The Use of Coronary Imaging for Predicting Future Cardiovascular Events.

Background: Despite advancements in coronary artery disease (CAD) treatment with drug-eluting stent, its morbidity and mortality remain high. In context, intravascular imaging-guided percutaneous coronary intervention (PCI) is increasingly recommended for better clinical outcomes in patient with CAD. Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), as one of the intravascular imaging methods, is effective in detecting lipid-rich plaques, which is crucial for identifying high-risk or vulnerable plaques employing near-infrared light. High lipid core burden, as identified by NIRS-IVUS, correlates with an increased risk of adverse cardiac events and shows varying degrees of efficacy in plaque management and event prevention. Summary: This article addresses about how NIRS-IVUS can be used to predict event of CAD. The study highlights the crucial role of NIRS-IVUS in predicting future cardiovascular events. Findings indicate that the presence of high lipid core burden is related to increased risks of periprocedural myocardial infarction and reduced coronary flow during PCI. The study also outlines the predictive value of NIRS-IVUS in non-culprit lesions, where plaques with high lipid core burden significantly increase the occurrence of major adverse cardiac events as demonstrated in the PROSPECT II trial. In terms of therapeutic strategies, the study reviews the effectiveness of high-intensity lipid-lowering strategies in stabilizing vulnerable plaques, as evidenced in trials such as the YELLOW and PACMAN AMI trials. Key Messages: NIRS-IVUS emerges as a valuable diagnostic tool in treating CAD. It effectively identifies vulnerable plaques and aids in predicting and preventing future adverse cardiac events. However, to enhance its practicality and promote widespread adoption in clinical settings, further long-term outcome research of NIRS-IVUS-guided PCI is necessary. These efforts can potentially make NIRS-IVUS a more accessible and indispensable tool in cardiovascular disease management.

The accuracy of detailed analysis of optical coherence tomography in detection of plaque lipid content: dual-imaging study with optical coherence tomography and near-infrared spectroscopy.

BACKGROUND: Lipid-rich plaque covered by a thin fibrous cap (FC) has been identified as a frequent morphological substrate for the development of acute coronary syndrome. Optical coherence tomography (OCT) permits the identification and measurement of the FC. Near-infrared spectroscopy (NIRS) has been approved for detection of coronary lipids. AIMS: We aimed to assess the ability of detailed OCT analysis to identify coronary lipids, using NIRS as the reference method. METHODS: In total, 40 patients with acute coronary syndrome underwent imaging of a non-culprit lesion by both NIRS and OCT. For each segment, the NIRS-derived 4 mm segment with maximal lipid core burden index (maxLCBI4mm) was assessed. OCT analysis was performed using a semi-automated method including measurement of the fibrous cap thickness (FCT) of all detected fibroatheromas. Subsequent quantitative volumetric evaluation furnished FCT, FC surface area (FC SA), lipid arc, and FC (fibrous cap) volume data. OCT features of lipid plaques were compared with maxLCBI4mm. Predictors of maxLCBI4mm >400 was assessed by using univariable and multivariable analysis. RESULTS: OCT features (mean FCT, total FC SA, FC volume, maximal, mean, and total lipid arcs) strongly correlated with the maxLCBI4mm (p = 0.012 for the mean FCT, respectively p < 0.001 for all other aforementioned features). The strongest predictors of maxLCBI4mm >400 were the maximal (p = 0.002) and mean (p = 0.002) lipid arc, and total FC SA (p = 0.012). CONCLUSIONS: We found a strong correlation between the OCT-derived features and NIRS findings. Detailed OCT analysis may be reliably used for detection of the presence of coronary lipids.

Quantification of Low-Attenuation Plaque Burden from Coronary CT Angiography: A Head-to-Head Comparison with Near-Infrared Spectroscopy Intravascular US.

