Plaque Morphology Research Articles

Sodium Danshensu Inhibits Macrophage Inflammation in Atherosclerosis via the miR-200a-3p/MEKK3/NF-κB Signaling Pathway.

Macrophages are fundamental cellular components of atherosclerotic plaques, and inhibition of macrophage inflammation can delay the development of atherosclerotic plaques. Sodium danshensu (SDSS) can inhibit inflammatory responses and thus delay atherosclerosis, but the specific mechanism remains unclear.The effect of SDSS in inhibiting atherosclerosis was confirmed by observing and detecting atherosclerotic plaque area, morphology and lipid levels in the aorta. The mechanism by which SDSS attenuated atherosclerotic plaques was elucidated by in vivo and in vitro detection of inflammation-related mRNA and protein expression. In addition, bioinformatics analysis, RT-qPCR and dual-luciferase assays were used to predict and validate the potential miRNAs of SDSS to attenuate atherosclerosis. miR-200a-2p mimic and inhibitor were then compared for their effects on the efficacy of SDSS.SDSS inhibited atherosclerotic plaque formation and suppressed the expression of MEKK3, TNF-α, and IL-1β as well as nuclear factor-κB (NF-κB) phosphorylation and nuclear translocation to attenuate inflammatory responses. Bioinformatic predictions combined with RT-qPCR results and dual-luciferase assays indicated that miR-200a-3p negatively regulated MEKK3 expression by directly targeting the 3'UTR region of MEKK3, thereby blocking MEKK3. Further studies showed that miR-200a-3p inhibitor, but not miR-200a-3p mimic, reversed the beneficial effects of SDSS on inflammation.SDSS inhibited macrophage inflammation by modulating the miR-200a-3p/MEKK3/NF-κB signaling pathway.

High-risk features in non-culprit lesions and clinical outcome after NSTEMI versus STEMI.

Complete non-culprit (NC) revascularization may help reduce recurrent events after NSTEMI, especially if NC lesions would harbor high-risk plaque features similar to STEMI. The study aimed to assess differences in fractional flow reserve (FFR)-negative NC plaque morphology in patients presenting with NSTEMI versus STEMI and assess the association of high-risk plaque morphology and clinical outcome. In the prospective PECTUS-obs study, 438 patients presenting with myocardial infarction (MI) underwent optical coherence tomography (OCT) of all FFR-negative intermediate NC lesions. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE, all-cause mortality, non-fatal MI or unplanned revascularization) at two-year follow-up. Four hundred and twenty patients had at least one analyzable OCT, including 203 (48.3%) with NSTEMI and 217 (51.7%) with STEMI. The prevalence of high-risk plaques (HRP), including thin-cap fibroatheromas (TCFA), plaque rupture and thrombus, was comparable between groups. MACE occurred in 29 (14.3%) NSTEMI patients and 16 (7.4%) STEMI patients (Punivariable=0.025 and Pmultivariable=0.270). Incidence of MACE was numerically higher among patients with HRP, irrespective of the clinical presentation at index (Pinteraction=0.684). Among high-risk plaque criteria, plaque rupture was associated with MACE in both NSTEMI (p<0.001) and STEMI (p=0.020). Presence of NC HRP is comparable between NSTEMI and STEMI and leads to numerically higher event rates in both. These results call for additional research on complete revascularization in NSTEMI and treatment of HRP.

Significance of myeloperoxidase, pentraxin-3 and soluble urokinase plasminogen activator receptor determination in patients with moderate carotid artery stenosis

We investigated serum concentrations of specific inflammatory parameters in patients with significant carotid artery stenosis (CAS) of 50–99%, with an additional focus on patients with moderate stenosis (50–69%), in terms of both symptomatic status and plaque morphology, to determine whether there are certain parameters that can be associated with plaque instability before the progression of CAS to a high degree. The study included 119 CAS patients, 29 of whom had moderate stenosis, and 46 controls. Ultrasonography of the carotid arteries was performed using color flow Doppler and B-mode duplex ultrasound, and serum inflammatory parameters were measured using commercially available enzyme immunoassays. When comparing patients with 50–99% stenosis, only serum amyloid A (SAA) was higher in symptomatic patients, while in the group of patients with 50–69% stenosis, myeloperoxidase (MPO) was higher and pentraxin-3 (PTX-3) was lower in symptomatic compared to asymptomatic patients, and soluble urokinase plasminogen activator receptor (suPAR) was higher in patients with carotid plaque of unstable compared to stable morphology. Our results suggest that the importance of different inflammatory parameters in patients with moderate CAS is not the same as in CAS patients in general, and therefore their separate investigation in patients with high and moderate stenosis may be beneficial. SAA has the potential to be further considered in research to predict CAS symptom risk. There is a possibility that MPO and PTX-3 play a role in the development of CAS symptoms originating from less stenotic plaques and that suPAR is involved in the destabilisation of such plaques.

