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

{“questions”:{“u22op”:{“id”:”u22op”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Author: Michael A. Evans, MD; Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Northwestern Feinberg School of Medicine \r\n\r\nA 25-year-old woman with a history of hypoplastic left heart syndrome status-post Fontan palliation presents at 35-weeks gestation in active labor after spontaneous rupture of membranes. Which of the following complications is MOST LIKELY to occur in a parturient with single ventricle physiology intrapartum or postpartum?”,”desc”:”EXPLANATION \r\nMaternal congenital heart disease (CHD) poses a major risk to mother and child. There is a higher risk of spontaneous abortions and fetal demise in mothers with CHD when compared to the general population, a higher preterm birth rate (10-12% for all CHD), a higher frequency of adverse neonatal events (small for gestational age, respiratory distress syndrome, intraventricular hemorrhage), and a higher perinatal mortality rate (>4x higher than the general population). \r\n\r\nWhen pregnancies in mothers with Fontan physiology are examined, the adverse event rates throughout pregnancy, delivery, and postpartum are all increased when compared to other forms of CHD and in mothers without CHD. The most commonly observed complications in Fontan pregnancies and parturients include preterm delivery (59-82%), thromboembolic events (2-15%), postpartum hemorrhage or bleeding events (14-50%), fetal growth restriction (46-70%), small for gestational age (20-57%), pregnancy loss (27-69%), arrhythmia (0-29%), ventricular dysfunction or heart failure (4-14%), and neonatal death (2-7%). \r\n\r\nThe risk of preterm delivery (59-82% of Fontan pregnancies) is consistently significantly higher than any of the listed other observed complications, thus Answer D is correct. Although arrhythmias (Answer A, 0-29% of Fontan pregnancies) are more common in single ventricle mothers compared to the general population, they are not more common than preterm \r\ndeliveries. The same is true of postpartum hemorrhage (Answer B, 14-50%) and thromboembolic events (Answer C, 2-15%), which are both clinically important and contribute significantly to maternal morbidity in Fontan pregnancies. \r\n\r\nA summary of selected literature examining mothers with Fontan physiology and perinatal outcomes can be found below: \r\n\r\n\r\nREFERENCES \r\nClark DE, Staudt G, Byrne RD, et al. Anesthetic Management in Parturients With Fontan Physiology. J Cardiothorac Vasc Anesth. <\/em>2023;37(1):167-176. doi:10.1053\/j.jvca.2022.07.009 \r\n\r\nGirnius A, Zentner D, Valente AM, et al. Bleeding and thrombotic risk in pregnant women with Fontan physiology. Heart.<\/em> 2021;107(17):1390-1397. doi:10.1136\/heartjnl-2020-317397 \r\n\r\nGarcia Ropero A, Baskar S, Roos Hesselink JW, et al. Pregnancy in Women With a Fontan Circulation: A Systematic Review of the Literature. Circ Cardiovasc Qual Outcomes.<\/em> 2018;11(5):e004575. doi:10.1161\/CIRCOUTCOMES.117.004575 \r\n\r\nCauldwell M, Steer PJ, Bonner S, et al. Retrospective UK multicentre study of the pregnancy outcomes of women with a Fontan repair. Heart.<\/em> 2018;104(5):401-406. doi:10.1136\/heartjnl-2017-311763 \r\n\r\nCanobbio MM, Warnes CA, Aboulhosn J, et al. Management of Pregnancy in Patients With Complex Congenital Heart Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association. Circulation.