Purpose: To determine the association between low-attenuation plaque (LAP) burden at coronary CT angiography (CCTA) and plaque morphology determined with near-infrared spectroscopy intravascular US (NIRS-IVUS) and to compare the discriminative ability for NIRS-IVUS-verified high-risk plaques (HRPs) between LAP burden and visual assessment of LAP. Materials and Methods: This Health Insurance Portability and Accountability Act-compliant retrospective study included consecutive patients who underwent CCTA before NIRS-IVUS between October 2019 and October 2022 at two facilities. LAPs were visually identified as having a central focal area of less than 30 HU using the pixel lens technique. LAP burden was calculated as the volume of voxels with less than 30 HU divided by vessel volume. HRPs were defined as plaques with one of the following NIRS-IVUS-derived high-risk features: maximum 4-mm lipid core burden index greater than 400 (lipid-rich plaque), an echolucent zone (intraplaque hemorrhage), or echo attenuation (cholesterol clefts). Multivariable analysis was performed to evaluate NIRS-IVUS-derived parameters associated with LAP burden. The discriminative ability for NIRS-IVUS-verified HRPs was compared using receiver operating characteristic analysis. Results: In total, 273 plaques in 141 patients (median age, 72 years; IQR, 63-78 years; 106 males) were analyzed. All the NIRS-IVUS-derived high-risk features were independently linked to LAP burden (P < .01 for all). LAP burden increased with the number of high-risk features (P < .001) and had better discriminative ability for HRPs than plaque attenuation by visual assessment (area under the receiver operating characteristic curve, 0.93 vs 0.89; P = .02). Conclusion: Quantification of LAP burden improved HRP assessment compared with visual assessment. LAP burden was associated with the accumulation of HRP morphology.Keywords: Coronary CT Angiography, Intraplaque Hemorrhage, Lipid-Rich Plaque, Low Attenuation Plaque, Near-Infrared Spectroscopy Intravascular Ultrasound Supplemental material is available for this article. See also the commentary by Ferencik in this issue.© RSNA, 2023.

Determination of lipid-rich plaques by artificial intelligence-enabled quantitative computed tomography using near-infrared spectroscopy as reference.

BACKGROUND AND AIMS: Artificial intelligence quantitative CT (AI-QCT) determines coronary plaque morphology with high efficiency and accuracy. Yet, its performance to quantify lipid-rich plaque remains unclear. This study investigated the performance of AI-QCT for the detection of low-density noncalcified plaque (LD-NCP) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). METHODS: The INVICTUS Registry is a multi-center registry enrolling patients undergoing clinically indicated coronary CT angiography and IVUS, NIRS-IVUS, or optical coherence tomography. We assessed the performance of various Hounsfield unit (HU) and volume thresholds of LD-NCP using maxLCBI4mm ≥ 400 as the reference standard and the correlation of the vessel area, lumen area, plaque burden, and lesion length between AI-QCT and IVUS. RESULTS: This study included 133 atherosclerotic plaques from 47 patients who underwent coronary CT angiography and NIRS-IVUS The area under the curve of LD-NCP<30HU was 0.97 (95% confidence interval [CI]: 0.93-1.00] with an optimal volume threshold of 2.30 mm3. Accuracy, sensitivity, and specificity were 94% (95% CI: 88-96%], 93% (95% CI: 76-98%), and 94% (95% CI: 88-98%), respectively, using <30 HU and 2.3 mm3, versus 42%, 100%, and 27% using <30 HU and >0 mm3 volume of LD-NCP (p < 0.001 for accuracy and specificity). AI-QCT strongly correlated with IVUS measurements; vessel area (r2 = 0.87), lumen area (r2 = 0.87), plaque burden (r2 = 0.78) and lesion length (r2 = 0.88), respectively. CONCLUSIONS: AI-QCT demonstrated excellent diagnostic performance in detecting significant LD-NCP using maxLCBI4mm ≥ 400 as the reference standard. Additionally, vessel area, lumen area, plaque burden, and lesion length derived from AI-QCT strongly correlated with respective IVUS measurements.

Coronary Atherosclerosis Phenotypes in Focal and Diffuse Disease.