Morphological characterization of coronary plaques in young indian patients with acute coronary syndrome: A multicentric study

ObjectivesThe prevalence of atherosclerosis and acute coronary syndrome (ACS) is increasing in young Indians (18–50 years of age). However, the characteristics of atherosclerotic plaques in such individuals are poorly understood, presenting distinct challenges for the management of ACS. This study aims to analyze plaque characteristics in young Indian patients with ACS who underwent percutaneous coronary intervention (PCI) using optical coherence tomography (OCT) imaging. MethodsThis was a prospective, multicentric, non-interventional study on patients aged 18–50 years presenting with ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction, or unstable angina, and were scheduled to undergo OCT-guided PCI. Major adverse cardiac events (MACE) were assessed post-procedure and at the 6-month and 12-month follow-ups. ResultsThe study included 100 ACS patients (mean age = 43.6 ± 5.2 years), with 51% presenting with STEMI. Pre-PCI OCT assessment showed that fibrous plaques (75%) were most common followed by plaques containing macrophages (27%), microchannels (20%), and calcified nodules (14%). In addition, plaque rupture, plaque erosion, and lipid-rich plaques, along with red, white, and mixed thrombi, were observed in 31%, 25%, 24%, 21%, 14%, and 17% (total thrombus occurrence = 52%) of the patients, respectively. At 12 months, the MACE (coronary artery bypass graft) rate was 1%. ConclusionsYoung Indian patients with ACS displayed a range of plaque morphologies identified through pre-PCI OCT. Among these, fibrous plaques were the most prominent type, followed by plaques containing macrophages. Additionally, plaque rupture, plaque erosion, and lipid-rich plaques were also observed in this population.

Location-specific prognostic significance of plaque burden, stenosis, and plaque morphology in coronary artery disease

Abstract Background The prognostic significance of coronary plaque localization, percentage atheroma volume (PAV), stenosis, and plaque morphology has been underexplored. Purpose To investigate the prognostic significance of plaque localization beyond plaque burden, presence of stenosis and plaque morphology. Methods Patients with no cardiac history who underwent coronary CTA were included. PAV, maximum diameter stenosis, and plaque morphology were assessed and classified into proximal, mid, or distal segments of the coronary tree. Major adverse cardiac events (MACE) were defined as death or non-fatal myocardial infarction. Results Among 2819 patients 267 events (9.5%) occurred during a median follow-up of 6.9 years. PAV of the proximal segments was strongly correlated to PAV localized at of the mid (R= 0.76) and distal segments (R = 0.74, p &amp;lt; 0.01 for both). When adjusted for traditional risk factors and presence of plaque on other locations, only proximal PAV was independently associated with MACE (3rd quartile HR 2.08, 95% 1.17–3.71, p=0.01 and 4th quartile HR 2.29, 95% CI 1.21–4.34, p=0.01). Similar results were seen for presence of stenosis. Proximal, mid, and distal PAV as a solitary metric (unadjusted) had similar predictive value for MACE with an AUC of 0.73 (95% CI 0.69-0.76) for proximal PAV and 0.72 (95% CI 0.68-0.76) for both mid and distal localized plaque). Similar results were obtained using diameter stenosis instead of PAV. The presence of low-attenuation plaque (LAP) in the proximal segments had additional prognostic value. Calcified or noncalcified PAV did not provide additional value beyond total location-specific PAV and presence of low-attenuation plaque. Conclusions Proximal located PAV is an independent predictor of death and non-fatal MI, while there was no incremental prognostic value of plaque localized at the mid or distal coronary segments. The presence of LAP in the proximal segments provided additional prognostic value for prediction of MACE.

Arterial stiffness characterization of patients with different ACS-causing plaque morphologies quantified by optical coherence tomography

Abstract Background Optical coherence tomography (OCT) has refined acute coronary syndrome (ACS)-management by enabling in-depth characterization of culprit lesions. Differentiating between plaques with ruptured (RFC) and intact fibrous cap (IFC) has shaped clinical decision making. However, the systemic vascular changes associated with different plaque morphologies remain unexplored. Purpose To investigate arterial stiffness among different ACS-causing plaque morphologies (RFC vs. IFC) and its prognostic value post-ACS. Methods We conducted a secondary analysis of a prospective registry study, including patients who underwent OCT-characterization of the ACS-causing culprit lesion and received arterial stiffness assessment 90 days post-index event. The association between arterial stiffness parameters, such as pulse wave velocity (PWV), aortic pulse pressure (APP), heart rate-corrected augmentation index (AIx@75) and plaque morphologies was assessed using logistic regression, adjusted for age, sex, hypertension, presence of diabetes mellitus, smoking status, LDL-C and discharge medications (ACE-inhibitors/ARBs, beta blockers, calcium-channel blockers and diuretics). A multiparameter model additionally included intima-media-thickness and all arterial stiffness metrics. Cox regression, further adjusted for stroke history, prior percutaneous coronary intervention or stable coronary artery disease and Killip class, evaluated the link between arterial stiffness parameters and major adverse cardiovascular events plus (MACE+). Results In total, 110 patients with arterial stiffness and OCT data were included. Of these, 78 (70.9%) patients had RFC- and 32 (29.1%) IFC-ACS. The median age was 61.5 years and 80.0% of patients were male. Patients with RFC- had significantly higher PWV (8.35 vs. 7.50 m/s, p=0.015) compared to IFC-ACS. Both groups received similar regimens of antihypertensive, diuretic and lipid-lowering pharmacological therapy at discharge (p&amp;gt;0.1). After multivariable adjustment, increased PWV (4th Quartile [Q4] vs. 1st Quartile [Q1] Adjusted Hazard Ratio [aHR]: 1.38 [95% Confidence Interval (CI) 1.02-1.88], p=0.043) was associated with RFC- while high APP was significantly associated with IFC-ACS as the underlying plaque morphology (Q4 vs. Q1 aHR: 0.65 [95% CI 0.48-0.87], p=0.005) (Figure 1). Furthermore, per one-unit increment in APP we observed a 10% increase in risk for MACE+ in patients with RFC-ACS (aHR: 1.10 [95% CI 1.02-1.19], p=0.016) but not IFC-ACS (aHR: 0.95 [95% CI 0.82-1.11], p=0.54). No risk modification with increases in PWV and AIx@75 were observed, regardless of underlying plaque pathology (p&amp;gt;0.05). Conclusion There are distinct differences in arterial stiffness between patients with RFC- and IFC-ACS. These results underscore the value of a patient-specific approach that integrates invasive and non-invasive vascular characterization for identifying high-risk individuals and guiding therapy to enhance clinical outcomes.

