Left ventricular dysfunction in the fetus: relation to aortic valve anomalies and endocardial

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1 Br Hert J 199 1;66: Deprtment of Perintl rdiology, Guy's Hospitl, London G K Shrlnd S K hit L D lln Deprtment of Pthology, Guy's Hospitl, London N L K Fgg ook Deprtment of Peditric rdiology, Guy's Hospitl, London M Tynn Deprtment of Peditrics, Ntionl Hert nd Lung Institute, London R H nderson orrespondence to Dr Gurleen K Shrlnd, Deprtment of Perintl rdiology, 15th Floor, Guy's Tower, Guy's Hospitl, St Thoms Street, London S1 9RT. ccepted for publiction 29 pril 1991 Left ventriculr dysfunction in the fetus: reltion to ortic vlve nomlies nd endocrdil fibroelstosis Gurleen K Shrlnd, Sunder K hit, Nul L K Fgg, Robert H nderson, Michel Tynn, ndrew ook, Lindsey D lln bstrct Objective-To exmine the reltion between chrcteristic form of left ventriculr dysfunction in the fetus nd bnormlities of the ortic vlve nd endocrdil fibroelstosis of the left ventricle. Design- retrospective study to exmine the correltion between echocrdiogrphic findings in the fetus nd postntl or necropsy findings. Setting-Tertiry referrl centre for fetl echocrdiogrphy. Ptients-Thirty fetuses showing chrcteristic echocrdiogrphic picture of left ventriculr dysfunction. Min outcome mesures-the reltion between the prentl echocrdiogrphic fetures nd the postntl nd necropsy findings. Results-t presenttion the size of the left ventriculr cvity ws norml or enlrged in ll cses. The mesurements of the orifice of the ortic root nd mitrl vlve were either norml or smll for the gesttionl ge. The echocrdiogrphic dignosis mde t presenttion ws criticl ortic stenosis in ll cses. t necropsy or postntl exmintion the ortic vlve ws dysplstic nd stenotic in 15 cses nd the left ventricle hd become hypoplstic in one of these. ortic tresi ws present in seven ptients, three of whom hd hypoplstic left ventricle. In six ptients the ortic vlve ws bicuspid lthough not obstructive. One of these ptients hd hypoplsi of the ortic rch nd one hd hypoplstic left ventricle but in the remining four ptients endocrdil fibroelstosis of the left ventricle ws the only bnormlity found. No follow up informtion ws vilble in two. Of 26 ptients for whom there ws postmortem informtion, 24 hd evidence of some degree of endocrdil fibroelstosis of the left ventricle. Sequentil observtions showed tht five cses developed into the hypoplstic left hert syndrome. onclusions-this type of left ventriculr dysfunction in the fetus is the result of n overlp of diseses, including primry left ventriculr endocrdil fibroelstosis, criticl ortic stenosis, nd the hypoplstic left hert syndrome. 419 Over the pst 1 yers echocrdiogrphy hs become estblished s relible technique for the detection of structurl hert disese in prentl life.'2 s the number of nomlies detected increses it becomes possible to exmine groups of cses in seprte dignostic ctegories. The chrcteristic echocrdiogrphic nd ntomicl fetures of the defect s encountered in the fetus cn then be described, while the severity nd outcome of the lesion seen ntentlly cn be compred with postntl experience. The nturl history nd progression of lesions cn be observed from the second trimester. With these ims we retrospectively exmined series of 3 cses seen over 1 yer period in which there were the chrcteristic echocrdiogrphic fetures of left ventriculr dysfunction. Ptients nd methods The cse mteril ws derived from ptients referred for fetl echocrdiogrphy to our unit since Februry 198. We now hve experience of 7 pregnncies t incresed risk of congenitl hert disese.3 Between 198 nd 1983 we evluted the fetl hert with cross sectionl imging only on n dvnced Technicl Lbortories Mrk 3 mechnicl sector scnner. Lter, Doppler evlution ws dded to the exmintion. Since 1985, n dvnced Technicl Lbortories Ultrmrk 4 nd Hewlett-Pckrd 772 phsed rry imging system hve been used. The 5 MHz trnsducer ws used routinely but 3-5 MHz trnsducer ws lso vilble. olour flow mpping becme vilble in The gesttionl ge t the time of exmintion ws between 18 nd 4 weeks nd ws confirmed by mesuring the femorl length or biprietl dimeter. Of 462 cses of detected structurl hert mlformtion, 3 were considered to hve similr echocrdiogrphic fetures ffecting the left ventricle t presenttion. The dignostic criteri for inclusion in the group were poorly contrcting left ventricle where there ws no mesurble difference in the dimensions of the cvity between systole nd distole nd left ventriculr cvity size where either the mximum width or length ws norml or incresed for the gesttionl ge. ll the cses included in this study were initilly dignosed s hving criticl ortic stenosis. No other cses of criticl ortic stenosis hve been excluded. During the sme time period 77 cses were dignosed t presenttion s hypoplstic left Br Hert J: first published s /hrt on 1 December Downloded from on 29 October 218 by guest. Protected by copyright.

