UNASSIGNED: Mechanical stress and strain conditions play an important role in atherosclerosis plaque progression, remodeling and potential rupture and may be used in plaque vulnerability assessment for better clinical diagnosis and treatment decisions. Single layer plaque models without residual stress have been widely used due to unavailability of multi-layer image segmentation method and residual stress data. However, vessel layered structure and residual stress have large impact on stress/strain calculations and should be included in the models.
UNASSIGNED: In this study, intravascular optical coherence tomography (OCT) data of coronary plaques from 10 patients were acquired and segmented to obtain the three-layer vessel structure using an in-house automatic segmentation algorithm. Multi- and single-layer 3D thin-slice biomechanical plaque models with and without residual stress were constructed to assess the impact of residual stress on stress/strain calculations.
UNASSIGNED: Our results showed that residual stress led to a more uniform stress distribution across the vessel wall, with considerable plaque stress/strain decrease on inner wall and increase on vessel out-wall. Multi-layer model with residual stress inclusion reduced inner wall maximum and mean plaque stresses by 38.57% and 59.70%, and increased out-wall maximum and mean plaque stresses by 572.84% and 432.03%.
UNASSIGNED: These findings demonstrated the importance of multi-layer modeling with residual stress for more accurate plaque stress/strain calculations, which will have great impact in plaque cap stress calculation and plaque rupture risk assessment. Further large-scale studies are needed to validate our findings.

OBJECTIVE: The definitive impacts of intensive lipid-lowering therapy (LLT) on plaque stabilization and the relationship between the key markers during LLT and plaque stability remain unquestioned. Thus, these meta-analysis and meta-regression intend to holistically evaluate the influence exerted by rigorous LLT on the minimum fibrous cap thickness (FCT) and maximum lipid arc as discerned through optical coherence tomography (OCT). This study further scrutinizes the correlation of this impact with variations in high-sensitivity C-reactive protein (hs-CRP), low-density lipoprotein cholesterol (LDL-C), or additional parameters within patients diagnosed with coronary artery disease (CAD).
METHODS: Comprehensive searches were conducted on platforms including PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) published until June 1, 2023. The search was language agnostic and targeted RCTs elaborating on the correlation between high-intensity statin therapy or statins used concomitantly with other lipid-lowering medications and the minimum FCT and maximum lipid arc as assessed by OCT. The meta-analyses were executed employing a standard mean difference (SMD) algorithm with random-effects on continuous variables. These methodologies align with the Preferred Reporting Items for Systematic and Meta-analysis (PRISMA) guidelines.
RESULTS: A spectrum of 12 RCTs engaging 972 patients were identified and mobilized for these analyses. Meta-analysis outcomes depicted a conspicuous correlation between intensive LLT and an enhanced minimum FCT (12 studies with 972 participants; SMD, 0.87; 95% CI, 0.54 to 1.21; P < 0.01), reduced maximum lipid arc (9 studies with 564 participants; SMD, -0.43; 95% CI, -0.58 to -0.29; P < 0.01). Meta-regression analysis has determined an association of elevated minimum FCT with decreased LDL-C (β, -0.0157; 95% CI, -0.0292 to -0.0023; P = 0.025), total cholesterol (TC) (β, -0.0154; 95% CI, -0.0303 to -0.0005; P = 0.044), and apolipoprotein B (ApoB) (β, -0.0209; 95% CI, -0.0361 to -0.0057; P = 0.022). However, no significant association was discerned relative to variations in hs-CRP/CRP (β, -0.1518; 95% CI, -1.3766 to -1.0730; P = 0.772), triglyceride (TG) (β, -0.0030; 95% CI, -0.0258 to -0.0318; P = 0.822), and high-density lipoprotein cholesterol (HDL-C) (β, 0.0313; 95% CI, -0.0965 to 0.1590; P = 0.608). Subsequent subgroup meta-analysis demonstrated that high-intensity statin therapy (5 studies with 204 participants; SMD, 1.03; 95% CI, 0.67 to 1.39; P < 0.01), as well as a combinative approach including PCSK9 antibodies and statins (3 studies with 522 participants; SMD, 1.17; 95% CI, 0.62 to 1.73; P < 0.01) contributed to an increase in minimum FCT. Parallelly, high-intensity statin therapy (4 studies with 183 participants; SMD, -0.42; 95% CI, -0.65 to -0.19; P < 0.01) or the combined application of PCSK9 antibodies and statins (2 studies with 222 participants; SMD, -0.98; 95% CI, -1.26 to -0.70; P < 0.01) was evidenced to decrease the maximum lipid arc.
CONCLUSIONS: Intensive LLT, mainly high-intensity statin therapy and combined PCSK9 antibody with statin, has a beneficial effect on coronary plaque stabilization derived from OCT in patients with CAD. Coronary plaque stabilization is primarily due to lipid-lowering effect, not anti-inflammatory effect. Moreover, the lipid-lowering effect has nothing to do with the changes in HDL-C and TG, but is mainly related to the reduction of LDL-C, TC, and ApoB.

