Proteomics associated with coronary high-risk plaques by optical coherence tomography.

Biomarkers are widely used for the diagnosis and monitoring of cardiovascular disease. However, markers for coronary high-risk plaques have not been identified. The aim of this study was to identify proteins specific to coronary high-risk plaques. Fifty-one patients (71.2 ± 11.1 years, male: 66.7%) who underwent intracoronary optical coherence tomography imaging and provided blood specimens for proteomic analysis were prospectively enrolled. A total of 1470 plasma proteins were analyzed per patient using the Olink® Explore 1536 Reagent Kit. In patients with thin-cap fibroatheroma, the protein expression of Calretinin (CALB2), Corticoliberin (CRH) and Alkaline phosphatase, placental type (ALPP) were significantly increased, while the expression of Neuroplastin (NPTN), Folate receptor gamma (FOLR3) and Serpin A12 (SERPINA12) were significantly decreased. In patients with macrophage infiltration, the protein expressions of Fatty acid-binding protein, intestinal (FABP2), and Fibroblast growth factor 21 (FGF21) were significantly decreased. In patients with lipid-rich plaques, the protein expression of Interleukin-17 C (IL17C) was significantly increased, while the expression of Fc receptor-like protein 3 (FCRL3) was significantly decreased. These proteins might be useful markers in identifying patients with coronary high-risk plaques. Clinical Trial Registration: https://www.umin.ac.jp/ctr/ , UMIN000041692.

Layered plaque is associated with high levels of vascular inflammation and vulnerability in patients with stable angina pectoris.

Layered plaque, a signature of previous plaque destabilization and healing, is a known predictor for rapid plaque progression; however, the mechanism of which is unknown. The aim of the current study was to compare the level of vascular inflammation and plaque vulnerability in layered plaques to investigate possible mechanisms of rapid plaque progression. This is a retrospective, observational, single-center cohort study. Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) for stable angina pectoris (SAP) were selected. Plaques were defined as any tissue (noncalcified, calcified, or mixed) within or adjacent to the lumen. Perivascular inflammation was measured by pericoronary adipose tissue (PCAT) attenuation at the plaque levels on CTA. Features of plaque vulnerability were assessed by OCT. Layered plaques were defined as plaques presenting one or more layers of different optical densities and a clear demarcation from underlying components on OCT. A total of 475 plaques from 195 patients who presented with SAP were included. Layered plaques (n = 241), compared with non-layered plaques (n = 234), had a higher level of vascular inflammation (-71.47 ± 10.74 HU vs. -73.69 ± 10.91 HU, P = 0.026) as well as a higher prevalence of the OCT features of plaque vulnerability, including lipid-rich plaque (83.8% vs. 66.7%, P < 0.001), thin-cap fibroatheroma (26.1% vs. 17.5%, P = 0.026), microvessels (61.8% vs. 34.6%, P < 0.001), and cholesterol crystals (38.6% vs. 25.6%, P = 0.003). Layered plaque was associated with a higher level of vascular inflammation and a higher prevalence of plaque vulnerability, which might play an important role in rapid plaque progression.Clinical trial registration: https://classic.clinicaltrials.gov/ct2/show/NCT04523194 .

Layered plaque and plaque volume in patients with acute coronary syndromes.

BACKGROUND: Layered plaque is a signature of previous subclinical plaque destabilization and healing. Following plaque disruption, thrombus becomes organized, resulting in creation of a new layer, which might contribute to rapid step-wise progression of the plaque. However, the relationship between layered plaque and plaque volume has not been fully elucidated. METHODS: Patients who presented with acute coronary syndromes (ACS) and underwent pre-intervention optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of the culprit lesion were included. Layered plaque was identified by OCT, and plaque volume around the culprit lesion was measured by IVUS. RESULTS: Among 150 patients (52 with layered plaque; 98 non-layered plaque), total atheroma volume (183.3 mm3[114.2 mm3 to 275.0 mm3] vs. 119.3 mm3[68.9 mm3 to 185.5 mm3], p = 0.004), percent atheroma volume (PAV) (60.1%[54.7-60.1%] vs. 53.7%[46.8-60.6%], p = 0.001), and plaque burden (86.5%[81.7-85.7%] vs. 82.6%[77.9-85.4%], p = 0.001) were significantly greater in patients with layered plaques than in those with non-layered plaques. When layered plaques were divided into multi-layered or single-layered plaques, PAV was significantly greater in patients with multi-layered plaques than in those with single-layered plaques (62.1%[56.8-67.8%] vs. 57.5%[48.9-60.1%], p = 0.017). Layered plaques, compared to those with non-layered pattern, had larger lipid index (1958.0[420.9 to 2502.9] vs. 597.2[169.1 to 1624.7], p = 0.014). CONCLUSION: Layered plaques, compared to non-layered plaques, had significantly greater plaque volume and lipid index. These results indicate that plaque disruption and the subsequent healing process significantly contribute to plaque progression at the culprit lesion in patients with ACS. CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov , NCT01110538, NCT03479723, UMIN000041692.

