Sining Hu

In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography.

OBJECTIVES The aim of this study was to characterize the morphological features of plaque erosion and calcified nodule in patients with acute coronary syndrome (ACS) by optical coherence tomography (OCT). BACKGROUND Plaque erosion and calcified nodule have not been systematically investigated in vivo. METHODS A total of 126 patients with ACS who had undergone pre-intervention OCT imaging were included. The culprit lesions were classified as plaque rupture (PR), erosion (OCT-erosion), calcified nodule (OCT-CN), or with a new set of diagnostic criteria for OCT. RESULTS The incidences of PR, OCT-erosion, and OCT-CN were 43.7%, 31.0%, and 7.9%, respectively. Patients with OCT-erosion were the youngest, compared with those with PR and OCT-CN (53.8 ± 13.1 years vs. 60.6 ± 11.5 years, 65.1 ± 5.0 years, p = 0.005). Compared with patients with PR, presentation with non-ST-segment elevation ACS was more common in patients with OCT-erosion (61.5% vs. 29.1%, p = 0.008) and OCT-CN (100% vs. 29.1%, p < 0.001). The OCT-erosion had a lower frequency of lipid plaque (43.6% vs. 100%, p < 0.001), thicker fibrous cap (169.3 ± 99.1 μm vs. 60.4 ± 16.6 μm, p < 0.001), and smaller lipid arc (202.8 ± 73.6° vs. 275.8 ± 60.4°, p < 0.001) than PR. The diameter stenosis was least severe in OCT-erosion, followed by OCT-CN and PR (55.4 ± 14.7% vs. 66.1 ± 13.5% vs. 68.8 ± 12.9%, p < 0.001). CONCLUSIONS Optical coherence tomography is a promising modality for identifying OCT-erosion and OCT-CN in vivo. The OCT-erosion is a frequent finding in patients with ACS, especially in those with non-ST-segment elevation ACS and younger patients. The OCT-CN is the least common etiology for ACS and is more common in older patients. (The Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538).

Distinct Morphological Features of Ruptured Culprit Plaque for Acute Coronary Events Compared to Those With Silent Rupture and Thin-Cap Fibroatheroma : A Combined Optical Coherence Tomography and Intravascular Ultrasound Study

OBJECTIVES The study sought to identify specific morphological characteristics of ruptured culprit plaques (RCP) responsible for acute events, and compare them with ruptured nonculprit plaques (RNCP) and nonruptured thin-cap fibroatheroma (TCFA) in patients presenting with acute coronary syndromes (ACS). BACKGROUND Nonruptured TCFA and multiple ruptured plaques are detected in the same patients with ACS. It remains unknown whether certain morphological characteristics determine rupture of TCFA and subsequently result in ACS. METHODS We analyzed 126 plaques (RCP = 49, RNCP = 19, TCFA = 58) from 82 ACS patients using optical coherence tomography (OCT) and intravascular ultrasound (IVUS). Fibrous cap thickness was determined by OCT. Plaque burden and lumen area were measured with IVUS. RESULTS Fibrous cap was thinner in RCP (43 ± 11 μm) and RNCP (41 ± 10 μm) than in TCFA (56 ± 9 μm, p < 0.001 and p < 0.001, respectively). Plaque burden was greater in RCP (82 ± 7.2%), compared with RNCP (64 ± 7.2%, p < 0.001) and TCFA (62 ± 12.5%, p < 0.001). Lumen area was smaller in RCP (2.1 ± 0.9 mm(2)), compared with RNCP (4.6 ± 2.3 mm(2), p = 0.001) and TCFA (5.1 ± 2.7 mm(2), p < 0.001). The fibrous cap thickness <52 μm had good performance in discriminating ruptured plaque from TCFA (area under the curve [AUC] = 0.857, p < 0.001), and plaque burden >76% and lumen area <2.6 mm(2) had good performance in discriminating RCP from RNCP and TCFA (AUC = 0.923, p < 0.001 and AUC = 0.881, p < 0.001, respectively). CONCLUSIONS Fibrous cap thickness is a critical morphological discriminator between ruptured plaques and nonruptured TCFA, while plaque burden and lumen area appear to be important morphological features of RCP. These findings suggest that plaque rupture is determined by fibrous cap thickness, and a combination of large plaque burden and luminal narrowing result in ACS.

