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Coronary Artery Disease: HELP
Articles by Michail I. Papafaklis
Based on 30 articles published since 2010
(Why 30 articles?)
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Between 2010 and 2020, M. Papafaklis wrote the following 30 articles about Coronary Artery Disease.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Intravascular hemodynamics and coronary artery disease: New insights and clinical implications. 2016

Zaromytidou, Marina / Siasos, Gerasimos / Coskun, Ahmet U / Lucier, Michelle / Antoniadis, Antonios P / Papafaklis, Michail I / Koskinas, Konstantinos C / Andreou, Ioannis / Feldman, Charles L / Stone, Peter H. ·Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States. · Mechanical and Industrial Engineering, Northeastern University, Boston, MA, United States. · Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States. Electronic address: pstone@partners.org. ·Hellenic J Cardiol · Pubmed #27894949.

ABSTRACT: Intracoronary hemodynamics play a pivotal role in the initiation and progression of the atherosclerotic process. Low pro-inflammatory endothelial shear stress impacts vascular physiology and leads to the occurrence of coronary artery disease and its implications.

2 Review Heterogeneity of Coronary Plaque Morphology and Natural History: Current Understanding and Clinical Significance. 2016

Zaromytidou, Marina / Antoniadis, Antonios P / Siasos, Gerasimos / Coskun, Ahmet Umit / Andreou, Ioannis / Papafaklis, Michail I / Lucier, Michelle / Feldman, Charles L / Stone, Peter H. ·Vascular Profiling Research Laboratory, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, USA. · Vascular Profiling Research Laboratory, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, USA. PSTONE@PARTNERS.ORG. ·Curr Atheroscler Rep · Pubmed #27822680.

ABSTRACT: PURPOSE OF REVIEW: Despite the important progress in identifying high-risk atherosclerotic plaques, many key elements are elusive. Advanced imaging modalities provide valuable information about the anatomic and functional plaque characteristics and underscore the presence of multiple plaque morphologies. However, how the heterogeneity of atherosclerotic plaque can alter our current understanding of coronary artery disease is not fully understood. RECENT FINDINGS: Along the length of an individual plaque, the morphology patterns display marked heterogeneity. Contrary to previous beliefs, plaque morphology is also highly dynamic over time, with the vast majority of high-risk plaques becoming quiescent and mild plaques becoming severely obstructive in a short period of time. Endothelial shear stress, a local hemodynamic factor known for its critical effects in plaque initiation and progression, also displays longitudinal heterogeneity contributing to the arterial wall response in all time points. Risk stratification of plaques based on the morphological characteristics at one region of the plaque, usually the minimal lumen diameter, and at one point in time may be misleading. The evaluation of both morphological and hemodynamic characteristics along the length of a plaque will improve the risk assessment of individual plaques.

3 Review Fibroblast growth factors in cardiovascular disease: The emerging role of FGF21. 2015

Domouzoglou, Eleni M / Naka, Katerina K / Vlahos, Antonios P / Papafaklis, Michail I / Michalis, Lampros K / Tsatsoulis, Agathoklis / Maratos-Flier, Eleftheria. ·Department of Pediatrics, Medical School, University of Ioannina, Ioannina, Greece; · Second Department of Cardiology, Medical School, University of Ioannina, Ioannina, Greece; · Department of Endocrinology, Medical School, University of Ioannina, Ioannina, Greece; · Division of Endocrinology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts emaratos@bidmc.harvard.edu. ·Am J Physiol Heart Circ Physiol · Pubmed #26232236.

ABSTRACT: Early detection of risk factors for enhanced primary prevention and novel therapies for treating the chronic consequences of cardiovascular disease are of the utmost importance for reducing morbidity. Recently, fibroblast growth factors (FGFs) have been intensively studied as potential new molecules in the prevention and treatment of cardiovascular disease mainly attributable to metabolic effects and angiogenic actions. Members of the endocrine FGF family have been shown to increase metabolic rate, decrease adiposity, and restore glucose homeostasis, suggesting a multiple metabolic role. Serum levels of FGFs have been associated with established cardiovascular risk factors as well as with the severity and extent of coronary artery disease and could be useful for prediction of cardiovascular death. Furthermore, preclinical investigations and clinical trials have tested FGF administration for therapeutic angiogenesis in ischemic vascular disease, demonstrating a potential role in improving angina and limb function. FGF21 has lately emerged as a potent metabolic regulator with multiple effects that ultimately improve the lipoprotein profile. Early studies show that FGF21 is associated with the presence of atherosclerosis and may play a protective role against plaque formation by improving endothelial function. The present review highlights recent investigations suggesting that FGFs, in particular FGF21, may be useful as markers of cardiovascular risk and may also serve as protective/therapeutic agents in cardiovascular disease.

4 Review In-vivo assessment of the natural history of coronary atherosclerosis: vascular remodeling and endothelial shear stress determine the complexity of atherosclerotic disease progression. 2010

Papafaklis, Michail I / Koskinas, Konstantinos C / Chatzizisis, Yiannis S / Stone, Peter H / Feldman, Charles L. ·Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ·Curr Opin Cardiol · Pubmed #20838338.

ABSTRACT: PURPOSE OF REVIEW: Atherosclerotic disease progression is determined by localized plaque growth, which is induced by systemic and local hemodynamic factors, and the nature of the wall remodeling response. The purpose of this review is to summarize the processes underlying the heterogeneity of coronary atherosclerosis progression in relation to the local hemodynamic and arterial remodeling environment. RECENT FINDINGS: Multiple competing biological processes in the extracellular matrix define the extent of vascular remodeling and disease progression. The remodeling phenomenon is not consistent but is characterized by great phenotypical heterogeneity which reflects the complex effect of systemic, genetic and hemodynamic factors on the arterial wall response to plaque formation and progression. The exaggeration of expansive remodeling (i.e., excessive expansive remodeling) likely contributes to the transformation of an initially favorable action into an excessive course of vessel expansion, continued disease progression and plaque instability. Extremely low endothelial shear stress and excessive expansive remodeling establish a vicious cycle which leads to the formation of severe plaques with high-risk characteristics. SUMMARY: The dynamic interplay between the local hemodynamic environment and the wall remodeling behavior determines the complexity of the natural history of atherosclerosis and explains the development of localized plaque vulnerability.

