RESUMO
OBJECTIVES: Pathological studies demonstrate the dual significance of plaque burden (PB) and lipid composition for mediating coronary plaque vulnerability. We evaluated relationships between intravascular ultrasound (IVUS)-derived PB and arterial remodeling with near-infrared spectroscopy (NIRS)-derived lipid content in ex vivo and in vivo human coronary arteries. APPROACH AND RESULTS: Ex vivo coronary NIRS and IVUS imaging was performed through blood in 116 coronary arteries of 51 autopsied hearts, followed by 2-mm block sectioning (n=2070) and histological grading according to modified American Heart Association criteria. Lesions were defined as the most heavily diseased 2-mm block per imaged artery on IVUS. IVUS-derived PB and NIRS-derived lipid core burden index (LCBI) of each block and lesion were analyzed. Block-level analysis demonstrated significant trends of increasing PB and LCBI across more complex atheroma (Ptrend <0.001 for both LCBI and PB). Lesion-based analyses demonstrated the highest LCBI and remodeling index within coronary fibroatheroma (Ptrend <0.001 and 0.02 versus all plaque groups, respectively). Prediction models demonstrated similar abilities of PB, LCBI, and remodeling index for discriminating fibroatheroma (c indices: 0.675, 0.712, and 0.672, respectively). A combined PB+LCBI analysis significantly improved fibroatheroma detection accuracy (c index 0.77, P=0.028 versus PB; net-reclassification index 43%, P=0.003), whereas further adding remodeling index did not (c index 0.80, P=0.27 versus PB+LCBI). In vivo comparisons of 43 age- and sex-matched patients (to the autopsy cohort) undergoing combined NIRS-IVUS coronary imaging yielded similar associations to those demonstrated ex vivo. CONCLUSIONS: Adding NIRS to conventional IVUS-derived PB imaging significantly improves the ability to detect more active, potentially vulnerable coronary atheroma.
Assuntos
Doença da Artéria Coronariana/diagnóstico , Vasos Coronários , Lipídeos/análise , Placa Aterosclerótica , Espectroscopia de Luz Próxima ao Infravermelho , Ultrassonografia de Intervenção , Idoso , Autopsia , Biomarcadores/análise , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/patologia , Doença da Artéria Coronariana/terapia , Vasos Coronários/química , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Valor Preditivo dos Testes , Prognóstico , Remodelação VascularRESUMO
AIMS: While the relationship between epicardial coronary vasomotor reactivity and cardiovascular events is well established, this observation has yet to be evaluated within the left main coronary artery (LMCA) in humans in vivo. Our aims were to test the endothelium-dependent vasomotor properties of the LMCA, and to compare these responses to downstream epicardial segments. METHODS AND RESULTS: Thirty patients referred for coronary angiography underwent intracoronary (IC) salbutamol provocation during intravascular ultrasound imaging within a non-critically diseased, left-sided conduit vessel. Macrovascular vasomotor response [change in average lumen area (LA) at baseline and following 5 min of 0.30 µg/min IC salbutamol] and percent atheroma volume (PAV) were evaluated in 30 LMCA, 42 proximal, 109 mid, and 132 distal epicardial coronary segments. In comparison with all other segments, the LMCA had the greatest lumen and vessel areas (P < 0.001), yet the proximal epicardial segments contained the greatest PAV (P < 0.02). The mid and distal epicardial segments displayed significant endothelium-dependent vasodilatation from baseline (P = 0.017 and <0.001, respectively); however, the proximal epicardial and LMCA segments did not (P = 0.45 and 0.16, respectively). Significant segmental vasomotor heterogeneity was noted in all 30 patients, with opposing vasomotor responses between adjacent LMCA and epicardial segments. Across all segments, baseline LA inversely correlated with the % change in LA (r = -0.16, P = 0.0005). CONCLUSION: Endothelium-dependent vasomotor reactivity is heterogenous within the conduit coronary system. Vascular dynamic responses were less prominent in the larger calibre LMCA and proximal epicardial segments. This may, in part, relate to higher shear stress in smaller, distal segments and yet also may explain the propensity for culprit plaques to cluster proximally.
Assuntos
Doença da Artéria Coronariana/diagnóstico por imagem , Endotélio Vascular/efeitos dos fármacos , Placa Aterosclerótica/diagnóstico por imagem , Ultrassonografia de Intervenção , Agonistas de Receptores Adrenérgicos beta 2/farmacologia , Albuterol/farmacologia , Biomarcadores/sangue , Angiografia Coronária , Endotélio Vascular/diagnóstico por imagem , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , VasodilataçãoRESUMO
OBJECTIVES: The aim of this study was to evaluate the progression of atherosclerosis within the left main coronary artery (LMCA) in association with risk factor modifying therapies. BACKGROUND: Despite studies demonstrating slowing of disease progression within epicardial coronaries with risk factor modification, little is known about the natural history and clinical sequelae of atherosclerosis progression within the LMCA. METHODS: In 340 patients with angiographic coronary artery disease who underwent serial intravascular ultrasound imaging to evaluate the effects of anti atherosclerotic therapies across 7 clinical trials, LMCA and epicardial disease progression was characterized. Relationships between changes in plaque burden with remodeling parameters and the incidence of major adverse cardiovascular events (MACE) (death, myocardial infarction, hospital stay for unstable angina, and coronary revascularization) were investigated. RESULTS: Plaque regression was observed in the LMCA segment, and progression was observed in adjacent epicardial segments (percent atheroma volume [PAV] -0.39 ± 0.1% vs. +0.37 ± 0.1%, p < 0.001). Changes in LMCA lumen volume correlated strongly with changes in external elastic membrane (beta coefficient 0.91, p < 0.001) and negatively with the change in PAV (beta coefficient -0.55, p < 0.001). Patients who experienced a MACE had smaller baseline LMCA minimum lumen area (11.6 vs. 12.2 mm(2), p = 0.05) and greater progression of PAV in the LMCA (+0.51 ± 0.3% vs. -0.35 ± 0.2%, p = 0.02) compared with those who were MACE-free. Significant reductions from baseline in both external elastic membrane (-4.7 ± 1.7 mm(3), p < 0.01) and lumen volumes (-4.0 ± 1 mm(3), p < 0.01) were also observed in those having an event. CONCLUSIONS: Left main coronary atherosclerosis responds to systemic risk factor modification. Patients experiencing a MACE were more likely to demonstrate progressive disease and constrictive arterial remodeling within the LMCA segment.