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

{“questions”:{“q9ozc”:{“id”:”q9ozc”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Arturo Marrero MD, Georgetown Public Hospital Corporation, Georgetown, Guyana and \r\nDestiny F. Chau MD, Arkansas Children\u2019s Hospital \/University of Arkansas for Medical Sciences, Little Rock, AR, USA \r\n\r\nPaciente femenina de 21 a\u00f1os se presenta para la reducci\u00f3n abierta y fijaci\u00f3n interna de una fractura de h\u00famero sufrida durante un episodio sincopal. En el examen f\u00edsico, se observa severa acropaquia (dedos en palillos de tambor) en los dedos de los pies. Los signos vitales son los siguientes: SpO2 97% (dedo de la mano derecha), SpO2 83% (dedo del pie derecho), pulso 118, presi\u00f3n arterial 100\/62. \u00bfCu\u00e1l de los siguientes hallazgos es M\u00c1S probable que se demuestre en una ecocardiograf\u00eda transtor\u00e1cica? \r\nA 21-year-old woman presents for open reduction and internal fixation of a humeral fracture sustained during a syncopal episode. On physical examination, severe clubbing of the toes is noted. The vital signs are as follows: SpO2 97% (right finger), SpO2 83% (right toe), HR 118 bpm, BP 100\/62. Which of the following findings is the MOST likely to be demonstrated on transthoracic echocardiography? “,”desc”:”Explicaci\u00f3n\/ Explanation \r\n\r\nLa acropaquia (dedos en palillos de tambor, hipocratismo digital, o clubbing) diferencial es un hallazgo f\u00edsico en pacientes con s\u00edndrome de Eisenmenger como consequencia del conducto arterioso persistente (CAP). \r\n\r\nLa evoluci\u00f3n natural del CAP es el empeoramiento de la hipertensi\u00f3n arterial pulmonar secundaria a la derivaci\u00f3n de izquierda a derecha de larga duraci\u00f3n, con la eventual reversi\u00f3n de la derivaci\u00f3n cuando la presi\u00f3n arterial pulmonar aumenta hasta alcanzar el nivel de la presi\u00f3n arterial sist\u00e9mica. La inversi\u00f3n de la derivaci\u00f3n da como resultado la perfusi\u00f3n de la parte inferior del cuerpo con sangre relativamente desaturada a trav\u00e9s del CAP y hacia la aorta descendente. En este caso, la oximetr\u00eda de pulso de las extremidades inferiores registrar\u00e1 una SpO2 m\u00e1s baja que la de las extremidades superiores. Esto es en contraste con las arterias car\u00f3tida y subclavia que reciben sangre completamente saturada del ventr\u00edculo izquierdo, lo que da como resultado una oximetr\u00eda de pulso normal en las extremidades superiores. La hipoxia cr\u00f3nica en las extremidades inferiores resulta en la acropaquia de los dedos de los pies, mientras que las extremidades superiores se salvan, dando como resultado la acropaquia diferencial. \r\nEl desarrollo de hipertensi\u00f3n arterial pulmonar con el s\u00edndrome de Eisenmenger resultante impide el cierre del conducto. La terapia m\u00e9dica con vasodilatadores pulmonares puede ser beneficiosa para reducir la presi\u00f3n de la arteria pulmonar y brindar alivio sintom\u00e1tico. El trasplante de coraz\u00f3n y pulm\u00f3n puede ser una opci\u00f3n en pacientes adecuadamente seleccionados. \r\n\r\nLa acropaquia es una manifestaci\u00f3n de numerosas condiciones y no es exclusiva de la hipoxia cr\u00f3nica. Aproximadamente el 75 % de las condiciones asociadas con la acropaquia implican enfermedades pulmonares en ausencia de hipoxia, como tumores pulmonares malignos y bronquiectasias, mientras que el 15 % son enfermedades card\u00edacas, como endocarditis infecciosa y cardiopat\u00edas cong\u00e9nitas cian\u00f3ticas. Otro 10% son enfermedades gastrointestinales como la enfermedad de Crohn y la cirrosis, y el resto incluye condiciones como la osteoartropat\u00eda hipertr\u00f3fica y el hipertiroidismo. El mecanismo para el desarrollo de la acropaquia no est\u00e1 completamente dilucidado. Los factores contribuyentes incluyen la hipoxia local, la activaci\u00f3n plaquetaria, la estimulaci\u00f3n de la angiog\u00e9nesis y la liberaci\u00f3n de prote\u00ednas se\u00f1alizadoras como el factor de crecimiento del endotelio vascular. \r\n\r\nEn el escenario de este caso, los hallazgos ecocardiogr\u00e1ficos mostrar\u00edan un CAP grande