Cardiac Malpositions - Circulationcirc.ahajournals.org/content/circulationaha/56/2/159.full.pdfasplenia and polysplenia are regarded as having cardiac malpositions. From the Cardiovascular

Cardiac MalpositionsAn Overview Based on

Study of Sixty-five Necropsy Specimens

PAUL STANGER, M.D., ABRAHAM M. RUDOLPH, M.D., AND JESSE E. EDWARDS, M.D.

Cardiac malformations associated with cardiac malposi-tions are so complex that even angiographic studies may notafford as accurate information as direct examination ofnecropsy specimens. This communication will attempt tooutline a systematic approach to cardiac malpositions basedupon necropsy studies of 65 cases. Where possible, morpho-logic features characteristic of the entities are correlated withclinical, roentgenographic, electrocardiographic andcatheterization findings. Embryologic considerations arealso discussed.The problems of terminology in complex congenital car-

diac anomalies, particularly those with abnormalities ofposition, are well known. For an excellent discussion, thereader is referred to the recent article by Wilkinson andAcerete.5 Rather than creating new terms, the authorsselected existing terms which they considered the least am-biguous and least confusing. We have used the selected termsas defined in that article with three exceptions. 1) Theasplenia and the polysplenia syndromes are sufficiently dis-tinct to warrant separate categories, rather than groupingthem as situs ambiguus. The reasons for this are discussed inthe sections dealing with these entities. 2) Transpositionherein refers only to transposition of the great arteries asdefined by Van Praagh,2 i.e., aorta arising from themorphologic right, and pulmonary artery from themorphologic left, ventricle. 3) We concur with Van Praagh inclassifying Taussig-Bing anomaly as a form of double outletright ventricle with a subpulmonic ventricular septal defect.3

Definitions

Cardiac malposition. Normally the major portion of theheart lies to the left of midline. For the purposes of thisstudy, any heart other than a left-sided heart in a situs solitusindividual represents a cardiac malposition. This definitionrefers not only to the cardiac position but also the ap-propriateness of the cardiac position in relation to the totalbody situs. A right-sided heart is clearly unusual even thoughit may be appropriate in an individual with situs inversus. Aleft-sided heart, however, is inappropriate in situs inversusand is also an example of cardiac malposition.

For theoretical reasons to be discussed later, all cases ofasplenia and polysplenia are regarded as having cardiacmalpositions.

From the Cardiovascular Research Institute and Department ofPediatrics, University of California, San Francisco, California, and theDepartments of Pathology, United Hospitals-Miller Division, St. Paul andUniversity of Minnesota, Minneapolis, Minnesota.Supported by Public Health Service Research Grant HE 05694, National

Heart Institute Research Training Grant HE 05570, Program Project GrantHL 06285 and Training Grant HL 05886 from the NHLBI; the St. PaulFoundation and the Bremer Foundation, St. Paul, Minnesota.Address for reprints: Paul Stanger, M.D., Cardiovascular Research

Institute, University of California, San Francisco, California 94143.Received September 13, 1976; revision accepted March 11, 1977.

Levocardia, dextrocardia and mesocardia are generalterms indicating cardiac position only. They do not give anyindication of cardiac structure, body situs, or electrocardio-graphic findings. Levocardia denotes a left-sided heart; dex-trocardia denotes a right-sided heart; and mesocardiadenotes a midline heart.

Cardiac displacement is the shifting of the heart within thethorax by extracardiac factors such as a hypoplastic lung.This has also been referred to in the literature as dextro-position, mesoposition or levoposition, depending on thedirection of the shift.

Inversion is an alteration in the lateral relationships ofasymmetric body structures so that a structure which nor-mally lies on the right side of the body is situated on the leftand vice versa. Inversion may involve the entire body (situsinversus) or only certain structures such as the great arteries.Heterotaxy is abnormal arrangement of organs different

from the orderly arrangement of either situs solitus or situsinversus, e.g., malrotation of bowel.

Transposition means that the aorta arises from themorphologic right ventricle (RV), and the pulmonary arteryfrom the morphologic left ventricle (LV). With rare excep-tions,2 there is aortic-mitral discontinuity. The aorta isusually anterior to, but may be lateral to, the mainpulmonary artery.

Single L V or single R V is a situation in which one ventri-cle receives the entire portion of both atrioventricular valvesor a common atrioventricular valve. This also has beentermed double inlet left ventricle or double inlet right ventri-cle.Double outlet right ventricle (DOR V) denotes both great

arteries arising from the morphologic right ventricle.Usually neither semilunar valve has continuity with themitral valve (subaortic and subpulmonic conus).Double outlet left ventricle (DOL V) denotes both great

arteries arising from the morphologic left ventricle. The co-nus anatomy in this situation is variable but is usuallybilate.rally deficient.

It should be noted that as used herein DORV differs fromthe broader use proposed by Lev,' i.e., aorta and pulmonaryartery completely or almost completely arising from theright ventricle regardless of semilunar valve mitral con-tinuity. The latter definition focuses entirely on the positionof the great arteries. As such it includes cases of tetralogywith severe overriding of the aorta and excludes those casesof Taussig-Bing anomaly in which a substantial portion ofthe pulmonary artery overrides the left ventricle.6

General Features of Cardiac Anatomy

In describing an anatomic cardiac complex, threesegments must be considered: 1) the total body configura-tion or situs, including the atria; 2) the ventricular positions

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and connections to the atria; 3) the positions of the greatarteries and connections to the ventricles.

Anatomic Features of Body Configuration or Situs

Although many paired structures of the body are normallysymmetrical (e.g., brain, kidneys, ureters), several pairedviscera are asymmetric (e.g., tracheobronchial tree, lungs,atria). The liver, although a solitary organ, has two unequallobes. Solitary structures, such as the spleen and gastroin-testinal tract, have a specific rightward-leftward orientationwithin the abdominal cavity. The positions of these asym-metric structures express the situs or body configuration ofan individual. Classically, these have been divided into twoasymmetrical body configurations: 1) situs solitus or conven-tional normal, and 2) situs inversus or complete inversion(fig. 1). In situs solitus, the right lung has three lobes and aneparterial bronchus while the left has two lobes and ahyparterial bronchus. The larger lobe of the liver is on theright and the stomach and spleen are on the left. Themorphologic left atrium is posterior and leftward. In situs in-versus, the left lung has three lobes and the right lung hastwo. The tracheobronchial tree and atria are similarly in-verted. The larger lobe of the liver is on the left while thestomach and spleen are situated on the right.

In addition, two symmetrical body configurations havebeen found to be associated with splenic anomalies. Aspleniasyndrome is characterized by bilateral right-sidedness orduplication of right-sided structures6 10 including bilateralright lungs with bilateral eparterial bronchi. Both atriamorphologically resemble right atria, the liver issymmetrical and horizontal and the stomach tends to be near

C Asplenia it..Polysplenia

FIGURE 1. A natomic features of thoracic and abdominal organs

in each of the body configurations. Organs outlined in dots showvariation in position.

the midline. Polysplenia syndrome is characterized by atendency toward bilateral left-sidedness 11, 12 which may in-clude bilateral left atria and bilateral left lungs with bilateralhyparterial bronchi. The latter is the most constant featureof symmetry.'2 The abdominal organs tend less towardsymmetry than in asplenia. Although the liver may have tworoughly equal halves, the major portion often lies to one sideof the abdomen. Similarly, the stomach is seldom midlineand considerable abdominal heterotaxy is often present. Themultiple spleens in this condition are situated adjacent to thestomach and usually resemble a cluster of grapes or a bi-lobed or tri-lobed spleen. In a given case, the size of the in-dividual spleens may vary but each is much smaller than anormal spleen. This is in contrast to accessory spleenswherein one or more spleniculi are present in addition to anormal-sized spleen. The absence of a spleen or the presenceof multiple spleens also may be regarded as additionalmanifestations of the bilateral right-sidedness or left-sidedness, respectively.'2 Although there may be someoverlap of the anatomic features of asplenia and polyspleniasyndromes, the differences are considerably more frequentand are sufficiently consistent to warrant designations asseparate body configurations.