<\/em> 2017;135(8):e50-e87. doi:10.1161\/CIR.0000000000000458 \r\n\r\nBonner SJ, Asghar O, Roberts A, Vause S, Clarke B, Keavney B. Cardiovascular, obstetric and neonatal outcomes in women with previous fontan repair [published correction appears in Eur J Obstet Gynecol Reprod Biol. 2018 Jan 4;:]. Eur J Obstet Gynecol Reprod Biol. <\/em>2017;219:53-56. doi:10.1016\/j.ejogrb.2017.10.013 \r\n\r\nMonteiro RS, Dob DP, Cauldwell MR, Gatzoulis MA. Anaesthetic management of parturients with univentricular congenital heart disease and the Fontan operation. Int J Obstet Anesth. <\/em>2016;28:83-91. doi:10.1016\/j.ijoa.2016.08.004 \r\n\r\nGouton M, Nizard J, Patel M, et al. Maternal and fetal outcomes of pregnancy with Fontan circulation: A multicentric observational study. Int J Cardiol. <\/em>2015;187:84-89. doi:10.1016\/j.ijcard.2015.03.344\r\n”,”hint”:””,”answers”:{“oheyk”:{“id”:”oheyk”,”image”:””,”imageId”:””,”title”:”A. Cardiac Arrhythmia”},”wyzn6″:{“id”:”wyzn6″,”image”:””,”imageId”:””,”title”:”B. Postpartum Hemorrhage”},”r51uh”:{“id”:”r51uh”,”image”:””,”imageId”:””,”title”:”C. Thromboembolic Event”},”3j4cf”:{“id”:”3j4cf”,”image”:””,”imageId”:””,”title”:”D. Preterm Delivery”,”isCorrect”:”1″}}}}}

{“questions”:{“h76h7”:{“id”:”h76h7″,”mediaType”:”video”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:”https:\/\/ccasociety.org\/wp-content\/uploads\/2023\/01\/PRE-REPAIR_-Mid-Esophageal-Aortic-Valve-Long-Axis.mp4″,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Author: Kevin Spellman, MD and Michael A. Evans, MD; Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Northwestern Feinberg School of Medicine \r\n\r\nA 3-year-old male toddler with a history of balanced, complete atrioventricular septal defect who is status post a two-patch repair presents to the operating room for resection of a subaortic membrane. Pre- and post-repair intraoperative transesophageal echocardiogram (TEE) images are illustrated below. \r\n\r\nBased on the TEE findings, which of the following is the MOST appropriate course of clinical management? \r\n\r\nTop: Clip 1 Preoperative: Mid Esophageal Aortic Valve Long Axis \r\nBottom: Clip 2 Post-Repair: Mid Esophageal Aortic Valve Long Axis \r\n”,”desc”:””,”hint”:””},”y9atq”:{“id”:”y9atq”,”mediaType”:”video”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:”https:\/\/ccasociety.org\/wp-content\/uploads\/2023\/01\/POST-REPAIR_-Mid-Esophageal-Aortic-Valve-Long-Axis.mp4″,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:””,”desc”:”EXPLANATION \r\nA subaortic membrane may occur alone or in combination with other congenital heart defects – such as Shone\u2019s complex, Tetralogy of Fallot, or ventricular septal defect. Discrete membranous subaortic stenosis (DMSS) is the most common type of congenital subvalvar aortic stenosis, which can occur alone or in association with other cardiac anomalies of the aortic and mitral valves. Mitral valve anomalies are present in 48% of patients with DMSS due to the close relationship between the mitral valve and the aortic valve. \r\n\r\nPatients with complete atrioventricular septal defects (AVSDs) are at risk for developing a subaortic membrane throughout life due to turbulent flow that occurs secondary to an elongated and narrowed left ventricular outflow tract (LVOT). Common complications that may occur after surgical resection of a subaortic membrane include residual or recurrent subaortic stenosis, heart block, septal perforation, mitral valve perforation, and mitral valve regurgitation. Often, a septal myotomy or myectomy is performed along with a subaortic membrane resection, which is associated with a decreased risk of subaortic membrane recurrence in patients who have had previous cardiac surgery. This benefit has not been reproduced in patients with an isolated subaortic membrane. \r\n\r\n\r\nTEE Clip 2, obtained after surgical resection of the subaortic membrane, demonstrates moderate to severe left atrioventricular valve (LAVV) regurgitation. Thus, the correct answer choice is B – resume cardiopulmonary bypass and repair the LAVV. \r\n\r\n\r\nThe close association of the subaortic membrane with the anterior leaflet of the LAVV creates a potential hazard for anterior leaflet perforation or injury when resecting a subaortic membrane. Acute LAVV regurgitation is not tolerated well hemodynamically due to a sudden development of left atrial