con derivaci\u00f3n de derecha a izquierda, presiones sist\u00f3licas ventriculares derechas elevadas, hipertrofia y dilataci\u00f3n ventricular derecha y aplanamiento sist\u00f3lico del tabique intraventricular. Los hallazgos de una presi\u00f3n sist\u00f3lica del ventr\u00edculo derecho normal y derivaci\u00f3n de izquierda a derecha no son consistentes con el s\u00edndrome de Eisenmenger debido al CAP en una persona adulta. \r\n\r\n————————————————— \r\n\r\nDifferential clubbing is a physical finding in patients with Eisenmenger syndrome resulting from a persistent patent ductus arteriosus (PDA). The natural history of a persistent PDA is worsening pulmonary arterial hypertension secondary to long-standing left to right shunt with eventual reversal of shunting as pulmonary arterial pressure increases to systemic pressure. The reversal of shunting results in the lower body being perfused with relatively desaturated blood through the PDA and into the descending aorta. In this setting, pulse oximetry of the lower extremities will register a lower SpO2 than the upper extremities. In contrast, the carotid and subclavian arteries receive fully saturated blood from the left ventricle resulting in normal pulse oximetry in the upper extremities. Chronic hypoxia in the lower extremities leads to clubbing of the toes, whereas the upper extremities would be spared which results in differential clubbing. The development of pulmonary arterial hypertension with resultant Eisenmenger syndrome precludes ductal closure. Medical therapy with pulmonary vasodilators may be beneficial in reducing pulmonary artery pressure and providing symptomatic relief. Heart-and-lung transplantation may be an option in appropriately selected patients. \r\n\r\nClubbing is a manifestation of numerous conditions and is not unique to chronic hypoxia. Approximately 75% of conditions associated with clubbing involve pulmonary diseases in the absence of hypoxia, such as lung malignancies and bronchiectasis while 15% are cardiac diseases such as infective endocarditis and cyanotic congenital heart disease. Another 10% are gastrointestinal diseases such as Crohn\u2019s disease and cirrhosis, and the rest include conditions such as hypertrophic osteoarthropathy and hyperthyroidism. The mechanism for the development of digital clubbing is not fully understood. Contributing factors include local hypoxia, platelet activation, stimulation of angiogenesis, and release of signal proteins such as vascular endothelial growth factor. \r\n\r\nIn this case scenario, echocardiographic findings would show a large PDA with right-to-left shunting, elevated right ventricular systolic pressures (RVSP), right ventricular hypertrophy and dilation, and systolic flattening of the intraventricular septum. A normal RVSP and left-to-right shunting are not consistent with Eisenmenger syndrome due to a persistent PDA in an adult. \r\n\r\nReferencias\/ References \r\n\r\n\r\nSrinivas SK, Manjunath CN. Differential clubbing and cyanosis: classic signs of patent ductus arteriosus with Eisenmenger syndrome. Mayo Clin Proc<\/em>. 2013;88(9): e105-e106. doi:10.1016\/j.mayocp.2013.02.016 \r\n\r\nUribe-Valencia MA, Ocampo Chaparro JM, Parra-Camarillo M. Hipocratismo digital: conociendo sus causas. Reporte de caso. Rev Fac Med <\/em>. 2019;6: 543-546. https:\/\/doi.org\/10.15446\/revfacmed.v67n3.69592 \r\n\r\n\r\nWald R, Crean A. Differential clubbing and cyanosis in a patient with pulmonary hypertension. CMAJ<\/em>. 2010;182(9):E380. doi:10.1503\/cmaj.091003 \r\n\r\nDimopoulos K. Eisenmenger syndrome in an adult patient with a large patent ductus arteriosus. Eur Respir Rev <\/em>. 2013;22(130):558-564. doi:10.1183\/09059180.00007013\r\n\r\nRutherford JD. Digital clubbing. Circulation <\/em>. 2013;127(19): 1997-1999. doi:10.1161\/CIRCULATIONAHA.112.000163\r\n\r\n\r\n”,”hint”:””,”answers”:{“iouxi”:{“id”:”iouxi”,”image”:””,”imageId”:””,”title”:”A.\tConducto arterioso persistente\/Patent ductus arteriosus”,”isCorrect”:”1″},”yg5fh”:{“id”:”yg5fh”,”image”:””,”imageId”:””,”title”:”B.\tPresi\u00f3n sist\u00f3lica del ventr\u00edculo derecho normal\/Normal right ventricular systolic pressure”},”wlkt2″:{“id”:”wlkt2″,”image”:””,”imageId”:””,”title”:”C.\tPresencia de derivaci\u00f3n de izquierda a derecha\/Presence of left-to-right shunting”}}}}}

