Diagnostic Method for Cardiac Malposition

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This entry is adapted from the peer-reviewed paper 10.3390/children9121977

A significant number of patients with dextrocardia and other cardiac malpositions have other congenital heart defects (CHDs). The incidence of CHDs in subjects with cardiac malpositions is significantly greater than that in normal children, and the prevalence varies with the associated visceroatrial situs. The most useful approach to diagnosis is segmental analysis. Firstly, dextroposition should be excluded. In segmental analysis, the visceroatrial situs, ventricular location, status of atrioventricular connections, the great artery relationship, and conotruncal relationship are determined with the use of electrocardiogram (ECG), chest X-ray, and echocardiographic studies, and, when necessary, other imaging studies, including angiography. Following identification of the afore-mentioned segments, the associated defects in the atrial and ventricular septae, valvar and vascular stenosis or atresia may be determined by a review of the historical information, physical examination, and analysis of chest roentgenogram, ECG, and echocardiographic studies. Along the way, a pictorial rendition of the terminology and diagnosis of cardiac malpositions is undertaken.

dextrocardia levocardia dextroposition situs solitus

1. Cardiac Malpositions

Dextrocardia and other cardiac malpositions are often associated with complicated congenital heart defects (CHDs). In addition, most physicians are confused when evaluating patients with cardiac malposition.

2. Prevalence

The prevalence of dextrocardia is estimated to be 0.12 per 1000 new patients of all age groups, while it is slightly higher at 0.29/1000 in neonates. In patients with dextroposition, the incidence of CHD is similar ^[1] to that seen in the normal population, which is 8 per 1000 live-born babies ^[2]^[3]^[4]. However, in patients with dextrocardia, the prevalence of CHDs is higher than that seen in normal populations and differs with the accompanying status of the visceroatrial situs ^[5]^[6]. In subjects with situs inversus totalis, the incidence of CHD is 3 to 10% ^[1], while it is almost 100% in babies with isolated dextrocardia and isolated levocardia ^[7]. As mentioned above, this is in contrast to the CHD prevalence of less than 1% in the otherwise normal population.

3. Diagnostic Method for Cardiac Malposition

3.1. Why Is the Heart in the Right Side of the Chest?

The first step is to determine the reason why the heart is in the right chest; is it due to intrinsic malposition of the heart (true dextrocardia), or is it due to being pushed or dragged to the right side by abnormalities of the thoracic cage or pulmonary pathology (dextroposition). Careful inspection of the tracheal position usually reveals that the trachea is shifted to the right in patients with dextroposition of the heart, while the trachea is close to the midline in subjects with innate dextrocardia. The apex of the heart is usually pointed towards the left in dextroposition patients. In addition, chest X-ray will show bony thoracic abnormality or pulmonary pathology.

The reasons for taking this step are two-fold; first, the prevalence of associated CHD is vastly different between both groups (see the section on Prevalence), and second, most commonly, the pulmonary pathology seen in dextroposition needs to be addressed on a relatively urgent basis.

3.2. Where Are the Atria Located?

Following the exclusion of dextroposition and confirmation that the position of the heart in the right chest is due to intrinsic cardiac malposition, the site of the atria should be determined. There is a consistent relationship between the atrial site and abdominal viscera (as exemplified by liver and stomach), described as viscero-atrial concordance ^[7]^[8]^[9]: a left-sided stomach and right-sided liver are seen with morphologic left atrium (LA) on the left side and morphologic right atrium (RA) on the right side, meaning situs solitus. Similarly, a left-sided liver and right-sided stomach are seen with right-sided morphologic LA and left-sided morphologic RA, meaning situs inversus. Cardiac malposition may be seen with 1. Situs solitus. Normal relationship of the viscera and atria (right to left), 2. Situs inversus. Left-to-right reversal of the viscera and atria, or 3. Situs ambiguous with indeterminate situs. The situs ambiguous is usually accompanied by heterotaxy syndromes (asplenia and polysplenia). The situs of the atria may be investigated by means of several principles/methodologies.

3.2.1. P Waves in the Electrocardiogram (ECG)

In normal individuals, the cardiac electrical impulse is initiated in the sino-atrial (SA) node. The SA node is situated at the junction of the superior vena cava and RA. The cardiac impulse travels to the left and inferiorly ^[10]. The ensuing depolarization of the atria results in P waves of the ECG tracing. The resultant P wave is positive in both leads I and AVF with a P wave axis of approximately +45° . Such normal P waves are indicative of situs solitus of the atria with the RA on the right side and the LA on the left side.

