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Innovative 2-Step Management Strategy Utilizing EXIT Procedure for a Fetus With Hypoplastic Left Heart Syndrome and Intact Atrial Septum
CASE REPORT
Innovative 2-Step Management Strategy Utilizing EXIT Procedure for a Fetus With Hypoplastic Left Heart Syndrome and Intact Atrial Septum Sameh M. Said, MD; Muhammad Yasir Qureshi, MBBS; Nathaniel W. Taggart, MD; Heather N. Anderson, MD; Patrick W. O’Leary, MD; Frank Cetta, MD; Layan Alrahmani, MD; Shelagh A. Cofer, MD; Leal G. Segura, MD; Roxann B. Pike, MD; Emily E. Sharpe, MD; Douglas P. Derleth, MD; Michael E. Nemergut, MD, PhD; Charlotte S. Van Dorn, MD; Stephen J. Gleich, MD; Carl H. Rose, MD; Christopher A. Collura, MD; and Rodrigo Ruano, MD, PhD Abstract Hypoplastic left heart syndrome (HLHS) with intact atrial septum (HLHS-IAS) carries a high risk of mortality and affects about 6% of all patients with HLHS. Fetal interventions, postnatal transcatheter interventions, and postnatal surgical resection have all been used, but the mortality risk continues to be high in this subgroup of patients. We describe a novel, sequential approach to manage HLHS-IAS and progressive fetal hydrops. A 28-year-old, gravida 4 para 2 mother was referred to Mayo Clinic for fetal HLHS. Fetal echocardiography at 28 weeks of gestation demonstrated HLHS-IAS with progressive fetal hydrops. The atrial septum was thick and muscular with no interatrial communication. Ultrasound-guided fetal atrial septostomy was performed with successful creation of a small atrial communication. However, fetal echocardiogram at 33 weeks of gestation showed recurrence of a pleural effusion and restriction of the atrial septum. We proceeded with an Ex utero Intrapartum Treatment (EXIT) delivery and open atrial septectomy. This was performed successfully, and the infant was stabilized in the intensive care unit. The infant required venoarterial extracorporeal membrane oxygenator support on day of life 1. The patient later developed hemorrhagic complications, leading to his demise on day of life 9. This is the first reported case of an EXIT procedure and open atrial septectomy performed without cardiopulmonary bypass for an open-heart operation and provides a promising alternative strategy for the management of HLHS-IAS in select cases. ª 2018 Mayo Foundation for Medical Education and Research
For editorial comment, see page 194. From the Department of Cardiovascular Surgery (S.M.S.), Division of Pediatric Cardiology (M.Y.Q., N.W.T., H.N.A., P.W.O., F.C.), Division of Obstetrics and Maternal Fetal Medicine (L.A., C.H.R., R.R.), Division of Pediatric Otorhinolaryngology (S.A.C.), Division of Pediatric AnesAffiliations continued at the end of this article.
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ypoplastic left heart syndrome (HLHS) with an intact or severely restrictive atrial septum (HLHSIAS) carries a high risk of mortality and affects about 6% of all patients with HLHS.1 Emergent relief of obstruction at the atrial level is needed for survival. However, the best strategy for relief of left atrial hypertension is not established. Fetal interventions, postnatal transcatheter interventions, and postnatal surgical resection have all been used, but mortality risk continues to be high.2 We describe a novel, sequential approach to manage a fetus
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with HLHS-IAS and progressive fetal hydrops. This staged approach consisted of initial percutaneous in utero fetal atrial septostomy followed by Ex utero Intrapartum Treatment (EXIT) to surgical atrial septectomy (a 2-step process). CASE PRESENTATION A 28-year-old, gravida 4 para 2 mother was referred to Mayo Clinic for further management of fetal HLHS. Fetal echocardiogram performed at 28 weeks of gestation demonstrated HLHS-IAS with mitral valve hypoplasia, aortic
Mayo Clin Proc. n February 2019;94(2):356-361 n https://doi.org/10.1016/j.mayocp.2018.08.004 www.mayoclinicproceedings.org n ª 2018 Mayo Foundation for Medical Education and Research
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valve atresia, hypoplastic left ventricle, and hypoplastic ascending aorta. The left atrium was small with dilated pulmonary veins, and the atrial septum was thick and muscular with no interatrial communication or thin primum septum (Figure 1A). Pulmonary venous Doppler showed to-and-fro flow with prominent flow reversal during atrial systole and absent early diastolic forward flow, consistent with severe left atrial hypertension (Figure 1B). There was no decompressing vein or antegrade flow through the left heart. A new small right-sided pleural effusion and a pericardial effusion were seen on subsequent imaging. Because of the development of these early signs of fetal hydrops, percutaneous fetal intervention was proposed. ULTRASOUND-GUIDED PERCUTANEOUS FETAL ATRIAL SEPTOSTOMY Under ultrasound guidance, the fetal atrial septostomy was performed at 30 weeks of gestation under monitored sedation and