Differences in non-flow limiting non-culprit plaque characteristics after myocardial infarction in patients with versus without chronic kidney disease

Abstract Background Patients with chronic kidney disease (CKD) are at increased risk for recurrent cardiovascular events after myocardial infarction compared to patients with preserved renal function. This disparity may be related to differences in plaque morphology. Purpose To compare non-flow limiting non-culprit (NC) plaque characteristics as assessed by optical coherence tomography in patients with versus without chronic kidney disease presenting with myocardial infarction. Methods 438 patients presenting with myocardial infarction with additional non-flow limiting (defined as a fractional flow reserve &amp;gt;0.80) NC lesions were included in the prospective observational PECTUS-obs study after treatment of the infarct related artery. An independent core laboratory performed all quantitative and qualitative OCT analyses. For the present subgroup analysis, patients were grouped according to the presence or absence of CKD, which was defined as an estimated glomerular filtration rate (eGFR) &amp;lt;60 ml/min/1.73 m². Baseline characteristics were compared between groups on a patient-level and OCT characteristics were compared on a lesion-level while accounting for within-patient clustering. Results Out of 420 patients with at least one analyzable OCT, baseline renal function was known in 416. Among them, there were 55 patients with and 361 patients without CKD (mean eGFR 47.4 ± 9.2 vs 84.7 ± 15.0 ml/min/1.73 m², p&amp;lt;0.001). Patients with CKD were older (mean age 73 ± 9 vs 62 ± 10 years, p&amp;lt;0.001), more frequently were female (29.1% vs 17.2%, p=0.035) and predominantly presented with a non-ST-segment elevation myocardial infarction (72.2% vs 44.9%, p&amp;lt;0.001). Comorbid disease was more prevalent among patients with CKD, including a higher prevalence of hypertension (p=0.010), hypercholesterolemia (p=0.020), diabetes (p&amp;lt;0.001), history of myocardial infarction (p&amp;lt;0.001), carotid artery disease (p=0.019) and peripheral artery disease (p=0.002). Coronary lesions in patients with CKD on average had a larger maximal calcium arc (188 ± 114 vs 137 ± 87º, p=0.003) and length (11.9 ± 10.3 vs 8.4 ± 7.4 mm, p=0.021). Lipid plaques were less prevalent among lesions in patients with CKD (63.6% vs 78.0%, p=0.016) and less frequently had a lipid arc ≥90º (60.6% vs 76.1%, p=0.018). Although the mean minimal fibrous cap thickness was lower in patients with CKD (p=0.025), no difference was observed in the prevalence of thin-cap fibroatheromas (p=0.984) or high-risk plaques according to the PECTUS-obs criteria (p=0.665). Conclusion Non-flow limiting NC lesions in patients with CKD differ from those in patients without CKD in a cohort of patients presenting with myocardial infarction. Overall, plaques in patients with CKD show more extensive calcification, whereas lesions in patients without CKD more often consist of lipid plaques, but the prevalence of high-risk plaques was comparable.

Predictors of percutaneous coronary intervention derived from CCTA in patients with chronic coronary syndrome

Abstract Background To identify anatomical and morphological plaque features predictors of percutaneous coronary intervention (PCI) and create a multiparametric score to increase the predictive yield. Moreover, we assessed the incremental predictive value of FFRCT (Fractional Flow Reserve derived from CCTA) trans-lesion gradient (ΔFFRCT) when integrated into the score. Methods Observational cohort study including patients undergoing CCTA for suspected coronary artery disease, with FFRCT available, referred to invasive coronary angiogram and assessment of fractional flow reserve. Plaque analysis was performed using validated semi-automated software. Logistic regression was performed to identify anatomical and morphological plaque features predictive of PCI. Optimal thresholds were defined by area under the receiver-operating characteristics curve (AUC) analysis. A scoring system was developed in a derivation cohort (70% of the study population) and tested in a validation cohort (30% of patients). Results The overall study population included 340 patients (455 vessels), among which 238 patients (320 vessels) were included in the derivation cohort. At multivariate logistic regression analysis, absence of left main disease, diameter stenosis (DS), non-calcified plaque (NCP) volume, and percent atheroma volume (PAV) were independent predictors of PCI. Optimal thresholds were: DS³50%, volume of NCP&amp;gt;113 mm3 and PAV&amp;gt;17%. A weighted score (CT-PCI Score) ranging from 0 to 11 was obtained. The AUC of the score was 0.80 (95%CI 0.74-0.86). The integration of ΔFFRCT in the CT-PCI score led to a mild albeit not significant increase in the AUC (0.82, 95%CI 0.77-0.87, p=0.328). Conclusions Plaque anatomy and morphology derived from CCTA could aid in identifying patients amenable to PCI.Central IllustrationPredictive accuracy of the CT-PCI score

