Totalanomalouspulmonary venous return Prenatal damage ... · 514 Clinicalfeatures All the babies presented withcyanosis duringthefirst six hours oflife. Nonehad a murmursave case

Br Heartj 1982; 48: 513-24

Total anomalous pulmonary venous returnPrenatal damage to pulmonary vascular bed andextrapulmonary veins

SHEILA G HAWORTH

From the Department ofPaediatric Cardiology, Institute ofChild Health, Guilford Street, London

SUMMARY To investigate the possibility that pulmonary vascular disease may be present at birth inchildren presenting with obstructed total anomalous pulmonary venous return in the neonatal period,pulmonary vascular structure was analysed in the lungs of six babies who died during the first week oflife. Five babies had infradiaphragmatic total anomalous return and in one the pulmonary veins drainedto the right atrium. In all cases mean percentage arterial medial thickness was greater than is normal at5 hours. The most striking change occurred in the intra- and extrapulmonary veins. Within the lung, inall six cases mean percentage vein wall thickness was significantly increased and in two cases intimalproliferation occurred in preacinar veins. The extrapulmonary veins were generally small in all fivecases of infradiaphragmatic total anomalous pulmonary venous return, microscopically were

abnormally thick walled in four, and showed intimal proliferation in three cases. In two cases thedescending vertical vein was severely narrowed or occluded.A prenatal increase in intrapulmonary arterial and venous muscularity may encourage episodic

pulmonary hypertension in the immediate postoperative period. In the infradiaphragmatic type ofanomaly, prenatal structural changes in the extrapulmonary veins may predispose to the laterdevelopment of pulmonary vein steniosis despite a successful surgical repair.

The mortality rate for correction of total anomalouspulmonary venous return has improved considerablyduring the past 10 years. Two recent series quote ahospital survival rate of 87%' and 88%.2 Age isbecoming less important as a determinant of survivalprobably because of earlier patient referral andimprovements in surgical technique. In one recentstudy age was shown to have no effect on survival. ' AtThe Hospital for Sick Children, Great Ormond Street,however, during the past five years the hospital survivalrate for children aged 1 week or more was 87% while forthose less than 1 week of age it was only 36%. Thehigher mortality in the younger age group may perhapsbe the result not of age itself but of other factorsassociated with the early development of pulmonaryvenous obstruction. Little is known about the state ofthe pulmonary vascular bed at birth in these babies,

SGH is supported by the British Heart Foundation.

Accepted for publication 3 August 1982

but, in slightly older patients, pulmonary vasculardisease has been considered to be an importantdeterminant of survival.?5

In order to investigate the possibility that pulmonaryvascular disease may be present at birth in childrenpresenting with obstructed total anomalous pulmonaryvenous return in the neonatal period, pulmonaryvascular structure has been analysed in the lungs of sixbabies who died during the first week of life. Previouspathological studies on the lung in total anomalouspulmonary venous return have concentrated onpulmonary arterial structure.5 6 Recently, however,there have been several clinical reports of pulmonaryvein stenosis developing in patients who have had anapparently successful repair of the anomalous venousdrainage.' 2 The stenosis developed in the pulmonaryvein, proximal to the anastomosis between the venousconfluence and the left atrium, and was not related tothe suture lines. In the present study, therefore, thestructure of the intra- and extrapulmonary veins hasbeen analysed in addition to that of the arteries.

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Clinical features

All the babies presented with cyanosis during the firstsix hours of life. None had a murmur save case 5 inwhom a soft systolic murmur was heard at the upperleft sternal border. In cases 2 and 6, the liver was

enlarged below the right costal margin by 2 and 5 cm,respectively. The electrocardiogram showed signs ofright ventricular hypertrophy in all except case 4. In allcases the chest radiograph showed a heart of normalsize. The lung fields had a fine granular appearance inall save cases 1 and 4. At cardiac catheterisation thepulmonary arterial pressure was equal to, or exceeded,the systemic arterial pressure and the arterial oxygensaturation was similar in the pulmonary artery andaorta in all cases (Table). In five cases pulmonaryangiography showed total anomalous pulmonaryvenous return to an infradiaphragmatic site, except incase 4, where the left upper lobe only drained into a leftsuperior vena cava. In the remaining case (case 5) a

diagnosis of total anomalous pulmonary venous returnto the right atrium was made by two dimensionalechocardiography.Four babies died at or soon after surgical repair ofthe

anomaly at between 1 and 6 days of age. Cases 4 and 5died before operation could be attempted. Theinteratrial defect was a secundum atrial defect found at