BACKGROUND: The interplay between coronary hemodynamics and plaque characteristics remains poorly understood. OBJECTIVES: The aim of this study was to compare atherosclerotic plaque phenotypes between focal and diffuse coronary artery disease (CAD) defined by coronary hemodynamics. METHODS: This multicenter, prospective, single-arm study was conducted in 5 countries. Patients with functionally significant lesions based on an invasive fractional flow reserve ≤0.80 were included. Plaque analysis was performed by using coronary computed tomography angiography and optical coherence tomography. CAD patterns were assessed using motorized fractional flow reserve pullbacks and quantified by pullback pressure gradient (PPG). Focal and diffuse CAD was defined according to the median PPG value. RESULTS: A total of 117 patients (120 vessels) were included. The median PPG was 0.66 (IQR: 0.54-0.75). According to coronary computed tomography angiography analysis, plaque burden was higher in patients with focal CAD (87% ± 8% focal vs 82% ± 10% diffuse; P = 0.003). Calcifications were significantly more prevalent in patients with diffuse CAD (Agatston score per vessel: 51 [IQR: 11-204] focal vs 158 [IQR: 52-341] diffuse; P = 0.024). According to optical coherence tomography analysis, patients with focal CAD had a significantly higher prevalence of circumferential lipid-rich plaque (37% focal vs 4% diffuse; P = 0.001) and thin-cap fibroatheroma (TCFA) (47% focal vs 10% diffuse; P = 0.002). Focal disease defined by PPG predicted the presence of TCFA with an area under the curve of 0.73 (95% CI: 0.58-0.87). CONCLUSIONS: Atherosclerotic plaque phenotypes associate with intracoronary hemodynamics. Focal CAD had a higher plaque burden and was predominantly lipid-rich with a high prevalence of TCFA, whereas calcifications were more prevalent in diffuse CAD. (Precise Percutaneous Coronary Intervention Plan [P3]; NCT03782688).

Characterization of plaque phenotypes exhibiting an elevated pericoronary adipose tissue attenuation: insights from the REASSURE-NIRS registry.

Inflammation has been considered to promote atheroma instability. Coronary computed tomography angiography (CCTA) visualizes pericoronary adipose tissue (PCAT) attenuation, which reflects coronary artery inflammation. While PCAT attenuation has been reported to predict future coronary events, plaque phenotypes exhibiting high PCAT attenuation remains to be fully elucidated. The current study aims to characterize coronary atheroma with a greater vascular inflammation. We retrospectively analyzed culprit lesions in 69 CAD patients receiving PCI from the REASSURE-NIRS registry (NCT04864171). Culprit lesions were evaluated by both CCTA and near-infrared spectroscopy/intravascular ultrasound (NIRS/IVUS) imaging prior to PCI. PCAT attenuation at proximal RCA (PCATRCA) and NIRS/IVUS-derived plaque measures were compared in patients with PCATRCA attenuation ≥ and < -78.3 HU (median). Lesions with PCATRCA attenuation ≥ -78.3 HU exhibited a greater frequency of maxLCBI4mm ≥ 400 (66% vs. 26%, p < 0.01), plaque burden ≥ 70% (94% vs. 74%, p = 0.02) and spotty calcification (49% vs. 6%, p < 0.01). Whereas positive remodeling (63% vs. 41%, p = 0.07) did not differ between two groups. On multivariable analysis, maxLCBI4mm ≥ 400 (OR = 4.07; 95%CI 1.12-14.74, p = 0.03), plaque burden ≥ 70% (OR = 7.87; 95%CI 1.01-61.26, p = 0.04), and spotty calcification (OR = 14.33; 95%CI 2.37-86.73, p < 0.01) independently predicted high PCATRCA attenuation. Of note, while the presence of only one plaque feature did not necessarily elevate PCATRCA attenuation (p = 0.22), lesions harboring two or more features were significantly associated with higher PCATRCA attenuation. More vulnerable plaque phenotypes were observed in patients with high PCATRCA attenuation. Our findings suggest PCATRCA attenuation as the presence of profound disease substrate, which potentially benefits from anti-inflammatory agents.

Disparities among Black and White patients in plaque burden and composition and long-term impact.

