Presence Of Thin-cap Fibroatheroma Research Articles

Influence of intracoronary hemodynamic forces on atherosclerotic plaque phenotypes

Background and aimsCoronary hemodynamics impact coronary plaque progression and destabilization. The aim of the present study was to establish the association between focal vs. diffuse intracoronary pressure gradients and wall shear stress (WSS) patterns with atherosclerotic plaque composition. MethodsProspective, international, single-arm study of patients with chronic coronary syndromes and hemodynamic significant lesions (fractional flow reserve [FFR] ≤ 0.80). Motorized FFR pullback pressure gradient (PPG), optical coherence tomography (OCT), and time-average WSS (TAWSS) and topological shear variation index (TSVI) derived from three-dimensional angiography were obtained. ResultsOne hundred five vessels (median FFR 0.70 [Interquartile range (IQR) 0.56–0.77]) had combined PPG and WSS analyses. TSVI was correlated with PPG (r = 0.47, [95% Confidence Interval (95% CI) 0.30–0.65], p < 0.001). Vessels with a focal CAD (PPG above the median value of 0.67) had significantly higher TAWSS (14.8 [IQR 8.6–24.3] vs. 7.03 [4.8–11.7] Pa, p < 0.001) and TSVI (163.9 [117.6–249.2] vs. 76.8 [23.1–140.9] m−1, p < 0.001). In the 51 vessels with baseline OCT, TSVI was associated with plaque rupture (OR 1.01 [1.00–1.02], p = 0.024), PPG with the extension of lipids (OR 7.78 [6.19–9.77], p = 0.003), with the presence of thin-cap fibroatheroma (OR 2.85 [1.11–7.83], p = 0.024) and plaque rupture (OR 4.94 [1.82 to 13.47], p = 0.002). ConclusionsFocal and diffuse coronary artery disease, defined using coronary physiology, are associated with differential WSS profiles. Pullback pressure gradients and WSS profiles are associated with atherosclerotic plaque phenotypes. Focal disease (as identified by high PPG) and high TSVI are associated with high-risk plaque features. Clinical trial registrationhttps://clinicaltrials,gov/ct2/show/NCT03782688

Abstract 14321: High Sensitivity C-Reactive Protein is Associated With Plaque Vulnerability and Increased Incidence of Adverse Events in Patients With Stable Coronary Disease

Introduction: Higher level of high sensitivity C-reactive protein (hsCRP) is associated with an increased risk of cardiovascular events in patients with coronary artery disease (CAD). However, the pathogenesis of the worse clinical outcomes in CAD patients with high hsCRP remains to be elucidated. Hypothesis: Higher hsCRP is associated with a higher prevalence of vulnerable characteristics in coronary plaques and an increased incidence of adverse events in patients with CAD. Methods: A total of 793 consecutive patients with stable CAD, who underwent intra coronary optical coherence tomography (OCT) imaging of the culprit vessel during percutaneous coronary intervention were included. Patients were classified into the higher hsCRP group (hsCRP ≥ 0.2 mg/dL, n=247) or the lower hsCRP group (hsCRP &lt; 0.2 mg/dL, n=546). OCT characteristics and clinical outcomes were investigated according to the level of hsCRP. Results: The prevalence of thin-cap fibroatheroma (TCFA) (32.0% vs. 20.9%, p &lt;0.001) and plaque with macrophage (53.9% vs. 46.2%, p =0.045) was significantly higher in the higher hsCRP group than in the lower hsCRP group (Panel A). The incidence of myocardial infarction was significantly higher in the higher hsCRP group than in the lower hsCRP group (log-rank p =0.006) during a median 938 days follow-up (Panel B) although the incidence of the composite of major adverse cardiac events was comparable (log-rank p =0.282). Among the four groups classified by the hsCRP level and the presence of TCFA, the incidence of myocardial infarction was the highest in the group with higher hsCRP and TCFA (log-rank p =0.017). Conclusions: Higher level of hsCRP was associated with a higher prevalence of vulnerable characteristics in coronary plaques and worse clinical outcomes in patients with stable CAD. The risk of recurrent myocardial infarction in patients with high hsCRP levels was further increased by the presence of TCFA.

Thin-cap fibroatheroma and increased coronary intima-media thickness are associated with an altered balance of arginine metabolites.

Arginase inhibition increases plasma citrulline and citrulline / ornithine (C/O) ratio, and reduces plasma ornithine and ornithine / arginine (O/A) ratio in an animal model of myocardial infarction (MI). We hypothesized that the presence of thin‑cap fibroatheroma (TCFA) in the culprit lesion and increased non‑culprit intima‑media thickness of an infarct‑related artery (IRA) are associated with an altered balance of arginine metabolites. Arginine and its metabolites were measured using liquid chromatography and tandem mass spectrometry in 100 consecutive MI patients upon admission and at 6‑month follow‑up. TCFA and adjacent to culprit lesion proximal and distal 10‑mm segments were assessed with optical coherence tomography in the acute phase. Twenty five patients without coronary lesions on angiography served as controls. The C/O ratio increased 5.33 times (P <0.001), while the O/A ratio decreased 2.53 times (P <0.001) at the 6‑month follow‑up, as compared with the acute phase of MI. The patients with (n = 75) vs without (n = 25) TCFA had lower C/O ratio by 29% (P = 0.003), while the mean intima‑media diameter of adjacent non‑culprit region correlated with the follow‑up O/A ratio (R = 0.337; P = 0.003). In a multivariable analysis, a higher acute phase C/O ratio was associated with a lower risk of TCFA presence (odds ratio, 0.978; 95% CI, 0.962-0.994; P = 0.006), whereas a higher follow‑up O/A ratio correlated with larger intima‑media diameter of the adjacent segments (β coefficient, 0.227; 95% CI for β coefficient, 0.045-0.409; P = 0.018). Enhanced arginase activity over nitric oxide synthase following ischemia was associated with the presence of TCFA in the culprit lesion, while a similar metabolic shift in the chronic phase correlated with a greater thickness of the intima‑media in the adjacent non‑culprit IRA segments.

