Author + information
- Received April 5, 2018
- Revision received August 6, 2018
- Accepted August 7, 2018
- Published online December 12, 2018.
- Lorenz Räber, MD, PhDa,∗ (, )
- Konstantinos C. Koskinas, MD, MSca,
- Kyohei Yamaji, MD, PhDa,b,
- Masanori Taniwaki, MDa,c,
- Marco Roffi, MDd,
- Lene Holmvang, MD, PhDe,
- Hector M. Garcia Garcia, MD, PhDf,
- Thomas Zanchin, MDa,
- Rafaela Maldonado, MDa,
- Aris Moschovitis, MDa,
- Giovanni Pedrazzini, MDg,
- Serge Zaugg, MSch,
- Jouke Dijkstra, PhDi,
- Christian M. Matter, MDj,
- Patrick W. Serruys, MD, PhDk,
- Thomas F. Lüscher, MDl,
- Henning Kelbaek, MD, PhDm,
- Alexios Karagiannis, PhDh,
- Maria D. Radu, MD, PhDe and
- Stephan Windecker, MDa
- aDepartment of Cardiology, Bern University Hospital, Bern, Switzerland
- bDepartment of Cardiology, Kokura Memorial Hospital, Kitakyushu, Japan
- cTokorozawa Heart Center, Saitama, Japan
- dDivision of Cardiology, University Hospital Geneva, Geneva, Switzerland
- eHeart Center, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- fMedStar Cardiovacular Research Network, MedStar Washington Hospital Center, Washington
- gCardiocentro, Lugano, Switzerland
- hClinical Trials Unit (CTU), Bern, and Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
- iLeiden University Medical Center, Leiden, the Netherlands
- jDepartment of Cardiology, Zurich University Hospital, Zurich, Switzerland
- kInternational Centre for Circulatory Health, National Heart and Lung Institute, Imperial College, London, London, United Kingdom
- lRoyal Brompton and Harefield Hospital Trust and Imperial College, London, United Kingdom
- mDepartment of Cardiology, Zealand University Hospital, Roskilde, Denmark
- ↵∗Address for correspondence:
Dr. Lorenz Räber, Department of Cardiology, Bern University Hospital, Freiburgstrasse, 3010 Bern, Switzerland.
Objectives This study assessed changes in optical coherence tomography (OCT)-defined plaque composition in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin treatment.
Background OCT is a high-resolution modality capable of measuring plaque characteristics including fibrous cap thickness (FCT) and macrophage infiltration. There is limited in vivo evidence regarding the effects of statins on OCT-defined coronary atheroma composition and no evidence in the context of STEMI.
Methods In the IBIS-4 (Integrated Biomarker Imaging Study-4), 103 patients underwent intravascular ultrasonography and OCT of 2 noninfarct-related coronary arteries in the acute phase of STEMI. Patients were treated with high-dose rosuvastatin for 13 months. Serial OCT imaging was available in 153 arteries from 83 patients. We measured FCT by using a semi-automated method. Co-primary endpoints consisted of the change in minimum FCT (measured in fibroatheromas) and change in macrophage line arc.
Results At 13 months, median low-density lipoprotein cholesterol had decreased from 128 mg/dl to 73.6 mg/dl. Minimum FCT, measured in 31 lesions from 27 patients, increased from 64.9 ± 19.9 μm to 87.9 ± 38.1 μm (p = 0.008). Macrophage line arc decreased from 9.6° ± 12.8° to 6.4° ± 9.6° (p < 0.0001). The secondary endpoint, mean lipid arc, decreased from 55.9° ± 37° to 43.5° ± 33.5°. In lesion-level analyses (n = 191), 9 of 13 thin-cap fibroatheromata (TCFAs) at baseline (69.2%) regressed to non-TCFA morphology, whereas 2 of 178 non-TCFA lesions (1.1%) progressed to TCFAs.
Conclusions In this observational study, we found significant increase in minimum FCT, reduction in macrophage accumulation, and frequent regression of TCFAs to other plaque phenotypes in nonculprit lesions of patients with STEMI treated with high-intensity statin therapy.
