Congenital Cardiac Anesthesia Society
A Section of the the Society for Pediatric Anesthesia

{“questions”:{“363zz”:{“id”:”363zz”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Ahmed Zaghw, MD and Destiny F. Chau, MD – Arkansas Children\u2019s Hospital\/University of Arkansas for Medical Sciences, Little Rock, AR \r\nA 19-year-old patient with autism and severe anxiety presents for dental restoration under general anesthesia prior to ventricular septal defect (VSD) repair. The patient has neither cardiac symptoms nor a history of infective endocarditis. A yearly transthoracic echocardiogram demonstrates a 4 mm perimembranous VSD with left to right shunt and a gradient of 90 mmHg across the defect. Both ventricles are of normal size and function. The right aortic cusp prolapses into the VSD, resulting in mild aortic valve insufficiency. In this patient, prevention of which of the following diagnoses is the MOST likely indication for VSD closure? “,”desc”:”EXPLANATION \r\nIsolated ventricular septal defect (VSD) is the most common form of congenital heart disease (CHD). VSDs allow the shunting of blood between the systemic and pulmonary circulations, increasing the volume load of the left heart. The magnitude and direction of the intracardiac shunt depends on the pressure gradient between the ventricular chambers and the resistance to flow, which is largely determined by the size of the shunt. Over time, patients with untreated VSD suffer from decreased exercise tolerance, heart failure, and pulmonary arterial hypertension (PAH). The onset and progression of symptoms are associated with the degree of the intracardiac shunt. Patients with moderate and large VSDs exhibit symptoms of heart failure during early infancy. Volume and pressure overload from intracardiac shunting leads to the development of left atrial and ventricular dilatation with eventual heart failure. Without treatment, the effective systemic cardiac output progressively decreases as a larger proportion of the left ventricular output is circulated through the intracardiac shunt to the pulmonary circulation (Qp) rather than the systemic circulation (Qs), resulting in a Qp:Qs of greater than one. Over time, this increase in pulmonary blood flow may also result in pulmonary vascular disease and pulmonary arterial hypertension (PAH). With long standing, unrestricted left to right intracardiac shunt, pulmonary arterial pressure may exceed systemic arterial pressure, leading to the shunt reversal and Eisenmenger syndrome. \r\n\r\nA long-term follow-up study by Corone et al. of 790 patients with unrepaired VSDs provides interesting insights into the natural history of unrepaired defects. The study showed that the overall survival rate of patients at 25 years of age with small, moderate, and large unrepaired VSDs was 96%, 86%, and 61%, respectively. Patients with Eisenmenger syndrome had the lowest survival rate of 42%. Small restrictive VSDs are usually associated with small intracardiac shunts, a Qp:Qs < 1.5, and near normal pulmonary vascular resistance. Patients with moderately restrictive VSDs and a Qp:Qs \u2265 1.5:1 and < 2:1 often have mild to moderate PAH. Patients with large, nonrestrictive defects are at high risk for early development of PAH and Eisenmenger syndrome. A 2023 Danish study by Eckerstrom et al. examining survival of patients with repaired and unrepaired VSDs demonstrated that the causes of death were cardiac-related in approximately a third of patients with unrepaired defects and approximately two thirds of patients with surgically repaired VSDs. Interestingly, although repaired VSDs have a higher survival than unrepaired patients, their survival is still lower compared with the general population, after excluding operative mortality. The reasons for these differences in mortality are unclear but the authors speculate that the delayed effects of surgery such as intraoperative myocardial injury, residual intraventricular conduction defects, and ventricular dyssynchrony may be contributing factors. Approximately 6% of patients with isolated VSDs develop aortic valve prolapse, which can lead to aortic valve insufficiency (AI). The most affected cusp of the aortic valve is the right cusp. The Venturi effect is hypothesized to be a predominant factor in the development of AI associated with VSD.