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Neonatal presentation of Ebstein anomaly (EA) represents the most severe form of this condition. Despite significant advances, operative mortality remains high and management decisions represent a formidable challenge. We used a strategy aimed to match anatomy and physiology with type and time of intervention to increase survival.
We performed a review of all patients with fetal or neonatal diagnosis of EA managed at a single center between 2007 and 2020.
Among 18 patients with EA, 8 underwent neonatal intervention. The most common indication included cyanosis and heart failure (8/8), end organ dysfunction (6/8), and maldistribution of cardiac output (6/8). Only 2/8 had antegrade pulmonary blood flow. Associated conditions included pulmonary regurgitation in 4/8, atrial tachyarrhythmia in 4, and a ventricular septal defect in 3. Three patients underwent initial stabilization with main pulmonary artery occlusion including bilateral pulmonary artery banding in 2. Five patients underwent biventricular repair with conversion to right ventricle exclusion in 2 cases. Three others underwent the Starnes procedure as initially planned. The median age at surgery was 10 days (range, 1-30) and median weight 2.6 kg (range, 1.9-4.0). The median duration of mechanical ventilation and intensive care unit stay were 9 days (range, 5-34) and 30 days (range, 15-100), respectively. Operative mortality was 1/8. At a median follow-up of 130 months (range, 5-146), there were no late deaths, and all survivors remain in functional class I and free of valvular reintervention.
Symptomatic neonates with EA can be effectively managed with good outcomes. Preoperative stabilization and choice of management pathway on the basis of anatomy and physiology can help reduce morbidity and mortality.
Surgical intervention for symptomatic neonates with Ebstein anomaly carries a significant operative risk based on the challenging physiology, technical demands, and the limited experience with this patient population. A management strategy based on anatomic features and physiology, preoperative stabilization, and recognition of the deleterious effect of RVOT obstruction might lead to increased survival rates.
Neonatal presentation of Ebstein anomaly (EA) represents the most severe clinical form of this condition characterized by significant impairment in the function of the tricuspid valve, massive cardiomegaly, decreased effective antegrade pulmonary blood flow, right heart failure, metabolic acidosis, as well as end organ dysfunction.
Although a significant number of patients can be managed with supportive measures to promote pulmonary blood flow and attain appropriate oxygen delivery during the early period until pulmonary vascular resistance decreases, others require an intervention to modify the pathophysiology during this critical period.
Despite significant advances in surgical technique and perioperative care, overall operative mortality for individuals who require an intervention remains very high and the decision regarding the optimal management strategy in consideration for a biventricular or a single ventricle management represents a significant challenge.
and raises the question of selection criteria or the need for modifications with this approach.
Moreover, in contradistinction to other clinical conundrums, the management of these critically ill newborns has remained problematic in no small measure, because of the low volume seen at individual centers. Therefore, it has taken a long time to solve essential questions regarding the optimal management pathway, timing of intervention, and other technical aspects.
We performed a review of our experience on the basis of a strategy that considers anatomic (tricuspid valve morphology and pulmonary atresia) as well as functional variables (antegrade pulmonary blood flow, pulmonary regurgitation, right ventricular pressure, direction of flow across the patent ductus arteriosus) to inform the management and improve the outcomes of this complex group of patients.
Between 2007 and 2020, 18 consecutive patients with a fetal or neonatal diagnosis of EA were managed at our center. All diagnoses were made using echocardiogram with standard criteria, and all fetal and postnatal studies were reviewed by 2 senior cardiologists (G.B., M.A.B.). Diagnosis of EA was on the basis of the apical displacement of the septal and/or posterior leaflet of the tricuspid valve with obvious atrialization of the RV. The presence of additional cardiac defects, namely atrial and ventricular septal defects, pulmonary stenosis or pulmonary atresia, patent ductus arteriosus, and left ventricular hypoplasia as well as the presence of antegrade flow across the native pulmonary valve was documented. The diagnosis of anatomic pulmonary atresia was made in the presence of a muscular or membranous plate on 2-dimensional images with complete absence of antegrade flow or regurgitation through this area. Functional pulmonary atresia was described as the presence of well formed pulmonary valve leaflets, which did not open and therefore did not exhibit any antegrade pulmonary blood flow or the presence of a normal-appearing pulmonary valve with a trace of insufficiency but no antegrade flow.