BACKGROUND: Despite extensive evidence demonstrating the beneficial effects of the additional PCSK9 antibodies with high-density statins treatment on cardiovascular clinical outcomes, the potent causes underlying these effects remain elusive. This meta-analysis aimed at exploring the underlying causes to assess the effect of PCSK9 antibodies on the regression and stabilization of coronary plaque derived from intravascular imaging in statin-treated patients with coronary artery disease (CAD).
METHODS: PubMed, Embase, and Cochrane Library were searched from inception to February 1, 2023, for randomized controlled trials (RCTs), nonrandomized studies without language restrictions if they described the association between PCSK9 antibodies with coronary plaque regression and stabilization evaluated by intravascular imaging in statin-treated patients with CAD. Meta-analyses were performed for mean difference (MD) and odds ratio (OR) using a random-effects model. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
RESULTS: A total of 9 studies (7 RCTs and 2 non-RCTs) with 2290 CAD patients were identified and included. Among statin-treated CAD patients, the addition use of PCSK9 antibodies was associated with IVUS-derived percent atheroma volume (PAV) (4 studies with 1875 participants; MD, -1.26; 95% CI, -1.51 to -1.00; P < 0.01), total atheroma volume (TAV) (4 studies with 1875 participants; MD, -7.23; 95% CI, -11.28 to -3.18; P < 0.01), incidence of PAV regression (4 studies with 1875 participants; OR, 2.24; 95% CI, 1.81 to 2.77; P < 0.01) and incidence of TAV regression (3 studies with 1256 participants; OR, 1.66; 95% CI, 1.33 to 2.09; P < 0.01) in Caucasians instead of Asians from multiple countries; OCT-derived minimum fibrous cap thickness (FCT) (6 studies with 841 participants; MD, 25.16; 95% CI, 14.06 to 36.27; P < 0.01), incidence of thin-capped fibroatheroma (TCFA) regression (2 studies with 222 participants; OR, 2.56; 95% CI, 1.42 to 4.61; P < 0.01) and maximum lipid arc (4 studies with 280 participants; MD, -14.96; 95% CI, -22.10 to -7.83; P < 0.01) in Asians and Caucasians without races restrictions.
CONCLUSIONS: PCSK9 antibodies resulted in significantly greater coronary plaque regression and stabilization in statin-treated CAD patients, mostly Caucasians from multiple countries. Further studies are needed to assess the effect for Asian patients.

Mechanical stress and strain conditions are closely related to atherosclerotic plaque progression and rupture and have been under intensive investigations in recent years. It is well known that arteries have a three-layer structure: intima, media and adventitia. However, in vivo image-based multilayer plaque models are not available in the current literature due to lack of multilayer image segmentation data. A multilayer segmentation and repairing technique was introduced to segment coronary plaque optical coherence tomography (OCT) image to obtain its three-layer vessel structure. A total of 200 OCT slices from 20 patients (13 male; 7 female) were used to construct multilayer and single-layer 3D thin-slice models to calculate plaque stress and strain and compare model differences. Our results indicated that the average maximum plaque stress values of 20 patients from multilayer and single-layer models were 385.13 ± 110.09 kPa and 270.91 ± 95.86 kPa, respectively. The relative difference was 42.2%, with single-layer stress serving as the base value. The average mean plaque stress values from multilayer and single-layer models were 129.59 ± 32.77 kPa and 93.27 ± 18.20 kPa, respectively, with a relative difference of 38.9%. The maximum and mean plaque strain values obtained from the multilayer models were 11.6% and 19.0% higher than those from the single-layer models. Similarly, the maximum and mean cap strains showed increases of 9.6% and 12.9% over those from the single-layer models. These findings suggest that use of multilayer models could improve plaque stress and strain calculation accuracy and may have large impact on plaque progression and vulnerability investigation and potential clinical applications. Further large-scale studies are needed to validate our findings.