2 42 hert syndrome nd these were excluded from this study. In nother three ptients there ws evidence of left ventriculr dysfunction but there ws lso right ventriculr dysfunction nd the ort seemed norml. These were excluded from this study becuse they were dignosed s hving different disese both on prentl echocrdiogrphic exmintion nd on subsequent exmintion fter delivery. There ws one further fetus, with n ortic-left ventriculr tunnel, tht lso hd evidence of left ventriculr dysfunction. However, there ws considerble ortic incompetence t presenttion which distinguished this cse from the study group. ll cses of isolted left ventriculr endocrdil fibroelstosis were included in this study. There were five cses of endocrdil fibroelstosis involving more thn one crdic chmber; these were excluded from the study becuse they did not hve the fetures of criticl ortic stenosis nd were considered to belong in different dignostic group t presenttion. In 28 of the 3 cses forming the study group the ptient ws referred becuse of the suspicion of fetl hert disese on routine obstetric scn. The reson for referrl in one cse ws cystic hygrom nd this ws the only fetus in which n extrcrdic nomly ws found. Fetl hydrops ws the reson for referrl in the lst cse. videotpe recording of ech study ws reviewed retrospectively nd the echocrdiogrphic findings noted. vidence of fetl hydrops, s shown by fetl skin oedem, scites, nd pleurl or pericrdil effusions, ws sought nd recorded. The orifices of the mitrl vlve nd the ortic root nd the length nd mximum width of the left ventricle were mesured nd compred with the norml vlues for the gesttionl ge.45 The ortic vlve ws qulittively exmined nd grded s being indequtely visulised, norml, or Figure 1 Four chmber echocrdiogrm of the hert of typicl cse. The overll size of the hert is incresed. The left ventricle ppers lrger thn the right nd the left trium is enlrged. The wlls of the left ventricle show incresed echogenicity compred with the right ventricle. The rrow indictes the tril septum which is restricted. The wlls of the left ventricle show incresed echogenicity. LV, left ventricle; RV, right ventricle; L, left trium; R, right trium. Shrlnd, hit, Fgg, nderson, Tynn, ook, lln * - ', D 8 i5-6- > Gesttionl ge (weeks) e 36 4 Figure 2 Distribution of mitrl vlve orifice size in 27 of the fetuses in reltion to gesttionl ge. The vlues re compred with the men of the norml rnge for gesttionl ge (solid line). For the men, MV = gesttionl ge. thickened. The sizes of the left nd-right tri were compred nd the left tril size ws grded s norml nd s mildly or modertely enlrged reltive to the right trium. The crdiothorcic rtio ws mesured on four chmber view in stndrd fshion nd compred with the norml rnge.6 The Doppler chrcteristics offlow of blood cross the mitrl nd ortic vlves recorded on videotpe were noted. Five ptients hd sequentil studies during pregnncy. The necropsy specimens of 21 cses were vilble for exmintion nd the postmortem reports of further five cses were studied. In 16 cses the specimens were vilble for postmortem exmintion soon fter the echocrdiogrphic study. In these we clculted the greement between the mesurements mde echocrdiogrphiclly nd those mde t necropsy.7 In four cses necropsy ws refused but in two of these postntl echocrdiogrphy hd been performed. No follow up informtion ws vilble in two cses. The clinicl fetures nd outcome of ech cse were nlysed. Results There ws evidence of fetl hydrops t presenttion in totl of nine cses. HORDIOGRPHI FTURS Mitrl vlve, ortic vlve, left ventricle The chrcteristic echocrdiogrphic fetures re best seen on four chmber view (fig 1). The mitrl vlve orifice nd the ortic root