Patients with corrected transposition of the great arteries and other cardiac anomalies associated with Ebstenoid malformation of the tricuspid valve were excluded. Operative mortality was defined according to the Society of Thoracic Surgeons Congenital Heart Surgery Database criteria. Primary outcome measures included: 1) operative and late mortality, 2) need for reintervention, 3) perioperative extracorporeal membrane oxygenation (ECMO) support, and 4) need for permanent pacemaker.
Follow-up was obtained by direct contact with the primary cardiologist as of July 2020. The study was approved by the institutional review board (study 711848-11; April 6, 2015) and need for consent was waived.
Of the 18 patients in this cohort, 16 patients presented with moderate to severe clinical signs. Eight of these were medically managed, allowing eventual closure of the patent ductus arteriosus and progression of antegrade pulmonary blood flow, while exhibiting oxygen saturations above 80%. These patients were subsequently discharged, and all achieved a biventricular circulation. The remaining 8 patients received an operative intervention, which consisted of right ventricular exclusion with a fenestrated patch and a systemic to pulmonary artery shunt (modified Starnes) or a biventricular repair (BVR; Figure 1, Table E1).
The most common indications for intervention were progressive and/or severe hypoxemia, defined as a partial arterial oxygen pressure (Pao2) of <30 mm Hg with mechanical ventilation, and receiving supplemental oxygen and nitric oxide. Additional criteria for intervention included persistent ductal dependent pulmonary blood flow (beyond a week) as well as heart failure characterized by the presence of pleural effusion, ascites and/or anasarca, maldistribution of cardiac output, persistent lactate elevation, and end organ dysfunction. Nearly half of the patients exhibited new onset of arrhythmias, most commonly supraventricular tachycardia. All patients met more than 2 criteria for intervention.
Characteristics of the cohort are shown in Table 1. These characteristics are similar to the previously published national benchmark study, including age and size at first intervention.
However, in our cohort most had a prenatal diagnosis, and a greater proportion of genetic abnormalities was observed, including cri du chat, trisomy X, and other chromosomal deletions. Associated anatomic diagnoses were common, including an atrial septal communication in all patients, a ventricular septal defect in nearly half, and a patent ductus arteriosus in all but 1 patient. Anatomic pulmonary atresia was documented in 1 patient, whereas only 2 patients had evidence of antegrade pulmonary blood flow on echocardiogram leaving the diagnosis of functional pulmonary atresia for the remaining 5 patients. Considering traditional risk criteria, all patients exhibited a cardiothoracic ratio >0.8 on chest radiograph, and a Great Ormond Street (GOS) score >1.1, which, in association with cyanosis, placed all patients in a high-risk category with near 100% mortality.
Regarding the preoperative patient condition (Table 2), a large proportion of patients received preoperative mechanical ventilation and a prostaglandin infusion. A significant number also presented evidence of end organ dysfunction, most commonly renal, which was evident by persistent and/or progressive creatinine elevation associated with low urine output. As shown in Figures 2 and 3 patients underwent an initial stabilizing intervention, within the first 48 hours of life, to optimize the hemodynamics in preparation for a more definitive intervention with cardiopulmonary bypass. These patients had a median lactate of 6.7, and as high as 12 mmol/dL, due to circulatory compromised largely associated with a circular shunt in the presence of significant tricuspid regurgitation, pulmonary valve regurgitation, and a patent ductus arteriosus. The stabilizing interventions included clip occlusion of the pulmonary valve in 3 patients, 1 of whom also received a bilateral pulmonary artery banding. These interventions were aimed at elimination of the circular shunt and control of the pulmonary blood flow to facilitate the overall balance of distribution of cardiac output, which commonly led to normalization of lactates and a prompt recovery of end organ dysfunction. The median preoperative lactate at the time of the main intervention was 1.5 mg/dL.