Noninvasive predictors of residual coronary microvascular dysfunction after elective percutaneous coronary intervention

Abstract Backgrounds Coronary computed tomographic angiography (CCTA) provides noninvasive assessments of coronary plaque morphologies and perivascular inflammation. Morphological features associated with residual coronary microvascular dysfunction (CMD) after elective percutaneous coronary intervention (PCI) remains unknown. Purpose This study aimed to examine prevalence and predictors of residual CMD and its phenotypes after elective PCI. Methods We investigated consecutive patients who were scheduled for elective fractional flow reserve (FFR)-guided PCI for de novo single lesions with pre-PCI CCTA data. Pre- and post-PCI comprehensive physiological assessments including coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) were performed by using pressure temperature sensor-tipped guidewire in all patients. Patients with periprocedural myocardial infarction were excluded. Residual CMD was defined as lesions with post-PCI coronary flow reserve (CFR) &amp;lt;2.0, which was further categorized as functional (IMR&amp;lt;25) or structural (IMR ≥25) CMD. Results A total of 198 de novo lesions in 198 patients were included in the final dataset. Pre- and post-PCI mean CFR were 1.79 [1.27, 2.53] and 2.72 [2.00, 4.04], respectively. Residual CMD was observed in 24.7% (49/198) of patients, categorized as functional (n=26) or structural (n=23). Patients with residual CMD showed older age, less frequent diabetes mellitus, current smoking and a culprit lesion in left anterior descending artery (LAD), and higher CCTA-defined calcium score in the culprit vessel compared with those in patients without residual CMD. Multivariable logistic regression analysis showed that age (adjusted odds ratio [OR]:1.04; 95% confidence interval [CI]: 1.00 to 1.08; p=0.04) and non-LAD (adjusted OR: 2.18; 95%CI: 1.03 to 4.63; p=0.04) were independently associated with residual CMD. In patients with residual CMD, patients with structural CMD tended to have more frequent diabetes mellitus (43.5% vs 19.2%, P=0.13) and atrial fibrillation (26.1% vs 7.7%) and showed significantly lower pericoronary adipose tissue attenuation (PCATA) in right coronary artery (RCA) by CCTA (-79.9 HU vs -74.6 HU, P=0.04) compared with patients with functional CMD. CCTA-detected epicardial fat volume and attenuation showed no significant differences between patients with residual functional CMD, those with residual structural CMD, and those without residual CMD. Multivariable analysis revealed that diabetes mellitus (adjusted OR: 5.18; 95%CI: 1.14 to 23.7; p=0.03) and PCATA in RCA (adjusted OR: 0.93; 95% CI: 0.85 to 1.00; p=0.05) were independently predictive of residual structural CMD. Conclusions Residual CMD was observed in approximately 25% of patients undergoing elective PCI. CCTA-defined calcium score and PCATA, along with clinical factors could be potential predictors of post-PCI residual CMD and its phenotypes.

A meta-analysis of randomised controlled trials comparing optical coherence tomography-guided against angiography-guided revascularisation

Abstract Optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) offers more in-depth assessment of plaque morphology, vessel sizing and post-PCI stent deployment characteristics than angiography guidance alone. Previous studies have demonstrated superiority of OCT-guided compared to angiography-guided PCI in stent implantation and expansion, with no difference in safety outcomes. Despite this, adoption of OCT-guided PCI remains low in clinical practice due to its increased procedural time, larger contrast volume, and added cost. Two large multicentre international randomised controlled trials (RCTs) were recently published. We therefore aimed to perform an up-to-date meta-analysis of RCTs comparing OCT-guided revascularisation against angiography-guided revascularisation on hard clinical outcomes. A comprehensive search of PubMed/MEDLINE and Ovid/Embase was performed, of which only RCTs were included. Two authors identified relevant articles and extracted the data independently. Any disagreements were resolved by a third author. Clinical outcome data was extracted from each study and then pooled to determine the overall risk ratio (RR) and confidence interval (CI) collectively. This was calculated with random-effects model using the Mantel-Haenszel method. All reported P values are two-sided, with significance set at P&amp;lt;0.05. A total of ten RCTs involving a total of 5062 patients were included. After an average follow-up of 20 months, there was no significant difference in the trial-defined composite endpoint between OCT-guided versus angiography guided revascularisation [6.8% versus 7.9%, RR 0.85, 95% CI (0.69 to 1.03), P=0.10, heterogeneity (I2)=0%]. There was also no significant difference in cardiac death [1.0% versus 1.6%, RR 0.61, 95% CI (0.36 to 1.02), P=0.06, heterogeneity (I2)=0%, Figure 1a], myocardial infarction [3.2% versus 3.7%, RR 0.86, 95% CI (0.65 to 1.15), P=0.31, I2=0%, Figure 1b] and target lesion or vessel repeat revascularisation [3.8% versus 4.1%, RR 0.95, 95% CI (0.72 to 1.25), P=0.70, I2=0%, Figure 1c] between the two arms. However, the OCT-guided revascularisation arm was associated with a significantly lower rate of stent thrombosis [0.8% versus 1.5%, RR 0.57, 95% CI (0.33 to 0.97), P=0.04, I2=0%, Figure 1d] than the angiography-guided revascularisation arm. The number-needed-to-treat (NNT) by OCT-guided revascularisation to reduce one additional stent thrombosis event was 143. In conclusion, our findings show the use of OCT-guided revascularisation led to a significant reduction in stent thrombosis compared to angiography-guided revascularisation, but there was no difference in cardiac death, myocardial infarction and repeat revascularisation. The NNT for stent thrombosis was 143 patients. Further research is needed to identity those subgroups most likely to benefit from OCT-guided revascularisation before it can be more widely adopted to significantly impact on clinical care.