Biomarkers associated with coronary high-risk plaques.

Vascular inflammation, lipid metabolism, and thrombogenicity play a key role not only in atherogenesis but also in the development of acute coronary syndromes. Biomarkers associated with coronary high-risk plaques defined according to intravascular imaging have not been systematically studied. A total of 69 patients with coronary artery disease who underwent both optical coherence tomography and intravascular ultrasound imaging, and who provided blood specimens were included. Comprehensive biomarkers for inflammation, lipid, and coagulation were analyzed. Composite models sought biomarker patterns associated with thin-cap fibroatheroma (TCFA) and "high-risk plaques" (TCFA and large plaque burden). Two different composite models were developed for TCFA, based on the finding that high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor-1, fibrinogen, IL-6, homocysteine and amyloid A levels were elevated, and high-density lipoprotein cholesterol (HDL) and bile acid levels were decreased in these patients. Both composite models were highly accurate for detecting patients with TCFA (area under curve [AUC]: 0.883 in model-A and 0.875 in model-B, both p < 0.001). In addition, creatinine, hsCRP, fibrinogen, tumor necrosis factor-α, IL-6, homocysteine, amyloid A, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques". Two composite models were highly accurate for detection of patients with "high-risk plaques" (AUC: 0.925 in model-A and 0.947 in model-B, both p < 0.001). Biomarkers useful for detection of patients with high-risk coronary plaques defined according to intravascular imaging have been identified. These biomarkers may be useful to risk stratify patients and to develop targeted therapy.Clinical Trial Registration https://www.umin.ac.jp/ctr/ , UMIN000041692. Biomarkers and high-risk plaques hsCRP, PAI-1, fibrinogen, IL-6, homocysteine, amyloid A, HDL, and bile acid were useful for detecting patients with TCFA. hsCRP, fibrinogen, IL-6, homocysteine, amyloid A, creatinine, TNFα, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques" (plaque which has both TCFA and large plaque burden). White arrowhead denotes TCFA. Red and green dashed lines denote lumen area and external elastic membrane area, respectively.

Degree of luminal narrowing and composition of thrombus in plaque erosion.

As the degree of luminal narrowing increases, shear stress increases, and high shear stress is known to activate platelets. However, the relationship between the degree of luminal narrowing and the composition of thrombus in patients with plaque erosion has not been studied. A total of 148 patients with plaque erosion and thrombus detected by optical coherence tomography were divided into tertiles based on the minimum lumen area (MLA) at the culprit lesion. Thrombus was categorized as platelet-rich or fibrin-rich. Among 148 patients, 50 (34%) were in the mild stenosis group, 49 (33%) were in the moderate stenosis group, and 49 (33%) were in the severe stenosis group. The composition of thrombus was significantly different among the 3 groups (prevalence of platelet-rich thrombus was 60% in the mild stenosis group; 78% in the moderate stenosis group; and 84% in the severe stenosis group; P = 0.021). The pattern of fibrin-rich thrombus showed the opposite: 40%, 22%, and 16%, respectively. In the multivariate analysis, current smoking was independently associated with fibrin-rich thrombus (odds ratio [OR] 2.364 [95% CI 1.004-5.567], P = 0.049). This study demonstrated that platelet-rich thrombus was the predominant type of thrombus in plaque erosion. The prevalence of fibrin-rich thrombus was highest in the mild stenosis group.

Determinants of ST-segment elevation myocardial infarction as clinical presentation of acute coronary syndrome.

