AUDREY SMITH, MPhil, FIMLS-JAMES L. WILKINSON, MB, ChB, MRCPROBERT ARNOLD, MB, ChB, MRCPDAVID F. DICKINSON, MB, MRCP, DCHROBERT H. ANDERSON, MD, MRCPatht
Liverpool, England
From The Institute of Child Health, University ofLiverpool, Alder Hey Children's Hospital, Liver-pool, England and the Department of Paediatrics,Cardiothoracic Institute, Brompton Hospital,London, England. Manuscript received October 21,1980, revised manuscript received July 7, 1981,accepted July 14, 1981 .
Supported by the National Heart ResearchFund, Halifax, England-
' Supported by the Joseph Levy Foundationtogether with the British Heart Foundation, London,England-
Address for reprints : Audrey Smith, MPhil, TheInstitute of Child Health, Alder Hey Children'sHospital, Eaton Road, Liverpool L12 2AP, En-gland .
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February 1982 The American Journal of CARDIOLOGY Volume 49
A morphometric assessment of the ventricles was made in a series of 31normal hearts and in 69 hearts with complete transposition of the greatarteries and intact septum (simple transposition). Specimens representingdifferent age groups were compared in order to investigate the develop-ment of the ventricular walls during infancy and early childhood .
In the series of normal hearts the left ventricular wall was always thickerthan the right ventricular wall when related to both age and body weight .The increase in thickness of the left ventricular wall showed some linearcorrelation with both increasing age and weight ; that of the right ventricularwall did not. In the hearts with simple transposition, the mean thicknessof the left ventricular wall was similar to that of the normal wall at birth,but thereafter the rate of Increase was less than normal . There was nolinear relation between increasing wall thickness and either age or weight .The thickness of the right ventricular wall (already significantly greaterthan normal at birth) showed a weak linear relation with increasing agebut not with body weight . Right ventricular muscle volume index washigher than that of the normal heart but right ventricular cavity volumeindex was not increased . Left ventricular cavity volume index increasedwith age, but muscle volume showed no difference from the normal .
At birth the left ventricle in simple transposition is in some respectsmorphologically better adapted than the right ventricle to support thesystemic circulation . However, increase in cavity size and failure of thewall thickness to develop may prevent the left ventricle from supportingthe systemic circulation after the 1st months of life . The right ventriclein transposition, although structurally unsuited to support the systemiccirculation, is able to adapt by increasing wall thickness, at least in earlylife .
Recent successes in the anatomic correction of complete transpositionof the great arteries have focused attention on the status of the ventriclesin this condition ." For the cardiologist and surgeon the choice of pro-cedure for repair is not easy . In contemplating redirection of blood flowat the atrial level, they must consider reports of early and late compli-cations occurring after the well established Mustard and Senning pro-cedures,5's knowing that these complications can be minimized by ca-pable surgeons and that the operative mortality is 10W .7 9 If anatomiccorrection is chosen the problems are those inherent in conversion of theright and left ventricles from systemic and pulmonary to pulmonary andsystemic chambers, respectively. This procedure restores to the ventriclesthe functions that they subserve in the normal heart. However, specu-lation about the long-term function of each ventricle in simple completetransposition may not be valid because it may not be directly comparablewith that of the normal heart . In this respect, our unpublished obser-vations have shown that in a large proportion of specimens with completetransposition and intact ventricular septum the morphology of the
ventricles differs in important respects from that of thenormal heart, although it is not clear to what extentthese differences affect the function of such ventricles .The differences include anomalies of the membranouspart of the septum, shape, size and orientation of theventricles and, frequently, bizarre morphologic featuresof the valve tension apparatus .
In consideration of these observations and the an-ticipated changes in ventricular wall thickness in com-plete transposition, we attempted to gain further insightinto the problem by making a series of measurementsin hearts with complete transposition and intact ven-tricular septum and comparing these data with mea-surements of a series of normal hearts . Similar studieshave been performed by other investigators .10-13
MethodsCase material: Complete transposition of the great arteries
as described in this report is the combination of atrioven-tricular concordance and ventriculoarterial discordance. Situssolitus was present in all cases . Nevertheless, the terms rightand left ventricle are used to denote only the morphologiccharacteristics of the ventricles and not their anatomic posi-tion .