The composition of coronary atherosclerotic plaques displays substantial heterogeneity and affects the clinical sequelae of individual lesions according to autopsy studies (1). Currently, intracoronary imaging modalities can assess indices of plaque morphology in vivo (2). Owing to its high spatial resolution, optical coherence tomography (OCT) is capable of measuring fibrous cap thickness (FCT) and assessing inflammatory cell infiltration (2).
Statins lower blood lipid levels and improve clinical outcomes in patients with atherosclerotic cardiovascular disease (3). The clinical benefit of statins is associated with little effect on angiographic stenosis (4) and modest reductions in plaque burden by intravascular ultrasonography (IVUS) (5), suggesting additional vascular protective effects. Although preclinical investigations and human pathology studies have demonstrated plaque-stabilizing effects of statins (6), in vivo evidence remains elusive. Previous OCT studies reported that FCT may be increased by statin treatment (7–9) but focused mainly on less intensive statin regimens, despite the fact that maximal clinical benefits have been achieved with high-intensity statins (3,5). Those previous investigations included lower risk patients with stable coronary artery disease (CAD) or unstable angina; currently, the impact of statins on OCT-defined plaque composition in patients with acute myocardial infarction (MI) is unknown.
In IBIS-4 (Integrated Biomarker Imaging Study-4), serial, multimodality intracoronary imaging of 2 noninfarct-related arteries (non-IRA) was performed in patients with ST-segment elevation MI (STEMI) who were receiving treatment with high-intensity statin (10). The IVUS study found significant regression in atheroma volume without relevant changes in virtual histology IVUS-derived plaque morphology (10). In the present analysis, we report changes in OCT-defined plaque composition.
IBIS-4 (Clinical Trials.gov; NCT00962416) (10) was a prospective cohort study nested in the COMFORTABLE-AMI (Comparison of Biolimus Eluted From an Erodible Stent Coating With Bare Metal Stents in Acute ST-Elevation Myocardial Infarction) trial, a randomized trial that compared biolimus-eluting with bare-metal stents in STEMI patients undergoing primary percutaneous coronary intervention (PCI). This observational intracoronary imaging study included 103 patients enrolled at 5 centers. Serial IVUS and OCT were applied to assess changes in coronary atherosclerosis in non-IRA patients following 13 months of high-intensity statin therapy (10). All patients provided written informed consent, and the study was approved by the institutional review boards of participating centers.
Patients included in the COMFORTABLE-AMI trial were considered for enrollment in IBIS-4 if they fulfilled the following additional criteria: age <90 years old; preserved renal and liver function; hemodynamic stability; a Thrombolysis In Myocardial Infarction flow ≥2 of the IRA after completion of primary PCI; and coronary anatomy deemed suitable for intracoronary imaging in 2 major coronary arteries in the absence of a lesion qualifying for treatment. Intracoronary imaging focused on the nontreated proximal part (50 mm) of the non-IRA. Patients received treatment with rosuvastatin at an initial dose of 20 mg during the first 2 weeks to assess compliance and adverse effects, followed by up-titration to 40 mg. Dose reduction or change to another statin was discouraged and was left to the discretion of treating physicians in cases of intolerance deemed to necessitate such adjustments (e.g., muscle symptoms or elevated creatine kinase or liver enzymes). Blood lipid levels were measured at baseline, at 30 days, and at 13 months, using standard institutional methods.
OCT image acquisition
Following successful primary PCI of the IRA, intracoronary imaging of the 2 non-IRA was performed. The region of interest (ROI) was selected between 2 anatomical landmarks (distally: the side branch; proximally: the left-main bifurcation or ostium or side branches close to the ostium of the right coronary artery). OCT images were acquired using the Fourier domain C7-XR imaging system, using the Dragonfly imaging catheter (St. Jude Medical, St. Paul, Minnesota). Patients were scheduled for repeat intracoronary imaging at 13 months. Serial OCT and IVUS examinations in IBIS-4 were safe and without complications resulting in clinical sequelae (11).