hypertension, diminished stroke volume due to regurgitant blood flow, and a subsequent reduction in cardiac output. Recognition of acute LAVV regurgitation on a TEE can be delayed when the severity is underestimated due to a low flow state across the valve secondary to acute heart failure. \r\n\r\n\r\nAnswer A (to resect additional subaortic membrane) is incorrect, as the post-repair TEE demonstrates more laminar flow in the LVOT. Answer C (perform aortic valve replacement) is incorrect, as the post-repair echo demonstrates only trivial aortic insufficiency. Aortic insufficiency is commonly seen in patients with a subaortic membrane and typically improves after resection of the membrane. Answer D (administer protamine) is incorrect because the acute LAVV regurgitation should be repaired as it may not be well tolerated hemodynamically and may worsen over time. \r\n\r\n\r\n \r\nREFERENCES \r\nSerraf A, Zoghby J, Lacour-Gayet F, et al. Surgical treatment of subaortic stenosis: a seventeen-year experience. J Thorac Cardiovasc Surg<\/em>. 1999;117(4):669-678. doi:10.1016\/S0022-5223(99)70286-2 \r\n\r\n\r\nOzyuksel A, Yildirim O, Onsel I, Bilal MS. Severe mitral regurgitation due to anterior mitral leaflet perforation after surgical treatment of discrete subaortic stenosis. BMJ Case Rep<\/em>. 2014;2014:bcr2014204463. Published 2014 May 23. doi:10.1136\/bcr-2014-204463 \r\n\r\n\r\nCohen L, Bennani R, Hulin S, et al. Mitral valvar anomalies and discrete subaortic stenosis. Cardiol Young<\/em>. 2002;12(2):138-146. doi:10.1017\/s104795110200029x \r\n\r\n\r\nEdwards H, Mulder DG. Surgical Management of Subaortic Stenosis. Arch Surg<\/em>.1983; 118(1): 79-83. doi:10.1001\/archsurg.1983.01390010055013 \r\n\r\n\r\nFong LS, Betts K, Bell D, et al. Complete atrioventricular septal defect repair in Australia: Results over 25 years. J Thorac Cardiovasc Surg<\/em>. 2020;159(3):1014-1025.e8. doi:10.1016\/j.jtcvs.2019.08.005 \r\n\r\n\r\nPerez Y, Dearani JA, Miranda WR, Stephens EH. Subaortic Stenosis in Adult Patients With Atrioventricular Septal Defect [published online ahead of print, 2022 Aug 17]. Ann Thorac Surg<\/em>. 2022;S0003-4975(22)01115-8. doi:10.1016\/j.athoracsur.2022.08.011 \r\n\r\n\r\nTalwar S, Anand A, Gupta SK, et al. Resection of subaortic membrane for discrete subaortic stenosis. J Card Surg<\/em>. 2017;32(7):430-435. doi:10.1111\/jocs.13160 \r\n\r\n\r\nZoghbi WA, Adams D, Bonow RO, et al. Recommendations for Noninvasive Evaluation of Native Valvular Regurgitation: A Report from the American Society of Echocardiography Developed in Collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc Echocardiogr<\/em>. 2017;30(4):303-371. doi:10.1016\/j.echo.2017.01.007 \r\n\r\n\r\nHirata Y, Chen JM, Quaegebeur JM, Mosca RS. The role of enucleation with or without septal myectomy for discrete subaortic stenosis. J Thorac Cardiovasc Surg<\/em>. 2009;137(5):1168-1172. doi:10.1016\/j.jtcvs.2008.11.039 \r\n”,”hint”:””,”answers”:{“8kxug”:{“id”:”8kxug”,”image”:””,”imageId”:””,”title”:”A.\tResume cardiopulmonary bypass and resect residual subaortic membrane\r\n”},”oq2a9″:{“id”:”oq2a9″,”image”:””,”imageId”:””,”title”:”B.\tResume cardiopulmonary bypass and repair the left atrioventricular valve “,”isCorrect”:”1″},”bxt2p”:{“id”:”bxt2p”,”image”:””,”imageId”:””,”title”:”C.\tResume cardiopulmonary bypass and perform aortic valve replacement”},”6400w”:{“id”:”6400w”,”image”:””,”imageId”:””,”title”:”D.\tAdminister protamine “}}}}}