{“questions”:{“bmvzk”:{“id”:”bmvzk”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Gokul Thimmarayan, MD and Destiny F. Chau, MD – Arkansas Children\u2019s Hospital \/University of Arkansas for Medical Sciences, Little Rock, AR \r\n\r\nAn 18-month-old toddler with a history of Trisomy 21 is undergoing a full repair of a partial atrioventricular canal with cardiopulmonary bypass. Ten times the intended dose of tranexamic acid is administered during the procedure in error. In the early post-operative period, generalized tonic-clonic seizures are noted. Tranexamic acid induces seizures by the competitive antagonism of which of the following receptors?\r\n”,”desc”:”EXPLANATION \r\nTranexamic acid (TXA) is an analog of lysine, which binds to plasminogen and prevents its conversion to plasmin, thereby inhibiting fibrinolysis and improving hemostasis. TXA use decreases the risk of bleeding after cardiac surgery with cardiopulmonary bypass in both the adult and pediatric populations. Epsilon aminocaproic acid (EACA), another lysine derivative, and aprotinin, a serine protease inhibitor, are other antifibrinolytic agents. \r\n \r\nThe reported dosing ranges and protocols for TXA differ greatly from a 10 to 100 mg\/kg bolus prior to cardiopulmonary bypass (CPB) followed by an infusion at variable rates and\/or an additional bolus in the pump prime. TXA use has been associated with an increased risk of thromboembolism, seizure, and renal dysfunction. Seizure frequency is correlated positively with higher doses of TXA (total TXA dose of >100 mg\/kg), which was demonstrated in study of adult cardiac surgical patients by Kalavrouziotis et al. TXA-related seizures are most frequently reported in the early postoperative period after cardiac surgery and are associated with increased morbidity and mortality. In a propensity-score matched study of 3,739 pairs of pediatric patients undergoing cardiac surgery, Maeda et al. demonstrated an incidence of seizures of 1.6% in the patients treated with TXA versus 0.2% in those not treated with TXA.\r\n\r\n \r\nA 2012 study by Lecker et al. used the mouse neuron as a model to investigate the mechanism of seizure due to TXA. The study demonstrated that TXA, which is a structural analog of the inhibitory neurotransmitter glycine, competitively binds to and inhibits the activity of glycine receptors. Thus, the authors postulated that blockade of inhibitory glycine receptors by TXA leads to neuronal hyperexcitability and lowers seizure threshold. The authors temporally measured the TXA concentration in serum and cerebrospinal fluid (CSF) in patients undergoing vascular surgery or cardiac surgery with cardiopulmonary bypass. The authors found that the peak TXA concentration in CSF occurs after<\/em> the peak TXA concentration in serum. The peak concentration of TXA in CSF correlated with the reported observation that seizures occur more frequently in the early postoperative period. This time frame also coincides with the waning anti-convulsant effects of general anesthetic agents after surgery. The authors also postulated that enhancing glycine inhibitory potential could suppress seizures associated with TXA. Therefore, agents such as isoflurane, sevoflurane, and propofol, which are known to stimulate glycine receptor activity, could potentially be used to prevent or treat seizures induced by TXA. \r\n\r\nEACA, which is also an analogue of lysine, is associated with a much lower incidence of seizures because it is a much weaker inhibitor at glycine receptors than TXA. In a study comparing the incidence of seizures in adult cardiac surgical patients treated with TXA or EACA, Martin et al. reported an incidence of 7.6% in the TXA group versus 3.3% in the EACA group. \r\n\r\nAspartate, and acetylcholine are excitatory neurotransmitters in the central nervous system. Thus far, they have not been associated with seizures caused by TXA. \r\n\r\nThe most effective way to prevent TXA-induced seizures is by utilizing doses at the lower end of the range known to be effective in reducing blood loss after surgery and by lowering the dose administered to patients with renal dysfunction, as it is primarily eliminated in the urine. Currently, there is not a clearly defined safe, yet effective dose of TXA. \r\n \r\nREFERENCES \r\n\r\nMaeda T, Sasabuchi Y, Matsui H, Ohnishi Y, Miyata S, Yasunaga H. Safety of tranexamic acid in pediatric cardiac surgery: a nationwide database study. J Cardiothorac Vasc Anesth <\/em>. 