Haworth

operation in cases 2, 3, and 6, and a stretched foramenovale was present in cases 1, 4, and 5.At necropsy, in four of the cases with

infradiaphragmatic total anomalous pulmonary venous

return, the descending vertical vein entered the portahepatis, and in the fifth case (case 1) it entered theinferior gastric vein. The ductus arteriosus was or hadbeen patent in all cases, having been ligated in thosepatients submitted to operation. Case 1 also had a smallsubaortic ventricular septal defect measuring 3 mm indiameter and partial juxtaposition of the left atrialappendage. In all cases the left ventricle was of normalsize.

Pathological studies

The pulmonary vessels were injected in only twopatients, cases 4 and 5. The pulmonary arteries were

injected under pressure with a barium sulphate gelatinmixture in the right lung ofcase 4 and in the middle andlower lobes of the right lung in case 5. The pulmonaryveins of the right upper lobe in case 5 were also injectedusing the same technique. The lungs of these two cases

were fixed by injecting the airways with formol saline at

constant pressure. Blocks of tissue 1 cm square were

taken for histological examination from the lungs of allcases, as indicated in Fig. 1.

Table Clinical data

Case Diagnosis Age at Pulmonary Systemic % 02 saturation Age atNo. cardiac arterial arterial death

catheterisation or right or left Pulmonary Aorta (d)(d) ventricular ventricular artery

pressure pressure(mmHg) (mmHg)

1 Infradiaphragmatic 1 85/50 75/50 60 62 1total anomalouspulmonary venous 60 60return


3 Infradiaphragmatic 3 55/3 59/35 64 67 3total anomalouspulmonary venous 43return

4 Infradiaphragmatic 3 95/55 55/40 64 64 4total anomalouspulmonary venous 70 45 No operationreturn

5 Total anomalous 3 70/50 70/50 61 56 5pulmonary venousreturn to right 56 56 No operationatrium




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Prenatal changes in total anomalous pulmonary venous return

In both the injected and uninjected uninflated tissue,pulmonary vascular structure was analysed usingquantitative morphometric techniques.68 In each case,the percentage wall thickness of both arteries and veinswas determined. The vessels were grouped accordingto their external diameter and the mean percentage wallthickness was calculated for each size range. For eachcase, percentage wall thickness was determined in eachlobe separately. The mean external diameter and theproportion of non-muscular, partially muscular, orentirely muscularised arteries accompanying each typeof peripheral airway (terminal bronchioli, respiratorybroncholi, and alveolar ducts) were assessed for eachlobe. The results in each lobe and, where possible, eachlung were compared using Student's t test.

In order to estimate the number of intra-acinar*arteries and veins the ratio of alveoli to arteries andalveoli to veins was determined in the injected tissue ofcases 4 and 5.On the fixed specimens the lumen diameter of the

extrapulmonary veins was measured in all except case4. In four cases of infradiaphragmatic total anomalouspulmonary venous return the lumen diameter of thedescending vertical vein was also measured. Fig. 1indicates those extrapulmonary veins and regions ofthedescending vertical vein selected for histologicalexamination. The descending vertical vein was thick

*An acinus is all lung tissue distal to a terminal bronchiolus.

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515

walled for a distance of 1-5 cm proximal to its enteringthe porta hepatis in case 2, and the lumen was occludedin this region in case 6. In both cases, a serialreconstruction was made of this part of the descendingvertical vein.

All histological sections of lung and venous tissuewere 4 ,um thick and stained with haematoxylin andeosin and with Miller's elastic stain counterstained withvan Gieson's stain. The serial sections were all stainedwith Miller's elastic stain.

Results

On microscopical examination of the lung tissue, in allcases the alveoli appeared normal, were mature, andnot saccular. The lymphatic channels wereconsiderably dilated in all sections of lung tissueexamined. In the injected specimens, the twopostmortem arteriograms and one lobar venogramshowed a normal branching pattern and no stenoses.