Altogether 31 normal hearts and 69 hearts with completetransposition of the great arteries and intact ventricularseptum were available for study. The hearts were well fixedin formaldehyde before examination . It was possible to as-certain the body weight at death in only 15 cases with a normalheart and 24 cases of transposition . Two patients with trans-position had survived 4 and 5 months respectively, afterundergoing the Mustard procedure . Twenty-four of the re-maining patients had died in the immediate postoperativeperiod. Forty three patients were not subjected to surgery .Right ventricular measurements: Atrioventricular and
arterial valve circumferences were measured with calipersacross each separate leaflet or cusp at the anulus after thevalve was divided and opened flat . Linear dimensions in theright ventricle were measured in the following way : betweenthe internal apical point and (1) the lowest point of insertionof the arterial valve on the infundibular septum (RAA, rightventricular outlet length), and (2) a point on the tricuspidanulus below the coronary sinus at the junction between theinterventricular septum and the posterior wall of the heart(TA, right ventricular inlet length) .
Using the system devised by Lev et al .") "the internal partialperimeter" of the inlet part of the right ventricle (PRVi) andthe internal perimeter of the outlet part of the right ventricle(PRVo) were assessed . From these measurements it waspossible to calculate a "crude ventricular cavity volume"index. Parallel measurements were taken on the externalsurface of the ventricles and the difference between the ex-ternal and internal "crude ventricular volume" indexes gavea "crude ventricular muscle volume" index . The calculationmakes use of the shape of the right ventricle which simulatestwo cones :
Crude cavity volume index (right ventricle)= (TA X PltVi2) + (RAA X PRVov)
Left ventricular measurements : Measurements weretaken between the internal apical point and (1) the junctionof the arterial valve and the infundibular septum (LAA, leftventricular outlet length) anterior to the membranous septumor central fibrous body, and (2) the junction of the mitral valveanulus, the interventricular septum and the posterior wall of
VENTRICULAR WALLS IN SIMPLE COMPLETE TRANSPOSITION--SMITH ET AL .
the heart (MA, left ventricular inlet length) . The internal"crude ventricular cavity volume index" was calculated ac-cording to Lev et al . 10 by measuring the "perimeter" of the leftventricle (PLV) and including this in the calculation
MA + LAA x PLV 2.2Parallel measurements were taken on the external surface ofthe left ventricle and the "crude ventricular muscle volume"index calculated, being the difference between the externaland internal ventricular volume indexes .
Measurements of ventricular wall thickness were takenwith a needle gauge at points of maximal thickness of the freewalls between free standing trabeculae . In the morphologicallyright ventricle this point was below the tricuspid valve leafleton the shoulder of the heart, clear of the crista supraven-tricularis* of the normal heart specimens and of the rightventriculoinfundibular fold of the series with transposition .In the left ventricle the point was below the mural leaflet ofthe mitral valve in both groups .
ResultsVentricular wall thickness correlated with age (Fig .
1) : In the series of 31 normal hearts, there was a significantcorrelation (probability [pj <0.001) between increasing leftventricular wall thickness and increased age but no significantcorrelation between right ventricular wall thickness and age .In the series of 69 hearts with complete transposition of thegreat arteries and intact septum a low level of correlation (p<0.01) was noted between right ventricular wall thickness andage, whereas no significant correlation could be demonstratedbetween left ventricular wall thickness and age .Ventricular wall thickness correlated with body
weight (Fig. 2): There was a weak correlation between in-creased left ventricular wall thickness and body weight in thenormal series (p <0 .1) but no significant correlation betweenright ventricular wall thickness and body weight . No corre-lation was shown between either right or left ventricular wallthickness and increased body weight in the series withtransposition .
Left and right ventricular wall thicknesses correlatedwith left and right ventricular outlet lengths (Fig. 3) :There was a low linear correlation between left ventricular wallthickness and left ventricular outlet length in both the normalseries (p <0 .02) and the series with transposition (p <0 .02) butno significant correlation between right ventricular wallthickness and right 'ventricular outlet length in eithergroup.