Coronary artery plaque characteristics in smokers assessed by intracoronary multi-modality imaging: a NIRS-IVUS guided PROSPECT II substudy

Abstract Background Smoking is a risk factor for coronary artery disease and myocardial infarction. Purpose Among patients with myocardial infarction, we hypothesized smokers would have increased prevalence of nonculprit high-risk plaque characteristics as assessed by intracoronary multimodality imaged when compared to nonsmokers. Method This is a prespecified post-hoc analysis of the PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree). Altogether 898 patients with acute myocardial infarction with or without ST-segment elevation who after successful percutaneous coronary intervention had near-infrared spectroscopy and intravascular ultrasound imaging performed. Data on lesion location, plaque burden, and lipid content were collected. Current, former, and nonsmokers were examined regarding the presence of high-risk plaques in both culprit and nonculprit lesions as well as plaque location. High-risk plaque characteristics were defined as a maximum plaque burden (maxPB) of ≥70% and a maximum 4 mm lipid core burden index (maxLCBI4mm) of ≥324.7. Results Out of 886 patients with known smoking history, 32% were smokers, 32% former, and 37% nonsmokers. Smokers were younger (median age: smokers 59.0; former 65.5; nonsmokers 64.0 years, p&amp;lt;0.001) with fewer co-morbidities and presented more often with STEMI (% presenting with STEMI: smokers 22.2%; former 18.9%; nonsmokers 19.4%, p=0.006). LDL was similar but CRP was higher in smokers (median µg/mL: smokers 4.0; former 3.1; nonsmokers 2.9, p=0.004). In multivariate models of nonculprit lesion morphology smoking history was not associated with maxPB or maxLCBI4mm but was associated with presence of calcified nodules (OR: 2.88 (95% CI 1.46–5.69) p=0.002 [smokers vs nonsmokers]). Calcified nodules were also associated with number of years smoked (OR: 1.02 (95% CI 1.01–1.03) p=0.004). Smoking was not associated with presence of ≥1 lesions with MaxLCBI4mm, ≥ 324.7, maxPB &amp;gt;=70% or the combination of both. Smoking was not associated with presence of plaque rupture or thrombus. Right coronary artery culprit lesions were more common in smokers and former smokers (smokers 29.9%; former 30.9%; nonsmokers 21.6%; OR: 1.12 (95% CI 1.04–1.21) p&amp;lt;0.001 [smokers vs nonsmokers]). Conclusion In this prospective intracoronary multimodality imaging study of patients with recent acute myocardial infarction, smoking was not associated with a higher rate of high-risk nonculprit plaques based on lipid content by NIRS or PB by IVUS when compared to former or nonsmokers. However, smoking was associated with higher presence of IVUS-detected calcified nodules, higher CRP-levels, and the right coronary artery as it angiographically was a more common site for culprit lesions. These results indicate that the elevated risk in smokers is unrelated to vulnerable plaque morphology defined by high PB and lipid content, and instead possibly related to inflammation, calcification, or hemodynamic changes.Table 1

Analysis of risk factors in high-risk plaque in acute coronary syndrome based on LASSO regression

Abstract Background The CLIMA Study (Relationship between OCT Coronary Plaque Morphology and Clinical Outcome) put forward the concept of High-risk plaque (HRP) and demonstrated that HRP were correlated with the high risk of major coronary events[1, 2]. HRP were defined as the presence of four simultaneous characteristics: minimum lumen area (MLA) &amp;lt;3.5mm2, fibrous cap thickness (FCT) &amp;lt;75 μm, lipid arc circumferential extension &amp;gt;180°, and the presence of macrophage infiltration. Early prediction of HRP formation are of great significance for the prevention and treatment of Acute Coronary Syndrome (ACS), but there are no relevant studies. Purpose To identify the risk factors related to OCT HRP in ACS and establish risk prediction model for HRPs in ACS. Methods A prospective observational cohort study was carried out on the patients with ACS from September 2019 to August 2022. A total of 169 patients were divided into OCT HRP (n=55) and OCT non-HRP (n=114) groups. Clinical information, laboratory examination and the OCT characteristics of the patients were collected. LASSO regression was used to screen variables, and multivariate logistic regression was used to establish risk prediction model. A nomogram was formulated, use the ROC curve to evaluate the discrimination of the model and the Bootstrap method to internally validate the model. Results The most frequently observed HRP characteristic was Lipid plague&amp;gt;180°(147 patients），followed by MLA&amp;lt;3.5mm2(141 patients), macrophages(127 patients), FCT&amp;lt;75μm(64 patients). The LASSO regression model was used to screen variables and construct an HRP risk factor model. This final model included age, BMI≥25, TC, LDL-C and Log NT-proBNP. The model is well differentiated (AUC 0.780, 95%CI 0.705-0.855) and calibrated. Decision Curve Analysis shows that the model has good net benefits. Conclusion This prediction model can accurately predict the risk of OCT HRP in patients with ACS, and is expected to assist clinicians in diagnosis and prevention of plaque stability.