2017;31(2):549-553. doi:10.1053\/j.jvca.2016.10.001 \r\n\r\nLecker I, Wang DS, Romaschin AD, Peterson M, Mazer CD, Orser BA. Tranexamic acid concentrations associated with human seizures inhibit glycine receptors.J Clin Invest<\/em>. 2012;122(12):4654-4666. doi:10.1172\/JCI63375 \r\n\r\nKalavrouziotis D, Voisine P, Mohammadi S, Dionne S, Dagenais F. High-dose tranexamic acid is an independent predictor of early seizure after cardiopulmonary bypass. Ann Thorac Surg <\/em>. 2012;93(1):148-155. doi: 10.1016\/j.athoracsur.2011.07.085 \r\n\r\nLecker I, Wang D, Whissell P, Avramescu S, Mazer C, Orser B. Tranexamic acid-associated seizures: causes and treatment. Ann Neurol <\/em>. 2016;79(1):18-26. Doi:10.1002\/ama.24558 \r\n\r\nMartin K, Knorr J, Breur T et al. Seizures after open heart surgery: a comparison of E-aminocaproic acid versus tranexamic acid. J Cardiothorac Vasc Anesth<\/em>. 2011;25:20-5. doi: 10.1053\/j.jvca.2010.10.007.\r\n\r\n”,”hint”:””,”answers”:{“zzf35”:{“id”:”zzf35″,”image”:””,”imageId”:””,”title”:”A.\tAspartate”},”4o24p”:{“id”:”4o24p”,”image”:””,”imageId”:””,”title”:”B.\tGlycine”,”isCorrect”:”1″},”2ngc9″:{“id”:”2ngc9″,”image”:””,”imageId”:””,”title”:”C.\tAcetylcholine”}}}}}

{“questions”:{“8td7c”:{“id”:”8td7c”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Destiny F. Chau, MD and Jorge Guerrero, MD – Arkansas Children\u2019s Hospital \/University of Arkansas for Medical Sciences, Little Rock, AR \r\n\r\nA 9 y\/o female child with a history of an extracardiac fenestrated Fontan presents for tonsillectomy and adenoidectomy. A recent cardiac catheterization demonstrated a Fontan pressure of 19 mmHg. Home medications include aspirin and sacubitril\/valsartan. Which class of medication does sacubitril belong to? \r\n”,”desc”:”EXPLANATION \r\nSacubitril is a neprilysin inhibitor, which is a naturally occurring endopeptidase enzyme that degrades neuropeptides that are known to contribute to the pathophysiology of heart failure. Chronic heart failure is associated with elevated neprilysin levels and faster clearance of neuropeptides. \r\n\r\nHeart failure results in the activation of both the sympathetic nervous system and the renin-angiotensin-aldosterone system leading to increased levels of renin, angiotensin II, aldosterone, and anti-diuretic hormone. The end result is increased vascular tone and blood pressure, which are compensatory mechanisms to increase organ perfusion. However, this activation impairs the function of endogenous neuropeptides such as atrial natriuretic peptide and B-type natriuretic peptide, bradykinin, and adrenomedullin. These peptides cause vasodilation, natriuresis, diuresis, and counteract the abnormal sympathetic response implicated in maladaptive vascular and cardiac remodeling. \r\n\r\nThe inhibition of neprilysin prevents the degradation of endogenous neuropeptides leading to an increased concentration of bradykinin, natriuretic peptides, adrenomedullin and angiotensin II. Therefore, a neprilysin inhibitor is paired with an angiotensin receptor blocker (ARB) to mitigate the effects of elevated angiotensin II levels. This class of drug, termed an ARNI (angiotensin receptor neprilysin inhibitor), received FDA approval in 2015 for the treatment of symptomatic heart failure with reduced ejection fraction. Patients must demonstrate tolerability to an angiotensin-converting enzyme inhibitor (ACEI) or ARB before starting sacubitril\/valsartan. \r\n\r\nAngiotensin II effects can reduced by using an ACEI. However, the combination of both a neprilysin inhibitor and an ACEI was found to cause significant angioedema due to the fact that both drugs increase bradykinin levels thus worsening angioedema. Therefore, the combination of an ACEI and ARNI should be avoided. Coadministration of a neprilysin inhibitor within 36 hours of an ACEI is contraindicated.