If the P waves, on the other hand, are negative in lead I and positive in lead AVF with a P wave axis of approximately +135°, the atria are likely to be inverted with morphologic LA on the right and morphologic RA on the left, i.e., situs inversus.

If the P waves are negative in lead AVF and positive in lead I, giving an axis is −45°, it is generally termed low atrial or coronary sinus rhythm. Such a P wave axis is not useful in assessing the situs of the atria. Nevertheless, such coronary sinus (low atrial) rhythms are frequently seen in subjects with infrahepatic interruption of the inferior vena cava (IVC) and persistent left superior vena cava; these venous anomalies are often associated with heterotaxy syndromes (asplenia/polysplenia).

ECG is frequently obtained during a routine investigation of any CHD, and review of the P wave morphology in the ECG is an easy and inexpensive way of identifying atrial situs in patients with cardiac malposition.

3.2.2. Visceroatrial Concordance

The principle of visceroatrial concordance ^[9], as stated above, dictates that a liver on the right side and stomach on the left side are suggestive of situs solitus, i.e., the morphologic LA is on the left side, and the morphologic RA is on the right side. Similarly, a right-sided stomach and a left-sided liver are indicative of situs inversus, i.e., the morphologic RA on the left and the morphologic LA on the right.

To utilize the principle of visceroatrial concordance, the locations of the liver (by its whitish opacity) and stomach (by its black gaseous opacity) should be visualized in posteroanterior view of chest radiographs. Occasionally, the stomach bubble may not be present on routine chest X-rays. In such situations, reviewing all the available chest X-rays or even injecting small quantities of air or barium via a nasogastric tube may be warranted. However, the authors have not resorted to this since some chest X-rays exhibited a gaseous stomach bubble.

If the lobes of the liver are of equal size or if the liver is located in the midline, regardless of the location of the gaseous opacity of the stomach, situs ambiguous is likely, and the possibility of heterotaxy syndromes (asplenia/polysplenia) exists ^[7]^[8]. The rule of visceroatrial concordance appears to have a greater degree of dependability than the P wave axis in an ECG in accurately detecting the situs of the atria ^[5]^[6]^[7]. Although this well-established principle of visceroatrial concordance is fairly helpful, it has been found to be misleading in a few cases ^[11].

3.2.3. Tracheobronchial Tree Pattern

In typical patients with situs solitus, the bronchus on the right side is short and wide and descends somewhat steeply, whereas the bronchus on the left side is longer and narrower than the right bronchus and descends rather horizontally. On the contrary, in patients with situs inversus, the tracheobronchial tree configuration is inverted ^[5]^[6]^[7]^[8]. The tracheobronchial tree pattern seems more correct than the above two approaches to identifying the atrial situs ^[8]^[12]^[13]. Tomography has been used in the past ^[13] to more accurately determine bronchial morphology and measure the bronchial lengths but is not routinely used at the present time because of increased radiation exposure associated with tomography and the availability of other imaging studies.

If both bronchi (right and left) have the appearance of morphologic right bronchi, asplenia syndrome is likely to be present, whereas morphologic left bronchi on both sides is indicative of polysplenia syndrome ^[7]^[8]^[12]^[13]. Exceptions to these observations have been seen but are uncommon ^[7]^[14]^[15].

3.2.4. Vena Cava–Aorta Relationship

A predictable relationship between the locations of the aorta (Ao) and the IVC at the level of the diaphragm with the atrial situs seems to exist ^[5]^[6]^[16]. The location of the IVC and Ao at the level of the diaphragm can easily be imaged on short-axis echo views. The IVC is typically larger than the Ao. In addition, the Doppler flow patterns with the venous flow for the IVC and arterial flow for the Ao confirm the identity of the respective vessel.

In patients with situs solitus, the Ao is on the left of the spine, and the IVC is on the right of the spine. In subjects with situs inversus, the positions of the IVC and Ao are reversed, left to right, with the IVC on the left side and Ao on the right side. In subjects with dextro-isomerism (asplenia syndrome), the IVC and Ao are placed together on either the right or left side of the spine. The Ao is usually anterior to the IVC. In subjects with levo-isomerism (polysplenia syndrome), the Ao is typically in the midline, anterior to the spine, and the azygos vein is located behind the aorta. The location of the azygos vein is on the right of the spine in subjects with azygos continuation of the interrupted infrahepatic IVC, while its location is on the left side of the spine in subjects with hemiazygos continuation of the interrupted infrahepatic IVC. Consequently, the comparative locations of the Ao and IVC are valuable in the assessment of the atrial situs ^[5]^[6]^[16].