5 Article Characterization of functionally significant coronary artery disease by a coronary computed tomography angiography-based index: a comparison with positron emission tomography. 2019

Anagnostopoulos, Constantinos D / Siogkas, Panagiotis K / Liga, Riccardo / Benetos, Georgios / Maaniitty, Teemu / Sakellarios, Antonis I / Koutagiar, Iosif / Karakitsios, Ioannis / Papafaklis, Michail I / Berti, Valentina / Sciagrà, Roberto / Scholte, Arthur J H A / Michalis, Lampros K / Gaemperli, Oliver / Kaufmann, Philipp A / Pelosi, Gualtiero / Parodi, Oberdan / Knuuti, Juhani / Fotiadis, Dimitrios I / Neglia, Danilo. ·Biomedical Research Foundation of Academy of Athens, 4 Soranou Ephesiou, Athens, Greece. · University of Ioannina, Materials Science and Engineering, Ioannina, Greece. · Biomedical Research Institute, FORTH, Ioannina, Greece. · Institute of Clinical Physiology, National Research Council, Pisa, IT, Italy. · First Department of Cardiology, Hippokration Hospital, National and Kapodistrian University Medical School, Athens, Greece. · Turku PET Centre, Turku, Finland. · University of Ioannina Medical School Ioannina, Greece. · Department of Biomedical, Experimental and Clinical Sciences, Mario Serio, Nuclear Medicine Unit, University of Florence, Largo Brambilla 3, Florence, FI, Italy. · Leiden University Medical Center, Leiden, Netherlands. · University Hospital Zurich, Zurich, Switzerland. · Fondazione Toscana Gabriele Monasterio, Pisa, IT, Italy. ·Eur Heart J Cardiovasc Imaging · Pubmed #30629151.

ABSTRACT: AIMS: To test the hypothesis that virtual functional assessment index (vFAI) is related with regional flow parameters derived by quantitative positron emission tomography (PET) and can be used to assess abnormal vasodilating capability in coronary vessels with stenotic lesions at coronary computed tomography angiography (CCTA). METHODS AND RESULTS: vFAI, stress myocardial blood flow (MBF), and myocardial flow reserve (MFR) were assessed in 78 patients (mean age 62.2 ± 7.7 years) with intermediate pre-test likelihood of coronary artery disease (CAD). Coronary stenoses ≥50% were considered angiographically significant. PET was considered positive for significant CAD, when more than one contiguous segments showed stress MBF ≤2.3 mL/g/min for 15O-water or <1.79 mL/g/min for 13N-ammonia. MFR thresholds were ≤2.5 and ≤2.0, respectively. vFAI was lower in vessels with abnormal stress MBF (0.76 ± 0.10 vs. 0.89 ± 0.07, P < 0.001) or MFR (0.80 ± 0.10 vs. 0.89 ± 0.07, P < 0.001). vFAI had an accuracy of 78.6% and 75% in unmasking abnormal stress MBF and MFR in 15O-water and 82.7% and 71.2% in 13N-ammonia studies, respectively. Addition of vFAI to anatomical CCTA data increased the ability for predicting abnormal stress MBF and MFR in 15O-water studies [AUCccta + vfai = 0.866, 95% confidence interval (CI) 0.783-0.949; P = 0.013 and AUCccta + vfai = 0.737, 95% CI 0.648-0.825; P = 0.007, respectively]. An incremental value was also demonstrated for prediction of stress MBF (AUCccta + vfai = 0.887, 95% CI 0.799-0.974; P = 0.001) in 13N-ammonia studies. A similar trend was recorded for MFR (AUCccta + vfai = 0.780, 95% CI 0.632-0.929; P = 0.13). CONCLUSION: vFAI identifies accurately the presence of impaired vasodilating capability. In combination with anatomical data, vFAI enhances the diagnostic performance of CCTA.

6 Article Coronary plaque erosion developing in an area of high endothelial shear stress: insights from serial optical coherence tomography imaging. 2019

Vergallo, Rocco / Papafaklis, Michail I / D'Amario, Domenico / Michalis, Lampros K / Crea, Filippo / Porto, Italo. ·Department of Cardiovascular and Thoracic Sciences, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome. · Second Department of Cardiology, University Hospital of Ioannina, Ioannina, Greece. · Department of Cardiology, IRCCS AOU San Martino IST, Università di Genova, Genova, Italy. ·Coron Artery Dis · Pubmed #30407208.

ABSTRACT: -- No abstract --

7 Article Noninvasive CT-based hemodynamic assessment of coronary lesions derived from fast computational analysis: a comparison against fractional flow reserve. 2019

Siogkas, Panagiotis K / Anagnostopoulos, Constantinos D / Liga, Riccardo / Exarchos, Themis P / Sakellarios, Antonis I / Rigas, George / Scholte, Arthur J H A / Papafaklis, M I / Loggitsi, Dimitra / Pelosi, Gualtiero / Parodi, Oberdan / Maaniitty, Teemu / Michalis, Lampros K / Knuuti, Juhani / Neglia, Danilo / Fotiadis, Dimitrios I. ·Unit of Medical Technology and Intelligent Information Systems, Dept. of Materials Science and Engineering, University of Ioannina, Ioannina, Greece. · Center for Experimental Surgery, Clinical and Translational Research, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou St., 115 27, Athens, Greece. cdanagnostopoulos@bioacademy.gr. · Cardio-Thoracic and Vascular Department, University Hospital of Pisa, Pisa, Italy. · Department of Nuclear Medicine, University Hospital Zurich, Zürich, Switzerland. · Biomedical Research Institute - FORTH, GR 45110 Ioannina, Ioannina, Greece. · Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands. · Michaelideion Cardiac Center, Dept. of Cardiology in Medical School, University of Ioannina, 451 10, Ioannina, Greece. · CT & MRI Department Hygeia-Mitera Hospitals, Athens, Greece. · Fondazione Toscana G. Monasterio and CNR Institute of Clinical Physiology, Pisa, Italy. · Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland. ·Eur Radiol · Pubmed #30324382.

ABSTRACT: OBJECTIVES: Application of computational fluid dynamics (CFD) to three-dimensional CTCA datasets has been shown to provide accurate assessment of the hemodynamic significance of a coronary lesion. We aim to test the feasibility of calculating a novel CTCA-based virtual functional assessment index (vFAI) of coronary stenoses > 30% and ≤ 90% by using an automated in-house-developed software and to evaluate its efficacy as compared to the invasively measured fractional flow reserve (FFR). METHODS AND RESULTS: In 63 patients with chest pain symptoms and intermediate (20-90%) pre-test likelihood of coronary artery disease undergoing CTCA and invasive coronary angiography with FFR measurement, vFAI calculations were performed after 3D reconstruction of the coronary vessels and flow simulations using the finite element method. A total of 74 vessels were analyzed. Mean CTCA processing time was 25(± 10) min. There was a strong correlation between vFAI and FFR, (R = 0.93, p < 0.001) and a very good agreement between the two parameters by the Bland-Altman method of analysis. The mean difference of measurements from the two methods was 0.03 (SD = 0.033), indicating a small systematic overestimation of the FFR by vFAI. Using a receiver-operating characteristic curve analysis, the optimal vFAI cutoff value for identifying an FFR threshold of ≤ 0.8 was ≤ 0.82 (95% CI 0.81 to 0.88). CONCLUSIONS: vFAI can be effectively derived from the application of computational fluid dynamics to three-dimensional CTCA datasets. In patients with coronary stenosis severity > 30% and ≤ 90%, vFAI performs well against FFR and may efficiently distinguish between hemodynamically significant from non-significant lesions. KEY POINTS: Virtual functional assessment index (vFAI) can be effectively derived from 3D CTCA datasets. In patients with coronary stenoses severity > 30% and ≤ 90%, vFAI performs well against FFR. vFAI may efficiently distinguish between functionally significant from non-significant lesions.