Choice of surgical strategy was on the basis of a combination of anatomic and physiologic variables. In broad terms, a BVR was planned in the presence of a functional tripartite RV with a patent outflow and an estimated RV pressure >35 mm Hg. Patients left the operating room with a BVR unless the residual tricuspid regurgitation was greater than moderate, the tricuspid valve repair was not deemed durable, and/or there was inadequate effective pulmonary blood flow associated with severe hypoxemia. In contradistinction, patients with a functional unipartite RV, with poor function and muscular pulmonary atresia were planned for RV exclusion (Figure 3). Five patients were scheduled to have a BVR whereas right ventricular exclusion was planned in 3. Among those planned for a BVR, 1 patient underwent a conventional BVR creating a bileaflet tricuspid valve with commissural plication of as well as a Sebening stitch.
Two of these patients had an intraoperative conversion from BVR to a right ventricular exclusion because of inadequate tissue to pursue a Cone repair or the reconstruction was deemed nonsatisfactory because of moderate to severe residual regurgitation. Therefore, 3 patients left the operating room with a BVR whereas 5 received a single-ventricle palliation, which consisted of a right ventricular exclusion with a systemic to pulmonary artery shunt (Figure 4). The source of pulmonary blood flow was a 3.5-mm right modified Blalock-Taussig shunt in 4 patients, whereas a central shunt was used in a patient with a chromosomal anomaly, severe branch pulmonary artery hypoplasia, and left diaphragmatic eventration (Table 3).
Table 3Intraoperative variables
Preoperative lactate, mmol/dL
Aortic crossclamp time, min
CPB time, min
Shunt size, mm
Central shunt, %
Open sternum, %
Data are presented as median (range). CPB, Cardiopulmonary bypass.
The median aortic crossclamp was 51 minutes, and the median cardiopulmonary bypass duration was 110 minutes. Analysis of the perfusion conduct during the operative intervention revealed that although the duration of cardiopulmonary bypass was not significantly different for each strategy, patients who underwent BVR had a median period of myocardial ischemia approximately 20 minutes longer compared with those who underwent single-ventricle palliation, even if intraoperative conversion had occurred. This was likely a reflection of the fact that the decision to pursue conversion was made relatively early during the operation and while attempting to minimize the period of myocardial ischemia in these vulnerable newborns. A delayed sternal closure was performed in nearly all (6/8) patients.
As shown in Table 4, there was a single death in 8 patients. This was a low birth-weight neonate with EA and trisomy X, who had low Apgar scores, pulmonary atresia, hypoplastic central pulmonary arteries associated with moderate lung hypoplasia, and a diaphragmatic eventration, who in the early phase of this experience underwent right ventricular exclusion and placement of a 4-mm central shunt because of anticipated difficulty in providing enough pulmonary blood flow. Despite appropriate hemodynamics and gas exchange in the first 24 hours, the patient exhibited acute decompensation secondary to ectopic atrial tachycardia which required cardiopulmonary resuscitation with extracorporeal support and subsequently exhibited maldistribution of cardiac output, acute kidney injury, and subsequently expired on postoperative day 37.
Table 4Surgical outcome measures
Operative mortality, %
Postoperative mechanical support, %
2 Occurrences of E-CPR; rhythm-related
Unplanned cardiac reoperation, %
1 Case of RV reduction and 1 case of tamponade
Reoperation for shunt placement or revision, %
Permanent pacemaker, %
E-CPR, Cardiopulmonary resuscitation with extracorporeal support; RV, right ventricle; AKI, acute kidney injury.
Two patients received postoperative mechanical circulatory support. One of these just was described. A second patient with a birth weight of 2.3 kg and cri du chat underwent initial stabilization with clip occlusion of the pulmonary valve because of maldistribution of cardiac output associated with severe tricuspid regurgitation and a circular shunt, followed by right ventricular exclusion with a 3.5-mm right modified Blalock-Taussig shunt. Early in the postoperative period he presented with acute hemodynamic decompensation secondary to supraventricular tachyarrhythmia for which he received emergency ECMO cannulation. After 48 hours of support, the patient was successfully weaned, then discharged and eventually underwent Fontan completion.