Antiplatelet agents and statin therapies are widely used in patients with known cardiovascular disease. Plaque rupture (PR) and plaque erosion (PE) are the most frequent underlying mechanisms of acute coronary syndromes (ACS). The conditions and medications that are associated with ST-segment elevation myocardial infarction (STEMI) following PR or PE have not been systematically studied. A total of 838 ACS patients (494 with STEMI, 344 with NSTE-ACS) who were diagnosed with PR or PE by optical coherence tomography were included. The patients were categorized into two groups based on underlying pathology, and the baseline characteristics and culprit plaque morphology associated with STEMI were investigated within each group. Among 838 patients, 467 (55.7%) had PR, and 371 (44.3%) were diagnosed with PE. Among patients with PR, older age, hyperlipidemia, no antiplatelet therapy, higher level of low-density lipoprotein cholesterol, and greater lipid burden and macrophage infiltration were associated with increased probability of STEMI. Among patients with PE, no dual antiplatelet therapy and no statin therapy were associated with increased probability of STEMI. The incidence of STEMI caused by PR was significantly lower on antiplatelet therapy (P < 0.001), and the incidence of STEMI caused by PE was significantly lower on antiplatelet therapy (P < 0.001) or on statin therapy (P < 0.001). Antiplatelet therapy is associated with lower probability of STEMI, regardless of underlying pathology, and statin therapy is associated with lower probability of STEMI in PE as clinical presentation of ACS. Statin therapy prior to the onset of acute coronary syndromes (ACS) may reduce the probability of plaque rupture. Antiplatelet therapy prior to the onset of ACS is associated with reduced probability of ST-segment elevation myocardial infarction (STEMI) following both plaque rupture and plaque erosion, and dual antiplatelet therapy offers additional protection compared to a single antiplatelet agent in plaque erosion. The combination of statin and antiplatelet therapy may have an additive effect on reducing the probability of STEMI caused by plaque erosion. Yellow: lipid pool(necrotic core); red: fibrin-rich thrombus; gray; platelet-rich thrombus.

Spatial heterogeneity of neoatherosclerosis and its relationship with neovascularization and adjacent plaque characteristics: optical coherence tomography study.

BACKGROUND: Development of neoatherosclerosis (NA) has been reported to be a potential cause of late stent failure. However, the distribution of NA and its relationship with neovascularization (NV) and adjacent plaque characteristics remain unclear. METHODS: We investigated 167 stents (40 bare-metal stents, 84 sirolimus-eluting stents, and 43 everolimus-eluting stents) with optical coherence tomography. Each stent was divided into the proximal section (PS), mid section (MS) and distal section (DS). Neoatherosclerosis was defined as lipid-laden neointima or calcification inside stent. Adjacent plaque characteristics were evaluated within 5 mm proximal and distal reference segments. RESULTS: Neoatherosclerosis was more frequent in PS and DS than in MS (PS 19.8% vs. MS 3.6% vs. DS 21%: PS vs. MS, P < .001: MS vs. DS, P < .001). Neovascularization in PS and DS was also more prevalent compared with that in MS (PS 15% vs. MS 5.4% vs. DS 13.8%: PS vs. MS, P = .001: MS vs. DS, P = .001). Neoatherosclerosis was more frequently observed in stents with intraintima NV (68.6% vs. 20.5%, P < .001). The incidence of NA was higher, when adjacent plaque was lipid (43.2% with lipid plaque vs. 12.2% without lipid plaque, P < .001). CONCLUSION: Neoatherosclerosis occurs more frequently at PS and DS. Neoatherosclerosis was associated with NV and adjacent lipid plaque, suggesting potential interrelationship between development of NA and NV and adjacent plaque characteristics.

Pancoronary plaque vulnerability in patients with acute coronary syndrome and ruptured culprit plaque: a 3-vessel optical coherence tomography study.

