Ebstein anomaly Q22.5

In 1866, the Göttingen internist Wilhelm Ebstein was the first to describe the clinical picture of the Ebstein anomaly, which was then named after him (Apitz 2002).

An Ebstein anomaly is the malformation of one or more sails of the tricuspid valve. The severity of the disease is mainly determined by the displacement of the septal and mural sails towards the apex. The heart is divided by the apical displacement of the sails into a right atrium, an atrialized right ventricle (aRV) and a functional residual ventricle (fRV) (Herold 2019). The displacement of the tricuspid valve closure plane causes a rotation in the direction of the outflow tract of the right ventricle (Vogt 2014).

The Ebstein anomaly has a considerable morphological variance. The classification is therefore based on anatomical aspects. The most commonly used classification is that of Alain Carpentier:

• Type A: Also known as "light". The displacement of the anterior and septal sails is only moderate. The anterior part is freely movable. There is a small atrialized chamber.
• Type B: In type B there is a clear displacement of the septal and posterior sails or in valve closure. In this case the atrialized chamber is large and surrounded by a thin, non-contractile wall.
• Type C: Here the anterior sail is additionally restrictive. Sometimes the septal sail is strongly hypoplastic. There is a small functional right ventricle with restricted function.
• Type D: Also called "severe form". The anterior sail is strongly adherent to the front wall. Thus the atrialized part of the right ventricle appears like a tricuspid "sack" (Vogt 2014)

Due to the systolic regurgitation of blood from the right residual ventricle via the insufficient tricuspid valve into the right atrium or the atrialized ventricle a volume load of both the right atrium and the atrialized right ventricle occurs. The stroke volume is small if the right ventricle is small. This in turn causes a low pulmonary blood flow (Herold 2019).

Due to the reduced net transpulmonary forward flow, there is a reduced preload of the left ventricle and thus a decreased cardiac output. (Vogt 2014)

In 80 % - 94 % there is an additional intraatrial connection, which leads to a right-left shunt in case of increased pressure in the right ventricle (Pinger 2019). A left-right shunt occurs less frequently.

M. Ebstein is a rarely occurring vitium. It accounts for only about 0.5% of all congenital heart defects (Pinger 2019).

The incidence is 1 per 20,000 live births (Poels 2018). Male newborns are more frequently affected. The sex ratio is 1.4: 1 (m: w) (Herold 2019).

A study from 1984 (Long 1984) gave rise to the suspicion that after maternal intake of lithium during early pregnancy, more children are born with M. Ebstein. However, this could not be confirmed by studies from 1990 (Apitz 2002).

A controlled study by Boyle et al. in 2016 included 264 newborns with Ebstein's anomaly. Here an association of the anomaly with maternal mental illness was shown, but not generally after ingestion of lithium, rather the malformation occurred dose-dependently. It is therefore important to check the mother's lithium level regularly.

Close cooperation with psychiatrists is recommended. The continuation of treatment with lithium should be decided on a case-by-case basis, as a relapse would also pose a high risk - both for the mother and the unborn child (stress, alcohol or drug abuse, lack of compliance with medical care, etc.).

Another option would be to switch medication before conception, e.g. to lamotrigine (Poels 2018).

Occasionally there is a family clustering (Blum 2015)

In 38 % - 42 % of cases, additional cardiovascular malformations are found (Schumacher 2008), such as:

• tricuspid valve insufficiency
• Functional disorders of the left ventricle
• Mitral valve anomalies
• an open foramen ovale
• Atrial septal defect
• accessory pathways (e.g. WPW syndrome)

Associated non-cardiac diseases are described in up to 19 % of cases (Schumacher 2008). These include:

• malformations of the face
• malformations of the jaw
• unilateral renal aplasia
• Inguinal hernia
• Megacolon
• Bile duct atresia etc. (Blum 2015)

In < 5 % of cases, additional chromosomal anomalies such as:

• trisomy 18
• Apert- Syndrome
• Noonan syndrome
• CHARGE- Association (Blum 2015)

The Ebstein anomaly is a congenital malformation. It is caused in the embryonic phase by a missing or incomplete detachment of the valve leaflets from the myocardium (Vogt 2014). The free valve opening is shifted towards the trabecular zone of the right ventricle (Muntau 2018). In about 15% of the affected patients a microdeletion on chromosome 22q11 is found.

The mutation leads to an abnormality of the tricuspid valve. This is shifted to the right ventricle (Kasper 2015). The valve itself is dysplastic, resulting in tricuspid valve insufficiency of varying degrees (Kasper 2015). Due to the displacement of the valve, the right ventricle is divided in two. Above the valve lies the so-called atrialized part, below the actual functional part of the right ventricle, which can be enlarged depending on the severity of the tricuspid valve insufficiency (Vogt 2014).