Effective anti-thrombotic therapy without stenting: intravascular optical coherence tomography-based management in plaque erosion (the EROSION study)

Aims Plaque erosion, compared with plaque rupture, has distinctly different underlying pathology and therefore may merit tailored therapy. In this study, we aimed to assess whether patients with acute coronary syndrome (ACS) caused by plaque erosion might be stabilized by anti-thrombotic therapy without stent implantation. Methods and results This was a single-centre, uncontrolled, prospective, proof-of concept study. Patients with ACS including ST-segment elevation myocardial infarction were prospectively enrolled. If needed, aspiration thrombectomy was performed. Patients diagnosed with plaque erosion by optical coherence tomography (OCT) and residual diameter stenosis <70% on coronary angiogram were treated with anti-thrombotic therapy without stenting. OCT was repeated at 1 month and thrombus volume was measured. The primary endpoint was >50% reduction of thrombus volume at 1 month compared with baseline. The secondary endpoint was a composite of cardiac death, recurrent ischaemia requiring revascularization, stroke, and major bleeding. Among 405 ACS patients with analysable OCT images, plaque erosion was identified in 103 (25.4%) patients. Sixty patients enrolled and 55 patients completed the 1-month follow-up. Forty-seven patients (47/60, 78.3%; 95% confidence interval: 65.8-87.9%) met the primary endpoint, and 22 patients had no visible thrombus at 1 month. Thrombus volume decreased from 3.7 (1.3, 10.9) mm3 to 0.2 (0.0, 2.0) mm3. Minimal flow area increased from 1.7 (1.4, 2.4) mm2 to 2.1 (1.5, 3.8) mm2. One patient died of gastrointestinal bleeding, and another patient required repeat percutaneous coronary intervention. The rest of the patients remained asymptomatic. Conclusion For patients with ACS caused by plaque erosion, conservative treatment with anti-thrombotic therapy without stenting may be an option.

Effect of statin therapy on the progression of coronary atherosclerosis

BackgroundAn increasing number of authors employing intravascular ultrasound (IVUS) and virtual histology (VH-IVUS) have investigated the effect of statin use on plaque volume (PV) and plaque composition. However, inconsistent results have been reported. Therefore, we conducted a meta-analysis to determine the appropriate regimen of statins to effectively stabilize vulnerable coronary plaques.MethodsOnline electronic databases were carefully searched for all relevant studies. We compared mean values of PV and plaque composition between baseline and follow-up in patients receiving statin therapy. We pooled treatment effects and calculated mean differences (MD) with the 95% confidence interval (CI) using a random-effects model. By stratified analyses, we explored the influence of clinical presentation, dose and duration of statin treatment, and low-density lipoprotein-cholesterol (LDL-C) levels on the effects of statins.ResultsSeventeen studies involving 2,171 patients were analyzed. Statin therapy significantly decreased PV (−5.3 mm3; 95% CI: –3.3 mm3 to −7.2 mm3; P < 0.001), without heterogeneity. When considering the dose and duration of statins used, only subgroups employing a high dose and long duration demonstrated a significant reduction in PV (p < 0.001). A significant decrease in PV was noted if achieved LDL-C levels were <100 mg/dL (p < 0.001). Statin treatment could induce a twofold decrease in PV in patients with acute coronary syndrome (ACS) compared with that observed in patients with stable angina pectoris (SAP). A regressive trend was seen for necrotic core volume (MD: –2.1 mm3; 95% CI: –4.7 mm3 to 0.5 mm3, P = 0.11). However, statin use did not induce a significant change for fibrotic, fibro-fatty, or dense calcium compositions.ConclusionsOur meta-analysis demonstrated that statin therapy (especially that involving a high dose and long duration and achieving <100 mg/dL LDL-C levels) can significantly decrease PV in patients with SAP or ACS. These data suggested that statins can be used to reduce the atheroma burden for secondary prevention by appropriately selecting the statin regimen. No significant change in plaque composition was seen after statin therapy.

Pancoronary plaque vulnerability in patients with acute coronary syndrome and ruptured culprit plaque: a 3-vessel optical coherence tomography study.

BACKGROUND Recent studies described different clinical and underlying plaque characteristics between patients with and without plaque rupture presenting with acute coronary syndrome (ACS). In light of the systemic nature of atherosclerosis, we hypothesized that nonculprit plaques might also express different morphological features in these 2 groups of patients. METHODS Thirty-eight patients with ACS who underwent 3-vessel optical coherence tomography imaging were identified from the Massachusetts General Hospital Optical Coherence Tomography Registry. Based on culprit plaque morphology, the study population was divided into 2 groups: patients with plaque rupture at the culprit lesion (group 1) and patients with nonruptured plaque at the culprit lesion (group 2). Prevalence and features of nonculprit plaques were compared between the 2 groups. RESULTS A total of 118 nonculprit plaques were analyzed. Patients in group 1 (n = 17) had nonculprit plaques with higher prevalence of thin-cap fibroatheroma (52.9% vs 19.0%, P = .029) and disruption (35.3% vs 4.8%, P = .016) compared with patients in group 2 (n = 21). Nonculprit plaques in group 1 showed wider maximum lipid arc (198.9° ± 41.7° vs 170.2° ± 41.9°, P = .003), greater lipid length (7.8 ± 4.4 mm vs 5.1 ± 2.4 mm, P = .003), higher lipid index (1196.9 ± 700.5 vs 747.7 ± 377.3, P = .001), and thinner fibrous cap (107.0 ± 56.5 μm vs 137.3 ± 69.8 μm, P = .035) compared with those in group 2. CONCLUSIONS The present study showed distinctive features of nonculprit plaques between patients with ACS caused by plaque rupture and patients with ACS caused by nonruptured plaques. Patients with plaque rupture had increased pancoronary vulnerability in nonculprit plaques, suggesting that a more aggressive treatment paradigm aiming at the stabilization of vulnerable plaques may offer additional benefit to these patients.

