Carotid-Subclavian Artery Index: New Echocardiographic Index to Detect Coarctation in Neonates and Infants

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1 CARDIOVASCULAR Carotid-Subclavian Artery Index: New Echocardiographic Index to Detect Coarctation in Neonates and Infants Ali Dodge-Khatami, MD, PhD, Stephanie Ott, MD, Stefano Di Bernardo, MD, and Felix Berger, MD Division of Cardiovascular Surgery and Congenital Cardiology, University Children s Hospital, Zürich, Switzerland, and Clinic for Congenital Heart Diseases, Deutsches Herzzentrum, Berlin, Germany Background. In neonates and young infants (less than 3 months), coarctation may be missed or underestimated by echocardiography, especially with a patent ductus arteriosus or severe concurrent illness. A reliable noninvasive screening tool for coarctation would be useful for these patients. Methods. From 1997 to 2003, echocardiographic evaluation was performed in 63 consecutive patients with coarctation (47 neonates and 16 infants) as well as in 23 controls (16 neonates and 7 infants). End-systolic measurements were obtained from 12 different sites of the aortic arch. Results. In patients, the diameters of the ascending and descending aorta were comparable to controls, but the dimensions of the transverse arch were significantly smaller. The distances between the origins of the great vessels were longer in patients with coarctation than in controls. The ratio of the aortic arch diameter at the left subclavian artery, to the distance between the left carotid artery and the left subclavian artery, which we propose as the carotid-subclavian artery index, was significantly smaller in patients with coarctation. A cut-off point at 1.5 showed a sensitivity of 97.7% and 94.7%, and a specificity of 92.3% and 100%, for neonates and young infants, respectively. The positive predictive value to have coarctation was 97.7% and 100%, for neonates and infants, respectively. Conclusions. The carotid-subclavian artery index is a simply obtainable noninvasive screening parameter, showing high sensitivity and specificity for coarctation, and may be useful in unstable patients or in those with a patent ductus arteriosus in which coarctation may be overlooked. (Ann Thorac Surg 2005;80:1652 8) 2005 by The Society of Thoracic Surgeons Coarctation of the aorta is a very common congenital heart malformation that occurs in approximately 5% of all congenital heart diseases [1]. It is frequently associated with other abnormalities such as tubular hypoplasia of the aortic arch (63%), left ventricular outflow obstruction (40%), bicuspid aortic valve (40%), ventricular septal defect (28%), and atrial septal defect (12%). It is defined as a narrowing of the aorta immediately distal to the origin of the subclavian artery. In most cases, a ridge protrudes into the lumen of the vessel from the posterior and lateral walls. In older children, clinical manifestations range from mild clinical symptoms such as hypertension in the upper extremity, a systolic murmur, or diminished femoral pulses, and echocardiographic diagnosis is straightforward [2]. In newborns or young infants, the presentation is often more severe, in the form of shock or severe congestive heart failure. A concomitant large patent ductus arteriosus (PDA) may render the Accepted for publication April 25, Address correspondence to Dr Dodge-Khatami, Division of Congenital Cardiovascular Surgery, Children s University Hospital Zürich, Steinwiesstrasse 75, 8032 Zürich, Switzerland; ali.dodgekhatami@kispi.unizh.ch. diagnosis difficult, thus delaying surgical intervention until after the ductus closes [3]. In these situations, an easily measurable, yet sensitive and specific parameter would be useful, to reliably screen for and diagnose coarctation in all neonates and young infants. Importantly, the timing of diagnosis should be established before closure of a patent ductus arteriosus to avoid deterioration of cardiac function and global systemic perfusion. This study aims at finding a noninvasive echocardiography parameter to predict coarctation, independent of clinical status or other confounding factors relating to the patient. Material and Methods Approval for this study was given by our Institutional Review Board, and informed parent consent was obtained systematically. Between January 1997 and February 2003, preoperative echocardiographic studies and demographics of 63 consecutive neonates and young infants with coarctation who underwent corrective cardiac surgery at our hospital were recorded. Young infants were included until an age of 3 months. Echocardiographic investigations were performed by two cardiologists (S.D.B. and F.B.) with the 2005 by The Society of Thoracic Surgeons /05/$30.