Author + information
- Received September 4, 2018
- Revision received October 12, 2018
- Accepted October 24, 2018
- Published online May 6, 2019.
- Francesco Fracassi, MDa,
- Filippo Crea, MDb,
- Tomoyo Sugiyama, MD, PhDa,
- Erika Yamamoto, MD, PhDa,
- Shiro Uemura, MD, PhDc,
- Rocco Vergallo, MD, PhDb,
- Italo Porto, MD, PhDb,
- Hang Lee, PhDd,
- James Fujimoto, PhDe,
- Valentin Fuster, MD, PhDf and
- Ik-Kyung Jang, MD, PhDa,g,∗ (, )@MGHHeartHealth
- aCardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- bDepartment of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Rome, Italy
- cDepartment of Cardiology, Kawasaki Medical School, Kurashiki, Okayama, Japan
- dBiostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
- eThe Research Laboratory of Electronics, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts
- fZena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York
- gDivision of Cardiology, Kyung Hee University Hospital, Seoul, South Korea
- ↵∗Address for correspondence:
Dr. Ik-Kyung Jang, Cardiology Division, Massachusetts General Hospital, 55 Fruit Street, GRB 800, Boston, Massachusetts 02114.
Background Healed plaques, morphologically characterized by a layered phenotype, are frequently found in subjects with sudden cardiac death. However, in vivo data are lacking.
Objectives The purpose of this study was to determine the prevalence, morphological characteristics, and clinical significance of healed culprit plaques in patients with acute coronary syndromes (ACS) using optical coherence tomography (OCT).
Methods A total of 376 ACS patients (252 ST-segment elevation myocardial infarction [MI] and 124 non–ST-segment elevation acute coronary syndrome) who had undergone pre-intervention OCT imaging of the culprit lesion were enrolled. Patients were stratified according to the presence of layered phenotype, defined as layers of different optical density at OCT. Clinical and laboratory data, OCT characteristics, and 1-year outcome were compared between the 2 groups.
Results Among 376 patients, 108 (28.7%) healed plaques were identified. Hyperlipidemia, diabetes, and history of MI were more frequent in patients with healed plaques (44.4% vs. 33.2%; p = 0.041; 35.2% vs. 23.5%; p = 0.021; and 15.7% vs. 6.3%; p = 0.009, respectively). High-sensitivity C-reactive protein was significantly higher in patients with healed plaques (median 4.98 mg/l [interquartile range: 1.00 to 11.32 mg/l] vs. 3.00 mg/l [interquartile range: 0.30 to 10.15 mg/l]; p = 0.029). Plaque rupture (64.8% vs. 53.0%; p = 0.039), thin cap fibroatheroma (56.5% vs. 42.5%; p = 0.016), and macrophage accumulation (81.1% vs. 63.4%; p = 0.001) were common in the layered group. OCT also revealed greater area stenosis in plaques with layered phenotype (79.2 ± 9.5% vs. 74.3 ± 14.3%; p = 0.001). The incidence of major adverse cardiovascular events was similar between the 2 groups, except that the all-cause rehospitalization rate was higher among healed plaques (32.7% vs. 16.5%; p = 0.013).
Conclusions Healed plaques, a signature of prior plaque destabilization, were found at the culprit site in more than one-quarter of ACS patients. Such patients more frequently were diabetic, were hyperlipidemic, or had a history of MI. Healed plaques frequently showed OCT features of vulnerability with evidence of local and systemic inflammation. The combination of plaque vulnerability, local inflammation, and greater plaque burden in addition to systemic inflammation may outweigh the protective mechanism of plaque healing and predispose those plaques to develop occlusive thrombus.