8 Article Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis. 2018

Siasos, Gerasimos / Sara, Jaskanwal D / Zaromytidou, Marina / Park, Kyoung H / Coskun, Ahmet Umit / Lerman, Lilach O / Oikonomou, Evangelos / Maynard, Charles C / Fotiadis, Dimitris / Stefanou, Kostas / Papafaklis, Michail / Michalis, Lampros / Feldman, Charles / Lerman, Amir / Stone, Peter H. ·Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Division of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota. · 1(st) Department of Cardiology, National and Kapodistrian University of Athens Medical School, Hippokration Hospital, Athens, Greece. · University of Washington, Seattle, Washington. · Medical School, University of Ioannina, Ioannina, Greece. · Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: pstone@bwh.harvard.edu. ·J Am Coll Cardiol · Pubmed #29747829.

ABSTRACT: BACKGROUND: Local hemodynamic factors are important determinants of atherosclerotic plaque development and progression. OBJECTIVES: The goal of this study was to determine the association between low endothelial shear stress (ESS) and microvascular and epicardial endothelial dysfunction in patients with early atherosclerosis. METHODS: Sixty-five patients (mean age 52 ± 11 years) with nonobstructive coronary atherosclerosis (luminal diameter stenosis <30%) were included. Microvascular and epicardial coronary endothelial function was assessed by using intracoronary acetylcholine infusion. Vascular profiling, using 2-plane coronary angiography and intravascular ultrasound, was used to reconstruct the three-dimensional anatomy of the left anterior descending artery. Each reconstructed artery was divided into sequential 3-mm segments and analyzed for local ESS with computational fluid dynamics; that is, lower ESS levels at both a 3-mm regional level (average ESS and low ESS) and at a vessel level (lowest ESS per artery) and for plaque characteristics (plaque area, plaque thickness, and plaque burden). RESULTS: Coronary segments in arteries with abnormal microvascular function exhibited lower ESS compared with segments in arteries with normal microvascular function (average ESS: 1.67 ± 1.04 Pa vs. 2.03 ± 1.72 Pa [p = 0.050]; lowest ESS: 0.54 ± 0.25 Pa vs. 0.72 ± 0.32 Pa [p = 0.014]). Coronary segments in arteries with abnormal epicardial endothelial function also exhibited significantly lower ESS compared with segments in arteries with normal epicardial function (average ESS: 1.49 ± 0.89 Pa vs. 1.93 ± 1.50 Pa [p < 0.0001]; low ESS: 1.26 ± 0.81 Pa vs. 1.56 ± 1.30 Pa [p = 0.001]; lowest ESS: 0.51 ± 0.27 Pa vs. 0.65 ± 0.29 Pa [p = 0.080]). Patients with abnormal microvascular endothelial function exhibited a progressive decrease in average and low ESS, starting from patients with normal epicardial endothelial function to those with both microvascular and epicardial endothelial dysfunction (p < 0.0001 and p = 0.004, respectively). CONCLUSIONS: These data indicate an association between dysfunction of the microvascular and epicardial endothelium and local ESS at the early stages of coronary atherosclerosis in humans.

9 Article Association between fractional flow reserve, instantaneous wave-free ratio and dobutamine stress echocardiography in patients with stable coronary artery disease. 2018

Panoulas, Vasileios F / Keramida, Kalliopi / Boletti, Olga / Papafaklis, Michail I / Flessas, Dimitris / Petropoulou, Maria / Nihoyannopoulos, Petros. ·Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom. ·EuroIntervention · Pubmed #28966160.

ABSTRACT: AIMS: The association between fractional flow reserve (FFR) and dobutamine stress echocardiography (DSE) in real-world stable angina patients is scant and controversial whereas no such comparison exists with instantaneous wave-free ratio (iFR). The current retrospective study aimed to investigate the associations among these modalities in patients with stable coronary artery disease (CAD) and intermediate coronary lesions. METHODS AND RESULTS: We studied 62 consecutive stable angina patients who underwent DSE and subsequently coronary angiography with FFR (in all 62) and iFR (in 46/62 patients) assessment of intermediate single-vessel lesions between 2014 and 2015. Using receiver operating characteristic (ROC) curves we sought to identify the optimal FFR and iFR cut-off points with the highest discriminative power to predict the DSE result. The kappa coefficient was used to assess the agreement between FFR, iFR and DSE. The mean age of the study cohort was 63.5±12 years and 35 (56.5%) were males. Thirteen (21%) lesions were adjudicated as causing reversible ischaemia on DSE. Using ROC (FFR predicting DSE result), the area under the curve was 0.952 (95% CI: 0.902 to 1), whereas for iFR it was 0.743 (95% CI: 0.560 to 0.927), pAUC comparison=0.03. The optimal FFR cut-off point predicting positive DSE was 0.80. There was strong agreement between DSE and FFR (kappa 0.682, p<0.001). There was only modest agreement between iFR and DSE (kappa 0.258, p=0.068) using a cut-off value of 0.9. CONCLUSIONS: In patients referred for evaluation of stable CAD, there was good agreement between DSE and FFR (87%) but less so with iFR (71.7%).

10 Article Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events: The PROSPECT Study. 2018

Stone, Peter H / Maehara, Akiko / Coskun, Ahmet Umit / Maynard, Charles C / Zaromytidou, Marina / Siasos, Gerasimos / Andreou, Ioannis / Fotiadis, Dimitris / Stefanou, Kostas / Papafaklis, Michail / Michalis, Lampros / Lansky, Alexandra J / Mintz, Gary S / Serruys, Patrick W / Feldman, Charles L / Stone, Gregg W. ·Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School Boston, Massachusetts. Electronic address: pstone@partners.org. · Division of Cardiology, New York Presbyterian Hospital, Columbia University Medical Center, and the Cardiovascular Research Foundation, New York, New York. · Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School Boston, Massachusetts. · Department of Health Services, University of Washington, Seattle, Washington. · Department of Materials Science and Engineering, University of Ioannina, Ioannina, Greece. · Section of Cardiology, Yale University School of Medicine, New Haven, Connecticut. · International Centre for Cardiovascular Health, Imperial College, London, United Kingdom. ·JACC Cardiovasc Imaging · Pubmed #28917684.

