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

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

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

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

Potent platelet inhibition with peri-procedural tirofiban may attenuate progression of atherosclerosis in patients with acute coronary syndromes.

Organization of platelet-rich thrombus at the site of plaque disruption may contribute to rapid progression of atherosclerosis. This study was conducted to investigate if potent platelet inhibition therapy in patients with acute coronary syndromes (ACS) mitigates plaque progression. Patients enrolled in the EROSION study who presented with ACS caused by plaque erosion and underwent serial imaging of the culprit lesion by optical coherence tomography at baseline, 1 month, and 1 year were included. Among 49 patients, 32 (65.3%) patients were treated with glycoprotein IIb/IIIa inhibitor (GPI) in addition to aspirin and ticagrelor. The increase in area stenosis from baseline to 1-year follow-up was significantly smaller in patients treated with GPI, compared to those without GPI therapy (4.8% [- 1.6 to 10.9] vs. 9.6% [4.0 to 21.3], p = 0.031). The cohort was divided into 2 groups based on culprit lesion phenotype at 1 year: Group A, new layer formation at 1-year that was not present at baseline (n = 18); Group B, no new layer formation (n = 31). A new layer was less frequently found at 1 year in patients treated with GPI than in those without GPI (25.0% vs. 58.8%, p = 0.019). Group A, compared to Group B, was associated with a greater increase in area stenosis (19.0 ± 16.4% vs. 3.7 ± 7.1%; p < 0.001). Potent platelet inhibition with GPI in patients with ACS caused by plaque erosion was associated with lower incidence of new layer formation and less plaque progression.

Comparison of post-stent optical coherence tomography findings: Layered versus non-layered culprit lesions.

OBJECTIVES: This study aimed to investigate the vascular response of lesions with a layered phenotype. BACKGROUND: Recent studies have shown that layered plaques at culprit lesions detected by optical coherence tomography (OCT) have greater plaque burden and more inflammatory features than non-layered plaques. METHODS: This is a retrospective observational study. A total of 193 target lesions from 193 patients [100 patients with acute coronary syndromes (ACS) and 93 with stable angina pectoris (SAP)] who had undergone OCT imaging of the culprit lesion both before and after stenting were included. Layered plaques were identified by OCT as plaques with layers of different optical density. Patients were divided into two groups based on the presence or absence of a layered phenotype at the culprit lesion, and pre- and post-procedure OCT findings were compared. RESULTS: Among 193 patients, 36 (36.0%) lesions in ACS patients and 56 (60.2%) lesions in SAP patients were found to have a layered phenotype at the culprit lesion. At baseline, percent area stenosis was greater in layered plaque than in non-layered plaque (p = .019). Following stent implantation, the stent expansion ratio and mean stent eccentricity index were significantly lower in layered plaques than in non-layered plaques (p = .041, p = .017, respectively), mainly derived from ACS patients. CONCLUSION: Following stent implantation, plaques with a layered phenotype had less stent expansion and more eccentric lumens. Aggressive balloon dilation may be required to obtain optimal stent outcomes in patients with a layered plaque phenotype at the culprit lesion.

Clinical significance of healed plaque detected by optical coherence tomography: a 2-year follow-up study.

Recent studies have shown that healed plaque at the culprit lesion detected by optical coherence tomography (OCT) is a sign of pan-vascular vulnerability and advanced atherosclerosis. However, the clinical significance of healed plaque is unknown. A total of 265 patients who had OCT imaging of a culprit vessel and 2-year clinical follow-up data were included. Patients were stratified based on the presence or absence of a layered plaque phenotype, defined as layers of different optical density by OCT at either culprit or non-culprit lesions. The association between layered plaque and major adverse cardiac events (MACE), defined as cardiac death, acute coronary syndromes (ACS), or revascularization, was studied. Among 265 patients, 96 (36.2%) had the layered plaque phenotype. Layered plaque was more frequently observed in stable angina pectoris patients than in ACS patients (57.8%vs. 25.1%, p < 0.001). The average clinical follow-up period was 672 ± 172 days. Cumulative MACE was significantly higher in patients with layered plaque (p = 0.041), which was primarily driven by the high revascularization rate at 2 years (p = 0.002). Multivariate regression analysis showed that presence of layered plaque and low-density lipoprotein cholesterol levels were independently associated with an increased risk of revascularization (p = 0.026, p = 0.008, respectively). Patients with healed plaque in the culprit vessel had a higher incidence of revascularization, as compared to those without healed plaque, at 2 years.