3.2.5. Venoatrial Concordance

During embryonic development, the IVC is connected to the sinus venosus, which later (post-natal) becomes the RA. Consequently, the side of the IVC determines the location of the RA. Therefore, the IVC is on the right side in subjects with situs solitus, while the IVC is on the left side in subjects with situs inversus. The position of the IVC can easily be defined by echo imaging in the subcostal view. The absence of IVC entrance into the right atrium in subjects with interrupted IVC (infrahepatic) with azygos or hemiazygos can also be shown in careful subcostal echo studies.

More invasive techniques, such as nuclear angiography or cardiac catheterization, may also define the atrial situs but are not required for the sole purpose of atrial situs determination. In subjects who have infrahepatic interruption of the IVC with either azygos or hemiazygos continuation, the position of the azygos vein is not useful in determining the atrial situs.

3.2.6. Atrial Morphology

Atrial morphology may be assessed by transesophageal echocardiography (TEE), selective atrial angiography, or by surgical inspection. If these procedures are performed for some other reason, such data may be used to determine the atrial situs. The atrial appendages have characteristic shapes in that the RA appendage is large and broad, while the LA appendage is narrow, tubular, and small. If TEE, selective atrial angiography, or surgical inspection is undertaken for any other reason, securing such data at that time is helpful in evaluating the atrial situs.

If the above methods of atrial situs evaluation are at variance with each other, asplenia/polysplenia syndromes (heterotaxy) should be suspected. Other features that support heterotaxy are 1. Symmetric bronchial pattern, namely, bilateral morphologic right bronchi (dextroisomerism) or bilateral morphologic left bronchi (levoisomerism), 2. The divergence between visceroatrial situs and position of the heart, i.e., isolated dextrocardia or isolated levocardia, 3. Midline or symmetric liver on X-ray, 4. Roentgenographic, echographic or angiographic evidence for infrahepatic interruption of the IVC, and 5. Evidence for malrotation of the intestine. Blood smear for Howell-Jolly bodies & Heinz bodies, barium gastrointestinal series to detect malrotation of the midgut, abdominal ultrasound to identify the spleen and liver, radio-isotopic scanning of the liver and spleen and rarely, selective angiography may help clarify the existence of asplenia/polysplenia syndrome.

3.3. Are There Two Ventricles or One? If Two, Where Are the Ventricles Located in Relation to Each Other?

In theory, patients with cardiac malposition may have one (single) or two ventricles. The distinction between one and two ventricles is feasible by echocardiography and angiography.

In case there are two ventricles, the question to address is: are the ventricles normally positioned with the right ventricle (RV) on the right side and the left ventricle (LV) on the left side? Or, are the ventricles inverted with morphologic RV on the left side and morphologic LV on the right side? Several methods have been used to make this assessment:

3.3.1. Electrocardiogram

It is imperative to record right chest leads (RV5 and RV6) in addition to the usual left chest leads to make an adequate interpretation of ECG of dextrocardia patients.

QRS Morphology

In normal children (or even in adults), the pattern of QRS complex, namely, an rS pattern in the leads V1 and V2, is indicative that the underlying ventricle is RV and a qRs pattern in the leads V5 and V6 is suggestive that the underlying ventricle is LV ^[17]^[18]^[19]. Such a logic of using QRS patterns to assess the ventricular location does not apply to cardiac malpositions ^[5]^[6]^[7] because most patients with cardiac malposition have RV hypertrophy or a single ventricle in addition to varying degrees of rotation of ventricular chambers.

Initial QRS Vector

While QRS morphology is not helpful, the initial QRS vector may be more useful. In normal hearts, the initial component of the QRS complex is derived from the depolarization of the ventricular septum. Normally, although the interventricular septum is depolarized from both the left and right sides, the left portion of the interventricular septum is activated a bit sooner than the right septal component. The ensuing initial electrical activity is directed to the right, anteriorly, and slightly superiorly ^[10]. Such depolarization will produce q waves in the left chest leads, no q waves in the right chest leads, and a q wave in lead AVF.