Cases of isolated absence of the spleen, i.e., withoutassociated visceral and cardiac anomalies, are hereinregarded as not having the developmental complex ofasplenia syndrome.

Anatomic Features of Cardiac Chambers

The morphologic features of right and left atria are listedin table 1. Van Praagh has stated that the atria follow thebody situs; however; he designated the atria and situs ofasplenia as uncertain.13, 14 In our experience, themorphologic atria conform to the situs even in cases ofasplenia or polysplenia, i.e., bilateral morphologic right atriain asplenia and a distinct tendency toward bilateral left atriain polysplenia. The atrial symmetry has also been reportedby Van Mierop.6' 12The morphologic features of right and left ventricles are

listed in table 1 and illustrated in figure 2. When themorphologic right ventricle is situated on the right and themorphologic left ventricle is situated on the left, the ven-tricles are considered to be noninverted and the result of ad-bulboventricular loop.'4 Conversely, when the morphologicright ventricle is on the left and the morphologic left ventricleis on the right, the ventricles are considered to be invertedand the result of an I -bulboventricular loop.14 Regardless ofwhere the morphologic right ventricle lies, the infundibulumis almost always the most anterior cardiac structure and con-nects with the anterior great artery. The left ventricular out-flow tract lies posterior to the infundibulum and connectswith the posterior great artery. The terms noninversion andinversion of the ventricles correspond to the d- and I-loops inthe nomenclature of Van Praagh."4The atrioventricular valve of each ventricle is

characteristic of that ventricle. While the atrioventricularnode and the initial segment of the bundle of His lie in theright atrial wall, the branches of the bundle follow therespective ventricles.'5'IA d-loop is normal for situs solitus and an 1-loop for situs

inversus. Van Praagh termed these concordant loops.

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CARDIAC MALPOSITIONS/Stanger, Rudolph, Edwards

TABLE 1. Anatomic Features of Cardiac Chambers*Morphologic right Morphologic left

Atria Lies on same side as trilobed lung. Lies on same side as bilobed lung.Receives the inferior vena cava.Crista terminalis.Pectinate muscles in the atrial Trabeculated appendage but without

appendage. parallel muscles of pectinate type.Fossa ovalis lies on the right side of the Interatrial ostium II on the left side of

atrial septum. atrial septum.

Ventricles Tricuspid valve. Mitral valve.Trabeculated septum with coarse, Smooth walled septum with fine,

parallel trabeculations. oblique trabeculations in apex.Crista supraventricularis separates Fibrous continuity between mitral and

tricuspid and semilunar valves. semilunar valves.Papillary muscle of the conus. No septal papillary muscles.Right branch of the bundle of His. Left branch of the bundle of His.

*The above anatomic features are the usual for the atria and ventricles. Individual chambers may lack one or more of the usualfeatures and identification of the chamber is presumptive and based on how many of the features are present. In rare cases identifi-cation may be impossible.

Discordant loops are an I-loop in situs solitus and a d-loop insitus inversus. With rare exceptions,17 discordant loops areassociated with abnormally related great arteries. We havechosen to designate all cases of splenic anomalies as havingdiscordant loops because symmetry of the atria, by defini-tion, precludes connection with the appropriate morphologicventricles.

Anatomic Features of the Great Arteries

The anatomy of the great arteries may best be defined interms of their lateral interrelationships and ventricular at-tachments. Normally attached great arteries are char-acterized by the pulmonary artery arising from the right ven-tricle and the aorta from the left ventricle. In this situation,the origin of the pulmonary artery lies anterior to the originof the aorta. As the infundibulum is longer than the left ven-tricular outflow tract, the pulmonary valve is usually morecephalad than the aortic. In transposition of the greatarteries, the origin of the aorta usually lies anterior to that ofthe pulmonary artery and arises from the infundibulum. As aresult, the aorta is the more cephalad semilunar valve andthere is no fibrous continuity between the aortic and mitralvalves. The latter was considered by some authors an essen-tial feature of transposition;18 however, exceptions have beenfound.2The lateral interrelationships of the great arteries are best

described using "d" and "I" terms. With "d" related greatarteries, the ascending aorta sweeps toward the right and liesto the right of the main pulmonary artery. With "I" related

great arteries, the ascending aorta sweeps to the left and liesto the left of the main pulmonary artery. These lateralrelationships apply to normally related great arteries,transposed great arteries, and to situations in which bothgreat arteries arise from one ventricle. In addition, there aretranspositions in which the aorta lies directly in front of thepulmonary artery, a situation which has been designated asa-trans (for anterotransposition).'9

Nomenclature

The original Van Praagh nomenclature", 20 has been par-ticularly useful in describing complex cardiac anatomy andin focusing attention on the embryological development ofcomplex anomalies. Certain exceptions, however, did notconform to the loop rule and made use of the original VanPraagh nomenclature in these cases difficult, e.g., situssolitus with complete transposition but with the greatarteries in the I-transposition configuration. Thenomenclature was subsequently enlarged so that in situationswhere the great artery interrelationship might be confused bythe designation d- or 1-transposition and in double outletright ventricle, the term d- or 1- malposition was used.21 22

More recently, Van Praagh has introduced anomenclature modified from the original. The modificationis an entirely symbolic representation of the basic cardiacstructure, designating the situs, ventricular interrelation-ships and great artery interrelationships in that se-quence.23' 24 Although the symbolic representation mayprove quite useful for pediatric cardiologists and cardiac

FIGURE 2. Diagrammatic representation of thefeatures of morphologic right (RV) and left ven-tricles (LV). SL septal limb of the crista supra-ventricularis, PL parietal limb, PMC = papillarymuscle of the conus, PA = pulmonary artery,S -septal tricuspid leaflet, MS membraneousseptum, Ao Aorta, AM = anterior mitral leaflet.

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pathologists, we find it of limited value in trying to convey in-formation to other physicians who may also be involved inthe patient's care - surgeons, house officers, referringphysicians, etc. Each physician requires a lengthy explana-tion of both the anatomy and the "code," a quantum of in-formation which may not be readily absorbed in a singlesitting.