size were norml or smll for the gesttionl ge nd figures 2 nd 3 show the sctter of vlues compred with the men of the norml rnge. The excursion of the leflets of the mitrl vlve ws limited in ll cses. Direct exmintion of the ortic vlve ws indequte in 11 cses but thickened leflets were seen in 13 ofthe remining cses. The qulity of imges depended on dequte visulistion, whtever the gesttionl ge of the subject; thickened leflets were more convincingly identifible in lter pregnncy. The mximum left ventriculr Br Hert J: first published s /hrt on 1 December Downloded from on 29 October 218 by guest. Protected by copyright.

3 Left ventriculr dysfunction in the fetus: reltion to ortic vlve nomlies nd endocrdilfibroelstosis 421 Figure 3 Distribution of the ortic root size mesured in 29 of the fetuses nd plotted ginst gesttionl ge. The vlues in two fetuses were the sme. The vlues re compred with the men of the norml rnge for gesttionl ge (solid line). For the men, o = gesttionl ge. Figure 4 () Mximum left ventriculr width mesured on four chmber view in 29 fetuses nd plotted ginst the gesttionl ge on grph showing the norml rnge for this vrible. For the men of the norml rnge, LV width = gesttionl ge. (B) Mximum left ventriculr length mesured on four chmber view in 29 fetuses nd plotted ginst the gesttionl ge vlues in two fetuses were the sme. Men of the norml rnge, LV length = gesttionl ge. -8- ~6' 5,! o o 3.t ' 16 2 Gesttionl ge (weeks) Doppler echocrdiogrphy In 18 of the 22 cses tht were exmined by pulsed or colour Doppler echocrdiogrphy there ws no forwrd flow into the left ventricle. Mitrl regurgittion ws detected in six cses. Forwrd flow ws demonstrted in the ort in 15 cses; in five of them the velocity ws greter thn the norml vlues for gesttionl ge.58 In 36 4, six cses reverse flow only could be demonstrted in the ort nd in one cse no flow ws detectble. In three cses there ws lso tricus- width ws either within the norml rnge or incresed compred with the norml rnge in ll cses (fig 4); the length ws norml or incresed in most (fig 4B) >i ~ 2, -i * Og **~ - -I L - S Left ventriculr echogenicity In 28 cses the left ventricle ws more echogenic thn the right ventricle-in 14 to considerble extent. pid regurgittion. SQUNTIL STUDIS Five ptients hd sequentil studies: t 31 nd 36 weeks, 22 nd 28 weeks, 22 nd 32 weeks, 32 tril septum, left tril size, nd crdiiothorcic nd 34 weeks, nd 31 nd 41 weeks respectively. The mesurements of the mitrl orifice rtio The left trium ws norml in 18, slightly nd ortic root tended to remin sttic or grow enlrged in five, nd modertely en lrged in t slower rte thn expected s pregnncy seven. The crdiothorcic rtio, which vried, dvnced, with the result tht the vlues depended minly on the left tril size nd the becme smller compred with the norml presence or bsence of fetl hydrops (fiig 5). The men for gesttionl ge. Similrly, sequentil rtio ws incresed in ll hydropic fe tuses nd mesurements of the left ventriculr cvity in ll those with lrge left trium nd showed either no growth or reduced rte of ssocited intct tril septum. The tril sep- growth so tht with dvncing gesttionl ge tum seemed to be intct in 11 cses, with the the left ventricle becme progressively smller septum bulging from left to right. In ll these compred with the men for gesttion nd lso cses the left trium ws enlrged. In six cses with the size of the right ventricle (figs 6 nd left to right shunting through the tril septum B). In one cse the cvity size ws initilly very ws clerly shown on colour Doppler echocr- lrge nd lthough the left ventricle remined diogrphy. In these cses the flp vlive of the lrge, the rte of growth ws reduced so tht the formen