Atherosclerotic Coronary Plaque features in patients with Acute Coronary Syndrome and Chronic Obstructive Pulmonary Disease

Abstract Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder characterized by airflow limitation, persistent respiratory symptoms and chronic lung inflammation. Previous studies reported a robust relationship between COPD and coronary artery disease (CAD). Local and systemic inflammation, known to play a role in atherosclerosis development, has been reported in patients with COPD, and has been proposed as one of the possible pathogenetic factors linking COPD and CAD. However, data on atherosclerotic coronary pattern and coronary inflammation in COPD patients are lacking. Purpose To study the characteristics of atherosclerotic coronary plaques and local inflammation by using optical coherence tomography (OCT) in COPD patients presenting with acute coronary syndromes (ACS). Methods ACS patients undergoing intracoronary OCT imaging of the culprit vessel were retrospectively identified. Coronary plaque characteristics and OCT-defined macrophage infiltration (MØI) were assessed by OCT. ACS patients were divided into 2 groups according to the presence or the absence of an established diagnosis of COPD, and coronary plaque features and MØI both at the culprit plaque site and along the culprit vessel were compared between the two groups. Results Among 146 ACS patients (mean age, 66,1±12,7 years, 109 males), 47 (32,2%) had COPD. Patients with COPD were older, were more frequently on therapy with an angiotensin receptor blocker, had lower hemoglobin, total cholesterol and triglycerides levels, and had higher serum creatinine levels. The prevalence of different mechanisms of ACS were similar between COPD and noCOPD patients (plaque rupture: 57,4% vs. 45,4%, plaque erosion: 23,4% vs. 32,3%, calcified plaque: 19,1% vs. 22,2%, respectively, overall p=0,381). OCT analysis of plaque microstructures showed that COPD patients had significantly higher prevalence of MØI (78,7% vs. 54,4%, p=0,005), thin cap fibroatheroma (TCFA) (48,9% vs. 22,2%, p=0,001), spotty calcium (68,1% vs. 26,3%, p&amp;lt;0,001) and calcifications (83,0% vs. 66,7%, p=0,040) at the culprit site than noCOPD patients. In the multivariate logistic regression analysis performed to adjust for clinical features, COPD was independently associated with MØI both at the culprit site (OR: 4,726, CI: 1,599; 13,971, p=0,005) and along the culprit vessel (OR: 2,193, CI: 1,110; 4,332, p=0,024). Similarly, COPD was independently associated with the presence of TCFA both at the culprit site (OR: 5,737, CI: 1,877; 17,540, p=0,002) and along the culprit vessel (OR: 2,796, CI: 1,408; 5,553, p=0,003). Conclusions In ACS patients undergoing OCT imaging of the culprit vessel, COPD was an independent predictor of local plaque inflammation and plaque vulnerability both at the culprit site and along the culprit vessel. Our results may suggest that a higher inflammatory milieu in COPD patients might enhance local coronary inflammation, promoting CAD development and plaque vulnerability. Funding Acknowledgement Type of funding sources: None.

Comparison of neoatherosclerosis and a clinical outcomes between bioabsorbable versus durable polymer drug-eluting stent: Verification by optical coherence tomography analysis.

Neoatherosclerosis after drug-eluting stent (DES) implantation is known to be related with increased risk of late restenosis and stent thrombosis. Neoatherosclerosis and relevant clinical outcomes between bioabsorbable polymer DES (BP-DES) and second-generation durable polymer DES (DP-DES) were evaluated by optical coherence tomography (OCT) analysis. A total of 311 patients (319 lesions) undergoing OCT analysis after DES implantation were enrolled and divided into two groups according to stent type (BP-DES [150 patients, 153 lesions] and DP-DES [161 patients, 166 lesions]). Follow-up OCT analysis was performed at least 9 months after index stent implantation. Neoatherosclerosis was defined as presence of thin-cap fibroatheroma, calcified plaque, and lipid plaque. Primary endpoint was the incidence of neoatherosclerosis, and the secondary endpoints were the occurrence of major adverse cardiac events (MACE), defined as a composite of death, myocardial infarction, target lesion revascularization, or stent thrombosis and to find independent predictors of neoatherosclerosis. The incidence of neoatherosclerosis was lower in the BP-DES group than the DP-DES group (5.2% vs. 14.5%, p = 0.008), which was driven by lipid plaque. However, the incidence of MACE did not show statistical difference between the two groups in median 4-year follow-up (3.3% vs. 7.8%, hazard ratio 1.964, 95% confidence interval 0.688-5.611, p = 0.207). Less use of angiotensin converting enzyme inhibitors/angiotensin II receptor blockade and higher degree of neointimal hyperplasia remained independent predictors of neoatherosclerosis on Cox regression analysis. Patients undergoing BP-DES implantation had lower incidence of neoatherosclerosis than DP-DES, which did not reach statistically better clinical outcomes.