- coronary vulnerability
- healed plaques
- layered plaques
- optical coherence tomography
- subclinical thrombosis
Acute coronary syndromes (ACS) are mainly caused by abrupt changes in atherosclerotic plaque structure secondary to plaque rupture or plaque erosion, leading to occlusive thrombosis (1–3). This abrupt change in plaque architecture may also take place silently, especially in the cases of low plaque burden and small thrombus volume (4,5). The subsequent repair process leads to stabilization of the ruptured or eroded site, which results in a healed plaque, characterized by distinct layers of organized thrombus and/or collagen (3,6). During the repair process, type III collagen is gradually replaced by type I collagen, which appears as a band of high backscattering signal on optical coherence tomography (OCT). Autoptic studies have shown that healed plaques are frequent in men who died from coronary events, with a prevalence up to 61% to 73% in the whole coronary tree (7,8). However, in vivo data are still lacking. OCT is an intravascular imaging technique that is able to visualize detailed structures in the coronary arterial walls. Healed plaques are identified by distinct layers of different optical characteristics that constitute the signature of previous acute events that had undergone a healing process (6,9,10). It is believed that subclinical episodes of thrombosis may contribute to an increase in plaque volume and develop high-degree stenosis (8,11). A recent serial OCT study, investigating plaque progression in stable angina patients, showed that 29% of nonculprit lesions that had progressed over time showed evidence of healed plaques (9). However, the prevalence and plaque characteristics of a healed plaque at the culprit site in patients with ACS are still unknown. In the present report, we studied the prevalence, morphological features, and significance of healed plaques at the culprit site in patients with ACS using OCT.
Between August 2010 and April 2016, patients presenting with ACS who underwent pre-intervention OCT imaging of the culprit lesion were selected from the Massachusetts General Hospital (MGH) OCT Registry (NCT01110538) and the EROSION (Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography–Based Management In Plaque Erosion) study database (NCT02041650). The MGH OCT registry is an international, multicenter, prospective, all-comer registry that includes cases with coronary OCT imaging involving 20 sites across 6 countries. The EROSION study is a single-center, prospective, single-arm study that includes ACS patients undergoing OCT (12). Diagnosis of ACS, which included ST-segment elevation myocardial infarction (STEMI) and non–ST-segment elevation acute coronary syndromes (NSTE-ACS), were made according to the current American Heart Association (AHA)/American College of Cardiology (ACC) guidelines (13,14) as follows. STEMI was defined as continuous chest pain that lasted >30 min, arrival at the hospital within 12 h from the onset of symptoms, ST-segment elevation >0.1 mV in ≥2 contiguous leads or new left bundle-branch block on the 12-lead electrocardiogram, and elevated cardiac markers (creatine kinase-MB or troponin I) (13). NSTE-ACS included non–ST-segment elevation myocardial infarction (MI) and unstable angina pectoris. The former was defined as ischemic symptoms in the absence of ST-segment elevation on the electrocardiogram with elevated cardiac markers. Unstable angina pectoris was defined as having newly developed/accelerating chest symptoms on exertion or rest angina within 2 weeks without biomarker release (14).
The culprit plaque was first identified by the treating cardiologist who performed angiography at each participating site; the information about location of the culprit plaque was included in the data collection form. In the majority of cases, the culprit lesion was easily identified using electrocardiogram and angiogram (abrupt total or subtotal occlusion with or without visible filling defect or complex lesion). When it was unclear, regional wall motion abnormality on left ventricular angiogram or on echocardiogram were used. The culprit plaque was re-evaluated and confirmed by 2 reviewers (F.F., T.S.) who were blinded to the site investigator’s evaluation at the MGH Cardiology Laboratory for Integrative Physiology and Imaging. Demographic and clinical data were prospectively collected from each participating site and sent to the OCT core laboratory at MGH. Among the initial population of 1,504 patients, demographic, clinical, or angiographic data were not available in 218 patients; cases with stent-related events, post-interventional imaging only, or use of time-domain OCT (n = 482) were excluded; in 214 cases, OCT images were of poor quality due to blood artifacts, due to a too short pull-back, or because the culprit lesion was not identifiable. Additionally, 99 cases were excluded because of large residual thrombus that hampered the visualization of the underlying plaque. Moreover, etiologies of ACS different from plaque rupture and erosion (calcified nodule, spontaneous coronary artery dissection, spasm, microvascular disease, or tight stenosis) (n = 115) were not included in the final analysis. In particular, calcium-related acute events were excluded because data on calcified plaques at the culprit site are still limited. The final study population consisted of 376 patients (Figure 1). The study protocol was approved by the institutional review board at each participating site and written informed consent was obtained from all patients before enrollment.