BACKGROUND: Recent studies described different clinical and underlying plaque characteristics between patients with and without plaque rupture presenting with acute coronary syndrome (ACS). In light of the systemic nature of atherosclerosis, we hypothesized that nonculprit plaques might also express different morphological features in these 2 groups of patients. METHODS: Thirty-eight patients with ACS who underwent 3-vessel optical coherence tomography imaging were identified from the Massachusetts General Hospital Optical Coherence Tomography Registry. Based on culprit plaque morphology, the study population was divided into 2 groups: patients with plaque rupture at the culprit lesion (group 1) and patients with nonruptured plaque at the culprit lesion (group 2). Prevalence and features of nonculprit plaques were compared between the 2 groups. RESULTS: A total of 118 nonculprit plaques were analyzed. Patients in group 1 (n = 17) had nonculprit plaques with higher prevalence of thin-cap fibroatheroma (52.9% vs 19.0%, P = .029) and disruption (35.3% vs 4.8%, P = .016) compared with patients in group 2 (n = 21). Nonculprit plaques in group 1 showed wider maximum lipid arc (198.9° ± 41.7° vs 170.2° ± 41.9°, P = .003), greater lipid length (7.8 ± 4.4 mm vs 5.1 ± 2.4 mm, P = .003), higher lipid index (1196.9 ± 700.5 vs 747.7 ± 377.3, P = .001), and thinner fibrous cap (107.0 ± 56.5 µm vs 137.3 ± 69.8 µm, P = .035) compared with those in group 2. CONCLUSIONS: The present study showed distinctive features of nonculprit plaques between patients with ACS caused by plaque rupture and patients with ACS caused by nonruptured plaques. Patients with plaque rupture had increased pancoronary vulnerability in nonculprit plaques, suggesting that a more aggressive treatment paradigm aiming at the stabilization of vulnerable plaques may offer additional benefit to these patients.

Comparison of near-infrared spectroscopy and optical coherence tomography for detection of lipid.

OBJECTIVES: To compare intracoronary near-infrared spectroscopy (NIRS) and optical coherence tomography (OCT) for the detection of lipid, to identify NIRS signals to differentiate superficial lipid, and to characterize the plaque with yellow block (YB) chemograms on NIRS. BACKGROUND: Intracoronary NIRS has been developed to detect lipid core plaque (LCP). METHODS: We investigated a total of 17 patients who underwent both OCT and NIRS. NIRS analysis included plaque lipid core burden index (LCBI), LCP length, and the presence of YB on the block chemogram. OCT analysis included maximum lipid arc (LA), the length of lipid (LL), lipid index, and the thinnest fibrous cap thickness (FCT). RESULTS: Twenty-five plaques with >40% plaque burden were analyzed. LCP, showing LCBI > 0, was observed in 20 plaques (80%) and YB was detected in seven plaques (28%). Plaque LCBI showed modest correlations with maximum LA and lipid index by OCT (r(2) = 0.319, P = 0.003 and r(2) = 0. 404, P = 0.001, respectively). Lipid length showed a significant correlation between NIRS and OCT measurements (r(2) = 0.581, P < 0.001). There was no significant difference in NIRS parameters between superficial and deep lipid. Plaques with YB compared with those without YB showed a larger LA, longer LL, and thinner FCT (185 ± 29° vs. 105 ± 76°, P = 0.014; 8.5 ± 3.3 mm vs. 3.3 ± 2.7 mm, P = 0.001; 112 ± 42 vs. 166 ± 61 µm, P = 0.033). CONCLUSIONS: NIRS and OCT parameters showed modest linear correlations in the measurement of lipid. The accurate depth of lipid in the vessel wall could not be identified by quantitative NIRS parameters. YB chemograms represented more vulnerable features on OCT.

Protruding Aortic Plaque and Coronary Plaque Vulnerability.

BACKGROUND: Protruding aortic plaque is known to be associated with an increased risk for future cardiac and cerebrovascular events. However, the relationship between protruding aortic plaque and coronary plaque characteristics has not been systematically investigated. METHODS AND RESULTS: A total of 615 patients who underwent computed tomography angiography, and preintervention optical coherence tomography imaging were included. Coronary plaque characteristics were compared to evaluate coronary plaque vulnerability in patients with protruding aortic plaque on computed tomography angiography. 615 patients, the 186 (30.2%) patients with protruding aortic plaque were older and had more comorbidities such as hypertension, chronic kidney disease, and a prior myocardial infarction than those without. They also had a higher prevalence of coronary plaques with vulnerable features such as thin-cap fibroatheroma (85 [45.7%] versus 120 [28.0%], P<0.001), lipid-rich plaque (165 [88.7%] versus 346 [80.7%], P=0.014), macrophages (147 [79.0%] versus 294 [68.5%], P=0.008), layered plaque (117 [62.9%] versus 213 [49.7%], P=0.002), and plaque rupture (96 [51.6%] versus 111 [25.9%], P<0.001). Patients with protruding aortic plaque experienced more major adverse cardiac and cerebrovascular events, including all-cause mortality, nonfatal acute coronary syndromes, and stroke (27 [14.7%] versus 21 [4.9%], P<0.001; 8 [4.3%] versus 1 [0.2%], P<0.001; 5 [2.7%] versus 3 [0.7%], P=0.030; and 5 [2.7%] versus 2 [0.5%], P=0.013, respectively). CONCLUSIONS: The current study demonstrates that patients with protruding aortic plaque have more features of coronary plaque vulnerability and are at increased risk of future adverse events.