Predictors of Near-Infrared Spectroscopy-Detected Lipid-Rich Plaques by Optical Coherence Tomography-Defined Morphological Features in Patients With Acute Coronary Syndrome.

BackgroundNear-infrared spectroscopy (NIRS) provides the localization of lipid-rich components in coronary plaques. However, morphological features in NIRS-detected lipid-rich plaques (LRP) are unclear.MethodsA total of 140 de novo culprit lesions in 140 patients with the acute coronary syndrome (ACS) who underwent NIRS and optical coherence tomography (OCT) examinations for the culprit lesions at the time of percutaneous coronary interventions were investigated. We defined a NIRS-LRP as a lesion with a maximum lipid core burden index of 4 mm [LCBI4mm] > 500 in the culprit plaque. Clinical demographics, angiographic, and OCT findings were compared between the patients with NIRS-LRP (n = 54) vs. those without NIRS-LRP (n = 86). Uni- and multivariable logistic regression analyses were performed to examine the independent OCT morphological predictors for NIRS-LRP.ResultsClinical demographics showed no significant differences between the two groups. The angiographic minimum lumen diameter was smaller in the NIRS-LRP group than in the non- NIRS-LRP group. In OCT analysis, the minimum flow area was smaller; lipid angle, lipid length, the prevalence of thin-cap fibroatheroma, and cholesterol crystals were greater in the NIRS-LRP group than in the non-NIRS-LRP group. Plaque rupture and thrombi were more frequent in the NIRS-LRP group, albeit not significant. In a multivariable logistic regression analysis, presence of thin-cap fibroatheroma [odds ratio (OR): 2.56; 95% CI: 1.12 to 5.84; p = 0.03] and cholesterol crystals (OR: 2.90; 95% CI: 1.20 to 6.99; p = 0.02) were independently predictive of NIRS-LRP.ConclusionsIn ACS culprit lesions, OCT-detected thin-cap fibroatheroma and cholesterol crystals rather than plaque rupture and thrombi were closely associated with a great lipid-core burden.

246 Air pollution and coronary plaque vulnerability and instability: an optical coherence tomography study

Abstract Aims Air pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. We aimed at assessing the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). Methods and results ACS patients undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (M&amp;Oslash;I) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case’s home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO). Only patients with &amp;gt;2 years of available data on air pollution exposure prior to ACS were enrolled. We included 126 patients [median age 67.0 years (55.5–76.0), 97 (77.0%) male]. Sixty-six patients (52.4%) had PR as mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels compared to IFC, and PM2.5 was independently associated with PR [odds ratio per unit = 1.194, 95% CI: (1.036–1.377), P = 0.015]. Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of M&amp;Oslash;I at the culprit site. Interestingly, PM2.5, PM10, and CO levels were positively and significantly correlated with serum levels of C-reactive protein. ROC curves were constructed to assess the ability of PM2.5 to predict the presence of plaque rupture, TCFA or M&amp;Oslash;I. The AUC for PM2.5 to predict plaque rupture was 0.62 (95% CI: 0.52–0.71, P = 0.018), for TCFA was 0.71 (95% CI: 0.61–0.80, P &amp;lt;0.001) and for M&amp;Oslash;I was 0.80 (95% CI: 0.71–0.88, P &amp;lt;0.001). Using a PM2.5 cut-off value of 13.40 μg/m3, the sensitivity and specificity for M&amp;Oslash;I were 81% and 66%, respectively. Conclusions We provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is a risk factor for vulnerable plaque features and for plaque rupture as mechanism of coronary instability mediated by systemic and local plaque inflammation. Of importance, the thresholds of air pollutants that predicted the presence of vulnerable plaque features are far lower than commonly accepted safety thresholds used to start preventive measures for public health, suggesting that further efforts are needed in order to reduce the adverse effects on the cardiovascular system.

Abstract 13267: The Shifted Balance of Arginine Metabolites in Patients With Acute Myocardial Infarction and Its Association With the Composition of the Infarct-Related Culprit Lesion