local maternal anesthesia. Fetal anesthesia was administered into the left arm of the fetus. An 18-gauge Cook blunt-tip needle was advanced percutaneously into the amniotic space and was directed through the fetal chest wall into the right atrium. The atrial septostomy was performed with the needle trocar, and the trocar was removed. A 3.75 mm diameter 8 mm long Emerge coronary angioplasty balloon was advanced over a 0.014” Samurai coronary wire and inflated multiple times to dilate the atrial septostomy. Flow across the atrial septum was demonstrated by color Doppler. A small pericardial effusion was observed initially but remained stable over 20 minutes of monitoring and did not require additional intervention. Follow-up fetal echocardiogram 1 week later demonstrated resolution of pericardial and pleural effusions. The septal defect was still patent, although somewhat restrictive (mean Doppler gradient, 2-3 mm Hg) with
FIGURE 1. Ultrasound-guided intrauterine fetal atrial septostomy. A, Four-chamber view on fetal echocardiogram showing pleural and pericardial effusions (*). Arrows indicate dilated left and right pulmonary veins. B, Pulmonary venous Doppler with prominent atrial reversal of flow (A) with no early diastolic forward flow (D). C, Color Doppler demonstrating atrial-level shunt (arrow) after fetal intervention. D, Pulse wave Doppler interrogation of atrial shunt showing 2 to 3 mm Hg gradient across the atrial septum. LA ¼ left atrium; RA ¼ right atrium; RV ¼ right ventricle. Mayo Clin Proc. n February 2019;94(2):356-361 www.mayoclinicproceedings.org
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continuous blood flow across the septum noted (Figure 1C and D). The patient was closely monitored by maternal fetal medicine and pediatric cardiology weekly. Fetal echocardiogram performed at 33 weeks of gestation showed persistent patency of the atrial communication, but reappearance of a rightsided pleural effusion. Percutaneous reintervention was not felt to be beneficial in this setting due to thick and muscular atrial septum. Due to evolving fetal hydrops, EXIT to open atrial septectomy with possible need for extracorporeal membrane oxygenator (ECMO) support was offered. The added risks of the EXIT procedure and ECMO were discussed in detail with the parents. Alternative management options including compassionate comfort care and transcatheter atrial septal dilation were discussed. After extensive multidisciplinary discussion, the parents elected to proceed with the EXIT procedure and open septectomy. Pediatric Ethical Board reviewed the case, made recommendations, and agreed with proceeding. EXIT TO SURGICAL ATRIAL SEPTECTOMY An EXIT delivery was performed at 34 weeks of gestation under maternal general anesthesia (Figures 2 and 3). The fetus was partially delivered, and the fetal-placental circulation was maintained. Fetal anesthesia was maintained by placental circulation and additional intramuscular anesthesia in the left thigh of the fetus. After transthoracic echocardiographic confirmation of the status of the atrial septum, a median sternotomy was performed with standby ECMO. The pericardium was opened, providing access to the heart and great vessels. External inspection of the heart confirmed the fetal diagnosis of HLHS with severely hypoplastic ascending aorta, large main pulmonary artery, and a large ductus arteriosus that supplied the descending aorta. At that time, a central line that was secured to the chest wall to enable medication administration and any potential transfusion was placed in the right atrium. A long purse string suture was placed in the right atrial free wall. Using bicaval inflow occlusion technique, the superior and inferior venae cavae were temporarily occluded with vascular clamps. The heart was allowed to 358
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FIGURE 2. Postoperative subcostal echocardiographic image showing unrestrictive, surgically created interatrial communication between the left atrium (LA) and the right atrium (RA). SVC ¼ superior vena cava.
empty, and the right atrium was entered through an incision within the purse string suture. The atrial septum consisted entirely of muscular wall, and no thin primum portion was identifiable. Part of this muscular atrial septum was resected, and the heart was deaired by removing the temporary clamps on the venae cavae. Finally, the purse string was pulled to control the bleeding. Epicardial echocardiogram confirmed that the septum was open, but still restrictive. The decision was made to repeat the procedure to ensure adequate decompression of the left side of the heart. After perfusing for a few minutes, the procedure was repeated in the same fashion by bicaval inflow occlusion. The septectomy was extended inferiorly and anteriorly. Epicardial echocardiogram confirmed that the septum was nonrestrictive (Figure 2). Acidosis and anemia were corrected. Attention was then directed to airway management and intubation. Laryngoscopy was performed, and minimal airway secretions were suctioned. The newborn was then intubated with a 3.0 cuffed endotracheal tube that was threaded over a 2.7 mm Hopkin’s rod telescope. Visualization of normal airway structures was confirmed and the telescope was removed. After securing the endotracheal tube and suctioning, positive pressure ventilation was initiated by hand ventilation using room air with a sterile
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FIGURE 3. Diagram showing the position of the multidisciplinary teams within the operating room during the Ex utero Intrapartum Treatment (EXIT) procedure and atrial septectomy. (1) Obstetric anesthesiologist. (2) Maternal fetal surgeon. (3) Assistant to maternal surgeon. (4) Pediatric cardiologist. (5) Cardiac surgeon. (6) Assistant to cardiac surgeon. (7) Scrub nurse. (8) Otorhinolaryngologist.
