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Pulmonary Vein Stenosis in Children: a Programmatic Approach Employing Primary and Anatomic Therapy

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Pulmonary Vein Stenosis in Children: a Programmatic Approach Employing Primary and Anatomic Therapy children Perspective Pulmonary Vein Stenosis in Children: A Programmatic Approach Employing Primary and Anatomic Therapy James A. Kuo 1 and Christopher J. Petit 2,* 1 Division of Pediatric Cardiology, Children’s Healthcare of Atlanta, Emory University, Atlanta, GA 30322, USA; [email protected] 2 Division of Cardiology, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, Morgan Stanley Children’s Hospital of New York, BN-263a, Pediatric Cardiology, 3859 Broadway, New York, NY 10032, USA * Correspondence: [email protected] Abstract: Pulmonary vein stenosis (PVS) is a difficult condition to treat due to recurrence and progression. In 2017, we developed a comprehensive PVS Program at our center to address the multidisciplinary needs of these patients. We discuss the components of our program and our approach to these patients, using a combination of primary (medical) therapy in addition to anatomic therapy to preserve vessel patency. A multidisciplinary approach to treating these challenging patients is critical. Keywords: pulmonary vein stenosis; congenital heart defect; drug therapy 1. Introduction Citation: Kuo, J.A.; Petit, C.J. Pulmonary Vein Stenosis in Children: Pulmonary vein stenosis (PVS) in the pediatric population has been thought of as a A Programmatic Approach rare condition [1]. However, many clinicians are now recognizing the disease to be quite Employing Primary and Anatomic common, particularly among premature infants [2]. PVS has been typically classified as Therapy. Children 2021, 8, 663. primary PVS and secondary PVS. Secondary PVS is more easily understood, as it follows https://doi.org/10.3390/ surgical treatment of total or partial anomalous pulmonary venous connection (TAPVC and children8080663 PAPVC, respectively). Secondary PVS is seen as a post-operative complication in at least 10% of cases [3,4]. Primary PVS is an idiopathic condition associated with mesenchymal Academic Editor: Marco Carotenuto proliferation, leading to pulmonary venous vascular changes, often associated with chronic lung disease [5–7]. Both primary and secondary PVS have two unique aspects which Received: 7 June 2021 conspire to make the disease uniquely malignant: recurrence and progression. Accepted: 26 July 2021 Infants and young children with PVS endure a high exposure to morbidities and Published: 30 July 2021 mortality, particularly in the first 2 years of life [1,2,5,7]. These patients undergo a number of interventions in efforts to maintain patency of pulmonary veins (PV). Additionally, these Publisher’s Note: MDPI stays neutral patients experience growth failure for unclear reasons. with regard to jurisdictional claims in Recent studies have increased our understanding of the pathophysiology of this dis- published maps and institutional affil- ease. Animal models of PVS have demonstrated that anatomic PV narrowing can activate iations. a cascade of cellular and molecular pathways, which then lead to upstream conversion of vascular intima to myofibroblasts, as well as to cellular proliferation [8]. Clinicians have employed several approaches to relieving the obstructions resulting from PVS. Surgical and transcatheter therapies have provided temporary relief, but with disappointing mid- Copyright: © 2021 by the authors. and long-term outcomes. Licensee MDPI, Basel, Switzerland. This article is an open access article 2. PVS Program distributed under the terms and In 2017, we developed a comprehensive PVS Program at our center to address the conditions of the Creative Commons multidisciplinary needs of these patients. Recognizing that patients with PVS require Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ close surveillance and ongoing evaluation of their respiratory status, cardiac function, and 4.0/). growth failure, we developed a team which included input from cardiologists, a nutritionist, Children 2021, 8, 663. https://doi.org/10.3390/children8080663 https://www.mdpi.com/journal/children Children 2021, 8, x FOR PEER REVIEW 2 of 7 Children 2021, 8, 663 2 of 7 growth failure, we developed a team which included input from cardiologists, a nutri- tionist, and an oncologist, as well as occasionally from our pulmonary hypertension spe- and an oncologist, as well as occasionally from our pulmonary hypertension specialists. cialists. Based upon our review of prior studies, we felt strongly that immunomodulatory Based upon our review of prior studies, we felt strongly that immunomodulatory therapy therapy would be a critical component to our PVS Program. We also sought to make uni- would be a critical component to our PVS Program. We also sought to make uniform the form the follow-up, surveillance imaging, and reintervention necessary to improve sur- follow-up, surveillance imaging, and reintervention necessary to improve survival for this vival for this at-risk cohort [9,10]. at-risk cohort [9,10]. 