Introduction: We hypothesize that acute phase of myocardial infarction (MI) is associated with suppression of nitric oxide synthase (NOS) and enhanced arginase activity. Moreover, this altered metabolic balance might correlate with the composition of vulnerable culprit lesion in the infarct-related coronary artery (IRA). Methods: Arginine metabolites (μM) including ornithine, citrulline, proline, spermine, spermidine, agmatine, homoarginine, creatine, asymmetric dimethylarginine (ADMA) and monomethyl-L-arginine acetate were measured using liquid chromatography and tandem mass spectrometry in 85 consecutive MI patients upon admission and at 6-month follow-up and were compared with the composition of the IRA culprit lesion assessed with optical coherence tomography (OCT). Results: The concentration of ornithine in acute phase of MI was higher by 44% and homoarginine by 62% whereas level of arginine was lower by 39% and citrulline by 64% (P&lt;0.001 for all), when compared to 6-month stable conditions. Following ischemia, the ratios of citrulline/arginine (0.10 [0.08; 0.14] vs 0.22 [0.18; 0.28]) and citrulline/ornithine (0.09 [0.07; 0.12] vs 0.47 [0.36; 0.55]) were decreased while the indices of ornithine/arginine (1.48 [1.08, 2.39] vs 0.50 [0.41, 0.60]) and homoarginine/arginine (0.17 [0.12; 0.22] vs 0.04 [0.03; 0.05]) were higher as compared with 6-month results (P&lt;0.001 for all). Both, concentrations of arginine metabolites and their ratios were not associated with the mechanism of IRA occlusion, the amount of calcium or lipids and the presence of intramural hematoma. However, in patients with (n=67) versus without (n=18) thin-cap fibroatheroma (TCFA) in OCT the higher median concentrations of ornithine (10.24 [7.86; 12.52] vs 7.82 [4.38; 9.57]), ADMA (0.40 [0.29; 0.49] vs 0.29 [0.23; 0.42]), homoarginine (1.02 [0.81; 1.27] vs 0.74 [0.62; 1.00]) and a higher ornithine/arginine ratio (1.73 [1.29; 2.54] vs 1.18 [1.01; 2.07]) with a lower citrulline/ornithine ratio (0.07 [0.09; 0.11] vs 0.13 [0.09; 0.15]) were found (P&lt;0.05 for all). Conclusions: During acute phase of MI the altered balance of arginine metabolites indicates NOS suppression and enhanced arginase activation and is associated with the presence of TCFA in IRA culprit lesion.

Prognostic value of characteristics of plaque combined with residual syntax score among patients with STEMI undergoing primary PCI: an intravascular optical coherence tomography study

AimThe present study aimed to explore these characteristics, particularly thin-cap fibroatheroma (TCFA), in relation to residual syntax score (rSS) in patients who presented with acute MI.Methods and outcomesA total of 434 consecutive patients with MI aged ≥18 years who had STEMI underwent primary PCI. Notably, compared with other subgroups, the presence of TCFA in culprit lesions and a higher level of rSS, were significantly associated with MACE. When rSS was divided into three groups, high rSS levels were associated with a higher incidence of MACE, in the subgroups of without TCFA (P = 0.005), plaque erosion (P = 0.045), macrophage infiltration (P = 0.026), and calcification (P = 0.002). AUC of ROC curve was 0.794 and 0.816, whereas the AUC of the survival ROC was 0.798 and 0.846.ConclusionThe results of this study could be used in clinical practice to support risk stratification.Trial registrationThis study was registered at ClinicalTrials.gov as NCT03593928.

Air Pollution and Coronary Plaque Vulnerability and Instability: An Optical Coherence Tomography Study

ObjectivesWe assessed the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). BackgroundAir pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. MethodsPatients with ACS undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case’s home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), PM10, and carbon monoxide (CO). Only patients with >2 years of available data on air pollution exposure prior to ACS were enrolled. ResultsWe included 126 patients (median age: 67.0 years of age; IQR: 55.5-76.0; 97 male patients [77.0%]). Sixty-six patients (52.4%) had PR as the mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels than to IFC, and PM2.5 was independently associated with PR (odds ratio: 1.194; 95% CI: 1.036 to 1.377; P = 0.015). Moreover, exposure to higher levels of PM2.5 was independently associated with the presence of TCFA and of MØI at the culprit site. Interestingly, PM2.5, PM10, and Co levels were positively and significantly correlated with serum levels of C-reactive protein. ConclusionsWe provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is associated with the presence of vulnerable plaque features and with plaque rupture as a mechanism of coronary instability. An enhanced systemic and plaque inflammatory activation may explain these findings.

Prognostic implications of cholesterol chrystals at ACS causing culprit lesions, insights from the translational OPTICO-ACS study program

Abstract Aims Cholesterol chrystals (CC) represent a feature of advanced plaque remodeling. Optical coherence tomography (OCT) allows for detailed morphological assessment of the culprit lesion, including the presence of CCs, in vivo. Since CCs have been identified as prognostically relevant plaque feature in coronary artery disease (CAD), the present analysis aims to further characterize their impact on adverse cardiovascular outcome in a large cohort of patients, presenting with acute coronary syndrome (ACS). Methods Within the translational OPTICO-ACS study program, 371 consecutive ACS-patients were included into the final analysis. OCT-characteristics, including the presence of CCs, were assessed by a standardized CoreLab analysis following universal consensus standards for OCT-derived plaque features. All patients were followed up for 12 months after the index event and major adverse cardiac events (MACE) consisting of death, myocardial infarction, target vessel revascularization plus re-hospitalization due to unstable or progressive angina pectoris were documented. Results 215 patients (58.1%) presented with cholesterol chrystals (CCs) at the culprit lesion. Plaque rupture (RFC-ACS) represented the primary ACS-causing pathophysiology (75.3%) in those patients. Further, the presence of CCs was associated with other high-risk features within the culprit lesion, i.e. the presence of thin cap fibroatheroma (77.7% vs. 63.2%; p&amp;lt;0.05), plaque calcification (80.5% vs. 67.1; p&amp;lt;0.01) and microchannels (80.1% vs. 70.1; p&amp;lt;0.05) as well as an increased area stenosis (0.77 vs. 0.73 mm2; p&amp;lt;0.01) and a greater maximum lipid arc (282.8 vs. 242.6°; p&amp;lt;0.01) as compared to culprit lesions free of CCs. Of note, there was a strong association among the occurrence of macrophages within the plaque and cholesterol crystals. Finally, and most importantly MACE during 12 months follow-up, consisting of cardiac death, myocardial infarction, target vessel revascularization and re-hospitalization due to progressive or unstable angina pectoris, occurred with nearly twice the frequency in CC-patients (20.3% vs. 10.6%; p&amp;lt;0.01) as compared to patients without CCs at the culprit site. Conclusion The present analysis introduces cholesterol chrystals as a novel prognostically relevant high-risk plaque feature allowing individual risk stratification for patients after ACS. Funding Acknowledgement Type of funding sources: None.