Comparison of perinatal group with I month to 1 yearage group : The thickness of the left ventricular wall in heartswith simple complete transposition was similar to that innormal hearts in the perinatal group but in the older groupwas significantly thinner (Table IA) . The right ventricularwall in the series with simple transposition was significantlythicker than that of the normal series even in the perinatal agegroup (Table 113) . The left ventricular outlet length in theheart with simple transposition was significantly longer thanthat of the normal heart in the older age group (Table IIA) .
* The crisis supraventricularis of the normal right ventricle is astructure that is morphologically complex, being composed of the rightventrlculoinfundibular fold and the parietal extension of the infundibularseptum . h has no direct counterpart in complete transposition 14 andso it was excluded as an index of the thickness of the morphologicallyright ventricular wall, as were areas where free-standing trabeculaecontributed to wall thickness . However, the "spongy" right ventricularwall was included in the measurement taken .
February 1982 The American Journal of CARDIOLOGY Volume 49 363
VENTRICULAR WALLS IN SIMPLE COMPLETE TRANSPOSITION-SMITH ET AL .
Flight ventricle
Age•
Left ventricle
C
In the perinatal group the difference did not achieve statisticalsignificance, although the probability level was borderline.The right ventricular outlet in simple transposition was sig-nificantly longer than that of the normal series in both agegroups (Table IIB) .
There were no significant differences between crude rightventricular cavity volume index in the hearts with transpo-sition and the normal hearts in either age group (Table IIIA) .The crude left ventricular cavity volume index in simpletransposition was similar to that of the normal series in theperinatal group but was significantly greater in the older agegroup (Table IIIB) . There was a greater crude right ventricularmuscle volume index in transposition than in the normal se-ries, although the observed difference achieved significanceonly in the older age group (Table IVA) . There were no sig-nificant differences between the crude left ventricular musclevolume indexes in either age group (Table IVB) .
There were no significant differences between the tricus-pid, mitral and pulmonary valves of the normal hearts andthe hearts with transposition at eitherage (Table V) . How-ever, the mean aortic valve circumference in the perinatalperiod was significantly larger in the hearts with transpositionthan in the normal hearts . Although the mean tricuspid valvecircumference in simple transposition was similar to that ofthe normal group, some abnormalities of the tricuspid leaflets(in approximately 3 percent of the group with transposition)could have caused tricuspid regurgitation . These findings areto he published at a later date .
DiscussionThe morphologically right and left ventricles in
complete transposition with intact septum at birth al-ready show the effects of the embryologic error . Afterbirth the right ventricle alone must carry the load of the
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February 1982 The American Journal of CARDIOLOGY Volume 49
Right testicle •Left testicle
111
F-r3--r~l
tl1 2 3 4 5 5 7 2 3 4 2 4 6 6 10 1
2 3 4 5.-Days---Y eks-, FMonths- --Years -r
Age
FIGURE 1 . Age and ventricular wall thickness . A, linear re-gression between right and left ventricular wall thickness andpatient age in a group of 31 normal hearts from children agedfrom birth to 5 years and 69 hearts with complete transpositionof the great arteries (TGA) and intact septum from patients agedfrom birth to 40 months. Correlation with age for the normal rightventricle was 0.21 (differences not significant [NS]) and for thenormal left ventricle 0.68 (p <0 .001) . Correlation for the rightventricle in transposition was 0.35 (p <0 .01) and for the leftventricle in transposition 0.03 (NS) . B, data for the normal rightand left ventricular wall thickness used to calculate the re-gression on age shown in A. C, data for the group of hearts withtransposition of the great arteries and intact septum used for theregression of right and left ventricular wall thickness on ageshown in A. The regression analysis (A) shows a significant slope(p <0.01) for right ventricular thickness on age, but the scat-tergram indicates a leveling out of points among the older agegroup-
systemic circulation whereas the left ventricle supplyingonly the pulmonary circulation functions at lowerpressure. After anatomic correction, therefore, it maywell be difficult for them to adjust to the sudden tran-sition to pulmonary and systemic ventricular status, andthe timing of such correction may be crucial in deter-mining operative success. With this in mind, we evalu-ated the development of the ventricles in a series ofhearts with complete transposition and intact septum,as Bano-Rodrigo et al ." had previously done .