Mapleson circuit and surfactant was administered. Inspiratory pressures were limited by manometry, and the fetal response was determined by continuous pulse oximetry. The umbilical cord pulsations started dampening soon after the initiation of ventilation; however, oxygen saturation increased from 60% to 85% over several minutes. With improved oxygenation despite reduced placental support, decision was made to deliver the fetus rather than cannulate for ECMO. The fetus was then completely delivered, and the umbilical cord was clamped. The neonate was transferred to a separate operating room where umbilical arterial and venous catheters were placed and the chest was closed after placement of standard surgical drains. The oxygen saturation remained in high 80s, and the first arterial blood gas was pH 7.07, PaCO2 83, PaO2 39, Base 6 while being ventilated in room air. The neonate was then transferred to the cardiac surgical intensive care unit (ICU). No intraoperative complications for either the mother or the neonate were encountered. Mayo Clin Proc. n February 2019;94(2):356-361 www.mayoclinicproceedings.org
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FOLLOW-UP IN THE ICU The newborn was admitted to the ICU intubated and mechanically ventilated with a primed ECMO circuit outside the patient’s room. Hemodynamics were within agedependent norms, supported by continuous infusions of epinephrine (0.05 mg/kg/min), dopamine (5 mg/kg/min), calcium chloride (8.3 mg/kg/h), and alprostadil (0.01 mg/kg/ min). Routine blood and metabolic work were obtained. Initial room air, postductal arterial blood gas demonstrated a pH of 7.48, PaCO2 32, PaO2 34, Base 0, and lactate 10 mmol/L. Overnight, hemodynamics stabilized on decreasing doses of epinephrine (nadir, 0.03 mg/kg/min) while blood lactate steadily decreased (nadir of 5) until an abrupt event induced by repositioning and endotracheal tube suctioning resulted in hypoxia followed by bradycardia and hypotension refractive to supplemental oxygen, analgesic administration, neuromuscular blockade, inhaled nitric oxide, fluid resuscitation, and titration of vasoactive medications. A bedside cardiac
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ultrasound demonstrated poor ventricular function, and subsequent diagnoses of low cardiac output syndrome and pulmonary hypertension were made and the decision was made to place the neonate on central VA ECMO for stabilization. Cannulation occurred at the bedside, with direct arterial cannulation of the pulmonary artery with advancement through the large ductus arteriosus into the proximal descending aorta. An additional cannula was placed into the common atrium for venous drainage. The metabolic derangements rapidly corrected on ECMO. Additional ICU measures included hydrocortisone administration for presumptive adrenal insufficiency, surfactant administration for respiratory distress syndrome, and phototherapy as well as a double-volume exchange transfusion for hyperbilirubinemia of prematurity. Oxygen saturation and perfusion status remained satisfactory on ECMO support. We were successful in achieving good expansion and aeration of both lungs with adequate respiratory system compliance. Repeat echocardiogram showed good ventricular function (ventricular ejection fraction, 55%-60%) with unrestrictive atrial septum. Unfortunately, the neonate developed a grade I intraventricular hemorrhage that rapidly progressed to grade III on serial cranial ultrasounds. These findings, in the context of the neonate’s underlying diagnoses, were discussed with the family and the decision was made to separate from ECMO and, in accordance with the parents’ wishes, a do-notresuscitate order was placed. Separation was successfully performed after a total of 5 days of ECMO support. The chest was left opened, and the neonate remained with adequate hemodynamics and with satisfactory arterial blood gases after separation. The ultimate plan was to postpone the Norwood stage I palliation and continue prostaglandin without ductal stenting due to prematurity. In the event of pulmonary overcirculation, we planned to proceed with bilateral branch pulmonary arteries banding and ductal stenting or simply continue the prostaglandin therapy. On day of life 9, the neonate had a second acute decompensation with bradycardia and hypotension associated with increase in 360