OCT image analysis
Details for OCT analyses are provided in the Online Appendix. OCT recordings were analyzed by experienced investigators at the Bern University OCT core laboratory, blinded to time-point of assessment and patient characteristics. Analyses were performed offline using Quantitative Coronary Ultrasound-Clinical Measurement Solutions version 4.69 software (Medis, Leiden, the Netherlands) at an interval of 0.4 mm within matched ROIs. A nondiseased vessel was defined by 3-layered architecture of the vessel wall (intima, media, adventitia), with no or little evidence of intimal thickening. Plaque was defined as a mass lesion (focal thickening >600 μm) or loss of the 3-layered structure of the vessel wall in more than 1 quadrant. A lipid pool/necrotic core (collectively referred to as lipid pool) was characterized by a signal-poor region >45°, with diffuse border between the signal-poor region and surrounding tissue (12). Calcium was defined as a signal-poor region with sharply delineated borders. When a lipid pool was present, the extension of lipid arc was recorded within each frame; mean and maximum values were calculated within the ROI. Fibrous cap was defined as a signal-rich tissue layer overlying a lipid pool. If lipid was present, FCT was measured using a previously validated, highly reproducible, semiautomated method that was developed specifically for this study (13) (Online Appendix). Plaque classification by OCT was performed according to the international consensus statement (14) (Online Figure S1). Fibroatheroma was defined as plaque with evidence of lipid pool >90° and no lateral delineation. Thin-cap fibroatheromas (TCFA) were defined by a minimum FCT ≤65 μm, whereas thick-cap fibroatheromas (ThCFA) were fibroatheromas with minimum FCT >65 μm. Fibrocalcific plaque was defined by evidence of calcification >90°. Fibrous plaque was defined by homogeneous OCT signal with high backscatter and was any plaque not meeting either fibroatheroma or fibrocalcific plaque definitions (Figure 1). A lesion was defined as the presence of a plaque in ≥3 consecutively analyzed frames (i.e., longitudinal extension ≥1.2 mm). Macrophages were defined as signal-rich, distinct, or confluent structures causing strong light attenuation with dark shadowing of underlying structures that was sharply delineated and typically had variable transparency on consecutive frames and rapid changes in configuration between frames, and typically not co-located with calcific pools but in the presence of fibrous plaques (14,15). Macrophages could be present as dots (single bright spots or cluster of dots without formation of clear line) or as lines (confluent accumulations forming a thin bright line) with lateral extension ≥20° (Figure 1).
Interobserver agreement for measurements was determined by the intraclass correlation coefficient (ICC) for continuous variables (FCT) and by the Cohen kappa test for categorical variables (TCFA vs. ThCFA lesion type; presence of macrophage accumulations). As previously reported in a frame-level analysis of randomly selected fibroatheromas in this dataset, measurements for minimum FCT showed excellent interobserver agreement (ICC = 0.99) (13). For classification of OCT-defined TCFA vs. ThCFA, the kappa value was 0.97 for interobserver agreement. Kappa values for the presence of macrophage dots, lines, and overall macrophages were 0.62, 0.71, and 0.79, respectively (13).
Study assessments and endpoints
Pre-specified co-primary endpoints for the OCT analysis in IBIS-4 were change in minimum FCT and macrophage accumulation angle. During the study, we defined the arc of macrophage lines as the respective co-primary endpoint, based on evidence that other (less confluent) bright spots are less specific for identification of macrophages in coronary lesions (16–18). Secondary endpoints were change in mean FCT, lipid pool arc, and plaque type by OCT. Exploratory endpoints included macrophage dots. Consistent with the IVUS report (10), primary OCT analyses were performed at a vessel (ROI) level, with secondary analyses at a lesion level.
