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 .

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 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.

The Impact of Aortic Valvular Calcium on Transcatheter Heart Valve Distortion.

OBJECTIVES: To investigate the relationship between the eccentric calcification of aortic valve and transcatheter heart valve (THV) distortion and the impact of THV distortion on echo parameters and clinical outcomes. BACKGROUND: The effects of eccentric calcification of the aortic valve on the THV distortion and the relationship between THV distortion and clinical impact were not fully understood. METHODS: Patients with symptomatic severe aortic stenosis who were undergoing THV implantation were enrolled. Patients underwent preprocedural, postprocedural multislice computed tomography (MSCT), and follow-up transthoracic echocardiogram (TTE). Delta calcium score (ΔCS) is defined as the difference between the maximum and minimal calcium scores of the three cusps, while valve distortion score (VDS) is defined as the difference between the longest and shortest stent frame, as obtained using MSCT. Patients were divided into two groups according to ΔCS: "noneccentric calcification group" and "eccentric calcification group." RESULTS: A total of 118 patients were enrolled (59 patients in noneccentric and 59 in eccentric calcification groups). VDS was significantly lower in the noneccentric calcification group than in the eccentric calcification group (1.31 ± 0.82 mm vs. 1.73 ± 0.76 mm, p=0.004). VDS was not associated with the degree of paravalvular leak (PVL) and aortic valvular mean pressure gradient (AVPG) at 30-day and 1-year follow-up TTE and the cumulative rates of all-cause death and rehospitalization at 2-year clinical follow-up. CONCLUSIONS: Eccentric valvular calcification was associated with longitudinal THV distortion. However, THV distortion was not associated with PVL, AVPG, and adverse clinical events during midterm follow-up.

Clinical significance of the presence of puff-chandelier ruptures detected by nonobstructive aortic angioscopy.

OBJECTIVE: This study aimed to investigate the prevalence and prognostic significance of atherosclerotic aortic plaques (AAPs) or specific AAP types detected by nonobstructive angioscopy (NOA) in patients who underwent percutaneous coronary intervention (PCI). BACKGROUND: Although recent studies have reported the presence of various patterns of AAPs, identified by NOA, the clinical significance of the presence of AAPs remains elusive. METHODS: In this retrospective, multicenter cohort study, a total of 167 patients who underwent PCI and intra-aortic scans with NOA were studied. The association between AAPs and the incidence of major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, stroke, and clinically driven unplanned revascularizations, was assessed. RESULTS: AAPs were detected in 126 patients (75%) who underwent NOA. MACEs occurred in 28 (17%) patients during the follow-up (median 2.9 years [range 2.1-3.8]). Among all types of AAPs, only puff-chandelier rupture (PCR) showed a significant difference in frequency between patients with and those without MACEs: 21 (75%) and 49 (35%), respectively (p < .001). Multivariable Cox proportional hazard analysis revealed that PCR (hazard ratio [HR] 3.73, 95% confidence interval [CI] 1.57-8.87, p = .004) and chronic kidney disease (HR 2.97, 95% CI 1.37-6.44, p = .010) were independent predictors of MACEs. Kaplan-Meier analysis revealed that PCR was significantly associated with more frequent MACEs. CONCLUSION: The detection of PCR in the aorta using NOA was significantly associated with an increased risk of subsequent adverse events after PCI.

Prognostic Value of Phase-Contrast Cine-Magnetic Resonance Imaging-Derived Global Coronary Flow Reserve in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome Treated With Urgent Percutaneous Coronary Intervention.

BACKGROUND: Phase-contrast cine-magnetic resonance imaging (PC-CMR) of the coronary sinus (CS) is a promising approach for quantifying coronary sinus flow (CSF) and global coronary flow reserve (G-CFR). We evaluated the prognostic value of G-CFR using PC-CMR in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS).Methods and Results:The study prospectively enrolled 116 NSTE-ACS patients who underwent uncomplicated urgent PCI within 48 h of symptom onset. Post-PCI (median, 20 days) PC-CMR images of the CS were acquired to assess absolute CSF at rest and during maximum hyperemia. The association of G-CFR with major adverse cardiac events (cardiac death, nonfatal myocardial infarction, late revascularization, or hospitalization for congestive heart failure) was investigated. Rest and maximal hyperemic CSF and corrected G-CFR were 1.27 [interquartile range, 0.79-1.73] mL/min/g, 2.95 [2.02-3.84] mL/min/g, and 2.42 [1.69-3.34], respectively. At a median follow-up of 17 months, cardiac event-free survival was significantly worse in patients with a corrected G-CFR <2.33 (log-rank χ2=19.5, P<0.001). Cox proportional-hazards analysis showed that corrected G-CFR (hazard ratio, 0.434, 95% CI, 0.270-0.699, P<0.001) and NT-pro BNP at admission (hazard ratio, 1.0001, 95% CI, 1.0000-1.0001, P=0.007) were independent predictors of adverse cardiac events during follow-up. CONCLUSIONS: In NSTE-ACS patients successfully revascularized within 48 h of onset, post-PCI PC-CMR-derived G-CFR provided significant prognostic information independent of infarct size and conventional risk scores.