\r\nIn a prospective, randomized trial by McMurray et al. (widely known as PARADIGM-HF – Prospective Comparison of ARNI [Angiotensin Receptor\u2013Neprilysin Inhibitor] with ACEI [Angiotensin-Converting\u2013Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial) of adult patients with symptomatic heart failure and reduced ejection fraction, the use of sacubitril\/valsartan demonstrated increased efficacy in reducing morbidity and mortality versus standard treatment with enalapril. Adverse effects of sacubitril\/valsartan included hypotension, hyperkalemia, renal failure, cough, and angioedema. Compared to enalapril, treatment with sacubitril\/valsartan resulted in a higher incidence of hypotension and symptomatic hypotension but a lower risk of increased serum potassium and creatinine and lower risk of cough. Although not statistically significant, angioedema in the sacubitril\/valsartan group was higher than in the enalapril group, with no reported cases of angioedema causing airway compromise. \r\n\r\nAccording to the most recent 2022 AHA\/ACC\/HFSA guidelines (Heidenreich et al.), treatment with sacubitril\/valsartan is a Class I recommendation for the management of symptomatic heart failure with reduced ejection fraction. Additionally, treatment with sacubitril\/valsartan is a Class 2b recommendation for the management of heart failure with preserved ejection fraction. This drug is also known to enhance right sided ejection fraction and reduce pulmonary artery pressures independent of an improvement in left ventricular function. Sacubitril\/valsartan use in pediatric patients is based upon data from the adult population. However, there are current ongoing studies in the pediatric population. \r\n\r\nThe effect of general anesthesia on the blood pressure of patients taking an ARNI is currently unknown. Given the presence of an ARB in this combination drug and the reports of a higher risk of hypotension with ARNI use as compared to enalapril, it is reasonable to deduce that ARNI use may also be associated with severe refractory hypotension under general anesthesia. Therefore, vigilance and preparation for severe hypotension in patients taking an ARNI whilst undergoing general anesthesia is warranted. As of yet, there are no guidelines on how to best manage perioperative ARNI use. \r\n\r\n \r\nREERENCES \r\nMcMurray JJV, Packer M, Desai AS et al. Angiotensin-Neprolysin inhibition versus enalapril in heart failure. N Engl J Med. 2014; 371:993-1004. DOI: 10.1056\/NEJMoa1409077 \r\n\r\nHeidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA\/ACC\/HFSA Guideline for the management of heart failure: A Report of the American College of Cardiology\/American Heart Association Joint Committee on Clinical Practice Guidelines [published correction appears in Circulation. 2022 May 3;145(18):e1033] [published correction appears in Circulation. 2022 Sep 27;146(13):e185] [published correction appears in Circulation. 2023 Apr 4;147(14):e674]. Circulation<\/em>. 2022;145(18):e895-e1032. doi:10.1161\/CIR.0000000000001063\r\n\r\nDas BB, Scholl F, Vandale B, Chrisant M. Sacubitril\/Valsartan: potential treatment for paediatric heart failure. Cardiol Young<\/em>. 2018;28(9):1077-1081. doi:10.1017\/S1047951118001014 \r\n\t\r\nNicolas D, Kerndt CC, Reed M. Sacubitril\/Valsartan. [Updated 2022 May 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK507904\/ \r\n\r\nZhang J, Du L, Qin X, Guo X. Effect of sacubitril\/valsartan on the right ventricular function and pulmonary hypertension in patients with heart failure with reduced ejection fraction: a systematic review and meta-analysis of observational studies. J Am Heart Assoc<\/em>. 2022;11(9):e024449doi:10.1161\/JAHA.121.024449\r\n”,”hint”:””,”answers”:{“xzyl1”:{“id”:”xzyl1″,”image”:””,”imageId”:””,”title”:”A.\tNeprilysin inhibitor”,”isCorrect”:”1″},”pxwle”:{“id”:”pxwle”,”image”:””,”imageId”:””,”title”:”B.\tAngiotensin converting enzyme inhibitor”},”anjbt”:{“id”:”anjbt”,”image”:””,”imageId”:””,”title”:”C.\tPhosphodiesterase inhibitor”},”r5utx”:{“id”:”r5utx”,”image”:””,”imageId”:””,”title”:”D.\tCalcium channel blocker”}}}}}