The right and left ventricular thicknesses in thenormal neonate : Although it may be dangerous tomake comparisons between the normal right (pulmo-nary) ventricle and the right (systemic) ventricle incomplete transposition, 15 it is only by using the normalventricle as a standard that the effects of completetransposition may be judged . However, in this context"normality" is difficult to define, the controversy sur-rounding the relative thicknesses of the ventricular wallsin the normal neonate attesting to this . Harvey 16 ob-served that in the embryo "there is not such a differencebetween the two ventricles ; but as in a double nut theyare nearly equal in all respects ." As far as we can judge,he made no specific reference to the walls being equalin thickness. Nevertheless, he has been frequentlyquoted 17,18 as having stated that the thickness of theright and left ventricles is equal in fetal life and this hasbecome the classically accepted teaching . L 9 The problemwas recognized by Taussig, 20 who qualified her state-ment that the "ventricular walls are almost equal atbirth" by adding that "the right ventricular wall isproportionately thicker" and "the left ventricular wall
mm 1lotmet --to- T)IF GA -u 96 -8- e7 ---TGA 5
E5 -
87
5- 3 52 4- 4
3 Normal 32- 2
720
30
A
Age in months
B
Right ventricleLeft
"
11 -8y 10 - .5
-go -
5s-5 -4-3- eaa
.
. • .
I1 2 3 4 5 6 7 2 3 4 2 4 6 8 10 1
2 3 4 5-Days -i (Weeks-r -a-Months- Years w
mm-10-9-e-6- _TGA5-4-3
TGANormal
4
5
6
9Weight in Kilograms
A Right ventricle
Let' ventncIS
FIGURE 2. Body weight and ventricular wall thickness . A, linearregression between right and left ventricular wall thickness andweight at death in a group of 15 normal hearts and 24 hearts withtransposition of the great arteries (TGA) and intact septum . Corre-lation with weight at death for the normal right ventricle was 0 .05and for the normal left ventricle 0 .48 . Correlation for the right ven-tricle in transposition was 0 .08 and for the left ventricle in trans-position -0 .18 . These values are not statistically significant . B,scatter data for the normal series used to plot the regression in A .C, wide scatter of data for the transposition series used to plot theregression in A.
C
proportionately thinner" in infancy than in the adultheart.
The results of our present study (Fig. 1, Table 1) un-equivocally substantiate the findings of De la Cruz etal.21 These investigators believe that, contrary to theaccepted view, the thickness of the left ventricular wallin the heart of premature and postnatal infants, andindeed from 6 months of intrauterine life to age 12 years,is always greater than and generally double that of theright ventricle. Similar results have recently been re-ported in the developing pig heart 22 Furthermore, inour experience light microscopy of serial sections of fetaland neonatal hearts has shown that the trabeculationand undermining that characterize the ventricles nearlyalways extend deeper into the myocardium of the rightthan into that of the left ventricle . The wall thicknessis much less variable in the left than in the right ven-tricle in both the anterior to posterior and the base toapex directions. In this way the left ventricular wall canhe seen to be thicker and more compact than the rightin embryos at least as young as 12 weeks' ovulation (Fig .4) .
Left and right ventricular thicknesses in com-plete transposition: In our specimens with completetransposition and intact septum, the mean ratio ofmorphologically left to right ventricular wall thicknesswas greater than unity both in the perinatal group(mean 1 .15, range 0.66 to 1 .66) and in the group from Imonth to age 1 year (mean 1 .02, range 0.57 to 2 .0) . Incontrast, Bano-Rodrigo et al ." found a considerablylower ratio (0.66) in a series of hearts from patients aged3 hours to 4.3 years . This difference may be due to theinclusion of specimens from older patients in their data,but may also reflect differences in their measurement
VENTRICULAR WALLS IN SIMPLE COMPLETE TRANSPOSITION-SMITH ET AL
nu,S 10Z 9Y aS 70 55m 4y 32
B•
Flirt veruncisLeft
11
Right wedricil)Left ,,
techniques, which were not specified in detail. Never-theless, both their results and ours indirectly show aninverse relation between a decreasing left to right ven-tricular wall thickness ratio and increasing age in pa-tients with transposition of the great arteries and intactseptum (Fig . 1) .Right ventricular thickness and muscle volume
in transposition: Statistical analysis of our findingsshowed that the mean thickness and crude muscle vol-ume index of the right ventricle in simple completetransposition were greater than those of the normalventricle even in the perinatal group (Tables I and TV) .