Continuous variables are summarized as mean ± SD and categorical ones as counts (percentage). Changes in blood lipid levels were compared using paired Student’s t-tests. Serial OCT changes were compared using linear mixed models, adjusting for patient and for vessel within patient in the lesion-level analysis. Each of the 2 co-primary endpoints was tested at a significant level of 2.5% to adjust for multiplicity, using the Bonferroni correction. For these 2 endpoints, p values <0.025 were considered significant. No adjustment was performed for secondary endpoints, and p values were reported for exploratory purposes without any claims of significance. Stratified analyses of OCT changes were conducted, and p values of mixed-effects analysis of variance were reported for the categorical effects of stratification variables. Stratification variables chosen were: age, body mass index, sex, family history of CAD, diabetes mellitus, smoking, hypertension, statin at baseline, and change in low-density lipoprotein cholesterol (LDL-C). Differences between strata were derived from linear mixed models. We also measured linear association of OCT outcomes with changes in LDL-C, modeled as a continuous variable. Two-sided p values are reported throughout. Analyses were performed using R version 3.4.0 software (R Foundation for Statistical, Vienna, Austria) and Stata version 14.2 software (StataCorp LP, College Station, Texas).
Baseline patient characteristics
A total of 103 STEMI patients underwent imaging of non-IRA using IVUS and OCT following primary PCI (10). The present analysis included 83 patients with serial evaluable OCT in 153 vessels (Online Figure S2). Baseline clinical characteristics are summarized in Table 1 and Online Table S1. Statin use was low prior to enrollment (10.8%). At 13 months, 89.2% of patients received high-dose rosuvastatin (40 mg or 20 mg), and 94% were taking high-intensity statin (Online Tables S2 and S3). LDL-C levels decreased from a median of 128 mg/dl to 73.6 mg/dl (Online Figure S3). At follow-up, 43% of patients had LDL-C levels <70 mg/dl.
Table 2 summarizes serial OCT findings at vessel-level analyses. In total, 31 arteries from 27 patients had evidence of fibroatheroma (ThCFA or TCFA) at both time points. In this subgroup, minimum FCT (over the vessel length) increased from 64.9 ± 19.9 μm to 87.9 ± 38.1 μm (p = 0.008). In all investigated arteries (n = 153), the mean arc of macrophage lines decreased from 9.6° ± 12.8° to 6.4° ± 9.6° (p < 0.001) (Table 2). Figure 2 shows representative examples of lesions with fibrous cap thickening and reduction of macrophage accumulation over time.
There was a linear association between changes in LDL-C and changes in the arc of macrophage lines (p = 0.012) but no association of ΔLDL-C with changes in minimum FCT (p = 0.89). In stratified analyses, the increase in minimum FCT was greater in patients with than in those without diabetes (p interaction = 0.003) without evidence of heterogeneity in relation to other baseline clinical characteristics (Figure 3A). There was no heterogeneity between subgroups regarding change in macrophage line arc (Figure 3B). Diabetes mellitus emerged as a multivariate predictor of change in minimum FCT (greater increase; p = 0.013) (Online Table S4). Notably, minimum FCT at baseline was smaller in patients with than in those without diabetes (40.8 ± 13.2 μm vs. 69.3 ± 16.9 μm, respectively).
Mean FCT increased from 248.6 ± 65.8 μm to 313.8 ± 88.7 μm, and mean lipid arc (over the vessel length) decreased from 55.9° ± 37.0° to 43.5° ± 33.5°. With respect to plaque type by OCT, we found a reduction in the proportion of frames with fibrous plaque or TCFA and an increase in frames with fibrocalcific plaque (Table 2).
Table 3 summarizes plaque type by OCT in individual lesions (n = 191) at baseline and at follow-up. The most frequent changes in lesion type were observed in OCT TCFAs at baseline; 9 of 13 TCFAs (69.2%) regressed to non-TCFA morphology. Conversely, only 2 of 178 non-TCFA lesions (1.1%) progressed to TCFA at follow-up (both were ThCFA at baseline). Overall, changes in plaque morphology were infrequent, with 1.6% of lesions (n = 3) showing worsening morphology, 5.8% (n = 11) changing to a presumably more stable lesion, and 92.6% of lesions (n = 177) without change of lesion category (Figure 4).