BACKGROUND: Black patients presenting to the catheterization laboratory have more risk factors and worse long-term outcomes. This sub-analysis of the Lipid Rich Plaque (LRP) study quantifies the plaque burden and composition of Black vs White patients and associated outcomes. METHODS: Patients with a singular, self-reported race presenting for cardiac catheterization were enrolled if near-infrared spectroscopy/intravascular ultrasound (NIRS-IVUS) imaging of non-stented, non-culprit (NC) vessels was performed. Lipidic content was quantified at the 4-mm region with maximum Lipid Core Burden Index (maxLCBI4mm). NC major adverse cardiac events (NC-MACE) were defined as: cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization, and hospital readmission for angina with >20 % disease progression through 2 years. RESULTS: Among 1346 patients with a singular, self-reported race, 182 were Black. Black vs White patients were more likely to be female, had higher rates of traditional risk factors, and were more likely to present acutely. Both patients and segments were more likely to have maxLCBI4mm > 400 (46.7 % vs 30.6 %, p < 0.001, respectively; 15.5 % vs 8.9 %, p < 0.001, respectively). Vessel size and plaque burden were larger for Black vs White patients. At 2 years, maxLCBI4mm > 400 and Black race were independently predictive of NC-MACE (hazard ratio [HR] maxLCBI4mm > 400: 2.37 [95 % confidence interval (CI) 1.50-3.76, p < 0.001], Black race: 2.8 [95 % CI 1.27-3.42, p = 0.004], pinteraction = 0.137). CONCLUSIONS: Compared to White patients, Black patients had more lipid-rich plaques with greater plaque burden. Both high lipidic burden and Black race were independently predictive of NC-MACE within 2 years. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02033694, NCT02033694.

Multimodality imaging to identify lipid-rich coronary plaques and predict periprocedural myocardial injury: Association between near-infrared spectroscopy and coronary computed tomography angiography.

Background: This study compares the efficacy of coronary computed tomography angiography (CCTA) and near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with significant coronary stenosis for predicting periprocedural myocardial injury during percutaneous coronary intervention (PCI). Methods: We prospectively enrolled 107 patients who underwent CCTA before PCI and performed NIRS-IVUS during PCI. Based on the maximal lipid core burden index for any 4-mm longitudinal segments (maxLCBI4mm) in the culprit lesion, we divided the patients into two groups: lipid-rich plaque (LRP) group (maxLCBI4mm ≥ 400; n = 48) and no-LRP group (maxLCBI4mm < 400; n = 59). Periprocedural myocardial injury was a postprocedural cardiac troponin T (cTnT) elevation of ≥5 times the upper limit of normal. Results: The LRP group had a significantly higher cTnT (p = 0.026), lower CT density (p < 0.001), larger percentage atheroma volume (PAV) by NIRS-IVUS (p = 0.036), and larger remodeling index measured by both CCTA (p = 0.020) and NIRS-IVUS (p < 0.001). A significant negative linear correlation was found between maxLCBI4mm and CT density (rho = -0.552, p < 0.001). Multivariable logistic regression analysis identified maxLCBI4mm [odds ratio (OR): 1.006, p = 0.003] and PAV (OR: 1.125, p = 0.014) as independent predictors of periprocedural myocardial injury, while CT density was not an independent predictor (OR: 0.991, p = 0.22). Conclusion: CCTA and NIRS-IVUS correlated well to identify LRP in culprit lesions. However, NIRS-IVUS was more competent in predicting the risk of periprocedural myocardial injury.

Additive Effect of Multiple High-Risk Coronary Artery Segments on Patient Outcomes: LRP Study Sub-Analysis.

BACKGROUND: The Lipid Rich Plaque (LRP) Study established the association between high volume of lipidic content (maximum Lipid Core Burden Index [maxLCBI4mm] >400) in the coronary arteries and subsequent non-culprit major adverse cardiac events (NC-MACE). This analysis sought to assess the clinical impact of more than one lipid-rich plaque in the coronary tree. METHODS: The LRP patient population was divided into four cohorts: 1) patients with all segments with maxLCBI4mm = 0; 2) patients with all coronary segments maxLCBI4mm < 400, but >0; 3) patients with 1 segment maxLCBI4mm > 400; and 4) patients with 2+ coronary segments with maxLCBI4mm > 400. Baseline characteristics, plaque-level characteristics, and follow-up outcomes were described. RESULTS: Among 1550 patients, only 3.2 % had all segments with maxLCBI4mm = 0; 65.1 % had segments with maxLCBI4mm > 0 but <400; 22.5 % had one segment with maxLCBI4mm > 400; and 9.5 % had 2+ coronary segments with maxLCBI4mm > 400. Distribution within the coronary tree (one versus multiple arteries) did not differ. Overall, 1269 patients were allocated to follow-up (per study design). The composite of all-cause death, cardiac death, any revascularization, and NC-MACE was statistically higher in patients with 1 segment maxLCBI4mm > 400 and numerically even higher in patients with 2+ segments with maxLCBI4mm > 400. Patients with maxLCBI4mm = 0 had no events within two years. CONCLUSION: There is a stepwise increased risk of all-cause death, cardiac death, any revascularization, and NC-MACE according to the number of coronary segments with maxLCBI4mm > 400. In contrast, maxLCBI4mm = 0 results in a low event rate. CLINICAL TRIAL REGISTRATION: The Lipid-Rich Plaque Study (LRP), https://clinicaltrials.gov/ct2/show/NCT02033694, NCT02033694.