Ebstein's disease shows an unusually varied clinical presentation. It ranges from cases already diagnosed prenatally with subsequent intrauterine amniotic death to intravital primary diagnosis in a former farmer at the age of 85 (Apitz 2002).

Newborns are conspicuous for:

• central cyanosis

Infants mostly by:

• signs of right heart failure
• Neck vein congestion
• edema in the dependent parts of the body
• liver enlargement
• nocturia
• Pleural effusions
• Exertional dyspnea
• Enlargement of the vena cava (Lasserre 2002)

Schoolchildren due to:

• uncharacteristic heart murmur

Adolescents or young adults due to:

• Tachyarrhythmias (Vogt 2014).

Other common symptoms - regardless of age - may include:

• Dyspnea
• Fatigue
• Exercise limitations
• thoracic pain (atypical angina pectoris symptoms [Stier 2014])
• palpitations (Herold 2019)
• paradoxical emboli
• sudden cardiac death (Pinger 2019) For more details, see "Course and prognosis" below (Attenhofer Jost 2018).

Chest X-ray

There is marked cardiomegaly with narrow cardiac waist (typical of Ebstein's disease). The causes are:

• enlargement of the right atrium and tricuspid insufficiency (so-called Bocksbeutel-form)
• in case of additional obstruction of the right ventricle occurring reduced perfusion of the lung (Pinger 2019)
• the left ventricle and the right ventricular outflow tract are displaced to the left side
• Superior vena cava is not dilated (despite enlargement of the right ventricle)
• aorta has a narrow caliber
• decreased pulmonary vascularity
• Normal sized pulmonary artery (Stierle 2014).

Echocardiography

Echocardiography plays a major role in the diagnosis of Ebstein's anomaly. In 1974, only 17% of patients were younger than 1 year at initial diagnosis. In 1994, due to the further development of echocardiography, the diagnosis could already be made in 49 % of affected newborns (not older than 1 month) (Apitz 2002).

M- mode shows:

• delayed closure of the tricuspid valve (> 40 ms after the closure of the mitral valve)
• the anterior tricuspid leaflet shows overshooting excursion movements

In the 2-D echo there is:

• a dilated right atrium in the apical 4-ventricle view
• the right ventricle is enlarged
• the right atrium is reduced
• the septal leaflet of the tricuspid valve is displaced towards the right ventricle - apex
• the anterior leaflet shows excessive mobility (Stierle 2014)

Doppler sonography

With Doppler- sonography the following statements can be made:

• Determination of the extent of tricuspid valve insufficiency
• at the atrial level visualization of the right-left shunt
• detection or exclusion of obstruction of the right ventricular outflow tract
• in the four-chamber view, the area of the right atrium can be put in relation to the remaining sectional area with the help of an area index (this allows graduation of the severity from a prognostic point of view) (Apitz 2002)

Cardio- MRI

Cardio- MRI should be performed only if echocardiography did not yield clear findings.

However, it can be helpful preoperatively in complex lesions.

It also plays an important role in follow-up (Stierle 2014).

Cardiac catheterization

Cardiac catheterization is usually unnecessary. It is only important for the exclusion or detection of CHD (Herold 2019) or associated malformations (Apitz 2002).

In the case of accessory pathways, an electrophysiological examination can be performed (Pinger 2019).

Inspection and palpation:

Depending on the severity of the stenosis and the progression of the disease, different symptoms can be found, such as:

• Congestion of the neck vein
• Hepatomegaly
• signs of central cyanosis (occurs with right-left shunt and/or low cardiac output [Herold 2019]; bluish discoloration of the skin plus the central mucosa) (Stierle 2014)
• glowing red cheeks, partly with purple shading
• Teleangiectasia
• bloated face
• slight systolic buzzing in the 4th ICR left
• slight lifting pulsations above the 2nd - 3rd ICR left parasternal are possible (Schumacher 2008)
• Precordium mostly normal, so-called "silent thorax" (Herold 2019)

Auscultation

The auscultation is often unobtrusive. If not, the following noise phenomena may exist:

• the 1st heart sound is quiet, split (Schumacher 2008) and has a loud 2nd component due to the delayed closing of the tricuspid valve (also called "sail sound" [Stierle 2014])
• the 2nd heart tone may also be widely split and show a weakening of the final tone of the pulmonary artery valve (PaV) due to the reduced pulmonary artery flow (Schumacher 2008)
• serial clicks
• often there is a third and sometimes also a 4th heartbeat (so-called triple or quadruple rhythm)
• an immediate systolic murmur of tricuspid valve insufficiency can be auscultated at the lower left sternal margin
• short mesodiastolic noise (Herold 2019)

ECG

If the ECG shows a WPW syndrome and a central cyanosis is present at the same time, Ebstein's disease should always be excluded (Pinger 2019).