{“questions”:{“eblde”:{“id”:”eblde”,”mediaType”:”video”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:”https:\/\/ccasociety.org\/wp-content\/uploads\/2023\/01\/Mid-Esophageal-RV-Inflow-Outflow-with-Color-MP4.mp4″,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Author: Kevin Spellman, MD; Michael A. Evans, MD; Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Northwestern Feinberg School of Medicine \r\n\r\nA 5-month-old female infant with a history of congenital pulmonary valve stenosis status post transcatheter pulmonary valvuloplasty presents for surgical pulmonary valve repair due to residual stenosis with a peak gradient of 51 mmHg. In the operating room, a transannular patch is performed in addition to a commissurotomy secondary to the discovery of a bicuspid pulmonary valve with fused and thickened valve leaflets. Following separation from cardiopulmonary bypass, transesophageal echocardiography (TEE) demonstrates free pulmonary insufficiency in addition to the images illustrated below: \r\n\r\nBased on the TEE findings, which of the following is the MOST appropriate course of clinical management? \r\n\r\nImage 1. Deep Transgastric RV Outflow Doppler Across Pulmonary Annulus \r\n \r\n\r\nClip 1. Mid Esophageal RV Inflow Outflow “,”desc”:”EXPLANATION \r\nPulmonary valve stenosis can be present at the valve region (valvar), above the valve (supravalvar), or below the valve (subpulmonary\/infundibular). Pulmonary valvar stenosis is graded based on the transpulmonary gradient, as planimetry is not possible given the available image planes. The pressure gradient is calculated based on the modified Bernoulli equation (\u2206P=4v^{2 <\/sup>), which is dependent on the precision of the doppler measurements. If the ultrasound beam is not parallel to the direction of blood flow, velocity may be underestimated. The severity of pulmonary stenosis may also be graded by utilizing spectral doppler. Pulmonary stenosis is mild if the peak velocity is <3 m\/s and peak gradient is <36 mmHg. Moderate disease consists of a peak velocity of 3-4 m\/s and peak gradient of 36-64 mmHg. Lastly, severe disease consists of a peak velocity >4 m\/s and peak gradient >64 mmHg. \r\n\r\nThe question stem highlights a finding on the postoperative TEE of residual pulmonary valve stenosis. Clip #1 represents a Mid Esophageal RV Inflow Outflow View with the highest velocities measured near the pulmonary valve annulus. Continuous doppler over the pulmonary annulus (Image 1) demonstrates a peak velocity of 41 mmHg, which nearly matches the pre-operative value of 51 mmHg, and indicates that there is significant stenosis present despite surgery. Thus, in a patient who presented with symptomatic, moderate pulmonary stenosis while under general anesthesia (peak gradient of 51 mmHg) and had little improvement after the initial surgical repair (peak gradient of 41 mmHg) as illustrated by echo, the appropriate course of action is to reinitiate bypass and undergo further surgical intervention. \r\n\r\nThe surgeons must take down the transannular patch, and either 1) extend the ventriculotomy incision further into the right ventricular outflow tract or infundibulum thus revising the transannular patch or 2) resect the pulmonary valve. Often, extension of ventriculotomy and patch revision is limited by coronary anatomy. In this case, the question stem states that free pulmonary insufficiency is achieved, which in the setting of residual pulmonary stenosis indicates valve tissue and\/or the small annulus continue to be obstructive. Thus, the correct answer is C, to resect the pulmonary valve. To avoid this complication, many surgeons resect pulmonary valve leaflets with the annular incision prior to sewing in the transannular patch. \r\n\r\nAdministration of protamine (answer A) would not be correct as there is a residual gradient requiring surgical correction. \r\n\r\nThe provided echocardiographic images do not indicate that right ventricular muscle bundles are responsible for residual stenosis (answer B), but rather that an area of stenosis at the level of the pulmonary valve is responsible. \r\n\r\nREFERENCES \r\nBaumgartner H, Hung J, Bermejo J, et al. Echocardiographic assessment of valve stenosis: EAE\/ASE recommendations for clinical practice [published correction appears in Eur J Echocardiogr.<\/em> 2009 May;10(3):479]. Eur J Echocardiogr.