INTRAPULMONARY ARTERIESIn all cases the media of the intrapulmonary arteriesappeared thicker than normal. In each case, in bothinjected and uninjected tissue, mean percentagearterial medial thickness in arteries of all sizes wassignificantly greater than is normal at 5 hours of age inall parts of the lung examined (Fig. 2 and 3). Theincrease in muscularity was similar in different parts of

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Fig. 1 Diagram to show the type of total anomalous pulmonary venous return and the lumen diameter ofthe extrapulmonary veins anddescending vertical vein (mm). The lobes oflung examined histologically are indicated by a continuous outline to the lung, and those lobesnot examined histologically are indicated by an interrupted line. The extrapulmonary and descending vertical veins examinedhistologically are shown by a +.



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the same lung and in the two lungs of the same casewhere the tissue was available for such a comparison tobe made. Microscopical examination of the lung tissuefrom all cases and the quantitative studies on theinjected lung specimens of cases 4 and 5 showed thatmuscle was present in smaller and more peripheralarteries than is normal (Fig. 3 and 4).

Intimal proliferation was not seen.The mean external diameter of arteries ac-

companying peripheral airways in both injected anduninjected tissue was within normal limits for age.Within each case there was no significant regionalvariation in intra-acinar arterial size. In all cases thenumber of intra-acinar arteries appeared normal ongeneral microscopical examiriation. More precisely,the ratio of alveoli to arteries was normal in the injectedtissue ofcases 4 and 5, being 10 4 and 9 4, respectively.

INTRAPULMONARY VEINSLike the arteries, the intrapulmonary veins seen in allthe sections of lung tissue examined microscopicallyfrom all six cases showed an increase in wall thicknessof both pre- and intra-acinar vessels. The intra-acinarveins had a thickened media and a well-definedexternal elastic lamina, and resembled arteries (Fig. 5).The media of the large preacinar veins consisted ofthick continuous elastic fibres separated by anincreased amount of smooth muscle (Fig. 6). A thick

44

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Fig. 2 Uninjected lung tissue. Mean percentage arterial medialthickness related to external diameter (,um), showing the increasein muscularity infour cases oftotal anomalous pulmonary venous

return as compared with the normal atS hours and in older infants.Case I O-O;case2 A-A;case3 E-* ;case6 # #;SEI.

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Fig. 3 Injected lung tissue. Mean percentage arterial medialthickness related to external diameter(,Im) showing the increase inmuscularity in cases 4 andS as compared with the normal at 3 daysand in older children.Case 4 A-A; case S U-*; SEI.

adventitia was composed of densely arranged collagenfibres.

Like the arteries, intimal proliferation was not foundin the intra-acinar veins in any ofthe cases. By contrast,the preacinar intrapulmonary veins showed intimalproliferation in two cases, being found in both lowerlobes of case 3, and in the right upper and lower lobe ofcase 5.Mean percentage vein wall thickness was

significantly greater than normal in all cases, usinguninjected tissue in five cases and injected tissue in case5 (Fig. 7). The normal tissue used for comparisonincluded that of stillborn fetuses aged 36 and 38 weeksand full-term infants up to 6 hours of age. In normalinfants mean percentage vein wall thickness does notchange significantly after birth.9 At 1 to 6 days (the ageat which the children in the study group died)muscularity would certainly not be greater than inthese controls. In the cases of total anomalouspulmonary venous return analysis of the tissueavailable showed no significant difference in vein wallmuscularity between different lobes or betweendifferent lungs of the same case.

Accurate counts of the number of smallintrapulmonary veins related to the number of alveoliwere possible only in the injected specimen of case 5,where the alveolar to vein ratio was normal at 4:1. The

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Prenatal changes in total anomalous pulmonary venous return 517

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Fig. 5 Photomicrograph of thick walled muscular small pulmonary veins which resemble arteries. (Originalmagnification x367.)



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'.,;rr f . . ..:IS',; ' : :. . e. ..Fig. 6 Photomicrograph ofa large preacinar pulmonary vein with a thickened media (M) and adventitia (A) andintimal proliferation (IPi). (Original magnification x38).

Fig. 7 Mean percentage vein wall thickness in uninjected tissue,related to external diameter (,um), showing an increase in veinwall thickness infive cases oftotal anomalous pulmonary venousreturn as compared with the normal ofsimilar age.Case I U--; case 2 [-O; case30 0; case 4 ,- ;case 6 A-A; SEI.

