium, and multiple old stent strut layers are important determinants of new stent underexpansion which is then associated with adverse long-term outcomes.

Background A myocardial bridge (MB) is a coronary variant in which an epicardial coronary artery tunnels through the myocardial band. Although MBs have been reported to cause ischaemia, physiological assessment of an MB has not been fully established. Case summary We encountered a case with exertional chest pain who underwent coronary angiography showing an MB at the mid-left anterior descending artery with systolic compression. Optical coherence tomography showed an MB defined as a homogeneous intermediate intensity surrounding the epicardial artery. The full-cycle ratio, defined as the lowest ratio of distal coronary pressure (Pd) to aortic pressure (Pa) during the entire cardiac cycle, measured 0.89 at rest and 0.73 with intravenous dobutamine of 20 µg/kg/min with a distinctive waveform pattern (early diastolic Pd drop) during a dobutamine challenge. Metoprolol succinate dosage was increased. The patient has been free from chest pain for 7 months after the discharge. Discussion Optical coherence tomography may contribute to anatomical detections of MBs. Because a systolic compression of the MB and release of the vascular lumen during early diastole leads to an early steep pressure loss, early diastolic Pd drop should be one of the specific haemodynamic characteristics of MBs. On the other hand, in a severe atherosclerotic stenosis, Pd drop is typically observed in late diastole, which could be differentiated from that of MBs. Because full-cycle ratio reflects the whole cardiac cycle including early diastole, this might be more useful than other physiological indices for detection of MB-related ischaemia induced by a dobutamine challenge.

Objectives This study sought to determine if plaque structural stress (PSS) and other plaque stress parameters are increased in plaques that cause future major adverse cardiovascular event...