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

{“questions”:{“ev9ue”:{“id”:”ev9ue”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Author: Melissa Colizza, MD – Stollery Children\u2019s Hospital – University of Alberta – Edmonton Canada \r\n\r\nA 2.2 kg boy with hypoplastic left heart syndrome is born at 34 weeks of gestation. A decrease in which of the following mortality outcomes is MOST likely if this patient undergoes a Stage I Hybrid versus a Stage I Norwood palliation? “,”desc”:”EXPLANATION \r\nHypoplastic left heart syndrome (HLHS) is associated with significant morbidity and mortality as compared to other forms of congenital heart disease. HLHS is typically palliated with a series of three surgical procedures but may also be treated with cardiac transplantation. The Stage 1 Norwood was first described in 1979 and is comprised of a Damus-Kaye-Stansel (DKS) anastomosis to provide systemic blood flow, a systemic-to-pulmonary shunt to provide pulmonary blood flow, ascending aorta and aortic arch reconstruction, and an atrial septectomy to provide unrestricted flow of pulmonary venous blood to the right atrium and right ventricle. It remains associated with an interstage mortality of 10-15%, as parallel circulation results in a labile ratio of pulmonary to systemic blood flow with an increased risk of coronary ischemia. The Stage I Hybrid palliation (HP) was developed as an alternative to the Stage I Norwood to avoid cardiopulmonary bypass (CPB) in neonates at a higher risk for morbidity and mortality. While the specifics of the procedure vary amongst congenital cardiac surgical programs, it is typically approached via median sternotomy and consists of placement of bilateral pulmonary artery (PA) bands to restrict pulmonary blood flow and a patent ductus arteriosus stent to supply systemic blood flow, with or without stenting or balloon septostomy of the atrial septum. \r\n\r\nThere remains considerable practice variability concerning indications and execution of the Stage I HP amongst various congenital cardiac surgical programs, making comparisons of outcomes challenging. Zanaboni et al. surveyed 54 centers in North America, resulting in a 50% response rate. The majority of respondents use the Stage I HP for neonates deemed to be \u201chigh risk\u201d. Two centers use the Stage I HP for all single ventricle patients. The most common determinants of \u201chigh risk\u201d were prematurity, low birth weight, reduced ventricular dysfunction, severe tricuspid regurgitation, and additional cardiac or non-cardiac anomalies. Procedural techniques varied, with 95% using bilateral Gore-tex PA bands, 67% using ductal stents versus a prostaglandin infusion, and 23% routinely performing atrial septal enlargement. Interstage management was variable, with some centers opting for the Stage I Norwood at a time point four to six weeks after the Stage I HP and others opting for a comprehensive Stage II bidirectional Glenn at a time point five to six months later.\r\n\r\nA 2024 meta-analysis by Iskander et al. analyzed 21 studies, including 1,182 patients with HLHS. The authors compared mortality and morbidity in patients who underwent the Stage I Norwood procedure to those who underwent the Stage I HP. They found no difference in in-hospital mortality or transplantation rate. Further, the authors found a statistically significant difference in one-year mortality (43.99% for the Stage I Hybrid vs 30.72% for the Stage I Norwood), which did not persist at three or five years. Five studies that specifically evaluated \u201chigh-risk\u201d patients found an in-hospital mortality and\/or transplantation rate of 19.5% for the Stage I Hybrid vs 35.59% for the Stage I Norwood group. The most common \u201chigh risk\” factors included prematurity, other cardiac anomalies such as intact atrial septum and tricuspid valve insufficiency, and genetic or other non-cardiac anomalies. Nonetheless, the decrease in in-hospital mortality