**5.2. Electrocardiography**

The electrocardiograms for patients with EA are usually abnormal. The most common finding on ECG are tall P waves and right bundle branch block. The tall P waves are indicative of a large right atrium. The right bundle branch block occurs because abnormal development of the right bundle branch which appears to be associated with septal leaflet and medial papillary muscle development on necropsy studies [5]. Some patients may have a prolonged PR interval from long intra-atrial conduction times from a large right atrium. Wolff-Parkinson-White syndrome is associated with EA, thus ventricular pre-excitation may be seen on ECG.

#### **5.3. Echocardiography**

Echocardiography is the gold standard for obtaining the diagnosis for EA. Two dimensional (2-D) echocardiography can evaluate the tricuspid valve leaflets and their excursion. The apical four

the lungs. Furthermore, cyanosis results from systemic venous return being shunted across the ASD to the left side of the heart. Neonatal pulmonary vascular resistance (PVR) is elevated and this is a major impediment to effective antegrade flow from the diminutive and myopathic RV. In the first week of life when pulmonary vascular resistance is high pulmonary blood flow is dependent upon the PDA. This results in a physiological state referred to as "functional" pulmonary atresia. When the PVR decreases over the first week of life, the RV may then be able to overcome the afterload to establish antegrade flow. True anatomical pulmonary atresia where there is luminal discontinuity between RV and pulmonary artery is also often seen in these symptomatic neonates. These patients will have ductal dependent pulmonary circulation until a surgical procedure is performed to establish pulmonary blood flow. Left ventricular dysfunction can also play a critical role in the development of decompensated heart failure. This is related to left ventricular displacement of the interventricular septum as a result the severely dilated dysfunctional RV. This "pancaking" of the LV cavity impedes filling and diminishes systemic cardiac output. In less severe forms of EA the RV can generate effective antegrade flow especially when the PVR decreases. Antegrade flow across the RV outflow tract is accompanied by clinical improvement in symptoms. Neonates with severe TR or gross cardiomegaly who are otherwise asymptomatic have an associated mortality of 45% within the first year of life without intervention [17, 18]. The natural history of being diagnosed with EA during infancy is sobering [19]. However those who survive early childhood can expect reasonable longevity. When the disease is mild symptoms are not noticed until later in adult life. Symptoms are often related to

exercise intolerance or cyanosis from progressive tricuspid regurgitation.

sive cardiomegaly with decreased pulmonary vascular markings (**Image 1**).

Depending on the severity of disease, the chest roentgenograms usually demonstrates mas-

The electrocardiograms for patients with EA are usually abnormal. The most common finding on ECG are tall P waves and right bundle branch block. The tall P waves are indicative of a large right atrium. The right bundle branch block occurs because abnormal development of the right bundle branch which appears to be associated with septal leaflet and medial papillary muscle development on necropsy studies [5]. Some patients may have a prolonged PR interval from long intra-atrial conduction times from a large right atrium. Wolff-Parkinson-White syndrome is associated with EA, thus ventricular pre-excitation may be seen on ECG.

Echocardiography is the gold standard for obtaining the diagnosis for EA. Two dimensional (2-D) echocardiography can evaluate the tricuspid valve leaflets and their excursion. The apical four

**5. Diagnostic evaluation**

152 Congenital Anomalies - From the Embryo to the Neonate

**5.2. Electrocardiography**

**5.3. Echocardiography**

**5.1. Chest X-ray**

**Image 1.** Chest x-ray of an infant with EA. there is marked cardiomegaly with a significant cardiothoracic ratio. With marked cardiomegaly lung development can be impaired.