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central venous pressure to 25 mm Hg. In accordance with the family’s wishes, chest compressions were withheld, and the neonate was transitioned to comfort care and died in the presence of the family. DISCUSSION Intact or severely restrictive atrial septum poses a high risk of mortality in patients with HLHS.1,3 Development of hydrops commonly portends in utero fetal demise. Many in utero or postnatal interventions can be futile due to secondary abnormalities including the pulmonary vasculature (diffuse hypoplasia of pulmonary arteries, “arterialization” of pulmonary veins with muscular media, and severe pulmonary hypertension).4 Ultrasound-guided fetal atrial septostomy was first described in 2004 to provide prenatal left atrial decompression in HLHS-IAS.5 Initial percutaneous intervention in this case allowed resolution of developing hydrops early on, avoiding fetal demise. The atrial septal communication had flow across it, but continued to be restrictive due to the muscular nature of the septum. Recurrence of hydrops required more definitive management because waiting until term would have likely led to in utero fetal demise. Previous reports have described the EXIT procedure for HLHS to facilitate transition to cardiopulmonary bypass and atrial septectomy.6 As the neonate begins breathing and the lungs expand, there is an increase in pulmonary blood flow resulting in severe pulmonary congestion and pulmonary edema if the obstruction is not relieved. This would be the case with the previously proposed Immediate Post-partum Access to Cardiac Therapy procedure in which the infant is delivered in the operating room with immediate transition to cardiovascular surgery after initial intubation and stabilization. However, EXIT to surgical septectomy without cardiopulmonary bypass allowed for the relief of atrial level obstruction, before the neonate’s first breath. The choice of EXIT to ECMO vs EXIT to septectomy is challenging. Although both options were offered to the family and could have been performed at the time of delivery, we did not see a clear indication
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for ECMO support for several reasons. First, the neonate was stable and was being ventilated in room air, with acceptable oxygen saturation indicating adequate pulmonary function, at least for the time being. Second, managing the neonate with single-ventricle physiology on ECMO with a large patent ductus arteriosus is very challenging, as was experienced in this case later. The goal was to simplify postoperative care and avoid all the morbidity and complications associated with ECMO in such a preterm neonate. Unfortunately, those complications still occurred in this neonate, but we hope that these can be avoided in future cases. We believe that the choice of ECMO should be reserved for cases that require active resuscitation and those who are better served with primary heart transplantation. This is the first reported case of an EXIT procedure being used without cardiopulmonary bypass for an open-heart operation to provide a promising alternative strategy for the management of HLHS-IAS. Although the infant described in this case ultimately died, the primary cause of death was complication related to prematurity and ECMO support (ie, intracranial hemorrhage) rather than directly related to the EXIT procedure itself. We believe that the EXIT procedure to open fetal atrial septectomy may be an option for select candidates primarily as a second step if the atrial septum becomes restrictive after ultrasound-guided fetal cardiac intervention. It is also important to recognize that this procedure required extensive coordination between multiple provider groups including obstetrics, pediatric cardiology, neonatology, cardiovascular surgery, otorhinolaryngologist, and anesthesia (both obstetric and cardiac). This procedure was performed in a children’s hospital that resides with in a larger adult hospital; however, obstetrical care is typically not provided at this hospital. In that respect, this case still required a consciously coordinated effort between the participating groups. This would be vital for such a procedure to be performed at a free-standing children’s hospital. Furthermore, this case reflects the importance of early fetal diagnosis to allow for coordinated care and delivery of these patients Mayo Clin Proc. n February 2019;94(2):356-361 www.mayoclinicproceedings.org
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in a tertiary care setting that is able to provide for the unique and complex needs of both the neonate and the mother. CONCLUSION This is the first reported case of an EXIT procedure being used without cardiopulmonary bypass for the management of HLHS-IAS. This strategy may be an option for select candidates as a subsequent step if the atrial septum becomes restrictive after ultrasoundguided percutaneous fetal atrial septostomy. Abbreviations and Acronyms: ECMO = extracorporeal membrane oxygenator; EXIT = ex utero intrapartum treatment; HLHS = hypoplastic left heart syndrome; HLHSIAS = hypoplastic left heart syndrome with intact septum; ICU = intensive care unit Affiliations (Continued from the first page of this article.): thesiology (L.G.S., M.E.N., S.J.G.), Division of Cardiovascular Anesthesia (R.B.P.), Department of Anesthesiology and Perioperative Medicine (E.E.S.), Department of Pediatric and Adolescent Medicine (D.P.D., C.S.V.D.), and Division of Neonatal Medicine, Mayo Clinic College of Medicine (C.A.C.), Rochester, MN.
Potential Competing Interests: The authors report no competing interests. Correspondence: Address to Rodrigo Ruano, MD, PhD, Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine and Science, 200 First St SW, Rochester, MN 55905 ([email protected]).