Consequently, we have sought to use Van Praagh'ssegmental approach but to modify it so that a) existing,easily understood terms are used; b) only a few terms are ab-breviated and each abbreviated term is self-explanatory; c)the terms describe the interrelationships within a given seg-ment as well as connections with the previous segment. Theterms used are:

Situssolitusinversusaspleniapolysplenia

Ventriclesd- or 1-loopd- or 1-single RVd- or 1-single LV

Great Arteriesd- or 1-normald- or 1- or a-transd- or l-DORVd- or I-DOLVd- or 1-malpositiontruncus

The segmental set is written as follows: situs/ven-tricles/great arteries, e.g., inversus/d-loop/d-trans.The situs portion of the segmental set implies the atrial

anatomy since there is visceroatrial concordance even incases of asplenia or polysplenia.The ventricular segment includes three terms which

describe three distinct aspects of ventricular anatomy; i.e.,ventricular interrelationships, the connections to the atriaand the position of the ventricular portion of the heart withinthe thorax. As in the Van Praagh nomenclature, a "d"-symbol indicates that the morphologic right ventricle lies tothe right of the morphologic left ventricle, while an "1"-

symbol indicates that the morphologic right ventricle lies tothe left of the morphologic left ventricle.The second term in the ventricular designation has been

modified from the original Van Praagh nomenclature inorder to permit description of the atrial connections. If thereare two ventricles and atrial-ventricular connections are ofthe simple type, i.e., right-sided atrium to right-sided ventri-cle, and left-sided atrium to left-sided ventricle, then nomodification is necessary and the terms d-loop or I-loop areused. These designations are also used for cases in which oneof the atrioventricular valves straddles the ventricular sep-tum. If, however, both atria connect to one ventricle this isdesignated as d or 1-single LV or RV. The third portion ofthe ventricular segment describes the position of the ventric-ular portion of the heart within the thorax. The latter mayvary considerably for a given bulboventricular loop in agiven situs, e.g., a d-loop in situs solitus may have the ven-tricular portion of the heart in the right hemithorax (R), lefthemithorax (L), or in midline (M) (fig. 3). The variable posi-tion within the thorax is the result of varying degrees ofpivoting of the bulboventricular loop toward the oppositehemithorax in early fetal development. Normally, a d-bulbo-ventricular loop pivots into the left hemithorax. Failure tocomplete this pivoting is particularly common with discor-dant loops. Clearly, the positional term may be deleted if theventricular position is appropriate for the type of bulbo-ventricular loop, e.g., left hemithorax for a d-loop and righthemithorax for an 1-loop.The great artery attachments to the ventricles may be

described as normal (pulmonary artery from RV, aorta fromLV), transposition (aorta from RV, pulmonary artery fromLV), DORV (double outlet right ventricle), DOLV (doubleoutlet left ventricle), truncus (truncus arteriosus) ormalposition21' 22 (a nonspecific term indicating an abnormalspatial relation between the aortic and pulmonary valves).Each of these is designated d- or 1- to indicate the lateral in-

solitus / d-loop (R) solitus / d- loop (M) solitus / d - Ioop (L)

solitus / -loop (R) solitus/1-loop (M) solitus / I-loop (L)

FIGURE 3. Diagram ofcardiac positions with concordant and discordant bulboventricular loops. A 11 six diagrams areof situs solitus. A, B and C each have concordant loops (d-loops); however, in A the heart is in the right hemithoraxbecause offailure of the bulboventricular loop to pivot into the opposite hemithorax. B) Midline heart associated withpartial pivoting. C) Complete pivoting into the left hemithorax, i.e., normal cardiac position for d-loop in situs solitus.D,E and F each contain discordant loops (I-loops) with complete, partial and no pivoting, respectively. Concordant loopswith partial pivoting and a sagitally oriented ventricular septum tend to show mesocardia. In contrast, discordant loopswith partial pivoting and a sagittally oriented septum are often moreprominent on the side ofthe morphologic right ven-tricle.

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terrelationships of the great arteries. In cases of transposi-tion of the great arteries in which the aorta lies directly infront of the pulmonary artery and there is no clear d- or1-relationship, the designation a-trans (for anterotransposi-tion) is used. The great artery lateral interrelationships neednot correspond to the bulboventricular anatomy, e.g., a

d-loop may be associated with great arteries in the 1-posi-tion.The following are examples of the use of this

nomenclature in complex cardiac lesions.1) Taussig Bing: solitus/d-loop/d-DORV with sub-

pulmonic VSD.2) Corrected transposition in situs inversus: inversus/

d-loop/d-trans.3) Complete transposition in situs solitus with 1-posi-

tioned great arteries (an exception to the loop rule): soli-tus/d-loop/l-trans.

4) Complicated double outlet right ventricle (situs solituswith ventricular inversion and double outlet right ventricle):In this example, the d-prefix indicates that the aorta arises tothe right of the pulmonary artery: solitus/l-loop/d-DORV.

Obviously, in each of these cases the associated malforma-tions (VSD, ASD, stenosis, etc.) must be described. If theconus anatomy is the usual for a given great artery attach-ment, no special mention is made.The great majority of patients do not have complex car-

diac anomalies or cardiac malposition. Consequently,segmental designation is unnecessary in patients with a com-

bination of situs solitus, a d-loop and levocardia. If, however,any aspect of cardiac malposition is present, or there is ab-normal connection of the ventricles to the atria or greatarteries, the entire designation is used.

Clearly, no nomenclature can be all encompassing. Rareand bizarre cases such as the criss-cross hearts described byAnderson et al.2' require special descriptions. Although theseauthors favored the terms discordant and concordant ven-

tricles as proposed by Kirklin and coworkers,2' such termsare not applicable in the splenic syndromes since thesymmetrical atria preclude concordance.We favor our method of describing cardiac anatomy

because it uses only a few self-explanatory abbreviations andis quite descriptive. House officers and others not well versedin complex cardiac anatomy can understand it after only a

brief explanation.

Pathologic Material

Sixty-five necropsy specimens exhibiting cardiac malposi-tion were found among approximately 3,000 specimens inthe Cardiovascular Registry of the United Hospitals, MillerDivision, St. Paul, Minnesota. A summary of the bodysituses and the cardiac positions may be found in table 2. Theanatomic features of the 65 cases with malposition are listedin table 3. The tabulation includes the situs and the structureof the cardiac chambers and great arteries as well as theassociated intracardiac and vascular anomalies. It is ap-

parent from table 3 that each situs is associated with a

relatively small number of structural complexes but that theassociated intracardiac and vascular anomalies varymarkedly.

In most cases the lung fissure patterns were those expected for

the situs. There were, however, sufficient variations due to in-complete and/or accessory fissures to make this an un-reliable method of assessing lung morphology. In contrastthe pulmonary arterial - tracheobronchial interrelation-ships almost always reflected the situs. This interrelation-ship and bronchial branching patterns were also used indetermining the number of lobes.

Situs Solitus

There were twelve cases of dextrocardia in situs solitus.Six of these cases exhibited the normal cardiac complex ofsitus solitus, i.e., noninversion of the ventricles and normallyconnected great arteries (solitus/d-loop/d-normal). Dextro-cardia in five of these cases was the result of displacement ofthe heart (dextroposition) associated with a hypoplasticor absent right lung. The sixth case exhibited dextrorotation(solitus/d-loop (R)/d-normal). Associated cardiacanomalies were found in four of these six cases.The remaining six cases exhibited ventricular inversion

and transposition of the great arteries (solitus/l-loop (R)/1-trans) or corrected transposition in situs solitus. In additionto the six cases of corrected transposition in situs solitus withdextrocardia, there were nineteen cases of corrected trans-position with levocardia, i.e., without malposition, a dis-tribution similar to that in previous reports.262' Ventricularinversion is a feature common to all cases of correctedtransposition in situs solitus; however, the presence of dex-trocardia or levocardia appears related to the degree ofpivoting of the bulboventricular loop. The latter may best becharacterized by the orientation of the ventricular septum.When dextrocardia was present, the ventricular chambersand septum were oriented in typical inverted fashion as il-lustrated in figure 4A- 1. The ventricular septum lay orientedtoward the right in a plane midway between coronal andsagittal, and the aorta was medially situated. With levocar-dia, the ventricles were incompletely pivoted and oriented asin figure 4A-2 with the septum perpendicular or nearlyperpendicular to the coronal plane. The aorta was displacedtoward the left and formed the shoulder seen in chest roent-genograms. The greater portion of the heart lay in the lefthemithorax and the apparent cardiac "apex" was formed bythe lateral convexity of the morphologic right ventricle. Theabove represent the two most common orientations of theventricles and ventricular septum, and were the only types inthis series; however, other forms have been described2' (seefig. 3).