in the Stage I HP group did not translate into an interstage survival benefit (interstage mortality rate of 23.7% for Stage I HP vs 14.06% for Stage I Norwood). Interestingly, the Stage I HP patients experienced a higher rate of unplanned reinterventions, were less likely to reach stage II and III palliations, and had longer ICU and hospital length-of-stay. This likely reflects the fact that patients undergoing Stage I HP typically present with the above-mentioned risk factors and require a more extensive stage II palliation. \r\n\r\nThe correct answer is B. With the current available data, decreased in-hospital mortality in high-risk patients after the Stage I HP is the most likely benefit. Stage I Norwood patients had increased survival rates in the interstage period and at one year. However, it remains important to consider these conclusions in light of the fact that the hybrid procedure is most often performed in high-risk patients with a greater likelihood of morbidity and mortality. There is also considerable variation in procedural factors between congenital cardiac programs, which may impact outcomes, making direct comparisons of the two strategies susceptible to statistical error. \r\n\r\n\r\n\r\n \r\nREFERENCES \r\nDiaz-Berenstain L, Abbasi RK, Riegger LO, Steven JM, Nicolson SC, Andropoulos DB. Anesthesia for the Patient with a Single Ventricle. In: Andropoulos DB, Mossad EB, Gottlieb EA, eds. Anesthesia for Congenital Heart Disease<\/em>. 4th edition. John Wiley & Sons, Inc.; 2023: 744-746.\r\n\r\nIskander C, Nwankwo U, Kumanan KK, et al. Comparison of Morbidity and Mortality Outcomes between Hybrid Palliation and Norwood Palliation Procedures for Hypoplastic Left Heart Syndrome: Meta-Analysis and Systematic Review. J Clin Med<\/em>. 2024;13(14):4244. doi:10.3390\/jcm13144244\r\n\r\nZanaboni DB, Sower CT, Yu S, Lowery R, Romano JC, Zampi JD. Practice variation using the hybrid stage I procedure in congenital heart disease: Results from a national survey. JTCVS Open<\/em>. 2024;21:248-256. doi:10.1016\/j.xjon.2024.07.020\r\n”,”hint”:””,”answers”:{“o4yeu”:{“id”:”o4yeu”,”image”:””,”imageId”:””,”title”:”A.\tInterstage mortality”},”f4p37″:{“id”:”f4p37″,”image”:””,”imageId”:””,”title”:”B.\tIn-hospital mortality “,”isCorrect”:”1″},”7mm4l”:{“id”:”7mm4l”,”image”:””,”imageId”:””,”title”:”C.\tOne-year mortality\r\n\r\n”}}}}}

{“questions”:{“hf9oe”:{“id”:”hf9oe”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Author: Melissa Colizza, MD – Stollery Children\u2019s Hospital – Edmonton Canada \r\nA 3.8 kg, 4-day-old term girl presents with pulmonary edema and lactate of 3. Transthoracic echocardiography demonstrates a type B interrupted aortic arch, posterior malalignment ventricular septal defect, and severe left-ventricular outflow tract obstruction. Which of the following procedures is the MOST appropriate surgical strategy to correct this defect? \r\n”,”desc”:”EXPLANATION \r\nInterrupted aortic arch (IAA) has an incidence of 1% of all congenital heart disease. It is classified into the following subtypes: 1) Type A (interruption distal to left subclavian artery); 2) Type B (interruption between left common carotid and left subclavian arteries); and 3) Type C (interruption between the innominate and left common carotid arteries). IAA is commonly associated with other congenital cardiac anomalies, including ventricular septal defect (VSD), which may contribute to left-ventricular outflow tract obstruction (LVOTO), as well as aortic annular hypoplasia, bicuspid aortic valve, and left ventricular (LV) muscle bundles. Type B IAA is commonly associated with a posterior malalignment VSD and an aberrant right subclavian artery. The posterior malalignment VSD can contribute to LVOTO with deviation of the conal septum. Neonates born with IAA typically remain asymptomatic until the ductus arteriosus closes, resulting in decreased lower body perfusion and, eventually, congestive heart failure and cardiogenic