ABSTRACT: OBJECTIVES: This study sought to determine whether low endothelial shear stress (ESS) adds independent prognostication for future major adverse cardiac events (MACE) in coronary lesions in patients with high-risk acute coronary syndrome (ACS) from the United States and Europe. BACKGROUND: Low ESS is a proinflammatory, proatherogenic stimulus associated with coronary plaque development, progression, and destabilization in human-like animal models and in humans. Previous natural history studies including baseline ESS characterization investigated low-risk patients. METHODS: In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with ACS underwent 3-vessel intracoronary imaging. Independent predictors of MACE attributable to untreated nonculprit (nc) coronary lesions during 3.4-year follow-up were large plaque burden (PB), small minimum lumen area (MLA), and thin-cap fibroatheroma (TCFA) morphology. In this analysis, baseline ESS of nc lesions leading to new MACE (nc-MACE lesions) and randomly selected control nc lesions without MACE (nc-non-MACE lesions) were calculated. A propensity score for ESS was constructed for each lesion, and the relationship between ESS and subsequent nc-MACE was examined. RESULTS: A total of 145 lesions were analyzed in 97 patients: 23 nc-MACE lesions (13 TCFAs, 10 thick-cap fibroatheromas [ThCFAs]), and 122 nc-non-MACE lesions (63 TCFAs, 59 ThCFAs). Low local ESS (<1.3 Pa) was strongly associated with subsequent nc-MACE compared with physiological/high ESS (≥1.3 Pa) (23 of 101 [22.8%]) versus (0 of 44 [0%]). In propensity-adjusted Cox regression, low ESS was strongly associated with MACE (hazard ratio: 4.34; 95% confidence interval: 1.89 to 10.00; p < 0.001). Categorizing plaques by anatomic risk (high risk: ≥2 high-risk characteristics PB ≥70%, MLA ≤4 mm CONCLUSIONS: Local low ESS provides incremental risk stratification of untreated coronary lesions in high-risk patients, beyond measures of PB, MLA, and morphology.

11 Article Targeted Near-Infrared Fluorescence Imaging of Atherosclerosis: Clinical and Intracoronary Evaluation of Indocyanine Green. 2016

Verjans, Johan W / Osborn, Eric A / Ughi, Giovanni J / Calfon Press, Marcella A / Hamidi, Ehsan / Antoniadis, Antonios P / Papafaklis, Michail I / Conrad, Mark F / Libby, Peter / Stone, Peter H / Cambria, Richard P / Tearney, Guillermo J / Jaffer, Farouc A. ·Cardiovascular Research Center, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts; Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands. · Cardiovascular Research Center, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts; Cardiology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. · Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Cardiovascular Research Center, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts. · Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Division of Vascular Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: gtearney@mgh.harvard.edu. · Cardiovascular Research Center, Division of Cardiology, Massachusetts General Hospital, Boston, Massachusetts; Cardiology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: fjaffer@mgh.harvard.edu. ·JACC Cardiovasc Imaging · Pubmed #27544892.

ABSTRACT: OBJECTIVES: This study sought to determine whether indocyanine green (ICG)-enhanced near-infrared fluorescence (NIRF) imaging can illuminate high-risk histologic plaque features of human carotid atherosclerosis, and in coronary atheroma of living swine, using intravascular NIRF-optical coherence tomography (OCT) imaging. BACKGROUND: New translatable imaging approaches are needed to identify high-risk biological signatures of atheroma. ICG is a U.S. Food and Drug Administration-approved NIRF imaging agent that experimentally targets plaque macrophages and lipid in areas of enhanced endothelial permeability. However, it is unknown whether ICG can target atheroma in patients. METHODS: Eight patients were enrolled in the BRIGHT-CEA (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque) trial. Five patients were injected intravenously with ICG 99 ± 25 min before clinically indicated carotid endarterectomy. Three saline-injected endarterectomy patients served as control subjects. Excised plaques underwent analysis by intravascular NIRF-OCT, reflectance imaging, microscopy, and histopathology. Next, following ICG intravenous injection, in vivo intracoronary NIRF-OCT and intravascular ultrasound imaged 3 atheroma-bearing coronary arteries of a diabetic, cholesterol-fed swine. RESULTS: ICG was well tolerated; no adverse clinical events occurred up to 30 days post-injection. Multimodal NIRF imaging including intravascular NIRF-OCT revealed that ICG accumulated in all endarterectomy specimens. Plaques from saline-injected control patients exhibited minimal NIRF signal. In the swine experiment, intracoronary NIRF-OCT identified ICG uptake in all intravascular ultrasound-identified plaques in vivo. On detailed microscopic evaluation, ICG localized to plaque areas exhibiting impaired endothelial integrity, including disrupted fibrous caps, and within areas of neovascularization. Within human plaque areas of endothelial abnormality, ICG was spatially related to localized zones of plaque macrophages and lipid, and, notably, intraplaque hemorrhage. CONCLUSIONS: This study demonstrates that ICG targets human plaques exhibiting endothelial abnormalities and provides new insights into its targeting mechanisms in clinical and experimental atheroma. Intracoronary NIRF-OCT of ICG may offer a novel, clinically translatable approach to image pathobiological aspects of coronary atherosclerosis. (Indocyanine Green Fluorescence Uptake in Human Carotid Artery Plaque [BRIGHT-CEA]; NCT01873716).

12 Article Effect of the local hemodynamic environment on the de novo development and progression of eccentric coronary atherosclerosis in humans: insights from PREDICTION. 2015

Papafaklis, Michail I / Takahashi, Saeko / Antoniadis, Antonios P / Coskun, Ahmet U / Tsuda, Masaya / Mizuno, Shingo / Andreou, Ioannis / Nakamura, Shigeru / Makita, Yasuhiro / Hirohata, Atsushi / Saito, Shigeru / Feldman, Charles L / Stone, Peter H. ·Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. · Shonan Kamakura General Hospital, Kamakura, Japan. · Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA. · Kyoto Katsura Hospital, Kyoto, Japan. · Hakodate Municipal Hospital, Hakodate, Japan. · Sakakibara Heart Institute of Okayama, Okayama, Japan. · Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: pstone@partners.org. ·Atherosclerosis · Pubmed #25801012.

ABSTRACT: BACKGROUND: Eccentric distribution of atheroma has been associated with plaques likely to rupture and cause an acute coronary syndrome, but the factors responsible for the development of eccentricity remain unknown. Endothelial shear stress (ESS) drives plaque formation. We aimed to investigate the role of the local ESS characteristics in the de novo development and progressive worsening of plaque eccentricity in humans. METHODS: Vascular profiling (3-vessel 3D coronary reconstruction by angiography/intravascular ultrasound, and blood flow simulation for ESS computation) was performed in 374 patients at baseline & 6-10 months follow-up. At baseline, we identified (i) disease-free segments (n=2157), and (ii) diseased regions of luminal obstructions (n=408). RESULTS: In disease-free regions, baseline low ESS magnitude (p<0.001), marked ESS circumferential heterogeneity (p=0.001), and their interaction (p=0.026) were associated with an increased probability of de novo eccentric plaque formation at follow-up. In diseased regions, baseline low ESS (odds ratio [OR]: 2.33, p=0.003) and large plaque burden (OR: 2.46, p=0.002) were independent predictors of substantially increasing plaque eccentricity index with worsening lumen encroachment. This combined outcome was more frequent in obstructions with both features vs. all others (33 vs. 12%; p<0.001). The incidence of percutaneous coronary intervention in worsening obstructions with increasing plaque eccentricity was higher (13.3 vs. 4.3%, p=0.011). CONCLUSIONS: The local hemodynamic environment has a critical effect on the development of eccentric coronary plaques at both an early and advanced stage of atherosclerosis. Local ESS assessment could help in predicting sites prone to plaque disruption and acute coronary syndromes in humans.