\r\n\r\nThe 2018 American Heart Association (AHA) guidelines for management of adults with congenital heart disease recommend conservative, watchful management of small restrictive VSDs in the absence of aortic valve prolapse or more than trivial aortic valve insufficiency. Once aortic valve prolapse develops, there is a likelihood of progression and development of AI. Since the likelihood of spontaneous closure of a perimembranous VSD is low, closure may prevent further progression of AI and later need for aortic valve replacement. At the time of the VSD closure, the aortic valve can be inspected and repaired if indicated.\r\n\r\n \r\nPatients with unrepaired VSD have an increased risk of infective endocarditis, usually affecting the tricuspid and pulmonary valves. Those patients with restrictive VSDs and a history of infective endocarditis warrant VSD closure per AHA guidelines. \r\n\r\n\r\nIn summary, the patient in the stem has a restrictive VSD with a high-pressure gradient across the defect (>90 mmHg), lack of left heart enlargement, and lack of cardiac symptoms. Both aortic cusp prolapse and mild AI were newly demonstrated on a yearly echocardiogram, which fall into the AHA criteria for VSD closure. \r\n\r\n\r\n\r\n \r\nREFERENCES \r\nTweddell JS, Pelech AN, Frommelt PC. Ventricular septal defect and aortic valve regurgitation: pathophysiology and indications for surgery. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu<\/em>. 2006:147-52. doi: 10.1053\/j.pcsu.2006.02.020. \r\n\r\nEckerstr\u00f6m F, Nyboe C, Maagaard M, Redington A, Hjortdal VE. Survival of patients with congenital ventricular septal defect. Eur Heart J<\/em>. 2023 Jan 1;44(1):54-61. doi: 10.1093\/eurheartj\/ehac618. \r\n\r\nStout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA\/ACC Guideline for the Management of Adults with Congenital Heart Disease: Executive Summary: A report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in J Am Coll Cardiol. 2019 May 14;73(18):2361]. J Am Coll Cardiol<\/em>. 2019;73(12):1494-1563. doi: 10.1016\/j.jacc.2018.08.1028 \r\n\r\nBukhari SM, Desai M, Zurakowski D, et al. Fate of aortic regurgitation after isolated repair of ventricular septal defect with concomitant aortic regurgitation in children. JTCVS Open<\/em>. 2023; 13:271-277. Published 2023 Jan 28. doi: 10.1016\/j.xjon.2022.12.015\r\n\r\nCorone P, Doyon F, Gaudeau S et al. Natural history of ventricular septal defect. A study involving 790 cases. Circulation<\/em>. 1977; 55:908-15. \r\n\r\n”,”hint”:””,”answers”:{“azy0y”:{“id”:”azy0y”,”image”:””,”imageId”:””,”title”:”A.\tPulmonary arterial hypertension “},”7xeyn”:{“id”:”7xeyn”,”image”:””,”imageId”:””,”title”:”B.\tModerate\/Severe aortic valve insufficiency “,”isCorrect”:”1″},”hd3gc”:{“id”:”hd3gc”,”image”:””,”imageId”:””,”title”:”C.\tInfective endocarditis”}}}}}

{“questions”:{“szdh6”:{“id”:”szdh6″,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Ahmed Zaghw, MD and Destiny F. Chau, MD – Arkansas Children\u2019s Hospital\/University of Arkansas for Medical Sciences, Little Rock, AR \r\n\r\nA 55-year-old woman presents for urgent eye surgery. A review of systems reveals decreasing exercise tolerance and palpitations over the previous six months. No prior medical history is available. An echocardiogram demonstrates a secundum atrial septal defect (ASD). What is the MOST likely long-term complication associated with an unrepaired secundum ASD? “,”desc”:”EXPLANATION \r\nAn atrial septal defect (ASD) allows for intracardiac shunting of blood. The direction of intracardiac shunting depends on the pressure gradient between atrial chambers, the compliance of the ventricles, and the resistance to blood flow which is largely determined by the size of the defect. A low-pressure gradient between the atria will result in a low volume shunt. Consequently, this leads to slow clinical progression and allows most patients to remain asymptomatic for many years, thereby delaying the diagnosis of ASD. The age when symptoms start is highly variable. Atrial septal defect is the most common congenital heart disease diagnosed in adults, accounting for 25-30% of