shock. \r\n\r\n\r\nThere are several surgical options available for the repair of IAA. In contemporary practice, primary complete neonatal repair has become standard of care. In children without LVOTO, repair typically consists of aortic arch repair with VSD closure. In low-birthweight or premature children, as well as those with contra-indications to CPB, palliative options include pulmonary artery banding along with either PDA stenting in the catheterization laboratory or off-bypass arch repair via thoracotomy. However, in the setting of significant LVOTO, management remains challenging with technically difficult procedures and a high rate of reintervention. Surgical options for this group of patients include the following: (1) aortic arch repair, VSD closure, and conal muscle resection; (2) initial neonatal Norwood or hybrid palliation with staged, biventricular repair in later infancy or (3) a neonatal Ross-Konno. In some patients with severe LVOTO, these procedures have a high probability of significant residual LVOTO, and an alternative approach for consideration is the Yasui procedure. It was first published in 1987 and consists of a Damus-Kaye-Stansel anastomois, baffled VSD closure that incorporates the native pulmonary valve, and a right ventricle to pulmonary artery conduit. \r\n\r\n\r\nGreene et al. reported a single institution\u2019s experience with the Yasui procedure at Boston Children\u2019s Hospital, including 25 cases over 32 years. They reported a survival rate of 91% at 5 years; freedom from LVOT reintervention was 91% and freedom from RV-PA conduit reintervention was 52%. All patients had normal biventricular function. The authors concluded that the Yasui procedure compared favorably to the Staged single ventricle palliative pathway and the Ross-Konno procedure in terms of mortality and LVOT reintervention. Furthermore, patients who underwent the Yasui procedure did not require a greater number of reinterventions overall. \r\n\r\n \r\nA multicenter study by Luo et al. analyzed outcomes in 150 neonates with IAA. They found that patients undergoing a Ross-Konno or a Yasui procedure had a lower <\/em> risk of LVOT reintervention compared to standard arch repair, especially when combined with conal resection. Mortality after the Yasui procedure was seven percent, but most of those children had undergone a two-stage Yasui, with an interstage period characterized by single-ventricle physiology with a shunt. Interestingly, the mortality rate in children undergoing a Ross-Konno procedure was 0%. The authors attributed this mortality rate to patient selection, as children with IAA and LVOTO are more likely to have normal LV and mitral valve size and function as compared to patients with critical aortic stenosis and hypoplastic LV. Children who underwent IAA repair with VSD closure without conal resection had similar rates of LVOT reintervention as those with the Yasui procedure, but the authors noted that those children were less likely to have severe LVOTO. While most centers favor a single-stage neonatal repair whenever possible, the hybrid procedure, consisting of bilateral PA banding and ductal stenting, has been gaining traction. This approach is typically reserved for high-risk neonates, including those with prematurity, low birth weight, genetic disorders, extra-cardiac malformations, or clinical conditions such as sepsis, necrotizing enterocolitis, or intracranial hemorrhage. Conversely, some centers successfully use the hybrid approach in the absence of the listed risk factors.\r\n\r\n\r\nThe correct answer among those choices is B, the Yasui procedure, consisting of a complete repair and relief of LVOTO. Aortic arch repair with VSD closure remains the standard operation for IAA with a VSD, but is likely to require reintervention, especially in children with pre-existing LVOTO. The patient described in the stem also has severe LVOTO and would likely require conal muscle resection in addition to aortic arch repair and VSD closure. PA banding with off-bypass aortic arch repair is typically reserved for children with high-risk features or contraindications to cardiopulmonary bypass, which are not present in the patient in the stem. It is important to note that IAA remains a heterogeneous disease, and management requires multidisciplinary planning tailored to each patient and each surgical program\u2019s expertise.