Exploratory, lesion-level analyses
In 148 vessels from 82 patients, we found 191 individual lesions at least at 1 time point (lesion length: 16.1 ± 12.5 mm at baseline). Consistent with vessel-level findings, minimum FCT (within each lesion) increased from 74.0 ± 32.3 μm to 94.2 ± 39.9 μm. The mean arc of macrophage lines decreased by 31.7% (Online Table S5). Changes in minimum FCT in each fibroatheroma lesion are shown in Figure 5A. The overall increase in minimum FCT was driven by changes in lesions with TCFA morphology at baseline (n = 13 of 36 lesions with fibroatheroma type at both time points) (Figure 5B). Any increase in minimum FCT was observed in 92.3% of TCFA compared with 52.2% of ThCFA lesions at baseline.
The clinical benefit of statins in patients with atherosclerotic cardiovascular disease is well established, but the mechanisms underlying these effects are not fully understood. The present study is the first serial analysis of coronary plaque composition as assessed by OCT in patients presenting with STEMI. We found modest but significant increases in minimum FCT and decreases in macrophage lines in the noninfarct-related coronary arteries following 13-month treatment with high-intensity statin. Although changes in plaque type were overall infrequent, two-thirds of OCT TCFAs regressed to other lesion phenotypes. These findings provide novel in vivo evidence of changes in nonculprit lesions among STEMI patients receiving intensive statin therapy but should be interpreted in the context of the modest sample size and limitations inherent to observational studies.
Plaque composition appears to be an important determinant of clinical manifestations of coronary atherosclerotic lesions (1,19,20). In human autopsy studies, plaques that rupture and cause fatal coronary events typically exhibit thin fibrous caps, large lipid pools, and marked inflammatory cell infiltration (1). OCT is the only available imaging modality with sufficient spatial resolution to quantify FCT in vivo (2). We found that high-intensity statin treatment was associated with significant increases in minimum FCT. Notably, cap thickening appeared to be more pronounced in regions with critically thin caps at baseline and, along the same lines, was more pronounced in patients with diabetes (i.e., those with thinner caps at baseline). The latter observation is in line with IVUS studies showing that intensive statin treatment can halt the progressive nature of diabetic coronary atherosclerosis (21).
The finding of fibrous cap thickening following statin treatment builds upon previous evidence from OCT studies (7) including the randomized EASY-FIT (Effect of AtorvaStatin therapY on FIbrous cap Thickness) study (8). Previous reports should be interpreted in light of essential differences and methodological limitations. First, these studies included Asian patients, possibly limiting generalizability of findings. Second, earlier reports mostly used low- to moderate-intensity statins, whereas maximal atheroma regression (5) and greatest clinical benefit (3) have been observed with high-intensity statin regimens. Third, previous studies applied manual, nonstandardized measurements of FCT, which have been associated with substantial interobserver variability and limited reproducibility (22). A computer-assisted, semiautomated method applied in our study outperformed manual assessments with respect to FCT measurement and plaque classification as TCFA versus ThCFA (13). Finally, our observations of FCT increase were derived from a population with significant plaque burden reduction, as documented by serial IVUS analyses of the same arterial segments. Although no causality between statin treatment and increase in FCT could be deduced due to the observational nature of this study, our findings are biologically plausible (based on pre-clinical investigations of the plaque-stabilizing effects of statins) and consistent with randomized studies in different, more stable patient populations (8,9).
The YELLOW-II (Reduction in Coronary Yellow Plaque, Lipids and Vascular Inflammation by Aggressive Lipid Lowering II) trial recently reported an average increase in FCT of 9 μm in 85 stable CAD patients treated with rosuvastatin, 40 mg, over 8 weeks (23). The pathobiology of chronic stable CAD versus that of STEMI differs substantially. Acute MI is characterized by a burst of systemic inflammation that has been shown to precipitate plaque progression and destabilization in experimental animals (24). Moreover, patients with MI harbor greater atherosclerotic burden with more frequent high-risk lesions (25) and show greater potential for atheroma regression following high-intensity statin therapy (26). The present findings extend those of the YELLOW-II study in a different clinical setting. At variance to the YELLOW-II study (in which obstructive coronary lesions were evaluated), inclusion in IBIS-4 was unselected with respect to baseline plaque status and is therefore more representative of global residual disease burden following primary PCI.