13 Article Anatomically correct three-dimensional coronary artery reconstruction using frequency domain optical coherence tomographic and angiographic data: head-to-head comparison with intravascular ultrasound for endothelial shear stress assessment in humans. 2015

Papafaklis, Michail I / Bourantas, Christos V / Yonetsu, Taishi / Vergallo, Rocco / Kotsia, Anna / Nakatani, Shimpei / Lakkas, Lampros S / Athanasiou, Lambros S / Naka, Katerina K / Fotiadis, Dimitrios I / Feldman, Charles L / Stone, Peter H / Serruys, Patrick W / Jang, Ik-Kyung / Michalis, Lampros K. ·Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. ·EuroIntervention · Pubmed #24974809.

ABSTRACT: AIMS: To develop a methodology that permits accurate 3-dimensional (3D) reconstruction from FD-OCT and angiographic data enabling reliable evaluation of the ESS distribution, and to compare the FD-OCT-derived models against the established models based on angiography/IVUS. METHODS AND RESULTS: Fifteen patients (17 coronary arteries) who underwent angiography, FD-OCT and IVUS examination during the same procedure were studied. The FD-OCT and IVUS lumen borders were placed onto the 3D luminal centreline derived from angiographic data. Three-dimensional geometry algorithms and anatomical landmarks were used to estimate the orientation of the borders appropriately. ESS was calculated using computational fluid dynamics. In 188 corresponding consecutive 3-mm segments, FD-OCT- and IVUS-derived models were highly correlated for lumen area (r=0.96) and local ESS (r=0.89) measurements. FD-OCT-based 3D reconstructions had a high diagnostic accuracy for detecting regions exposed to proatherogenic low ESS identified on the IVUS-based 3D models, considered as the gold standard (receiver operator characteristic area under the curve: 94.9%). CONCLUSIONS: FD-OCT-based 3D coronary reconstruction provides anatomically correct models and permits reliable ESS computation. ESS assessment in combination with the superior definition of plaque characteristics by FD-OCT is expected to provide valuable insights into the effect of the haemodynamic environment on the development and destabilisation of high-risk plaques.

14 Article Endothelial shear stress and coronary plaque characteristics in humans: combined frequency-domain optical coherence tomography and computational fluid dynamics study. 2014

Vergallo, Rocco / Papafaklis, Michail I / Yonetsu, Taishi / Bourantas, Christos V / Andreou, Ioannis / Wang, Zhao / Fujimoto, James G / McNulty, Iris / Lee, Hang / Biasucci, Luigi M / Crea, Filippo / Feldman, Charles L / Michalis, Lampros K / Stone, Peter H / Jang, Ik-Kyung. ·From the Department of Medicine, Cardiology Division (R.V., T.Y., I.M., I.-K.J.) and Department of Medicine, Biostatistics Center (H.L.), Massachusetts General Hospital, and Department of Medicine, Cardiovascular Division, Brigham & Women's Hospital (M.I.P., I.A., C.L.F., P.H.S.), Harvard Medical School, Boston, MA; Department of Interventional Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands (C.V.B.); Department of Electrical Engineering and Computer Science, and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA (Z.W., J.G.F.); Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy (L.M.B., F.C.); and Department of Cardiology, Medical School, University of Ioannina, Ioannina, Greece (L.K.M.). · From the Department of Medicine, Cardiology Division (R.V., T.Y., I.M., I.-K.J.) and Department of Medicine, Biostatistics Center (H.L.), Massachusetts General Hospital, and Department of Medicine, Cardiovascular Division, Brigham & Women's Hospital (M.I.P., I.A., C.L.F., P.H.S.), Harvard Medical School, Boston, MA; Department of Interventional Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, The Netherlands (C.V.B.); Department of Electrical Engineering and Computer Science, and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, MA (Z.W., J.G.F.); Department of Cardiovascular Medicine, Catholic University of the Sacred Heart, Rome, Italy (L.M.B., F.C.); and Department of Cardiology, Medical School, University of Ioannina, Ioannina, Greece (L.K.M.) ijang@partners.org. ·Circ Cardiovasc Imaging · Pubmed #25190591.

ABSTRACT: BACKGROUND: Despite the exposure of the entire vasculature to the atherogenic effects of systemic risk factors, atherosclerotic plaques preferentially develop at sites with disturbed flow. This study aimed at exploring in vivo the relationship between local endothelial shear stress (ESS) and coronary plaque characteristics in humans using computational fluid dynamics and frequency-domain optical coherence tomography. METHODS AND RESULTS: Three-dimensional coronary artery reconstruction was performed in 21 patients (24 arteries) presenting with acute coronary syndrome using frequency-domain optical coherence tomography and coronary angiography. Each coronary artery was divided into sequential 3-mm segments and analyzed for the assessment of local ESS and plaque characteristics. A total of 146 nonculprit segments were evaluated. Compared with segments with higher ESS [≥1 Pascal (Pa)], those with low ESS (<1 Pa) showed higher prevalence of lipid-rich plaques (37.5% versus 20.0%; P=0.019) and thin-cap fibroatheroma (12.5% versus 2.0%; P=0.037). Overall, lipid plaques in segments with low ESS had thinner fibrous cap (115 μm [63-166] versus 170 μm [107-219]; P=0.004) and higher macrophage density (normalized standard deviation: 8.4% [4.8-12.6] versus 6.2% [4.2-8.8]; P=0.017). Segments with low ESS showed more superficial calcifications (minimum calcification depth: 93 μm [50-140] versus 152 μm [105-258]; P=0.049) and tended to have higher prevalence of spotty calcifications (26.0% versus 12.0%; P=0.076). CONCLUSIONS: Coronary regions exposed to low ESS are associated with larger lipid burden, thinner fibrous cap, and higher prevalence of thin-cap fibroatheroma in humans. Frequency-domain optical coherence tomography-based assessment of ESS and wall characteristics may be useful in identifying vulnerable coronary regions. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538.

15 Article Short- and long-term implications of a bioresorbable vascular scaffold implantation on the local endothelial shear stress patterns. 2014

Bourantas, Christos V / Papafaklis, Michail I / Garcia-Garcia, Hector M / Farooq, Vasim / Diletti, Roberto / Muramatsu, Takashi / Zhang, Yaojun / Kalatzis, Fanis G / Naka, Katerina K / Fotiadis, Dimitrios I / Onuma, Yoshinobu / Michalis, Lampros K / Serruys, Patrick W. ·ThoraxCenter, Erasmus Medical Center, Rotterdam, the Netherlands. · Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. · Department of Materials Science and Engineering, University of Ioannina, Ioannina, Greece. · Department of Cardiology, University of Ioannina, Ioannina, Greece. · ThoraxCenter, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address: p.w.j.c.serruys@erasmusmc.nl. ·JACC Cardiovasc Interv · Pubmed #24456718.