High-Risk Plaques on Coronary Computed Tomography Angiography: Correlation With Optical Coherence Tomography.

BACKGROUND: Although patients with high-risk plaque (HRP) on coronary computed tomography angiography (CTA) are reportedly at increased risk for future cardiovascular events, individual HRP features have not been systematically validated against high-resolution intravascular imaging. OBJECTIVES: The aim of this study was to correlate HRP features on CTA with plaque characteristics on optical coherence tomography (OCT). METHODS: Patients who underwent both CTA and OCT before coronary intervention were enrolled. Plaques in culprit vessels identified by CTA were evaluated with the use of OCT at the corresponding sites. HRP was defined as a plaque with at least 2 of the following 4 features: positive remodeling (PR), low-attenuation plaque (LAP), napkin-ring sign (NRS), and spotty calcification (SC). Patients were followed for up to 3 years. RESULTS: The study included 448 patients, with a median age of 67 years and of whom 357 (79.7%) were male, and 203 (45.3%) presented with acute coronary syndromes. A total of 1,075 lesions were analyzed. All 4 HRP features were associated with thin-cap fibroatheroma. PR was associated with all OCT features of plaque vulnerability, LAP was associated with lipid-rich plaque, macrophage, and cholesterol crystals, NRS was associated with cholesterol crystals, and SC was associated with microvessels. The cumulative incidence of the composite endpoint (target vessel nontarget lesion revascularization and cardiac death) was significantly higher in patients with HRP than in those without HRP (4.7% vs 0.5%; P = 0.010). CONCLUSIONS: All 4 HRP features on CTA were associated with features of vulnerability on OCT. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194).

Computed Tomography Angiography Characteristics of Thin-Cap Fibroatheroma in Patients With Diabetes.

BACKGROUND: It was recently reported that thin-cap fibroatheroma (TCFA) detected by optical coherence tomography was an independent predictor of future cardiac events in patients with diabetes. However, the clinical usefulness of this finding is limited by the invasive nature of optical coherence tomography. Computed tomography angiography (CTA) characteristics of TCFA have not been systematically studied. The aim of this study was to investigate CTA characteristics of TCFA in patients with diabetes. METHODS AND RESULTS: Patients with diabetes who underwent preintervention CTA and optical coherence tomography were included. Qualitative and quantitative analyses were performed for plaques on CTA. TCFA was assessed by optical coherence tomography. Among 366 plaques in 145 patients with diabetes, 111 plaques had TCFA. The prevalence of positive remodeling (74.8% versus 50.6%, P<0.001), low attenuation plaque (63.1% versus 33.7%, P<0.001), napkin-ring sign (32.4% versus 11.0%, P<0.001), and spotty calcification (55.0% versus 34.9%, P<0.001) was significantly higher in TCFA than in non-TCFA. Low-density noncalcified plaque volume (25.4 versus 15.7 mm3, P<0.001) and remodeling index (1.30 versus 1.20, P=0.002) were higher in TCFA than in non-TCFA. The presence of napkin-ring sign, spotty calcification, high low-density noncalcified plaque volume, and high remodeling index were independent predictors of TCFA. When all 4 predictors were present, the probability of TCFA increased to 82.4%. CONCLUSIONS: The combined qualitative and quantitative plaque analysis of CTA may be helpful in identifying TCFA in patients with diabetes. REGISTRATION INFORMATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.

Higher Noncalcified Plaque Volume Is Associated With Increased Plaque Vulnerability and Vascular Inflammation.