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right upper lobe venogram in case 5 showed a normallumen diameter of 1 to 1-8 mm in the veins situatedmidway between the hilum and pleural surface.

PULMONARY VEIN-BRONCHIAI VEINANASTOMOSESConnections between dilated thick walled pulmonaryveins and thin walled bronchial veins were identifiedmore readily than in the normal lung in both uninjectedand injected tissue. In addition, injecting thepulmonary veins filled enlarged bronchial veins withinjection material more frequently than is normal (Fig.8).

EXTRAPULMONARY VEINSIn the normal fixed specimen the lumen diameter oftheundistended pulmonary veins during the first week oflife is 2 to 3 mm. Histologically, the wall has a thinmedia and an adventitia containing a layer ofmyocardial fibres (Fig. 9a). In the five cases of totalanomalous pulmonary venous return in which theextrapulmonary veins were examined the veins variedin size within and between cases, were generallysmaller than normal, and only in case 5 were all theveins at least 2 mm in diameter (Fig. 1).Macroscopically, the wall was abnormally thick in theveins of cases 2, 3, and 6. Microscopically, the thick

extrapulmonary veins in these three cases and in case 5showed similar structural features (Fig. 9b). Withinthe wall three or four thick continuous elastic fibresseparated by muscle cells could be distinguished andthis layer resembled the media of a normalextrapulmonary vein. Occasionally, this layer wasimmediately beneath the intima, but more commonly itlay beneath several layers of elastic fibres withinterspersed muscle cells and collagen (Fig. 9b).Because the adventitia contained long, thick elasticfibres, the walls of all the extrapulmonary veinsexamined contained 12 to 20 layers of elastic fibres. Incases 2, 3, and 6 the extrapulmonary veins containedeccentric areas of amorphous intimal tissue (Fig. 9b).No myocardial muscle fibres were seen in any of theextrapulmonary veins.

DESCENDING VERTICAL VEINIn four of the five children with infradiaphragmatictotal anomalous pulmonary venous return, thedescending vertical vein was patent throughout exceptin case 6 when it was occluded for a distance of 4 mmimmediately proximal to its connection with the portalsystem. In all except case 1, the descending verticalvein had a diameter of 3 to 3-5 mm throughout all ormost of its length. In case l it measured only 1 to 2mmin diameter. The microscopical features were similar in

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Fig. 8 Photomnicrograph ofinjected lung tissue in case 4. Injection ofthe pulmonary veins (PV)filled the bronchialveins (BV). BA, bronchial artery. (Original magnification x38.)

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(a)

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Fig. 9 (a) Photomicrograph ofthe wall ofan extrapulmonary veinfrom a nornal lung at the age of3 days. Musclelayer (M) is thin. Myocardialfibres (Myo) are present in the adventitia (A). (Original magnification x38.) (b)Photomicrograph ofthe left lower lobe pulmonary vein in case 3. Internal elastic lamina (IL) demarcates the musclelayer (M)from the intimal proliferation (IP). The adventitia (A) is abnormally thick and dense and contains muchelastin. (Original magnification x38.)

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all three specimens examined histologically. Beneaththe endothelium lay a thin layer composed of three tofour long unfragmented elastic fibres interspersed withsmooth muscle cells A thick adventitia was composedof dense collagen, and long continuous elastic fibreswere concentrated in the outer half of the wall. Nomyocardial fibres were present. In case 2 a serialreconstruction showed that as the vein approached thediaphragm the wall became thicker, and smalleccentric unobtrusive mounds of intimal tissueprojected into the lumen. In case 6 these changes weremore pronounced until the descending vertical veinbecame occluded with collagen fibres (Fig. 10).

In all four children who had undergone a surgicalrepair the anastomosis between the left atrium andcommon pulmonary vein was wide and measured 7 to 8mm in diameter in the fixed specimen.

Summary of pathological findingsOf the five patients with infradiaphragmatic totalanomalous pulmonary venous return, the descendingvertical vein was patent in four, the extrapulmonaryveins were generally smaller than normal in all, and thevein wall was abnormally thick and showed intimal

proliferation in three cases. In the one case of totalanomalous pulmonary venous return to the rightatrium the extrapulmonary veins were normal in sizeand thickness, though the histological features weresimilar to those in cases of the infradiaphragmatic typeof drainage. The extrapulmonary veins were composedof an increased amount of collagen and elastin, withoutmyocardial fibres in the adventitia.