Situs Inversus

There were thirteen cases of situs inversus which includedeight with concordant loops. Of these, three had normalhearts (inversus/l-loop/l-normal), three had double outlet

TABLE 2. Cardiac Position and Situs in Approximately 3000Specimens

Situs Dextrocardia Mesocardia Levocardia Malposition

Solitus 12 '3000 12Inversus 11 2 13Asplenia 11 7 5 23Polysplenia 9 8 17Total 65

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TAiBLE 3. Anatomic Featurcs

Case Cardiac _ Cardiovascular anomalies per lungno. \ge Sex Segmental set position SVC APVC Other R L Miscellaneous

solituis / d-loop (L) / d-normalsolitus / d-loop (L) / d-normal

solitus / d-loop (L) d-normalsolitus / d-loop (L) d-normalsolituis / d-loop (L) / d-normal

solitus / d-loop (R) / d-normal

solitus / 1-loop (R) / I-transsolitus / 1-loop (R) / 1-trans

solitus / I-loop (R) / 1-transsolitus / 1-loop (R) / I-transsolitus / 1-loop (R) / I-trans

solitus / 1-loop (R) / 1-trans

Situs SolitusR** RR** R Total

R** R (i2(RSVC)

R** RR** R

R R

R RR R

R RR RR RQ

R R

Tricuspid atresia, bifid apex

VSD, ASDAnomalous LPA from RPAPDA

VSD, inf. PS., anomalousufmbilical vein

VSD, ASD, pulm. atresiaVSD, subpulm. atresia,

Valvar PSVSDSubvalvar PS, cleft mitralCor triatriatum, MultipleVSDs

VSD, ASD, subvalvar PS,PDA

3 212

23 23 2

3 2

3 23 2

3 2

3 2

3 2

Hypoplastic R lungHypoplastic R lung

Absent R lungR bronchusuisHypoplastic R lung,L lobar emphysema

Juxtaposed atrialappendages

inversus / 1-loop (R) / 1-normalinversus / 1-loop (R) / I-normalinversus / l-loop (R) / 1-normalinversus / 1-loop (R) 1-DORVinversus / 1-loop (R) 1-DORVinversus / I-loop (R) /I-DORVinversus / 1-loop (R) / 1-transinversus / I-loop (R) / 1-transinversus / d-loop (R) / d-DORVinversus d-loop (L) / d-DORV

inversus d-loop (R) / d-trans

inversus / d-loop (L) / d-transinversus

/ d-loop (R) /d-trans

asplenia / 1-loop (R) /1-DORVasplenia / 1-loop (R) /1-DORV

asplenia / 1-loop (M) / 1-transasplenia I-loop (R) / 1-transasplenia / I-loop (R) /1-transasplenia / l-loop (R) / l-trans

asplenia / 1-loop (R) / I-transasplenia / 1-loop (R) / 1-trans

asplenia / I-loop (M) / 1-trans

asplenia / 1-loop (M) /1-DORVasplenia / d-loop (L) / d-DORV

asplenia / d-loop (L) / d-transasplenia / d-loop (R) / d-trans

asplenia / d-loop (R) / d-transasplenia / d-single LV (L) / d-trans

asplenia / d-single LV (R) / d-trans

asplenia / d-single LV (R) / d-trans

asplenia / d-single LV (L) / d-normal

asplenia / I-single LV (M) / 1-trans

RRRRRRRRRL

R

LR

RR

M

RRR

RR

M

M

L

LR

RL

R

R

L

M

Situs InversusLLLL

LLL

L

L

LL

AspleniaLL

R L

RLRR L

R LR L

R L

R LR L

R LR L

R LRL

L

RL

R L

TotaltTotal(LSVC)

PartialTotal§Total

(RSVC)

Total(LSVC)

Total(RSVC)

Total(RSVC)

Total(RSVC)Total(LSVC)Total

(LSVC)Total(RA)

Primary pulm. hypertension

VSD, ASD, PDAVSD, valvar and inf. PSVSD, valvar and inf. PSASDVSD, PDAAV canalVSD, ASD, PDA, valvar and

subvalvar PSASD, subvalvar PS,

subvalvar ASVSD, ASD, PSVSD, pulm. atresia, PDA

AV canalAV canal, inf. PS,

AV canal, pulm. atresia,AV canal, pulm. atresia,AV canal, pulm. atresiaAV canal, pulm. atresia,

AV canal, pulm. atresia,AV canal, PS, cor

triatriatumAV canal, pulm. atresia,PDA,

AV canal, PS,AV canal, mild PS,

AV canal, PS,AV canal, pulm. atresia,

AV canal, PS,AV canal, pulm. atresia,PDA,

AV canal, PS, PDA,

AV canal, no PS, subvalvarAS, bilateral PDAs

AV canal, PS,

AV canal, PS, cortriatriatum - mild

2 3

2 32 32 32 32 32 32tt 3tt2 3 Bilateral eparterial

bronchi2 3

2 32 3 Accessory spleen

33

333

3

3

33

33

33

3

3

3

3

33

33

3

3

3

33

33

33

3

3

3

3

Rudimentary spleen

Bilateral bronchosuis

right ventricle (inversus/l-loop/l-DORV), and two hadtransposition of the great arteries in situs inversus(inversus/l-loop/l-trans). There were five cases of situs inver-sus with discordant loops. Three of these had correctedtransposition of situs inversus (inversus/d-loop/d-trans) andtwo had double outlet of the noninverted right ventricle insitus inversus (inversus/d-loop/d-DORV). Those cases withconcordant loops all exhibited dextrocardia, i.e., cardiacposition appropriate for that situs. The cases with discordantloops demonstrated variation in cardiac position. The com-

bination of situs inversus and a d-loop may be regarded as a

mirror image of situs solitus with an 1-loop, and similar butinverted anatomic features were found.When the discordant ventricles were associated with com-

plete pivoting, the cardiac apex was in the hemithorax op-

posite to that appropriate for the situs. In these cases theventricular septum was oriented toward the apex (fig. 4A-1

and B- 1). With incomplete pivoting, the ventricles were

separated by a septum oriented in the sagittal plane, the ap-

parent apex was formed by the convexity of the morphologicright ventricle, and the characteristic shoulder was formedby the aorta and infundibulum (fig. 4A-2 and B-2). Note thatin situs inversus the shoulder is on the right side as one mightexpect.