In subjects with normally related ventricles, i.e., the RV on the right side and the LV on the left side, the initial ventricular (septal) depolarization produces q waves in leads V5 and V6 without a q wave in leads V1 and V2.. This is irrespective of cardiac position (dextrocardia, levocardia, or mesocardia)

In patients with reversed ventricles, i.e., the morphologic LV on the right side and the morphologic RV on the left side, the conduction system is also inverted, following the rule that the conduction system follows the ventricles. This will result in q waves in the right chest leads and no q waves in the left chest leads.

Though the examination of the initial QRS vector has a sound theoretical basis, the usual occurrence of either RV hypertrophy or single ventricle and varying amounts of rotation of the cardiac structures suggests that such an analysis is not completely dependable in firming up of the ventricular location.

3.3.2. Echocardiography and Angiography

Several characteristic anatomical features of the ventricles themselves, the relationship of the atrioventricular (AV) to semilunar valves, and attachments of AV valves to the septum are useful in defining relative ventricular location. Other established principles/rules that are helpful in ventricular localization will also be reviewed in this section. These can be evaluated by echocardiographic and angiographic examination.

Ventricular Trabeculations and Shape

The morphologic LV is a smooth-walled structure with fine trabeculations and a foot-shaped appearance, whereas the morphologic RV has coarse trabeculations and a triangular shape. These features are demonstrated by echocardiographic and angiographic studies. It should be noted that the characteristic trabecular pattern of the ventricles is seen irrespective of great vessel relationship: normally related great vessels, transposed great arteries in levocardia or transposed great arteries in dextrocardia.

Atrioventricular Valve-to-Semilunar Valve Relationship

It has been established that AV valves go with the respective ventricular chambers in that the mitral valve is an essential part of the LV while the tricuspid valve is an integral part of the RV ^[14]^[20]^[21]^[22]. The morphologic LV has little or no conus musculature, and consequently, the mitral valve and aortic valve are in fibrous continuousness with each other. However, in the morphologic RV, a muscular structure (crista supraventricularis) separates the tricuspid valve from the pulmonary valve, and therefore, fibrous continuity between the AV valve and semilunar valve cannot be demonstrated. These features may be demonstrated in echocardiography and angiography.

Atrioventricular Valve Attachments to the Septum

The attachments of the AV valve leaflets to the interventricular septum have a characteristic pattern. In subjects with the normal left to right ventricular relationship, attachment of the tricuspid valve to the interventricular septum is at a lower level than that of the medial leaflet of the mitral valve. On the contrary, in patients with ventricular inversion, the valvar attachments to the interventricular septum are reversed with the right-sided AV (morphologic mitral) valve attachment higher than the left-sided AV (morphologic tricuspid) valve attachment.

Loop Rule

The principle of the loop rule ^[5]^[6]^[7]^[9]^[20]^[21] dictates that the relationship of semilunar valves is predictive of the looping of the ventricles (d-loop or l-loop), and the loop status, in turn, helps to indicate the site of the ventricles. The loop rule is formulated on the basis of the embryonic development of the heart. In the 3 to 4 week-embryo (when the embryo is about 2.2 mm long), the developing cardiac structure is a straight tube in the pericardium ^[23]^[24]. The heart tube grows faster than the pericardium. Due to this length discrepancy during normal growth and development, the cephalic part of the heart tube is forced to bend; it usually bends in a ventral and caudal way and right-ward ^[9]^[23]^[24]. This right-ward direction is a d-loop which results in the placement of the bulbus cordis (future RV) to the right and the embryonic ventricle (future LV) to the left. On the contrary, if the cardiac tube bends to the left side, an l-loop occurs, in which case, the morphologic RV is located on the left side while the morphologic LV is placed on the right side ^[5]^[6]^[7]^[9]^[20]^[23]^[24].

Based on the loop rule, the aortic valve to the right side of the pulmonary valve indicates a d-loop, and d-loop predicts that the RV is located on the right side and the LV on the left side. Similarly, the aortic valve positioned to the left of the pulmonary valve suggests an l-loop, which suggests that the morphologic RV is on the left while the morphologic LV is on the right (inverted) ^[5]^[6]^[7]^[9]^[20]^[23]^[24]. All the features described above can be defined by both echocardiography and selective cine angiography and are helpful in evaluating the looping status. Examples of d-loop in subjects with normally related great vessels, those with d-transposition of the great vessels and those with dextrocardia, and those with l-loop illustrating inverted ventricles are shown.