BACKGROUND: Recently, it was reported that noncalcified plaque (NCP) volume was an independent predictor for cardiac events. Pericoronary adipose tissue (PCAT) attenuation is a marker of vascular inflammation and has been associated with increased cardiac mortality. The aim of this study was to evaluate the relationships between NCP volume, plaque vulnerability, and PCAT attenuation. METHODS: Patients who underwent preintervention coronary computed tomography angiography and optical coherence tomography were enrolled. Plaque volume was measured by computed tomography angiography, plaque vulnerability by optical coherence tomography, and the level of coronary inflammation by PCAT attenuation. The plaques were divided into 2 groups of high or low NCP volume based on the median NCP volume. RESULTS: Among 704 plaques in 454 patients, the group with high NCP volume had a higher prevalence of lipid-rich plaque (87.2% versus 75.9%; P<0.001), thin-cap fibroatheroma (38.1% versus 20.7%; P<0.001), macrophage (77.8% versus 63.4%; P<0.001), microvessel (58.2% versus 42.9%; P<0.001), and cholesterol crystal (42.0% versus 26.7%; P<0.001) than the group with low NCP plaque volume. The group with high NCP volume also had higher PCAT attenuation than the group with low NCP volume (-69.6±10.0 versus -73.5±10.6 Hounsfield unit; P<0.001). In multivariable analysis, NCP volume was significantly associated with thin-cap fibroatheroma and high PCAT attenuation. In the analysis of the combination of PCAT attenuation and NCP volume, the prevalence of thin-cap fibroatheroma was the highest in the high PCAT attenuation and high NCP volume group and the lowest in the low PCAT attenuation and low NCP volume group. CONCLUSIONS: Higher NCP volume was associated with higher plaque vulnerability and vascular inflammation. The combination of PCAT attenuation and NCP volume may help identify plaque vulnerability noninvasively. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.

Sex-Specific Association Between Perivascular Inflammation and Plaque Vulnerability.

BACKGROUND: It is not known whether there is a sex difference in the association between perivascular inflammation and plaque vulnerability. The aim of this study was to investigate the sex-specific association between perivascular inflammation and plaque vulnerability. METHODS: Patients who underwent coronary computed tomography angiography and optical coherence tomography were enrolled. All images were analyzed at a core laboratory. The level of perivascular inflammation was assessed by pericoronary adipose tissue attenuation on computed tomography angiography and the level of plaque vulnerability by optical coherence tomography. Patients were classified into 3 groups according to tertile levels of culprit vessel pericoronary adipose tissue attenuation (low inflammation, ≤-73.1 Hounsfield units; moderate inflammation, -73.0 to -67.0 Hounsfield units; or high inflammation, ≥-66.9 Hounsfield units). RESULTS: A total of 968 lesions in 409 patients were included: 184 lesions in 82 women (2.2 plaques per patient) and 784 lesions in 327 men (2.4 plaques per patient). Women were older (median age, 71 versus 65 years; P<0.001) and had less severe coronary artery disease with a lower plaque burden than men. In women, it was found that perivascular inflammation was significantly associated with plaque vulnerability, with a higher prevalence of thin-cap fibroatheroma and greater macrophage grades in the high inflammation group compared with the low inflammation group (low versus moderate versus high inflammation in women: 18.5% versus 31.8% versus 46.9%, P=0.002 for low versus high inflammation; 3 versus 4 versus 12, P<0.001 for low versus high inflammation, respectively). However, no significant differences were observed among the 3 groups in men. CONCLUSIONS: Perivascular inflammation was associated with a higher prevalence of thin-cap fibroatheroma and more significant macrophage accumulation in women but not in men. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04523194.

Coronary plaque phenotype associated with positive remodeling.

BACKGROUND: Positive remodeling is an integral part of the vascular adaptation process during the development of atherosclerosis, which can be detected by coronary computed tomography angiography (CTA). METHODS: A total of 426 patients who underwent both coronary CTA and optical coherence tomography (OCT) were included. Four machine learning (ML) models, gradient boosting machine (GBM), random forest (RF), deep learning (DL), and support vector machine (SVM), were employed to detect specific plaque features. A total of 15 plaque features assessed by OCT were analyzed. The variable importance ranking was used to identify the features most closely associated with positive remodeling. RESULTS: In the variable importance ranking, lipid index and maximal calcification arc were consistently ranked high across all four ML models. Lipid index and maximal calcification arc were correlated with positive remodeling, showing pronounced influence at the lower range and diminishing influence at the higher range. Patients with more plaques with positive remodeling throughout their entire coronary trees had higher low-density lipoprotein cholesterol levels and were associated with a higher incidence of cardiovascular events during 5-year follow-up (Hazard ratio 2.10 [1.26-3.48], P â€‹= â€‹0.004). CONCLUSION: Greater lipid accumulation and less calcium burden were important features associated with positive remodeling in the coronary arteries. The number of coronary plaques with positive remodeling was associated with a higher incidence of cardiovascular events.