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg DODGE-KHATAMI ET AL 2005;80: CAROTID-SUBCLAVIAN ARTERY INDEX 1653 CARDIOVASCULAR Fig 1. Scheme of a normal aortic arch (left) and of coarctation of the aorta (right). The following measurements were obtained: d1 proximal ascending aorta diameter (measured at the level of the right pulmonary artery); d2 distal ascending aorta diameter (at the origin of the brachiocephalic trunk); d3 proximal transverse arch diameter (at the origin of the left carotid artery); d4 distal transverse arch diameter (at the origin of the left subclavian artery); d5 descending aorta diameter (distal to the isthmic region); d6 distance between the origin of the brachiocephalic trunk and the origin of the left carotid artery; d7 distance between the origin of the left carotid artery and the origin of the left subclavian artery; d8 distance between the origin of the left subclavian artery and the coarctation of the aorta; d9 diameter of the origin of the brachiocephalic trunk; d10 diameter of the origin of the left carotid artery; d11 diameter of the origin of the left subclavian artery; and d12 narrowest diameter of the coarctation. same ultrasonography equipment, and recorded on video for retrospective analysis. Measurements of the aortic arch were obtained by two-dimensional echocardiography at the end of systole from the suprasternal notch view, after calibrating the system using the two-dimensional centimeter scale. Morphologic parameters and distances (d1 to d12) were measured by three independent observers (S.O, S.D.B, and F.B.) as described in Figure 1, and noted separately. During the same time frame, 23 controls (16 neonates and 7 infants) were admitted to the hospital because of infectious diseases or respiratory distress syndrome, but with a structurally normal heart, and underwent the same detailed echocardiographic measurements. For this group of patients, the measurement of d8 was left out, and d12 was defined as the narrowest diameter of the isthmus of the aorta. Statistical Methods Masked interobserver variability pertaining to echocardiographic measurements was not significant. Measurements were recorded in millimeters and represent absolute values. All data are presented as mean values and standard deviations in parentheses. Windows Excel Version 97 and the Statview 5.01 statistical program were used for calculations and statistical analysis. Mean values and standard deviations of demographic and echocardiography data of both groups were compared with the unpaired Student t test. Statistical significance was defined as a p value of less than Results Of the 47 neonates and 16 infants undergoing surgical repair for coarctation, there was no surgical mortality. Two neonates with severe aortic arch hypoplasia required early redo surgery for residual coarctation (3.2%), and subsequently fared well. There was no morbidity in the infant group. The data are hereafter regrouped and presented for the 63 neonates and 23 infants. The demographic and echocardiographic data of the 63 neonates are summarized in Table 1. Associated cardiac defects in the group with coarctation (n 47) were as follows: patent ductus arteriosus in 20 patients (42%), ventricular septal defect in 20 patients (42%), bicuspid aortic valve with or without aortic valve stenosis in 20 patients (42%), and atrial septal defect or foramen ovale in 14 patients (30%). Two patients had chromosomal abnormalities, 1 with Down syndrome, and 1 with Turner syndrome. During the same period, echocardiographic measurements from 23 infants were obtained; 16 of these underwent surgery for repair of coarctation, and 7 belong to the control group. The demographic and echocardiographic data of these infants are summarized in Table 2. Associated cardiac defects in the group with coarctation were bicuspid aortic valve with or without aortic valve stenosis in 12 patients (75%), ventricular septal defect in 10 patients (63%), and patent ductus arteriosus in 3 patients (19%). None of the controls had associated cardiac defects or a PDA. Great Vessel and Aortic Arch Dimensions The diameters of the ascending and descending aorta were not significantly different in patients with coarctation, neither for neonates nor for infants, as compared with controls. The dimensions of the transverse arch were significantly smaller in the coarctation group, especially in neonates. The distances between the origins of the great vessels were larger in patients with coarctation