ABSTRACT: -- No abstract --

16 Article Synergistic effect of local endothelial shear stress and systemic hypercholesterolemia on coronary atherosclerotic plaque progression and composition in pigs. 2013

Koskinas, Konstantinos C / Chatzizisis, Yiannis S / Papafaklis, Michail I / Coskun, Ahmet U / Baker, Aaron B / Jarolim, Petr / Antoniadis, Antonios / Edelman, Elazer R / Stone, Peter H / Feldman, Charles L. ·Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States; Harvard-MIT Division of Health Sciences & Technology, Massachusetts Institute of Technology, Cambridge, MA, United States. ·Int J Cardiol · Pubmed #24148915.

ABSTRACT: BACKGROUND: Systemic risk factors and local hemodynamic factors both contribute to coronary atherosclerosis, but their possibly synergistic inter-relationship remains unknown. The purpose of this natural history study was to investigate the combined in-vivo effect of varying levels of systemic hypercholesterolemia and local endothelial shear stress (ESS) on subsequent plaque progression and histological composition. METHODS: Diabetic, hyperlipidemic swine with higher systemic total cholesterol (TC) (n=4) and relatively lower TC levels (n=5) underwent three-vessel intravascular ultrasound (IVUS) at 3-5 consecutive time-points in-vivo. ESS was calculated serially using computational fluid dynamics. 3-D reconstructed coronary arteries were divided into 3mm-long segments (n=595), which were stratified according to higher vs. relatively lower TC and low (<1.2Pa) vs. higher local ESS (≥1.2Pa). Arteries were harvested at 9months, and a subset of segments (n=114) underwent histopathologic analyses. RESULTS: Change of plaque volume (ΔPV) by IVUS over time was most pronounced in low-ESS segments from higher-TC animals. Notably, higher-ESS segments from higher-TC animals had greater ΔPV compared to low-ESS segments from lower-TC animals (p<0.001). The time-averaged ESS in segments that resulted in significant plaque increased with increasing TC levels (slope: 0.24Pa/100mg/dl; r=0.80; p<0.01). At follow-up, low-ESS segments from higher-TC animals had the highest mRNA levels of lipoprotein receptors and inflammatory mediators and, consequently, the greatest lipid accumulation and inflammation. CONCLUSIONS: This study redefines the principle concept that "low" ESS promotes coronary plaque growth and vulnerability by demonstrating that: (i.) the pro-atherogenic threshold of low ESS is not uniform, but cholesterol-dependent; and (ii.) the atherogenic effects of local low ESS are amplified, and the athero-protective effects of higher ESS may be outweighed, by increasing cholesterol levels. Intense hypercholesterolemia and very low ESS are synergistic in favoring rapid atheroma progression and high-risk composition.

17 Article Prediction of coronary atherosclerosis progression using dynamic Bayesian networks. 2013

Exarchos, Konstantinos P / Exarchos, Themis P / Bourantas, Christos V / Papafaklis, Michail I / Naka, Katerina K / Michalis, Lampros K / Parodi, Oberdan / Fotiadis, Dimitrios I. · ·Conf Proc IEEE Eng Med Biol Soc · Pubmed #24110581.

ABSTRACT: In this paper we propose a methodology for predicting the progression of atherosclerosis in coronary arteries using dynamic Bayesian networks. The methodology takes into account patient data collected at the baseline study and the same data collected in the follow-up study. Our aim is to analyze all the different sources of information (Demographic, Clinical, Biochemical profile, Inflammatory markers, Treatment characteristics) in order to predict possible manifestations of the disease; subsequently, our purpose is twofold: i) to identify the key factors that dictate the progression of atherosclerosis and ii) based on these factors to build a model which is able to predict the progression of atherosclerosis for a specific patient, providing at the same time information about the underlying mechanism of the disease.

18 Article Thin-capped atheromata with reduced collagen content in pigs develop in coronary arterial regions exposed to persistently low endothelial shear stress. 2013

Koskinas, Konstantinos C / Sukhova, Galina K / Baker, Aaron B / Papafaklis, Michail I / Chatzizisis, Yiannis S / Coskun, Ahmet U / Quillard, Thibaut / Jonas, Michael / Maynard, Charles / Antoniadis, Antonios P / Shi, Guo-Ping / Libby, Peter / Edelman, Elazer R / Feldman, Charles L / Stone, Peter H. ·Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ·Arterioscler Thromb Vasc Biol · Pubmed #23640495.

ABSTRACT: OBJECTIVE: The mechanisms promoting the focal formation of rupture-prone coronary plaques in vivo remain incompletely understood. This study tested the hypothesis that coronary regions exposed to low endothelial shear stress (ESS) favor subsequent development of collagen-poor, thin-capped plaques. APPROACH AND RESULTS: Coronary angiography and 3-vessel intravascular ultrasound were serially performed at 5 consecutive time points in vivo in 5 diabetic, hypercholesterolemic pigs. ESS was calculated along the course of each artery with computational fluid dynamics at all 5 time points. At follow-up, 184 arterial segments with previously identified in vivo ESS underwent histopathologic analysis. Compared with other plaque types, eccentric thin-capped atheromata developed more in segments that experienced lower ESS during their evolution. Compared with lesions with higher preceding ESS, segments persistently exposed to low ESS (<1.2 Pa) exhibited reduced intimal smooth muscle cell content; marked intimal smooth muscle cell phenotypic modulation; attenuated procollagen-I gene expression; increased gene and protein expression of the interstitial collagenases matrix-metalloproteinase-1, -8, -13, and -14; increased collagenolytic activity; reduced collagen content; and marked thinning of the fibrous cap. CONCLUSIONS: Eccentric thin-capped atheromata, lesions particularly prone to rupture, form more frequently in coronary regions exposed to low ESS throughout their evolution. By promoting an imbalance of attenuated synthesis and augmented collagen breakdown, low ESS favors the focal evolution of early lesions toward plaques with reduced collagen content and thin fibrous caps-2 critical determinants of coronary plaque vulnerability.

19 Article Relation of distribution of coronary blood flow volume to coronary artery dominance. 2013

Sakamoto, Shingo / Takahashi, Saeko / Coskun, Ahmet U / Papafaklis, Michail I / Takahashi, Akihiko / Saito, Shigeru / Stone, Peter H / Feldman, Charles L. ·Sakurakai Takahashi Hospital, Kobe, Japan. ·Am J Cardiol · Pubmed #23540543.