Impact of the eicosapentaenoic acid to arachidonic acid ratio on plaque characteristics in statin-treated patients with coronary artery disease.

BACKGROUND: A low eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio is associated with an increased risk of cardiovascular events in patients with coronary artery disease (CAD). OBJECTIVE: To clarify the impact of the EPA/AA ratio on the characteristics of non-culprit coronary plaques in statin-treated patients with CAD. METHODS: A total of 370 consecutive stable coronary disease patients treated with statins, who underwent percutaneous coronary intervention for the culprit lesion and optical coherence tomography (OCT) imaging of the non-culprit plaque in a culprit vessel were included. The characteristics of non-culprit plaques assessed using OCT were compared between the lower EPA/AA group (EPA/AA <0.4, n = 255) and the higher EPA/AA group (EPA/AA ≥0.4, n = 115). RESULTS: The prevalence of lipid-rich plaque (58.8 vs. 41.7%, p = 0.003) and plaque with macrophages (56.5 vs. 31.3%, p <0.001) was significantly higher in the lower EPA/AA group than in the higher EPA/AA group. This association was observed even if the LDL-C level was <100 mg/dL. The prevalence of thin-cap fibroatheroma was significantly higher in patients with lower EPA/AA and higher LDL-C (≥100 mg/dL) than in those with higher EPA/AA and lower LDL-C (<100 mg/dL) (odds ratio: 2.750, 95% confidence interval: 1.182-6.988, p = 0.024). An EPA/AA <0.4 was independently associated with a higher prevalence of lipid-rich plaque, plaque with macrophages, and cholesterol crystals. CONCLUSION: Lower EPA/AA ratio was associated with higher prevalence of vulnerable characteristics in non-culprit plaques. The present results suggest the importance of EPA/AA ratio on the secondary prevention of CAD.

Clinical features and lipid profiles of plaque erosion over lipid-rich plaque versus fibrous plaque in patients with acute coronary syndrome.

BACKGROUND AND AIMS: Pathological reports have shown that plaque erosion (PE), a common cause of acute coronary syndrome (ACS), can form in both fibrous plaque and lipid-rich plaque (LRP). In plaque rupture (PR), which is the main cause of ACS, the underlying plaque is LRP with a thin fibrous cap. In this study, we aimed to investigate the clinical features and lipid profiles of PE with or without LRP in comparison with those of PR. METHODS: A total of 166 patients with ACS, who underwent percutaneous coronary intervention using optical coherence tomography (OCT) and met the criteria for PR or PE, were included. LRP was defined as plaque with a maximal lipid arc (>180°). Culprit lesions were categorized into PR and PE with/without LRP [PE(Lipid) or PE(Fibrous)]. RESULTS: The prevalence of PR, PE(Lipid), and PE(Fibrous) was 104 (62.7%), 43 (25.9%), and 19(11.4%), respectively. The patients with PR and PE(Lipid) had a significantly higher peak creatine kinase level (1338 and 1584U/L, respectively, p < 0.01) and prevalence of ST-elevation myocardial infarction (71.2% and 79.1%, respectively, p < 0.01) than those with PE(Fibrous) (214U/L and 21.1%, respectively). The various lipid profiles were mostly comparable between the patients with PE(Lipid) and PR, but different in those with PE(Fibrous). The levels of small dense low-density lipoprotein cholesterol were significantly higher in the patients with PR and PE(Lipid) than in those with PE(Fibrous) (39.0, 35.3, and 25.7 mg/dL, respectively, p = 0.02). CONCLUSIONS: The clinical features and lipid profiles are substantially different between PE(Lipid) and PE(Fibrous), but are somewhat similar between PE(Lipid) and PR.

Correlation between lipidic content and arterial-wall plaque burden: A Lipid Rich Plaque study sub-analysis.

