Pediatr Cardiol 18:376–380, 1997

Pediatric Cardiology © Springer-Verlag New York Inc. 1997

Case Reports Coarctation of the Left Pulmonary Artery: Effects on the Pulmonary Vasculature of Infants E.A. Zevallos-Giampietri,* W.L. Thelmo, V.M. Anderson Department of Pathology, SUNY Health Science Center at Brooklyn, 450 Clarkson Avenue, Box 25, Brooklyn, NY 11203, USA

Abstract. At autopsy, two infants had unsuspected coarctation of the left pulmonary artery (CoLPA), which was produced by an extension of ductal tissue into the wall of the left pulmonary artery. The first case, a 4-month-old girl, also had a ventricular septal defect and an anomalous branching pattern of the innominate arterial trunk. Pulmonary arterial hypertensive changes were noted in the right lung. In contrast, the left lung showed thin-walled pulmonary arteries. The second case, a term female newborn, had exhibited severe unexplained respiratory distress since birth. Histologic sections of the right lung showed dilated pulmonary arteries with thinned media, whereas the left lung showed a persistent fetal arterial pattern. It is believed that the peripheral pulmonary arterial changes are age-dependent and associated with asymmetric blood flow between the right and left pulmonary arteries. CoLPA is a rare pulmonary artery defect, and early diagnosis of this abnormality is important. Key words: Pulmonary artery — Ductus arteriosus — Pulmonary hypertension — Congenital heart disease

Coarctation of the left pulmonary artery (CoLPA) is a congenital malformation characterized by a circumscribed narrowing of the left pulmonary artery (LPA) produced by a ductal ridge extension. Elzenga et al. described this abnormality associated with congenital heart disease [8]. A differential degree of perfusion can have a profound effect on the development of the pulmonary arteries. The effects of hyper- and hypoperfusion on the peripheral pulmonary vessels have been established using LPA ligation models [13, 14, 16, 22]. These changes have not been well documented in humans. Therefore * Present address: Department of Pathology and Laboratory Medicine, Woodhull Medical and Mental Health Center, 760 Broadway, Brooklyn, NY 11206, USA Correspondence to: E.A. Zevallos-Giampietri

CoLPA may also allow a comparative analysis of the asymmetric perfusion effects on the pulmonary vasculature. Two cases of CoLPA are reported.

Materials and Methods Autopsies were performed on two infants with a history of unexplained severe respiratory distress. Pregnancy and maternal histories were not contributory. Case 1: A 4-month-old girl was admitted to the hospital for dyspnea, lung congestion, and failure to thrive. The patient’s weight, length, and head circumference were below the 5th percentile for her age. She died in severe respiratory failure. Case 2: A term female, vaginally-delivered neonate suffered from severe respiratory distress beginning at birth. She died 9 days after delivery. Complete autopsies were performed in both cases. Meticulous dissection and gross description of the heart, aortic arch (AoA), main pulmonary artery (MPA), and its bifurcation were carried out. Longitudinal and transverse sections of the aorta, MPA, pulmonary artery bifurcation, right pulmonary artery (RPA), left pulmonary artery (LPA), ductus arteriosus (DA), and ‘‘mirror-image’’ lung sections were obtained. Tissue sections were fixed in 10% buffered formalin and embedded in paraffin. Histologic sections were stained with hematoxylin and eosin, trichrome, and elastic van Geison preparations.

Results Case 1 showed considerable disparity in the caliber of the RPA (0.5 cm) and LPA (1.5 cm). The diameter of the DA was 0.4 cm. The DA had vertically originated from the inferior aspect of the AoA and connected to the MPA at the origin of the LPA. A ridge was found on the inner surface of the LPA at the insertion of the DA. Maximal coarctation of the LPA was seen at this site. An aneurysmal dilatation of the MPA (2.6 cm circumference) was noted. The position of the MPA and its bifurcation were normal. The right ventricle outflow tract and pulmonary valve ring were dilated. There was also a 0.5 cm

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Fig. 1. Longitudinal section at the junction of the left pulmonary artery (LPA) with the ductus arteriousus. A ridge (arrowhead ) is produced by the underlying ductal tissue (DT) extending into the wall of the left pulmonary artery. (H&E, original magnification ×40)

diameter membranous ventricular septal defect (VSD) and biventricular hypertrophy. The right arterial innominate trunk was elongated. The right subclavian artery arose at the level of the angle of the jaw. The left vertebral artery arose from the aortic arch between the left carotid and subclavian arteries. Histologic examination demonstrated displaced ductal tissue into the proximal half of the LPA wall (Fig. 1), identified by its characteristic fibrointimal proliferation, disrupted elastic fibers, and fibromuscular media. The LPA wall was recognized by its relatively thinner media with abundant uninterrupted elastic fibers. Sections of the right lung demonstrated features of pulmonary arterial hypertension characterized by redundant buckled arteries, intimal proliferation, medial hypertrophy, and muscularization of septal vessels (Fig. 2). Comparatively, the left lung showed pulmonary arteries with thin media. In case 2 the cardiac anatomy was unremarkable. The body measurements were appropriate for gestational age. No somatic congenital abnormalities were found. Examination of the great vessels disclosed a patent ductus arteriosus (PDA) and a ridge of ductal tissue in the LPA. The sections of lungs demonstrated significant morphologic differences in the intrapulmonary arteries. Those from the left lung had a fetal pattern characterized by a narrow lumen, thick muscular media, and prominent adventitia (Fig. 3). In contrast, those from the right lung were dilated and had thin muscular media.