3 CARDIOVASCULAR 1654 DODGE-KHATAMI ET AL Ann Thorac Surg CAROTID-SUBCLAVIAN ARTERY INDEX 2005;80: Table 1. Demographic Data and Variables in Neonates: Coarctation and Controls Neonates Coarctation Patients n 47 Controls n 16 p Value Table 2. Demographic Data and Variables in Infants: Coarctation and Controls Infants Coarctation Patients n 16 Controls n 7 p Value Demographic data Age (days) 12 (10) 16 (12) 0.15 Weight (kg) 3.0 (0.6) 3.2 (0.9) 0.37 Length (cm) 50 (7) 50 (4) 0.90 Body surface (m 2 ) 0.20 (0.02) 0.20 (0.04) 0.52 Further measurements Shortening fraction 34 (9) 36 (7) of LV (%) Gradient maximum 31 (18) at COA (mm Hg) Flow velocity 267 (80) 130 (28) maximum at COA (cm/s) Aortic dimension d1 (mm) 6.8 (1.5) 7.5 (1.3) d2 (mm) 5.6 (1.1) 7.1 (1.2) d3 (mm) 4.3 (1.0) 6.2 (1.3) d4 (mm) 3.4 (0.8) 5.9 (1.4) d5 (mm) 6.2 (1.4) 5.9 (1.1) d6 (mm) 2.8 (1.5) 1.5 (0.4) d7 (mm) 7.3 (3.0) 2.4 (0.8) d8 (mm) 3.6 (1.6) d9 (mm) 4.1 (0.9) 3.8 (1.1) d10 (mm) 2.8 (0.6) 2.4 (0.5) d11 (mm) 2.2 (1.2) 2.2 (0.4) d12 (mm) 2.1 (0.9) 5.0 (1.1) Mean values are given, followed by standard deviation in parentheses. COA coarctation; LV left ventricle. Demographic data Age (days) 75 (34) 55 (12) Weight (kg) 4.43 (1.38) 4.45 (0.64) Length (cm) 56 (6) 55 (3) Body surface (m 2 ) 0.23 (0.07) 0.24 (0.02) Further measurements Shortening fraction 34 (6) 38 (5) of LV (%) Gradient maximum 48 (26) at COA (mm Hg) Flow velocity 319 (116) 121 (12) maximum at COA (cm/s) Aortic dimension d1 (mm) 7.8 (1.1) 8.2 (2.2) d2 (mm) 6.8 (1.1) 7.4 (1.8) d3 (mm) 5.5 (1.4) 6.6 (0.8) d4 (mm) 4.5 (0.9) 6.3 (0.9) d5 (mm) 7.3 (1.9) 6.5 (0.8) d6 (mm) 3.9 (1.8) 2.0 (0.6) d7 (mm) 7.3 (2.4) 2.7 (0.8) d8 (mm) 5.6 (2.5) d9 (mm) 4.7 (1.2) 4.4 (0.5) d10 (mm) 3.3 (0.8) 2.4 (0.2) d11 (mm) 2.5 (0.5) 2.4 (0.2) d12 (mm) 2.3 (0.8) 5.6 (0.9) Mean values are given, followed by standard deviation in parentheses. COA coarctation; LV left ventricle. than in controls, both in neonates and infants: the mean distance from the brachiocephalic trunk to the carotid artery (d6) in neonate patients with coarctation was 2.8 mm, compared with 1.5 mm in controls (p ). In infants, the distance in patients with coarctation was 3.9 mm, compared with 2 mm in controls. The mean distance from the left carotid artery (LCA) to the left subclavian artery (LSA [d7]) in the neonate group with coarctation was 7.32 mm, compared with 2.37 mm in neonate controls (p ). In infants, the mean distance from the LCA to the LSA (d7) was 7.27 mm in those with coarctation, compared with 2.67 mm in controls (p ) (Fig 2). The diameters of the great vessels were larger in the coarctation group for neonates and infants; however, significant increases were found in d10 only. Upon subgroup analysis of patients with associated intracardiac shunts or a PDA, there was no significant difference in great vessel or arch dimensions, as compared with patients without associated defects. To have a comparative parameter, we calculated the ratios d1 to d7, d3 to d7, and d4 to d7. These indices were proportionally significantly smaller in coarctation patients, when compared with either control neonates or control infants (Table 3). We used these ratios, d1/d7, d3/d7, and d4/d7, to find predictive accuracy of two-dimensional echocardiography in the diagnosis of coarctation for neonates, as well Table 3. Ratios of Aortic Arch Dimensions to Great Vessel Distances: Coarctation and Controls Coarctation Patients n 63 Controls n 23 p Value Neonates Index d1/d (0.83) 3.56 (1.55) Index d3/d (0.87) 3.38 (1.43) Index d4/d (0.86) 2.95 (1.24) Infants 16 7 Index d1/d (0.43) 3.17 (0.83) Index d3/d (0.43) 2.94 (0.88) Index d4/d (0.29) 2.66 (0.78) Mean values are given, followed by standard deviation in parentheses.