Coronary angiography analysis
Angiograms were also sent by each participating institution to the core laboratory. All analyses were performed by 2 independent investigators blinded to clinical data and OCT analysis results. Angiographic images were analyzed using a quantitative coronary angiography analysis program (CAAS 5.10.1, Pie Medical Imaging BV, Maastricht, the Netherlands). Lesion length, minimum lumen diameter, and reference diameter were measured and percent diameter stenosis calculated. All lesions were evaluated according to the AHA/ACC classification (15), and type B2 and C lesions were considered complex.
OCT image acquisition
OCT imaging was performed using a frequency-domain OCT system (C7-XR OCT Intravascular Imaging System, St. Jude Medical, St. Paul, Minnesota), as previously reported (16). In patients with Thrombolysis In Myocardial Infarction flow grade ≤2 and large thrombus burden, aspiration thrombectomy was allowed before intravascular imaging, while balloon pre-dilation was not allowed. All OCT images were submitted for offline analysis to the MGH OCT core laboratory, where they were analyzed by 2 independent investigators blinded to clinical and angiographic data, using an offline review work station (Ilumien Optis, St. Jude Medical).
OCT image analysis
OCT images were analyzed using the previously established criteria (2,17). Healed plaques were defined as plaques with 1 or more layers with different optical density and a clear demarcation from underlying components on OCT, as proposed in the previous ex vivo and OCT studies (6,9) and a recent histology validation study (10). Because layered phenotype constitutes the morphological counterpart of a healed plaque, the terms layered plaque and healed plaque are used interchangeably in the present work. In particular, the expression “layered plaque” describes the morphological appearance, whereas the terminology “healed plaque” implicates the biology of that plaque type. According to the number of identifiable layers, healed plaques were further classified as single or multilayered. Plaque rupture was identified by the presence of fibrous cap discontinuity with cavity formation; plaque erosion was defined as the presence of intracoronary thrombus attached to the luminal surface with no detectable signs of fibrous cap rupture or luminal surface irregularity at the culprit lesion in the absence of thrombus (2). Plaques were classified as follows: 1) fibrous (homogeneous, high backscattering region); or 2) lipid (low-signal region with diffuse border) (16). In lipid plaques, fibrous cap thickness was measured 3 times at the thinnest part, and the average value was calculated. Lipid arc was measured at 1-mm intervals, and lipid length was measured on the longitudinal view. Lipid index was defined as the product of mean lipid arc multiplied by lipid length. Thin cap fibroatheroma (TCFA) was defined as a plaque with the thinnest part of the fibrous cap measuring <65 μm and with a lipid arc wider than 90° (18). Macrophage accumulation was defined as the presence of highly backscattering focal granular regions in the fibrous cap. Thrombus was defined as an irregular mass floating in or protruding into the lumen with a dimension of at least 250 μm. Microvessels were defined as signal-poor vesicular or tubular structure delineated in multiple contiguous frames. Calcification was defined as an area with low backscattering signal and a sharp border inside of a plaque. Reference lumen area was defined as the mean of the largest lumen area proximal and distal to the stenosis; minimal lumen area was the smallest lumen area within the length of the lesion. Percent area stenosis was calculated as the percentage decrease of lumen area at the narrowest frame according to the following formula: ([mean reference lumen area − minimal lumen area]/mean reference lumen area) × 100. Interobserver and intraobserver variability were assessed by the evaluation of random samples of 90 patients by 2 independent observers and by the same observer at 2 separate timepoints with a 2-week interval. The interobserver Kappa coefficients were 0.88 for layered phenotype and 0.90 for diagnosis of rupture or erosion. The intraobserver Kappa coefficients were 0.92 for layered phenotype and 0.95 for diagnosis of rupture or erosion. Any discordance was resolved by consensus with a third reviewer.