REFERENCES 1. Rychik J, Rome JJ, Collins MH, DeCampli WM, Spray TL. The hypoplastic left heart syndrome with intact atrial septum: atrial morphology, pulmonary vascular histopathology and outcome. J Am Coll Cardiol. 1999;34(2):554-560. 2. Jantzen DW, Moon-Grady AJ, Morris SA, et al. Hypoplastic left heart syndrome with intact or restrictive atrial septum: a report from the International Fetal Cardiac Intervention Registry. Circulation. 2017;136(14):1346-1349. 3. Atz AM, Feinstein JA, Jonas RA, Perry SB, Wessel DL. Preoperative management of pulmonary venous hypertension in hypoplastic left heart syndrome with restrictive atrial septal defect. Am J Cardiol. 1999;83(8):1224-1228. 4. Chaturvedi RR, Ryan G, Seed M, van Arsdell G, Jaeggi ET. Fetal stenting of the atrial septum: technique and initial results in cardiac lesions with left atrial hypertension. Int J Cardiol. 2013; 168(3):2029-2036. 5. Marshall AC, van der Velde ME, Tworetzky W, et al. Creation of an atrial septal defect in utero for fetuses with hypoplastic left heart syndrome and intact or highly restrictive atrial septum. Circulation. 2004;110(3):253-258. 6. Peng E, Howley L, Cromblehome TM, Jaggers J. Ex-utero intrapartum treatment as a novel bridging strategy to surgery in hypoplastic left heart syndrome with intact atrial septum-crosscirculation revisited. J Thorac Cardiovasc Surg. 2015;149(3):935-937.
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Innovative 2-Step Management Strategy Utilizing EXIT Procedure for a Fetus With Hypoplastic Left Heart Syndrome and Intact Atrial Septum Sameh M. Said, MD; Muhammad Yasir Qureshi, MBBS; Nathaniel W. Taggart, MD; Heather N. Anderson, MD; Patrick W. O’Leary, MD; Frank Cetta, MD; Layan Alrahmani, MD; Shelagh A. Cofer, MD; Leal G. Segura, MD; Roxann B. Pike, MD; Emily E. Sharpe, MD; Douglas P. Derleth, MD; Michael E. Nemergut, MD, PhD; Charlotte S. Van Dorn, MD; Stephen J. Gleich, MD; Carl H. Rose, MD; Christopher A. Collura, MD; and Rodrigo Ruano, MD, PhD Abstract Hypoplastic left heart syndrome (HLHS) with intact atrial septum (HLHS-IAS) carries a high risk of mortality and affects about 6% of all patients with HLHS. Fetal interventions, postnatal transcatheter interventions, and postnatal surgical resection have all been used, but the mortality risk continues to be high in this subgroup of patients. We describe a novel, sequential approach to manage HLHS-IAS and progressive fetal hydrops. A 28-year-old, gravida 4 para 2 mother was referred to Mayo Clinic for fetal HLHS. Fetal echocardiography at 28 weeks of gestation demonstrated HLHS-IAS with progressive fetal hydrops. The atrial septum was thick and muscular with no interatrial communication. Ultrasound-guided fetal atrial septostomy was performed with successful creation of a small atrial communication. However, fetal echocardiogram at 33 weeks of gestation showed recurrence of a pleural effusion and restriction of the atrial septum. We proceeded with an Ex utero Intrapartum Treatment (EXIT) delivery and open atrial septectomy. This was performed successfully, and the infant was stabilized in the intensive care unit. The infant required venoarterial extracorporeal membrane oxygenator support on day of life 1. The patient later developed hemorrhagic complications, leading to his demise on day of life 9. This is the first reported case of an EXIT procedure and open atrial septectomy performed without cardiopulmonary bypass for an open-heart operation and provides a promising alternative strategy for the management of HLHS-IAS in select cases. ª 2018 Mayo Foundation for Medical Education and Research
For editorial comment, see page 194. From the Department of Cardiovascular Surgery (S.M.S.), Division of Pediatric Cardiology (M.Y.Q., N.W.T., H.N.A., P.W.O., F.C.), Division of Obstetrics and Maternal Fetal Medicine (L.A., C.H.R., R.R.), Division of Pediatric Otorhinolaryngology (S.A.C.), Division of Pediatric AnesAffiliations continued at the end of this article.
