Heart Vessels (2010) 25:187–194 DOI 10.1007/s00380-009-1196-4
© Springer 2010
ORIGINAL ARTICLE Helen Triantafyllidi · Ioannis Rizos · Loukianos Rallidis Spiridon Tsikrikas · Andreas Triantafyllis Ignatios Ikonomidis · Fotis Panou · Angelos Rigopoulos Dimitrios Th. Kremastinos
Aortic distensibility associates with increased ascending thoracic aorta diameter and left ventricular diastolic dysfunction in patients with coronary artery ectasia Received: March 2, 2009 / Accepted: August 14, 2009
Abstract Coronary artery ectasia is usually linked to coronary atherosclerosis. Its primary defect is a destruction of vascular media, which leads to coronary dilatation. The aim of the present study is to evaluate whether ascending aorta present anatomical and functional wall changes in patients with coronary ectasia compared with patients without ectasia. Forty patients with known coronary ectasia (group A) underwent echocardiography in order to study aortic lumen diameter and wall properties (distensibility and stiffness index). Twenty-five patients with coronary artery disease (group B) and 40 individuals with normal coronary arteries (group C) served as control groups. Both ascending aorta diameter and ascending aorta index were significantly increased in group A compared with groups B and C (P < 0.05 and P < 0.001, respectively). Furthermore, in patients with ectatic coronary arteries ascending aorta index, systolic blood pressure and diastolic dysfunction independently associate with aortic distensibility. In patients with coronary artery ectasia, ascending aortic diameter could be enlarged while aortic stiffness is related to diastolic dysfunction. We suggest that coronary ectasia is not an isolated lesion but a reflection of a generalized vascular media defect, and should not be recognized as a benign entity. Key words Coronary ectasia · Aortic distensibility · Ascending aorta diameter
Introduction Incidence of coronary artery ectasia (CAE), defined as a localized or diffuse dilatation of the epicardial coronary
H. Triantafyllidi (*) · I. Rizos · L. Rallidis · S. Tsikrikas · A. Triantafyllis · I. Ikonomidis · F. Panou · A. Rigopoulos · D.Th. Kremastinos Second Department of Cardiology, Medical School, University of Athens, Attikon Hospital, 83, Agiou Ioannou Theologou, Holargos, 155 61 Athens, Greece Tel. +30-69442-68623; Fax +30-210-652-2947 e-mail:
[email protected]
arteries, varies between 0.3% and 4.9% in the autopsy and cardiac catheterization series.1 The luminal dilatation of ectatic coronary arteries exceeds the 1.5-fold of normal adjacent segment or vessel diameter.1,2 Although occasionally related to congenital anomalies, inflammatory and connective tissue diseases, or representing an iatrogenic complication after coronary intervention, the etiology of CAE is linked to coronary atherosclerosis.1,3,4 Histopathological examination of ectatic segments has revealed mainly destruction of the media layer of the artery with replacement of coronary artery media smooth muscle cells with hyalinized collagen. Thus progressive dilatation of the coronary artery occurs.5,6 The incidence of abdominal aortic aneurysms is increased in patients with coronary artery ectasia,7 while a few cases regarding the coexistence of CAE and intracranial aneurysms have been reported.8,9 It seems that CAE and aneurysms in other vascular beds may share a common pathogenetic mechanism, leading to the hypothesis that coronary ectasia is not an isolated lesion but a reflection of a generalized vascular media defect.10 Arterial stiffness caused by the loss of the elastic tissue in the arterial wall leads to arterial rigidity and reduced widening capacity of the artery. Arterial stiffness is increased in patients with coronary artery disease, and represents an independent predictor of coronary artery disease (CAD).11 It has been shown that as the stiffness of large arteries such as aorta increases, cardiovascular morbidity and mortality also increase, while aortic stiffness has been recognized recently as a risk factor that needs to be treated.12,13 Two recent studies confirmed that arterial stiffness is increased both in patients with CAE and CAD compared with normal controls,14,15 whilst the increased arterial stiffness might be responsible for left ventricular diastolic dysfunction.14 However, no comparison has ever been made between CAE and CAD patients regarding arterial stiffness. Since CAE may coexist with abdominal aortic aneurysms, we hypothesized that ascending thoracic aortic diameter may also be increased in patients with coronary artery ectasia, and that an association should exist between
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increased ascending thoracic aortic diameter and arterial stiffness leading to left ventricular diastolic dysfunction.