Patients were followed-up at 1 year after discharge. Cardiac death, acute myocardial infarction (AMI), ischemia-driven revascularization, and rehospitalization were recorded and compared between the 2 study groups. AMI was defined as STEMI and non-ST-segment elevation MI by AHA/ACC guidelines (13,14). Ischemia-driven revascularization was defined as a repeat percutaneous coronary revascularization or bypass surgery for AMI, unstable angina, stable angina, or documented silent ischemia. Rehospitalization included all causes of hospital readmission.
The study population was divided into 2 groups according to the presence or absence of layered phenotype in the culprit plaque, and each study’s variables were compared accordingly. Further comparisons were made within the layered phenotype group between single-layered and multilayered plaques. Categorical data were compared using either a chi-square test or Fisher exact test, and are presented as counts (proportions). Continuous variables were tested for normal distribution by the nonparametric 1-sample Kolmogorov-Smirnov test. Continuous variables are expressed as mean ± SD for normally distributed variables and as median (25th to 75th percentiles) for non-normally distributed variables, and were compared using the independent sample Student’s t-test or Mann-Whitney U test, as appropriate. All tests were 2-sided, and a p value <0.05 represented statistical significance. All analyses were performed using the SPSS version 23.0 (SPSS, Inc., Chicago, Illinois).
A total of 376 ACS patients who underwent pre-intervention OCT imaging of the culprit lesion constituted the study population (age 57.5 years; 76.3% male). Among them, 252 (67.0%) were admitted for STEMI and 124 (33.0%) for NSTE-ACS. On OCT analysis, among ACS caused by plaque rupture or erosion, 108 (28.7%) patients showed a layered phenotype at the culprit site, while 268 (71.3%) did not have any layered structure. Representative cases are shown in Figure 2.
Clinical data and layered phenotype
Patients with a layered culprit plaque, compared with those without layered plaque, had a higher prevalence of hyperlipidemia and diabetes (44.4% vs. 33.2%; p = 0.041; and 35.2% vs. 23.5%; p = 0.021, respectively) as well as history of MI (15.7% vs. 6.3%; p = 0.009). Patients with a layered phenotype presented more frequently with NSTE-ACS and those with a nonlayered phenotype with STEMI. The levels of high-sensitivity C-reactive protein were significantly higher in patients with layered phenotype (median 4.98 mg/l [interquartile range: 1.00 to 11.32 mg/l] vs. 3.00 mg/l [interquartile range: 0.30 to 10.15 mg/l]; p = 0.029). No significant differences were found in other clinical characteristics between the 2 groups (Table 1, Figure 3).
Layered plaques were more frequently complex (B2/C type) (72.2% vs. 59.0%; p = 0.018) and had a higher prevalence of multivessel disease (55.6% vs. 39.2%; p = 0.004) on angiogram. The degree of stenosis was significantly higher in layered than in nonlayered plaques (70.0 ± 14.1% vs. 65.7 ± 14.7%; p = 0.028) (Table 2, Figure 3).
Plaque rupture and lipid plaque were more frequent in layered plaques than in nonlayered plaques (64.8% vs. 53.0%; p = 0.039, and 83.3% vs. 70.9%; p = 0.013). The prevalence of TCFA was significantly higher in layered plaques (56.5% vs. 42.5%; p = 0.016). Moreover, macrophage accumulation was more frequently found in layered plaques (79.6% vs. 56.3%; p = 0.001). Layered plaques had a higher percent area stenosis than nonlayered plaques (79.23 ± 9.49% vs. 74.27 ± 14.32%; p = 0.001) (Table 3, Figure 3). The prevalence of layered phenotype increased with increasing degree of percent area stenosis (Figure 4).