chamber views allow calculation of the displacement index, which measures the distance from the true septal annulus to the level of the apically displaced septal leaflet hinge point (**Image 2**). Distance is indexed to body surface area and values >8 mm/m<sup>2</sup> are consistent with EA [20]. Color Doppler echocardiography can demonstrate the presence and location of tricuspid valve regurgitation (**Image 3**) [21]. However, severity can be difficult to quantitate due to apical displacement. RV dysfunction and functional or anatomic pulmonary atresia can be evaluated by 2-D and color echocardiography [21] **Image 4**. The Great Ormond Street Echocardiogram (G.O.S.E.) score is a mortality risk stratification score for neonates with EA.It is calculated from the apical four chamber view by adding the right atrium and atrialized right ventricular volume and dividing by the sum of the functional right ventricular volume, left atrial and ventricular volumes. (18) A G.O.S.E score of 3 (ratio of 1.1–1.4) with cyanosis or 4 (ratio > 1.5) has a mortality of nearly 100% [18] **Image 5**.

Echocardiography can define other associated abnormalities with EA such as the presence of a patent ductus arteriosus, size and direction of shunting through the atrial septal defect/patent foramen ovale, presence of a ventricular septal defect, and hypertrabeculated left ventricle suggesting left ventricular non-compaction cardiomyopathy.

Fetal echocardiography is a useful diagnostic tool for prenatal diagnosis and monitoring progression of disease in utero. The 4-chamber view of the fetal heart will demonstrate apical displacement of the tricuspid valve annulus, enlarged right ventricular and atrial size, and large tricuspid valve annulus (**Image 6**). Color flow imaging can be used to evaluate the degree of tricuspid valve regurgitation. The pulmonary valve can be evaluated by 2-D and color flow imaging to assess for pulmonary atresia. M-mode assessment can determine any rhythm abnormalities such as supraventricular tachycardia [22]. In addition, signs of hydrops such as pericardial effusions can be visualized (**Image 7**).

Fetal echocardiogram is important for monitoring clinical status of the fetus during pregnancy. A large multicenter study performed by Freud et al. evaluated over 400 fetal echocardiograms of patients with EA. They demonstrated that larger cardiothoracic ratio, more than moderate

**Image 2.** Apical 4 chamber view of Ebstein's anomaly with severe enlargement of the right atrium and atrialized portion of the right ventricle. There is apical displacement of the tricuspid valve with tethering of the septal leaflet leading to poor coaptation and tricuspid valve regurgitation. RA: Right atrium. LA: Left atrium. aRV: Atrialized right ventricle. LV: Left ventricle. fRV: Function right ventricle.

**Image 3.** Apical 4 chamber with color flow imaging of the tricuspid valve. There is severe tricuspid valve regurgitation

Neonatal Ebstein's Anomaly

155

http://dx.doi.org/10.5772/intechopen.72891

**Image 4.** Color compare parasternal short axis view demonstrates the small functional right ventricle and pulmonary atresia. The tricuspid valve is rotated in a fashion that the effective orifice opens to the right ventricular outflow tract. Color Doppler demonstrates swirling of blood in the functional right ventricle, tricuspid regurgitation, and no antegrade

due to poor coaptation of the tricuspid valve leaflets.

pulmonary blood flow. aRV: Atrialized right ventricle.

tricuspid regurgitation, larger tricuspid annulus diameter z-score, larger diameter vena contracta for tricuspid regurgitation, lack of antegrade pulmonary blood flow, pulmonary regurgitation, and pericardial effusion were associated with increased perinatal mortality [4]. Furthermore, Tierney et al. demonstrated that only 31% of fetuses had no predictive risk factors for poor hemodynamic status at time of diagnosis, and of those, 61% went on to develop one or more signs later in gestation. As such, frequent fetal echocardiograms are necessary to monitor the clinical status of fetuses with EA [23].

#### **5.4. Computed tomography/magnetic resonance imaging**

There is limited utility for the use of CT, MRI, or cardiac catheterization in neonatal EA.