Predictors for layered coronary plaques: an optical coherence tomography study.

Healed coronary plaques, morphologically characterized by a layered pattern, are signatures of previous plaque disruption and healing. Recent optical coherence tomography (OCT) studies showed that layered plaque is associated with vascular vulnerability. However, factors associated with layered plaques have not been studied. The aim of this study was to investigate predictors for layered plaque at the culprit plaques and at non-culprit plaques. Patients with coronary artery disease who underwent pre-intervention OCT imaging of the culprit lesion were included. Layered plaques were defined as plaques with one or more layers of different optical density and a clear demarcation from underlying components. Among 313 patients, layered plaque at the culprit lesion was observed in 18.8% of ST-segment elevation myocardial infarction patients, 36.3% of non-ST-segment elevation acute coronary syndrome patients, and 53.4% of stable angina pectoris (SAP) patients (p < 0.001). In the multivariable model, SAP, multivessel disease, type B2/C lesion, and diameter stenosis > 70% were independent predictors for layered plaque at the culprit lesion. In addition, 394 non-culprit plaques in 190 patients were assessed to explore predictors for layered plaques at non-culprit lesions. SAP, and thin-cap fibroatheroma and layered plaque at the culprit lesion were independent predictors for layered plaques at non-culprit lesions. In conclusion, clinical presentation of SAP was a strong predictor for layered plaque at both culprit plaques and non-culprit plaques. Development and biologic significance of layered plaques may be related to a balance between pan-vascular vulnerability and endogenous anti-thrombotic protective mechanism.

Prevalence and Clinical Significance of Layered Plaque in Patients With Stable Angina Pectoris　- Evaluation With Histopathology and Optical Coherence Tomography.

BACKGROUND: Healed plaques are identified as a layered pattern with optical coherence tomography (OCT) imaging, but the exact relationship between healed plaques and the development of significant coronary stenosis in stable angina pectoris (SAP) is not fully understood.Methods and Results:A retrospective clinincal study investigated the OCT characteristics of culprit lesions of SAP patients (n=205), and a prospective study examined the histopathological characteristics of layered plaque in directional coronary atherectomy (DCA) samples (42 samples from 18 SAP patients). In the retrospective study, layered plaque was observed in 36.6% of the SAP culprit lesions. Compared with patients with non-layered plaque, male sex and smoking were more frequent, and HbA1c level was significantly higher in the patients with layered plaque (81.3% vs. 65.9%, P<0.05; 62.7% vs. 41.8%, P<0.05; 6.6±1.3% vs. 6.2±1.0%, P<0.05, respectively). Furthermore, layered plaque was accompanied by higher plaque vulnerability and smaller minimal lumen area. In the histopathological study, the layered plaques had a significantly higher rate of intramural thrombus and macrophages infiltration than non-layered plaques (75.0% vs. 14.3%, P<0.05; 75.0% vs. 38.1%, P<0.05, respectively). CONCLUSIONS: Healed plaque containing intramural thrombus is identified as layered plaque by OCT, and was frequently observed, even in SAP patients. Intramural thrombus might play an important role in the development of coronary plaque with a high degree of stenosis in SAP patients.

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

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

Implementation of the kissing balloon technique using a perfusion balloon in acute myocardial infarction: a case report.