<\/em> 2009;10(1):1-25. doi:10.1093\/ejechocard\/jen303\r\n\r\nLinglart L, Gelb BD. Congenital heart defects in Noonan syndrome: Diagnosis, management, and treatment. Am J Med Genet C Semin Med Genet.<\/em> 2020;184(1):73-80. doi:10.1002\/ajmg.c.31765\r\n\r\nRobertson M, Benson LN, Smallhorn JS, et al. The morphology of the right ventricular outflow tract after percutaneous pulmonary valvotomy: long term follow up. Br Heart J. <\/em>1987;58(3):239-244. doi:10.1136\/hrt.58.3.239\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<\/em>. 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\nWaller BF, Howard J, Fess S. Pathology of pulmonic valve stenosis and pure regurgitation. Clin Cardiol.<\/em> 1995;18(1):45-50. doi:10.1002\/clc.4960180112\r\n\r\nPuchalski MD, Lui GK, Miller-Hance WC, et al. Guidelines for Performing a Comprehensive Transesophageal Echocardiographic: Examination in Children and All Patients with Congenital Heart Disease: Recommendations from the American Society of Echocardiography [published correction appears in J Am Soc Echocardiogr.<\/em> 2019 May;32(5):681] [published correction appears in J Am Soc Echocardiogr<\/em>. 2019 Oct;32(10):1373-1378]. J Am Soc Echocardiogr.<\/em> 2019;32(2):173-215. doi:10.1016\/j.echo.2018.08.016\r\n\r\n\r\n\r\n”,”hint”:””,”answers”:{“103or”:{“id”:”103or”,”image”:””,”imageId”:””,”title”:”A.)\tAdminister protamine”},”6itp0″:{“id”:”6itp0″,”image”:””,”imageId”:””,”title”:”B.)\tReinitiate cardiopulmonary bypass and resect right ventricular muscle bundles “},”4gn5y”:{“id”:”4gn5y”,”image”:””,”imageId”:””,”title”:”C.)\tReinitiate cardiopulmonary bypass and resect the pulmonary valve”,”isCorrect”:”1″}}}}}}

{“questions”:{“0cquf”:{“id”:”0cquf”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Author: Michael A. Evans, MD; Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Northwestern Feinberg School of Medicine \r\n\r\nA three-year-old female toddler with severe idiopathic pulmonary arterial hypertension presents to the emergency department with two months of worsening lethargy. Routine labs demonstrate a hemoglobin of 8.2 g\/dL. Which of the following medications for the treatment of pulmonary hypertension is MOST LIKELY associated with the observed hemoglobin level?”,”desc”:”EXPLANATION \r\nMacitentan is an orally-active endothelin receptor antagonist (ERA) used in the treatment of pulmonary hypertension. Currently, three oral ERAs are prescribed in children for the treatment of pulmonary hypertension: macitentan, bosentan, and ambrisentan. Currently, the only FDA-approved oral ERA in children is bosentan. A fourth oral endothelin receptor antagonist, sitaxsentan, was withdrawn from the market in 2010 due to several reports of fatal liver injury. \r\n\r\nA meta-analysis of 4894 patients taking macitentan, bosentan, or ambrisentan from 24 randomized trials found that the most common adverse effects of oral ERAs were abnormal liver function, peripheral edema, and anemia. Interestingly, the adverse effects stratified differently by drug type. \r\n\r\n\u2022\tBosentan use poses a statistically significant risk of elevated hepatic enzymes when compared to placebo, whereas macitentan does not demonstrate an increased risk. Ambrisentan significantly decreases the risk of abnormal liver function. \r\n\u2022\tBosentan and ambrisentan have a statistically significant risk of causing peripheral edema when compared to placebo, but there is no increased risk with macitentan. \r\n\u2022\tBosentan and macitentan pose a significantly higher risk of anemia when compared to placebo, but there is no increased risk with ambrisentan.