4 Ann Thorac Surg DODGE-KHATAMI ET AL 2005;80: CAROTID-SUBCLAVIAN ARTERY INDEX Table 4. Sensitivity, Specificity, Positive and Negative Predictive Values According to Cut-Off Sensitivity % Specificity % Positive Predictive Value % Negative Predictive Value % Neonates Index d1/d Index d1/d Index d1/d Index d1/d Index d3/d Index d3/d Index d3/d Index d3/d Index d4/d Index d4/d Index d4/d Index d4/d Infants Index d1/d Index d1/d Index d1/d Index d1/d Index d3/d Index d3/d Index d3/d Index d3/d Index d4/d Index d4/d Index d4/d Index d4/d CARDIOVASCULAR as for infants. To facilitate the recognition of coarctation, we defined the index d4/d7 as the carotid-subclavian artery index. This ratio was significantly smaller in the coarctation group in neonates and infants, compared with their respective controls. If the cut-off point for the carotid-subclavian artery index is fixed at 1.5, there is a sensitivity of 97.7% and a specificity of 92.3% for a neonate to have coarctation, with a positive predictive value of 97.7%, and a negative predictive value of 92.3%. With a similar cut-off for the carotid-subclavian artery index in infants, our data show a sensitivity of 94.7% and a specificity of 100%. The positive predictive value is 100%, and the negative predictive value 90.9% (Table 4). Regarding neonates only, an index d4/d7 below 2 gives a very specific and sensitive result, but when infants are included, a d4/d7 index below 1.5 gives the most accurate results taking both age groups into consideration. Comment Since the early 1980s, the method of diagnosis for coarctation has changed from using clinical data, with or without preoperative catheter confirmation, to relying almost exclusively on echocardiography [4]. Echocardiography can allow noninvasive assessment of the aortic arch, identification of the narrowing at the aortic isthmus, flow measurement, and determination of the instant gradient over the coarctation [5 7]. However, a significant number of patients with coarctation are not properly diagnosed during the neonatal period [5, 6]. That may be due to patent ductus arteriosus without flow acceleration at the isthmus of the aorta, to poor image quality, or to a location further downstream in the descending aorta. Furthermore, clinical judgment may be impaired in situations with diminished contractility of the left ventricle and poor cardiac output, or other reasons such as infection or breathing artifacts [8]. Another potential problem is, that even with the use of Doppler flow assessment in the descending aorta, the anatomic severity of coarctation cannot always be assessed [2, 9 11]. Other authors have tried to find a reliable echocardiographic parameter to predict aortic coarctation in the newborn using morphologic measurements, including aortic arch diameters at different sites, calculations and comparison of diameter ratios, or measurements of distances between the great vessels of the aortic arch [12, 13]. That has to date not given satisfying results to clearly identify a coarctation in difficult situations, and too many diagnoses have gone unrecognized. The study by Morrow and coworkers [12] enforces our results, reporting significant alterations in the dimensions of arch diameters, although by invasive angiogra-

5 CARDIOVASCULAR 1656 DODGE-KHATAMI ET AL Ann Thorac Surg CAROTID-SUBCLAVIAN ARTERY INDEX 2005;80: Fig 2. Echocardographic images of two different aortic arches with a large distance between the left carotid artery and the left subclavian artery and significant narrowing of the transverse arch. Calculation of the carotid-subclavian index is highly specific for the presence of coarctation. (AAO ascending aorta; LCA left carotid artery; LSA left subclavian artery; TAA transverse aortic arch; Tr. brach. brachiocephalic trunk.) phy. They found no differences between patients and controls concerning the descending aorta and left subclavian artery diameters, but demonstrated that the length of the transverse arch between the LCA and LSA was significantly increased in patients with coarctation [12]. Our results support his findings and add a useful and reproducible index, with the use of a noninvasive diagnostic tool. Nihoyannopoulos and associates [14] assessed the predictive accuracy of two-dimensional echocardiography in defining aortic arch obstruction. Using viewing of the aortic arch only, the overall sensitivity of the method was only 88%. They found twodimensional echocardiography to be more specific than sensitive for the prediction of aortic