Asplenia

There were 23 cases of asplenia in the present series; 11

with dextrocardia, seven with mesocardia, and five with levo-cardia. All were regarded as cardiac malpositions as no ap-

propriate cardiac position could be assigned in a

symmetrical situs.There were 21 specimens in which lungs were attached and

each showed bilateral eparterial bronchi and bilateral right

2

45

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23

2425

2627

28293031

3233

34

3536

3738

3940

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42

43

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35y40y65ygd7y

45y10d

7m2y

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No. lobes*Case Cardiac Cardiovascular anomalies per lungno. Age Sex Segmental set position SVC APVC Other R L Miscellaneous

45 2m F asplenia / 1-single LV (M) / 1-trans M R L Total AV canal, PS, 3 3(RSVC)

46 4w M asplenia / 1-single LV (M) / 1-trans M R L AV canal, PDA, no PS 3 347 33d F asplenia / 1-single LV (L) / 1-trans L R L Total AV canal, PS, 3 3

(RSVC)48 3w M asplenia / 1-single LV (M) / 1-trans M R L Total AV canal, Ps 3 3

(LSVC)Polysplenia

49 9y M polysplenia / d-loop (R) / d-normal R R Partial ASD, PDA, 2 2 R bronchusuis50 7y M polysplenia / d-loop (L) / d-normal L R PS, primum ASD, sub AS 3ft 2tf51 27d F polysplenia / d-loop (L) / d-normal L R L Partial AV canal, ASD, PDA, sub- 3 3 Common atrium

valvar AS, inter. IVC52 2d F polysplenia / d-loop (L) / d-normal L R L Partial ASD, aortic atresia, 2tt 2tt53 18y F polysplenia / d-loop (R) / d-normal R R L Partial ASD, subvalvar AS, 2 2 Common atrium54 16h F polysplenia / d-loop (R) / d-normal R R Partial ASD 2 255 2m M polysplenia / d-loop (R) / d-normal R R Partial VSD, ASD, interrupted IVC 2 256 2m M polysplenia / d-loop (L) / d-DORV L R Total VSD, ASD, interrupted IVC 2 257 3m M polysplenia / d-loop (L) / d-DORV L R L Partial VSD, ASD, interrupted IVC 2 258 4w M polysplenia / d-loop (R) / d-DORV R L Partial VSD, ASD, PDA, coarct, 2 2

interrupted IVC59 low F polysplenia / d-loop (L) / d-DORV L R L Partial AV canal, ASD, PDA, 3 3

subvalvar AS60 5y M polysplenia / d-loop (L) / d-trans L R L Total VSD, AS cleft mitral, 2 2

sub PS61 18m M polysplenia / 1-loop (R) / 1-normal R L Partial ASD, PDA, VSD, 2 2

interrupted IVC62 lm F polysplenia / I-loop (L) / 1-normal L R Total AV canal, ASD, PDA, 2 2

interrupted IVC63 ld F polysplenia / l-loop (R) / I-normal R R L Total AV canal, ASD, PDA, 2 2

cor triatriatum64 3'y F polysplenia / 1-loop (R) / 1-normal R L VSD, interrupted IVC, 5ff 3ff

coarct65 10y F polysplenia / I-loop (R) / I-DORV R L Partial AV canal, interrupted IVC, 2 2

ASD

*Lung morphology as determined not only by fissure pattern but by bronchial branching patterns and relationships with pulmonary arteries.**Cardiac displacement due to extracardiac forces.tRUPV to innominate vein; remaining pulmonary veins connect to portal vein.§Connect to mesenteric vessels.ftFrom necropsy report. Lungs and tracheobronchial tree not available for inspection.Abbreviations: VSD = ventricular septal defect; ASD = atrial septal defect; PDA = patent ductus arteriosus; PS = pulmonic stenosis; AS = aortic

stenosis; Pulm = pulmonary; AV canal = atrioventricular canal; IVC = inferior vena cava; SVC = superior vena cava; RPA = right pulmonary artery;LPA = left pulmonary artery; R = right; L = left;®orr'D = right or left superior vena cava connecting to coronary sinus. If no circle the superior venacava connects to the ipsilateral atrium.

bronchial branching patterns. Fissures were a less reliable in-dicator of lung symmetry since not all lungs externallyshowed a bilateral right pattern.The cardiac anomalies associated with asplenia were: a)

anomalous systemic venous connection; b) large atrial septaldefect; c) atrioventricular canal; d) common ventricle orlarge ventricular septal defect as part of the A-V canal; e)transposition of the great arteries; f) severe pulmonicstenosis or atresia; g) anomalous pulmonary venous connec-tion; and h) cardiac malposition.

In all cases, both atria bore resemblance to right atria(right atrial isomerism). Two large interatrial communica-tions were commonly found. The first was an atrial septaldefect of the foramen ovale type. The fossa ovalis (a rightatrial structure) was usually present; however, the valve ofthe foramen ovale (a left atrial structure) was absent. Thesecond interatrial communication was the atrial portion ofthe complete atrioventricular canal. Both defects were usu-ally quite large with only a strand of septal tissue separatingthem so that functionally there was a common atrium (fig. 5).

There were two ventricles in 14 cases and a single ventriclein nine cases. All cases had a complete atrioventricular(A-V) canal. When two ventricles were present, the intra-ventricular portion of the A-V canal was sufficiently large toresult in a hemodynamic common ventricle with a rudimen-tary septum. When two ventricles were present, there wascommonly inversion of the ventricles (nine of fourteencases).

Severe pulmonic stenosis or atresia was found in all buttwo cases and was usually of both the subvalvar and valvar

types. Transposition of the great arteries was found in 19cases, double outlet right ventricle in three cases, and nor-mally related great arteries in only one case.Anomalous systemic venous connection was also a com-

mon feature. Twenty cases exhibited bilateral superior venacavae and in each case right and left superior vena cavae con-nected directly to their respective atria. The inferior venacava terminated in either atrium.

Anomalies of pulmonary venous connection occurred in16 of the 23 cases of asplenia. The majority of these weretotal anomalous pulmonary venous connection. The sites ofconnection of the anomalous pulmonary veins were the por-tal system or a superior vena cava, i.e., anastomoses withvessels derived from the umbilicovitelline or anterior car-dinal systems, respectively.

Thirteen of the cases of asplenia in the present series (cases28-33, 35, 37, 40, 43-45 and 48) have been reportedpreviously.9

Polysplenia

There were 17 cases of polysplenia in the present series;nine with dextrocardia and eight with levocardia.Some, if not all, of the features of bilateral left-sidedness

were found in each case. These included a tendency towardbilateral left atria and bilateral left lungs. There were 14specimens in which the lungs were available and 12 showedbilateral hyparterial bronchi and bilateral left bronchialbranching patterns. The remaining two specimens showedbilateral eparterial bronchi and bilateral right bronchial

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B Situs Inversus

6 cases

(9 cases) 3 cases

FIGURE 4. Cardiac position in situs solitus and situs inversuswith discordant loops. The orientation of the ventricular septum isclosely related to cardiac position. When the ventricular septum isin the sagittal plane, the right ventricular outflow tract and ascend-ing aorta form the characteristic shoulder deformity (A2, B2).

branching patterns. Lung fissures varied somewhat but inmost cases were of the bilateral left pattern. As in theasplenia group, lung fissures were less reliable thanpulmonary artery-bronchial relationships in evaluating lungsymmetry. The abdominal organs displayed less symmetrythan in asplenia; malrotation of the bowel was present in atleast three cases.

The cardiovascular manifestations of polysplenia in-cluded: a) anomalous systemic venous connection; b)anomalous pulmonary venous connection; c) atrial septaldefects; d) ventricular septal defects; e) double outlet rightventricle; f) left-sided obstructive lesions; and g) cardiacmalposition. In contrast to asplenia, transposition of thegreat arteries and pulmonic stenosis were unusual.