Nonculprit Coronary Plaque Characteristics of Chronic Kidney Disease

Background— Chronic kidney disease (CKD) promotes the development of atherosclerosis and increases the risk of cardiovascular disease. The aim of the present study was to compare the coronary plaque characteristics of patients with and without CKD using optical coherence tomography. Methods and Results— We identified 463 nonculprit plaques from 287 patients from the Massachusetts General Hospital (MGH) optical coherence tomography registry. CKD was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2. A total of 402 plaques (250 patients) were in the non-CKD group and 61 plaques (37 patients) were in the CKD group. Compared with non-CKD plaques, plaques with CKD had a larger lipid index (mean lipid arc×lipid length, 1248.4±782.8 mm° [non-CKD] versus 1716.1±1116.2 mm° [CKD]; P=0.003). Fibrous cap thickness was not significantly different between the groups. Calcification (34.8% [non-CKD] versus 50.8% [CKD]; P=0.041), cholesterol crystals (11.2% [non-CKD] versus 23.0% [CKD]; P=0.048), and plaque disruption (5.5% [non-CKD] versus 13.1% [CKD]; P=0.049) were more frequently observed in the CKD group. In the multivariate linear regression model, a lower estimated glomerular filtration rate and diabetes mellitus were independent risk factors for a larger lipid index. Conclusions— Compared with non-CKD patients, the patients with CKD had a larger lipid index with a higher prevalence of calcium, cholesterol crystals, and plaque disruption. The multivariate linear regression model demonstrated that a lower estimated glomerular filtration rate was an independent risk factor for a larger lipid index. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538.

Correlation between degree of neointimal hyperplasia and incidence and characteristics of neoatherosclerosis as assessed by optical coherence tomography

Emerging evidence suggests that neointimal degenerative changes with development of neoatherosclerosis (NA) may represent an important mechanism for late stent failure. The aim of the present study was to investigate the relation between degree of neointimal hyperplasia and incidence and characteristics of NA using optical coherence tomography. We identified a total of 252 stents with mean neointimal thickness (NIT) >100 μm in 212 patients: 100 bare metal stents (BMSs) and 152 drug-eluting stents (DESs). Based on the values of mean NIT, we divided stents into tertiles and compared neointimal characteristics among the 3 groups. NA was defined as the presence of lipid-laden intima and/or calcification inside the stent. In both BMS and DES, there was a difference in the prevalence of lipid-laden intima among the tertiles (18.2% vs 36.4% vs 47.1%, p = 0.042 [BMS]; 19.6% vs 56.9% vs 88.0%, p <0.001 [DES]). However, no difference in the prevalence of in-stent calcification was observed (21.2% vs 21.2% vs 2.9%, p = 0.053 [BMS]; 5.9% vs 9.8% vs 2.0%, p = 0.252 [DES]). In a multivariate model adjusting for stent type, follow-up duration, conventional coronary risk factors, statin, and angiotensin-converting enzyme inhibitor or angiotensin II receptor blockade use, mean NIT was independently associated with the presence of NA (odds ratio 2.53, 95% confidence interval 1.96 to 3.27, p <0.001). This study demonstrates the presence of a positive correlation between degree of neointimal hyperplasia after stent implantation and presence of lipid-laden intima. This association is independent from stent type and time from implantation and suggests a possible pathogenic link between the two processes.

Comparison of Intensive Versus Moderate Lipid-Lowering Therapy on Fibrous Cap and Atheroma Volume of Coronary Lipid-Rich Plaque Using Serial Optical Coherence Tomography and Intravascular Ultrasound Imaging.