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ypoplastic left heart syndrome (HLHS) with an intact or severely restrictive atrial septum (HLHSIAS) carries a high risk of mortality and affects about 6% of all patients with HLHS.1 Emergent relief of obstruction at the atrial level is needed for survival. However, the best strategy for relief of left atrial hypertension is not established. Fetal interventions, postnatal transcatheter interventions, and postnatal surgical resection have all been used, but mortality risk continues to be high.2 We describe a novel, sequential approach to manage a fetus
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with HLHS-IAS and progressive fetal hydrops. This staged approach consisted of initial percutaneous in utero fetal atrial septostomy followed by Ex utero Intrapartum Treatment (EXIT) to surgical atrial septectomy (a 2-step process). CASE PRESENTATION A 28-year-old, gravida 4 para 2 mother was referred to Mayo Clinic for further management of fetal HLHS. Fetal echocardiogram performed at 28 weeks of gestation demonstrated HLHS-IAS with mitral valve hypoplasia, aortic
Mayo Clin Proc. n February 2019;94(2):356-361 n https://doi.org/10.1016/j.mayocp.2018.08.004 www.mayoclinicproceedings.org n ª 2018 Mayo Foundation for Medical Education and Research
EXIT TO ATRIAL SEPTECTOMY IN HLHS
valve atresia, hypoplastic left ventricle, and hypoplastic ascending aorta. The left atrium was small with dilated pulmonary veins, and the atrial septum was thick and muscular with no interatrial communication or thin primum septum (Figure 1A). Pulmonary venous Doppler showed to-and-fro flow with prominent flow reversal during atrial systole and absent early diastolic forward flow, consistent with severe left atrial hypertension (Figure 1B). There was no decompressing vein or antegrade flow through the left heart. A new small right-sided pleural effusion and a pericardial effusion were seen on subsequent imaging. Because of the development of these early signs of fetal hydrops, percutaneous fetal intervention was proposed. ULTRASOUND-GUIDED PERCUTANEOUS FETAL ATRIAL SEPTOSTOMY Under ultrasound guidance, the fetal atrial septostomy was performed at 30 weeks of gestation under monitored sedation and
local maternal anesthesia. Fetal anesthesia was administered into the left arm of the fetus. An 18-gauge Cook blunt-tip needle was advanced percutaneously into the amniotic space and was directed through the fetal chest wall into the right atrium. The atrial septostomy was performed with the needle trocar, and the trocar was removed. A 3.75 mm diameter 8 mm long Emerge coronary angioplasty balloon was advanced over a 0.014” Samurai coronary wire and inflated multiple times to dilate the atrial septostomy. Flow across the atrial septum was demonstrated by color Doppler. A small pericardial effusion was observed initially but remained stable over 20 minutes of monitoring and did not require additional intervention. Follow-up fetal echocardiogram 1 week later demonstrated resolution of pericardial and pleural effusions. The septal defect was still patent, although somewhat restrictive (mean Doppler gradient, 2-3 mm Hg) with
FIGURE 1. Ultrasound-guided intrauterine fetal atrial septostomy. A, Four-chamber view on fetal echocardiogram showing pleural and pericardial effusions (*). Arrows indicate dilated left and right pulmonary veins. B, Pulmonary venous Doppler with prominent atrial reversal of flow (A) with no early diastolic forward flow (D). C, Color Doppler demonstrating atrial-level shunt (arrow) after fetal intervention. D, Pulse wave Doppler interrogation of atrial shunt showing 2 to 3 mm Hg gradient across the atrial septum. LA ¼ left atrium; RA ¼ right atrium; RV ¼ right ventricle. Mayo Clin Proc. n February 2019;94(2):356-361 www.mayoclinicproceedings.org
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continuous blood flow across the septum noted (Figure 1C and D). The patient was closely monitored by maternal fetal medicine and pediatric cardiology weekly. Fetal echocardiogram performed at 33 weeks of gestation showed persistent patency of the atrial communication, but reappearance of a rightsided pleural effusion. Percutaneous reintervention was not felt to be beneficial in this setting due to thick and muscular atrial septum. Due to evolving fetal hydrops, EXIT to open atrial septectomy with possible need for extracorporeal membrane oxygenator (ECMO) support was offered. The added risks of the EXIT procedure and ECMO were discussed in detail with the parents. Alternative management options including compassionate comfort care and transcatheter atrial septal dilation were discussed. After extensive multidisciplinary discussion, the parents elected to proceed with the EXIT procedure and open septectomy. Pediatric Ethical Board reviewed the case, made recommendations, and agreed with proceeding. EXIT TO SURGICAL ATRIAL SEPTECTOMY An EXIT delivery was performed at 34 weeks of gestation under maternal general anesthesia (Figures 2 and 3). The fetus was partially delivered, and the fetal-placental circulation was maintained. Fetal anesthesia was maintained by placental circulation and additional intramuscular anesthesia in the left thigh of the fetus. After transthoracic echocardiographic confirmation of the status of the atrial septum, a median sternotomy was performed with standby ECMO. The pericardium was opened, providing access to the heart and great vessels. External inspection of the heart confirmed the fetal diagnosis of HLHS with severely hypoplastic ascending aorta, large main pulmonary artery, and a large ductus arteriosus that supplied the descending aorta. At that time, a central line that was secured to the chest wall to enable medication administration and any potential transfusion was placed in the right atrium. A long purse string suture was placed in the right atrial free wall. Using bicaval inflow occlusion technique, the superior and inferior venae cavae were temporarily occluded with vascular clamps. The heart was allowed to 358
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FIGURE 2. Postoperative subcostal echocardiographic image showing unrestrictive, surgically created interatrial communication between the left atrium (LA) and the right atrium (RA). SVC ¼ superior vena cava.