\r\n\r\n\r\n\r\n\r\n\r\n \r\nREFERENCES \r\n\r\nLaPar DJ, Baird CW. Surgical Considerations in Interrupted Aortic Arch. Semin Cardiothorac Vasc Anesth<\/em>. 2018;22(3):278-284. doi:10.1177\/1089253218776664\r\n\r\nGreene CL, Scully B, Staffa SJ, et al. The Yasui operation: A single institutional experience over 30 years. JTCVS Open<\/em>. 2023;15:361-367. Published 2023 Jul 18. doi:10.1016\/j.xjon.2023.06.019\r\n\r\n\r\nLuo S, Schoof PH, Hickey E, et al. The Fate of the Left Ventricular Outflow Tract Following Interrupted Aortic Arch Repair. World J Pediatr Congenit Heart Surg<\/em>. 2024;15(5):562-570. doi:10.1177\/21501351241236742\r\n\r\n\r\nAlsoufi B. Hybrid First-stage Palliation and Other Strategies to Achieve Biventricular Repair in High-Risk Neonates With Complex Heart Anomalies and Aortic Arch Obstruction. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu<\/em>. 2023;26:40-49. doi:10.1053\/j.pcsu.2022.12.009\r\n\r\n\r\nYasui H, Kado H, Nakano E et al. Primary repair of interrupted aortic arch and severe aortic stenosis in neonates. J Thorac Cardiovasc Surg<\/em>. 1987; 93:539-545.\r\n”,”hint”:””,”answers”:{“1kmuq”:{“id”:”1kmuq”,”image”:””,”imageId”:””,”title”:”A)\tAortic arch reconstruction and ventricular septal defect repair”},”j8idw”:{“id”:”j8idw”,”image”:””,”imageId”:””,”title”:”B)\tYasui procedure”,”isCorrect”:”1″},”kig6l”:{“id”:”kig6l”,”image”:””,”imageId”:””,”title”:”C)\tPulmonary artery banding with off-bypass arch repair\r\n\r\n”}}}}}

{“questions”:{“mfzs3”:{“id”:”mfzs3″,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Author: Melissa Colizza, MD, Stollery Children\u2019s Hospital, Edmonton, Canada \r\n\r\nA 25-year-old, G1P0 woman with tricuspid atresia palliated with the Fontan procedure presents in active labor at 33 weeks of gestation. Her most recent cardiology evaluation demonstrated stable single ventricular function. Which of the following cardiovascular complications is MOST likely during her hospitalization?”,”desc”:”EXPLANATION \r\nThe Fontan procedure is the final operation in the single ventricle palliative pathway. Fontan physiology is characterized by the absence of a subpulmonary ventricle and drainage of systemic venous blood directly into the pulmonary arterial circulation, resulting in passive blood return to the lungs for oxygenation. With surgical and perioperative advancements, Fontan patients are reaching reproductive age due to an estimated survival rate nearing 80% at 20 years. However, morbidity remains high as a result of the deleterious consequences of Fontan physiology, such as elevated systemic vascular resistance (SVR), high arrhythmia burden, single ventricular diastolic dysfunction, chronic elevation in central venous pressure (CVP), and reduced preload\/filling of the single ventricle from the cavo-pulmonary anastomosis. Additionally, Fontan physiology is characterized by low cardiac output despite higher central venous pressures, high pulmonary vascular resistance, and increased preload dependence. The physiologic effects of pregnancy, positive pressure ventilation and sustained arrhythmias can lead to negative hemodynamic effects.