Long-term exposure to ambient air pollution portends a higher risk of coronary plaque vulnerability and instability in patients with acute coronary syndrome: an optical coherence tomography study

Abstract Background Air pollution is an emerging key player in determining the residual risk of coronary events. However, pathophysiological mechanisms linking air pollution and coronary events have been not adequately investigated. Purpose We assessed the relationship between exposure to air pollutants and mechanisms of coronary instability evaluated by optical coherence tomography (OCT) in patients with acute coronary syndrome (ACS). Methods ACS patients undergoing OCT imaging were retrospectively selected. Mechanism of culprit lesion instability was classified as plaque rupture (PR) or intact fibrous cap (IFC) by OCT, and the presence of macrophage infiltrates (MØI) and thin-cap fibroatheroma (TCFA) at the culprit site was also assessed. Based on each case's home address, exposure to several pollutants was evaluated, including particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO). Only patients with &amp;gt;2 years of available data on air pollution exposure prior to ACS were enrolled. Results We included 136 patients [median age 67.0 years (56.2–76.0), 104 (76.5%) male]. Sixty-six patients (48.5%) had PR as mechanism of plaque instability. Patients with PR were exposed to significantly higher PM2.5 levels compared to IFC, and PM2.5 was an independent predictor for PR (OR=1.133, 95% CI [1.020–1.258], p=0.019). Moreover, exposure to higher levels of PM2.5, PM10 and CO was an independent predictor for the presence of TCFA, while PM2.5 and CO levels predicted the presence of MØI. Interestingly, PM2.5, PM10 and CO levels were positively and significantly correlated with serum levels of C-reactive protein. ROC curves were constructed to assess the ability of PM2.5 to predict the presence of plaque rupture, TCFA or MØI. The AUC for PM2.5 to predict plaque rupture was 0.62 (95% CI: 0.52–0.71, p=0.018), for TCFA was 0.71 (95% CI: 0.61–0.80, p&amp;lt;0.001) and for MØI was 0.80 (95% CI: 0.71–0.88, p&amp;lt;0.001). Using a PM2.5 cut-off value of 13.40 μg/m3, the sensitivity and specificity for MØI were 81% and 66%, respectively. Conclusions We provide novel insights into the missing link between air pollution and increased risk of coronary events. In particular, exposure to higher concentrations of air pollutants is a risk factor for vulnerable plaque features and for plaque rupture as mechanism of coronary instability mediated by systemic and local plaque inflammation. Of importance, the thresholds of air pollutants that predicted the presence of vulnerable plaque features are far lower than commonly accepted safety thresholds used to start preventive measures for public health, suggesting that further efforts are needed in order to reduce the adverse effects on the cardiovascular system. Funding Acknowledgement Type of funding sources: None. Air pollutants exposure and OCT featuresROC curve analysis

Relationship among clinical characteristics, morphological culprit plaque features, and long-term prognosis in patients with acute coronary syndrome.

Culprit lesions of acute coronary syndrome (ACS) could be classified as plaque rupture (PR), erosion, or calcified nodule (CN). We aimed to determine the relationship among clinical characteristics, morphological plaque features, and long-term prognosis in ACS. Patients with ACS, who underwent pre-intervention optical coherence tomography between April 2013 and July 2018 were retrospectively enrolled, and classified into the three groups based on the culprit lesion morphology. In the 436 patients enrolled, incidences of PR, erosion, and CN in ACS culprit lesions were 46.1, 39.9, and 14.0%, respectively. Plaque erosion was more frequent in men aged < 60 years and CN was more frequent in older adults in both sexes (≥ 80 years) (P < 0.001). Patients with CN had a higher incidence of hemodialysis treatment (P < 0.001) and diabetes (P = 0.003). Multivariate analysis revealed that ST elevation myocardial infarction (STEMI) (P = 0.049) and presence of thin-cap fibroatheroma (TCFA) at the culprit lesion were independently associated with PR; in younger patients (< 60 year), preserved left ventricular ejection fraction and lower incidence of TCFA were correlated with plaque erosion; and older age, non-STEMI, or unstable angina pectoris, higher serum brain natriuretic peptide levels, and lower incidence of TCFA were independently associated with CN. Multivariable analysis revealed that CN (odds ratio [OR] 1.990, P = 0.005), male sex (OR 2.012, P = 0.004), and older age (OR 1.036, P < 0.001) were independently associated with future adverse events during a median follow-up of 757 days. Different patient characteristics and morphological features were associated with the type of culprit lesion in patients with ACS.