Anomalies of the systemic venous drainage may involvethe superior and/or inferior vena cavae. In eight cases ofpolysplenia, bilateral superior vena cavae connected directlyto their respective atria, while in two cases the secondsuperior cava connected to the coronary sinus. Nine cases

also exhibited interruption of the hepatic portion of the in-ferior vena cava with drainage into a superior vena cava bythe hemiazygos or azygos system. When interruption of theinferior vena cava was present, the hepatic veins draineddirectly into one or both atria. The atrium into which the in-ferior vena cava drained, either directly or by the azygos

system, received most of the systemic venous return and we

have designated this the systemic venous atrium.Often both atria morphologically resembled left atria (left

atrial isomerism) and each contained a smooth-walled atrialappendage. Both sides of the atrial septum frequently boreresemblance to the normal left atrial aspect of the atrial sep-

tum (septum primum) and in these cases the foramen ovalewas absent (fig. 6).Anomalous pulmonary venous connection was found in 15

cases. Eleven were partial with the right pulmonary veinsconnecting directly to the right-sided atrium. There were

four cases of total anomalous pulmonary venous connectionand in each the veins connected with the systemic venous

atrium directly or through a confluens.Defects of the atrial and/or ventricular septum were pres-

ent in all 17 cases of polysplenia. There were 12 specimenswith ventricular communications; in five the ventricular sep-

tal defect was part of an atrioventricular canal and in seven itwas a discrete lesion. Fifteen specimens had one or more

defects of the atrial septum. In one the defect was of the os-

tium primum type, and in two the atrial septum was com-

pletely lacking. Twelve specimens exhibited atrial septaldefects which were the result of fenestrations or deficiencies

FIGURE 5. Photograph of atrial septum in asplenia. A) Right atrial view. B) Left atrial view. Two large defects are

present. ASD = secundum atrial septal defect, ECD = atrial portion of a large endocardial cushion defect. A thin

strand of muscle separates the two defects

A. Situs Solitus

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FIGURE 6. Photograph of the atrial septum in polysplenia. A) Right atrial view. B) Left atrial view. The fossa ovalis is ab-sent.

in the valve of the foramen ovale and/or absence of both lrm-bi of the fossa ovalis. Seven cases also had patency of theductus arteriosus. The above communications, as well as theanomalous pulmonary venous connections, are lesionswhich, in the absence of pulmonary stenosis, would result inpulmonary overcirculation.Pulmonic stenosis was uncommon, being found in only

two cases. In contrast, left-sided obstructive lesions werecommon. There were five cases with aortic outflow obstruc-tion and two with aortic coarctation.

Twelve of the cases of polysplenia in the present series(cases 49-52, 56, 57 and 60-65) have been reportedpreviously.'1

Discussion

The anatomic findings in the present series were verysimilar to those of Lev and associates30 and Van Praagh andassociates,'4 although neither study classified polysplenia asa distinct situs. Tetralogy of Fallot with cardiac malpositionwas virtually absent in both these series as well as in ourcases. This differed considerably from the earlier work of Ar-cilla and Gasul' which reported seven cases of tetralogy;however, only two of their seven cases of tetralogy were ex-amined at necropsy. It is possible that some of the cases oftetralogy may have had ventricular inversion (i.e., "correctedtransposition" with pulmonic stenosis and ventricular septaldefect).The large proportion of cases of malposition associated

with splenic anomalies is noteworthy and is in agreementwith the findings of others.'3 80, 1' It is quite likely that manyof the cases previously reported as "mixed situs or "in-complete situs inversus" were, in reality, examples of splenicanomaly syndromes, particularly polysplenia.The findings in the asplenia and polysplenia cases are

similar to those reported by Van Mierop"2 and Rose and co-workers;32 however, the latter reported an unusually high in-cidence of pulmonary outflow obstruction in polysplenia(four of 12 cases). Pulmonic stenosis was present in only twoof 17 cases in the present series. In contrast, seven of 17 casesin the present series showed aortic outflow obstruction orcoarctation.

Ivemark reported four cases of type IV truncus arteriosusin association with asplenia;33 truncus was not present in any

of the asplenia cases in this series as well as others.'4' s 31

The high incidence of cardiac anomalies in cases of situsinversus (11 of 13 cases) exceeded that found by Arcilla andGasul3' and contrasted sharply with the findings of Keith andco-workers," Grant,33 and Torgersen."3 The latter study wasbased, in part, on screening chest roentgenograms of personsover 15 years of age and excluded cases with severeanomalies which caused an early death. The present necrop-sy study is probably weighted to the opposite extreme. Thetrue incidence of cardiac anomalies in situs inversusprobably lies somewhere in between.

Similarly, the incidence and severity of congenital cardiacanomalies associated with polysplenia is probably greater innecropsy series than in catheterization series. Although therewere no cases of polysplenia without cardiac anomalies inthe present series, the authors have catheterized two patientswith probable polysplenia, dextrocardia, an interrupted in-ferior vena cava and no intracardiac anomalies. Individualswith polysplenia, levocardia and no intracardiac anomaliesmight not even come to a physician's attention.

Clinical Correlates of Anatomic Features

Identifying the Situs

The situs of the individual patient is best determined bychest and abdomen roentgenograms with additionallaboratory studies (table 4).

In situs solitus, the viscera are normally situated while insitus inversus inverted viscera are evident. In asplenia, theabdominal viscera are very symmetrical with a horizontalliver and a stomach bubble which tends to lie toward themidline."0 In polysplenia, the tendency toward symmetry isalso present but is not as striking as in asplenia. As bothlungs are often bilobed in polysplenia, the presence of aminor lobe fissure on chest roentgenograms is strongevidence against polysplenia. In contrast, the finding of theupper abdominal portion of the aorta on the side oppositethe stomach is strong evidence for polysplenia.37 Roentgeno-grams showing the symmetrical bronchial patterns in thesplenic anomaly syndromes have also been helpful."Malrotations of the bowel are common in both asplenia andpolysplenia.Y9 Radioisotopic scanning may demonstrate ab-sent or multiple spleens.2" 40, 41

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TABLE 4. Clinical and Laboratory Features of the Four Body Configurations

Presenting symptoms

Roentgenograms -

Abdomen

ChestMinor fissuresPattern of bronchiVascularity

P axis in ECG

MiscellaneousHeinz or Howell Jolly

bodiesBiliary atresiaSpleen scan

CatheterizationSVcInterrupted IVCAPVC

Pulmonary arterialinterrelationship tobronchi

Solitus

Varies

Normal

RNormalVaries

Inversus Asplenia

Varies Cyanosis (-95%)CHF (-5%)

Inverted Horizontal liverMidline stomachMalrotation

LInvertedVaries

/

R,LBilat. rightUsually increased

\,, and/or /

+

L

R

Normal

R

L

Absent

Usually bilat.

To systemic orportal veins

Inverted Bilat. right

Polysplenia

Cyanosis (-20%)CHF (,80%)

i Horizontal liverStomach not midlineMalrotation- Absent IVC

Usually bilat. leftUsually decreased

T (-65 o)

Multiple but notalways evident

Frequently bilat.(+ 510% )

To atria

Usually bilat. leftThe numbers in parentheses are approximate incidences based on information in the literature as well as the authors' clinical ex-

perience. (R = right; IL = left; SVC = superior vena cava; IVC = inferior vena cava; APVC = anomalous pulmonary venousconnection; CHF = congestive heart failure.)