Layered phenotype subgroup analysis
Layered plaques (n = 108) were further classified based on the number of detectable layers into a single-layer group (n = 76; 70.4%) and a multilayer group (n = 32; 29.6%). No significant differences between the 2 subgroups were found in clinical characteristics. Angiographic analysis showed a higher prevalence of complex (B2/C type) lesions in the multilayered group compared with the single-layered group (87.5% vs. 66.7%; p = 0.043). On OCT analysis, area stenosis significantly increased from nonlayered (74.3 ± 14.3%) to single-layered (78.2 ± 10.3%) and to multilayered phenotype (81.8 ± 6.5%; p = 0.002). None of the other OCT parameters were different between the 2 subgroups.
The median time at follow-up was 1.08 years (interquartile range: 1.00 to 1.09 years). Data were available for 226 (60.1%) patients. The incidence of death, AMI and ischemia-driven revascularization were similar between the 2 study groups. Only rehospitalization rate was higher in patients with layered plaque compared with patients with nonlayered plaques (32.7% vs. 16.5%; p = 0.013).
To the best of our knowledge, this is the first in vivo study investigating the prevalence, detailed morphological characteristics, and clinical significance of healed plaques at the culprit site in the ACS population. In this study, healed plaques, a signature of previous subclinical thrombosis, at the culprit lesion: 1) are found in 29% of the most commonly seen types of ACS lesions, and one-third of them have a multilayered pattern; 2) are more frequent in ACS patients with hyperlipidemia, diabetes mellitus, and a history of MI; 3) are often complex on angiogram and more frequently found in patients with multivessel disease; 4) are frequently associated with plaque rupture, TCFA, and macrophage infiltration; and 5) multilayered plaques present the most severe luminal narrowing compared with single-layered or nonlayered ones.
In vivo detection of healed plaques
Healed plaques, morphologically characterized by a layered phenotype, are the result of 1 or more silent episodes of plaque rupture or erosion with nonocclusive thrombus formation (3,7). In the initial stages of healing, thrombus is organized and gradually replaced by granulation tissue rich in proteoglycans and type III collagen. Over time, the type III collagen is gradually replaced by type I collagen, forming a new fibrous layer, which is later completely re-endothelialized (3,6). Otsuka et al. (6) compared the OCT appearance of healed plaque with histology, demonstrating that healed plaques are characterized by layers of different optical density consisting of fibrous tissue, lipids, and/or calcium; a typical band of high OCT signal can extend between different layers, especially when the healing process is complete and high backscattering type I collagen has replaced type III collagen. Recently, the identification of healed plaques by OCT has been validated against histology in a study by Shimokado et al. (10); a healed plaque was defined as a plaque with heterogeneous signal rich layers of different optical density on OCT. They reported very high sensitivity, specificity, positive predictive value, and negative predictive value for OCT to detect histologically defined healed plaques. In the current study, we report that an in vivo prevalence of healed plaques at the culprit lesion is 29% in ACS patients. Previous studies reported a higher prevalence of healed plaques, up to 61% to 73%. However, those were autopsy studies, and the entire coronary trees (culprit and nonculprit vessels) were examined (7). The findings of the current study confirm and extend the concept that plaque instability often precedes symptomatic thrombosis proposed by Rittersma et al. (19).
Patient characteristics and healed plaques
In the present study, patients with healed plaques had a higher prevalence of hyperlipidemia and diabetes mellitus. Burke et al. (7), described similar findings in an autoptic study of 142 men with sudden coronary death. Of note, hyperlipidemia and diabetes mellitus are known to be associated with a higher risk of thrombosis (20–22). In the presence of hypercoagulable state, thrombogenic stimulus will outweigh endogenous thrombolytic activity, leading to a formation of mural thrombus. History of previous MI was more common in patients with a healed plaque. This indicates that these patients are at high risk for recurrent plaque disruption and thrombosis. Although the previous culprit site might have healed with a layered plaque phenotype, it is important to note that we looked at the new culprit plaque responsible for the present admission. Of note, unrecognized MIs, documented by electrocardiogram or imaging techniques, were found in 22% to 44% of all MIs (23). Consistently, one-half of plaques related to healed infarcts were stable at the time of autopsy in a study by Virmani et al. (3). These findings suggest that a flow-limiting thrombus, most likely present at the time of ischemia, had undergone endogenous lysis and/or healing.