Close Association of Matrix Metalloproteinase-9 Levels With the Presence of Thin-Cap Fibroatheroma in Acute Coronary Syndrome Patients: Assessment by Optical Coherence Tomography and Intravascular Ultrasonography

BackgroundThin-cap fibroatheroma (TCFA) has been suggested as a precursor lesion of coronary plaque rupture. As elevated plasma matrix metalloproteinase-9 (MMP-9) levels have been documented in patients with acute coronary syndrome (ACS), we sought to determine whether the presence of TCFA is linked to MMP-9 levels in these patients. MethodsWe evaluated 51 ACS patients with de novo culprit lesions who were examined via optical coherence tomography and intravascular ultrasound. Blood samples were obtained from the peripheral vein (PV) and the ostium and culprit lesion of the infarct-related coronary artery (CA) in the acute phase of ACS and from the PV in the chronic phase (8 months after ACS). ResultsThe plasma MMP-9 level in the acute phase was significantly higher than that in the chronic phase. Plasma MMP-9 levels at the culprit lesion of the infarct-related CA were significantly higher than, but positively correlated with those in the PV (10.9 (5.9–16.1) ng/mL and 8.9 (5.6–13.0) ng/mL, p < 0.0001, respectively; Spearman ρ = 0.84, p < 0.0001). Significantly higher PV plasma MMP-9 levels were observed in patients with TCFA than in patients without TCFA (12.1 (7.0–13.5) and 5.7 (4.0–8.2) ng/ml, p<0.0001, respectively). Further, plasma MMP-9 levels in the PV were positively correlated with the remodeling index (Spearman ρ = 0.29, p = 0.039) and negatively correlated with fibrous cap thickness (Spearman ρ = −0.42, p = 0.0021). Receiver operating characteristic curve analysis showed that the plasma MMP-9 levels in the PV could predict the presence of TCFA at a cut-off value of 9.9 ng/mL. ConclusionsPlasma MMP-9 levels were closely associated with MMP-9 levels in the CA and were further linked with TCFA in patients with ACS.

Thin cap fibroatheroma and plaque rupture is associated with carotid thermal heterogeneity in patients presenting with acute myocardial infarction

Abstract Microwave radiometry (MWR) has been applied successfully in the evaluation of carotid atherosclerosis, measuring reliably temperature heterogeneity of atherosclerotic plaques. Recent studies have shown an association between increased carotid temperature heterogeneity (ΔT) detected by MWR and cardiovascular events. Vulnerable plaques of the coronary arteries, share common characteristics such as the thin cap fibrous cap, that make the prone to rupture in the presence of stimulus such as shear stress or inflammation. Optical coherence tomography (OCT) is an imaging method, by which the fibrous cap and the presence of plaque rupture can be accurately in vivo visualized. Purpose To evaluate the impact of carotid temperature heterogeneity on the culprit plaque morphology on patients presenting with acute myocardial infarction. Method A total of 37 patients undergoing percutaneous coronary intervention (PCI) for an acute myocardial infarction who had an identifiable de novo culprit lesion in a native coronary artery, were enrolled in this study. All patients underwent PCI and Optical Coherence Study (OCT) within 12 hours since symptom onset. The OCT study was performed according to the standard techniques and acquired images were analyzed by 2 independent investigators., After the completion of the PCI all patients underwent MWR of both carotid arteries and ΔT was defined as maximal temperature detected along each carotid artery minus minimum. Results Thirty four patients with acute myocardial infarction 21 with STEMI (61.76%) and 13 (38.23%) with NSTEMI were included in the study. Thin cap fibroatheroma (TCFA) was present in 31 patients (91.1%), while all ruptured plaques had a TCFA compared to 11 TCFA (78.57%) observed in plaques that had no rupture (p=0.03). HsCRP was significantly increased in ruptured plaques compared to non ruptured ones (14.41±4.02 versus 9.9±2.5, p&amp;lt;0.005). Mean ΔT was significantly increased in ruptured plaques compared to no ruptured ones (1.01±0.31 versus 0.51±0.14°C, p&amp;lt;0.005), as well as in plaques with TCFA compared to those without a TCFA (0.82±0.37 versus 0.60±0.05°C, p=0.001). In the multivariate analysis DM, hsCRP, and ΔT were entered from which DM (OR 4.12; 95% CI 0.77–22.07; P=0.07) and ΔTau ((OR for 0.1°C increase 1.43; 95% CI 1.03–1.98; P=0.03) remained in the final model, with ΔT being the only variable independently associated with the presence of TCFA. Similarly regarding plaque rupture, STEMI, hsCRP, and ΔT were entered in the multivariate analysis from which hsCRP (OR 1.51; 95% CI 0.99–2.28; P=0.051) and ΔTau ((OR for 0.1°C increase 3.40; 95% CI 1.29–8.96; P=0.013) remained in the final model, with ΔT being the only variable independently associated with the presence of rupture. Conclusions Carotid thermal heterogeneity is associated with TCFA and plaque rupture in patients with acute myocardial infarction. Funding Acknowledgement Type of funding source: None

Lack of statin therapy is associated with plaque instability in non-culprit non-ischemic lesions of diabetic patients – data from the COMBINE OCT-FFR study