NIR-II scattering gold superclusters for intravascular optical coherence tomography molecular imaging.

Currently, intravascular optical coherence tomography (IV-OCT) is limited to anatomical imaging, providing structural information about atherosclerotic plaque morphology, thrombus and dissection. Earlier detection and risk stratification would be possible through molecular characterization of endothelium but necessitates a purpose-engineered IV-OCT contrast agent. Here we developed gold superclusters (AuSCs) tailored to clinical instrumentation and integrated into clinically relevant workflows. AuSCs are aqueously dispersible clusters of closely packed small gold nanoparticles, affording plasmon hybridization to maximize light scattering at the IV-OCT laser line (~1,350 nm). A polymer coating fosters AuSC uniformity and provides a functionalizable handle, which we targeted to intravascular P-selectin, an early vascular endothelial marker of inflammation. In a rat model of intravascular inflammation, P-selectin-targeted AuSC facilitated IV-OCT molecular imaging, where the strength of the signal correlates with the severity of vascular inflammation.

Evaluation of non-target lesions in femoropopliteal disease using near-infrared spectroscopy intravascular ultrasound imaging

Abstract Aim This study aims to assess the plaque morphology of non-target lesions, especially lipid-core-containing plaque (LCP), and compare it to target lesions using near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with femoropopliteal disease. Methods We conducted a single-center prospective observational study on 14 patients who underwent endovascular therapy for femoropopliteal disease between July 2022 and November 2023. NIRS-IVUS assessment was performed on the whole femoropopliteal arterial segment. Forty-one LCP lesions &amp;gt; maximum lipid-core burden index in any 4-mm region (max LCBI4mm) 100 were detected by NIRS-IVUS. We evaluated patient and lesion characteristics. In addition, the LCP lesions were divided into two groups, the target lesion group (n=18) and the non-target lesion group (n=23), and compared. Results Patient characteristics were notable for advanced age (76.8±6.6 years), high incidence of male (78.7%), hypertension (100%), dyslipidemia (78.6%), diabetes (64.3%), statin use (71.4%). Lipid profiles were as follows: LDL-cholesterol 85.9±26.7 mg/dl, HDL-cholesterol 48.9±12.7 mg/dl, triglyceride 138.9±80.3 mg/dl, lipoprotein(a) 19.6±16.3 mg/dl. Ten participants had LCPs in the non-target lesion (71.4%). For IVUS findings, the target lesion group had significantly longer lesion length (34.6±11.9 mm vs. 22.6±8.7 mm, p=0.001), smaller minimum lumen area (7.0±2.8 mm2 vs. 14.8±5.4 mm2, p&amp;lt;0.001), and larger plaque burden (78.0±5.0 % vs. 53.0±12.0 %, p&amp;lt;0.001) than those in the non-target lesion group. No significant differences were observed in the prevalence of calcification (target lesion group vs. non-target lesion group: 83.3 % vs. 91.3 %, p=0.64) and the extent of calcification (p=0.76). For NIRS findings, the target lesion group contained a significantly smaller proportion of LCP in the lesion length (25.9±15.7 % vs. 50.6±29.2 %, p=0.002) than the non-target lesion group. On the other hand, there were no significant differences in the value of max LCBI4mm (284.4±153.4 vs. 289.5±113.1, p=0.90) and the length of LCP lesion (9.8±9.7 mm vs. 10.7±6.9 mm, p=0.74) and distribution of LCP (p=0.08) between both groups. In addition, the number of LCPs in the target femoropopliteal artery was positively correlated with max LCBI4mm in the target femoropopliteal artery (r=0.671, p=0.008) Conclusion NIRS-IVUS findings in this study demonstrated that the non-target lesions contained LCPs to the same degree as the target lesions.

Comprehensive Risk Assessment of LAD Disease Progression in CCTA: The CLAP Score Study