{“questions”:{“xv60e”:{“id”:”xv60e”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Dylan Trujillo, DO, Felipe Medeiros, MD, Destiny F. Chau, MD – Arkansas Children\u2019s Hospital \/University of Arkansas for Medical Sciences, Little Rock, AR \r\n\r\nTwo weeks following orthotopic heart transplantation for dilated cardiomyopathy, a 6-month-old male infant returns to the operating room for permanent pacemaker implantation. Which of the following is the MOST likely indication for permanent pacemaker implantation in this patient?\r\n\r\n”,”desc”:”EXPLANATION \r\nDysrhythmia following orthotopic heart transplantation (OHT) occurs in approximately 40% of pediatric recipients. Factors predisposing to dysrhythmia are multifactorial. One contributing factor relates to unopposed sympathetic tone secondary to donor heart denervation. Denervation leads to a lack of response to the modulating influence of the vagus nerve and to the higher baseline heart rate. Surgical techniques employed for orthotopic heart transplantation have also been implicated in the development of dysrhythmia. The biatrial technique preserves part of the recipient\u2019s right and left atrial tissue to facilitate the incorporation of the cardiac graft. The bicaval technique incorporates a cuff of the recipient\u2019s left atrial tissue. Scarring of the atria creates a predisposition to atrial flutter. In the biatrial method, P waves may be generated from both the cardiac graft and native atrial tissue which mimics atrial flutter. Additionally, sinus node activity from native atrial tissue may be conducted intermittently and thus manifest as ectopic atrial beats. As cuffs of atrial tissue are preserved in both techniques, all patients are expected to develop some degree of increased atrial size after OHT. Other factors which contribute to the risk of dysrhythmia after OHT include prolonged graft ischemic time, donor-recipient size mismatching (which contributes to atrial enlargement), acute and chronic rejection, and cardiac allograft vasculopathy. \r\n\r\nAtrial fibrillation and atrial flutter have been reported in 10% to 25% of patients after OHT with the majority of cases occurring in the first few weeks after transplantation and with eventual resolution in the majority of patients. Bradydysrhythmias occurring after OHT (which also frequently resolve spontaneously) include atrioventricular block and sinus bradycardia. Common causes include sinus node injury or ischemia, sympathetic denervation, and medication side effects. \r\nTemporary pacing for bradydysrhythmia is often utilized following OHT while the cardiac conduction system recovers from injury. Rarely, when normal cardiac conduction does not return, consideration of permanent pacemaker implantation is necessary. The 2021 PACES expert consensus on pediatric cardiovascular implantable electronic devices recommends waiting at least one week for spontaneous recovery of sinus node function. \r\nA systematic review of 11 studies by Mylonas et al. which included a total of 7,198 pediatric patients who underwent heart transplantation demonstrated that 1.9% of patients received a permanent pacemaker. However, although overall sinus node dysfunction was the most frequent indication for pacemaker placement (54.4% versus 45.6% for complete atrioventricular block), in almost half of the cases there was no indication reported. The need for pacemaker placement occurred earlier in the postoperative course in patients with complete atrioventricular block. The median time interval between OHT and permanent pacemaker implantation ranged from 17 days to 6.5 years in patients with complete heart block while it was 2.7 months to 12.5 years for sinus node dysfunction. The biatrial technique was utilized in 62.2% of patients and the bicaval technique in the remaining 37.8%. \r\n\r\nIn a single-center study by Mahmood et al., of 314 pediatric transplant recipients, 16 (5.1%) patients required permanent pacemaker placement. Indications for pacemaker placement were complete heart block in 75% of patients and sinus node dysfunction in 25% of patients. In 9 of 12 (75%) patients with complete heart block, the pacemaker was implanted within 21 days of the transplant. Three out of the four patients with sinus node dysfunction had pacemaker implantation at 61 days or longer after transplant. \r\nThe patient described in the question stem has undergone OHT two weeks prior without restoration of normal sinus rhythm and is most likely to have persistent complete atrioventricular block given the described time frame. Although symptomatic sinus bradycardia and second degree Mobitz Type II heart block can occur, they either resolve or persist to meet the indication for permanent pacemaker implantation at a later timepoint as compared to complete heartblock. At this early stage after OHT, close evaluation is important to rule out reversible causes of bradydysrhythmia such as acute rejection or antiarrhythmic medication side effects. \r\nREFERENCES \r\n\r\nNavas-Blanco JR, Modak RK. Perioperative care of heart transplant recipients undergoing non-cardiac surgery. Ann Card Anaesth<\/em>. 2021;24(2):141-148 doi: 10.4103\/aca.ACA_130_19. \r\n\r\n\r\nJoglar JA, Wan EY, Chung MK, et al. Management of arrhythmias after heart transplant: current\r\nstate and considerations for future research. Circ Arrhythm Electrophysiol <\/em>.2021;14(3):e007954. doi: 10.1161\/CIRCEP.120.007954. \r\n\r\nShah MJ, Silka MJ, Silva JNA, et al. 2021 PACES expert consensus statement on the indications and management of cardiovascular implantable electronic devices in pediatric patients. Cardiol Young<\/em>. 2021;31(11):1738-1769. doi:10.1017\/S1047951121003413\r\n\r\nMylonas KS, Repanas T, Athanasiadis DI, et al. Permanent pacemaker implantation in pediatric heart transplant recipients: A systematic review and evidence quality assessment. Pediatr Transplant<\/em>. 2020;24(3):e13698. doi: 10.1111\/petr.13698. \r\nMahmood A, Andrews R, Fenton M et al. Permanent pacemaker implantation after pediatric heart transplantation: Risk factors, indications, and outcomes. Clin Transplant <\/em>.2019;33(4) e13503. doi: 10.1111\/ctr.13503.\r\nHerrmann FEM, Wellmann P, Hagl C, Juchem G. Pediatric heart transplantation-What are the risk factors for pacemaker implantation and how much pacing is required? Pacing Clin Electrophysiol<\/em>. 2018;41(3):267-276. doi: 10.1111\/pace.13276.\r\n\r\n\r\n\r\n\r\n\r\n”,”hint”:””,”answers”:{“cl5cs”:{“id”:”cl5cs”,”image”:””,”imageId”:””,”title”:”A.\tComplete atrioventricular block “,”isCorrect”:”1″},”7mfo2″:{“id”:”7mfo2″,”image”:””,”imageId”:””,”title”:”B.\tSecond Degree (Mobitz) type II heart block”},”7278l”:{“id”:”7278l”,”image”:””,”imageId”:””,”title”:”C.\tSymptomatic sinus bradycardia “}}}}}

{“questions”:{“6ntww”:{“id”:”6ntww”,”mediaType”:”image”,”answerType”:”text”,”imageCredit”:””,”image”:””,”imageId”:””,”video”:””,”imagePlaceholder”:””,”imagePlaceholderId”:””,”title”:”Authors: Dylan Trujillo, DO, Felipe Medeiros, MD, Destiny F. Chau, MD; Arkansas Children\u2019s Hospital\/University of Arkansas for Medical Sciences, Little Rock, AR \r\n\r\nAn 8-year-old male child with history of an orthotopic heart transplantation six years prior due to dilated cardiomyopathy presents for laparoscopic appendectomy. The patient is compliant with transplant medications and the last cardiac catheterization demonstrated normal hemodynamics without rejection. The vital signs are as follows: BP 97\/55, HR 108, SpO2 99% in room air, RR 21, and T 37.8^{o<\/sup>C. Laboratory results show: WBC 18 x 109 <\/sup>\/L, Hb 13 g\/dL, platelets 245 x 109 <\/sup>\/L. At present, which of the following is the MOST likely cause of morbidity and mortality in this patient?