ovle, normlly prominentt mid-left rtio of the left to the right ventricle decresed tril structure, ws seen herniting into the right trium. & O ~~~~ with dvncing gesttionl ge. ll five cses hd evidence of forwrd flow cross the ortic vlve on Doppler echocrdiogrphy t presenttion. In two cses, however, no forwrd flow could be demonstrted on the subsequent study. Both of these cses progressed to hypoplstic left hert syndrome. In one of these, hypoplstic left hert ws dignosed on the Intct tril septum Hydropic Non-hydropic, ptent formen *,&, o o _ Gettinl g ( 2 3 Gesttionl ge (weeks) Figure S rdiothorcic (/ T) rtio in the study group (n = 3) compred with the norml rnge for gesttionl J.,;.- ge. ses tht were hydropic nd hd n intct septum I I I I I I I re indicted by solid circle within the tringle. The vlues for two hydropic fetuses nd one non-hydropic Gesttionl ge (weeks) fetus overlpped. 4 Br Hert J: first published s /hrt on 1 December Downloded from on 29 October 218 by guest. Protected by copyright.

4 422 Shrlnd, hit, Fgg, nderson, Tynn, ook, lln Figure 6 () Sequentil mesurements of left ventriculr width in five cses compred with the norml rnge for dvncing gesttionl ge. (B) Sequentil left ventriculr length mesurements in five cses compred with the norml rnge for dvncing gesttionl ge. - m c n o S ).. c o m N -,I._ OJ 4 3- I Gesttionl ge (weeks) sequentil echocrdiogrphic study nd in the second the dignosis ws mde t postmortem study fter intruterine deth few weeks fter the sequentil study. The tril septum in this cse, which ws first seen t 22 weeks' gesttion, ws initilly ptent wheres t 28 weeks' gesttion it ppered to be intct by echocrdiogrphy. This ws confirmed t necropsy. In ddition, in further three fetuses tht only hd one prentl study, necropsy three, four, nd eight weeks fter the echocrdiogrphic study showed tht the left ventricle ws hypoplstic reltive to the right ventricle nd hypoplstic left hert syndrome ws the finl dignosis..~~~men Men -2SD Finl dignosis Fifteen of 28 cses in whom postntl or postmortem study ws performed hd dysplstic nd stenotic ortic vlve (fig 9); in one of them hypoplstic left ventricle developed. Seven cses hd ortic tresi; in three of them hypoplstic left ventricle developed. In five of these seven forwrd flow ws detected pre- -2- * F Men of o length by echo nd t necropsy (cm) Figure 7 greement (differences versus men) between ortic root mesurements mde echocrdiogrphiclly nd in the sme fetuses t necropsy.7 Only fetuses in which the intervl between the two exmintions ws < two weeks re included (n = 16, men of differences -35, SD of differences = = 69). -8 OUTOM ighteen mothers presented before 24 weeks' gesttion nd 16 of these opted for termintion of pregnncy. There were two spontneous intruterine deths. Twelve ptients were born live, four of whom were in crdic filure t delivery. ll but one died within the first week of life, six on the first dy. One neonte who hd hd blloon dilttion of the ortic vlve prentlly died t 37 dys.9 Postntl blloon dilttion of vlve ws performed in six cses but despite successful relief of vlve obstruction the left ventriculr output ws indequte to mintin the circultion. POSTMORTM ND POSTNTL FINDINGS Left ventricle nd ort The dignosis of left ventriculr disese ws confirmed in ech cse where specimen ws vilble for exmintion. The left ventriculr cvity nd ort of ech specimen were mesured. Sixteen specimens were vilble for postmortem exmintion soon fter the echocrdiogrphic study nd in these there ws good greement between the echocrdiogrphic nd ntomicl mesurements. Figure 7 shows the greement between the mesurements for the ortic root nd fig 8 tht for the left ventriculr length. In