Coronary artery anatomy also has a predictive value in determining the looping status: the left anterior descending (LAD) coronary artery originates from the left coronary artery (LCA) in patients with d-loop, while the LAD originates from the right coronary artery in subjects with l-loop. Although these may be defined by carefully performed echo studies, the anatomy of the coronary artery is better defined by angiography.

Finally, chirality (right or left-handedness) has been used to assign loop status and, thus, ventricular localization ^[25]. When the direction of the RA to RV and RV outflow has a right-hand topology, it is likely to be a d-loop with RV on the right side and LV on the left side. If the RA to RV and RV outflow has a left-hand topology, an l-loop is expected with RV on the left side and LV on the right side.

3.4. What Is the Status of Atrioventricular Connections?

After the visceroatrial situs and the ventricular locations are defined, the relationship between atria and ventricles should be assessed. These relationships are: concordant, with the RA emptying into the RV and the LA emptying into the LV, and discordant, with the RA emptying into the morphologic LV and the LA emptying into the morphologic RV. Other AV connection abnormalities are: both the right and left atria emptying into a single ventricle (double-inlet left ventricle, both atria emptying into both ventricles via one common AV valve in the form of AV septal defect, a common atrium emptying into a single ventricle via a single AV valve (the so-called cor biloculare), a common atrium emptying into inverted ventricles via a single AV valve and atresia of either tricuspid or mitral valve. In addition, straddling or overriding of the AV valve over the ventricular septum may also occur. Such abnormalities may be defined by methodical echocardiographic imaging with the rare need for MRI, CT, and angiographic studies.

3.5. How Are the Great Arteries Related to Each Other and to the Ventricles?

The relationship between the great arteries is characterized as 1. Normal, in which case, the aortic valve is placed inferior to, posterior to, and to the right side of the pulmonary valve, 2. Transposed great arteries (d-TGA) with the aortic valve superior to, anterior to, and to the right side of the pulmonary valve, or 3. Inverted (l-TGA) with the aortic valve superior to, anterior to, and to the left side of the pulmonary valve. If the inter-relationship between the semilunar valves is abnormal but cannot be classified into one of the above groups, such abnormalities may be designated as malposition (d-malposition, l-malposition, AP-malposition).

The ventricle to great artery (Ao and PA) relationship may be classified into 1. Concordant with the RV giving origin to the PA and the LV giving origin to the Ao, as seen in normal individuals, 2. Discordant with A. the RV giving origin to the Ao and the LV giving origin to the PA, i.e., d-TGA in levocardia as well as d-TGA (d loop) in dextrocardia and B. the morphologically RV giving origin to the Ao and the morphologically LV giving rise to the PA (l-TGA with l-loop), 3. double-outlet ventricle with A. both great vessels arising from the RV, i.e., double-outlet right ventricle (DORV) or B. both great arteries from the LV, i.e., double-outlet left ventricle (DOLV).

Other ventriculo-arterial connection abnormalities are only one great vessel arising for the ventricles, i.e., truncus arteriosus, and atresia of one of the semilunar valves/great vessels, namely pulmonary and aortic atresia. As reviewed for the other anomalies in the preceding sections, these cardiac anomalies can also be defined by echocardiography with an infrequent necessity for other imaging tools, namely, MRI, CT, and angiography.

3.6. What Is the Conotruncal Relationship?

The position of the conal tissue relative to the pulmonary and aortic valves is characterized as subpulmonary or subaortic, or it may be present beneath both the semilunar valves, or it may be absent bilaterally. The conal tissue displaces the semilunar valve anteriorly and superiorly; the more conus tissue underneath a semilunar valve, the more superior and anterior that semilunar valve is displaced. Therefore, superior to inferior and anterior-to-posterior relationships of the semilunar valves indicate conal anatomy. In normal subjects, the conus is subpulmonary. In patients with transposition, subaortic conus is seen whether it is d-transposition or l-transposition. Bilateral conus is seen in DORV, and the conus is absent in the double-outlet left ventricle. The conal tissue and superior and anterior dislocation of the semilunar valves can be easily ascertained by echo imaging and may also be evaluated similarly if other imaging studies are performed.

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