Assessing Coronary Artery Flow Velocity Dynamics By Using Transthoracic Doppler Echocardiography In Children With Kawasaki Disease

Background Kawasaki disease,an illness of unknown etiology,is characterized by diffuse vasculitis that affects infants and young children.Coronary involvements are apparent in 5%～10%of patients during the acute stage,making Kawasaki disease the most common and important acquired heart disease in children.The long-term outcome of Kawasaki disease depends on the coronary complications.Coronary flow dynamics measurements have provided useful clinical and physiologic information. Recent advances in Doppler and color echocardiographic technique enable us to estimate noninvasively coronary flow dynamics in children and even in neonates.Objectives1.To demonstrate the feasibility of measurement of coronary flow velocity and coronary flow velocity reserve(CFVR) in the left anterior descending coronary artery(LAD) using transthoracic Doppler echocardiography(TTDE) in healthy children;2.To assess the characteristics of coronary flow dynamics in healthy children and establish 95%confidence interval of coronary flow velocity and CFVR;3.To evaluate the physiologic effects of the coronary sequelae of Kawasaki disease on coronary hemodynamics;4.To investigate the clinical value of CFVR measurement by TTDE in early diagnosis of epicardial coronary stenosis or coronary microcirculation dysfunction in children with Kawasaki disease.Methods1.The study group consisted of 85 healthy children referred for palpitation, precordial murmur or various occasional ectopic beats(aged 4 months to 13.6 years,mean 6.6±3.8 years),and 23 children with previous Kawasaki disease(aged 1.9 to14.4 years,mean 5.7±3.1 years;5 months to 9.7 years after the onset of Kawasaki disease,mean 3.3±2.3 years).2.The distal LAD peak diastolic velocity(PDV) and mean diastolic velocity(MDV) at rest were measured by Doppler echocardiography in these 85 healthy children.3.After stable baseline signals were obtained,25 healthy children(aged 7 months to 11.5 years,mean 5.4±3.5 years) included in this study were chosen for CFVR assessment.Adenosine triphosphate(ATP) was administered intravenously at a dose of 160μg/(kg.min) for six minutes.Data were recorded at rest and during the last minute of ATP infusion.The ratio of the hyperemic PDV or MDV to baseline was calculated as an index of CFVR(PDV) or CFVR(MDV).4.Twenty-three children with previous Kawasaki disease were classified into three groups according to the left coronary artery involvement assessed by TTDE,i.e., NL group(no lesion,n=9),RL group(regressive lesion,n=7) and PL(persistent lesion,n=7).The distal LAD peak diastolic velocity(PDV) at rest and during maximum hyperaemic response was measured by TTDE and CFVR(PDV) was calculated as well.5.Among the PL group,4 children with CFVR value lower than normal range were chosen for further assessments by magnetic resonance imaging(MRI),computerized tomography arteriography(CTA) or selective coronary angiography.Results1.The diastolic flow signals of LAD at rest were recorded in 94.1%(80/85),while the complete biphasic coronary flow could be detected in only 38.75%(31/80).2.The mean PDV and MDV were 33.49±7.91cm/s and 25.58±5.65cm/s in healthy children,respectively,both of which increased significantly with heart rate(r=0.377,0.406,p=0.001,0.000).3.Among the 25 healthy children,CFVR calculated from PDV and MDV were 2.66±0.78 and 2.35±0.70,both indicating significantly positive correlation with age(r=0.596,0.591,p=0.002,0.002).The 95%confidence interval of normal CFVR data were categorized by age as follows:≥1.22(＜2 years),≥1.94(2～8 years) and≥2.22(＞8 years).4.As for children with Kawasaki disease,the mean CFVR value in NL group and RL group were 2.43±0.51 and 3.21±0.75,respectively,without significant difference compared with that of healthy children.The baseline PDV of PL group was 51.30±15.79cm/s,much higher than that of healthy counterparts,NL group and PL group(p=0.007,0.017,0.019),while CFVR was much lower(1.61±0.36, p=0.000,0.004,0.000).A significant reduction in CFVR was noted in 8 of 23 patients(34.8%) compared with healthy children,including 1 in NL group,1 in RL group and 6 in PL group respectively.5.Among the 4 children with a much lower CFVR in PL group who underwent examinations of MRI,CTA or selective coronary angiography,two children were found coronary aneurysm in LAD,one suffered from severe stenosis of LAD and the other one from complete occlusion of left circumflex coronary artery(LCx).Conclusions1.The high success rate in detection provides a possibility for clinical application of TTDE in children to measure coronary hemodynamic variables in LAD.2.There are age-related changes in the LAD flow dynamics in normal children: coronary flow velocity at rest increases significantly with heart rate,while coronary flow velocity reserve increases significantly with age.3.Coronary aneurysm and(or) coronary stenosis may contribute to a lower CFVR value in children with Kawasaki disease.4.It must be taken into consideration that in the absence of epicardial coronary lesions,a decreased CFVR may indicate functional impairment of coronary microcirculation in children with Kawasaki disease.