Background: Prolonged antiplatelet-agent administration associated with stenting for acute myocardial infarction is not ideal in young patients. We successfully performed a perfusion balloon-based kissing balloon technique in the left anterior descending artery ostium in a young patient with acute myocardial infarction. Case summary: A 34-year-old female presenting with recurrent chest pain was diagnosed with ST-segment elevation acute myocardial infarction. Emergency coronary angiography revealed 90% stenosis of the left anterior descending artery ostium. Considering her age, lesion dilation using a perfusion balloon was preferred. This inadvertently impinged the left circumflex artery, causing chest pain and ischaemia-related hypotension with only a 10 s perfusion dilation balloon. We transitioned to an alternative 7 Fr guiding catheter and performed the kissing balloon technique using a perfusion balloon. This allowed prolonged inflation for 120 s, without complications. Optical coherence tomography of the lesion revealed layered plaques. Based on the patient's age and medical history, coronary spasm may be the aetiological factor underlying acute ST-segment elevation myocardial infarction. Coronary angiography 3 months post-discharge revealed no restenosis. Discussion: Regarding acute myocardial infarction, prolonged inflation with a perfusion balloon had higher frequency of non-stent-related interventions than that of semi-compliant or non-compliant balloons. In this case, the perfusion balloon resulted in chest pain and hypotension. Perfusion balloon-based kissing balloon technique was useful in this setting. Optical coherence tomography revealing the responsible lesions can help determine the cause of acute myocardial infarction in young patients; in our case, a layered plaque was observed. Layered plaques are associated with coronary spasm; therefore, initiating treatment of coronary spasm was considered herein.

Association between Eicosapentaenoic Acid to Arachidonic Acid Ratio and Characteristics of Plaque Rupture.

AIMS: Eicosapentaenoic acid (EPA) has shown beneficial effects on coronary plaque stabilization. Based on our previous study, we speculated that EPA might be associated with the development of healed plaques and might limit thrombus size. This study aimed to elucidate the association between EPA and arachidonic acid (AA) ratios and various plaque characteristics in patients with plaque rupture. METHODS: A total of 95 patients with acute coronary syndrome (ACS) caused by plaque rupture who did not take lipid-lowering drugs and underwent percutaneous coronary intervention using optical coherence tomography (OCT) were included. Clinical characteristics, lipid profiles, and OCT findings were compared between patients with lower and higher EPA/AA ratios (0.41) according to the levels in the Japanese general population. RESULTS: In the high EPA/AA (n=29, 30.5%) and low EPA/AA (n=66, 69.5 %) groups, the high EPA/AA group was significantly older (76.1 vs. 66.1 years, P＜0.01) and had lower peak creatine kinase (556 vs. 1651 U/L, P=0.03) than those with low EPA/AA. Similarly, patients with high EPA/AA had higher prevalence of layered and calcified plaque (75.9 vs. 39.4 %, P＜0.01; 79.3 vs. 50.0 %, P＜0.01, respectively) than low EPA/AA group. Multivariate logistic regression analysis demonstrated that a high EPA/AA ratio was an independent factor in determining the development of layered and calcified plaques. CONCLUSION: A high EPA/AA ratio may be associated with the development of layered and calcified plaques in patients with plaque rupture.

Sex Differences in Coronary Atherosclerotic Phenotype and Healing Pattern on Optical Coherence Tomography Imaging.

BACKGROUND: Layered plaque, a signature of previous plaque disruption, is a known predictor of rapid plaque progression. Layered plaque can be identified in vivo by optical coherence tomography. Studies have reported differences in plaque burden between women and men, but sex differences in the pattern of layered plaque are unknown. METHODS: Preintervention optical coherence tomography images of 533 patients with chronic coronary syndromes were analyzed. Detailed plaque characteristics of layered and nonlayered plaques of the target lesion were compared between men and women. RESULTS: The prevalence of layered plaque was similar between men (N=418) and women (N=115; 55% versus 54%; P=0.832). In men, more features of plaque vulnerability were identified in layered plaque than in nonlayered plaque: lipid plaque (87% versus 69%; P<0.001), macrophages (69% versus 56%; P=0.007), microvessels (72% versus 39%; P<0.001), and cholesterol crystals (49% versus 30%; P<0.001). No difference in plaque vulnerability between layered and nonlayered plaques was observed in women. Layered plaque in men had more features consistent with previous plaque rupture than in women: interrupted pattern (74% versus 52%; P<0.001) and a greater layer index (1198 [781-1835] versus 943 [624-1477]; P<0.001). CONCLUSIONS: In men, layered plaques exhibit more features of vascular inflammation and vulnerability as well as evidence of previous plaque rupture, compared with nonlayered plaques, whereas in women, no difference was observed between layered and nonlayered plaques. Vascular inflammation (plaque rupture) may be the predominant mechanism of layered plaque in men, whereas a less inflammatory mechanism may play a key role in women. REGISTRATION: URL: http://www. CLINICALTRIALS: gov; Unique Identifier: NCT01110538, NCT04523194.