three cses, where there ws n intervl of three, four, nd eight weeks between the echocrdiogrphic nd postmortem exmintions, the left ventriculr nd ortic mesurements were more suggestive of the dignosis of the hypoplstic left hert syndrome. Left ventriculr endocrdilfibroelstosis The left ventricle of ech vilble specimen ws inspected for evidence of fibroelstosis (fig 9). In two cses in which the left ventricle ws very echogenic there ws only mild fibroelstosis in the specimen. In one cse with severe fibroelstosis t necropsy there hd only been slight echogenicity. In the remining specimens the correltion between the two exmintions ws good. In 24 of the 26 specimens exmined t necropsy there ws some degree of endocrdil fibroelstosis of the._ men left ventricle. 1- tril septum The tril septum ws found to be intct in five cses, ll of which hd been suspected on echocrdiogrphy. In further four cses, the tril septum ws restrictive, three of which were thought to be intct echocrdiogrphiclly. One cse ws thought to be intct echocrdiogrphiclly but found to be ptent t necropsy. postmortem exmintion hd not been performed in the two remining cses in which n intct tril septum ws suspected. Br Hert J: first published s /hrt on 1 December Downloded from on 29 October 218 by guest. Protected by copyright.

5 Left ventriculr dysfunction in the fetus: reltion to ortic vlve nomlies nd endocrdilfibroelstosis 423 ) 4- -c > 1, -J '._._ * Men +2SD * v * * * v ~~~~~~~*s-- -.-Men Men -2SD :5 Men of LV length by echo t necropsy (cm) Figure 8 greement (differences versus men) between left ventriculr length mesurements mde echocrdiogrphiclly nd t necropsy in the sme fetuses.7 Only fetuses in which the intervl between the two exmintions ws < two weeks re included (n = 16, men of differences = 65, SD of differences 127). = Figure 9 View of the open left ventricle of one of the cses t necropsy. The left ventriculr cvity is dilted nd there is considerble endocrdil fibroelstosis lining the cvity of the ventricle. The ortic vlve is thickened nd dysplstic. ov, ortic vlve; LV, left ventricle; MV, mitrl vlve. 3: ntlly cross the ortic vlve. In six cses the ortic vlve ws bicuspid lthough not obstructive. One of these hd hypoplsi of the ortic rch nd one developed hypoplstic left ventricle, but endocrdil fibroelstosis of the left ventricle ws the only pthologicl finding in the remining four cses. Thus of those with follow up informtion five cses hd progressed to the hypoplstic left hert syndrome. Discussion We originlly designted this chrcteristic echocrdiogrphic picture of left ventriculr dysfunction s criticl ortic stenosis. There were six cses, however, tht were indistinguishble echocrdiogrphiclly from the rest but which proved to hve thin nd ptent ortic vlve t necropsy. There were five cses tht hd ptent ortic vlve on prentl Doppler echocrdiogrphic studies but in which the vlve hd become tretic by the time of necropsy. Development into the hypoplstic left hert syndrome ws seen in five cses, s the left-sided structures filed to grow t norml rte with dvncing gesttionl ge. This type of left ventriculr dysfunction in the fetus, therefore, represents n overlp of diseses including primry left ventriculr endocrdil fibroelstosis, criticl stenosis of the ortic vlve, nd the hypoplstic left hert syndrome. It constitutes over 6% of the bnormlities encountered in prentl life compred with frequency of 1*2% of criticl ortic stenosis in postntl series.' This discrepncy is ccounted for by the observtion tht some of these cses seen in erly pregnncy will progress to either ortic tresi or the hypoplstic left hert syndrome nd tht some cses hve primry left ventriculr disese nd