High-sensitivity cardiac troponin decrease after percutaneous coronary intervention in patients with stable coronary artery disease.

Baseline cardiac troponin is a strong predictor of major adverse cardiac events (MACE), and the high sensitive assay can provide risk stratification under the 99th percentile values. Currently, prognostic benefit of PCI has not been established in patients with stable coronary artery disease (CAD), and the influence on baseline troponin levels is unknown. This study aimed to investigate the impact of PCI on baseline high-sensitivity cardiac troponin-I (hs-cTnI) levels and the association with MACE incidence. For 401 patients with stable CAD who were indicated for PCI, baseline hs-cTnI levels were measured before PCI for two times (the average: pre-PCI hs-cTnI) and 10 months after PCI (post-PCI remote hs-cTnI). Hs-cTnI day-to-day variability was assessed based on the pre-PCI values and patients were divided into three groups (Increase/No change/Decrease group) according to the extent of hs-cTnI change (post-PCI remote hs-cTnI minus pre-PCI hs-cTnI) considering the day-to-day variability. A total of 77 patients were categorized into Decrease group. Although Decrease group had significantly higher pre-PCI hs-cTnI levels compared to the other groups, this group had lowest incidence of MACE (p < 0.001). Hs-cTnI changes were independently associated with MACE incidence after adjustment (HR 2.069, 95% CI 1.032-4.006, p = 0.041 for Increase group vs. No change group; HR 0.143, 95% CI 0.008-0.680, p = 0.009 for Decrease group vs. No change group). Hs-cTnI change following PCI was significantly predicted by pre-PCI hs-cTnI, hs-cTnI variability, the presence of dyslipidemia, multivessel disease, and lesions with chronic total occlusion or low quantitative flow ratio. In conclusion, PCI could lower hs-cTnI levels in a certain subset of patients, in whom prognostic benefit might be expected by the intervention.

Absolute Myocardial Blood Flow After Elective Percutaneous Coronary Intervention Evaluated on Phase-Contrast Cine Cardiovascular Magnetic Resonance Imaging.

BACKGROUND: Few studies have documented changes in myocardial blood flow (MBF) after percutaneous coronary intervention (PCI). Phase-contrast cine cardiovascular MRI (PC-CCMR) of the coronary sinus (CS) is a promising approach to quantify MBF. The aim of this study was to quantify CS flow (CSF) on PC-CCMR as a measure of volumetric MBF before and after elective PCI.Methods and Results:We prospectively studied 34 patients with stable angina undergoing elective PCI for a single de novo lesion. Breath-hold PC-CCMR of CS was acquired to assess CSF and coronary flow reserve (CFR) at rest and during maximum hyperemia both before and after PCI (median, 3 days before PCI and 10 days after PCI, respectively). In total, hyperemic CSF increased significantly after PCI (before PCI, median, 2.3 mL/min/g [IQR, 1.5-3.2 mL/min/g] after PCI, 3.0 [1.8-3.7] mL/min/g), although 13 patients (38.2%) had a decrease despite successful PCI and fractional flow reserve (FFR) improvement. Global CFR also significantly increased from a median of 2.5 (IQR, 1.5-3.5) to 3.4 (IQR, 2.1-4.2), whereas 12 patients had decreased CFR after PCI. Pre-PCI hyperemic CSF was the only independent factor of change in CSF following PCI. CONCLUSIONS: Serial PC-CCMR of CS as a measure of change in absolute MBF is feasible. Uncomplicated PCI does not necessarily increase hyperemic global MBF, despite regional FFR improvement.

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).

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.

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.

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.

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.

Clinical impact of aortic valve replacement in patients with moderate mixed aortic valve disease.