Background: a wider left main bifurcation angle (LMBA) has been linked to severe plaque development in the proximal left anterior descending artery (LAD). This study aimed to identify predictors of severe proximal LAD stenosis and major adverse cardiovascular events (MACE) using coronary computed tomography angiography (CCTA). Methods: from an initial cohort of 650 consecutive patients, we analyzed 499 patients who met the inclusion criteria after exclusions. Plaque morphology and characteristics were assessed by CCTA, and MACE occurrences were recorded at follow-up. A predictive score for LAD disease progression (CLAP score) was developed and validated. Results: severe proximal LAD stenosis was detected in 32% (160/499) of patients by CCTA. MACE occurred in 12.5% of patients at follow-up. Significant predictors of MACE were LMBA &gt; 80° (HR: 4.47; 95% CI: 3.80–6.70; p &lt; 0.001), diabetes (HR: 2.94; 95% CI: 1.54–4.63; p = 0.031), chronic kidney disease (HR: 1.71; 95% CI: 1.31–6.72; p = 0.041), high-risk plaques (HR: 2.30; 95% CI: 1.45–3.64; p &lt; 0.01), obstructive CAD (HR: 2.50; 95% CI: 1.50 to 4.10, p = 0.01), and calcium score (CAC) (HR: 1.05; 95% CI: 1.02–1.08, p = 0.004). The CLAP score demonstrated good discriminatory power in both the development (AUC 0.91; 95% CI: 0.86–0.96) and validation cohorts (AUC 0.85; 95% CI: 0.79–0.91); Conclusions: LMBA &gt; 80°, diabetes, chronic kidney disease, obstructive CAD, CAC score &gt;180 and high-risk plaques were significant predictors of MACE in CCTA patients. The CLAP score effectively predicted LAD disease progression, aiding in risk stratification and optimization of intervention strategies for suspected coronary artery disease.

Independent role of atherosclerotic plaque composition and extension in predicting the risk of cardiac events: a CLIMA substudy.

To investigate two different approaches to determine patient risk to develop cardiac events: the burden of coronary atherosclerosis, as assessed by the Gensini score, and plaque morphology, as assessed by intracoronary optical coherence tomography (OCT). We assessed the Gensini score and OCT features of plaque vulnerability in 847 patients from the CLIMA registry. Patients were divided into four Gensini quartiles. The main study endpoint was the 1-year composite of cardiac death, myocardial infarction (MI) and/or target vessel revascularization (TVR). A total of 56 patients (6.6%) experienced the one-year main composite endpoint. The composite endpoint was significantly affected by the Gensini score (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.11-1.81, p = 0.005), with a low incidence in the first Gensini quartile (Q1 1.3%) and a higher incidence in the remaining groups (Q2 8.3%, Q3 8.9% and Q4 8.3%). At the multivariable analysis, the combined four OCT criteria (HR 6.4, 95%CI 3.0-13.7, p < 0.001), thin fibrous cap (HR 2.9, 95%CI 1.7-5.0, p < 0.001), lipid arc > 180° (HR 2.1, 95%CI 1.2-3.6, p = 0.010), minimum lumen area < 3.5 mm2 (HR 1.7, 95%CI 1.01-3.0, p = 0.047) and the Gensini score (HR 1.4, 95%CI 1.1-1.8, p = 0.017) were independent predictors of the main composite endpoint. In this post-hoc analysis of the CLIMA study, the burden of coronary atherosclerosis as assessed by the Gensini score and OCT plaque characteristics were independent predictors of cardiac events. Patients with the largest atherosclerosis burden and with plaque vulnerability by OCT were at the highest risk of poor outcome. Clinicaltrials.gov identifier: NCT02883088.

Endothelium-targeted NF-κB siRNA nanogel for magnetic resonance imaging and visualized-anti-inflammation treatment of atherosclerosis

Atherosclerosis-induced lethal cardiovascular disease remains a severe healthcare threat due to the limited drug efficiency and untimely prediction of high-risk events caused by inadequate target specificity of medications, incapable recognition of insensitive patients, and variable morphology of vulnerable plaques. Therefore, it is necessary to develop efficient strategies to improve the diagnosis accuracy and achieve visualized treatment of atherosclerosis. Herein, we establish an inflamed endothelium-targeted three-in-one nucleic acid nanogel system that can reverse the inflammatory state of endothelial cells (ECs) in plaques and simultaneously achieve real-time monitoring of the therapy process for efficient atherosclerosis diagnosis and treatment. For this purpose, contrast agent (Gd-DOTA) and VCAM-1-targeted peptide (VP) are first covalently conjugated onto DNA strands by click reaction respectively, which could self-assemble into Y-shaped structures (Gd-Y1 and VP-Y2 motifs) with magnetic resonance (MR) imaging and endothelium targeting capacities. Thereafter, NF-κB subunit p65-targeting siRNA (siNF-κB) is crosslinked with Gd-Y1 and VP-Y2 motifs to construct the endothelium-targeting nanogel platform. With contrast agents inside, the nanogel enables MR-based diagnosis and visualized therapy of atherosclerosis, providing accurate prognostic analysis and indications for treatment results, which ensures timely disclosure of insensitive individuals and avoids acute lethal events. By delivering siNF-κB to inflammatory endothelium, the nanogel significantly regresses plaques in both the aorta and carotid artery with reduced inflammation cytokines, collagens, macrophages, and apoptotic cells, providing a potential anti-inflammation strategy to treat atherosclerosis and avoid acute cardiovascular disease.