\r\n\r\n\r\nBosentan-induced anemia has generally been mild in clinical trials and has not been associated with a need for discontinuation of the drug. Regardless, the current recommendation for clinical surveillance of anemia in patients on bosentan includes monitoring a hemoglobin level every three months. Macitentan-induced anemia appears to be dose-dependent and may warrant discontinuation of the medication. The mechanism by which oral ERAs cause anemia is not known, but it is suspected that fluid retention yields at least some dilutional anemia. \r\n\r\n\r\nSelexipag is an additional pulmonary hypertension medication that is used off-label in children. It is also associated with anemia. In fact, 8.6% of patients treated with selexipag will experience a decrease in hemoglobin concentration to less than 10 g\/dL during treatment. Selexipag and its metabolite selectively bind the prostacyclin PGI_{2<\/sub> receptor, which promotes pulmonary vasodilation, but also inhibits platelet aggregation. Fortunately, the largest trial to date, the GRIPHON trial, did not demonstrate an increased rate of bleeding in patients with PAH who were taking selexipag. Other side effects of selexipag include headache, jaw pain, and hyperthyroidism. \r\n\r\n\r\nSildenafil is a phosphodiesterase-5 inhibitor (PDE5-I) used in the treatment of pulmonary arterial hypertension in adults. It is often used off-label for the same indication in children. It induces smooth muscle relaxation in the pulmonary arterial bed. Side effects are relatively rare, but include headache, pyrexia, upper respiratory tract infection, vomiting, and diarrhea. Importantly, an increased risk of mortality was observed with increasing doses in children, especially after one to two years of chronic use. In 2012, the FDA revised the drug label for sildenafil to state that the \u201cuse of [sildenafil], particularly chronic use, is not recommended in children.\u201d Later, the FDA clarified that \u201cthis recommendation was not intended to suggest that [sildenafil] should never be used in children.\” It remains a mainstay of therapy in pediatric pulmonary hypertension.\r\n\r\n\r\n\r\nEpoprostenol is a prostanoid-type of pulmonary vasodilator used in the treatment of pulmonary arterial hypertension. Epoprostenol was the first and single drug that demonstrated a decrease in mortality with its use in patients with idiopathic or heritable pulmonary arterial hypertension. In children with higher risk of clinical deterioration, initiation of epoprostenol may be indicated. Epoprostenol acts as a synthetic analog of prostaglandin I2<\/sub> in endothelial cells and has a vasodilatory effect. The drug also has anti-inflammatory, anti-aggregation, and antiproliferative effects as well. The drug is administered in an intravenous formulation, thus complications include catheter-associated infection or thrombosis. Other common side effects include jaw pain, headache, nausea, or diarrhea. Anemia is not associated with epoprostenol use. \r\n\r\n\r\nKnowledge of the specific side effects of pulmonary hypertension medications is quite important, as it is common to treat pulmonary hypertension in children with a combination of medications. This practice may be referred to as \u201ctriple therapy,\u201d when it includes a phosphodiesterase-5 inhibitor, an endothelin receptor antagonist, and a prostanoid. While efficacious, triple therapy poses an increased risk of anemia given adverse effect overlap of the three medication classes. The risk of anemia may be further compounded in the presence of therapy with antiplatelet agents, vitamin K antagonists, or factor Xa inhibitors due to an increased risk of bleeding. \r\n\r\n\r\nOf the answer choices, macitentan is most likely to be associated with anemia. \r\n\r\n\r\n\r\n\r\n\r\n \r\n\r\nREFERENCES \r\n\r\nWei A, Gu Z, Li J, et al. Clinical Adverse Effects of Endothelin Receptor Antagonists: Insights from the Meta-Analysis of 4894 Patients From 24 Randomized Double-Blind Placebo-Controlled Clinical Trials. J Am Heart Assoc.<\/em> 2016;5(11):e003896. Published 2016 Oct 26. doi:10.1161\/JAHA.116.003896 \r\nHumbert M, Segal ES, Kiely DG, et al. Results of European post-marketing surveillance of bosentan in pulmonary hypertension. Eur Respir J.