The combination of coronary imaging assessment and blood flow perturbation estimation has the potential to improve percutaneous coronary intervention (PCI) guidance.
We aimed to evaluate a novel method for fast computation of Murray law-based quantitative flow ratio (μQFR) from coregistered optical coherence tomography (OCT) and angiography (OCT-modulated μQFR, OCT-μQFR) in predicting physiological efficacy of PCI.
Patients treated by OCT-guided PCI in the OCT-arm of the Fractional Flow Reserve versus Optical Coherence Tomography to Guide RevasculariZAtion of Intermediate Coronary Stenoses trial (FORZA, NCT01824030) were included. Based on angiography and OCT before PCI, simulated residual OCT-μQFR was computed by assuming full stent expansion to the intended-to-treat segment. Plaque composition was automatically characterized using a validated artificial intelligence algorithm. Actual post-PCI OCT-μQFR pullback was computed based on coregistration of angiography and OCT acquired immediately after PCI. Suboptimal functional stenting result was defined as OCT-μQFR ≤ 0.90.
Paired simulated residual OCT-μQFR and actual post-PCI OCT-μQFR were obtained in 76 vessels from 74 patients. Simulated residual OCT-μQFR showed good correlation (r = 0.80, p < 0.001), agreement (mean difference = -0.02 ± 0.02, p < 0.001), and diagnostic concordance (79%, 95% confidence interval: 70%-88%) with actual post-PCI OCT-μQFR. Actual post-PCI in-stent OCT-μQFR had a median value of 0.02 and was associated with left anterior descending artery lesion location (β = 0.38, p < 0.001), higher baseline total plaque burden (β = 0.25, p = 0.031), and fibrous plaque volume (β = 0.24, p = 0.026).
This study based on patients enrolled in a prospective OCT-guidance PCI trial shows that simulated residual OCT-μQFR had good correlation, agreement, and diagnostic concordance with actual post-PCI OCT-μQFR. In OCT-guided procedures, OCT-μQFR in-stent pressure drop was low and was significantly predicted by pre-PCI vessel/plaque characteristics.

Accumulated evidence shows that elevated urotensin II (UII) levels are associated with cardiovascular diseases. However, the role of UII in the initiation, progression, and regression of atherosclerosis remains to be verified. Different stages of atherosclerosis were induced in rabbits by a 0.3% high cholesterol diet (HCD) feeding, and either UII (5.4 μg/kg/h) or saline was chronically infused via osmotic mini-pumps. UII promoted atherosclerotic fatty streak formation in ovariectomized female rabbits (34% increase in gross lesion and 93% increase in microscopic lesion), and in male rabbits (39% increase in gross lesion). UII infusion significantly increased the plaque size of the carotid and subclavian arteries (69% increase over the control). In addition, UII infusion significantly enhanced the development of coronary lesions by increasing plaque size and lumen stenosis. Histopathological analysis revealed that aortic lesions in the UII group were characterized by increasing lesional macrophages, lipid deposition, and intra-plaque neovessel formation. UII infusion also significantly delayed the regression of atherosclerosis in rabbits by increasing the intra-plaque macrophage ratio. Furthermore, UII treatment led to a significant increase in NOX2 and HIF-1α/VEGF-A expression accompanied by increased reactive oxygen species levels in cultured macrophages. Tubule formation assays showed that UII exerted a pro-angiogenic effect in cultured endothelial cell lines and this effect was partly inhibited by urantide, a UII receptor antagonist. These findings suggest that UII can accelerate aortic and coronary plaque formation and enhance aortic plaque vulnerability, but delay the regression of atherosclerosis. The role of UII on angiogenesis in the lesion may be involved in complex plaque development.