new diagnoses. A 1970 study by Campbell that included patients with primum ASDs revealed mortality less than 1% in the first two decades of life; however, mortality sharply increases thereafter with 75% dying during the 3rd to 6th decades. \r\n\r\nOver time, patients with an untreated ASD have decreased exercise tolerance, dyspnea and experience worsened cardiopulmonary outcomes. Exercise intolerance is the most common initial presenting symptom. Long-term complications include atrial arrhythmias, heart failure, thromboembolism, and pulmonary arterial hypertension. Long-standing atrial level shunting leads to volume overload and dilatation of right ventricle and atrium, which has a detrimental impact on left ventricular geometry and function. The left ventricle becomes less compliant with age and acquires diastolic dysfunction due to the increased volume load, which in turn increases the degree of atrial level shunting. Additionally, increased pulmonary blood flow may lead to pulmonary hypertension and to the development of pulmonary vascular disease. \r\n\r\nThe most common complications of longstanding right atrial dilation and stretch are atrial arrhythmias, with atrial fibrillation and atrial flutter being most common. Although atrial arrhythmias seldom occur before the age of 40, greater than 50% of patients over the age of 60 experience atrial fibrillation and up to 20% experience atrial flutter. Atrial tachyarrhythmias may accelerate chronic heart failure and lead to decompensation, particularly in older patients. \r\n\r\nPulmonary hypertension (PH) is relatively rare even in patients with large unrepaired ASDs. Severe PH, along with Eisenmenger syndrome, is reported to occur in 5-10% of patients with unrepaired ASD. Patients with both repaired and unrepaired ASDs are at a higher risk of thromboembolic complications, such as stroke. In patients with unrepaired ASD, the frequency of stroke is 4% due to paradoxical embolization. The frequency of stroke in patients with repaired ASDs is 1.4%. Stoke in this patient population is thought to be related to atrial fibrillation or pulmonary vein remodeling after ASD closure. Anticoagulation for six to twelve months after ASD closure in older patients is recommended, regardless of the presence of an atrial arrhythmia. \r\n\r\nThe 2018 American Heart Association guidelines recommend ASD closure during childhood or early adulthood prior to the occurrence of symptoms. Older adults need to be evaluated for pulmonary hypertension and Eisenmenger syndrome prior to ASD closure. The goal of closure is to prevent further clinical deterioration, while managing the longstanding incurred complications such as arrhythmia and heart failure. In most patients, functional capacity often improves after ASD closure. In patients with unrepaired ASD, the most prevalent long-term complication is atrial tachyarrhythmia. The patient described in the stem has symptoms consistent with an atrial tachyarrhythmia. \r\n\r\n\r\n \r\n\r\nREFERENCES \r\nWebb G, Gatzoulis MA. Atrial septal defects in the adult: recent progress and overview. Circulation<\/em>. 2006;114(15):1645-1653. doi:10.1161\/CIRCULATIONAHA.105.592055\r\n\r\nBrida M, Chessa M, Celermajer D, et al. Atrial septal defect in adulthood: a new paradigm for congenital heart disease. Eur Heart J<\/em>. 2022;43(28):2660-2671. doi:10.1093\/eurheartj\/ehab646\r\n\r\nCampbell M. Natural history of atrial septal defect. Br Heart J<\/em>. 1970;32(6):820-826. doi:10.1136\/hrt.32.6.820\r\n\r\nStout KK, Daniels CJ, Aboulhosn JA, et al. 2018 AHA\/ACC Guideline for the Management of Adults with Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in J Am Coll Cardiol. 2019 May 14;73(18):2361]. J Am Coll Cardiol<\/em>. 2019;73(12):1494-1563. doi:10.1016\/j.jacc.2018.08.1028\r\n”,”hint”:””,”answers”:{“xy49q”:{“id”:”xy49q”,”image”:””,”imageId”:””,”title”:”A. Stroke “},”p0o6b”:{“id”:”p0o6b”,”image”:””,”imageId”:””,”title”:”B. Pulmonary hypertension “},”d7rzg”:{“id”:”d7rzg”,”image”:””,”imageId”:””,”title”:”C. Atrial tachyarrhythmia”,”isCorrect”:”1″}}}}}