Pulmonary arterial medial thickness was increased,and muscle was present in smaller more peripheralarteries than is normal for age. The intra-acinar arterieswere normal in size and appeared to be normal innumber. In all cases the mean percentage vein wallthickness was increased in pre- and intra-acinar veins.Intimal proliferation occurred in the large pre-acinarveins of two of the six cases, though in no case was itpresent in all parts of the lung examined. The numberof intra-acinar veins appeared normal. Anastomosesbetween small pulmonary and bronchial veins presentin the normal lung were prominent in uninjectedmaterial, and in the one injected specimen thepulmonary veins frequently filled the bronchial veinsalso. Within the group of six cases, there was norelation between the amount of pulmonary arterial orvenous muscularity and age.

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Fig. 10 Photomicrograph ofa descending vertical vein occluded byfibrous tissue just above the diaphragm.(Original magnification x38.)

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Discussion

In six patients dying with obstructed total anomalouspulmonary venous return during the first six days oflife, an increase in the muscularity of theintrapulmonary arteries and veins indicates thatobstruction to pulmonary venous outflow was presentbefore birth. The deposition of increased amounts ofsmooth muscle, elastin, and collagen in both extra- andintrapulmonary veins, and the narrowing or evenocclusion of the descending vertical vein by collagenrather than by amorphous acellular material suggestthat obstruction to pulmonary venous return had beenpresent for a considerable time before birth. Patientswith the infradiaphragmatic type of total anomalouspulmonary venous return are usually considered tohave obstruction to pulmonary venous return becauseof the length and relatively small cross-sectional area ofthe anomalous venous pathway and the resistance toblood flow through the hepatic sinusoids when theductus venosus is closed. In the present study, the sizeof the descending vertical vein appeared to obstructflow in three of the five cases with infradiaphragmatictotal anomalous pulmonary venous return. In the onepatient in whom the pulmonary veins drainedanomalously to the right atrium, an anatomical site ofobstruction was not identified. The structural changewithin the lungs and the severity of the pulmonaryhypertension were, however, as severe in all threepatients without demonstrated anatomical obstructionas in those with obstruction.

Despite partial or even total obstruction topulmonary venous drainage in all six cases the lungscontinued to grow in utero and after birth sustained lifefor up to six days. It has been suggested that in thepresence of pulmonary venous hypertension theanastomotic channels between pulmonary andbronchial veins present in the normal lung widen toallow blood to flow from the pulmonary veins to thepulmonary branches of the bronchial veins and thenceinto the azygos system and superior vena cava.'I 11 Inthe arterial circulation, anastonioses between thepulmonary and systemic circulations occur morefrequently in the newborn than in the older lungl2 andthe same may be true of the venous systems. In somepatients there was a considerable variation in the lumendiameter ofthe extrapulmonary veins, but there was nosignificant regional variation in either arterial or venousmuscularity in the cases studied. Ferencz andDammann'3 found arterial medial hypertrophy in bothlungs in the presence of unilateral pulmonary venousobstruction. Possibly the wealth ofvenous anastomosesin the lung and the pleurohilar network of bronchialveins help to reduce the effect ofregional differences inthe severity of obstruction to pulmonary venousoutflow. The pronounced dilatation of the lymphatic

channels in all cases in the present series attests to theincreased drainage of fluid from the lung by this route.

In the present study intrapulmonary arterial andvenous muscularity was increased<.< Using the sametechniques of quantitative morphometric analysis, asimilar increase in muscularity has been found in aslightly older group of children dying with obstructedtotal anomalous pulmonary venous return during thefirst three months of life.6 The structural changes in theveins were more severe in the present study,particularly in the preacinar veins which were verythick walled and showed intimal proliferation in twocases. Most of the structural changes present in botharteries and veins were, however, potentially reversiblein both series of cases. Newfeld et al.S studied an oldergroup of patients aged 5 days to 12 years (median 3months), and reported more advanced pulmonaryvascular disease. In that series, 12 of the 13 childrenaged 1 month or less had arterial cellular intimalproliferation and four had occlusive intimal fibrosis,though these changes were not necessarily found inmore than a few of the arteries examined. The presentstudy indicates that children with total anomalouspulmonary venous return who present to thecardiologist during the first days of life may have beenborn with significant pulmonary vascular disease.These findings help to explain the sudden andunexplained increases in pulmonary arterial pressureand resistance which occur in some young infantsimmediately after repair of the anomaly. 14 The increasein muscularity probably encourages both arteries andveins to vasoconstrict in response to hypoxia andacidosis, making the lung extremely vulnerable despitethe absence ofsevere occlusive intimal change in younginfants. The administration of pulmonary vasodilatorsubstances such as tolazolinel4 or dopamine has beenfound to lower the pulmonary vascular resistance onsuch occasions.The type of pathological change found in the arterial