ing (CABG), or aortic surgery were excluded from the study. Echocardiographic examination
Patients and methods Study population We retrospectively analyzed the coronary angiograms of 1562 consecutive patients who underwent coronary angiography at our hospital during a 30-month period. Both patients with CAE and hypertensives with normal coronary arteries were selected at the end of each month by two investigators, while patients with CAD were selected from the patients who underwent coronary angiography during the last month of our study. An echocardiographic study was scheduled for the participants in the study the first week after their selection. Forty patients with ectatic coronary arteries were assigned to the CAE group (group A, 31 men/9 women, mean age 63 ± 10 years), 25 patients with coronary artery disease to the CAD group (group B, 24 men/1 woman, mean age 62 ± 10 years), while 40 untreated hypertensive individuals with normal coronary arteries were also included in the study (group C, 27 men/13 women, mean age 63 ± 9 years). The indication for coronary angiography was either the presence of typical angina or positive or equivocal results of noninvasive screening tests for myocardial ischemia in all groups. Coronary ectasia was defined as the diffuse or localized dilatation of the coronary artery that exceeds the diameter of the proximal adjacent normal arterial segment at least by 1.5 times.1,2 A normal segment was described as a coronary artery segment without ectasia and/or stenosis according to coronary angiography. During coronary angiography, at least five views of the left and two of the right coronary artery were recorded 30 frames per second. Films of all participants in the study with evidence of CAE were reviewed by two investigators, and a consensus was reached without knowledge of the clinical or laboratory data. All patients with CAD as well as approximately 50% of the patients with ectatic lesions had significant coronary stenoses (coronary lesion causing >50% luminal narrowing in at least one coronary artery). The study was approved by the ethics committee of our hospital, and written informed consent was obtained from each patient.
Transthoracic echocardiographic examination was performed no later than 1 month after the angiogram by an experienced cardiologist who had no knowledge of the patients’ data and classification. All patients were advised to refrain from smoking as well as coffee or tea consumption on the day of the examination. All measurements were carried out while patients were in the left lateral position by M-mode, two-dimensional, Doppler, and tissue Doppler imaging (TDI) echocardiography. The basic measurements of left ventricular dimensions in diastole and systole, thickness of interventricular septum, and posterior wall were measured by the M-mode technique. Aortic diameter (Ao) was recorded at a level of 3 cm above the aortic valve by M-mode echocardiography. Internal aortic diameter was measured in systole and diastole as the distance between the trailing edge of the anterior wall and the leading edge of the posterior aortic wall. Aortic systolic diameter (AoS) was measured at the time of the full opening of the aortic valve, while diastolic diameter (AoD) was measured at the peak of QRS. Ten consecutive beats were measured and averaged. Ascending aorta index (AoI) was calculated as ascending aorta diameter during diastole divided by height, in order to eliminate any differences within groups. Inter- and intraobserver variability of aortic diameter during systole and diastole were 1% and 3% and 0.5% and 1.7%, respectively (Fig. 1).16 Left ventricular diastolic function was assessed by measuring isovolumic relaxation time (IVRT), deceleration time (DT), and peak E and A waves of transmitral flow (E/A ratio). Tissue Doppler imaging was performed in
Exclusion criteria Patients with a history of Kawasaki disease, congenital malformation of the coronary arteries, cardiomyopathy, resistant hypertension, rhythm disturbances, aortic wall disease (aneurysm, Marfan syndrome), chronic obstructive lung disease, connective tissue or other inflammatory disease, valvular heart disease, acute coronary syndrome, or congestive heart failure, as well as those patients with a history of transluminal coronary angioplasty (PTCA) in at least one coronary artery due to coexisting significant stenoses (stenoses >70%), or with previous coronary artery bypass graft-
Fig. 1. Aortic diameter was recorded at a level of 3 cm above the aortic valve by M-mode echocardiography. Internal aortic diameter was measured in systole and diastole as the distance between the trailing edge of the anterior wall and the leading edge of the posterior aortic wall. Aortic systolic diameter was measured at the time of the full opening of the aortic valve (2) while diastolic diameter was measured at the peak of QRS (1)
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order to measure peak Ea and Aa waves and subsequently Ea/Aa ratio at the endocardial portion of the basal site of the lateral wall on the apical four-chamber view of the left ventricle.17 Blood pressure measurement Patients rested in a supine position for at least 10 min before echocardiography and then blood pressure (systolic, diastolic, and pulse pressure) was measured with a mercury sphygmomanometer by the same physician during echocardiographic examination. Systolic (SBP) and diastolic (DBP) pressures were determined during Korotkoff sounds I and V, respectively, and the average of three readings were regarded as the clinical blood pressure. Pulse pressure (PP) value was defined as systolic minus diastolic blood pressure. Hypertension was diagnosed as having systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg or using antihypertensive medication. Aortic function parameters Indices of the elastic properties of the aorta were calculated using the following formulas: 1. Aortic distensibility (dyn−1 × cm2 × 10−6): 2 × AS/PP × 3.76 2. Aortic stiffness index: ln(SBP/DBP)/AS where AS stands for aortic strain [(ADC/AoDD) × 100], ADC is aortic diameter change in millimeters [AoSD – AoDD], AoSD and AoDD are aortic end-systolic and enddiastolic diameters, respectively, SBP and DBP are systolic and diastolic blood pressure, respectively, and PP is pulse pressure in mmHg [SBP – DBP].18,19
Statistical analysis All variables are expressed as mean ± SD or percentages. Unpaired Student’s t-test was used to compare mean values between groups. Pearson’s correlation coefficient was performed to identify relations between variables in each group of patients. Multiple linear regression analysis using backward and forward procedure was used in each group of patients. After adjustment for age and systolic blood pressure, ascending AoI, Ea/Aa ratio, and left ventricular mass were forced in the regression analysis model as independent variables, to take into account any possible relation with aortic distensibility which represented the examined dependent variable. A P value of less than 0.05 was considered as the level of statistical significance. Statistical analysis was performed on SPSS version 13 (SPSS, Chicago, IL, USA).