{“questions”:{“3gf66”:{“id”:”3gf66″,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Pedro Solorzano, MD and Destiny F. Chau, MD – Arkansas Children\u2019s Hospital\/University of Arkansas for Medical Sciences, Little Rock, AR \r\n\r\nA 4-year-old child with Kleefstra syndrome and obstructive sleep apnea presents for tonsillectomy and adenoidectomy. Which of the following cardiac defect is MOST commonly associated with Kleefstra syndrome? “,”desc”:”EXPLANATION \r\nKleefstra Syndrome, previously \u201c9q subtelomere deletion syndrome\u201d, is a rare disorder linked to microdeletions or mutations on 9q34.3, which is related to the Euchromatin Histone Methyl Transferase 1 (EHMT1) gene. This gene encodes a histone methyltransferase enzyme involved in chromatin remodeling. Although most reported cases to date involve de novo mutations, autosomal dominant familial inheritance occurs in cases of balanced translocations or somatic mosaicism. \r\n\r\n\r\nThe phenotype for Kleefstra syndrome includes microcephaly, arched eyebrows, synophrism (unibrow), hypertelorism, anteverted nares, mid-face hypoplasia, macroglossia, and prognathism. Typical facial features of a patient with Kleefstra syndrome are illustrated in the picture below. \r\n\r\n\r\n\r\nFigure: Phenotypical features of Kleefstra syndrome. Karlak et al. Creative Commons License\r\n\r\n\r\nMajor associated defects include congenital heart disease (40%), urogenital disease (50%), recurrent infections (60%), intellectual disability (100%), behavioral problems (75%), obesity (40%), hearing deficits (25%), and seizures (25%). The behavioral\/ psychiatric issues have been observed to worsen after puberty. An increasing number of EHMT1<\/em> mutations have been detected in patients with the Kleefstra syndrome phenotype in recent years. \r\n\r\nAnalysis of the two largest known Kleefstra syndrome registries has demonstrated a 40% prevalence of cardiovascular abnormalities including atrial septal defects (14%), ventricular septal defects (12%), Tetralogy of Fallot with pulmonary valve stenosis (8%), cardiomyopathy (1%) and vascular malformations (9%). It also revealed a prevalence (8%) of early-onset arrhythmias including atrial fibrillation, supraventricular tachycardia, and ventricular tachycardia, in the absence of structural heart disease. Pulmonary hypertension (PH) in patients with repaired congenital heart disease with severity out of proportion to the preoperative pathophysiology has been observed in patients with Kleefstra syndrome. Concurrent sleep apnea likely contributes to the severity of PH in some patients with this syndrome. \r\n\r\n\r\nPatients with Kleefstra syndrome present for a range of procedures necessitating anesthetic care. A thorough multisystem preoperative evaluation is essential for delineating anesthetic considerations and comprehensive perioperative planning. In addition to congenital heart disease, cardiovascular assessment should include screening for pulmonary hypertension and malignant arrhythmias, even in the absence of structural heart disease. Phenotypical facial features may cause difficulty with airway management. Associated congenital cardiac lesions warrant anesthetic management tailored to the specific cardiac defect. \r\n\r\n\r\nOf the three choices listed, this patient is most likely to have had an atrial septal defect (ASD). ASDs and ventricular septal defects are the most prevalent congenital cardiac lesions associated with Kleefstra syndrome. At present, left sided heart defects such as coarctation of the aorta and hypoplastic left heart syndrome are rarely reported in patients with Kleefstra syndrome. \r\n\r\n\r\n\r\n\r\n \r\n\r\nREFERENCES \r\n\r\nKleefstra Syndrome UK. Accessed November 14, 2023. https:\/\/www.kleefstrasyndrome.org\/ \r\n\r\n\r\nKarlak V, Jankowski J, Kolasi\u0144ska J, Nijakowski K. Kleefstra Syndrome\u2014Dental Manifestations and Needs: A Case Report with a Literature Review. Case Rep Dent<\/em>. 2023;2023:2478465. doi: 10.1155\/2023\/2478465\r\n\r\n \r\nWillemsen MH, Vulto-van Silfhout AT, Nillesen WM et al. Update on Kleefstra Syndrome. Mol Syndromol<\/em>. 2012;2(3-5):202-212. doi: 10.1159\/000335648\r\n \r\n\r\nVolkan Okur, Nees SN, Chung WK, Krishnan U. Pulmonary hypertension in patients with 9q34.3 microdeletion-associated Kleefstra syndrome. Am J Med Genet A<\/em>. 