Inflammation is a key process in atherosclerotic progression. Tearney at al. (15) first reported that OCT could identify macrophages in coronary plaques (15). Subsequent reports pointed to the potential for false-positive findings due to other structures within the plaque that can scatter light (cholesterol crystals, calcium) (12,17,18). Conceptually, resolution of inflammatory cell infiltration may involve transition from confluent accumulations to less dense infiltrations, which may explain the seemingly paradoxical finding of increase in single or clustered macrophage dots along with a significant (23%) decrease in macrophage lines in this study. A recent study applied an OCT bright spot algorithm which identified a variety of plaque components (including macrophages) and showed a reduction in bright spot density following treatment with moderate- (20 mg) or high-intensity (60 mg) atorvastatin (27). Although not directly comparable due to differing methodologies applied, our findings regarding change in macrophage accumulation conceptually align with the latter investigation. Moreover, our findings are consistent with histopathological observations of fewer inflammatory cells in noncoronary (carotid) lesions of patients treated with statins versus statin-naïve patients (28). Of potential clinical relevance, the CLIMA (Relationship Between OCT Coronary Plaque Morphology and Clinical Outcome) study, including 1,003 patients, recently reported that macrophage infiltration in angiographically nondiseased left anterior descending arteries of patients with CAD was a predictor of subsequent major cardiovascular events (29). Further studies should validate different patterns of macrophage accumulation detected by OCT and define their possible clinical implications.
Changes in lesion type by OCT were overall infrequent. Notably, two-thirds of nonculprit TCFAs at baseline regressed to non-TCFAs, whereas very few non-TCFA lesions (both proportionately and in absolute numbers) progressed to TCFA morphology. In a previous study that performed serial virtual histology IVUS in patients with myocardial infarction, the majority (78%) of lesions classified at baseline as TCFA remained TCFAs at 13-month follow-up (30); the differences with our present findings may reflect different properties of the applied imaging modalities (particularly the inability of virtual histology IVUS to measure FCT). According to preclinical and human autopsy studies, non-TCFA lesions are associated with a lower likelihood of rupture than TCFAs (1); however, in the absence of in vivo evidence with OCT, whether the changes observed in this as well as previous OCT studies (7–9) indeed reflect a plaque-stabilizing effect remains unclear and requires further investigation.
This study has several limitations. First, IBIS-4 is an observational study without a control group; however, inclusion of STEMI patients treated with lower intensity or no statin treatment would be unethical by current standards. Analysis was not based on a formal sample size calculation; rather, we analyzed 83 STEMI patients who were enrolled as part of an imaging substudy nested in a large randomized trial comparing 2 stent types for primary PCI. One of the 2 co-primary endpoints, FCT, was assessed in 27 of all included patients with 13 TCFAs at baseline; in view of the small numbers, the present findings should be interpreted as hypothesis-generating only. The follow-up duration, although longer than in previous studies (7,8), may not suffice to detect long-term changes in plaque composition. We focused specifically on macrophage lines as a co-primary endpoint because we aimed to enhance specificity (given that components of the atherosclerotic intima other than macrophages may give the OCT appearance of single bright spots). OCT consensus recommendations (14) describe features of any macrophage accumulation (ranging from single to punctuate bright spots to confluent formations), and histologic validation studies have not specifically addressed different patterns of macrophage accumulation by OCT. The hypothesis that macrophage lines by OCT are more specific for macrophage detection requires validation, and we cannot exclude false positive findings. Finally, although 94% of patients were receiving high-intensity statin therapy at follow-up, only 69% were taking the protocol-recommended regimen (rosuvastatin, 40 mg).
In patients with STEMI treated with high-intensity statin, we found a modest but significant increase in FCT, reduction in macrophage accumulation, and frequent regression of TCFAs to other lesion phenotypes in this observational OCT study. Future studies are warranted to assess the clinical relevance of OCT-defined coronary atheroma composition and of respective changes following statin treatment.
COMPETENCY IN MEDICAL KNOWLEDGE: Among patients with acute STEMI who underwent serial OCT of the noninfarct-related coronary arteries, 1-year treatment with high-intensity statin was associated with findings consistent with stabilization of nonculprit plaques, namely a significant increase in minimum fibrous cap thickness and reduction in macrophage accumulation. Moreover, we observed frequent regression of TCFAs to other, presumably more stable plaque phenotypes.