arch obstruction, noting that with a low origin of the LSA, particular attention should be paid to the visualization of the isthmus [14]. Contrary to our findings, Aluquin and coworkers [13] found the distal ascending root diameter and descending aorta to be significantly larger in patients with coarctation. Our data show that the proximal and distal diameters of the ascending aorta are smaller in patients with coarctation, and that the diameter of the descending aorta is larger in coarctation patients, either due to increased resistance before the stenosis or to poststenotic dilatation from turbulent flow. Nevertheless, our data concur with theirs regarding the transverse arch, which was notably longer in the coarctation group, as compared with controls. Excluding older invasive angiographic studies, newer noninvasive modalities to accurately assess and diagnose coarctation in the younger population exist, and are both reliable and reproducible [2, 15]. These include axial, multiplanar computed tomography scan and magnetic resonance imaging, which are more expensive, cumbersome, and could require anesthesia and intubation in the newborn and infant population. Because of the significant decrease in diameter of the distal transverse aortic arch just before the LSA (d4) in patients with coarctation, and the significant prolongation of the distance from the origin of the LCA to the origin of the LSA (d7), we found it useful to use these two variables as part of the carotid-subclavian artery index. Therefore, we propose the carotid-subclavian artery index, where the diameter of the transverse arch at the origin of the LSA (d4), is put in ratio to the distance from the origin of the LCA to the origin of the LSA (d7), as a screening tool for coarctation. In neonates and young infants with coarctation, the carotid-subclavian artery index yields a sensitivity of 97.7% for neonates and 94.7% for infants, using a cut-off point below 1.5. The longer the distance (d7) and the smaller the diameter of the aortic arch at the origin of the LSA (d4), the smaller the carotid-subclavian artery index, and the higher the predictability of coarctation. These findings remain valid regardless of the presence or absence of an associated intracardiac shunt or PDA. Study Limitations The results of our study are to be taken into the perspective of a retrospective design and its limitations. To achieve validity, the carotid-subclavian artery index should be prospectively assessed in patients with only mild hypoplasia of the aortic arch, with or without coarctation. Also, the numbers are relatively small, reducing the power of the finding. To establish the usefulness of the carotid-subclavian artery index as a screening tool for coarctation, a prospective study with a greater population of newborns and infants is needed, both with and without coarctation. In conclusion, the carotid-subclavian artery index is a simple screening parameter, readily obtained, and standardized from two-dimensional echocardiography visualization of the aortic arch. It shows high sensitivity and specificity for coarctation in our population of newborns and infants with a cut-off point below 1.5, independently of concomitant intracardiac or extracardiac shunts. In difficult subsets of patients with a large PDA and severe concurrent illness with hemodynamic instability, measuring the carotid-subclavian artery

6 Ann Thorac Surg DODGE-KHATAMI ET AL 2005;80: CAROTID-SUBCLAVIAN ARTERY INDEX index may lead to earlier diagnosis and subsequent surgical correction, before ductal closure and diminished cardiac output with reduced systemic perfusion occurs. References 1. Jenkins NP, Ward C. Coarctation of the aorta: natural history and outcome after surgical treatment. Q J Med 1999;92: Lim DS, Ralston MA. Echocardiographic indices of Doppler flow patterns compared with MRI or angiographic measurements to detect significant coarctation of the aorta. Echocardiography 2002;19: Rothman A. Coarctation of the aorta, an update. Curr Probl Pediatr 1998;28: Grech V. Diagnostic and surgical trends, and epidemiology of coarctation of the aorta in a population-based study. Int J Cardiol 1999;68: Strattford MA, Griffiths SP, Gersony WM. Coarctation of the aorta, a study in delayed detection. Pediatrics 1982;69: Thoele DG, Master AJ, Paul MH. Recognition of the coarctation of the aorta: a continuing challenge for the primary care physician. Am J Dis Child 1987;141: Robinson PJ, Wyse RKH, Deanfield JE, et al. Continues wave doppler velocimetry as