2018;176(8):1773-1777. doi: 10.1002\/ajmg.a.38852\r\n \r\n\r\nVasireddi SK, Draksler TZ, Bouman A et al. PO-04- 124 arrhythmias including atrial fibrillation in KLEEFSTRA syndrome: A possible epigenetic link. Heart Rhythm<\/em>. 2023;20(5): S597-S598. doi:10.1016\/j.hrthm.2023.03.1263\r\n\r\n\r\nCampbell CL, Collins RT, Zarate YA. Severe neonatal presentation of Kleefstra syndrome in a patient with hypoplastic left heart syndrome and 9q34.3 microdeletion. Birth Defects Res A Clin Mol Teratol<\/em>. 2014;100(12):985-990. doi:10.1002\/bdra.23324\r\n\r\n”,”hint”:””,”answers”:{“qo9cu”:{“id”:”qo9cu”,”image”:””,”imageId”:””,”title”:”A. Atrial septal defect “,”isCorrect”:”1″},”2t8qd”:{“id”:”2t8qd”,”image”:””,”imageId”:””,”title”:”B. Coarctation of the aorta”},”iypkr”:{“id”:”iypkr”,”image”:””,”imageId”:””,”title”:”C. Hypoplastic left heart syndrome “}}}}}

{“questions”:{“cgrip”:{“id”:”cgrip”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Author: Nicholas Houska, DO – University of Colorado, Children\u2019s Hospital Colorado \r\n\r\nAccording to recent data, which of the following percentages reflects the proportion of pediatric cardiac anesthesia programs in the United States that are actively recruiting more faculty? \r\n\r\n”,”desc”:”EXPLANATION \r\nIn the last decade there has been increasing focus on the training and workforce of pediatric cardiac anesthesiologists domestically and worldwide. While the recent addition of the subspecialty to the Accreditation Council for Graduate Medical Education (ACGME) aims to formalize education and training, there is still a question of the adequacy of the current and future workforce. In 2022, to address this dearth of information, Nasr et al. conducted a survey of 113 pediatric cardiac anesthesiology programs in the United States. Analysis of the fifty-nine respondent programs with complete data provides insight into the current practice of pediatric cardiac anesthesiology in the United States. \r\n\r\nInstitutions that took part in the survey provided data for 50,463 cases of the Society of Thoracic Surgeons Congenital Surgery Database (STS-CHD) over the two year time frame (before the COVID pandemic) representing 63% of the STS-CHD reported cases for the study. Across the fifty-nine institutions, the total practicing pediatric cardiac anesthesiologists numbered 307, with a median of five per institution. Pediatric cardiac anesthesiologists reported spending 35% of their time in the cardiac operating room (OR), 25% of their time in the catheterization lab, and 25% of their time in imaging\/other sites. The respondents reported that the median number of OR cases per year with and without cardiopulmonary bypass was 60 and 26 respectively. \r\n\r\nThe predominant practice model for pediatric cardiac anesthesiology was an academic institution with trainees (71.4%) at free-standing children\u2019s hospitals (42.9%). The staffing model for OR cases was overwhelmingly (90%) 1:1 supervision while 2:1 supervision was more common in the catheterization labs (40%). Supervised providers were most commonly pediatric anesthesia fellows (59.3%) followed by nurse anesthetists (54.2%), residents (33.9%), and pediatric cardiac anesthesia fellows (25.4%). \r\n\r\nThirty-eight percent of pediatric anesthesiologists caring for children with congenital heart disease reported having completed a fellowship in pediatric cardiac anesthesia. An additional 17% pursued other training pathways such as adult cardiac anesthesiology fellowships and pediatric critical care fellowships. The remaining 44% learned the practice through on the job training. Thirty-four percent of institutions had a pediatric cardiac anesthesia fellowship at the time of the survey.\r\n\r\nNearly half (49.2%) of the fifty-nine institutions surveyed reported they were actively recruiting pediatric cardiac anesthesiologists. Impending retirement of staff was reported by 10 (17%) of 59 institutions. About one third of institutions expected no immediate changes in staffing levels.