BACKGROUND: Large plaque burden (PB) has been linked to adverse coronary events. We sought to assess the correlation between lipidic content and arterial PB within the Lipid Rich Plaque (LRP) study. METHODS: This analysis included 1269 patients and 5743 coronary segments with both evaluable Lipid Core Burden Index (maxLCBI4mm) and PB. Non-culprit major adverse cardiac events (NC-MACE; defined as a composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization, and hospital readmission for angina with progressive stenosis) were assessed by hazard ratios (HR) at 2 years. RESULTS: NC-MACE for segment cohorts in the most vulnerable quadrant of maxLCBI4mm > 400 and PB >40% was the highest (HR, 3.78 [95% confidence interval (CI) 2.39-5.66]) with similar rates for just PB >40% (HR 1.31 [95% CI 0.81-2.02]) and just maxLCBI4mm > 400 (HR 1.11 [95% CI 0.10-5.38]). Fewer events occurred in the maxLCBI4mm ≤ 400 and PB ≤40% quadrant (HR 0.25 [95% CI 0.11-0.50]). CONCLUSIONS: Coronary segments with high lipid content but no measurable PB were still associated with events at 2 years. NC-MACE vulnerability increased as the lipidic content and PB increased, with the highest incidence within segments having maxLCBI4mm > 400 and plaque >40%. CLINICAL TRIAL REGISTRATION: The Lipid-Rich Plaque Study (LRP), NCT02033694, https://clinicaltrials.gov/ct2/show/NCT02033694.

Elevated Lipoprotein(a) as a potential residual risk factor associated with lipid-rich coronary atheroma in patients with type 2 diabetes and coronary artery disease on statin treatment: Insights from the REASSURE-NIRS registry.

BACKGROUND AND AIMS: The residual risk of atherosclerotic cardiovascular disease (ASCVD) in patients with diabetes on statin therapy warrants identification of other pro-atherogenic drivers. Lipoprotein(a) [Lp(a)] promotes the formation of necrotic cores within vessel walls. Given that patients with diabetes have an Lp(a)-associated ASCVD risk, Lp(a) might lead to plaque vulnerability in patients with diabetes on statin therapy. METHODS: We analyzed target lesions that underwent PCI in 312 patients with coronary artery disease (CAD) on statin treatment from the REASSURE-NIRS registry (NCT04864171). Maximum 4-mm lipid-core-burden index (maxLCBI4mm) in target lesions was measured with near-infrared spectroscopy (NIRS) imaging. The relationship between Lp(a) levels and maxLCBI4mm was investigated in patients with and without diabetes. RESULTS: High-intensity statin use (p = 0.49) and on-treatment low-density lipoprotein cholesterol (LDL-C) (p = 0.32) and Lp(a) levels (p = 0.09) were comparable between patients with and without diabetes. Lp(a) levels were significantly associated with maxLCBI4mm in patients with diabetes (p = 0.01) but not in patients without diabetes (p = 0.96). Multivariate analysis showed that LDL-C levels (p = 0.03) predict maxLCBI4mm in patients without diabetes, but not Lp(a) levels (p = 0.91). Both LDL-C (p = 0.01) and Lp(a) (p = 0.04) levels were independent predictors of maxLCBI4mm in patients with diabetes. Even in patients with diabetes achieving LDL-C <1.8 mmol/L (70 mg/dL), Lp(a) levels remained associated with maxLCBI4mm (p = 0.04). CONCLUSIONS: A significant relationship between Lp(a) and maxLCBI4mm exists in patients with diabetes and CAD on statin treatment, even with LDL-C <1.8 mmol/L (70 mg/dL). Lp(a) might be associated with more vulnerable coronary atheroma in patients with diabetes despite receiving statin therapy.

Near-infrared spectroscopy predicts events in men and women: Results from the Lipid Rich Plaque study.