Conventional prognostic risk analysis in patients undergoing noninvasive imaging is based upon a limited selection of clinical and imaging findings, whereas machine learning (ML) algorithms include a greater number and complexity of variables. Therefore, this paper aimed to explore the predictive value of integrating coronary plaque information from coronary computed tomographic angiography (CCTA) with ML to predict major adverse cardiovascular events (MACEs) in patients with suspected coronary artery disease (CAD). Patients who underwent CCTA due to suspected coronary artery disease with a 30-month follow-up for MACEs were included. We collected demographic characteristics, cardiovascular risk factors, and information on coronary plaques by analyzing CCTA information (plaque length, plaque composition and coronary artery stenosis of 18 coronary artery segments, coronary dominance, myocardial bridge (MB), and patients with vulnerable plaque) and follow-up information (cardiac death, nonfatal myocardial infarction and unstable angina requiring hospitalization). An ML algorithm was used for survival analysis (CoxBoost). This analysis showed that chest symptoms, the stenosis severity of the proximal anterior descending branch, and the stenosis severity of the middle right coronary artery were among the top three variables in the ML model. After the 22nd month of follow-up, in the testing dataset, ML showed the largest C-index and AUC compared with Cox regression, SIS, SIS score + clinical factors, and clinical factors. The DCA of all the models showed that the net benefit of the ML model was the highest when the treatment threshold probability was between 1% and 9%. Integrating coronary plaque information from CCTA based on ML technology provides a feasible and superior method to assess prognosis in patients with suspected coronary artery disease over an approximately three-year period.

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

OBJECTIVE: To analyse the correlation between the characteristics of coronary plaque in coronary heart disease (CHD) patients with phlegm-blood stasis syndrome (PBS) and blood stasis syndrome (BSS).
METHODS: Patients were divided into different groups based on Chinese medicine (CM) syndrome differentiation. The baseline demographics and clinical variables were collected from the medical records. Additionally, the characteristics of plaque and pathological manifestations in coronary artery were evaluated using intravascular ultrasound (IVUS).
RESULTS: A total of 213 CHD patients were enrolled in two groups: 184 were diagnosed with PBS and the remaining 29 were diagnosed with BSS. There were no significant differences in age, body mass index, proportions of patients with high blood pressure, diabetes mellitus, smoking, hyperlipidemia, history of coronary artery bypass graft and percutaneous coronary intervention, medications, index from cardiac ultrasound image, blood lipids and C-reactive protein between the two groups (P>0.05), except gender, weight and proportions of IVUS observed target vessels (P<0.05 or P<0.01). More adverse events such as acute myocardial infarction (P=0.003) and unstable angina (P=0.048) were observed in BSS. Additionally, dissection, thrombus and coronary artery ectasia were significantly increased in BSS (P<0.05 or P<0.01). In contrast, PBS had more patients with stable angina and chronic total occlusion with significantly higher SYNTAX (synergy between percutaneous coronary intervention with Taxus and coronary artery bypass surgery) scores (P<0.05 or P<0.01). Moreover, dense-calcium was significantly elevated in PBS (P<0.01).
CONCLUSIONS: Coronary plaque characteristics were correlated with different CM syndromes. Patients with PBS were associated with a higher degree of calcified plaque and severe coronary artery stenosis, indicating poor clinical prognosis but with a low probability of acute coronary events. In contrast, the degree of calcified plaque in patients with BSS remained relatively low, and plaque was more vulnerable, resulting in the possibility of the occurrence of acute coronary events remaining high.

Introduction: Mechanical forces are closely associated with plaque progression and rupture. Precise quantifications of biomechanical conditions using in vivo image-based computational models depend heavily on the accurate estimation of patient-specific plaque mechanical properties. Currently, mechanical experiments are commonly performed on ex vivo cardiovascular tissues to determine plaque material properties. Patient-specific in vivo coronary material properties are scarce in the existing literature. Methods: In vivo Cine intravascular ultrasound and virtual histology intravascular ultrasound (IVUS) slices were acquired at 20 plaque sites from 13 patients. A three-dimensional thin-slice structure-only model was constructed for each slice to obtain patient-specific in vivo material parameter values following an iterative scheme. Effective Young\'s modulus (YM) was calculated to indicate plaque stiffness for easy comparison purposes. IVUS-based 3D thin-slice models using in vivo and ex vivo material properties were constructed to investigate their impacts on plaque wall stress/strain (PWS/PWSn) calculations. Results: The average YM values in the axial and circumferential directions for the 20 plaque slices were 599.5 and 1,042.8 kPa, respectively, 36.1% lower than those from published ex vivo data. The YM values in the circumferential direction of the softest and stiffest plaques were 103.4 and 2,317.3 kPa, respectively. The relative difference of mean PWSn on lumen using the in vivo and ex vivo material properties could be as high as 431%, while the relative difference of mean PWS was much lower, about 3.07% on average. Conclusion: There is a large inter-patient and intra-patient variability in the in vivo plaque material properties. In vivo material properties have a great impact on plaque stress/strain calculations. In vivo plaque material properties have a greater impact on strain calculations. Large-scale-patient studies are needed to further verify our findings.