Impact of triglyceride levels on plaque characteristics in patients with coronary artery disease.

BACKGROUND: High triglyceride (TG) levels have been demonstrated to be a risk factor for coronary artery disease. This study aimed to clarify the impact of TG levels on the characteristics of coronary plaques. METHODS: A total of 850 consecutive patients who underwent optical coherence tomography (OCT) imaging of the culprit lesion were included. The morphologies of culprit plaques were compared between the higher TG group (nonfasting TG levels ≥150 mg/dL, n = 337) and the lower TG group (nonfasting TG <150 mg/dL, n = 513). RESULTS: The prevalence of lipid-rich plaques (43% vs. 33%, p = 0.005), thin-cap fibroatheromas (TCFAs) (24% vs. 17%, p = 0.015) and macrophages (40% vs. 31%, p = 0.006) was significantly higher in the higher TG group than in the lower TG group. In addition to a high low-density lipoprotein cholesterol (LDL-C) level (≥140 mg/dL), high TGs (≥150 mg/dL) were identified as an independent factor for the presence of TCFAs (odds ratio 1.465, 95% confidence interval 1.004-2.137, p = 0.048). Among patients with lower LDL-C levels (<100 mg/dL), the prevalence of macrophages (38% vs. 26%, p = 0.007) and layered plaques (48% vs. 38%, p = 0.019) was significantly higher in the higher TG group than in the lower TG group. CONCLUSIONS: Higher TG levels were associated with a higher prevalence of TCFAs in culprit coronary lesions. The prevalence of macrophages and layered plaques was more frequently observed in patients with higher TGs than those with lower TGs among patients with LDL-C < 100 mg/dL.

Increased Vulnerability and Distinct Layered Phenotype at Culprit and Nonculprit Lesions in STEMI Versus NSTEMI.

OBJECTIVES: This study aimed to investigate the pancoronary plaque vulnerability (including culprit and nonculprit lesions) and layered phenotype in patients with ST-segment elevation myocardial infarction (STEMI) vs non-STEMI (NSTEMI). BACKGROUND: Pancoronary vulnerability should account for distinct clinical manifestations of acute myocardial infarction (AMI). Layered plaque is indicative of previous coronary destabilization and thrombosis. METHODS: A total of 464 patients with AMI who underwent 3-vessel optical coherence tomography imaging were consecutively studied and divided into a STEMI group (318 patients; 318 culprit and 1,187 nonculprit plaques) and a NSTEMI group (146 patients; 146 culprit and 560 nonculprit plaques). Patients were followed up for a median period of 2 years. RESULTS: Compared with NSTEMI, culprit lesions in STEMI had more plaque rupture, thrombus, thin-cap fibroatheroma (TCFA), calcification, macrophage accumulation, and microvessels. The prevalence of plaque rupture (8.2% vs 4.8%; P = 0.018), microvessels (57.5% vs 45.2%; P < 0.001), and calcification (40.7% vs 30.2%; P = 0.003) at nonculprit lesions was higher in STEMI than NSTEMI. The layer area and thickness at the culprit and nonculprit lesions were significantly larger in STEMI than in NSTEMI. Multivariate analyses showed that culprit layer area (odds ratio: 1.443; 95% CI: 1.138-1.830; P = 0.002) was predictive of STEMI (vs NSTEMI), in addition to culprit TCFA, culprit thrombus, and non-left circumflex artery location of the culprit lesion. Although the type of AMI was not related to clinical outcomes, high-sensitivity C-reactive protein, culprit calcified nodule, and nonculprit TCFA predicted the 2-year major adverse cardiovascular events in patients with AMI. CONCLUSIONS: Patients with STEMI had increased plaque vulnerability (ie, more plaque rupture and microvessels) and distinct layered phenotype at the culprit and nonculprit lesions compared with patients with NSTEMI. Culprit lesion features of large layer area, TCFA, thrombus, and non-left circumflex artery location predicted the clinical presentation of STEMI.