endocrdil fibroelstosis. Though the universl echocrdiogrphic feture of this condition ws poorly contrcting left ventricle, there were vried ssocited echocrdiogrphic nd ntomicl findings. Left ventriculr size ws within the norml rnge for gesttionl ge t presenttion, but the size of the ortic root nd mitrl orifice ws either norml or smll for the gesttionl ge. The echocrdiogrphic dignosis of endocrdil fibroelstosis correlted well with the findings post mortem. ndocrdil fibroelstosis ws frequent but not constnt ssocition. It lso vried in extent nd severity. chocrdiogrphiclly it proved impossible ccurtely to predict the morphology of the ortic vlve in ll the cses. If the ortic vlve ws well imged, however, thickened doming vlve could be identified in some cses. t necropsy the leflets of the ortic vlve were commonly seen to be thickened nd disorgnised but in six cses they hd reltively norml ppernce. The difficulty in compring the echocrdiogrphic nd ntomicl results is tht in some cses there ws n intervl between the two nd, s we found, chnges cn tke plce with dvncing gesttion. Intruterine closure of the tril septum hs been suggested s cuse of mlformtions of the left hert" nd closed or restrictive tril septum ws confirmed t necropsy in eight cses. In one cse seen t 22 nd 28 weeks' gesttion, the septum ppered ptent t the first scn nd closed six weeks lter. It therefore seems possible tht in those with n intct septum the flp ws held shut by the rised left tril pressure nd becme dherent s secondry phenomenon. In five cses, furthermore, the left tril pressure ws forcing the flp vlve into the right trium nd left to right flow ws seen on colour flow mpping. Thus n intct tril septum my be consequence rther thn cuse of the lesions in the left hert. It is commonly ssumed tht crdic mlformtion is well tolerted by the fetus. There ws evidence of intruterine crdic filure, none the less, t the initil exmintion in nine cses. One of these fetuses died in utero. The four who reched term died on the first dy of life. ll 12 bbies tht were born live hd norml vginl delivery but were in poor condition from birth. It is possible tht cesren section might hve resulted in neonte in better condition for vlvotomy or blloon dilttion of the mitrl vlve nd this hs been previously suggested.'2'3 But, there is poor long term Br Hert J: first published s /hrt on 1 December Downloded from on 29 October 218 by guest. Protected by copyright.

6 424 Shrlnd, hit, Fgg, nderson, Tynn, ook, lln prognosis for this condition despite surgery'4 nd this hs to influence the obstetric mngement. It is likely tht those cses with severe fibrotic chnges or smll left ventricle in ddition to smll mitrl nd ortic orifices, s seen in mny of our cses, will not survive relief of the obstruction'5 16 nd therefore these cses perhps should continue to be delivered normlly. Our observtions hve shown tht some of these cses will develop into the hypoplstic left hert syndrome. This hs importnt implictions for mny spects of fetl echocrdiogrphy. The vlue of screening of the four chmber view of the hert during the routine obstetric scn t 18 weeks' gesttion is well estblished in the United Kingdom. The results of this study suggest tht some forms of severe left hert disese my not be fully developed t 18 weeks nd therefore my be overlooked in the screening progrme involving scnning t this time. lso, the progressive chnges tht my occur s pregnncy dvnces mke the ccurte prediction of prognosis in erly pregnncy difficult. Thirdly, the outcome of this form of disese of the left hert in the fetus is poor so tht vrious therpeutic options should be considered during fetl life. The dignosis ws mde erly enough