Discussion An intraluminal ridge was identified at the junction of the LPA with the DA at autopsy in both infants. The

caliber of the LPA was significantly less than half that of the RPA. Normally, both pulmonary arteries have the same diameter. Elzenga et al. [8] reported 41 cases of pulmonary valve atresia and pulmonary orifice atresia; in 12 cases they identified an intraluminal ridge in a pulmonary artery branch. Eight cases had ductal tissue extending into the pulmonary artery branch. Our cases are different from those in the series of Elzenga et al., as isolated CoLPA was present without right ventricle outflow tract obstruction. Pulmonary arterial stenoses are often associated with other cardiovascular anomalies [19]. Momma et al. [23], in an angiographic study, found nine cases of juxtaductal LPA stenosis and five cases of juxtaductal LPA atresia. Baum et al. [1], in a clinicoradiologic study, reported 26 cases of pulmonary arterial branch stenoses. However, the exact sites of the pulmonary stenoses were not described. Cases of pulmonary artery or branch atresia have also been reported in association with several congenital heart malformations [5, 26]. Congenital heart disease was reported in 88% of cases with a unilateral pulmonary artery [25]. Except for the VSD, no other congenital cardiac abnormality was noted. The DA was patent in our cases. However, PDA cannot be contemplated. An abnormal unfragmented subendothelial elastica lamina, characteristic of PDA [11], was not present. In normal neonates closure of the DA usually occurs about 10–15 hours after delivery and may extend to 15 days of age [3]. In cases of CoLPA the DA may be dysfunctional, which in turn may interfere with its closure. Aneurysmal dilatation of the MPA, in case 1, is considered a secondary event. VSD may be important to define the morphologic relations among the DA, PA, and aorta [21, 27]. The presence of VSD,

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Fig. 2. Section of the right lung, case 1. Pulmonary arteriole (arrowhead ) shows medial hypertrophy and narrow lumen. (H&E, original magnification ×200)

Fig. 3. Section of left lung, case 2. Pulmonary arterioles (arrowheads) show tortuosity, medial hypertrophy, and narrow lumens. (H&E, original magnification ×200)

with a right-to-left shunt, or vice versa, may affect the morphologic features of the pulmonary arteries. The DA and proximal portion of the LPA are derived from the sixth aortic arch. A ductal tissue ridge has been demonstrated in the aortic lumen in preductal coarctation of the aorta (CoA) [2, 7, 9]. With CoLPA the abnormal extension of ductal tissue into the LPA is analogous to that observed in cases of CoA. Cardiac neural crest cells are important in the embryogenesis of the sixth aortic arch [31]. Maldevelopment of neural crest cells has been implicated in CoA [18]. CoLPA may be related to a similar abnormality. This embryologic process may even be operative in other types of AoA defects [28]. The hemodynamic consequences of CoLPA can be

important. Disproportionate pulmonary vascular changes were observed. In case 1, the left lung showed small arteries with thinned media, whereas the right lung displayed medial muscular hypertrophy of the small arteries. In case 2 the opposite was noted: The small arteries of the left lung had a fetal appearance (thickened muscular media, constricted lumens, and abundant adventitia) [30], whereas the small arteries of the right lung displayed thinned muscular media. In these two cases the dissimilar features of the peripheral pulmonary arteries may be age-dependent. Newborn pigs with ligation of the LPA showed decreased left lung volume with small alveoli compared with that of the right lung [16]. Experimentally, a reduced number of resistant vessels with decreased medial/external ratios and thinning of their walls