\r\n\r\nDuring pregnancy, neurohormonal activation causes increased heart rate, blood volume, cardiac output, as well as vasodilation to favor uteroplacental perfusion. These factors add considerable hemodynamic stress to patients with Fontan physiology, who may already have tenuous cardiopulmonary function\/reserve. The pregnancy-induced decrease in SVR may not completely offset the intrinsic arterial stiffness present in Fontan patients, thereby increasing the work required from the single ventricle to meet the new metabolic requirements. The 45% increase in blood volume is usually well tolerated and contributes to increased cardiac output. The expansion in blood volume load typically reaches a maximum during labor, delivery, and the early post-partum period due to autotransfusion from uterine contractions and subsequent uterine involution. \r\n\r\nHowever, in some patients with elevated pulmonary vascular resistance (PVR), cavo-pulmonary pathway obstruction\/stenosis, valvular regurgitation, or diastolic dysfunction, the expansion in blood volume may precipitate heart failure (HF). Garcia Romero et al. conducted a systematic review to evaluate maternal and fetal outcomes in pregnant Fontan patients. The study analyzed outcomes in 225 pregnancies in 133 women that resulted in 115 live births. Supraventricular tachyarrhythmia was the most common adverse event affecting 8.4% (3% to 37%) of Fontan patients. The underlying mechanism is attributed to pregnancy-induced adrenergic activation and atrial stretch from fluid loading in individuals prone to tachyarrhythmias. Heart failure was the second most common complication affecting 3.9% (3% to 11%) of the pregnant Fontan patients. The low occurrence of heart failure is explained by the low rate of systolic ventricular failure and low incidence of severe Fontan-related complications in those Fontan patients who are able to get pregnant. Reassuringly, no maternal deaths were reported in this analysis. Whilst the Fontan circulation creates a prothrombotic state, exacerbated during pregnancy, thromboembolic events such as strokes and pulmonary embolism were infrequent in the study population. \r\n\r\nObstetric complications are common in the Fontan population. Both antepartum and post-partum bleeding are estimated to occur in roughly 15% of pregnant Fontan patients, compared to 2-11% in the general population. This is attributed to underlying liver disease, anticoagulation, a higher incidence of cesarian section delivery, and the restrictive use of uterotonics. Interestingly, Fontan patients without significant liver disease and higher resting saturation were more likely to become pregnant. Over 50% of Fontan patients who become pregnant experience miscarriages. Furthermore, 50% of live births occur prematurely, and 20% of these neonates are small for gestational age. These complications are thought to be caused by a chronically low cardiac output state and neuro-hormonal activation, leading to uteroplacental insufficiency. \r\n\r\nThe literature suggests many single-ventricle patients can safely carry a pregnancy close to term. According to the modified WHO classification of maternal cardiovascular risk, Fontan patients who do not have protein-losing enteropathy, systolic ventricular dysfunction, or atrioventricular valve regurgitation are considered to be at moderate-to-high risk of adverse cardiac or obstetric events (Class III) whereas those who do have the complications listed above are at extremely high risk (class IV). \r\n\r\nThe correct answer is C, arrhythmias, which occur more frequently than heart failure or thromboembolic events in pregnant Fontan patients with few other comorbidities.\r\n\r\n\r\n \r\nREFERENCES \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\nMaisat W, Yuki K. The Fontan Circulation in Pregnancy: Hemodynamic Challenges and Anesthetic Considerations. J Cardiothorac Vasc Anesth<\/em>. 2024;38(11):2770-2782. doi:10.1053\/j.jvca.2024.07.021\r\n\r\nBreviario S, Krishnathasan K, Dimopoulos K, et al. Pregnancy in women with a Fontan circulation: Short and long-term outcomes. Int J Cardiol<\/em>. 2024;415:132445. doi:10.1016\/j.ijcard.2024.132445\r\n\r\nvan Hagen IM, Roos-Hesselink JW. Pregnancy in congenital heart disease: risk prediction and counselling. Heart<\/em>. 2020;106(23):1853-1861. doi:10.1136\/heartjnl-2019-314702\r\n\r\nCannobio 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”,”hint”:””,”answers”:{“q6p2y”:{“id”:”q6p2y”,”image”:””,”imageId”:””,”title”:”A.\tHeart failure”},”kfvdd”:{“id”:”kfvdd”,”image”:””,”imageId”:””,”title”:”B.\tPulmonary embolism”},”h8eyb”:{“id”:”h8eyb”,”image”:””,”imageId”:””,”title”:”C.\tArrhythmias”,”isCorrect”:”1″}}}}}