#### **5.5. Treatment**

#### *5.5.1. Medical*

In a study of 415 neonates presenting with symptomatic EA the overall hospital mortality was 24% [19]. Furthermore, surgical intervention in the neonatal period across US hospitals is

**Image 3.** Apical 4 chamber with color flow imaging of the tricuspid valve. There is severe tricuspid valve regurgitation due to poor coaptation of the tricuspid valve leaflets.

tricuspid regurgitation, larger tricuspid annulus diameter z-score, larger diameter vena contracta for tricuspid regurgitation, lack of antegrade pulmonary blood flow, pulmonary regurgitation, and pericardial effusion were associated with increased perinatal mortality [4]. Furthermore, Tierney et al. demonstrated that only 31% of fetuses had no predictive risk factors for poor hemodynamic status at time of diagnosis, and of those, 61% went on to develop one or more signs later in gestation. As such, frequent fetal echocardiograms are necessary to

**Image 2.** Apical 4 chamber view of Ebstein's anomaly with severe enlargement of the right atrium and atrialized portion of the right ventricle. There is apical displacement of the tricuspid valve with tethering of the septal leaflet leading to poor coaptation and tricuspid valve regurgitation. RA: Right atrium. LA: Left atrium. aRV: Atrialized right ventricle. LV:

There is limited utility for the use of CT, MRI, or cardiac catheterization in neonatal EA.

In a study of 415 neonates presenting with symptomatic EA the overall hospital mortality was 24% [19]. Furthermore, surgical intervention in the neonatal period across US hospitals is

monitor the clinical status of fetuses with EA [23].

Left ventricle. fRV: Function right ventricle.

154 Congenital Anomalies - From the Embryo to the Neonate

**5.5. Treatment**

*5.5.1. Medical*

**5.4. Computed tomography/magnetic resonance imaging**

**Image 4.** Color compare parasternal short axis view demonstrates the small functional right ventricle and pulmonary atresia. The tricuspid valve is rotated in a fashion that the effective orifice opens to the right ventricular outflow tract. Color Doppler demonstrates swirling of blood in the functional right ventricle, tricuspid regurgitation, and no antegrade pulmonary blood flow. aRV: Atrialized right ventricle.

**Image 5.** Apical four chamber view demonstrating the right atrium, atrialized portion of the right ventricle, functional right ventricle, left atrium and left ventricle. There is a grade 3 GOSE score which correlates with 100% mortality in presence of cyanosis. RA = right atrium. aRV = atrialized right ventricle. fRV = functional right ventricle. LA = left atrium. LV = left ventricle.

> Relatively stable but symptomatic patients can be treated with prostaglandin infusion to maintain ductal patency if functional or anatomical pulmonary atresia is evident. Supplemental oxygen should not be greater than 21% fractional inspired oxygen to avoid pulmonary overcirculation and volume loading of the heart. During this phase oxygen saturation should be maintained between 75 and 85%. As the pulmonary vascular resistance decreases, prostaglandin therapy can be discontinued. This will also allow for proper evaluation of antegrade pulmonary blood flow as the ductus closes. If saturations decrease under 80% then agents to lower pulmonary vascular resistance can be administered to promote antegrade flow, these

> **Image 7.** Fetal echocardiogram at 22 weeks and 3 days gestation with a four chamber view of the heart. The heart mass takes up the entire thoracic cavity. There is severe enlargement of the right atrium with evidence of a pericardial

Neonatal Ebstein's Anomaly

157

http://dx.doi.org/10.5772/intechopen.72891

Use of prostaglandins in the presence of pulmonary valve regurgitation may exacerbate heart failure symptoms due to the development of a circular shunt. In this physiology blood flows from left ventricle to aorta, then it is shunted away from the systemic circulation via the large ductus to the pulmonary artery then retrograde via the pulmonary valve into the right ventricle to right atrium via the incompetent tricuspid valve then back to the left side of the heart via the ASD. This creates high output heart failure. Prostaglandins should be stopped if this

Further hemodynamic instability leads to cardiogenic shock. In these situations intubation and mechanical ventilation with large tidal volumes are key to promoting adequate ventilation in patients with massive cardiomegaly. Furthermore, sedation and possible paralysis to limit oxygen requirements may be required. Inotropic support in the form of milrinone complemented with low dose of dopamine or epinephrine may be necessary to assist with cardiac output. Tachyarrhythmias are common in this group of patients so utilization of cat-

include supplemental oxygen and nitric oxide.

effusion. RA: Right atrium. RV: Right ventricle. LA: Left atrium. LV: Left ventricle.

echolamine inotropes should be used sparingly.

physiology exists.