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were demonstrated when pulmonary arteries were banded [22]. Persistent fetal lung vascular pattern has been demonstrated as an initial response to pulmonary hypertension [13, 14]. In a case of accidental occlusion of the RPA the left lung showed changes of pulmonary hypertension, whereas the right lung had only minimal vascular changes [10]. In a case of RPA stenosis, the left lung showed narrowed small arteries with increased muscle, and the right lung had decreased muscularization of small arteries [17]. These changes are similar to those observed in the right lung of our first case. Pool et al. [25] reported hypertensive changes in 53% of contralateral lungs in cases of unilateral absence of the pulmonary artery (UAPA). CoLPA and UAPA are morphologically different, but their hemodynamics may be similar. Secondary pulmonary hypertensive changes may be associated with regional blood flow variations, as reported in cases of segmentary arterial stenoses [4, 24]. A systemic-pulmonary arterial anastomosis may produce secondary pulmonary hypertension [5]. In our cases there was neither peripheral pulmonary arterial stenosis nor systemic pulmonary collaterals. Therefore the pulmonary arterial features are likely secondary to hemodynamic changes. High resistance is a characteristic of the fetal pulmonary arterial system. Haworth et al. [15] have demonstrated that reduction of the pulmonary arterial pressure within the first 24 hours of life depends on vasodilatation and recruitment of small acinar arteries. During the second to third day of life there is a change from thick-narrow to thin-wide arterioles [30]. The decreasing wall thickness takes place rapidly after birth, and it is almost completed at 4 months of age [6]. In case 2 the persistent fetal pulmonary arterial pattern of the left lung may be related to hypoperfusion during the fetal period and failure of postnatal vasodilatation. On the other hand, the small arteries and arterioles of the right lung showed a wide lumen and thinned walls, as expected for this patient’s age. A congenital anomaly amenable of surgical correction, CoLPA must be considered in the differential diagnosis of infantile respiratory distress syndrome. Asymmetric lung circulation may cause serious disturbances of the ventilatory/perfusion ratio and ultimately may result in pulmonary hypertension of the hyperperfused right lung. Early diagnosis of CoLPA is important to avert irreversible changes in the pulmonary vasculature. Cardiac catheterization and angiography may be helpful [1, 19]. Two-dimensional Doppler echocardiography and magnetic resonance imaging may also permit visualization of the central pulmonary branches, aortic arch, and DA [12, 20, 29]. Failure to recognize this rare but potentially treatable condition can be fatal.

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Pediatric and Adult Congenital Cardiovascular Self-Assessment Program (PACCSAP) Edited by Ruth Collin-Nakai, M.D.; The American College of Cardiology This is the first American College of Cardiology self-assessment program designed as a multimedia program from the beginning. For the first time, embryonic development of the heart will be explained and will appear in three-dimensional images, thanks to refined multimedia technology. Overall, the program will be highly imageand audio-intensive. Targeted to pediatric cardiologists, pediatric cardiovascular surgeons, and adult congenital disease specialists, PACCSAP also will appeal to adult cardiologists and cardiovascular surgeons. Additionally, PACCSAP will offer information on the latest approaches to hot topics such as surgical techniques, myocardial mechanics, genetics, and congenital defects. More than 60 cardiac specialists contributed their expertise to the creation of this CD-ROM program. PACCSAP is divided into 10 interactive chapters. Chapter 1, Atherosclerosis and Children, reviews risk factors, detection of atherosclerosis, hypertension, and hyperlipidemia; while Chapter 2, Embryology and Pathology, delves into normal cardiac development, the role of cardiac neural crest, neural crest cardiovascular defects, pathology of cardiac defects, and syndromes. In Chapter 3, Cardiovascular Structure and Function, myocyte and cardiac mechanics, as well as pulmonary vascular development, are explored. Chapter 4, Diagnostic Imaging and Procedures, looks at venous techniques and procedures, including computed tomography, magnetic resonance imaging, positron emission tomography, nuclear imaging, transesophageal and quantitative echocardiography, intravascular ultrasound, fetal echocardiography, 3D reconstruction, and more. The subjects of hypoplastic left heart syndrome, pulmonary atresia, tetralogy of Fallot, single ventricle, and others are examined in Chapter 5, Congenital Heart Disease. Chapter 6, Medical Therapy, scrutinizes outpatient therapy for congestive heart failure, end-stage heart failure, thrombolytic therapy, atrial and ventricular tachycardia, and antiarrhythmic agents. Chapter 7, Surgical Therapy, covers right ventricular outflow re-operation, complex aortic valve disease, bidirectional Glenn and Fontan surgery, complex tetralogy/pulmonary atresia, hypoplastic left heart, and more. In the next chapter, Acquired Heart Disease, the experts review Kawasaki disease, hypertrophic and dilated cardiomyopathy, HIV infection and the heart myocarditis, rheumatic fever, endocarditis, and pediatric cardiac transplant. Chapter 9, Adult Congenital Heart Disease (ACHD), looks at Fontan, re-operation Marfan, and atrial switch adult patients; pregnancy and contraception, counseling and psychosocial issues in ACHD, and pulmonary vascular obstructive disease. The final chapter, Cardiac Intensive Care, delves into cardiac anesthesia, mechanical ventilation, management of low cardiac output, neurologic sequelae of cardiac surgery, postoperative arrhythmias, pulmonary hypertension, and postoperative management of single ventricle. PACCSAP will also include Medline abstracts and references, bookmark areas, places to write notes, and a method to track self-assessment scores. Schedules for an early 1998 debut, PACCSAP will be available in both Windows and Macintosh formats. Elizabeth Wilson American College of Cardiology