an diagnosis of critical left heart obstruction in neonates. Br Heart J 1984;52: Rinelli G, Marino B, Santoro G, et al. Pitfalls in echocardiographic-based repair of aortic coarctation. Am J Cardiol 1997;80: Stern HC, Locher D, Wallnofer K, et al. Noninvasive assessment of coarctation of the aorta: comparative measurements by two-dimensional echocardiography, magnetic resonance, and angiography. Pediatr Cardiol 1991;12: Muhler EG, Neuerburg JM, Ruben A, et al. Evaluation of aortic coarctation after surgical repair: role of magnetic resonance imaging and Doppler ultrasound. Br Heart J 1993;70: Seifert BL, DesRochers K, Ta M, et al. Accuracy of Doppler methods for estimating peak-to-peak instantaneous gradients across coarctation of the aorta: an in vitro study. J Am Soc Echocardiogr 1999;12: Morrow WH, Huhta JC, Murphy DJ, et al. Quantitative morphology of the aortic arch in neonatal coarctation. J Am Coll Cardiol 1986;8: Aluquin VPR, Shutte D, Nihill MR, et al. Normal aortic arch growth and comparison with isolated coarctation of the aorta. Am J Cardiol 2003;91: Nihoyannopoulos P, Karas S, Sapsford RN, et al. Accuracy of two-dimensional echocardiography in the diagnosis of aortic arch obstruction. J Am Coll Cardiol 1987;10: Lee EY, Siegel MJ, Hildebolt CF, Gutierrez FR, Bhalla S, Fallah JH. MDCT evaluation of thoracic aortic anomalies in pediatric patients and young adults: comparison of axial, multiplanar, and 3D images. AJR Am J Roentgenol 2004;182: CARDIOVASCULAR INVITED COMMENTARY This article [1] describes a novel and potentially important new echocardiographic index for the diagnosis of coarctation of the aorta in neonates and infants. The authors have proposed the index because of the frequent difficulty in confidently establishing the diagnosis of coarctation, particularly in the smallest and youngest patients. Three anatomic features create this difficulty: the coexistence of a large ductus arteriosus, the presence of hypoplasia of the aortic arch, and the lack of coplanarity of the aortic arch, ductus, and descending aorta. Previous investigators [2, 3] have suggested that specific dimensional thresholds for the aortic isthmus of 4.5 mm [2] or3mm[3] allow the diagnosis of coarctation. However the specificity and sensitivity of such a measure are far from perfect, and the application of either standard to very small infants will certainly lead to overdiagnosis of coarctation. The addition of Doppler assessments has variously been believed to be of limited value [4] or of significant help if combined with size criteria [3]. In present day practice, despite the several proposed diagnostic tests for coarctation, it is still quite common to allow the ductus to close under observation to allow a coarctation to declare itself if present. Such a declaration will take the form of the acute development of aortic obstruction with potential consequences of distal hypoperfusion and metabolic acidosis, renal injury, left ventricular dysfunction, pulmonary edema, and pulmonary hypertension. In effect, the patient is forced to prove he has a disease by becoming ill. The validation of the carotid-subclavian artery index would allow the relegation of observed ductal closure to the slagheap of history where it rightly belongs. The measurements required to calculate the index are readily obtained from standard suprasternal views of the distal arch. Accurately aligned Doppler windows are not required, and there is no necessity for co-planarity of the aortic arch, ductus, and descending aorta. There is also no requirement for detecting a coarctation shelf as described by other authors [5]. Another advantage of using the index is the fact that it is a ratio, and thus it would not be confounded by extremely small patient size. However several caveats are worth mentioning in regard to the new measure, which has not yet been tested in other centers. Despite the excellent sensitivity and specificity of this index, it is important that it not be applied in isolation. There is the occasional neonate, with transverse aortic arch hypoplasia and a large patent ductus arteriosus, who does not develop coarctation of the aorta, and an aggressive strategy of surgical intervention in these patients based on an as-yet unconfirmed echocardiographic index that could result in unnecessary procedures and exposure to potential late complications, such as recurrent arch obstruction and distortion. Beyond 2005 by The Society of Thoracic Surgeons /05/$30.00 Published by Elsevier Inc doi: /j.athoracsur