Results Patients’ demographic and clinical characteristics are listed in Table 1. There was no significant difference between patients with coronary ectasia (group A) and patients with either coronary stenosis (group B) or normal coronary arteries (group C) regarding age, weight, height, body mass index, body surface area, known risk factors for CAD (hypertension, hyperlipidemia), as well as office systolic and diastolic blood pressure and PP levels. However, more males participated in group B compared with group A (P = 0.02), while smokers (P = 0.01) and diabetics (P = 0.003) were fewer in group C compared with group A. Finally, the majority of patients in group C were untreated hypertensives by the time of cardiac catheterization. No significant differences were detected within groups A, B, and C regarding several echocardiographic parame-
Table 1. Clinical characteristics in patients with ectatic, stenotic, and normal coronary arteries Parameter
Ectatic
Stenotic
Normal
P*
P**
n Age (years) Males (%) Body weight (kg) Height (m) Body mass index (kg/m2) Body surface area (m2) Current smokers (%) Hypertension (%) Diabetes mellitus (%) Total cholesterol (mg/dl) Triglycerides (mg/dl) Systolic BP (mmHg) Diastolic BP (mmHg) Pulse pressure (mmHg) LMCA lesion (ectatic or stenotic) RCA lesion (ectatic or stenotic)
40 63 ± 10 31 (78%) 85 ± 15 1.7 ± 0.1 29.2 ± 3.6 1.95 ± 0.4 15 (38%) 28 (68%) 8 (20%) 188 ± 49 127 ± 50 129 ± 16 75 ± 11 54 ± 14 12 (30%) 30 (75%)
25 62 ± 10 24 (96%) 82 ± 12 1.7 ± 0.08 28.6 ± 3.5 1.96 ± 0.2 11 (44%) 15 (60%) 6 (23%) 175 ± 39 128 ± 55 130 ± 17 73 ± 10 56 ± 15 4 (16%) 17 (68%)
40 63 ± 9 27 (68%) 79 ± 11 1.7 ± 0.09 28.7 ± 4.7 1.91 ± 0.2 10 (25%) 28 (70%) 0 (0%) 209 ± 39 106 ± 34 148 ± 18 86 ± 10 62 ± 13 – –
NS 0.02 NS NS NS NS NS NS NS NS NS NS NS NS – –
NS NS NS NS NS NS 0.01 NS 0.003 NS NS NS NS NS – –
BP, blood pressure; LMCA, left main coronary artery; RCA, right coronary artery; NS, not significant * Statistical analysis between patients with ectatic and stenotic coronary arteries ** Statistical analysis between patients with ectatic and normal coronary arteries
190 Fig. 2. Ascending aorta diameter and ascending aorta index in patients with coronary ectasia (CAE), coronary artery disease (CAD), and normal coronary arteries (NORMAL). P values refer to comparison with CAE group
Table 2. Cardiac structural parameters assessed by echocardiography in patients with ectatic, stenotic, and normal coronary arteries Parameter
Ectatic
Stenotic
Normal
P*
P**
Aortic root (mm) Ascending aorta diastole (mm) AoI (ascending aorta/height) (mm−4) Aortic arch (mm) IVSd (mm) PWd (mm) LVEDd (mm) LV mass (g) LVMI (g/m2) Ejection fraction (%) Aortic distensibility (dyn−1 cm2 10−6) Aortic stiffness index Ea/Aa ratio
33 ± 4 35.1 ± 6 21 ± 4 29 ± 7 11 ± 2 10 ± 2 52 ± 4 220 ± 71 107 ± 39 58 ± 12 0.7 ± 0.4 17.3 ± 11 0.7 ± 0.5
32 ± 3 32.7 ± 3 19.5 ± 2 28 ± 6 11 ± 1.5 10 ± 2 50 ± 6 204 ± 55 103 ± 27 55 ± 15 0.6 ± 0.3 18 ± 11 0.8 ± 0.4
33 ± 4 30.6 ± 4 18 ± 3 27 ± 6 10 ± 2 10 ± 2 47 ± 4 165 ± 39 87 ± 18 60 ± 3 0.6 ± 0.6 17.5 ± 11 1 ± 0.5
NS 0.02