\r\n\r\n\r\n”,”desc”:”EXPLANATION \r\nThe primary causes of mortality following orthotopic heart transplantation (OHT) vary with the time elapsed since transplant. Common causes of death include acute rejection, infection, cardiac allograft vasculopathy (CAV) and malignancy. While acute rejection is the leading cause of death during the first 3 years following OHT, CAV predominates thereafter as the leading cause of mortality. \r\n\r\nAccording to data from the International Society of Heart and Lung Transplantation, approximately 20% of OHT recipients have some degree of CAV at 5 years and 25% at 10 years post-transplant. The mortality rate after CAV diagnosis is high across all age groups. There is 25% 2-year mortality in patients with any severity of CAV and 50% 2-year mortality in patients with moderate-to-severe CAV. Infants have the worst survival rates with a median of 2 years after CAV diagnosis. The clinical symptom of chest pain from myocardial ischemia is typically absent due to denervation of the transplanted heart. Therefore, severe CAV manifests as progressive deterioration in graft function, heart failure, or sudden death. For this reason, transplant recipients are usually screened on a yearly basis for CAV using coronary angiography or dobutamine stress echocardiography. The histologic appearance of CAV is that of concentric intimal and medial proliferation that ultimately results in luminal occlusion, diastolic dysfunction, and graft failure. Treatment of CAV includes percutaneous revascularization procedures such as balloon angioplasty and coronary artery stenting, but the success rate is low due to the diffuse nature of the disease. Cardiac re-transplantation should be considered for those patients with moderate to severe CAV and graft dysfunction. \r\n\r\nThe rate of infection in OHT patients is highest in the first year after transplantation, accounting for approximately 16% of deaths, but declines thereafter. As immunosuppressive therapy can potentiate the severity of infections, early diagnosis and aggressive therapy of infection is imperative. In a 2006 single institution, retrospective review by Savar et al. of 8000 solid organ transplants (which included four OHTs and one heart-kidney transplant), 17 patients underwent appendectomy with an average age of 37 years (range 6yrs-73yrs). They reported no deaths, no episodes of acute organ rejection, and no intraoperative complications after appendectomy. \r\n\r\nAcute rejection is the most frequent cause of death during the first year after OHT. Greater age at the time of transplantation increases the risk for acute rejection and is associated with lower survival. The risk of malignancy increases over time, with an incidence of approximately 10% at 10 years and 16% at 15 years post-transplant. Although post-transplant lymphoproliferative disorders account for the vast majority of malignancies and are associated with reduced survival, they are not one of the leading causes of mortality after OHT. \r\n\r\nThe patient\u2019s cardiac status appears to be optimized given compliance with medications, normal cardiac catheterization data and negative biopsy results. As immunosuppression can exacerbate acute appendicitis, prompt treatment is imperative with good outcomes having been reported after surgical management. Perioperative continuation of the anti-rejection therapy is important for recovery. Obtaining a preoperative echocardiogram would be helpful to confirm cardiac function but should not delay surgery. As six years have elapsed since OHT, this patient\u2019s risk for acute rejection and malignancy is lower than for CAV; thus, CAV would be the most likely cause of morbidity and mortality in this patient. \r\n\r\n\r\nREFERENCES \r\nDipchand AI, Laks JA. Pediatric heart transplantation: long-term outcomes. Indian J Thorac Cardiovasc Surg.<\/em>2020; 36(Suppl 2):175-189. \r\n\r\nRossano JW, Dipchand AI, Edwards LB, et al. The Registry of the International Society for Heart and Lung Transplantation: Nineteenth pediatric heart transplantation report-2016; Focus theme: Primary diagnostic indications for transplant. J Heart Lung Transplant. <\/em>2016; 35(10):1185-1195. \r\n\r\nDipchand AI. Current state of pediatric cardiac transplantation. Ann Cardiothorac Surg. <\/em>2018; 7(1):31-55. \r\n\r\nSavar A, Hiatt JR, Busuttil RW. Acute appendicitis after solid organ transplantation. Clin Transplant. <\/em>2006; 20(1):78-80.\r\n\r\n”,”hint”:””,”answers”:{“7b5nr”:{“id”:”7b5nr”,”image”:””,”imageId”:””,”title”:”A.\tAcute graft rejection”},”hrz7u”:{“id”:”hrz7u”,”image”:””,”imageId”:””,”title”:”B.\tCardiac allograft vasculopathy”,”isCorrect”:”1″},”jlc2f”:{“id”:”jlc2f”,”image”:””,”imageId”:””,”title”:”C.\tMalignancy”}}}}}}