Isolated coronary artery ectasia (CAE) is localized or diffuse dilation of epicardial coronary arteries, 1.5 times the diameter of the adjacent normal coronary segment without any specific symptoms [1-3]. It is either congenital or acquired and its incidence is reported to be between 0.3 - 10% in different studies [1,4,5]. Atherosclerosis, congenital causes, inflammatory or connective tissue disorders are among the probable etiologic factors; however, exact pathophysiologic mechanism remains unclear despite some molecular, cellular and vascular mechanisms defined in various studies [5,6]. In some studies, CAE was shown to be a generalized disease affecting other vascular beds [2]. The essential histopathological finding in the diagnosis of CE is the replacement of coronary artery media layer smooth muscle cells with hyalinized collagen, as a consequence of the increased degeneration of the media layer [7]. As a result, the loss of musculoelastic components is observed in the media [8]. Thus, progressive artery dilatation occurs. Moreover, along with this disease, the presence of extracardiac artery dilatation has been reported in the previous studies [9,10]. Arterial stiffness, which is defined as the arterial rigidity caused by the loss of elastic tissue in the artery wall, decreases the widening capacity of the artery. Arterial rigidity develops and arterial widening capacity is deteriorated. It has been established that as the stiffness of the large arteries such as aorta increases, cardiovascular mortality and morbidity also increase [11]. Consequently, aortic stiffness has recently been regarded as a risk factor that needs to be treated [12]. It has also been established that aortic stiffness is increased in individuals with coronary artery disease (CAD) and in those with atherosclerosis [13]. Although myocardial ischemia and left ventricular dysfunction have been found in patients with CAE who have no narrowness or obstruction in the coronary arteries, the ventricular function of these patients has not been well studied [14,15]. The left ventricular functions and diastolic parameters of a small set of patients with CAE and no obstructive coronary artery disease have been evaluated by conventional and tissue Doppler echocardiography (TDE) and compared to controls [16]. Equally important, right ventricular function, which is a prognostic indicator for most heart diseases [17,18], has not been studied in patients with CAE.

Aim: The aim of the study to determine both ventricular functions and TDE-derived MPI in patients with CAE, and to investigate the elastic properties of the aorta and the relationship between these parameters and LV diastolic functions.

Patients with isolated coronary ectasia, detected during coronary angiograms in El Minia university hospital between January 2011 and June 2015, were included in the study. 42 patients with isolated CAE and 26 control subjects with normal coronary arteries (NCA) were evaluated. The indication for coronary angiography was either the presence of typical angina or positive or equivocal results of stress test. All of the patients were questioned for their cardiovascular risk factors and the drugs used. Routine biochemical and hematologic laboratory tests were done.

Exclusion criteria

Previous history of myocardial infarction, percutaneous coronary intervention, cardiomyopathies, congenital heart diseases, cardiac valve diseases, ventricular hypertrophy, branch blocks, chronic obstructive lung disease and/or cor pulmonale, active infection, renal failure, neoplastic disease, antioxidant drug usage and alcohol abuse.

Coronary angiography

Coronary angiography was performed to all the patients by the General Electric (GE) Innova (USA), with the standard Judkins technique. Two cardiologists evaluated the coronary angiographies without knowing the clinical or routine bio-Chemistry results of the patients. When there was no identifiable adjacent normal segment, the mean diameter of the corresponding coronary segment in the control group served as the normal value.

Echocardiography

Two-dimensional pulsed-wave Doppler and TDE were performed for all patients using a 2.5 -MHz transducer (GE vivid 3, USA) in the left decubitus position during normal respiration according to the recommendations of American Society of Echocardiograpgy [19]. The diameters of the left ventricular and the thicknesses of diastolic walls were measured from the parasternal window with two-dimensional Mmode echocardiography. Left ventricular ejection fraction was calculated using the modified Simpson’s method [20].

From the apical four-chamber view, Doppler recordings were obtained with the pulsed sample volume placed at the tip of the mitral leaflets. The peak early (E) and late (A) velocities, E-wave deceleration time (DT) and isovolumetric relaxation time (IVRT) were measured.