Abstract Background Effect of statin therapy on coronary plaque stabilisation and reducing adverse cardiovascular events is well known both in primary and secondary prevention. Nevertheless, there is a paucity of data presenting the impact of statins on plaque morphology as assessed by optical coherence tomography (OCT). Purpose The goal of this analysis was to evaluate the plaque morphology using OCT within non-culprit, non-ischaemic coronary lesions in diabetes mellitus (DM) patients with or without statin pre-treatment. Methods All patients of the COMBINE (FFR-OCT) trial underwent fractional flow reserve (FFR) measurement followed by OCT in FFR negative lesions. OCT recorded the presence of thin-cap fibroatheroma (TCFA), plaque rupture (PR), plaque erosion (PE) and calcified nodule (CN). Results From the 391 patients, 82 (21%) had no statin at baseline. OCT was performed in 463 lesions of which 96 lesions assessed in statin naive and 367 lesions in statin treated group. The median angiographic diameter stenosis was 50% and the median FFR value was 0.88 in both groups (p=0.953 and p=0.448, respectively). Myocardial infarction (MI) at presentation was 16.6% and did not differ between groups (p=0.380). Patients without statin pre-treatment were characterized by lower rate of known hypercholesterolemia (47.6% vs. 63.0%; p=0.011), male gender (52.4% vs. 65.7%; p=0.027), active smokers (8.5% vs. 22.3%; p=0.004) and previous MI (22.0% vs. 35.3%; p=0.022) as compared to patients with statin pre-treatment, respectively. The results of the qualitative OCT findings see in Table 1. Conclusions Non-ischemic lesions of DM patients without statin pre-treatment showed more vulnerable and instable plaque features like wider lipid arc, thinner fibrotic cap and a higher prevalence of lipid-rich plaque, TCFA and PR suggesting a stabilizing effect of statins on non-ischemic atherosclerotic lesions. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): The trial is founded from the Department of Cardiology Zwolle Heart-centrum with support from a non-restricted grant from St Jude Medical (now Abbott)

The Interplay between Features of Plaque Vulnerability and Hemodynamic Relevance of Coronary Artery Stenoses

Fractional flow reserve (FFR) may not be immune from hemodynamic perturbations caused by both vessel and lesion related factors. The aim of this study was to investigate the impact of plaque- and vessel wall-related features of vulnerability on the hemodynamic effect of intermediate coronary stenoses. Methods and Results: In this cross-sectional study, patients referred to catheterization laboratory for clinically indicated coronary angiography were prospectively screened for angiographically intermediate stenosis (50–80%). Seventy lesions from 60 patients were evaluated. Mean angiographic stenosis was 62.1 ± 16.3%. After having performed FFR assessment, intravascular ultrasound (IVUS) was performed over the FFR wire. Virtual histology IVUS was used to identify the plaque components and thin cap fibroatheroma (TCFA). TCFA was significantly more frequent (65 vs. 38%, p = 0.026), and necrotic core volume (26.15 ± 14.22 vs. 16.21 ± 8.93 mm³, p = 0.04) was significantly larger in the positively remodeled than non-remodeled vessels. Remodeling index correlated with necrotic core volume (r = 0.396, p = 0.001) and with FFR (r = –0. 419, p = 0.001). With respect to plaque components, only necrotic core area (r = –0.262, p = 0.038) and necrotic core volume (r = –0.272, p = 0.024) were independently associated with FFR. In the multivariable model, presence of TCFA was independently associated with significantly lower mean FFR value as compared to absence of TCFA (adjusted, 0.71 vs. 0.78, p = 0.034). Conclusion: The current study demonstrated that for a given stenosis geometry, features of plaque vulnerability such as necrotic core volume, TCFA, and positive remodeling may influence the hemodynamic relevance of intermediate coronary stenoses.

Optical coherence tomography-defined plaque vulnerability in relation to functional stenosis severity stratified by fractional flow reserve and quantitative flow ratio.

We sought to investigate that the quantitative flow ratio (QFR) might be associated with optical coherence tomography (OCT)-defined plaque vulnerability. Both functional stenosis severity and plaque instability are related to adverse clinical outcomes in patients with coronary artery disease. Recent studies have shown an association between physiological stenosis severity and the presence of thin-cap fibroatheroma (TCFA). Measurement of QFR is a novel method for rapid computational estimation of fractional flow reserve (FFR). We investigated 327 de novo intermediate-to-severe coronary lesions in 295 stable patients who underwent OCT, FFR, and QFR computation. The lesions were divided into tertiles based on either the FFR or QFR. The OCT findings were compared among these tertiles of FFR and QFR. Each tertile was defined as follows: FFR-T1 (FFR < 0.72), FFR-T2 (0.72 ≤ FFR ≤ 0.79), and FFR-T3 (FFR > 0.79) and QFR-T1 (QFR < 0.73), QFR-T2 (0.73 ≤ QFR ≤ 0.78), and QFR-T3 (QFR > 0.78). The prevalence of OCT-defined TCFA showed graded differences in proportion to the QFR tertiles (25.0% vs. 12.8% vs. 6.6%, p = .003). An overall significant difference in the prevalence of TCFA was found among FFR tertiles (p = .048), although pairwise comparison did not show statistical significance. Compared with FFR-based classifications, the model that integrated the FFR and QFR categorization improved the incremental reclassification efficacy (relative integrated discrimination improvement, 0.069; p = .002; continuous net reclassification improvement, 0.356; p = .022) for predicting the presence of TCFA. OCT-defined plaque instability was associated with the QFR in angiographically intermediate-to-severe lesions. Compared with the FFR alone, the QFR can provide incremental efficacy in predicting the presence of TCFA.