As the atria almost always follow the situs, the direction ofthe P vector on the electrocardiogram may be of some valuein determining the situs (fig. 7). In situs solitus, atrialdepolarization proceeds from the sinoatrial node toward theleft and inferiorly resulting in an upright P in I, II, III, aVLand aVF. In situs inversus, the P vector is from left to rightand inferiorly with an upright P in II, III, aVF and inverted Pin I and aVL. In asplenia, both atria are morphologic rightatria and each may have a sinoatrial node.6 Consequently,either of the above P vectors may be present and both may bepresent in the same patient at different times. In poly-splenia, ectopic low atrial pacemakers are common42-" withnegative P waves in II, III and aVF. This may be the result ofbilateral left atria and absent sinoatrial nodes. We know ofno histologic studies of sinoatrial nodes in polysplenia.

Situs Solitus

Cardiac malpositions in situs solitus in this series were theresult of either cardiac displacement (dextroposition), dex-trorotation, or a discordant loop (solitus/l-loop).

Dextroposition may be recognized readily by anasymmetric thorax and decreased breath sounds on the rightas well as an absent or hypoplastic right lung in chestroentgenograms.The physical findings in corrected transposition in situs

solitus (solitus/l-loop/l-trans) are the result of the abnor-mally positioned semilunar valves and the associated cardiacanomalies. The anterior and leftward position of the aorticvalve results in a very loud aortic closure on auscultationwhich is usually maximal at the upper left sternal edge. Thesecond sound is usually single, but occasionally a split is

heard in the vicinity of the displaced pulmonary valve, i.e.,the mid or right sternal edge. When pulmonic stenosis ispresent, the murmur may be maximal retrosternally or to theright of the upper sternum. The murmur of the left atrio-ventricular valve insufficiency may be present in patientswith Ebstein's malformation of this valve.

FIGURE 7. Direction ofatrial depolarization in patients with car-diac malposition. A) Situs solitus. B) Situs inversus. C) Asplenia.D) Polysplenia. In asplenia there may be two sinoauricular nodesand the P vector may vary with time. Superiorly directed P vectorsare common in polysplenia.

-

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The roentgenographic features of corrected transpositionin situs solitus (solitus/l-loop/l-trans) are quite variable. Thetwo general forms of cardiac silhouette have been describedearlier. The pulmonary vascularity is related to the degree ofpulmonic stenosis and/or shunting at the ventricular level.Even in the absence of pulmonic stenosis, the mainpulmonary artery may not be evident because of its medialposition.The bundle branches also follow the respective ven-

tricles"' 16, " and this probably explains the electrocardio-graphic features of corrected transposition. In d-loops(including cardiac displacement) septal depolarizationproceeds from left to right and a Q wave is recorded in theleft precordial leads. With I-loops, septal depolarizationproceeds from right to left and a Q wave is frequentlyrecorded in the right but not over the left precordium. As thedegree of ventricular rotation and, therefore, septal positionmay vary, the Q waves may not be evident in V1 but may bepresent in the more rightward chest leads. This feature is notconstant and similar Q wave patterns may be found withright ventricular hypertrophy without ventricular inversion.In addition, atrioventricular conduction defects are common

in corrected transposition."The anatomic positions of the valves of the great arteries

result in unusual catheter positions during cardiaccatheterization.27 The location of the pulmonary valve orificebehind the venous atrioventricular valve and subpulmonicstenosis may preclude entering the pulmonary artery. Evenwhen the main pulmonary artery is entered the acute angula-tion of the catheter frequently prevents advancement to thepulmonary arterial wedge position unless a balloon tippedcatheter is used.

Situs Inversus

Cases of situs inversus with concordant ventricles showdextrocardia as a constant feature and this is evident byphysical and roentgenographic examination as well as

"6mirror image" progression of precordial QRS complexeson the electrocardiogram. There is a rightward inferior Paxis (fig. 7) and no findings suggestive of cardiac disease.The physical findings in corrected transposition in situs in-

versus (inversus/d-loop/d-trans) include a very loud aorticclosure maximal at the upper right sternal edge and thefeatures of associated anomalies. The two general forms ofcardiac silhouette seen on roentgenograms have beendescribed above (fig. 4). When a "shoulder" is present in cor-

rected transposition in situs inversus it is on the right heartborder, i.e., the same side as the apparent cardiac apex.When the heart is left-sided, a "shoulder" is notably absent.The electrocardiographic features are the rightward P axis ofsitus inversus and septal depolarization proceeding from leftto right.

Aspienia

The clinical picture begins with cyanosis in the neonatalperiod. Survival beyond infancy is unusual and serious infec-tions such as meningitis are not rare." 8 With the exceptionof a horizontal liver, the physical findings are not peculiar toasplenia.

dercirculation, a markedly symmetrical liver,'0 a midlinestomach bubble,10 malrotation of the bowel,3' symmetry ofthe tracheobronchial tree,8' and decreased pulmonaryvascularity. There is commonly mesocardia; however, dex-trocardia or levocardia sometimes occur. The abdominalaorta and inferior vena cava have also been found to lie onthe same side."As two sinoatrial nodes may be present, the electrocar-

diogram may show either an inferior rightward or inferiorleftward P axis. The same patient may show each at differenttimes. Although all cases of asplenia have an atrioventric-ular canal, the QRS axis in the cases exhibiting a single ven-tricle may be inferior and rightward while cases with twoventricles usually have a superior QRS axis.9The presence of Heinz or Howell-Jolly Bodies on a

peripheral blood smear is additional strong evidence ofasplenia." 47

Polyspienia

The clinical features of polysplenia are in marked contrastto those of asplenia. Cyanosis is usually absent or minimaland congestive heart failure is common as most patients withpolysplenia have cardiac anomalies resulting in pulmonaryovercirculation, either alone or in association with left-sidedobstructive lesions.The diagnosis of polysplenia may be suggested by a

clustering of clinical and laboratory findings. The findings onphysical examination are primarily those of the associatedcardiac anomalies and are not distinctive for polysplenia.Chest and abdomen roentgenograms show a variety ofhepatic and cardiac positions; however, mesocardia is rare.Focusing attention on the position of the heart and lungsmay result in cases of polysplenia being missed or categoriz-ing them as situs inversus or partial situs inversus. Ad-ditional roentgenographic findings that favor the diagnosis ofpolysplenia are bilateral left bronchial pattern,38 absence of aminor lobe fissure in both lungs and malrotation of thebowel.8' A feature peculiar to polysplenia is the upper ab-dominal aorta lying on the side opposite the stomachbubble.87, 42Low atrial pacemakers are found frequently on electro-

cardiogram.42-" Peripheral blood smears show no Heinz orHowell-Jolly Bodies (unpublished observations). Althoughmore than 100 cases of polysplenia have been documentedthere are no reports of unusual susceptibility to infection.Recent publications82 '" added six cases of extrahepaticbiliary atresia to the seven previously reported cases.At cardiac catheterization interruption of the inferior vena

cava with azygos continuation is strong evidence forpolyspleniall' 12, 82 and should alert the cardiologist to thispossibility even in the absence of cardiac or hepatic malposi-tion. Symmetry of the pulmonary arteries may be apparentin the posterior-anterior projection but the "bilateral-left"configuration is best verified in the lateral projection. In thisview both lower lobe pulmonary arteries lie in the same co-ronal plane and are posterior to the bronchi.Although there are several clinical indicators for

polysplenia, none are pathognomonic. Unless a radio-isotope splenic scan shows an irregular splenic masssuggestive of polysplenia the diagnosis is usually presump-tive and its likelihood depends on how many of the above

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features are present. A definitive diagnosis occasionally ismade at laparotomy for bowel obstruction or biliary atresia.