The ECG may show:

• predominantly sinus rhythm, more rarely AV node rhythm
• Legal situation type (Schumacher 2008)
• signs of right atrial hypertrophy
• deep Q in the derivatives II, III, aVF, V1 - V4
• WPW configuration
• right thigh block (occurs in up to 50 % [Pinger 2019], sometimes with a 2nd QRS complex preserved therein
• PR- interval can be extended
• supraventricular extrasystoles
• Low voltage possible (Herold 2019)
• P- dextroatrials with a peak positive P of > 0.2 mV (occurs in 71% of cases)
• AV block I. grade (found in 34 %)
• Delta-wave (at approx. 25 % there are accessory pathways that allow AV reentry tachycardia) (Pinger 2019)

Long term ECG

A long-term ECG is indicated to detect the frequently occurring supraventricular tachycardia (Muntau 2018).

• Tricuspid insufficiency of other genesis
• tricuspid valve dysplasia
• other cyanotic heart defects (in particular pulmonary atresia with intact ventricular septum)
• Cor triatriatum dextrum
• idiopathic dilatation of the right atrium (Vogt 2014)

The treatment of Ebstein's anomaly is divided into conservative and surgical therapy.

Conservative therapy: Patients who have only mild cardiomegaly without relative shunt and are asymptomatic should be treated conservatively first.

The first line of consideration is:

• Treatment of cardiac arrhythmias (by medication or ablation [Herold 2019]).
• oral anticoagulation (may be considered in case of right-left shunt or increased risk of thromboembolism [Herold 2019])
• Pacemaker implantation must be performed in about 3.7% (Pinger 2019); it is successful in about 80%, and 95% in otherwise healthy hearts; the recurrence rate is 30% (Vogt 2014)
• Diuretics for signs of right heart failure.
• Digitization questionable (contraindicated in WPW syndrome)
• immediate endocarditis prophylaxis (for more details see below "Follow-up")
• Prohibition of physical exertion (Schumacher 2008).

In critical cyanotic neonates, palliative measures include:

• Infusions with prostaglandin E1 infusions (to keep the ductus botalli open) (Stierle 2014).

Indications for surgical treatment are:

• symptomatic patients with > Nyha II and decreasing width of performance
• progressive increase in size of the heart and decreasing function of the right ventricle
• Symptomatic tricuspid regurgitation that is more than moderate in severity.
  • intermediate grade TI is defined as:
  • Morphology of the valve normal or abnormal.
  • V. contracta (mm) < 7
  • PISA radius (mm)x1 6 - 9
  • EROA (mm 2) not defined
  • R Vol (ml) not defined
  • PW- Signal of inflow normal
  • CW- signal of TI dense/ parabolic
  • Hepatic venous flow systolic attenuated (Pinger 2019).
• Progressive or higher grade cyanosis with arterial saturation at rest <90%.
• occurrence of paradoxical emboli
• outflow obstruction on the right side is relevant (Herold 2019)

1. indications according to ESC 2010 to perform surgical therapy are:

Indication class I:

Valve reconstruction and, if necessary, simultaneous closure of an ASD or VSD in severe tricuspid regurgitation and presence of:

• heart failure > NYHA II
• or arrhythmias
• or spirometric deterioration under stress

Indication class IIa:

Performance of valve repair in the presence of:

• an increasing dilatation of the right ventricle
• or a reduction of systolic function of the right ventricle
• or increasing cardiomegaly

2. indications according to ESC 2010 for performing interventional therapy are:

Indication class I:

• Electrophysiological study (EPU) with ablation in case of relevant arrhythmias.

Indication class IIa:

• in case of systemic emboli, which probably occur as paradoxical emboli, closure of the ASD or VSD should be performed (Pinger 2019).

Surgical measures available are:

1. interventional cardiac catheterization measures
2. surgical therapy
3. reconstructive surgery
4. tricuspid valve replacement
5. palliative surgical measures (Vogt 2014)

To 1. Interventional cardiac catheterization measures:

Ductus- stenting as an alternative to aortopulmonary shunting can be performed in the first months of life in individual cases. In addition, an ASD closure is possible. This may be indicated in the case of:

• mild expression of Ebstein's anomaly

and

• ASD hemodynamics with significant left-right shunt.

In the presence of cyanosis should always be decided on a case-by-case basis (Vogt 2014).

In critical cyanotic newborns can be performed as an interventional palliative measure:

• Rashkind balloon septostomy (Stierle 2014).