High-degree stenotic lesions and healed plaques
In our study, patients with a layered phenotype had a higher degree of luminal narrowing and more complex lesions; furthermore, the prevalence of healed plaques was significantly higher in highly stenotic lesions (OCT area stenosis ≥75%). A pathology study by Mann and Davies, with 256 plaques in 39 men who died from ischemic heart disease, reported healed ruptures in 73% of plaques with diameter stenosis >50%, but in only 17% of plaques with diameter stenosis <50% (8). The number of healed rupture sites correlated with the degree of luminal narrowing in acute rupture sites (7). Our study confirms this finding; among healed plaques at the culprit site, indeed, multilayered plaques, indicative of multiple previous thrombotic events, had more severe stenosis compared with single-layered plaques. These data support the concept that repetitive episodes of subclinical thrombosis and subsequent healing constitute a frequent mechanism of plaque progression. Traditionally, plaque growth was mostly ascribed to gradual smooth muscle cells proliferation leading to critical stenosis and ischemia for a supply-demand mismatch or plaque thrombosis (24). The idea of phasic plaque progression rather than linear was introduced by studies comparing plaque severity in serial angiographic assessments (25–27) and was confirmed, more recently, by intravascular ultrasonography and OCT studies (9,11,28). The same underlying pathobiology may explain the higher prevalence of complex lesions on angiogram and multivessel disease.
OCT features of healed plaque
In the present study, plaque rupture was identified more frequently in healed plaques. In addition, TCFA and macrophage accumulation were the other frequent features of healed plaques. TCFA, characterized by a large necrotic core with an overlying thin intact fibrous cap, is the prototype of vulnerable plaque, the precursor lesion prone to rupture (2,5,6); macrophages identified by both pathology and OCT studies, at the level of the fibrous cap, are the sign of plaque activity and play a pivotal role in extracellular matrix degradation and fibrous cap disruption (3,6). A recent OCT study showed that two-thirds of ACS patients with plaque rupture had evidence of macrophage infiltration in the region of the ruptured fibrous cap, and a positive correlation between macrophage density and circulating high-sensitivity C-reactive protein level was described (29). In our study, patients with healed plaque also had significantly higher high-sensitivity C-reactive protein levels compared with those without evidence of previous subclinical thrombosis.
Taken together, our results indicate that a greater coronary vulnerability constitutes the basis of recurrent thrombotic events leading to layer formation. A first thrombotic event can be either subclinical or symptomatic depending on the degree of plaque burden/luminal narrowing and local and systemic thrombogenicity. Fresh thrombus will be partially lyzed by endogenous thrombolytic system such as tissue plasminogen activator or urokinase type plasminogen activator. The residual thrombus will be organized and eventually replaced by collagen tissues, leading to rapid stepwise progression of the plaque. Persistence of molecular and cellular plaque activity can trigger repetitive events contributing to layers formation and plaque growth, resulting in a clinically evident thrombosis at the end of the natural history of the events (Central Illustration). Although the healing process itself seals the site of rupture or erosion with collagen deposition, our findings suggest that the presence of features of vascular vulnerability, and local and systemic inflammation along with a greater plaque burden may outweigh the protective mechanism of the repair phenomenon and predispose the patients with a healed plaque to develop an acute coronary event in the future. From this perspective, patients with healed plaques at the culprit lesion would present active systemic inflammation and hypercoagulability (high-sensitivity C-reactive protein, hyperlipidemia, and diabetes mellitus), vascular vulnerability (lipid plaque, TCFA, macrophage, and complex lesions), and advanced atherosclerosis (multivessel disease, frequent previous MI, and greater plaque burden).
Therefore, when a layered plaque is identified at the culprit lesion in an ACS patient, more intensive anti-inflammatory, antithrombotic therapy, and lipid-lowering therapy should be considered not only to prevent future major cardiac events, but also to minimize the chance of rapid plaque progression.