2
1 mm-
10-
g-E 8-6-
i
5
9weght in Keograns
4
5
6
7
8
12Weight in Kilograms
I TGA
Normal
30
40
50
00
mm
outlet lengthRight ventricle Left
11 FIGURE 3. LInear regression of right and left ventricular wall thick-
nesses on right and left ventricular outlet lengths in the series of 21normal hearts and 33 hearts with transposition of the great arteries(TGA) and intact septum from birth to age 1 year. Correlation for thenormal right ventricle was 0 .03 (difference not significant [NS]) andfor the normal left ventricle was 0 .51 (p <0 .02) . Correlation for the rightventricle in transposition was 0 .15 (NS) and for the left ventricle intransposition was 0 .42 (p <0 .02).
February 1982 The American Journal of CARDIOLOGY Volume 49
365
VENTRICULAR WALLS IN SIMPLE COMPLETE TRANSPOSITION-SMITH ET AL .
TABLE I
Comparison of Mean Ventricular Wall Thicknesses (mm) In the Normal Series and the Series With Transposition
n = number of hearts ; p = probability; SE = standard error of the mean ; TGA = transposition of the great arteries with intact septum .
TABLE II
Comparison of Mean Ventricular Outlet Lengths (mm) in the Normal Series and the Series With Transposition
Abbreviations as before .
TABLE III
Comparison of Mean Ventricular Cavity Volume Indexes (cm') in the Normal Series and the Series With Transposition
Abbreviations as before .
TABLE IV
Comparison of Mean Ventricular Muscle Volume Indexes (em') In the Normal Series and the Series With Transposition
Abbreviations as before .
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February 1982 The American Journal of CARDIOLOGY Volume 49
TABLE VComparison of Mean Tricuspid, Mitral, Pulmonary and Aortic Valve Circumferences (mm) in the Normal Series and the SeriesWith Transposition
Normal
Age
n
Mean
±SE
A. Tricuspid Valve1 mo-1 yr
16
44.50
1 .78Perinatal
5
37.40
3.31
1 mo-1 yr
18
37.56
1 .31Perinatal
5
29.40
0.93
This suggests altered hemodynamics in fetal life incomplete transposition . The contention that the findingof an increase in mean aortic valve circumference intransposition at birth (Table V) suggests that there mayhave been increased flow in fetal life is supported byRudolph's observation22 that there is frequently awidening of the aortic isthmus . However, no increase incavity volume index of the right ventricle was demon-strated, such indexes remaining the same in the olderseries with transposition as in the older normal series(Table III). There was no direct linear relation betweenincreasing right ventricular thickness and outlet lengthin transposition, and the correlation was similarly poorin the normal right ventricle (Fig. 3). The mean rightventricular outlet length was marginally longer in theseries with transposition than in the normal series(Table II), but this feature may be the product of de-velopmental differences .
Left ventricular thickness and outflow length intransposition: The wall of the morphologic left ven-tricle in the older subgroup was significantly thinner inthe series with transposition than in the normal series(Table I), a finding previously observed by Lev et al . 12There was also a tendency toward increased cavityvolume index with age (Table III) . The left ventricularoutlet length was significantly longer in the series withtransposition than in the normal series in the older agegroup (Table II), but it is possible that this feature ispartly accounted for by a morphologic difference be-tween the left ventricular outflow in the heart withtransposition and that in the normal heart . In completetransposition with intact septum the immediate sub-pulmonary zone is composed of proportionately moremuscle and less fibrous tissue than is the analogoussubaortic zone of the normal heart. Whether this feature
VENTRICULAR WALLS IN SIMPLE COMPLETE TRANSPOSITION-SMITH ET AL .