Level of Perivascular Inflammation Is Significantly Lower Around the Left Internal Mammary Artery Than Around Native Coronary Arteries.

BACKGROUND: The left internal mammary artery (LIMA) is protected from developing atherosclerosis. Perivascular inflammation, which is closely associated with atherosclerosis, can be measured by perivascular adipose tissue attenuation on computed tomography angiography. Whether the absence of atherosclerosis in LIMA is related to the lower level of perivascular inflammation is unknown. This study was performed to compare the level of perivascular inflammation between LIMA in situ and native coronary arteries in patients with coronary artery disease. METHODS AND RESULTS: A total of 573 patients who underwent both computed tomography angiography and optical coherence tomography imaging were included. The level of perivascular adipose tissue attenuation between LIMA in situ and coronary arteries was compared. Perivascular adipose tissue attenuation around LIMA in situ was significantly lower around the 3 coronary arteries (-82.9 [-87.3 to -78.0] versus -70.8 [-75.9 to -65.9]; P<0.001), irrespective of the level of pericoronary inflammation or the number of vulnerable features on optical coherence tomography. When patients were divided into high and low pericoronary inflammation groups, those in the high inflammation group had more target vessel failure (hazard ratio, 2.97 [95% CI, 1.16-7.59]; P=0.017). CONCLUSIONS: The current study demonstrated that perivascular adipose tissue attenuation was significantly lower around LIMA in situ than around native coronary arteries. The lower level of perivascular inflammation may be related to the low prevalence of atherosclerosis in LIMA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04523194.

Relationship between plaque burden and plaque vulnerability: Acute coronary syndromes versus chronic coronary syndrome.

BACKGROUND: The relationship between plaque burden and microscopic characterization of plaque features as it pertains to clinical presentation has not been fully investigated. The aim of this study was to compare the relationship between plaque burden and plaque vulnerability in patients with acute coronary syndromes (ACS) versus chronic coronary syndrome (CCS). METHODS: Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) before coronary intervention were enrolled. All plaques were detected in culprit vessels using CTA, and total plaque volume (TPV) and OCT features were assessed at the corresponding sites. All plaques were divided into three groups according to the tertile levels of TPV (low TPV: <96.5 â€‹mm3, moderate TPV: 96.5-164.7 â€‹mm3, high TPV: ≥164.8 â€‹mm3). RESULTS: A total of 990 plaques were imaged by OCT in 419 patients: 445 plaques in 190 (45.3%) patients with ACS and 545 in 229 (54.7%) with CCS. Macrophage was more prevalent in plaques with greater TPV in patients who presented with ACS but not in those who presented with CCS (low vs. moderate vs. high TPV group: macrophage 57.4% vs. 71.8% vs. 82.4% in ACS; 63.4% vs. 67.8% vs. 66.7% in CCS; interaction P â€‹= â€‹0.004). Lipid arc increased as TPV increased, especially in patients who presented with ACS. Conversely, the layer index increased as TPV increased in patients with CCS. CONCLUSION: Greater plaque burden was closely related to higher levels of plaque vulnerability in ACS and greater volume of layered plaque in CCS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT04523194.

Relationship Between Calcified Plaque Burden, Vascular Inflammation, and Plaque Vulnerability in Patients With Coronary Atherosclerosis.