Unplanned cardiac reoperations occurred in 2 patients. One patient who received ECMO support underwent right ventricular reduction because of progressive RV dilatation after the Starnes procedure, whereas another required evacuation of cardiac tamponade in the immediate postoperative period. Two patients exhibited postoperative worsening of the preoperative acute kidney injury (creatinine >2.0 from baseline and/or urine output <0.5 mL/kg/h for >12 hours), but did not require replacement therapy. There were no shunt-related reoperations or reinterventions and no permanent pacemaker implantations. At a median follow-up of 130 months (range, 5-146), there were no late deaths, and all survivors remained in functional class I and free of valvular reintervention (Figure 5).
Neonates with EA exhibit a complex physiology that is multifactorial, including the presence of severe tricuspid valve regurgitation, and physiological elevation pulmonary vascular resistance of the newborn. This is aggravated by abnormal lung development and pulmonary hypoplasia, with reduced generation of alveoli and alveolar simplification.
Moreover, in cases of EA, a myopathy of the right ventricular muscle can add to the inability to achieve effective antegrade pulmonary blood flow. Ineffective filling of the left ventricle and the frequent association of supraventricular arrhythmias can further aggravate a very precarious circulatory balance, which, in the presence of pulmonary regurgitation and a circular shunt could become unmanageable. Not surprisingly, the reported mortality rate for these symptomatic neonates remains very high.
In addition, the severity of the circulatory compromise can become evident in utero, with signs of heart failure, hydrops, and even fetal demise. These prenatal data convey a grim prognosis and has frequently led to a high rate of termination, further compromising the outlook of patients with this condition.
Although the ideal management strategy for these symptomatic neonates might be supportive allowing time for the physiologic decrease in pulmonary vascular resistance, this might not be attainable in some patients, particularly in those who present with anatomic obstruction of the RV outflow tract, those with RV dysfunction, or in those who exhibit circulatory compromise associated with arrhythmias or the presence of a circular shunt. In this cohort of 18 neonates, approximately half of those with clinical signs received medical management and achieved a biventricular circulation. This compares favorably with the Pediatric Health Information System (PHIS) cohort of >400 patients of whom nearly two-thirds were managed medically with a 22% early mortality.
Although this could be attributed to an era effect, this difference in mortality might raise questions about the selection criteria to pursue medical management and perhaps the possibility that some of these newborns might have benefited from a timely surgical intervention.
The other half of our cohort underwent neonatal intervention, which consisted of single ventricle palliation or BVR with a 2:1 ratio. The anatomic characteristic of the tricuspid valve, contractility of the RV (estimated right ventricular pressure >35 mm Hg in the absence of a ventricular septal defect), patency of the right ventricular outflow tract, direction of flow across the patent ductus, as well as patient's condition at the time of intervention were important considerations when planning for the type and timing of the surgical intervention. One strategy was to achieve a biventricular circulation on the basis of the repair of the tricuspid valve
whereas alternatively newborns with less favorable anatomy usually underwent a right ventricular exclusion procedure or insertion of a systemic to pulmonary artery shunt alone if the predominant issue was hypoxia in the absence of heart failure. Using the Society of Thoracic Surgeons Congenital Heart Surgery Database as a reference allowed us to ascertain the overall applicability of our observations against the benchmark experience with surgical management of EA in neonates.
Although a greater incidence of prenatal diagnosis and chromosomal anomalies were evident in our cohort, their effect remains unclear. Although prenatal diagnosis can lead to a higher level of preparedness, particularly for those with ductal-dependent pulmonary circulation, it also has led to an increased frequency of interruption of pregnancy,
therefore, the overall benefit of prenatal diagnosis on patient survival remains debatable. Additionally, an increased incidence of chromosomal anomalies has conferred an additional level of risk when it comes to outcomes in these complex newborns,
Refining the Society of Thoracic Surgeons Congenital Heart Surgery Database mortality risk model with enhanced risk adjustment for chromosomal abnormalities, syndromes, and noncardiac congenital anatomic abnormalities.
who reported that low birth weight newborns with EA who underwent a systemic to pulmonary artery shunt had a sevenfold increase in mortality. Although the median weight in our cohort was 2.7 kg and as low as 1.9 kg, weight did not have a significant effect on outcome. We would urge caution about this observation that perhaps could be explained by the deliberate measures taken to optimize overall patient condition and end organ function before surgery, as well a relatively short period of myocardial ischemia and a conservative management strategy in newborns with pulmonary atresia.