B . Mitral Valve
TGA
n
Mean
±SE
p
29
44.86
1 .549
32.67
2 .16
25
37.80
1 .4610
29.41
2.04
FIGURE 4 . Photomicrograph of a section through a fetal heart of 12weeks' gestational age illustrating the difference between the right andleft ventricular walls . The plane of section is in the long axis of the heartat right angles to the inlet part of the Interventricular septum . LV = leftventricle ; PV - pulmonary valve ; RV = right ventricle; S = interven-tricular septum (magnification X 12).
February 1982 The American Journal of CARDIOLOGY Volume 49
367
C . Pulmonary ValveI mo-1 yr 18 26.28 0.93 28 28.50 1 .00Perinatal 5 20.80 1 .56 11 23.09 0.94
VENTRICULAR WALLS IN SIMPLE COMPLETE TRANSPOSITION-SMITH ET AL .
contributes to the differences between outflow tractmeasurements in the normal heart and the heart withsimple transposition is uncertain . It was possible todemonstrate a linear relation between increased leftventricular wall thickness and left ventricular outflowlength in the heart with transposition, which approxi-mated that of the normal left ventricle (Fig . 3), showingthe potential of the left (pulmonary) ventricle in simpletransposition to behave like the normal left (systemic)ventricle .
Implications: The data described serve to stress thedegree of urgency in the choice of treatment of completetransposition of the great arteries with intact septum,
1 . Jatene AD, Fortes VF, Paullsta PP, at al . Successful anatomiccorrection of transposition of the great vessels, a preliminary re-port. Arq Bras Cardiol 1975;28:461-4.
2. Yacoub MH, Radley-Smith R, Hilton CJ. Anatomical correctionof complete transposition of the great arteries and ventricular septa)defect in infancy. Br Med J 1976;1 :1112-4.
3. Ross D, Rickards A; Somerville J . Transposition of the great ar-teries : logical anatomical arterial correction . Br Mad J 1976;1 :1109-11 .
4. Yacoub MH, Bernhard A, Lange P, at al . Further experience withanatomical correction of simple transposition of the great arteries .Proceedings of the British Cardiac Society (abstr) . Br Heart J1980;43:101 .
5 . Mustard WT. Successful two-stage correction of transposition ofthe great vessels . Surgery 1964 ;55:469-72 .
6. Senning A. Surgical correction of transposition of the great vessels .Surgery 1959:45:966-80 .
7. Ullal RR, Anderson RH, Lincoln C . Mustard's operation modifiedto avoid dysrhythmias and pulmonary and systemic venous ob-struction . J Thorac Cardiovasc Surg 1979 ;78 :431-9 .
8. oelert H, Boat HG . Transmitral resection of subpulmonary stenosisin transposition of the great arteries . Thorac Cardiovasc Surg1979;27(1):58-60 .
9 . Localelli G, Benedetto GD, Vlllanl M, Vanlnl V, Blanchi T, Par-enzan L . Transposition of the great arteries. Successful Senning'soperation in 35 consecutive patients . J Thorac Cardiovasc Surg1979:27:120-3 .
10 . Lev M, Rowlatt UF, Rlmoldl HJA . Pathologic methods for studyof congenially malformed heart . Methods for electrocardiographicand physiologic correlation . Arch Pathol 1961 ;72:493-511 .
11 . Rowlett UF, Rimoldi HJA, Lev M. The quantitative anatomy of thenormal child's heart . Pediatr Clin North Am 1963 ;10:499-588 .
12 . Lev M, Rbnoldi HJA, Palva R, ArcIlla RA . The quantitative anatomyof simple complete transposition . Am J Cardiol 1969;23:409-16.
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February 1982 The American Journal of CARDIOLOGY Volume 49
because the older the patient the further from normalare the internal dimensions and wall thickness of theventricles. `Thus the comparative failure of the leftventricular wall in simple complete transposition tothicken, combined with the tendency toward dilationof the chamber, underlines the importance of earlysurgical intervention if anatomic correction is contem-plated .
Acknowledgment'We express our thanks to Graham S . Triggs and Anthony
McLoughlin for their advice on statistical analysis, to KennethWalters for the illustrative work and to Irene Wright andMary Finch for secretarial help .
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