Layered Plaque in Organic Lesions in Patients With Coronary Artery Spasm.

Background Coronary artery spasm plays a vital role in the pathogenesis of coronary plaques. We sought to investigate the plaque characteristics of co-existing organic lesions in patients with coronary artery spasm in comparison to those without coronary artery spasm by intracoronary optical coherence tomography (OCT). Methods and Results We included 39 patients who presented with a symptom suspected of coronary spastic angina and had an organic lesion, defined as ≥plaque burden of 50% assessed by OCT. Coronary artery spasm was diagnosed by positive acetylcholine provocation test, or by spontaneous spasm detected during coronary angiography. A total of 51 vessels with an organic lesion were identified. Of these, coronary artery spasm was observed in 30 vessels (spasm), while not in 21 vessels (non-spasm). Organic lesions in the spasm vessels, compared with those in the non-spasm vessels, had a higher prevalence of layered plaque (93% versus 38%, P<0.001), macrophages (80% versus 43%, P=0.016), and intraplaque microchannels (73% versus 24%, P<0.001), and lower prevalence of macrocalcification (23% versus 62%, P=0.009) as assessed by OCT. Conclusions Layered plaque, macrophages, and intraplaque microchannels, were frequently observed in organic lesions in patients with coronary artery spasm. These findings suggest that coronary artery spasm induces local thrombus formation as well as active inflammatory response, therefore increasing the risk of rapid plaque progression and ischemic events in patients with coronary artery spasm.

Predictors of Rapid Plaque Progression: An Optical Coherence Tomography Study.

OBJECTIVES: This study sought to identify morphological predictors of rapid plaque progression. BACKGROUND: Two patterns of plaque progression have been described: slow linear progression and rapid step-wise progression. The former pattern will cause stable angina when the narrowing reaches a critical threshold, whereas the latter pattern may lead to acute coronary syndromes or sudden cardiac death. METHODS: Patients who underwent optical coherence tomography (OCT) imaging during the index procedure and follow-up angiography with a minimum interval of 6 months were selected. Nonculprit lesions with a diameter stenosis of ≥30% on index angiography were assessed. Lesion progression was defined as a decrease of angiographic minimum lumen diameter ≥0.4 mm at follow-up (mean, 7.1 months). Baseline morphological characteristics of plaques with rapid progression were evaluated by OCT. In a subgroup with follow-up OCT imaging for plaques with rapid progression, morphological changes from baseline to follow-up were assessed. RESULTS: Among 517 lesions in 248 patients, 50 lesions showed rapid progression. These lesions had a significantly higher prevalence of lipid-rich plaque (76.0% vs. 50.5%, respectively), thin-cap fibroatheroma (TCFA) (20.0% vs. 5.8%, respectively), layered plaque (60.0% vs. 34.0%, respectively), macrophage accumulation (62.0% vs. 42.4%, respectively), microvessel (46.0% vs. 29.1%, respectively), plaque rupture (12.0% vs. 4.7%, respectively), and thrombus (6.0% vs. 1.1%, respectively) at baseline compared with those without rapid progression. Multivariate analysis identified lipid-rich plaque (odds ratio [OR]: 2.17; 95% confidence interval [CI]: 1.02 to 4.62; p = 0.045]), TCFA (OR: 5.85; 95% CI: 2.01 to 17.03; p = 0.001), and layered plaque (OR: 2.19; 95% CI: 1.03 to 4.17; p = 0.040) as predictors of subsequent rapid lesion progression. In a subgroup analysis for plaques with rapid progression, a new layer was detected in 25 of 41 plaques (61.0%) at follow-up. CONCLUSIONS: Lipid-rich plaques, TCFA, and layered plaques were predictors of subsequent rapid plaque progression. A new layer, a signature of previous plaque disruption and healing, was detected in more than half of the lesions with rapid progression at follow-up. (Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538).