empty, and the right atrium was entered through an incision within the purse string suture. The atrial septum consisted entirely of muscular wall, and no thin primum portion was identifiable. Part of this muscular atrial septum was resected, and the heart was deaired by removing the temporary clamps on the venae cavae. Finally, the purse string was pulled to control the bleeding. Epicardial echocardiogram confirmed that the septum was open, but still restrictive. The decision was made to repeat the procedure to ensure adequate decompression of the left side of the heart. After perfusing for a few minutes, the procedure was repeated in the same fashion by bicaval inflow occlusion. The septectomy was extended inferiorly and anteriorly. Epicardial echocardiogram confirmed that the septum was nonrestrictive (Figure 2). Acidosis and anemia were corrected. Attention was then directed to airway management and intubation. Laryngoscopy was performed, and minimal airway secretions were suctioned. The newborn was then intubated with a 3.0 cuffed endotracheal tube that was threaded over a 2.7 mm Hopkin’s rod telescope. Visualization of normal airway structures was confirmed and the telescope was removed. After securing the endotracheal tube and suctioning, positive pressure ventilation was initiated by hand ventilation using room air with a sterile
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FIGURE 3. Diagram showing the position of the multidisciplinary teams within the operating room during the Ex utero Intrapartum Treatment (EXIT) procedure and atrial septectomy. (1) Obstetric anesthesiologist. (2) Maternal fetal surgeon. (3) Assistant to maternal surgeon. (4) Pediatric cardiologist. (5) Cardiac surgeon. (6) Assistant to cardiac surgeon. (7) Scrub nurse. (8) Otorhinolaryngologist.
Mapleson circuit and surfactant was administered. Inspiratory pressures were limited by manometry, and the fetal response was determined by continuous pulse oximetry. The umbilical cord pulsations started dampening soon after the initiation of ventilation; however, oxygen saturation increased from 60% to 85% over several minutes. With improved oxygenation despite reduced placental support, decision was made to deliver the fetus rather than cannulate for ECMO. The fetus was then completely delivered, and the umbilical cord was clamped. The neonate was transferred to a separate operating room where umbilical arterial and venous catheters were placed and the chest was closed after placement of standard surgical drains. The oxygen saturation remained in high 80s, and the first arterial blood gas was pH 7.07, PaCO2 83, PaO2 39, Base 6 while being ventilated in room air. The neonate was then transferred to the cardiac surgical intensive care unit (ICU). No intraoperative complications for either the mother or the neonate were encountered. Mayo Clin Proc. n February 2019;94(2):356-361 www.mayoclinicproceedings.org
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FOLLOW-UP IN THE ICU The newborn was admitted to the ICU intubated and mechanically ventilated with a primed ECMO circuit outside the patient’s room. Hemodynamics were within agedependent norms, supported by continuous infusions of epinephrine (0.05 mg/kg/min), dopamine (5 mg/kg/min), calcium chloride (8.3 mg/kg/h), and alprostadil (0.01 mg/kg/ min). Routine blood and metabolic work were obtained. Initial room air, postductal arterial blood gas demonstrated a pH of 7.48, PaCO2 32, PaO2 34, Base 0, and lactate 10 mmol/L. Overnight, hemodynamics stabilized on decreasing doses of epinephrine (nadir, 0.03 mg/kg/min) while blood lactate steadily decreased (nadir of 5) until an abrupt event induced by repositioning and endotracheal tube suctioning resulted in hypoxia followed by bradycardia and hypotension refractive to supplemental oxygen, analgesic administration, neuromuscular blockade, inhaled nitric oxide, fluid resuscitation, and titration of vasoactive medications. A bedside cardiac
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ultrasound demonstrated poor ventricular function, and subsequent diagnoses of low cardiac output syndrome and pulmonary hypertension were made and the decision was made to place the neonate on central VA ECMO for stabilization. Cannulation occurred at the bedside, with direct arterial cannulation of the pulmonary artery with advancement through the large ductus arteriosus into the proximal descending aorta. An additional cannula was placed into the common atrium for venous drainage. The metabolic derangements rapidly corrected on ECMO. Additional ICU measures included hydrocortisone administration for presumptive adrenal insufficiency, surfactant administration for respiratory distress syndrome, and phototherapy as well as a double-volume exchange transfusion for hyperbilirubinemia of prematurity. Oxygen saturation and perfusion status remained satisfactory on ECMO support. We were successful in achieving good expansion and aeration of both lungs with adequate respiratory system compliance. Repeat echocardiogram showed good ventricular function (ventricular ejection fraction, 55%-60%) with unrestrictive atrial septum. Unfortunately, the neonate developed a grade I intraventricular hemorrhage that rapidly progressed to grade III on serial cranial ultrasounds. These findings, in the context of the neonate’s underlying diagnoses, were discussed with the family and the decision was made to separate from ECMO and, in accordance with the parents’ wishes, a do-notresuscitate order was placed. Separation was successfully performed after a total of 5 days of ECMO support. The chest was left opened, and the neonate remained with adequate hemodynamics and with satisfactory arterial blood gases after separation. The ultimate plan was to postpone the Norwood stage I palliation and continue prostaglandin without ductal stenting due to prematurity. In the event of pulmonary overcirculation, we planned to proceed with bilateral branch pulmonary arteries banding and ductal stenting or simply continue the prostaglandin therapy. On day of life 9, the neonate had a second acute decompensation with bradycardia and hypotension associated with increase in 360