for termintion to be possible option in 18 cses. Sixteen mothers (89%) chose this course. lterntively, relief of ortic vlve obstruction during pregnncy might llow the left ventricle time for recovery nd improvement in growth before birth nd my prevent or even reverse the development of endocrdil fibroelstosis.9 However, there my be problems with prentl selection of ptients becuse it cn sometimes be difficult to be sure tht the ortic vlve is bnorml. But even with ccurte selection, by the time the ptient comes to our ttention it my be too lte in gesttion to prevent endocrdil fibroelstosis nd left ventriculr dmge. In summry, left hert dysfunction cn be identified in utero from echocrdiogrphic chrcteristics. The nturl history in cses seen in erly gesttion seemed to be n evolution into the hypoplstic left hert syndrome. The outlook for those in our series seen in lter pregnncy hs been universlly blek. These observtions llow more rtionl pproch to possible tretment. The options include termintion of pregnncy; the explortion of methods of chnging the course of the disese process during gesttion; plnning the delivery to obtin the best possible neontl condition; nd preprtion for immedite vlvotomy in selected infnts. GKS, SK,, RH, nd LD re supported by the British Hert Foundtion. MT is supported by the Joseph Levy Foundtion. 1 Kleinmn S, Hobbins J, Jffe, LynchD, TlnerNS. chocrdiogrphic studies of the humn fetus: prentl dignosis of congenitl hert disese nd crdic dysrhythmis. Peditrics 198;65: lln LD, rwford D, nderson RH, Tynn MJ. chocrdiogrphic nd ntomicl correltions in fetl congenitl hert disese. Br Hert J 1984;52: Shrlnd G, lln L. Detection of congenitl bnormlities of the crdiovsculr system by ultrsound. In: hmberlin G, ed. Modern ntentl cre of the fetus. Oxford: Blckwell Scientific Publictions, 199: lln LD. Mnul of fetl echocrdiogrphy. Lncster: MTP Press, 1986:52,65,7. 5 lln LD, hit SK, l-ghzli W, rwford D, Tynn M. Doppler echocrdiogrphic evlution of the norml humn fetl hert. Br Hert J 1987;57: Plldini D, hit SK, lln LD. Prentl mesurement of the crdiothorcic rtio in the evlution of hert disese. rch Dis hild 199;65: Blnd JM, ltmn DG. Sttisticl methods for ssessing greement between two methods of clinicl mesurement. Lncet 1986;i: Kenny JF, Plppert T, Doubilet P, et l. hnges in intrcrdic blood flow velocities nd right nd left ventriculr stroke volumes with gesttionl ge in the norml humn fetus: prospective Doppler echocrdiogrphic study. ircultion 1986;74: Mxwell D, lln L, Tynn MJ. Blloon dilttion of the ortic vlve in the fetus: report of two cses. Br Hert J 1991;65: Fyler D, Buckley LP, Hellenbrnd W, ohn H. Report of the New nglnd Regionl Infnt rdic re Progrm. Peditrics 198;65(suppl): tkins DL, lrk B, Mrvin WJ. Formen ovle/tril septum rtio: mrker or trnstril blood flow. ircultion 1982;66: Huht J, rpenter RJ, Moise KJ, Deter RL, Ott D, McNmr DG. Prentl dignosis nd postntl mngement of criticl ortic stenosis. ircultion 1987;75: Robertson M, Byrne PJ, Penkoske P. Perintl mngement of criticl ortic vlve stenosis dignosed by fetl echocrdiogrphy. Br Hert J 1989;61: Zeevi B, Kene JF, stend R, Perry SB, Lock J. Neontl criticl vlvr ortic stenosis: comprison of surgicl nd blloon diltion therpy. ircultion 1989;8: Ltson L, hethm JP, Gutgesell HP. Reltion of the echocrdiogrphic estimte of left ventriculr size to mortlity in infnts with severe left ventriculr outflow obstruction. m J rdiol 1981;48: Rhodes L, oln SD, Snders SP. Predictors of survivl in neontes with criticl ortic stenosis [bstrct]. ircultion 1989;8 (suppl II):186. Br Hert J: first published s /hrt on 1 December Downloded from on 29 October 218 by guest. Protected by copyright.