<\/em>2007;30(2):338-344. doi:10.1183\/09031936.00138706 \r\n\r\n\r\nPulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med.<\/em> 2013;369(9):809-818. doi:10.1056\/NEJMoa1213917 \r\n\r\n\r\nGabbay E, Fraser J, McNeil K. Review of bosentan in the management of pulmonary arterial hypertension. Vasc Health Risk Manag.<\/em> 2007;3(6):887-900. \r\n\r\n\r\nAversa M, Porter S, Granton J. Comparative safety and tolerability of endothelin receptor antagonists in pulmonary arterial hypertension. Drug Saf.<\/em> 2015;38(5):419-435. doi:10.1007\/s40264-015-0275-y \r\n\r\n\r\nBarst RJ, Ivy DD, Gaitan G, et al. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation.<\/em> 2012;125(2):324-334. doi:10.1161\/CIRCULATIONAHA.110.016667 \r\n\r\n\r\nBarst RJ, Beghetti M, Pulido T, et al. STARTS-2: long-term survival with oral sildenafil monotherapy in treatment-naive pediatric pulmonary arterial hypertension. Circulation.<\/em> 2014;129(19):1914-1923. doi:10.1161\/CIRCULATIONAHA.113.005698 \r\n\r\n\r\nDe A, Shah P, Szmuszkovicz J, et al. A Retrospective Review of Infants Receiving Sildenafil. J Pediatr Pharmacol Ther. <\/em>2018;23(2):100-105. doi:10.5863\/1551-6776-23.2.100 \r\n\r\n\r\nUS Food and Drug Administration. \u201cFDA Drug Safety Communication: FDA clarifies Warning about Pediatric Use of Revatio (sildenafil) for Pulmonary Arterial Hypertension.\u201d Published 03\/31\/2014. Updated 01\/15\/2016. Accessed 1\/1\/2023. URL: https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-drug-safety-communication-fda-clarifies-warning-about-pediatric-use-revatio-sildenafil-pulmonary \r\n\r\n\r\nBarst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med.<\/em> 1996;334(5):296\u2013301. \r\n\r\n\r\nRopero MJC, Cruz-Utrilla A, Escribano-Subias MP. Epoprostenol for the treatment of pulmonary arterial hypertension. Expert Rev. Clin. Pharmacol.<\/em> 2021; 14(8): 1003-1011. \r\n”,”hint”:””,”answers”:{“xf5zz”:{“id”:”xf5zz”,”image”:””,”imageId”:””,”title”:”A.\tSildenafil”},”c6brh”:{“id”:”c6brh”,”image”:””,”imageId”:””,”title”:”B.\tMacitentan”,”isCorrect”:”1″},”rb1xf”:{“id”:”rb1xf”,”image”:””,”imageId”:””,”title”:”C.\tAmbrisentan”},”ml8bc”:{“id”:”ml8bc”,”image”:””,”imageId”:””,”title”:”D.\tEpoprostenol”}}}}}}

{“questions”:{“8aym9”:{“id”:”8aym9″,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Author: Michael A. Evans, MD; Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Northwestern Feinberg School of Medicine \r\nAn 18-year-old male adolescent with a history Hypoplastic Left Heart Syndrome palliated with a fenestrated Fontan and who is anticoagulated with rivaroxaban presents to the emergency department with vomiting and altered consciousness. Computed tomography of the head reveals an intracranial hemorrhage. Which of the following agents is the BEST treatment to inhibit the anticoagulative effect of rivaroxaban?”,”desc”:”EXPLANATION \r\nRivaroxaban is a direct Factor Xa inhibitor that is FDA approved for anticoagulation in children over two years of age after the Fontan operation. The brand name of rivaroxaban is Xarelto\u00ae. It is currently the only direct oral anticoagulant (DOAC) that is FDA approved for this indication in the pediatric patient population. Routine blood tests to monitor anticoagulation and dietary restrictions are not required with the use of rivaroxaban, unlike warfarin anticoagulation. Other direct Factor Xa inhibitors include apixaban, enoxaparin, and edoxaban. \r\n\r\nAndexanet alfa (andexanet) is a reversal agent that neutralizes the anticoagulant effects of both direct and indirect factor Xa inhibitors. Andexanet is a catalytically inactive, recombinant modified human factor Xa protein that binds with high affinity to the active site of factor Xa (FXa) inhibitor thereby preventing FXa inhibitor from binding to Factor Xa and thus antagonizing its anticoagulant effect as assessed by