ABSTRACT: Coronary artery dominance influences the amount and anatomic location of myocardium that is perfused by the left or right coronary circulation. However, it is unknown whether coronary artery dominance also influences the distribution of coronary blood flow volume. The aim of this study was to evaluate volumetric coronary blood flow in 1,322 vessels from 496 patients in the Prediction of Progression of Coronary Artery Disease and Clinical Outcomes Using Vascular Profiling of Endothelial Shear Stress and Arterial Wall Morphology (PREDICTION) study. Patients were divided into 2 groups (right-dominant and left-dominant or balanced circulation). Coronary blood flow volume was calculated by coronary segment volume measurement using angiography and intravascular ultrasound and the contrast transit time through the segment. Coronary blood flow in the left circumflex coronary artery was significantly higher in left-dominant or balanced circulation than in right-dominant circulation (113 ± 43 vs 72 ± 37 ml/min, p <0.001), whereas flow in the right coronary artery was significantly lower in left-dominant or balanced circulation than in right-dominant circulation (56 ± 40 vs 113 ± 49 ml/min, p = 0.003). There was no significant difference in the left anterior descending coronary artery. In conclusion, coronary artery dominance has an impact on coronary blood flow volume in the left circumflex and right coronary arteries but not in the left anterior descending coronary artery. These findings suggest that the extent of myocardial perfusion area is associated with coronary blood flow volume.

20 Article The negative impact of incomplete angiographic revascularization on clinical outcomes and its association with total occlusions: the SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) trial. 2013

Farooq, Vasim / Serruys, Patrick W / Garcia-Garcia, Hector M / Zhang, Yaojun / Bourantas, Christos V / Holmes, David R / Mack, Michael / Feldman, Ted / Morice, Marie-Claude / Ståhle, Elisabeth / James, Stefan / Colombo, Antonio / Diletti, Roberto / Papafaklis, Michail I / de Vries, Ton / Morel, Marie-Angèle / van Es, Gerrit Anne / Mohr, Friedrich W / Dawkins, Keith D / Kappetein, Arie-Pieter / Sianos, Georgios / Boersma, Eric. ·Department of Interventional Cardiology, Erasmus University Medical Centre, Thoraxcenter, Rotterdam, the Netherlands. ·J Am Coll Cardiol · Pubmed #23265332.

ABSTRACT: OBJECTIVES: The study sought to evaluate the clinical impact of angiographic complete (CR) and incomplete (ICR) revascularization and its association with the presence of total occlusions (TO), after percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery in the "all-comers" SYNTAX (Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) trial. BACKGROUND: In patients with complex coronary artery disease undergoing PCI or CABG, the long-term prognostic implications of CR versus ICR is unsettled. METHODS: In this post hoc study, consisting of randomized (n = 1,800) and nested PCI (n = 198) and CABG (n = 649) registries, 4-year clinical outcomes were compared in groups, with and without angiographic CR, in the PCI and CABG arms. Clinical outcomes were analyzed with Kaplan-Meier estimates, log-rank comparisons, and Cox regression analyses. Multivariate predictors of ICR were determined. Similar analyses were undertaken in the TO and non-TO treated groups of both study arms. RESULTS: Angiographic CR was achieved in 52.8% of the PCI arm and 66.9% of the CABG arm. Within the PCI and CABG arms, ICR (compared with CR) seemed to be a surrogate marker of a greater burden of anatomical coronary complexity and clinical comorbidity and was associated with significantly higher frequencies of 4-year mortality, all-cause revascularization, stent thrombosis (PCI arm), and major adverse cardiac and cerebrovascular events. The presence of a TO was the strongest independent predictor of ICR after PCI (hazard ratio: 2.70, 95% confidence interval: 1.98 to 3.67, p < 0.001). Eight hundred and forty patients (PCI: 26.3%, CABG: 36.4%, p < 0.001) were identified to have 1,007 TOs, with 68.1% of TOs located in the proximal-mid coronary vasculature. The findings associating ICR (compared with CR) with higher frequencies of 4-year mortality and major adverse cardiac and cerebrovascular events remained consistent in the TO-treated groups in the PCI and CABG arms. CONCLUSIONS: Within the PCI and CABG arms of the all-comers SYNTAX trial, angiographically determined ICR has a detrimental impact on long-term clinical outcomes, including mortality. This effect remained consistent in patients with and without TOs.

21 Article Prediction of progression of coronary artery disease and clinical outcomes using vascular profiling of endothelial shear stress and arterial plaque characteristics: the PREDICTION Study. 2012

Stone, Peter H / Saito, Shigeru / Takahashi, Saeko / Makita, Yasuhiro / Nakamura, Shigeru / Kawasaki, Tomohiro / Takahashi, Akihiko / Katsuki, Takaaki / Nakamura, Sunao / Namiki, Atsuo / Hirohata, Atsushi / Matsumura, Toshiyuki / Yamazaki, Seiji / Yokoi, Hiroyoshi / Tanaka, Shinji / Otsuji, Satoru / Yoshimachi, Fuminobu / Honye, Junko / Harwood, Dawn / Reitman, Martha / Coskun, Ahmet U / Papafaklis, Michail I / Feldman, Charles L / Anonymous4980729. ·Brigham & Women's Hospital, Harvard Medical School, Boston, MA, USA. pstone@partners.org ·Circulation · Pubmed #22723305.

ABSTRACT: BACKGROUND: Atherosclerotic plaques progress in a highly individual manner. The purposes of the Prediction of Progression of Coronary Artery Disease and Clinical Outcome Using Vascular Profiling of Shear Stress and Wall Morphology (PREDICTION) Study were to determine the role of local hemodynamic and vascular characteristics in coronary plaque progression and to relate plaque changes to clinical events. METHODS AND RESULTS: Vascular profiling, using coronary angiography and intravascular ultrasound, was used to reconstruct each artery and calculate endothelial shear stress and plaque/remodeling characteristics in vivo. Three-vessel vascular profiling (2.7 arteries per patient) was performed at baseline in 506 patients with an acute coronary syndrome treated with a percutaneous coronary intervention and in a subset of 374 (74%) consecutive patients 6 to 10 months later to assess plaque natural history. Each reconstructed artery was divided into sequential 3-mm segments for serial analysis. One-year clinical follow-up was completed in 99.2%. Symptomatic clinical events were infrequent: only 1 (0.2%) cardiac death; 4 (0.8%) patients with new acute coronary syndrome in nonstented segments; and 15 (3.0%) patients hospitalized for stable angina. Increase in plaque area (primary end point) was predicted by baseline large plaque burden; decrease in lumen area (secondary end point) was independently predicted by baseline large plaque burden and low endothelial shear stress. Large plaque size and low endothelial shear stress independently predicted the exploratory end points of increased plaque burden and worsening of clinically relevant luminal obstructions treated with a percutaneous coronary intervention at follow-up. The combination of independent baseline predictors had a 41% positive and 92% negative predictive value to predict progression of an obstruction treated with a percutaneous coronary intervention. CONCLUSIONS: Large plaque burden and low local endothelial shear stress provide independent and additive prediction to identify plaques that develop progressive enlargement and lumen narrowing. CLINICAL TRIAL REGISTRATION: URL: http:www.//clinicaltrials.gov. Unique Identifier: NCT01316159.