Embryologic ConsiderationsSitus

The anatomic features of the viscera in each of the situsesmay be explained readily if one hypothesizes that there are

separate factors for controlling the development ofmorphologic right and morphologic left structures frompaired lateral isomers. When both factors are present, theresulting body configuration is either situs solitus or inversus,depending on the factors' interrelationships. When the fac-tors controlling right morphology are present bilaterally,asplenia syndrome may be expected to occur and withduplicate left factors, polysplenia syndrome. Although many

organs show symmetry in asplenia and polysplenia, others donot. The lungs, tracheobronchial tree, atria and liver are

symmetric or tend toward symmetry while the ventricles andgreat arteries are asymmetric. The symmetric organs

develop from midline anlage which have undergone a sagittaldivision into right and left isomers. Whatever factors controlright-left morphology probably influence these isomers to besymmetric in each of the splenic syndromes. On the otherhand, structures which result from cephalad-caudad or co-

ronal division are not symmetric. The great arteries are theresult of a coronal division of the truncus arteriosus intoanterior and posterior portions (aorta and pulmonary artery,respectively). Similarly, the right and left ventricles developfrom anlage that are at least partially cephalad-caudad in thecardiac tube. In each of these instances, the paired structuresare not derived from lateral isomers and might not be ex-

pected to be influenced by factors controlling right-leftmorphology.The gastrointestinal tract is asymmetric but has a specific

orderly arrangement in both situs solitus and situs inversus.This orderly arrangement within the body might require theinfluence of both right and left factors. The presence ofbilateral right or left factors might result in a disorderlyarrangement of the bowel, i.e., malrotation.The splenic anlage makes its appearance relatively late in

gestation (i.e., 30 days). Normally, the splenic anlageappears as a small bud on the left side of the dorsalmesogastrium. Van Mierop has examined the splenic tissueof patients with polysplenia at necropsy and found spleens on

each side of the dorsal mesogastrium.12 The latter lends sup-

port to the concept of bilateral left-sidedness.Conversely, absence of the spleen in asplenia syndrome is

probably another manifestation of bilateral right-sidedness

with either suppression or agenesis of the splenic anlage as

part of the developmental complex. On the other hand,isolated absence of the spleen, i.e., without visceral abnor-malities, is probably the result of agenesis of the splenicanlage as an independent event. There is one such case in theCardiovascular Registry of the United Hospitals, MillerDivision.The significance of accessory spleen in these developmen-

tal complexes is unclear. Accessory spleens are a fairly com-mon finding at routine postmortem examinations andusually are not associated with other congenital visceral orcardiac anomalies. Case 59, in the present series, is an excep-tion. Lung fissures, atrial morphology and atrial septalmorphology were similar to that in polysplenia; however,tracheobronchial and pulmonary arterial relationships weretypical of bilateral right-sidedness.

Cardiac Position

The d- or 1- bulboventricular loop determines the positionsof the ventricles relative to each other and to the atria. Theposition of the heart within the thorax is dependent not onlyon the type of bulboventricular loop but also on the degree ofpivoting of the ventricular portion of the heart. Normally, atfour weeks when a d-loop forms the ventricles, the ventric-ular portion of the heart is still directed toward the right withthe ventricles situated side by side. At nine weeks, the ven-tricular portion of the heart pivots toward the left, placingthe heart in the left hemithorax and the right ventricleanterior to the left ventricle. Conversely, with an 1-loop theventricular portion pivots toward the right hemithorax. Inour experience, when the loop was concordant with the situs,the pivoting was complete in almost all cases. The only ex-ception was the case of solitus/d-loop (R)/d-normal. Withdiscordant loops, the pivoting is frequently incompleteresulting in the varying cardiac positions found in correctedtransposition of situs solitus (solitus/l-loop/l-trans), as wellas corrected transposition of situs inversus (inversus/d-loop/d-trans). This same principle can be applied to casesof asplenia and polysplenia. The symmetry of these situsesprecludes designating concordant loops. Therefore, it is notsurprising that each type of bulboventricular loop in each ofthese situses showed variation in degrees of pivoting and car-

diac position (table 5).

Pulmonary Veins

The differing patterns of pulmonary venous connectionfound in asplenia and polysplenia syndromes have beenrelated to the type of atrial isomerism found in each. In

TABLE 5. Cardiac Position Related to Situs and Bulboventricular LoopSitus Loop Total no. cases Dextrocardia Mesocardia Levocardia

Solitus d-loop r3000 6t ('3000)tl-loop* 15 6 (19)t

Inversus d-loop* 5 3 2I-loop 8 8

Asplenia d-loop* 8 4 4l-loop* 15 7 7 1

Polysplenia d-loop* 12 5 7I-loop* 5 4 1

*Discordant bulboventricular loops.t5 cases of cardiac displacement and I of incomplete pivoting of the ventricles, i.e. solitus/ d-loop (R).( ) indicates specimens without cardiac malposition and not included in this study.

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r

RA I

'1

FIGURE 8. Anomalous pulmonary venous connection in asplenia.As both atria are morphologic right atria and there may be no

common pulmonary vein, persistence ofpulmonary venous connec-

tions to anterior cardinal or umbilicovitelline veins are common.

RA = morphologic right atrium, R V = morphologic right ventri-cle, L V = morphologic left ventricle.

Lung d

LA

LA La L A LA L A

Normal Partial

FIGURE 9. Anomalous pulmonary venous connection in poly-splenia. As both atria are morphologic left atria, each may have a

common pulmonary vein. The pulmonary veins may connect toeither atrium or both atria. LA = left atrium, C = common

pulmonary vein.

asplenia there are bilateral right atria and consequentlybilateral absence of the common pulmonary vein.6 As aresult, the sites of connection of the anomalous pulmonaryveins in asplenia are the superior vena cavae or the portalsystem (fig. 8). As there are two left atria in polysplenia, acommon pulmonary vein may develop from either or both12and the pulmonary veins may connect directly to either orboth atria. Partial anomalous pulmonary venous connectionmay be the result of a common pulmonary vein arising fromeach of the morphologic "left" atria, whereas totalanomalous pulmonary venous connection to the venousatrium may be the result of a common pulmonary veindeveloping from that atrium (fig. 9).

In cases of polysplenia where the pulmonary veins connectdirectly to both atria, they do so in a distinctive manner. Theright veins connect to the right-sided atrium and the leftveins to the left-sided atrium. Van Mierop has pointed outthat the sites of connection are not at the intercaval portionsderived from the sinus horns but rather more medially andadjacent to each side of the atrial septum.'2 The latter con-nections suggested that the partial anomalous pulmonaryvenous connection in polysplenia was the result of bilateralcommon pulmonary veins in bilateral left atria.

Acknowledgment

The authors wish to thank Dr. Julien I. E. Hoffman for his interest, con-structive criticism and advice.

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P Stanger, A M Rudolph and J E EdwardsCardiac malpositions. An overview based on study of sixty-five necropsy specimens.

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Cardiac Malpositions - Circulationcirc.ahajournals.org/content/circulationaha/56/2/159.full.pdfasplenia and polysplenia are regarded as having cardiac malpositions. From the Cardiovascular