\r\n\r\nThis survey helps to illustrate the heterogeneity of the practice, training, and staffing of the pediatric cardiac anesthesiology workforce in the United States. It also shows that there is a current and future need for anesthesiologists trained in the care of children with congenital heart disease. The combination of decreasing pediatric anesthesiology fellowship applicants and the pediatric cardiac anesthesiology subspecialty combined with impending retirement of senior practitioners may soon lead to a workforce crisis in the field. \r\n\r\n\r\n\r\n \r\nREFERENCES \r\nNasr VG, Staffa SJ, Vener DF, et al. The practice of pediatric cardiac anesthesiology in the United States. Anesth Analg<\/em>. 2022;134(3):532-539.\r\n”,”hint”:””,”answers”:{“i5hxl”:{“id”:”i5hxl”,”image”:””,”imageId”:””,”title”:”A.\t25%”},”6sa7u”:{“id”:”6sa7u”,”image”:””,”imageId”:””,”title”:”B.\t50%”,”isCorrect”:”1″},”mukf3″:{“id”:”mukf3″,”image”:””,”imageId”:””,”title”:”C.\t75%”}}}}}

{“questions”:{“vi0mc”:{“id”:”vi0mc”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Nicholas Fawley, DO – Children\u2019s Hospital Los Angeles \r\n\r\nA 21-year-old female with Trisomy 21, who underwent complete atrioventricular canal (CAVC) repair as an infant, presents with fatigue and progressive dyspnea on exertion. A transthoracic echocardiogram demonstrates an estimated right ventricular systolic pressure of 64 mmHg. Which of the following medications improves exercise capacity in adults with Trisomy 21 and pulmonary hypertension? \r\n”,”desc”:”EXPLANATION \r\nChildren with Trisomy 21 (T21) have an increased incidence of pulmonary hypertension (PH). There are a variety of risk factors that contribute to the development of pulmonary hypertension in these patients, including congenital heart disease. However, there are other genetic, pulmonary, vascular and metabolic factors that also contribute to the overall risk of developing PH. The most frequent congenital heart defects found in patients with T21 include atrioventricular septal defects and ventricular septal defects. Both defects are associated with left-to-right intracardiac shunting of blood, leading to increased pulmonary blood flow, increased pulmonary arterial pressure and increased arterial wall shear stress. Ultimately, over time, the result is endothelial dysfunction, altered vasoactive mediator expression, and vascular remodeling. Progressive endothelial intimal fibrosis leads to arterial narrowing and further shear stress. The vascular remodeling associated with increased pulmonary blood flow is a key component in the timing of corrective surgery. Although early surgical repair can prevent continued hemodynamic stress on the pulmonary vasculature, elevated pulmonary arterial pressures may persist after repair. There is some evidence to suggest intrinsic endothelial dysfunction is present in patients with T21. This is supported in this patient population with evidence of elevated endothelial vasoconstrictors such as endothelin-1, impaired production of nitric oxide, and an imbalance of vasoactive eicosanoid to prostacyclin ratios. Furthermore, upregulation of proinflammatory genes in patients with T21 contributes to endothelial dysfunction and impaired nitric oxide production. \r\n\r\nRespiratory disorders are prevalent in children with T21 and may contribute to the development of PH. Functional and anatomic upper airway obstruction, obstructive and central sleep apnea, chronic aspiration, and recurrent lower airway infections can lead to increased pulmonary vascular resistance secondary to hypoxic pulmonary vasoconstriction. Small studies in children with T21 provide evidence of pulmonary hypoplasia with reduced vascular surface area and impaired microvascular development. Pulmonary hypoplasia contributes to hypoxemia during periods of increased oxygen demand. Additionally, pulmonary vein stenosis may be underdiagnosed in this population, which results in pulmonary venous hypertension and upstream pulmonary arterial hypertension. Early identification of respiratory disorders, with intervention, can potentially circumvent the development of PH. Despite early resolution, subsequent respiratory disease can cause recurrence of PH later in life. \r\n\r\nPharmacologic treatment of PH in infants and children with T21 may be accompolished through targeted monotherapy or combination therapy. In 2023, Hopper and colleagues studied data from patients with T21 in the Pediatric Pulmonary