{“questions”:{“g8nc4”:{“id”:”g8nc4″,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Meera Gangadharan, MBBS, FAAP, FASA – Children\u2019s Memorial Hermann Hospital, University of Texas Health Science Center, Houston, TX
\r\nAND \r\nJehan Elliott, MD – Nemours Children\u2019s Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA \r\n\r\nA 2-year-old girl with developmental delay, hypertelorism, low-set ears, and a bulbous nose presents for a transthoracic echocardiogram due to a systolic murmur radiating to the upper left sternal border. A physical exam is normal, and a history of present illness is negative for failure to thrive. Genetic testing demonstrates a mutation in the RIT1<\/em> gene. Which of the following subtypes of cardiomyopathy is MOST likely in this patient?\r\n”,”desc”:”EXPLANATION \r\nNoonan syndrome (NS) is a RASopathy resulting from abnormalities in the RAS\/Mitogen-Activated-Protein-Kinase (MAPK) pathway. NS occurs in 1:1,000 to 2,500 live births. Most cases of NS are sporadic, but autosomal dominant forms also occur, leading to multiple cases in one family. Eighty percent of patients with NS will have a cardiac abnormality. Of these patients, 60% will have congenital heart disease and 20% will have hypertrophic cardiomyopathy. The most common congenital heart diseases associated with NS are pulmonary valve stenosis (40%), atrial septal defects (8%), and atrioventricular septal defects (15%). Left-sided lesions such as aortic stenosis, coarctation of the aorta, and mitral stenosis are less common. Combinations of pulmonary and aortic valve stenosis and hypertrophic cardiomyopathy have also been described in NS. \r\n\r\n\r\nMutations in several genes can result in NS, including the RAF1, MRAS, <\/em> and RIT1<\/em> genes, which are more commonly associated with a phenotype characterized by hypertrophic cardiomyopathy (HCM). According to one large registry, RASopathies, which include Noonan syndrome, Noonan syndrome with multiple lentigines, Cardiofaciocutaneous syndrome, Mazzanti syndrome, Costello syndrome, Type 1 Neurofibromatosis, and Legius syndrome, are associated with 18% of pediatric HCM. RASopathy-associated HCM differs from sarcomeric HCM in several ways. RASopathy-associated HCM presents earlier in life, at a mean age of six months versus adolescence in sarcomeric HCM. In addition, 24% will have congestive heart failure versus 9% of those with sarcomeric HCM. Finally, patients with RASopathy-associated HCM are more likely to require interventions, such as surgical myomectomy, pulmonary valvuloplasty, and hospitalization for heart failure treatment. Unlike patients with sarcomeric HCM, who experience progression of left ventricular hypertrophy with time, those with RASopathy-associated HCM often experience a reduction in left ventricular wall thickness and myocardial hypertrophy with reverse remodeling as they grow older. The role of the RAS\/MAPK pathway in the pathogenesis of HCM has been underscored by the resolution of myocardial hypertrophy in two patients with the RIT1<\/em> mutation who were treated with trametinib, an MEK inhibitor that targets the MAPK pathway. A marked reduction in myocardial hypertrophy was seen within four months of treatment with trametinib. \r\n\r\n\r\nThe correct answer is A. Hypertrophic cardiomyopathy is the most common type of cardiomyopathy associated with NS. Over 75% of these individuals have a RIT1<\/em> or RAF1<\/em> gene mutation. Dilated cardiomyopathy may occur with HCM when patients have progressed to heart failure. The patient in the stem is asymptomatic, making advanced heart failure and therefore dilated cardiomyopathy less likely. Restrictive cardiomyopathy has not been described in NS.