**Image 6.** Fetal echocardiogram performed at 22 weeks and 3 days gestation. There is severe enlargement of the right atrium with severe tricuspid valve regurgitation demonstrated on color Doppler evaluation. The tricuspid valve annulus dimension is markedly enlarged.

associated with a mortality of 27–36% depending on the procedure performed [19]. There is significant improvement in surgical outcome if the patient can be medically managed out of the neonatal period [24]. As such the best survival rates for EA occurs outside of the neonatal period, thus medical management with supportive care is crucial for improving outcomes.

**Image 7.** Fetal echocardiogram at 22 weeks and 3 days gestation with a four chamber view of the heart. The heart mass takes up the entire thoracic cavity. There is severe enlargement of the right atrium with evidence of a pericardial effusion. RA: Right atrium. RV: Right ventricle. LA: Left atrium. LV: Left ventricle.

Relatively stable but symptomatic patients can be treated with prostaglandin infusion to maintain ductal patency if functional or anatomical pulmonary atresia is evident. Supplemental oxygen should not be greater than 21% fractional inspired oxygen to avoid pulmonary overcirculation and volume loading of the heart. During this phase oxygen saturation should be maintained between 75 and 85%. As the pulmonary vascular resistance decreases, prostaglandin therapy can be discontinued. This will also allow for proper evaluation of antegrade pulmonary blood flow as the ductus closes. If saturations decrease under 80% then agents to lower pulmonary vascular resistance can be administered to promote antegrade flow, these include supplemental oxygen and nitric oxide.

Use of prostaglandins in the presence of pulmonary valve regurgitation may exacerbate heart failure symptoms due to the development of a circular shunt. In this physiology blood flows from left ventricle to aorta, then it is shunted away from the systemic circulation via the large ductus to the pulmonary artery then retrograde via the pulmonary valve into the right ventricle to right atrium via the incompetent tricuspid valve then back to the left side of the heart via the ASD. This creates high output heart failure. Prostaglandins should be stopped if this physiology exists.

Further hemodynamic instability leads to cardiogenic shock. In these situations intubation and mechanical ventilation with large tidal volumes are key to promoting adequate ventilation in patients with massive cardiomegaly. Furthermore, sedation and possible paralysis to limit oxygen requirements may be required. Inotropic support in the form of milrinone complemented with low dose of dopamine or epinephrine may be necessary to assist with cardiac output. Tachyarrhythmias are common in this group of patients so utilization of catecholamine inotropes should be used sparingly.

associated with a mortality of 27–36% depending on the procedure performed [19]. There is significant improvement in surgical outcome if the patient can be medically managed out of the neonatal period [24]. As such the best survival rates for EA occurs outside of the neonatal period, thus medical management with supportive care is crucial for improving outcomes.

**Image 6.** Fetal echocardiogram performed at 22 weeks and 3 days gestation. There is severe enlargement of the right atrium with severe tricuspid valve regurgitation demonstrated on color Doppler evaluation. The tricuspid valve annulus

**Image 5.** Apical four chamber view demonstrating the right atrium, atrialized portion of the right ventricle, functional right ventricle, left atrium and left ventricle. There is a grade 3 GOSE score which correlates with 100% mortality in presence of cyanosis. RA = right atrium. aRV = atrialized right ventricle. fRV = functional right ventricle. LA = left atrium.

dimension is markedly enlarged.