22 Article Augmented expression and activity of extracellular matrix-degrading enzymes in regions of low endothelial shear stress colocalize with coronary atheromata with thin fibrous caps in pigs. 2011

Chatzizisis, Yiannis S / Baker, Aaron B / Sukhova, Galina K / Koskinas, Konstantinos C / Papafaklis, Michail I / Beigel, Roy / Jonas, Michael / Coskun, Ahmet U / Stone, Benjamin V / Maynard, Charles / Shi, Guo-Ping / Libby, Peter / Feldman, Charles L / Edelman, Elazer R / Stone, Peter H. ·Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. pstone@partners.org ·Circulation · Pubmed #21282495.

ABSTRACT: Background- The molecular mechanisms that determine the localized formation of thin-capped atheromata in the coronary arteries remain unknown. This study tested the hypothesis that low endothelial shear stress augments the expression of matrix-degrading proteases and thereby promotes the formation of thin-capped atheromata. Methods and Results- Intravascular ultrasound-based, geometrically correct 3-dimensional reconstruction of the coronary arteries of 12 swine was performed in vivo 23 weeks after initiation of diabetes mellitus and a hyperlipidemic diet. Local endothelial shear stress was calculated in plaque-free subsegments of interest (n=142) with computational fluid dynamics. At week 30, the coronary arteries (n=31) were harvested and the same subsegments were identified. The messenger RNA and protein expression and elastolytic activity of selected elastases and their endogenous inhibitors were assessed. Subsegments with low preceding endothelial shear stress at week 23 showed reduced endothelial coverage, enhanced lipid accumulation, and intense infiltration of activated inflammatory cells at week 30. These lesions showed increased expression of messenger RNAs encoding matrix metalloproteinase-2, -9, and -12, and cathepsins K and S relative to their endogenous inhibitors and increased elastolytic activity. Expression of these enzymes correlated positively with the severity of internal elastic lamina fragmentation. Thin-capped atheromata developed in regions with lower preceding endothelial shear stress and had reduced endothelial coverage, intense lipid and inflammatory cell accumulation, enhanced messenger RNA expression and elastolytic activity of MMPs and cathepsins, and severe internal elastic lamina fragmentation. Conclusions- Low endothelial shear stress induces endothelial discontinuity and accumulation of activated inflammatory cells, thereby augmenting the expression and activity of elastases in the intima and shifting the balance with their inhibitors toward matrix breakdown. Our results provide new insight into the mechanisms of regional formation of plaques with thin fibrous caps.

23 Article Eight-year clinical outcome after radioactive stent implantation: a treatment failure without irreversible long-term clinical sequelae. 2011

Sianos, Georgios / Papafaklis, Michail I / van Domburg, Ron / Adams, Denise / van Nierop, Josephine Wi / van der Giessen, Willem J / Serruys, Patrick W. ·Department of Interventional Cardiology, Thoraxcenter, Erasmus Medical Centre, Rotterdam, The Netherlands. gsianos@guth.gr ·EuroIntervention · Pubmed #21205589.

ABSTRACT: AIMS: To assess the long-term outcome of patients who underwent radioactive stent (RS) implantation. METHODS AND RESULTS: The RS study population consisted of 133 consecutive patients who underwent RS implantation between November 1997 and July 2000. They were matched using the propensity score method with 266 patients who underwent bare metal stenting (BMS) in the same span. Long-term survival status and information on MACE (death, non-fatal myocardial infarction or any re-intervention) was retrospectively obtained. Eight-year cumulative survival (90.2% vs. 87.4%, p = 0.57) was similar between the RS and BMS group respectively, while 8-year cumulative MACE-free survival was significantly lower in RS patients (42.1% vs. 64.3%, p < 0.001) due to the difference in events (mainly target lesion revascularisations [TLRs]) during the first year of follow-up (cumulative 1-year MACE-free survival: 59.4% vs. 86.7%, p < 0.001); there was no difference in the MACE rate after the first year (p = 0.71). The TLR rate at six months in the RS group was 29.3%, mainly due to edge restenosis and at one year 36.2% (control group: 9.5%, p < 0.001). CONCLUSIONS: A high incidence of MACE and re-intervention was observed during the first year following RS implantation, mainly related to TLR for edge restenosis. After the first year, the clinical outcome of RS patients was similar to the control group indicating that there are no late adverse effects related to low dose-rate intracoronary radiation therapy.

24 Article Natural history of experimental coronary atherosclerosis and vascular remodeling in relation to endothelial shear stress: a serial, in vivo intravascular ultrasound study. 2010

Koskinas, Konstantinos C / Feldman, Charles L / Chatzizisis, Yiannis S / Coskun, Ahmet U / Jonas, Michael / Maynard, Charles / Baker, Aaron B / Papafaklis, Michail I / Edelman, Elazer R / Stone, Peter H. ·Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA. ·Circulation · Pubmed #20439786.

ABSTRACT: BACKGROUND: The natural history of heterogeneous atherosclerotic plaques and the role of local hemodynamic factors throughout their development are unknown. We performed a serial study to assess the role of endothelial shear stress (ESS) and vascular remodeling in the natural history of coronary atherosclerosis. METHODS AND RESULTS: Intravascular ultrasound-based 3-dimensional reconstruction of all major coronary arteries (n=15) was performed serially in vivo in 5 swine 4, 11, 16, 23, and 36 weeks after induction of diabetes mellitus and hyperlipidemia. The reconstructed arteries were divided into 3-mm-long segments (n=304). ESS was calculated in all segments at all time points through the use of computational fluid dynamics. Vascular remodeling was assessed at each time point in all segments containing significant plaque, defined as maximal intima-media thickness >/=0.5 mm, at week 36 (n=220). Plaque started to develop at week 11 and progressively advanced toward heterogeneous, multifocal lesions at all subsequent time points. Low ESS promoted the initiation and subsequent progression of plaques. The local remodeling response changed substantially over time and determined future plaque evolution. Excessive expansive remodeling developed in regions of very low ESS, further exacerbated the low ESS, and was associated with the most marked plaque progression. The combined assessment of ESS, remodeling, and plaque severity enabled the early identification of plaques that evolved to high-risk lesions at week 36. CONCLUSIONS: The synergistic effect of local ESS and the remodeling response to plaque formation determine the natural history of individual lesions. Combined in vivo assessment of ESS and remodeling may predict the focal formation of high-risk coronary plaque.

25 Minor Arterial Remodeling and Endothelial Shear Stress Exhibit Significant Longitudinal Heterogeneity Along the Length of Coronary Plaques. 2016

Antoniadis, Antonios P / Papafaklis, Michail I / Takahashi, Saeko / Shishido, Koki / Andreou, Ioannis / Chatzizisis, Yiannis S / Tsuda, Masaya / Mizuno, Shingo / Makita, Yasuhiro / Domei, Takenori / Ikemoto, Tomokazu / Coskun, Ahmet U / Honye, Junko / Nakamura, Shigeru / Saito, Shigeru / Edelman, Elazer R / Feldman, Charles L / Stone, Peter H. · ·JACC Cardiovasc Imaging · Pubmed #27491487.

ABSTRACT: -- No abstract --

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