\r\n\r\n\r\n\r\n \r\nREFERENCES \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\n\r\nLioncino M, Monda E, Verrillo F, et al. Hypertrophic Cardiomyopathy in RASopathies: Diagnosis, Clinical Characteristics, Prognostic Implications, and Management. Heart Fail Clin<\/em>. 2022;18(1):19-29. doi:10.1016\/j.hfc.2021.07.004\r\n\r\n\r\nMital S, Breckpot J., Genetic Aspects of Congenital Heart defects. In: Shaddy RE, Penny DJ, Cetta F, Feltes TF, Mital S, eds. Moss and Adams\u2019 Heart Disease in Infants, children and adolescents including the fetus and young adult<\/em>. 10th ed. Philadephia, PA: Wolters Kluwer; 2022: 98-100\r\n\r\n”,”hint”:””,”answers”:{“ec2ee”:{“id”:”ec2ee”,”image”:””,”imageId”:””,”title”:”A.\tHypertrophic”,”isCorrect”:”1″},”pjy6l”:{“id”:”pjy6l”,”image”:””,”imageId”:””,”title”:”B.\tDilated”},”1j6m6″:{“id”:”1j6m6″,”image”:””,”imageId”:””,”title”:”C.\tRestrictive”}}}}}

{“questions”:{“h00jw”:{“id”:”h00jw”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Meera Gangadharan, MBBS, FAAP, FASA – Children\u2019s Memorial Hermann Hospital, University of Texas Health Science Center, Houston, TX AND \r\nDestiny F. Chau, MD – Arkansas Children\u2019s Hospital, UAMS, Little Rock, AR \r\n\r\nAn 18-year-old girl with a history of tricuspid atresia palliated with a Fontan presents for emergent craniotomy after a motor vehicle collision. The patient is treated with rivaroxaban for thromboprophylaxis. Which of the following medications is MOST appropriate to reverse the anticoagulant effects of rivaroxaban?”,”desc”:”EXPLANATION \r\nPatients with the Fontan physiology are at risk for thromboembolism secondary to \u201cpassive\u201d pulmonary blood flow, venous hypertension, and hemostatic abnormalities. The risk for thromboembolism appears to be highest in the first three to twelve months following the Fontan operation, although a lower risk persists for life. The optimal anticoagulation strategy in children is still under debate. It is quite challenging with traditional medications such as warfarin and low-molecular-weight heparins, which require frequent blood draws for monitoring therapeutic levels and\/or are administered subcutaneously. These patients are usually maintained on acetylsalicylic acid (ASA) despite the paucity of data on optimal dosing and aspirin resistance. A new class of anticoagulant drugs known as direct oral anticoagulants (DOACs) are now available, with significant advantages over current medications. These include dabigatran, rivaroxaban, apixaban, edoxaban and betrixaban. Only rivaroxaban and dabigatran are FDA-approved for use in children.\r\n\r\nRivaroxaban is an orally administered anticoagulant that binds directly and reversibly to free factor Xa (activated factor X) and prothrombinase-bound factor Xa (see Fig. 1). Rivaroxaban was approved by the Federal Drug Administration (FDA) in 2021 for two pediatric indications, including treatment of venous thromboembolism and risk reduction of recurrent venous thromboembolism and for thromboprophylaxis in pediatric patients with the Fontan palliation. Advantages of rivaroxaban include oral administration, no requirement for therapeutic monitoring, eliminating the need for repeated venipunctures, and fewer drug-drug and drug-food interactions. Rivaroxaban is excreted and eliminated by the kidneys and in the feces. P-glycoprotein and cytochrome P450 3A4 enzyme inducers and inhibitors will affect the pharmacology of rivaroxaban. Although the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) are prolonged, there is no requirement to monitor these levels during therapy.\r\n\r\n\r\n\r\nFig. 1. Mechanisms of action of DOACs. From: Al-Ghafry M, Sharathkumar A. Direct oral anticoagulants in pediatric venous thromboembolism: Review of approved products rivaroxaban and dabigatran. Front Pediatr<\/em>. 2022;10:1005098. Used under Creative Commons License.