Improved diagnostic accuracy of vessel-specific myocardial ischemia by coronary computed tomography angiography (CCTA)

BackgroundDiscrepancies between stenosis severity assessed at coronary computed tomography angiography (CCTA) and ischemia might depend on vessel type. Coronary plaque features are associated with ischemia. Thus, we evaluated the vessel-specific correlation of CCTA-derived diameter stenosis (DS) and invasive fractional flow reserve (FFR) and explored whether integrating morphological plaque features stratified by vessel might increase the predictive yield in identifying vessel-specific ischemia. MethodsObservational cohort study including patients undergoing CCTA for suspected coronary artery disease, with at least one vessel with DS ​≥ ​50 ​% at CCTA, undergoing invasive coronary angiography and FFR. Plaque analysis was performed using validated semi-automated software. Coronary vessels were stratified in left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA). Per vessel independent predictors of ischemia among CCTA-derived anatomical and morphologic plaque features were tested at univariable and multivariable logistic regression analysis. The best cut-off to predict ischemia was determined by Youden's index. Ischemia was defined by FFR≤0.80. ResultsThe study population consisted of 192 patients, of whom 224 vessels (61 ​% LAD, 19 ​% LCX, 20 ​% RCA) had lesions with DS ​≥ ​50 ​% interrogated by FFR. Despite similar DS, the rate of FFR≤0.80 was higher in the LAD compared to LCX and RCA (67.2 ​% vs 43.2 ​% and 44.2 ​%, respectively, p ​= ​0.018). A significant correlation between DS and FFR was observed only in LAD (p ​= ​0.003). At multivariable analysis stratified by vessel, the vessel-specific independent predictors of positive FFR were percent atheroma volume (threshold>17 ​%) for LAD, non-calcified plaque volume (threshold >130 ​mm3) for LCX, and lumen volume (threshold <844 ​mm3) for RCA. Integrating DS and vessel-specific morphological plaque features significantly increased the predictive yield for ischemia compared to DS alone (AUC ranging from 0.51 to 0.63 to 0.76–0.80). ConclusionsIntegrating DS and vessel-specific morphological plaque features significantly increased the predictive yield for vessel-specific ischemia compared to DS alone, potentially improving patients’ referral to the catheterization laboratory.

Coronary Plaque Radiomic Phenotypes Predict Fatal or Nonfatal Myocardial Infarction: Analysis of the SCOT-HEART Trial

BackgroundCoronary computed tomography (CT) angiography–derived attenuation-based plaque burden assessments can identify patients at risk of myocardial infarction. ObjectivesThis study sought to assess whether more detailed plaque morphology assessment using patient-based radiomic characterization could further enhance the identification of patients at risk of myocardial infarction during long-term follow-up. MethodsPost hoc analysis of coronary CT angiography was performed within the SCOT-HEART (Scottish Computed Tomography of the HEART) clinical trial. Coronary plaque segmentations were used to calculate plaque burdens and eigen radiomic features that described plaque morphology. Univariable and multivariable Cox proportional hazard models were used to evaluate the association between clinical and image-based features and fatal or nonfatal myocardial infarction, whereas Harrell’s C-statistic and cumulative/dynamic area under the curve (AUC) values with cross-validation were used to evaluate prognostic performance. ResultsScans from 1,750 patients (aged 58 ± 9 years; 56% male) were analyzed. Over a median of 8.6 years of follow-up, 82 patients had a fatal or nonfatal myocardial infarction. Among the eigen radiomic features, 15 were associated with myocardial infarction in univariable analysis, and 8 features retained their association following adjustment for cardiovascular risk score and plaque burden metrics. Adding plaque burden metrics to a clinical model incorporating cardiovascular risk score, Agatston score and presence of obstructive coronary artery disease had similar prediction performance (C-statistic 0.70 vs 0.70), whereas further addition of eigen radiomic features improved model performance (C-statistic 0.74). In temporal analysis, the model including eigen radiomic features had higher cumulative/dynamic AUC values following the fifth year of follow-up. ConclusionsRadiomics-based precision phenotyping of coronary plaque morphology provided improvements to long-term prediction of myocardial infarction by CT angiography over and above clinical factors and plaque burden. (Scottish Computed Tomography of the HEART [SCOT-HEART]; NCT01149590)

Comparative study of the propagation and plaque titration conditions for human coronavirus OC43 as a surrogate for SARS-CoV-2.

The ongoing COVID-19 pandemic is threatening human health globally. The development of effective drugs and vaccines against SARS-CoV-2 is hindered by the limited access to high-biosafety-level facilities. Although human coronavirus (HCoV) OC43, a low-pathogenic endemic human coronavirus, has been used as a surrogate virus for SARS-CoV-2 research, a standard technique for HCoV-OC43 culture and plaque titration has not been established. Our objective was to establish optimized culture and titration protocols for HCoV-OC43. The growth kinetics and permissibility to HCoV-OC43 infection of seven different cell lines were examined concurrently at two different temperatures, 33°C and 37°C. Cell lines exhibiting a cytopathic effect (CPE) were selected for plaque titration. No significant difference in the rate of cell growth was observed at the two temperatures tested. Interestingly, HCoV-OC43 was found not to be a high-temperature-sensitive virus, since it grew well at 37°C. Although RD, LLC-MK2, MRC-5, and HCT-8 cell lines supported virus growth with an obvious cytopathic effect and a high yield of virus after two days of infection, only RD cells were suitable for producing countable plaques. The incubation of the cells with 1.2% low-viscosity Avicel as an overlay medium at 37°C for 4 days appeared to promote clearer and sharper plaque morphology. However, further optimization of the plaque titration protocol is still required due to the continued observation of plaque size variation and hazy zones. We propose a cost-effective protocol for HCoV-OC43 culture and plaque titration that can be implemented at a standard conventional temperature without the need for additional special equipment.