3284Quantification of macrophage presence and identification of thin-cap fibroatheroma by optical coherence tomography image: histopathological validation study

Abstract Background Intracoronary optical coherence tomography (OCT) is thought to be capable of identifying a vulnerable, rupture-prone plaque based on the presence of a thin-cap fibroatheroma (TCFA). Moreover, recent studies have reported that OCT may be able to identify macrophage infiltration of the fibrous cap, a key characteristic of vulnerable plaque. Purpose This study evaluated the accuracy of OCT image for characterizing TCFA and identifying macrophage infiltration in comparison with histopathology. Methods A total of 924 focal plaques in 206 coronary arteries from 78 autopsy hearts were examined to compare OCT and histological images. By histology, 16 plaques (1.7%) were classified as TCFAsthat contained a large necrotic core covered by a thin (&lt;65μm) fibrous-cap. Correlating OCT-histological sections were identified and OCT-derived tissue property indexes named normalized standard deviation (NSD) and signal attenuation ratio were applied on the fibrous-cap to identify inflamed fibrous-cap defined as a macrophage percentage &gt;10% by histology. Results With histology as standard, the sensitivity, specificity, and negative-predictive-value of TCFAs were extremely high (more than 90%). However, the positive-predictive-value of TCFAs was only 32%, which indicated a high proportion of false-positives. Most false-positive diagnoses of OCT for TCFAs contained large amounts of foam cell accumulations on luminal surface without necrotic core. Twelve of 16 fibrous-caps were considered as inflamed and the remaining 4 were non-inflamed on histology. However, no significant difference in NSD and signal attenuation ratio were identified between them. There was moderate correlation of the fibrous-cap thickness between OCT and histology (r2 = 0.41 and p&lt;0.01). Conclusions OCT is a promising intracoronary imaging modality for differentiating tissue characteristics (fibrous, calcified, or lipid-rich plaque) and identifying TCFA. However, it is still challenging to precisely identify inflammation, fibrous-cap thickness, and necrotic core in the native coronary artery. Therefore, careful interpretation is required to assess coronary vulnerable plaque by OCT. Acknowledgement/Funding None

P5508Impact of CD14++CD16+ monocytes on coronary plaque vulnerability assessed by optical coherence tomography in coronary artery disease patients

Abstract Background Diabetes mellitus has been known as an important factor of coronary artery disease (CAD) progression despite of widespread with lipid-lowering therapy. Although we have reported that large glucose fluctuation is associated with the development of cardiovascular disease in both diabetes mellitus (DM) and non-DM patients, the underlying mechanisms remain unclear. Monocytes play a key role for atherosclerotic plaque formation. Monocytes in human peripheral blood are divided into three subsets: CD14++CD16− monocytes, CD14++CD16+ monocytes, and CD14+CD16++ monocytes. The CD14++CD16+ monocyte subset has recently received attention because it is reported to be associated with future cardiovascular events such as acute myocardial infarction. However, their impact on coronary plaque vulnerability in coronary artery disease (CAD) patients with or without DM remains unclear. Purpose The aim of this study was to investigate the impact of CD14++CD16+ monocyte levels on coronary plaque vulnerability and glucose fluctuation in stable CAD patients with well-regulated lipid levels. Methods This prospective observational study included 50 consecutive patients with CAD (DM [n=22], Non-DM [n=28]), receiving lipid-lowering therapy and undergoing coronary angiography and optical coherence tomography (OCT). Patients were divided into 3 tertiles according to the CD14++CD16+ monocyte percentages assessed by flow cytometry. Standard OCT parameters including lipid arc, lipid length, fibrous cap thickness (FCT) on lipid rich plaque, were assessed for 97 angiographically intermediate lesions (diameter stenosis: 30–70%). The presence of thin-cap fibroatheroma (TCFA), defined as a thin fibrous cap (&lt;65μm) overlying a lipid-rich plaque (&gt;90°), was also assessed. Daily glucose fluctuation assessed by using continuous glucose monitoring system was analyzed by measuring the mean amplitude of glycemic excursion (MAGE). Results CD14++CD16+ monocytes negatively correlated with FCT on lipid rich plaque (r=0.508, p&lt;0.01) (Figure. 1). The presence of thin-cap fibroatheroma (TCFA) was increased stepwise according to the tertile of CD14++CD16+ monocytes (0 [tertile 1] vs. 5 [tertile 2] vs. 10 [tertile 3], p&lt;0.01). CD14++CD16+ monocytes were a significant determinant of TCFA (OR 1.279, p=0.001). Although CD14++CD16+ monocytes were not significantly correlated with MAGE in DM patients (r=0.259, p=0.244), a significant relationship was found between CD14++CD16+ monocytes and MAGE in non-DM patients (r=0.477, p=0.018) (Figure 2). Conclusions CD14++CD16+ monocytes were associated with coronary plaque vulnerability in CAD patients with well-regulated lipid levels both in DM and non-DM patients. Cross-talk between glucose fluctuation and CD14++CD16+ monocytes may enhance plaque vulnerability, particularly in non-DM patients. CD14++CD16+ monocytes could be a possible therapeutic target for coronary plaque stabilization.