Pulsed-wave TDE parameters were measured by an echocardiographic device with active TDE functions. A 3.5 mm sample volume was used. The TDE cursor was placed from the apical 4- chamber view on the mitral annulus opposite the septal and lateral walls. Peak systolic velocity (Sm), peak early (Em) and late (Am) diastolic velocities for each segment were measured and the Em/Am ratio was calculated. The isovolumetric relaxation time (IRT) was measured from the end of Sm to the beginning of Em, the isovolumetric contraction time (ICT) was measured from the end of Am to the beginning of Sm and the time period of Sm was measured as the ejection time (ET). The MPI was calculated using the equation (ICT+IRT)/ET. The average of the Sm, Em and Am time intervals obtained from the mitral annulus-lateral and interventricular septum was used to calculate left ventricular mean MPI M-mode echocardiography. The aortic diameter was recorded at 3 cm above the aortic valve [21]. Internal aortic diameters were measured by means of a caliper in systole and diastole as the distance between the trailing edge of the anterior aortic wall and the leading edge of the posterior aortic wall. Aortic systolic (AoS) diameter was measured at the time of full opening of the aortic valve and diastolic (AoD) diameter was measured at the peak of QRS. Ten consecutive beats were measured routinely and averaged. The AoS and AoD indexes for each participant were calculated by dividing the AoS and AoD by the body surface area. The percentage change of the aortic root was calculated as:

%Ao = 100 × (AoS -AoD)/AoD

Aortic elasticity was assessed using the following indexes [22]:

Aortic strain (%) = 100 × (AoS -AoD)/AoD

Aortic dispensability index (cm/ dyn 10) = 2 × aortic strain × (SBPDBP)

Aortic stiffens index beta = In (SBP/DBP)/aortic strain.

Statistical analysis

SPSS version 21 was used for the statistical analysis. All the data were expressed as mean ± standard deviation. Categorical variables were compared via chi-square test. Normally distributed variables were compared across groups by means of Student’s t test, whereas variables that were not normally distributed were compared by Mann-Whitney U test. Pearson’s correlation analysis was used to evaluate relations between the variables. A P value of < 0.05 was considered significant.

The clinical characteristics of patients with CAE and normal coronary angiography individuals are presented in (Table 1). Age, sex, body mass index, diabetes mellitus, dyslipidemia, family history, and smoking status did not differ between the CAE patients and the control group. Also, there were no significant differences as regards laboratory data (Table 1).

Table 1: Demographic and clinical data of both groups.

As regards conventional echocardiography parameters, there was no significant difference of LA, LVEDD, LVESD, PW, IVS, EF, and A velocity between the two groups. But the mitral E velocity was higher in the control group than the patients (88.6 ± 4.9, 71.2 ± 6.3) (p = 0.01), and E/A ratio was also higher in the control than the patients (1.2 ± 0.2, 1 ± 0.11) (p = 0.01).

Aortic strain, aortic distensibility and index values, which are the elasticity parameters of the aorta, were found to be lower in the CE (7.1 ± 2, 3.1 ± 0.1, 1.4 ± 0.1 respectively), as compared with the values of the control group (12.8 ± 1.2, 6.05 ± 0.6, 2.01 ± 0.03 respectively), (p = 0.01) (Table 2).

Table 2: Echocardiographic parameters of both groups.

The TDE parameters obtained from the left ventricle were given in (Table 3). There was no significant difference between the two groups as regards Sm, Am, while there was significant difference between the two groups as regards Em, Em/Am, IRT, ICT, and ET. The patients (7.3 ± 1.6, 0.87 ± 0.1, 99.6 ± 10.4, 79 ± 21, 264 ± 25 respectively) the controls (13.1 ± 2.2, 1 ± 0.1, 88 ± 10, 65 ± 15, 285 ± 24 respectively), and Left ventricular MPI was significantly higher in the CAE group as compared with the control (0.64 ± 0.05, Vs 0.50 ± 0.05) (p = 0,01).