3.3. Diagnosis Diagnosis and and Surveillance Surveillance AtAt our our center, center, most most patients patients with with PVS PVS have have been been identified identified with with echocardiography. echocardiography. However,However, we we have found aa concerningconcerning false-negativefalse-negative and and false-positive false-positive rate rate with with echocar- echo- cardiographydiography in in neonates neonates and and infants infants with with PVS.PVS. WeWe believebelieve therethere are multiple causes causes for for this.this. False False negative negative rates rates are are likely likely due due to to the the inability inability of of echocardiography echocardiography to to adequately adequately resolveresolve pulmonary pulmonary veinsveins andand toto identify identify true true anatomic anatomic obstruction obstruction in thein the setting setting of elevated of ele- vatedvelocities velocities in veins in whereveins left-to-rightwhere left-to-right shunts co-exist.shunts co-exist. Furthermore, Furthermore, PVS is a progressivePVS is a pro- dis- gressiveease. A comprehensivedisease. A comprehensive initial echocardiogram initial echocardiogram evaluating all evaluating cardiac structures—including all cardiac struc- tures—includingpulmonary veins—may pulmonary appear veins—may to rule out appear a pulmonary to rule out vein a anomaly,pulmonary such vein as anomaly, PVS. Sub- suchsequent as PVS. echocardiograms Subsequent echocardiograms on the same patient on the may same not patient focus may on thenot pulmonaryfocus on the veinspul- monaryagain, particularlyveins again, ifparticularly the indication if the for indi thecation subsequent for the subsequent echocardiograms echocardiograms is to evaluate is toventricular evaluate ventricular function, the function, status of the a persistentstatus of a ductus persistent arteriosus ductus (PDA), arteriosus or otherwise. (PDA), or It oth- can erwise.be difficult It can to be assess difficult in regionalto assessPVS in region as loweral PVS Doppler as lower gradients Doppler can gradients be seen can in affectedbe seen inveins affected and veins higher and gradients higher ingradients unaffected in unaffected veins due veins to redistribution due to redistribution of pulmonary of pulmo- blood naryflow blood [11]. Even flow the [11]. use Even of more the invasiveuse of more transesophageal invasive transesophageal echocardiography echocardiography can be difficult canto delineatebe difficult differences to delineate in gradient, differences especially in gradient, in the especially upper veins in the [12 upper]. veins [12]. GivenGiven the the limitations limitations of of echocardiography, echocardiography, we we rely rely on on computed computed tomographic tomographic angi- an- ographygiography (CTA) (CTA) (Figure (Figure 1)1 (Table) or catheter-based 1) or catheter-based angiography angiography for definitive for definitive diagnosis diagnosis of PVS. ofCTA PVS. has CTA been has preferred been preferred over cardiac over magneticcardiac magnetic resonance resonance imaging (cMR)imaging due (cMR) to its due shorter to itsacquisition shorter acquisition time and time higher and imaging higher resolution,imaging resolution, although although potential potential insights insights into regional into regionalpulmonary pulmonary blood flow blood may flow conceptually may conceptually be an advantage be an advantage of cMR [of13 cMR,14]. Serial[13,14]. CTA Serial for CTAour programfor our program has provided has provided insights insights not only not to distal only to pulmonary distal pulmonary artery and artery vein and anatomy, vein anatomy,but also airwaybut also anatomy airway andanatomy underlying and underlying lung parenchyma. lung parenchyma. Radiation doses Radiation from newerdoses fromCT scanners newer CT have scanners been significantly have been signific reducedantly with reduced optimized with imaging optimized techniques imaging [15 tech-]. We niqueshave used [15]. serial We have CTA used scans seri foral grading CTA scans and for tracking grading of progressionand tracking of of all progression pulmonary of veins all pulmonaryin each patient. veins Our in each PVS patient. Grading Our scale PVS is listedGrading in Table scale1 is. listed in Table 1. (A) (B) FigureFigure 1. 1. (A(A):): Coronal Coronal slice slice of of a aCT CT angiogram angiogram demonstrates demonstrates right right upper upper pulmonary pulmonary vein vein stenosis stenosis (green(green arrow). arrow). (B (B):): Posterior Posterior view view of of the the three-dimensiona three-dimensionall reconstruction reconstruction of
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