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central venous pressure to 25 mm Hg. In accordance with the family’s wishes, chest compressions were withheld, and the neonate was transitioned to comfort care and died in the presence of the family. DISCUSSION Intact or severely restrictive atrial septum poses a high risk of mortality in patients with HLHS.1,3 Development of hydrops commonly portends in utero fetal demise. Many in utero or postnatal interventions can be futile due to secondary abnormalities including the pulmonary vasculature (diffuse hypoplasia of pulmonary arteries, “arterialization” of pulmonary veins with muscular media, and severe pulmonary hypertension).4 Ultrasound-guided fetal atrial septostomy was first described in 2004 to provide prenatal left atrial decompression in HLHS-IAS.5 Initial percutaneous intervention in this case allowed resolution of developing hydrops early on, avoiding fetal demise. The atrial septal communication had flow across it, but continued to be restrictive due to the muscular nature of the septum. Recurrence of hydrops required more definitive management because waiting until term would have likely led to in utero fetal demise. Previous reports have described the EXIT procedure for HLHS to facilitate transition to cardiopulmonary bypass and atrial septectomy.6 As the neonate begins breathing and the lungs expand, there is an increase in pulmonary blood flow resulting in severe pulmonary congestion and pulmonary edema if the obstruction is not relieved. This would be the case with the previously proposed Immediate Post-partum Access to Cardiac Therapy procedure in which the infant is delivered in the operating room with immediate transition to cardiovascular surgery after initial intubation and stabilization. However, EXIT to surgical septectomy without cardiopulmonary bypass allowed for the relief of atrial level obstruction, before the neonate’s first breath. The choice of EXIT to ECMO vs EXIT to septectomy is challenging. Although both options were offered to the family and could have been performed at the time of delivery, we did not see a clear indication
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for ECMO support for several reasons. First, the neonate was stable and was being ventilated in room air, with acceptable oxygen saturation indicating adequate pulmonary function, at least for the time being. Second, managing the neonate with single-ventricle physiology on ECMO with a large patent ductus arteriosus is very challenging, as was experienced in this case later. The goal was to simplify postoperative care and avoid all the morbidity and complications associated with ECMO in such a preterm neonate. Unfortunately, those complications still occurred in this neonate, but we hope that these can be avoided in future cases. We believe that the choice of ECMO should be reserved for cases that require active resuscitation and those who are better served with primary heart transplantation. This is the first reported case of an EXIT procedure being used without cardiopulmonary bypass for an open-heart operation to provide a promising alternative strategy for the management of HLHS-IAS. Although the infant described in this case ultimately died, the primary cause of death was complication related to prematurity and ECMO support (ie, intracranial hemorrhage) rather than directly related to the EXIT procedure itself. We believe that the EXIT procedure to open fetal atrial septectomy may be an option for select candidates primarily as a second step if the atrial septum becomes restrictive after ultrasound-guided fetal cardiac intervention. It is also important to recognize that this procedure required extensive coordination between multiple provider groups including obstetrics, pediatric cardiology, neonatology, cardiovascular surgery, otorhinolaryngologist, and anesthesia (both obstetric and cardiac). This procedure was performed in a children’s hospital that resides with in a larger adult hospital; however, obstetrical care is typically not provided at this hospital. In that respect, this case still required a consciously coordinated effort between the participating groups. This would be vital for such a procedure to be performed at a free-standing children’s hospital. Furthermore, this case reflects the importance of early fetal diagnosis to allow for coordinated care and delivery of these patients Mayo Clin Proc. n February 2019;94(2):356-361 www.mayoclinicproceedings.org
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in a tertiary care setting that is able to provide for the unique and complex needs of both the neonate and the mother. CONCLUSION This is the first reported case of an EXIT procedure being used without cardiopulmonary bypass for the management of HLHS-IAS. This strategy may be an option for select candidates as a subsequent step if the atrial septum becomes restrictive after ultrasoundguided percutaneous fetal atrial septostomy. Abbreviations and Acronyms: ECMO = extracorporeal membrane oxygenator; EXIT = ex utero intrapartum treatment; HLHS = hypoplastic left heart syndrome; HLHSIAS = hypoplastic left heart syndrome with intact septum; ICU = intensive care unit Affiliations (Continued from the first page of this article.): thesiology (L.G.S., M.E.N., S.J.G.), Division of Cardiovascular Anesthesia (R.B.P.), Department of Anesthesiology and Perioperative Medicine (E.E.S.), Department of Pediatric and Adolescent Medicine (D.P.D., C.S.V.D.), and Division of Neonatal Medicine, Mayo Clinic College of Medicine (C.A.C.), Rochester, MN.
Potential Competing Interests: The authors report no competing interests. Correspondence: Address to Rodrigo Ruano, MD, PhD, Department of Obstetrics and Gynecology, Mayo Clinic College of Medicine and Science, 200 First St SW, Rochester, MN 55905 ([email protected]).
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