Table 3: Tissue Doppler parameters of the Left ventricle of both groups.

Table 4 showed the properties of the ectatic vessels of the CE patients. One vessel, 2 vessel and 3 vessel ectasia were found to be present in 7 (16%), 13 (31%) and 22 (52%) patients respectively. The stepwise linear multivariable analyses showed that aortic elasticity parameters had the strongest diagnostic power for detection of the abnormalities in the LV diastolic function. Among these parameters, the aortic strain had been found to possess the strongest diagnostic power for E/A rate, and IVRT (r=0.54; p=0.01, and r=0.42; p=0.01, respectively).

Table 4: Ectatic properties of the patients.

Coronary artery ectasia is the dilatation of epicardial coronary arteries more than 1.5 times and its basic pathophysiologic mechanisms are destruction of elastic layers of arterial tunica media and deposition of collagen and elastin which resulting in thinning of the arterial wall [23]. Coronary atherosclerosis is detected in more than 50% of the patients; however, connective tissue disorders and vasculitis can also be seen during pathologic examination [24]. Yetkin et al. [25] reported that carotid intima media thickness was thinner in CAE patients with stenotic CAD when compared to patients with CAD only and stated that ectasia was not an atherosclerotic process limited to coronary arteries. In some previous studies, peripheral artery disease, aortic aneurism, varicose dilatations of lower extremity veins, basilar artery aneurisms and varicoceles were shown to be increased in isolated CAE patients [26-28]. Papadakis et al. [29] found the coronary flow velocity measured using the TIMI frame count method to be lower in patients with CAE than both the obstructive CAD and control groups. The TIMI frame count method is a simple technique used to evaluate the quantitative index of coronary blood flow [30]. MPI of the CAE patients was significantly higher than the control group. This result consistent with the study of Gulec et al. [31]. Diastolic disorders in ischemic heart diseases are seen earlier than systolic dysfunctions [32]. In coronary artery disease a prolonged MPI has been shown to be an important precursor of the disease before the development of systolic dysfunction [33]. MPI is a simple, reproducible, and noninvasive method to assess systolic and diastolic functions [34,35]. Also, MPI is related to left ventricular dysfunction and clinical severity of heart failure and is a powerful parameter for the prognostic assessment of these patients [36]. Ozdemir et al. found that increased Doppler-derived MPI was related to mortality in a variety of cardiac diseases [37]. And also his study had shown that while Doppler-derived MPI was affected by preload and heart rate, TDEderived MPI was not affected by either [37]. In this study, left ventricular MPI was significantly higher in CAE patients than the control group.

Arterial stiffness is known as the arterial rigidity that develops because of the loss of elastic tissue in the arterial wall, resulting in the loss of widening capacity of the artery. It has been reported that, cardiovascular mortality and morbidity rates increase with the increase of the stiffness in the large arteries. Therefore, aortic stiffness has recently been regarded as a risk factor which needs to be treated [38]. Some structural changes occur in the myocardium when the endsystolic stress increases. Thus, systolic and [38] diastolic stiffness develops in the myocardium. However the systolic function is preserved, while the diastolic function is impaired at the first stage of these compensatory [39] changes. Systolic function is impaired in the later stages. Besides the ventricular geometry, aortic functions are also [40], presumed to be responsible for the end systolic stress. Increased stiffness can be a potential factor for wall stress. When afterload is increased, elevated intraventricular pressure has to be generated first to open the aortic valve, and then during the ejection phase these increases in afterload and intraventricular pressure lead to an increase in myocardial wall stress. In animal models, loss of aortic distensibility directly affects the mechanical performance of the left ventricle, with increases noted in LV systolic pressure and [41] wall tension.

Aortic stiffness increased in patients with CE. The increase in aortic stiffness might be responsible from LV diastolic dysfunction. These results explain that, CE is a generalized vascular disorder rather than a microvascular disease; more studies are needed to explain these changes.