First, this study was a retrospective analysis from a combined multicenter registry and a single-center study; in addition, a large number of cases were excluded in the final analysis. Therefore, selection bias cannot be excluded. Second, cases with massive thrombus or poor image quality were excluded, which naturally created selection bias. Third, we cannot exclude the presence of plaques undergone to intraplaque hemorrhage in the layered group; of note, intraplaque hemorrhage, that also is a mechanism of rapid plaque progression, may lead to intraplaque heterogeneity with a layered-like phenotype at OCT observation. Fourth, thrombus aspiration was performed in many cases prior to OCT imaging, which might have altered the underlying plaque morphology. However, extreme care was exercised to minimize the damage to the vessel. Finally, we acknowledge that the relevance of prognostic results is limited because 1-year follow-up data were available only in 60% of patients and the final study group did not consist of consecutive patients; furthermore, indications for rehospitalization were not available. A prospective large-scale study will answer the question of clinical significance of healed plaque at the culprit lesion.
Healed plaques, observed in more than one-quarter of ACS culprit lesions, identify a subgroup of patients with greater systemic inflammation and plaque vulnerability. This group of patients with ACS may benefit from more aggressive secondary prevention aiming at suppression of inflammation and platelet activity.
COMPETENCY IN MEDICAL KNOWLEDGE: More than one-quarter of patients with ACS undergoing OCT prior to intervention have healed plaques at the site of the culprit lesion. This observation in vivo reflects plaque vulnerability and suggests a high degree of systemic and vascular inflammation.
TRANSLATIONAL OUTLOOK: Future studies should investigate the impact of intensive secondary prevention therapies on these plaque characteristics and correlation with clinical outcomes.
Dr. Fujimoto has received royalties from intellectual property owned by MIT. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Khaled M. Ziada, MD, served as Guest Associate Editor for this paper.
Listen to this manuscript's audio summary by Editor-in-Chief Dr. Valentin Fuster on JACC.org.
- Abbreviations and Acronyms
- acute coronary syndromes
- Massachusetts General Hospital
- myocardial infarction
- non–ST-segment elevation acute coronary syndromes
- optical coherence tomography
- ST-segment elevation myocardial infarction
- thin cap fibroatheroma
- Received September 4, 2018.
- Revision received October 12, 2018.
- Accepted October 24, 2018.
- 2019 American College of Cardiology Foundation
- Partida R.A.,
- Libby P.,
- Crea F.,
- Jang I.K.
- Jia H.,
- Abtahian F.,
- Aguirre A.D.,
- et al.
- Virmani R.,
- Kolodgie F.D.,
- Burke A.P.,
- Farb A.,
- Schwartz S.M.
- Finn A.V.,
- Nakano M.,
- Narula J.,
- Kolodgie F.D.,
- Virmani R.
- Burke A.P.,
- Kolodgie F.D.,
- Farb A.,
- et al.
- Mann J.,
- Davies M.J.
- Yamamoto M.H.,
- Yamashita K.,
- Matsumura M.,
- et al.
- Shimokado A.,
- Matsuo Y.,
- Kubo T.,
- et al.
- Jang I.K.
- Jia H.,
- Dai J.,
- Hou J.,
- et al.
- O'Gara P.T.,
- Kushner F.G.,
- Ascheim D.D.,
- et al.
- Amsterdam E.A.,
- Wenger N.K.,
- Brindis R.G.,
- et al.
- Ryan T.J.,
- Faxon D.P.,
- Gunnar R.M.,
- et al.
- Kato K.,
- Yonetsu T.,
- Jia H.,
- et al.
- Yabushita H.,
- Bouma B.E.,
- Houser S.L.,
- et al.
- Rittersma S.Z.,
- van der Wal A.C.,
- Koch K.T.,
- et al.
- Flugelman M.Y.,
- Virmani R.,
- Correa R.,
- et al.
- Alderman E.L.,
- Corley S.D.,
- Fisher L.D.,
- et al.,
- for the CASS Participating Investigators and Staff
- Xie Z.,
- Hou J.,
- Yu H.,
- et al.
- Scalone G.,
- Niccoli G.,
- Refaat H.,
- et al.