Background: The Lipid Rich Plaque (LRP) study demonstrated that near-infrared spectroscopy imaging of non-obstructive lesions identified patients and segments at higher risk for subsequent non-culprit major adverse cardiac events (NC-MACE). Whether this is true for both men and women is not known. In this post hoc analysis of the LRP study, we sought to investigate whether the maximum 4-mm Lipid Core Burden Index (maxLCBI4mm) was of similar predictive value in men and women for NC-MACE. Methods: Patients with an evaluable maxLCBI4mm were stratified on the basis of sex at birth. A Cox proportional-hazards model was used to assess the predictive value of maxLCBI4mm on future NC-MACE at the patient and plaque levels. The primary endpoint was cumulative incidence of NC-MACE at 24 months. Results: Among 1271 patients, 388 (30.5%) were women. Women were older and had a higher cardiovascular risk profile. Cumulative incidence of NC-MACE at 24 months was 10.3% for women and 7.6% for men (log-rank p = 0.11). When comparing maxLCBI4mm > 400 to maxLCBI4mm ≤ 400, the hazard ratio (HR) for future NC-MACE was not significantly different between sexes: 2.10 (95% confidence interval [CI]: 1.28-3.44; p = 0.003) for men and 2.24 (95% CI: 1.18-4.28; p = 0.014) for women (p = 0.87). At the plaque level, the HR comparing maxLCBI4mm > 400 to maxLCBI4mm ≤ 400 was 3.49 (95% CI: 1.60-7.60, p = 0.002) for men and 4.79 (95% CI: 2.02-11.38, p < 0.001) for women, which was not significantly different (p = 0.57). Conclusions: The maxLCBI4mm was of similar predictive value for NC-MACE within 24 months in men and women.

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

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

Left main revascularization with optical coherence tomography in a young male with newly diagnosed homozygous familial hypercholesterolemia.

Familial hypercholesterolemia is the most common primary lipid disorder responsible for coronary artery disease. A 22-year-old male presented with history of accelerating angina and extensive xanthomatous lesions all over the body. Coronary angiography showed significant left main and left anterior descending artery disease. Optical coherence tomography (OCT) imaging revealed areas of lipid rich plaque with thin capped fibrous atheroma, and inflammatory cell infiltration. Area of maximum stenosis showed fibrous plaque with dense lipid pool. OCT in this patient clarified plaque characteristics and achieved optimal procedural results. There were only few case reports which described OCT findings in patients with familial hypercholesterolemia. .

Clinical impact of PCSK9 inhibitor on stabilization and regression of lipid-rich coronary plaques: a near-infrared spectroscopy study.

AIMS: This study aimed to determine the effects of a proprotein convertase subtilisin-kexin type 9 inhibitor (PCSK9i) on coronary plaque volume and lipid components in patients with a history of coronary artery disease (CAD). METHODS AND RESULTS: This prospective, open-label, single-centre study analysed non-culprit coronary segments using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) at baseline and follow-up angiography. Following changes in the lipid-lowering treatment based on the most recent guideline, the enrolled subjects were divided into two groups: treatment with PCSK9i and statins (PCSK9i: 21 patients and 40 segments) and statins only (control: 32 patients and 50 segments). The absolute and percent LDL-C reductions were significantly greater in the PCSK9i group than in the control group (between group difference: 59.3 mg/dL and 46.4%; P < 0.001 for both). The percent reduction in normalized atheroma volume and absolute reduction in percent atheroma volume (PAV) were also significantly greater in the PCSK9i group (P < 0.001 for both). Furthermore, the PCSK9i group showed greater regression of maximal lipid core burden index for each of the 4-mm segments (maxLCBI4mm) than the control group (57.0 vs. 25.5; P = 0.010). A significant linear correlation was found between the percent changes in LDL-C and maxLCBI4mm (r = 0.318; P = 0.002), alongside the reduction in PAV (r = 0.386; P < 0.001). CONCLUSION: The lipid component of non-culprit coronary plaques was significantly decreased by PCSK9i. The effects of statin combined with PCSK9i might be attributed to the stabilization and regression of residual vulnerable coronary plaques in patients with CAD.

Predicting future left anterior descending artery events from non-culprit lesions: insights from the Lipid-Rich Plaque study.