TRANSLATIONAL OUTLOOK: Further studies should confirm the findings of the present investigation. Moreover, additional studies are needed to address potential clinical implications of these findings, to test whether presumably favorable changes in plaque composition as assessed by OCT are associated with improved clinical outcomes in patients with STEMI.
The IBIS-4 trial was funded by Swiss National Science Foundation grants 33CM30-124112 and 310030-118353, St. Jude Medical/Abbott, Zurich, Switzerland, and Biosensors SA, Morges, Switzerland. Dr. Raber has received research grants from St. Jude Medical/Abbott, Sanofi, and Regeneron; and has received speaker fees from Amgen and Astra Zeneca. Dr. Radu has received lecture honoraria from St. Jude Medical/Abbott Vascular; and has received research grants from Abbott Vascular, Terumo, Boston Scientific, Biotronik, and Medtronic. Dr. Lüscher has received research grants and speaker fees from Amgen, AstraZeneca, Bayer Healthcare, Biosensors, Biotronik, Boston Scientific, Eli Lilly, Medtronic, Merck and Co., Roche, and Servier; Dr. Matter has received research grants and speaker fees from and consults for Eli Lilly, AstraZeneca, Roche, Amgen, and Merck and Co. Dr. Windecker has received research contracts from Bracco, Boston Scientific, and St Jude. All other authors have reported that they have no relationships with industry relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- coronary artery disease
- fibrous cap thickness
- infarct-related artery
- intravascular ultrasonography
- myocardial infarction
- optical coherence tomography
- region of interest
- ST-segment elevation myocardial infarction
- thin-cap fibroatheroma
- thick-cap fibroatheroma
- Received April 5, 2018.
- Revision received August 6, 2018.
- Accepted August 7, 2018.
- 2018 American College of Cardiology Foundation
- Koskinas K.C.,
- Siontis G.C.M.,
- Piccolo R.,
- et al.
- Ballantyne C.M.,
- Raichlen J.S.,
- Nicholls S.J.,
- et al.
- Fukumoto Y.,
- Libby P.,
- Rabkin E.,
- et al.
- Hattori K.,
- Ozaki Y.,
- Ismail T.F.,
- et al.
- Komukai K.,
- Kubo T.,
- Kitabata H.,
- et al.
- Taniwaki M.,
- Radu M.D.,
- Garcia-Garcia H.M.,
- et al.
- Phipps J.E.,
- Hoyt T.,
- Vela D.,
- et al.
- Radu M.D.,
- Yamaji K.,
- García-García H.M.,
- et al.
- Tearney G.J.,
- Regar E.,
- Akasaka T.,
- et al.
- Tearney G.J.,
- Yabushita H.,
- Houser S.L.,
- et al.
- Yabushita H.,
- Bouma B.E.,
- Houser S.L.,
- et al.
- Tearney G.J.
- Phipps Phipps J.E.,
- Vela D.,
- Hoyt T.,
- et al.
- Narula J.,
- Nakano M.,
- Virmani R.,
- et al.
- Stegman B.,
- Puri R.,
- Cho L.,
- et al.
- Kim S.J.,
- Lee H.,
- Kato K.,
- et al.
- Kini A.S.,
- Vengrenyuk Y.,
- Shameer K.,
- et al.
- Hong M.K.,
- Mintz G.S.,
- Lee C.W.,
- et al.
- Puri R.,
- Nissen S.E.,
- Shao M.,
- et al.
- Minami Y.,
- Hoyt T.,
- Phipps J.E.,
- et al.
- Puato M.,
- Faggin E.,
- Rattazzi M.,
- et al.
- ↵Prati F, Romagnolia E, Gattoa L, et al. Relationship between coronary plaque morphology of the left anterior descending artery and long term clinical outcome: the CLIMA study. Presented at EuroPCR, May 2018.
- Zhao Z.,
- Witzenbichler B.,
- Mintz G.S.,
- et al.