Francesco Fracassi1, Filippo Crea2, Tomoyo Sugiyama1, Erika Yamamoto1, Shiro Uemura3, Rocco Vergallo2, Italo Porto2, Hang Lee4, James Fujimoto5, Valentin Fuster6, Ik-Kyung Jang7. 1. Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 2. Department of Cardiovascular and Thoracic Sciences, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario Agostino Gemelli-IRCCS, Rome, Italy. 3. Department of Cardiology, Kawasaki Medical School, Kurashiki, Okayama, Japan. 4. Biostatistics Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 5. The Research Laboratory of Electronics, Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, Massachusetts. 6. Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York. 7. Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Cardiology, Kyung Hee University Hospital, Seoul, South Korea. Electronic address: ijang@mgh.harvard.edu.
Abstract
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.
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.
Authors: Chinmay Khandkar; Mahesh V Madhavan; James C Weaver; David S Celermajer; Keyvan Karimi Galougahi Journal: Cells Date: 2021-04-10 Impact factor: 6.600