BACKGROUND: Coronary artery calcification is an integral part of atherosclerosis. It has been suggested that early coronary artery calcification is associated with active inflammation, and advanced calcification forms as inflammation subsides. Inflammation is also an important factor in plaque vulnerability. However, the relationship between coronary artery calcium burden, vascular inflammation, and plaque vulnerability has not been fully investigated. OBJECTIVES: This study aimed to correlate calcified plaque burden (CPB) at the culprit lesion with vascular inflammation and plaque vulnerability. METHODS: Patients with coronary artery disease who had both computed tomography angiography and optical coherence tomography were included. The authors divided the patients into 4 groups: 1 group without calcification at the culprit lesion; and 3 groups based on the CPB tertiles. CPB was calculated as calcified plaque volume divided by vessel volume in the culprit lesion. The authors compared pericoronary adipose tissue (PCAT) attenuation for vascular inflammation and optical coherence tomography-derived vulnerable features among the 4 groups. RESULTS: Among 578 patients, the highest CPB tertile showed significantly lower PCAT attenuation of culprit vessel compared with the other groups. The prevalence of features of plaque vulnerability (including lipid-rich plaque, macrophage, and microvessel) was also lowest in the highest CPB tertile. In the patients with calcification, higher age, statin use, and lower PCAT attenuation were independently associated with CPB. CONCLUSIONS: Greater calcium burden is associated with a lower level of vascular inflammation and plaque vulnerability. A greater calcium burden may represent advanced stable plaque without significant inflammatory activity. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194).

Differences in total plaque burden between plaque rupture and plaque erosion: A combined computed tomography angiography and optical coherence tomography study.

BACKGROUNDS: Coronary computed tomography angiography (CTA) allows for the assessment of atherosclerotic plaque burden across the entire coronary vasculature. No studies have examined the relationship between the underlying pathology of the culprit lesion and total plaque burden in patients with acute coronary syndromes. The aim of this study was to compare the total plaque burden between patients with plaque rupture versus plaque erosion. METHODS: A total of 232 patients who presented with their first non-ST-segment elevation acute coronary syndrome and underwent both CTA and optical coherence tomography imaging before intervention were selected. Quantitative analysis was performed using semi-automated software (Autoplaque version 3.0, Cedars-Sinai Medical Center). An attenuation of <30 Hounsfield units defined low-density non-calcified plaque (LDNCP). All 3 vessels were assessed using the modified 17-segment American Heart Association model for coronary segment classification. RESULTS: Among 232 patients, 125 (53.9%) had plaque rupture and 107 (46.1%) had plaque erosion. Total plaque burden (48.2 [39.8-54.9] % vs. 44.1 [38.6-50.0] %, P â€‹= â€‹0.006), total non-calcified plaque (NCP) burden (46.6 [39.1-53.3] % vs. 43.0 [37.6-49.2] %, P â€‹= â€‹0.013), total LDNCP burden (2.3 [1.4-3.0] % vs. 1.7 [1.2-2.6] %, P â€‹= â€‹0.016), and total calcified plaque (CP) burden (0.8 [0.1-1.6] % vs. 0.4 [0.0-1.4] %, P â€‹= â€‹0.047) were significantly greater in patients with culprit plaque rupture than in those with culprit plaque erosion. CONCLUSION: Patients with plaque rupture, compared with those with plaque erosion, had a greater total plaque burden, NCP burden, LDNCP burden, and CP burden. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04523194.

Coronary Computed Tomography Angiography Findings of Plaque Erosion.

Compared with plaque rupture, plaque erosion has distinct features, which can be diagnosed only by intravascular optical coherence tomography. Computed tomography angiography (CTA) features of plaque erosion have not been reported. The aim of the present study was to identify the CTA features specific for plaque erosion in patients with non-ST-segment elevation acute coronary syndromes to enable a diagnosis of erosion without invasive procedures. Patients with non-ST-segment elevation acute coronary syndromes who underwent preintervention CTA and optical coherence tomography imaging of culprit lesions were enrolled. Plaque volume and high-risk plaque (HRP) features were assessed by CTA. Among 191 patients, plaque erosion was the underlying mechanism in 89 patients (46.6%) and plaque rupture in 102 patients (53.4%). The total plaque volume (TPV) was lower in plaque erosion than in plaque rupture (133.6 vs 168.8 mm3, p = 0.001). Plaque erosion had a lower prevalence of positive remodeling than plaque rupture (75.3% vs 87.3%, p = 0.033). As the number of HRP features decreased, plaque erosion became more prevalent (p = 0.014). In the multivariable logistic regression analysis, lower TPV and less prevalent HRP features were associated with a higher prevalence of plaque erosion. The addition of TPV ≤116 mm3 and HRP features ≤1 to the known predictors significantly increased the area under the curve of the plaque erosion prediction receiver operator characteristics. Plaque erosion, compared with plaque rupture, had a lower plaque volume and less prevalent HRP features. CTA may be helpful for identifying the underlying pathology of acute coronary syndromes.