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Backgroud Diastolic dysfunction (DD) is reported to affect up to 35% of the adult general population. The consequence of progressive DD is heart failure with preserved ejection fraction (HFpEF). Coronary microvascular dysfunction (CMD) has been suggested as one of the pathologic mechanisms leading to HFpEF. We investigated whether there was an association between coronary microvascular function and echocardiographic indices of left ventricular diastolic function at rest in patients with chest pain and unobstructed coronary arteries (CPUCA). Methods This retrospective observational study recruited patients referred to cardiology clinics assessment of chest pain who subsequently underwent assessment via CT coronary angiogram (CTA). Coronary microvascular dysfunction was determined by myocardial blood flow reserve (MBFR; <2.0) using myocardial contrast echocardiography. Echocardiographic indices of diastolic function (septal mitral annular e′; septal mitral annular E/e′, E/A ratio) were measured from baseline transthoracic echocardiogram. Results 149 patients (52% men) with a mean age 59.7(9.5) years were recruited. Mean (standard deviation) MBFR was 2.2 (0.51). 37% (55/149) had MBFR < 2.0. Median [interquartile range] septal mitral annular e′ velocity and septal mitral annular E/e′ were 7.6 cm/s [6.2, 8.9] and 9.5 [7.5, 10.8], respectively. Univariate regression analysis showed only age was a significant predictor of increasing septal mitral annular E/e′ (β = +0.20 95% CI 0.13, +0.28, P < .001) but not MBFR. Multivariable analysis also showed no association between these septal mitral annular E/e′ and MBFR after adjustment for cardiovascular risk factors. Conclusion There was no relationship found between echocardiographic indices of left ventricular diastolic function and coronary microvascular function at rest.

We performed real-time myocardial contrast echocardiography on a patient with cardiac amyloidosis and previous normal coronary angiography presenting with atypical chest pain to assess myocardial blood flow reserve (MBFR). Myocardial contrast echocardiography was performed and flash microbubble destruction and replenishment analysis was used to calculate myocardial blood flow. Dipyridamole was used to achieve hyperemia. MBFR was derived from the ratio of peak myocardial blood flow at hyperemia and rest. The results show a marked reduction in MBFR in our patient. Previous reports of luminal obstruction of intramyocardial rather than epicardial vessels by amyloid deposition may be causing microvascular dysfunction.

Myocardial blood flow reserve is impaired in patients with aortic valve calcification and unobstructed epicardial coronary arteries, International Journal of Cardiology (2017Cardiology ( ), doi:10.1016Cardiology ( /j.ijcard.2017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT Conflicts of interest: None to declareKeywords: Aortic valve calcification score, coronary microvascular dysfunction, calcific aortic valve disease. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT3 Abstract:Background: Although calcific aortic valve disease (CAVD) is associated with coronary atherosclerosis, it is not known whether early CAVD is associated with coronary microcirculatory dysfunction (CMD). We sought to investigate the relationship between myocardial blood flow reserve (MBFR) -a measure of CMD, and early CAVD in the absence of obstructive epicardial coronary artery disease. We also determined whether this relationship was independent of coronary artery disease (CAD) and hs-CRP, a marker of systemic inflammation.Methods: 183 patients with chest pain and unobstructed coronary arteries were studied. Aortic valve calcification score (AVCS), coronary total plaque length (TPL), and coronary calcium score were quantified from multislice CT. MBFR was assessed using vasodilator myocardial contrast echocardiography. Hs-CRP was measured from venous blood using a particle-enhanced immunoassay.Results: Mean(±SD) participant age was 59.8(9.6) years. Mean AVCS was 68 (258) Conclusion:Coronary microvascular function as determined by measurement of myocardial blood flow reserve is independently associated with early CAVD. This effect is independent of the presence of coronary artery disease and also systemic inflammation.

Epicardial fat (EF) is metabolically active adipose tissue positioned between the epicardial surface of the heart and the pericardium. We investigated whether there is a relationship between EF and Coronary Microvascular Dysfunction (CMD) in patients presenting with chest pain and unobstructed coronary arteries. Materials and Methods: This study recruited patients referred to cardiology clinics for assessment of chest pain who subsequently underwent assessment via CT coronary angiogram (CTA). Myocardial blood flow reserve (MBFR) was assessed using myocardial contrast echocardiography. Epicardial fat volume (EFV) was measured by tracing serial slices on CTA with corresponding Hounsfield units of-195 to-45. Results: We recruited 134 participants with a mean age of 59.2 (9.8) years. CMD was present in 54 (40%) patients, and the measured mean EFV was 128 mm 3 (96, 168). Fortythree patients (32%) had a coronary artery calcium score (CACS) of 0, 64 (48%) had a CACS of 1-100, 18 (13%) had a CACS of 101-400, and 9 (7%) had a CACS >400. Univariate regression analysis showed that EFV and MBFR had a correlation coefficient of R=-0.22, with a significant regression slope (β=-0.002, p=0.012). Multivariable linear regression analysis using MBFR as a continuous outcome variable revealed age (β=-0.012, p=0.011) and CACS (β=-0.003, p= 0.023) to be associated with MBFR. EFV was not associated with MBFR (β=-0.0007, p=0.538). Model repetition with MBFR as a dichotomous variable (MBFR ≥2 or <2) revealed no association with EFV. Conclusion: No relationship was found between EFV and MBFR when traditional cardiovascular risk factors and calcium score.

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Myocardial blood flow reserve is impaired in patients with aortic valve calcification and unobstructed epicardial coronary arteries, International Journal of Cardiology (2017Cardiology ( ), doi:10.1016Cardiology ( /j.ijcard.2017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT Conflicts of interest: None to declareKeywords: Aortic valve calcification score, coronary microvascular dysfunction, calcific aortic valve disease. A C C E P T E D M A N U S C R I P T ACCEPTED MANUSCRIPT3 Abstract:Background: Although calcific aortic valve disease (CAVD) is associated with coronary atherosclerosis, it is not known whether early CAVD is associated with coronary microcirculatory dysfunction (CMD). We sought to investigate the relationship between myocardial blood flow reserve (MBFR) -a measure of CMD, and early CAVD in the absence of obstructive epicardial coronary artery disease. We also determined whether this relationship was independent of coronary artery disease (CAD) and hs-CRP, a marker of systemic inflammation.Methods: 183 patients with chest pain and unobstructed coronary arteries were studied. Aortic valve calcification score (AVCS), coronary total plaque length (TPL), and coronary calcium score were quantified from multislice CT. MBFR was assessed using vasodilator myocardial contrast echocardiography. Hs-CRP was measured from venous blood using a particle-enhanced immunoassay.Results: Mean(±SD) participant age was 59.8(9.6) years. Mean AVCS was 68 (258) Conclusion:Coronary microvascular function as determined by measurement of myocardial blood flow reserve is independently associated with early CAVD. This effect is independent of the presence of coronary artery disease and also systemic inflammation.

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