To 2. Surgical therapy:

Here we differentiate between corrective op- methods and palliative op- methods.

In corrective surgery, either valve-preserving reconstructive surgery can be performed or by replacement of the tricuspid valve (mechanical or biological replacement)

(Vogt 2014)

Recently, Da Silva cone reconstruction has been increasingly performed, which involves pronounced mobilization of the valve leaflets, funneling reconstruction of the leaflets, and longitudinal shirring of the atrialized right ventricle (Eschenbach 2017)

Palliative procedures include:

• the aorto-pulmonary shunt to improve blood flow to the lungs
• the partial cavo- pulmonary anastomosis (also known as 1.5 ventricle heart) to unload the right ventricle
• the total cavo-pulmonary anastomosis (also called 1-ventricular heart) also to relieve the right ventricle (Vogt 2014)

To 3. Reconstructive surgery:

Plastic reconstruction of the native valve is currently favored, if anatomical conditions allow. There are differentiated concepts for this:

• exclusion (also called plication) of the ineffectively pumping right ventricle
• Modification of the valve suspension of the tricuspid valve (Vogt 2014).

Re 4. tricuspid valve replacement:

Both mechanical and bioprostheses are available (see valve replacement). The number of re-operations is similar for both valves. However, the 20-year survival rate showed a clear advantage of porkine bioprostheses: 75% versus 43% (Vogt 2014).

Re 5. Palliative surgical procedures:

Palliative surgical procedures are limited to symptomatic patients with severe Ebstein anomaly. Here, an aorto-pulmonary shunt and closure of the tricuspid valve ostium with a fenestrated patch (so-called Starnes surgery) are performed.

This procedure allows univentricular circulation. It is not limited to the neonatal period; partial cavo-pulmonary anastomosis may also be indicated in later years in addition to tricuspid valvuloplasty (Vogt 2014).

Spontaneous course: Most patients with Ebstein's anomaly are nowadays - thanks to increasingly precise diagnostic possibilities - diagnosed at an early stage. Nevertheless, mortality is very high, especially in the first year of life (23% [Schumacher 2008]). If the first diagnosis is made intrauterine, only 10% of children survive to the first year of life (Apitz 2002).

The average life expectancy is about 15 years if untreated. The risk of sudden cardiac death is increased compared to the general population (Attenhofer Jost 2018). On the other hand, there are also symptomless courses extending into adulthood, in which the initial manifestation is often manifested by:

• WPW syndrome
• atrial fibrillation
• paradoxical embolism (Pinger 2019)

Surgical mortality is 4.9% (Apitz 2002) and the rate of reoperation is approximately 2% to 5% per patient-year (Blum 2015).

Postoperatively, physical capacity usually remains limited. Cardiac arrhythmias are also not uncommon (Vogt 2014).

The 10-year survival rate is >90% (Pinger 2019).

Other residual findings that may occur postoperatively include:

• new-onset tricuspid regurgitation
• persistent tricuspid regurgitation
• residual shunt at atrial level
• failure of the right or left ventricle
• occurrence of arrhythmias (both supraventricular and ventricular)
• higher grade block images

Patients with Ebstein's anomaly are generally at increased risk for sudden cardiac death (PHT) throughout their lives. Studies suggest that clinical parameters such as pulmonary stenosis, heart failure, previous syncope, and ventricular tachycardia predict the likelihood of sudden cardiac death. Implantation of a defibrillator should be performed in these patients, as cardiac arrhythmias are the most likely cause of PHT.(Attenhofer Jost 2018).

Familial clusters of Ebstein's anomaly are extremely rare, but affected families should still be offered genetic counseling and prenatal diagnostics including fetal echocardiography (Vogt 2014).

Antibiotic prophylaxis should be administered as a single dose 30 - 60 minutes before an operation.

If oral administration is possible, amoxicillin or ampicillin 2 g p. o. can be administered

if oral administration is not possible, ampicillin or cefalexin 2 g i.v. is recommended

for ampicillin or penicillin allergy, clindamycin 600 mg should be given orally

with necessary i.v. administration Clindamycin 600 mg i.v.

It should be noted that cephalosporins must not be used in patients who have reacted with anaphylaxis, angioedema or urticaria after ampicillin or penicillin (Herold 2018).

Regular check-ups (once or twice a year) by a doctor specialising in congenital heart defects should be carried out throughout life. Scope of the check-ups:

• standard ECG
• Echocardiography
• and, if necessary, cardiac functional examinations such as:
• long-term ECG
• Exercise ECG
• Spirometry
• MRI examination (this is best suited to quantify right and left ventricular function) (Vogt 2014)

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