Despite marked clinical benefit, reduction in atheroma volume with statin therapy is minimal. Changes in plaque composition may explain this discrepancy. We aimed in the present study to assess the effect of statin therapy on coronary plaque composition and plaque volume using serial multimodality imaging. From an open-label, single-blinded study, patients with angiographically mild-to-moderate lesion were randomized to receive atorvastatin 60 (AT 60) mg or atorvastatin 20 (AT 20) mg for 12 months. Optical coherence tomography was used to assess fibrous cap thickness (FCT) and intravascular ultrasound to assess atheroma burden at 3 time points: baseline, at 6 months, and at 12 months. Thirty-six lipid-rich plaques in 27 patients with AT 60 mg and 30 lipid-rich plaques in 19 patients with AT 20 mg were enrolled in this study. Low-density lipoprotein cholesterol level was significantly decreased at 6 months without further reduction at 12 months. AT 60 mg induced greater reduction in low-density lipoprotein cholesterol compared with AT 20 mg. Optical coherence tomography revealed continuous increase in FCT from baseline to 6 months and to 12 months in both groups. AT 60 mg induced greater increase in FCT compared with AT 20 mg at both follow-up points. The prevalence of thin-cap fibroatheroma and the presence of macrophage at 6 months were significantly lower in AT 60 mg compared with AT 20 mg. Plaque burden did not change significantly in both groups. In conclusion, both intensive and moderate statin therapy stabilizes coronary plaques, with a greater benefit in the intensive statin group. However, no significant changes in plaque volume were observed over time regardless of the intensity of statin therapy.

Vasa vasorum and plaque progression, and responses to atorvastatin in a rabbit model of atherosclerosis: contrast-enhanced ultrasound imaging and intravascular ultrasound study.

Objectives To serially investigate the relationship between vasa vasorum (VV) proliferation and plaque progression in vivo, and the effects of atorvastatin on VV and atherosclerosis as assessed by contrast-enhanced ultrasound (CEUS) and intravascular ultrasound (IVUS) imaging. Methods Carotid atherosclerosis was induced in rabbits with a high-cholesterol diet for 20 weeks and balloon injury. At week 16, following the imaging of the right common carotid arteries by CEUS and IVUS, 20 rabbits were randomised into a control or atorvastatin group (2 mg/kg/day). At week 20, CEUS and IVUS were repeated. Normalised maximal video-intensity enhancement (MVE) was calculated to quantify the density of VV. Plaque volume was determined by IVUS. Results When compared with the control group, lipid levels were not significantly lower following 4 weeks of atorvastatin administration. The increases in the normalised MVE over time were greater in the control group than in the atorvastatin group (p=0.001). The increase in plaque volume from 16 to 20 weeks was significantly greater in the control group than in the atorvastatin group (p=0.001). There was a positive relationship between changes in normalised MVE and plaque volume (r=0.72, p=0.002). Conclusions There was a positive correlation between VV density and plaque progression. Atorvastatin significantly inhibits the development of adventitial VV and progression of atherosclerosis independent of lowering the cholesterol level.

Features of Coronary Plaque in Patients with Metabolic Syndrome and Diabetes Mellitus Assessed by 3-vessel Optical Coherence Tomography

Background— The pathophysiological basis for the association between metabolic syndrome (MetS) and coronary artery disease is not well understood. We sought to characterize coronary plaques in patients with MetS by using optical coherence tomography. Methods and Results— We identified 451 coronary plaques from 171 subjects who underwent optical coherence tomographic imaging in 3 coronary arteries. Subjects were divided into 3 groups: diabetes mellitus (DM, n=77), MetS (n=35), and a control group (C group, n=59) without DM or MetS. Optical coherence tomographic analysis included the presence of lipid-rich plaque, maximum lipid arc, lipid-core length, lipid index (LI), fibrous cap thickness, and thin-cap fibroatheroma. We defined LI as mean lipid arc multiplied by lipid-core length. Lipid-core length and LI were significantly greater in DM and MetS than in C group (lipid-core length: 7.7±4.0 and 7.0±3.8 versus 5.5±2.4 mm; P<0.001 and P=0.012, and LI: 1164±716 and 1086±693 versus 796±417 mm; P<0.001 and P=0.008). Maximum lipid arc was significantly greater in DM than in C group, whereas no significant difference was observed between MetS and C group (196±45°, 187±42° versus 176±52°; P=0.002 and P=0.182). Fibrous cap thickness and thin-cap fibroatheroma showed no significant difference among the 3 groups. In multivariate analysis, DM and MetS were independently associated with LI, whereas only acute coronary syndrome was the independent predictor for thin-cap fibroatheroma. Conclusions— Compared with control subjects, coronary plaques in MetS contain larger lipid. However, the MetS criteria used in this study could not distinguish the vulnerable features such as thin-cap fibroatheroma, suggesting the necessity of complementary information to identify patients at high risk for cardiovascular events.