Background: Information is scarce regarding the clinical implications of aortic valve replacement (AVR) for patients suffering from moderate mixed aortic valve disease (MAVD), characterized by a combination of moderate aortic stenosis (AS) and regurgitation (AR). The objective of this retrospective study was to explore the clinical effects of AVR in individuals with moderate MAVD. Methods: We examined the clinical data from patients with moderate MAVD and preserved left ventricular ejection fraction, who had undergone echocardiography in the period spanning from 2010 to 2018. Moderate AS was defined as aortic valve area index of 0.60-0.85 cm2/m2 and peak velocity of 3.0-4.0 m/s. Moderate AR was defined as a vena contracta width of 3.0-6.0 mm. The primary endpoint was a composite of all-cause death and heart failure hospitalization. Results: Among 88 patients (mean age, 74.4 ± 6.8 years; 48.9%, men), 44 (50.0%) required AVR during a median follow-up period of 3.3 years (interquartile range, 0.5-4.9). Mean values of specific aortic valve variables are as follows: aortic valve area index, 0.64 ± 0.04 cm2/m2; peak velocity, 3.40 ± 0.30 m/s; and vena contracta width, 4.1 ± 0.7 mm. The primary endpoint occurred in 32 (36.4%) patients during a median follow-up duration of 5.3 years (interquartile range, 3.2-8.0). Multivariable analysis revealed that AVR was significantly associated with the endpoint (hazard ratio, 0.248; 95% confidence interval, 0.107-0.579; p = 0.001) after adjusting for age, B-type natriuretic peptide, and the Charlson comorbidity index. Patients who underwent AVR during follow-up had significantly lower incidence rates of the endpoint than those managed with medical treatment (10.2% vs. 44.1% at 5 years; p < 0.001). Conclusions: Approximately half of the patients diagnosed with moderate MAVD eventually necessitated AVR throughout the period of observation, leading to positive clinical results. Vigilant tracking of these patients and watchful monitoring for signs requiring AVR during this time frame are essential.

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.

Coronary artery disease reporting and data system (CAD-RADS), vascular inflammation and plaque vulnerability.

BACKGROUND: Coronary artery disease reporting and data system (CAD-RADS) predicts future cardiovascular events in patients with coronary artery disease (CAD). However, information on vascular inflammation and vulnerability remains scarce. METHODS: Patients who underwent coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) prior to coronary intervention were enrolled. All three coronary arteries were evaluated for CAD-RADS score and pericoronary adipose tissue (PCAT) attenuation, while the culprit vessel was analyzed for plaque vulnerability by OCT. RESULTS: A total of 385 patients with 915 lesions were divided into two groups based on CAD-RADS score: 103 (26.8%) were categorized as CAD-RADS 4b/5 and 282 (73.2%) as CAD-RADS ≤4a. Patients with CAD-RADS 4b/5 had a higher level of PCAT attenuation (mean of 3 coronary arteries) than those with CAD-RADS ≤4a (-68.4 â€‹± â€‹6.7 HU vs. -70.1 â€‹± â€‹6.5, P â€‹= â€‹0.022). The prevalence of macrophage was higher, and lipid index was greater in patients with CAD-RADS 4b/5 than CAD-RADS ≤4a (94.2% vs. 83.0%, P â€‹= â€‹0.004, 1845 vs. 1477; P â€‹= â€‹0.003). These associations were significant in the culprit vessels of patients with chronic coronary syndrome but not in those with acute coronary syndromes. CONCLUSIONS: Higher CAD-RADS score was associated with higher levels of vascular inflammation and plaque vulnerability.

Coronary Plaque Characteristics and Underlying Mechanism of Acute Coronary Syndromes in Different Age Groups of Patients With Diabetes.

BACKGROUND: High cardiovascular mortality has been reported in young patients with diabetes. However, the underlying pathology in different age groups of patients with diabetes has not been studied. METHODS AND RESULTS: The aim of this study was to investigate the plaque characteristics and underlying pathology of acute coronary syndrome in different age groups of patients with or without diabetes in a large cohort. Patients who presented with acute coronary syndrome and underwent preintervention optical coherence tomography imaging were included. Culprit plaque was classified as plaque rupture, plaque erosion, or calcified plaque and stratified into 5 age groups. Plaque characteristics including features of vulnerability were examined by optical coherence tomography. Among 1394 patients, 482 (34.6%) had diabetes. Patients with diabetes, compared with patients without diabetes, had a higher prevalence of lipid-rich plaque (71.2% versus 64.8%, P=0.016), macrophage (72.0% versus 62.6%, P<0.001), and cholesterol crystal (27.6% versus 19.7%, P<0.001). Both diabetes and nondiabetes groups showed a decreasing trend in plaque erosion with age (patients with diabetes, P=0.020; patients without diabetes, P<0.001). Patients without diabetes showed an increasing trend with age in plaque rupture (P=0.004) and lipid-rich plaque (P=0.018), whereas patients with diabetes had a high prevalence of these vulnerable features at an early age that remained high across age groups. CONCLUSIONS: Patients without diabetes showed an increasing trend with age in plaque rupture and lipid-rich plaque, whereas patients with diabetes had a high prevalence of these vulnerable features at an early age. These results suggest that atherosclerotic vascular changes with increased vulnerability start at a younger age in patients with diabetes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT04523194, NCT03479723. URL: https://www.umin.ac.jp/ctr/. Unique identifier: UMIN000041692.