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      Defining Coronary Flow Patterns: Comprehensive Automation of Transthoracic Doppler Coronary Blood Flow

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          Abstract

          The coronary microcirculation (CM) plays a critical role in the regulation of blood flow and nutrient exchange to support the viability of the heart. In many disease states, the CM becomes structurally and functionally impaired, and transthoracic Doppler echocardiography can be used as a non-invasive surrogate to assess CM disease. Analysis of Doppler echocardiography is prone to user bias and can be laborious, especially if additional parameters are collected. We hypothesized that we could develop a MATLAB algorithm to automatically analyze clinically-relevant and non-traditional parameters from murine PW Doppler coronary flow patterns that would reduce intra- and inter-operator bias, and analysis time. Our results show a significant reduction in intra- and inter-observer variability as well as a 30 fold decrease in analysis time with the automated program vs. manual analysis. Finally, we demonstrated good agreement between automated and manual analysis for clinically-relevant parameters under baseline and hyperemic conditions. Resulting coronary flow velocity reserve calculations were also found to be in good agreement. We present a MATLAB algorithm that is user friendly and robust in defining and measuring Doppler coronary flow pattern parameters for more efficient and potentially more insightful analysis assessed via Doppler echocardiography.

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          Coronary microvascular dysfunction: an update.

          Many patients undergoing coronary angiography because of chest pain syndromes, believed to be indicative of obstructive atherosclerosis of the epicardial coronary arteries, are found to have normal angiograms. In the past two decades, a number of studies have reported that abnormalities in the function and structure of the coronary microcirculation may occur in patients without obstructive atherosclerosis, but with risk factors or with myocardial diseases as well as in patients with obstructive atherosclerosis; furthermore, coronary microvascular dysfunction (CMD) can be iatrogenic. In some instances, CMD represents an epiphenomenon, whereas in others it is an important marker of risk or may even contribute to the pathogenesis of cardiovascular and myocardial diseases, thus becoming a therapeutic target. This review article provides an update on the clinical relevance of CMD in different clinical settings and also the implications for therapy.
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            Coronary arterioles in type 2 diabetic (db/db) mice undergo a distinct pattern of remodeling associated with decreased vessel stiffness.

            Little is known about the impact of type 2 diabetes mellitus (DM) on coronary arteriole remodeling. The aim of this study was to determine the mechanisms that underlie coronary arteriole structural remodeling in type 2 diabetic (db/db) mice. Passive structural properties of septal coronary arterioles isolated from 12- to 16-week-old diabetic db/db and control mice were assessed by pressure myography. Coronary arterioles from 12-week-old db/db mice were structurally similar to age-matched controls. By 16 weeks of age, coronary wall thickness was increased in db/db arterioles (p < 0.01), while luminal diameter was reduced (control: 118 ± 5 μm; db/db: 102 ± 4 μm, p < 0.05), augmenting the wall-to-lumen ratio by 58% (control: 5.9 ± 0.6; db/db: 9.5 ± 0.4, p < 0.001). Inward hypertrophic remodeling was accompanied by a 56% decrease in incremental elastic modulus (p < 0.05, indicating decreased vessel coronary wall stiffness) and a ~30% reduction in coronary flow reserve (CFR) in diabetic mice. Interestingly, aortic pulse wave velocity and femoral artery incremental elastic modulus were increased (p < 0.05) in db/db mice, indicating macrovascular stiffness. Molecular tissue analysis revealed increased elastin-to-collagen ratio in diabetic coronaries when compared to control and a decrease in the same ratio in the diabetic aortas. These data show that coronary arterioles isolated from type 2 diabetic mice undergo inward hypertrophic remodeling associated with decreased stiffness and increased elastin-to-collagen ratio which results in a decreased CFR. This study suggests that coronary microvessels undergo a different pattern of remodeling from macrovessels in type 2 DM.
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              Coronary microvascular function is independently associated with left ventricular filling pressure in patients with type 2 diabetes mellitus

              Background Left ventricular (LV) diastolic dysfunction is known as an early marker of myocardial alterations in patients with diabetes. Because microvascular disease has been regarded as an important cause of heart failure or diastolic dysfunction in diabetic patients, we tested the hypothesis that coronary flow reserve (CFR), which reflects coronary microvascular function, is associated with LV diastolic dysfunction in patients with type 2 diabetes. Methods We studied asymptomatic patients with type 2 diabetes but without overt heart failure. Transthoracic Doppler echocardiography was performed that included pulsed tissue Doppler of the mitral annulus and CFR of the left anterior descending artery (induced by adenosine 0.14 mg/kg/min). The ratio of mitral velocity to early diastolic velocity of the mitral annulus (E/e′) was used as a surrogate marker of diastolic function. We also evaluated renal function, lipid profile, parameters of glycemic control and other clinical characteristics to determine their association with E/e′. Patients with LV ejection fraction 2.0 mg/dl) or type 1 diabetes were excluded. Patients with a CFR <2.0 were also excluded based on the suspicion of significant coronary artery stenosis. Results We included 67 asymptomatic patients with type 2 diabetes and 14 non-diabetic controls in the final study population. In univariate analysis, age, presence of hypertension, LV mass index, estimated glomerular filtration rate and CFR were significantly associated with E/e′. Multivariate analysis indicated that both LV mass index and CFR were independently associated with E/e′. In contrast, there were no significant associations between parameters of glycemic control and E/e′. Conclusions CFR was associated with LV filling pressure in patients with type 2 diabetes. This result suggests a possible link between coronary microvascular disease and LV diastolic function in these subjects.
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                Author and article information

                Contributors
                aaron.trask@nationwidechildrens.org
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                22 November 2018
                22 November 2018
                2018
                : 8
                : 17268
                Affiliations
                [1 ]ISNI 0000 0004 0392 3476, GRID grid.240344.5, Center for Cardiovascular Research, , The Research Institute at Nationwide Children’s Hospital, ; Columbus, OH USA
                [2 ]ISNI 0000 0001 2285 7943, GRID grid.261331.4, Department of Pediatrics, , The Ohio State University College of Medicine, ; Columbus, OH USA
                Article
                35572
                10.1038/s41598-018-35572-4
                6250694
                30467422
                eb5e89d9-cd66-48b7-9464-e119f08ac278
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 3 August 2018
                : 5 November 2018
                Funding
                Funded by: U.S. National Institutes of Health (R00116769 to AJT) and The Research Institute at Nationwide Children&amp;#x2019;s Hospital (to AJT)
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