Optical Coherence Tomography Predictors for a Favorable Vascular Response to Statin Therapy.

Background Specific plaque phenotypes that predict a favorable response to statin therapy have not been systematically studied. This study aimed to identify optical coherence tomography predictors for a favorable vascular response to statin therapy. Methods and Results Patients who had serial optical coherence tomography imaging at baseline and at 6 months were included. Thin-cap area (defined as an area with fibrous cap thickness <200 µm) was measured using a 3-dimensional computer-aided algorithm, and changes in the thin-cap area at 6 months were calculated. A favorable vascular response was defined as the highest tertile in the degree of reduction of the thin-cap area. Macrophage index was defined as the product of the average macrophage arc and length of the lesion with macrophage infiltration. Layered plaque was defined as a plaque with 1 or more layers of different optical density. In 84 patients, 140 nonculprit lipid plaques were identified. In multivariable analysis, baseline thin-cap area (odds ratio [OR] 1.442; 95% CI, 1.024-2.031, P=0.036), macrophage index (OR, 1.031; 95% CI, 1.002-1.061, P=0.036), and layered plaque (OR, 2.767; 95% CI, 1.024-7.479, P=0.045) were identified as the significant predictors for a favorable vascular response. Favorable vascular response was associated with a decrease in the macrophage index. Conclusions Three optical coherence tomography predictors for a favorable vascular response to statin therapy have been identified: large thin-cap area, high macrophage index, and layered plaque. Favorable vascular response to statin was correlated with signs of decreased inflammation. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01110538.

Coronary plaque and clinical characteristics of South Asian (Indian) patients with acute coronary syndromes: An optical coherence tomography study.

BACKGROUND: South Asians, and Indians in particular, are known to have a higher incidence of premature atherosclerosis and acute coronary syndromes (ACS) with worse clinical outcomes, compared to populations with different ethnic backgrounds. However, the underlying pathobiology accounting for these differences has not been fully elucidated. METHODS: ACS patients who had culprit lesion optical coherence tomography (OCT) imaging were enrolled. Culprit plaque characteristics were evaluated using OCT. RESULTS: Among 1315 patients, 100 were South Asian, 1009 were East Asian, and 206 were White. South Asian patients were younger (South Asians vs. East Asians vs. Whites: 51.6 ± 13.4 vs. 65.4 ± 11.9 vs. 62.7 ± 11.7; p < 0.001) and more frequently presented with ST-segment elevation myocardial infarction (STEMI) (77.0% vs. 56.4% vs. 35.4%; p < 0.001). On OCT analysis after propensity group matching, plaque erosion was more frequent (57.0% vs. 38.0% vs. 50.0%; p = 0.003), the lipid index was significantly greater (2281.6 [1570.8-3160.6] vs. 1624.3 [940.9-2352.4] vs. 1303.8 [1090.0-1757.7]; p < 0.001), and the prevalence of layered plaque was significantly higher in the South Asian group than in the other two groups (52.0% vs. 30.0% vs. 34.0%; p = 0.003). CONCLUSIONS: Compared to East Asians and Whites, South Asians with ACS were younger and more frequently presented with STEMI. Plaque erosion was the predominant pathology for ACS in South Asians and their culprit lesions had more features of plaque vulnerability. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov, NCT03479723.

Optical Coherence Tomography of Coronary Plaque Progression and Destabilization: JACC Focus Seminar Part 3/3.

The development of optical coherence tomography (OCT) has revolutionized our understanding of coronary artery disease. In vivo OCT research has paralleled with advances in computational fluid dynamics, providing additional insights in the various hemodynamic factors influencing plaque growth and stability. Recent OCT studies introduced a new concept of plaque healing in relation to clinical presentation. In addition to known mechanisms of acute coronary syndromes such as plaque rupture and plaque erosion, a new classification of calcified plaque was recently reported. This review will focus on important new insights that OCT has provided in recent years into coronary plaque development, progression, and destabilization, with a focus on the role of local hemodynamics and endothelial shear stress, the layered plaque (signature of previous subclinical plaque destabilization and healing), and the calcified culprit plaque.