measurement of thrombin generation and anti-factor Xa activity. Andexanet antagonizes the anticoagulant activity of apixaban, rivaroxaban, edoxaban, and enoxaparin. Andexanet was FDA approved in 2018, under its Accelerated Approval Program, for the reversal of life-threatening bleeding or uncontrolled bleeding in patients treated with apixaban or rivaroxaban. In the patient described in the question stem, andexanet administration would rapidly reverse systemic anticoagulation. \r\n\r\nThe side effect profile of andexanet alfa is most notable for venous and arterial thrombotic events. In fact, a 2020 meta-analysis of 16 prospective and retrospective studies enrolling patients treated with specific antidotes (idarucizumab and andexanet alfa) for anticoagulation reversal demonstrated a pooled incidence of 5.5% for thrombotic events. A systematic review of the studies on the safety and efficacy of nonvitamin K oral anticoagulants (NOACs) in adult patients with congenital heart disease (CHD) revealed a low annual incidence of thromboembolic events (0.98%) and major bleeding events (1.74%). Although the most common indication for anticoagulation in the adult patient population with congenital heart disease was atrial fibrillation in this study, the majority of both thromboembolic (3.13%) and hemorrhagic (3.17%) events occurred in patients with the Fontan palliation. \r\n\r\nIdarucizumab is a monoclonal antibody fragment used to reverse the effects of dabigatran, a direct thrombin inhibitor. It binds to dabigatran with 350 times greater affinity than thrombin. Idarucizumab would not be effective in reversing the anticoagulant effects of rivaroxaban in this patient. \r\n\r\nVitamin K is utilized for the reversal of coumadin anticoagulation. It would be expected to significantly lower the international normalized ratio (INR) in a 24 to 48 hour time period. It is not utilized as the sole reversal agent in the setting of a life-threatening hemorrhage due to coumadin anticoagulation but is administered concomitantly with fresh frozen plasma or prothrombin complex concentrates. \r\n\r\nPlatelet transfusion could be indicated in the setting of traumatic intracranial hemorrhage, especially to reverse the effects of antiplatelet medications or in the setting of thrombocytopenia. It would not be the first-line intervention in this patient treated with rivaroxaban. \r\n\r\nIn the setting of an intracranial hemorrhage in a patient treated with rivaroxaban, Andexanet alfa is the best initial treatment option. \r\nREFERENCES \r\nSiegal DM, Curnutte JT, Connolly SJ, et al. Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity. N Engl J Med. <\/em>2015;373(25):2413-2424. doi:10.1056\/NEJMoa1510991\r\n\r\nConnolly SJ, Crowther M, Eikelboom JW, et al. Full Study Report of Andexanet Alfa for Bleeding Associated with Factor Xa Inhibitors. N Engl J Med.<\/em> 2019;380(14):1326-1335. doi:10.1056\/NEJMoa1814051\r\n\r\nStalikas N, Doundoulakis I, Karagiannidis E, et al. Non-Vitamin K Oral Anticoagulants in Adults with Congenital Heart Disease: A Systematic Review. J Clin Med. <\/em>2020;9(6):1794. Published 2020 Jun 9. doi:10.3390\/jcm9061794\r\n\r\nPollack CV Jr, Reilly PA, Eikelboom J, et al. Idarucizumab for Dabigatran Reversal. N Engl J Med.<\/em> 2015;373(6):511-520. doi:10.1056\/NEJMoa1502000\r\n\r\nRodrigues AO, David C, Ferreira JJ, Pinto FJ, Costa J, Caldeira D. The incidence of thrombotic events with idarucizumab and andexanet alfa: A systematic review and meta-analysis. Thromb Res.<\/em> 2020;196:291-296. doi:10.1016\/j.thromres.2020.09.003\r\n”,”hint”:””,”answers”:{“ldtta”:{“id”:”ldtta”,”image”:””,”imageId”:””,”title”:”A.\tIdarucizumab”},”t7yzm”:{“id”:”t7yzm”,”image”:””,”imageId”:””,”title”:”B.\tAndexanet alfa”,”isCorrect”:”1″},”qs0e9″:{“id”:”qs0e9″,”image”:””,”imageId”:””,”title”:”C.\tVitamin K”},”pb1bd”:{“id”:”pb1bd”,”image”:””,”imageId”:””,”title”:”D.\tPlatelet transfusion”}}}}}