LV = left ventricle.

156 Congenital Anomalies - From the Embryo to the Neonate

Milrinone is a very effective drug since it has lusitropic and inotropic effects on the right ventricle. Furthermore, it decreases the pulmonary vascular resistance which promotes antegrade pulmonary blood flow. Frequent echocardiograms during the first week are useful to assess antegrade flow across the RV outflow tract and degree of TV regurgitation. This assessment will help guide weaning prostaglandins, and initiation of nitric oxide and inotropes.

The two competing strategies for surgical treatment for neonatal EA are whether to perform a

Neonatal Ebstein's Anomaly

159

http://dx.doi.org/10.5772/intechopen.72891

The decision for which type of repair is best for neonatal EA is controversial. Mizuno et al. described their center experience with neonatal EA repair. Their results demonstrated greater survival for the biventricular repair group compared to single ventricle palliation, 60 vs. 25% respectively [30]. A recent follow up study by Kumar et al. evaluated the median 7 year follow up for the Starnes procedure in 27 neonatal repairs [29]. Their overall survival for 5 year follow up was 81%. Boston et al. described their outcomes for neonatal biventricular repair for EA. Early survival was 78.1% in their series, while 15 year survival for EA with and without anatomical pulmonary atresia was 40 and 79% respectively. As such caution should be advised for biventricular repairs in EA neonates with anatomical pulmonary atresia [25, 36]. In summary, neonatal EA continues to carry a high perinatal mortality upon fetal diagnosis. A multidisciplinary approach is required for improved outcomes. Fetal echocardiography predicts outcome and is necessary for monitoring progression of EA complications. Comprehensive care with a multi-disciplinary team including high risk obstetrician, pediatric cardiologist, pediatric cardiothoracic surgeon, neonatal intensivist should occur at a tertiary care center. Surgical management during the neonatal period remains high. If possible medi-

biventricular repair or a single ventricle palliative procedure (Starnes Procedure).

cal management through the neonatal period improves mortality.

\*Address all correspondence to: uboston@uthsc.edu

Umar Boston\*, Ken-Michael Bayle, TK Susheel Kumar and Christopher Knott-Craig

Heart Institute at Le Bonheur Children's Hospital, University of Tennessee Health Science

[1] Ebstein W. Uber einen sehr seltenen fall von insufficienz der valvula tricuspidalis, bedingt durch eine angeborene hochgradige misshildung derselben. Archives of Anatomy

[2] Fyler DC, Buckley LP, Hellenbrand WE. Report of the New England regional infant

[3] Hornberger LK, Sahn DJ, Dleinman CS, Copel JA, Reed KL. Tricuspid valve disease with significant tricuspid insufficiency in the fetus: Diagnosis and outcome. Journal of the

[4] Freud LR, Escobar-Diaz MC, Kalish BT, et al. Outcomes and predictors of perinatal mortality in Fetuses with Ebstein anomaly or tricuspid valve dysplasia in the current era a

**Author details**

**References**

Center, Memphis, United States

and Physiology. 1866;**33**:238-254

cardiac program. Pediatrics 1980;**65**:375-461

American College of Cardiology. 1991;**17**:167-173

Multicenter study. Circulation 2015;**132**:481-489

In summary, medical management when pulmonary ductal dependency exists is analogous to single ventricle physiology whereby a balance between systemic and pulmonary circulation needs to be established. This is best done with maintenance of prostaglandins and low oxygen supplementation. Once the pulmonary vascular resistance drops and there is antegrade flow across the pulmonary valve then this management is more analogous to two ventricle physiology with a poor right ventricular pump. As such this is best managed by stopping prostaglandins and allowing for ductal closure. Concomitantly administration of nitric oxide, milrinone and higher oxygen supplementation will augment antegrade flow.

The goal of medical therapy is to avoid an operation particularly during the neonatal period when mortality is highest for any surgical procedure performed.