AIMS: The left anterior descending (LAD) artery is the most frequently affected site by coronary artery disease. The prospective Lipid Rich Plaque (LRP) study, which enrolled patients undergoing imaging of non-culprits followed over 2 years, reported the successful identification of coronary segments at risk of future events based on near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) lipid signals. We aimed to characterize the plaque events involving the LAD vs. non-LAD segments. METHODS AND RESULTS: LRP enrolled 1563 patients from 2014 to 2016. All adjudicated plaque events defined by the composite of cardiac death, cardiac arrest, non-fatal myocardial infarction, acute coronary syndrome, revascularization by coronary bypass or percutaneous coronary intervention, and rehospitalization for angina with >20% stenosis progression and reported as non-culprit lesion-related major adverse cardiac events (NC-MACE) were classified by NIRS-IVUS maxLCBI4 mm (maximum 4-mm Lipid Core Burden Index) ≤400 or >400 and association with high-risk-plaque characteristics, plaque burden ≥70%, and minimum lumen area (MLA) ≤4 mm2. Fifty-seven events were recorded with more lipid-rich plaques in the LAD vs. left circumflex and right coronary artery; 12.5% vs. 10.4% vs. 11.3%, P = 0.097. Unequivocally, a maxLCBI4 mm >400 in the LAD was more predictive of NC-MACE [hazard ratio (HR) 4.32, 95% confidence interval (CI) (1.93-9.69); P = 0.0004] vs. [HR 2.56, 95% CI (1.06-6.17); P = 0.0354] in non-LAD segments. MLA ≤4 mm2 within the maxLCBI4 mm was significantly higher in the LAD (34.1% vs. 25.9% vs. 13.7%, P < 0.001). CONCLUSION: Non-culprit lipid-rich segments in the LAD were more frequently associated with plaque-level events. LAD NIRS-IVUS screening may help identify patients requiring intensive surveillance and medical treatment.

Non-Culprit MACE Rate in LRP: The Influence of Optimal Medical Therapy Using DAPT and Statins.

BACKGROUND/PURPOSE: The Lipid Rich Plaque (LRP) study demonstrated the association between coronary plaque lipid content and outcomes. In this LRP substudy, we assessed the impact of optimal medical therapy (OMT) on the occurrence of non-culprit major adverse cardiac events (NC-MACE). Advanced intracoronary imaging modalities are able to identify patients with vulnerable coronary lesion morphology associated with future events. METHODS/MATERIALS: A total of 1270 patients who underwent cardiac catheterization for suspected coronary artery disease (CAD) with evaluable maxLCBI4mm in non-culprit vessels and known medical therapy after discharge were followed for 2 years. OMT was defined as the use of a statin and dual antiplatelet therapy (DAPT). RESULTS: Among the 1270 patients included in this substudy, 1110 (87.7%) had PCI for an index event, and 1014 (80%) patients received OMT. Estimated cumulative incidence functions of NC-MACE did not differ significantly between patients treated with or without OMT (log-rank p-value = 0.876). In patients labeled high risk (maxLCBI4mm > 400), cumulative incidence function also did not differ between patients treated with vs without OMT (log-rank p-value = 0.19). CONCLUSIONS: In the current LRP analysis, we could not identify a beneficial effect of OMT in the reduction of NC-MACE rate, even in patients with high-risk plaques, during 24-month follow-up.

Age and Phenotype of Patients With Plaque Erosion.

Background A recent study reported that the outcome of patients with plaque erosion treated with stenting is poor when the underlying plaque is lipid rich. However, the detailed phenotype of patients with plaque erosion, particularly as related to different age groups, has not been systematically studied. Methods and Results Patients with acute coronary syndromes caused by plaque erosion were selected from 2 data sets. Demographic, clinical, angiographic, and optical coherence tomography findings of the culprit lesion were compared between 5 age groups. Among 579 erosion patients, male sex and current smoking were less frequent, and hypertension, diabetes, and chronic kidney disease were more frequent in older patients. ST-segment-elevation myocardial infarction was more frequent in younger patients. Percentage of diameter stenosis on angiogram was greater in older patients. The prevalence of lipid-rich plaque (27.3% in age <45 years and 49.4% in age ≥75 years, P<0.001), cholesterol crystal (3.9% in age <45 years and 21.8% in age ≥75 years, P=0.027), and calcification (5.5% in age <45 years and 54.0% in age ≥75 years, P<0.001) increased with age. After adjusting risk factors, younger patients were associated with the presence of thrombus, and older patients were associated with greater percentage of diameter stenosis and the presence of lipid-rich plaque and calcification. Conclusions The demographic, clinical, angiographic, and plaque phenotypes of patients with plaque erosion distinctly vary depending on age. This may affect the clinical outcome in these patients. Registration URL: https://www.clinicaltrials.gov. Unique identifiers: NCT03479723, NCT02041650.