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Impaired aortic distensibility predicts reduced coronary flow velocity reserve in patients with suspected coronary artery disease Attila Nemes, Miklós Csanády, Tamás Forster University of Szeged, Medical Faculty, 2nd Department of Medicine and Cardiology Center Introduction • Coronary flow velocity reserve (CFR) and aortic stiffness are functional characteristics of the arterial system • Aortic stiffness / distensibility can be characterized by elastic parameters calculated from cyclic changes of aortic dimensions and blood pressures (as aortic elastic modulus) Peterson LN et al. Circ Res 1960 • CFR is a valuable index for evaluation of microvascular function in the absence of LAD stenosis and can be measured by echocardiography Iliceto S et al. Circulation 1991 Aortic stiffness Aortic stiffness describes the elastic resistance that the aorta sets against its distension. The inverse of stiffness is compliance (distensibility), which describes the ease of systolic aortic expansion. Aortic stiffness increases when the intraluminal pressure is high or due to physiologic (age, gender) or pathophysiologic conditions (vascular risk factors and diseases) In these conditions the aortic wall is characterized by • fibrosis • medial smooth muscle cell necrosis • breaks in elastin fibers • calcifications • diffusion of macromolecules into the arterial wall. Belz GG Cardiovasc Drug Ther 1995 Measurement of aortic elastic modulus [E(p)] during TEE Normal systolo-diastolic aortic diameter change Reduced - irregular systolo-diastolic aortic diameter change Aortic elastic modulus E(p) = (SBP-DBP)/[(DS-DD)/DD] Peterson LN et al. Circ Res 1960 Coronary flow (velocity) reserve • Severe flow limiting epicardial stenosis or microvascular pathologic state of the coronary arterioles result in diminution of CFR. • Disturbance in microcirculation = impaired flow in arteriolar resistance vessels and/or capillary system (↑ vascular resistance) Epicardial stenosis Normal epicardial artery 4x 4x 1x Arteriolar vasodilation 1x Microvascular disease 4x Arteriolar vasodilation 1x Arteriolar vasodilation Iliceto S et al. Circulation 1991 Coronary flow (velocity) reserve (TEE, TTE) CFR = Dmax / Drest Iliceto S et al. Circulation 1991 Parameters affecting CFR Micro- and macrovascular factors: Atherosclerosis (cardiovascular risk factors, hypertension, older age etc.) Extravascular compressive forces: Pathologic left ventricular hypertrophy (hypertension, HCM, AS) Metabolic factors: Diabetes mellitus, hypercholesterolaemia Rheologic factors: policythaemia, macrogobulinaemia Others: Tachycardia, increased contractility, insulin resistance, vegetative neuropathy, caffein intake, smoking, „red wine”, aortic stiffness etc. Nemes A et al. Can J Physiol Pharmacol 2007 Fukuda D et al. Heart 2006 Saito M et al. Heart 2008 Association between aortic stiffness and coronary artery disease • Aortic stiffening may lead to early pulse wave reflection causing an increase of central SBP and a decrease of DBP with increase of PP. • The elevation in SBP - increases myocardial oxygen demand - reduces EF - increases ventricular overload inducing LVH. • Myocardial blood supply depends largely on pressure throughout diastole and the duration of diastole • The contemporary decrease of DBP can compromise coronary perfusion resulting in subepicardial ischaemia. TEE evaluation of CFR and aortic stiffness The usefulness of dipyridamole stress TEE was extensively investigated for the simultaneous evaluation of CFR and aortic elastic properties: … in patients with coronary artery disease … post-LAD-PCI Nemes A et al. Int J Cardiol 2004 Nemes A et al. Echocardiography 2010 … in patients with negative coronary angiograms … and diabetes mellitus Nemes A et al. Can J Cardiol 2007 … and hypertension Nemes A et al. Heart Vessels 2007 … and hypercholesterolaemia Nemes A et al. Int J CV Imaging 2007 … and different ages Nemes A et al. Aging Clin Exp Res 2009 … and aortic valve stenosis Nemes A et al. J Heart Valve Dis 2004 … in patients with aortic atherosclerosis Nemes A et al. Int J CV Imaging 2004 Relationship between CFR and aortic stiffness • Significant correlations were found between simultaneously evaluated CFR and aortic elastic properties in different patient populations • Reduction of CFR could be demonstrated in patients with increased aortic stiffness Nemes A et al. Can J Physiol Pharmacol 2007 • Aortic distensibility seemed to provide complementary prognostic information over CFR only in patients without CAD and abnormal CFR Nemes A et al. Heart Vessels 2008 Aims The present study was designed to test whether impaired echocardiography-derived aortic distensibility predicts reduced CFR in patients with suspected coronary artery disease Patients • The present study consisted of 158 consecutive patients with suspected coronary artery disease. • Coronary angiography had been performed in 129 cases (82%). • Subjects with significant valvular heart disease, congenital or hypertrophic cardiomyopathy, myocarditis, or pericarditis were excluded. • Regarding to the literature, a CFR <2 was considered abnormal. Results All patients CFR >2 CFR <2 No. of patients 158 74 (47) 84 (53) Age (years) 58.0 ± 10.0 56.5 ± 10.1 59.9 ± 9.3 Diabetes mellitus (%) 41 (26) 17 (23) 24 (29) Hypertension (%) 109 (69) 51 (69) 58 (69) Hypercholesterolaemia (%) 74 (47) 34 (46) 40 (48) LV end-diastolic diameter (mm) 52.2 ± 8.3 49.2 ± 7.4 54.9 ± 8.1* Interventricular septum (mm) 10.8 ± 2.2 10.8 ± 2.1 10.8 ± 2.3 LV posterior wall (mm) 10.5 ± 2.1 10.5 ± 2.1 10.5 ± 2.1 145.8 ± 58.4 131.7 ± 50.1 158.8 ± 62.8* 62.9 ± 9.9 65.1 ± 8.6 60.9 ± 10.6 CFR 2.11 ± 0.81 2.74 ± 0.76 1.56 ± 0.28* mean AA grade 1.18 ± 0.79 1.02 ± 0.89 1.31 ± 0.68* E(p) (mm Hg) 813 ± 549 723 ± 495 892 ± 584* 129 (82) 60 (81) 69 (82) Normal epicardial coronaries 42 (33) 25 (42) 17 (25) LAD stenosis 33 (26) 9 (15) 24 (35)* Non-LAD stenosis 14 (11) 10 (17) 4 (6) Multivessel disease 40 (31) 16 (27) 24 (35) Echocardiography LVMI (g/m2) LV ejection fraction (%) Ttansoesophageal echocardiography Coronary angiography Diagnostic accuracy of E(p) in predicting impaired CFR Conclusions Prognostic impact of impaired E(p) for reduced CFR and therefore microcirculatory dysfunction could be demonstrated in patients with suspected coronary artery disease .