\r\n\r\nRivaroxaban was compared to ASA in the randomized, multi-center, 2-part, open-label UNIVERSE study to evaluate its dosing regimen, safety, and efficacy. Part A was a dose-finding and safety determination, while Part B enrolled 100 subjects with the Fontan palliation. A total of 66 patients received rivaroxaban, and 34 received ASA for thromboprophylaxis. One patient in the rivaroxaban group experienced a major bleeding episode consisting of epistaxis. No major bleeding was reported in the ASA group. Six percent of the rivaroxaban group and nine percent of the ASA group experienced a clinically relevant non-major bleeding event. With regards to efficacy, one patient (2%) in the rivaroxaban group experienced a pulmonary embolism. In contrast, three participants (9%) in the ASA group reported thrombotic events, two venous thromboses and one ischemic stroke. Notably, the study was not powered to determine efficacy. The authors concluded that rivaroxaban had similar safety<\/bold> as ASA for thromboprophylaxis in patients with Fontan physiology.\r\n\r\nPatients on rivaroxaban should have the medication stopped 24 to 48 hours before surgery, depending on the surgical procedure and renal function. If emergent reversal of anticoagulation by rivaroxaban is required, prothrombin complex concentrates (PCCs) or andexanet alfa may be administered. Andexanet alfa, an inactive recombinant factor Xa, has been approved for emergent reversal of rivaroxaban in adults. In a survey study, 44% of pediatric hematologists expressed that they prefer to administer andexanet alfa for emergent reversal of rivaroxaban in children versus PCCs. \r\n\r\nDabigatran is an orally administered direct thrombin inhibitor that has been FDA-approved for children older than three months of age. Dabigatran can be reversed with idarucizumab, an anti\u2010dabigatran monoclonal antibody fragment, which is approved for adults with major hemorrhage, and those requiring emergency surgery. Vitamin K antagonists (VKA) include warfarin, which works by inhibiting the vitamin K\u2010dependent coagulation factors, Prothrombin, Factor VII, Factor IX, and Factor X. Vitamin K should be given for reversal of VKA. However, it takes six hours for therapeutic effect after oral or intravenous administration of vitamin K. In emergent situations, four\u2010factor PCCs are recommended for rapid reversal of VKA if clinically indicated. \r\n\r\nThe correct answer is A. Andexanet alfa is recommended for reversal of rivaroxaban. Idarucizumab is recommended for reversal of dabigatran. Vitamin K is recommended for reversal of VKA,while four-factor PCCs are useful for emergent reversal.\r\n\r\n \r\nREFERENCES \r\nUS Food and Drug Administration. FDA approves drug to treat, help prevent types of blood clots in certain pediatric populations. Accessed on January 4 2025 at\r\nhttps:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/fda-approves-drug-treat-help-prevent-types-blood-clots-certain-pediatric-populations#:~:text=FDA%20has%20approved%20Xarelto%20(rivaroxaban,populations%20and%20for%20other%20uses\r\n\r\nMcCrindle BW, Michelson AD, Van Bergen AH, et al. Thromboprophylaxis for children post-Fontan procedure: Insights from the UNIVERSE Study J Am Heart Assoc<\/em>.2021;10(22):e021765. doi:10.1161\/JAHA.120.021765.\r\n\r\nAl-Ghafry M, Sharathkumar A. Direct oral anticoagulants in pediatric venous thromboembolism: Review of approved products rivaroxaban and dabigatran. Front Pediatr<\/em>. 2022;10:1005098. doi:10.3389\/fped.2022.1005098\r\n\r\nDoyle AJ, Crowley MP, Hunt BJ. Perioperative management of antithrombotic treatment in children. Paediatr Anaesth<\/em>. 2019;29(5):405-413. doi:10.1111\/pan.13511\r\n\r\n”,”hint”:””,”answers”:{“dey42”:{“id”:”dey42″,”image”:””,”imageId”:””,”title”:”A.\tAndexanet alfa “,”isCorrect”:”1″},”dkxmk”:{“id”:”dkxmk”,”image”:””,”imageId”:””,”title”:”B.\tProthrombin complex concentrate”},”71n6k”:{“id”:”71n6k”,”image”:””,”imageId”:””,”title”:”C.\tIdarucizumab”}}}}}