Frequency, Predictors, Distribution, and Morphological Characteristics of Layered Culprit and Nonculprit Plaques of Patients With Acute Myocardial Infarction: In Vivo 3-Vessel Optical Coherence Tomography Study.

BACKGROUND: Subclinical atherothrombosis and plaque healing may lead to rapid plaque progression. The histopathologic healed plaque has a layered appearance when imaged using optical coherence tomography. We assessed the frequency, predictors, distribution, and morphological characteristics of optical coherence tomography layered culprit and nonculprit plaques in patients with acute myocardial infarction. METHODS: A prospective series of 325 patients with acute myocardial infarction underwent optical coherence tomography imaging of all 3 native coronary arteries. Layered plaque phenotype had heterogeneous signal-rich layered tissue located close to the luminal surface that was clearly demarcated from the underlying plaque. RESULTS: Layered plaques were detected in 74.5% of patients with acute myocardial infarction. Patients with layered culprit plaques had more layered nonculprit plaques; and they more often had preinfarction angina, ST-segment-elevation myocardial infarction, higher low-density lipoprotein cholesterol, and absence of antiplatelet therapy. Layered plaques tended to cluster in the proximal segment of the left anterior descending artery and left circumflex artery but were more uniformly distributed in the right coronary artery. As compared with nonlayered plaques, layered plaques had greater optical coherence tomography lumen area stenosis at both culprit and nonculprit sites. The frequency of layered plaque phenotype (P=0.038) and maximum area of layered tissue (P<0.001) increased from nonculprit thin-cap fibroatheromas to nonculprit ruptures to culprit ruptures. CONCLUSIONS: Layered plaques were identified in 3-quarters of patients with acute myocardial infarction, especially in the culprit plaques of patients with ST-segment-elevation myocardial infarction. Layered plaques had a limited, focal distribution in the left anterior descending artery, and left circumflex artery but were more evenly distributed in the right coronary artery and were characterized by greater lumen narrowing at both culprit and nonculprit sites. Graphic Abstract: A graphic abstract is available for this article.

Characteristics of non-culprit plaques in acute coronary syndrome patients with layered culprit plaque.

AIMS: Layered plaques represent signs of previous plaque destabilization. A recent study showed that acute coronary syndrome (ACS) patients with layered culprit plaque have more vulnerability at the culprit lesion and systemic inflammation. We aimed to compare the characteristics of non-culprit plaques between patients with or without layered plaque at the culprit lesion. We also evaluated the characteristics of layered non-culprit plaques, irrespective of culprit plaque phenotype. METHODS AND RESULTS: We studied ACS patients who had undergone pre-intervention optical coherence tomography (OCT) imaging. The number of non-culprit lesions was evaluated on coronary angiogram and morphological characteristics of plaques were studied by OCT. In 349 patients, 99 (28.4%) had layered culprit plaque. The number of non-culprit plaques in patients with or without layered culprit plaque was similar (3.2 ± 0.8 and 2.8 ± 0.8, P = 0.23). Among 465 non-culprit plaques, 145 from patients with layered culprit plaque showed a higher prevalence of macrophage infiltration (71.0% vs. 60.9%, P = 0.050). When analysed irrespective of culprit plaque phenotype, layered non-culprit plaques showed higher prevalence of lipid (93.3% vs. 86.0%, P = 0.028), thin cap fibroatheroma (29.7% vs. 13.7%, P < 0.001), and macrophage infiltration (82.4% vs. 54.0%, P < 0.001) than non-layered plaques. Plaques with layered phenotype at both culprit and non-culprit lesions had the highest vulnerability. CONCLUSION: In ACS patients, those with layered phenotype at the culprit lesion demonstrated greater macrophage infiltration at the non-culprit sites. Layered plaque at the non-culprit lesions was associated with more features of plaque vulnerability, particularly when the culprit lesion also had a layered pattern.