Unfortunately, one of the biggest challenges we confronted was the high incidence of perioperative arrhythmias, which were particularly destabilizing, and led to cardiopulmonary resuscitation with extracorporeal support in 2 cases. Management of arrhythmias has proven to be particularly difficult in patients with a circular shunt and/or during the postoperative period, nevertheless no preemptive treatment strategies have been described, nor were used at our center to address this issue.
As expected, the overall preoperative condition had significant influence on the overall outcome of these patients. Approximately three-quarters of the patients exhibited inadequate circulation with significant lactate level elevation and important end organ dysfunction preoperatively. Directed interventions to eliminate a circular shunt
and/or balance the circulation by controlling pulmonary blood flow proved to be life-saving and had a profound salutary effect, allowing patients to arrive at the main intervention in an elective fashion after optimization of organ function had occurred. It should be noted that in patients with anatomic pulmonary atresia creation of pulmonary insufficiency by perforation of the pulmonary valve plate would be associated with the possibility of a circular shunt and therefore should be avoided. Although bilateral pulmonary artery banding might seem completely counterintuitive, it has become increasingly apparent that many patients who present with a circular shunt and severe volume overload might be affected by maldistribution of cardiac output, extreme systemic venous desaturation, and coronary perfusion issues, which ultimately contribute to unremitting shock. It has been our observation that when the circular shunt is eliminated, Pao2 levels can rise above 35 mm Hg and therefore create the opportunity to balance the pulmonary blood flow and improve coronary and systemic perfusion. This observation has been replicated by Hasegawa and colleagues
in a patient with prenatal diagnosis of severe hydrops, and is similar to the initial intervention described in neonates who present in shock with delayed diagnosis of a ductal-dependent systemic circulation.
Alternatively, ECMO support can provide the necessary stabilization, while avoiding the adverse effects associated with extreme ventilatory measures and suboptimal perfusion, particularly if surgery is anticipated in the immediate future. Success with preoperative circulatory stabilization has been previously reported, including the successful management of a newborn with a significant degree of hydrops at birth.
As the management of these sick neonates continues to improve, traditional risk criteria to predict outcomes like cardiothoracic ratio on chest x-ray and GOS echocardiographic score has been overcome, making predictions quite difficult. New imaging modalities that hold promise include lung volumetric calculation of the lung parenchyma using magnetic resonance imaging as well as evaluation of the pulmonary artery size and direction of flow.
Over the past 30 years, distinct surgical approaches have been used largely on the basis of anatomic variables including the size of the tricuspid valve, the size of the functional (nonatrialized) right ventricular cavity, and the presence of pulmonary atresia.
and should be considered a significant prognostic factor when it comes to deciding the type of intervention. More recently, physiologic inferences using echocardiogram suggest that an estimated RV pressure >30 mm Hg and antegrade flow across the RV outflow tract and pulmonary valve are associated with better outcomes after BVR.
In our cohort, we used these variables along with a careful consideration for preoperative patient condition to plan on a management strategy we believed would be the most reproducible and likely associated with survival.
Although the strategy of BVR has been traditionally on the basis of the creation of a double-orifice valve with some partial leaflet attachment and rotation as well as augmentation and annuloplasty, significant improvements were achieved with a better understanding of the plane of coaptation and management of the right ventricular outflow obstruction. Moreover, the introduction of the Cone reconstruction has improved the reproducibility of the tricuspid valve repair even in the newborn, having a favorable effect on outcomes.
Although clinical presentation of EA in the neonate is associated with life-threatening physiology, an initial intervention aimed at physiologic stabilization and recovery of end organ function can have a favorable effect on outcomes, mitigating morbidity and overall mortality. The choice of management pathway between right ventricular exclusion versus biventricular intervention should be on the basis of anatomic and physiologic variables rather than on arbitrary anatomic criteria. Risk markers traditionally associated with a poor outcome are no longer valid and new predictors should be identified to better inform decisions and counsel parents about the management options and their likelihood of success in patients with this complex form of congenital heart disease.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
Refining the Society of Thoracic Surgeons Congenital Heart Surgery Database mortality risk model with enhanced risk adjustment for chromosomal abnormalities, syndromes, and noncardiac congenital anatomic abnormalities.