Hypertension Network Registry and found that prescribing practices are similar for pediatric patients with and without T21. Unfortunately, there are few studies comparing the efficacy of PH pharmacotherapies in pediatric patients with T21. Due to upregulated endothelial vasoconstrictors and endothelial dysfunction in T21, there may be particular benefit of endothelin receptor antagonists (ERAs), such as bosentan. In adults with T21 and PH, D\u2019Alto and colleagues found that bosentan improved WHO functional classification, exercise capacity, and pulmonary hemodynamics. \r\n\r\nOther targeted PH pharmacotherapies include phosphodiesterase type V inhibitors (sildenafil), prostacyclins (treprostinil), calcium channel blockers, and selective prostacyclin receoptor agonists (selexipag). Sildenafil is a widely prescribed therapy in infants and children with PH and has been studied in the STARTS-1 and STARTS-2 trials. However, a STARTS-1 trial sub-analysis by Beghetti and colleagues demonstrated that when comparing children with T21 compared to those without T21, sildenafil was well-tolerated but did not lead to meaningful improvements in pulmonary vascular resistance or mean pulmonary pressure. There is a lack of strong evidence-based recommendations for prostacyclin therapy in children with T21, but reduced prostacyclin production in patients with T21 suggests a possible role in pharmacotherapy. In guidelines from the American Heart Association and American Thoracic Society (AHA-ATS) on pediatric pulmonary hypertension, prostacyclin pharmacotherapy is recommended for pediatric patients with higher-risk disease severity of PH, defined by the following features: clinical evidence of right ventricular (RV) failure, WHO functional class of III & IV, recurrent syncope, significant RV enlargement\/dysfunction by echocardiography, pulmonary vascular resistance index > 20 WU.m^{2 <\/sup>, cardiac index of less than 2.0 L\/min\/m2<\/sup>, pulmonary vascular resistance\/systemic vascular resistance ratio > 1, significantly elevated brain natriuretic peptide, shorter 6-minute walk distance, and peak VO_{2<\/sub> < 15 ml\/kg\/min. Bosentan is approved for pediatric patients aged 3 to 17 years, while sildenafil is approved for ages 1 to 17 years by the Federal Drug Administration for the treatment of pulmonary arterial hypertension. \r\n\r\nAlthough studies of targeted PH therapy in children and adults with Trisomy 21 are lacking, D\u2019Alto and colleagues demonstrated that bosentan improves WHO functional classification, exercise capacity, and pulmonary hemodynamics in adults with PH and Trisomy 21. \r\n\r\n\r\n \r\nREFERENCES \r\n\r\nAbman SH, Hansmann G, Archer SL, et al. Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society. Circulation <\/em>. 2015; 132: 2037-99. \r\n\r\nBarst RJ, Ivy D, Gaitan G, et al. A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study of Oral Sildenafil Citrate in Treatment-Na\u00efve Children With Pulmonary Arterial Hypertension. Circulation <\/em>. 2012; 125(2): 324-34. \r\n\r\nBarst RJ, Beghetti M, Tomas P, et al. STARTS-2: Long-Term Survival With Oral Sildenafil Monotherapy in Treatment-Na\u00efve Pediatric Pulmonary Arterial Hypertension. Circulation<\/em>. 2014; 129(13): 1914-23. \r\n\r\nBeghetti M, Rudzinski A, Zhang M. Efficacy and safety of oral sildenafil in children with Down syndrome and pulmonary hypertension. BMC Cardiovasc Disord<\/em>. 2017; 17(1): 177. \r\n\r\nBush D, Galambos C, Dunbar D. Pulmonary hypertension in children with Down Syndrome. Pediatr Pulmonol<\/em>. 2021; 56: 621-29. \r\n\r\nD\u2019Alto M, Romeo E, Argiento P, et al. Therapy for pulmonary arterial hypertension due to congenital heart disease and Down\u2019s syndrome. Int J Cardiology<\/em>. 2013; 164: 323-6. \r\n\r\nHopper RK, Abman SH, Elia EG, et al. Pulmonary Hypertension in Children with Down Syndrome: Results from the Pediatric Pulmonary Hypertension Network Registry. J Pediatr<\/em>. 2023; 252: 131-40.\r\n”,”hint”:””,”answers”:{“vb5ri”:{“id”:”vb5ri”,”image”:””,”imageId”:””,”title”:”A.\tSildenafil”},”jrr1s”:{“id”:”jrr1s”,”image”:””,”imageId”:””,”title”:”B.\tBosentan”,”isCorrect”:”1″},”xdusv”:{“id”:”xdusv”,”image”:””,”imageId”:””,”title”:”C.\tTreprostinil”}}}}}}}