walls ofyoung infants with total anomalous pulmonaryvenous return is generally considered to be reversible.In addition, the intra-acinar arteries are generallynormal in size and number. In practice, patients withtotal anomalous pulmonary venous return whoundergo repair and survive have a normal pulmonaryvascular resistance unless pulmonary venousobstruction is present for any reason.15 16

Several published follow-up studies on patients withtotal anomalous pulmonary venous return who hadundergone a satisfactory surgical repair in early infancyinclude one or more patients who developed stenosis ofat least one extrapulmonary vein.1 2 17 18 The presentstudy includes several instances of small thick walledextrapulmonary veins, sometimes showing intimalfibrosis. The lumen of the vessels was narrowedbecause the vessel was intrinsically small. There was no

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instance of narrowing by external compression or by alocalised stricture or a diaphragm. The normalpulmonary vein is thin walled and readily distensible.Abnormally thick walled, small veins may fail to grownormally as the cardiac output increases with growth,encouraging further intimal proliferation and fibrosis,to give an appearance similar to that described byFriedli et al.,'8 Katz et al.,2 and Whight et al.'5 in theircases. Haemodynamic studies on a group of apparentlyhealthy survivors suggested that relative narrowing ofthe pulmonary veins might occur frequently, but wasusually "unimportant and non-progressive".'5Pulmonary venous stenosis has occurred after repair

of the total anomalous pulmonary venous return to thecoronary sinus2 15 19 20 and to the liver.' 15 17 Babies withinfradiaphragmatic total anomalous pulmonary venousreturn may, however, be particularly disposed todevelop pulmonary vein stenosis. In the majority ofthese babies, pulmonary venous return is obstructed.Narrowing of the common pulmonary vein, as seen inthree cases in the present series, may help explain theincreased wall thickness of the extrapulmonary veins atbirth in such children, predisposing them to furtherocclusive pulmonary venous change after repair. In twochildren with infradiaphragmatic total anomalouspulmonary venous return who developed postoperativepulmonary vein stenosis, patch angioplasty wassuccessful initially, but the veins subsequently becamerestenosed.' It may perhaps be more difficult to achievesatisfactory permanent relief of pulmonary veinstenosis in patients with total anomalous pulmonaryvenous return because the whole vein is small, ratherthan there being a localised constriction.

In a recent surgical series patients with theinfradiaphragmatic type of total anomalous pulmonaryvenous return had a higher mortality, both early andlate, than did those with other types of total anomalouspulmonary venous return.' The present study alsosuggests that this group of patients is particularlyvulnerable. Five of the six consecutive specimensreferred for study from children dying with obstructedtotal anomalous pulmonary venous return during thefirst week of life showed the infradiaphragmatic type ofpulmonary venous return. Both the intrapulmonaryvessels and extrapulmonary veins showed structuralabnormalities likely to increase the operative risk andpredispose such patients to the development ofpulmonary vein stenosis after a technically successfulsurgical repair.

The author wishes to thank the physicians, surgeons,and pathologists of the Brompton Hospital, Guy'sHospital, and the Hammersmith Hospital forpermission to study their cases.

References

1 Turley K, Tucker WY, Ullyot DJ, Ebert PA. Totalanomalous pulmonary venous connection in infancy:influence of age and type of lesion. Amj Cardiol 1980; 45:92-7.

2 Katz NM, Kirklin JW, Pacifico AD. Concepts andpractices in surgery for total anomalous pulmonaryvenous connection. Ann Thorac Surg 1978; 25: 479-87.

3 Gersony WM, Bowman FO Jr, Steeg CN, Hayes CJ, JesseMJ, Malm JR. Management of total anomalouspulmonary venous drainage in early infancy. Circulation1971; 43, suppl I: 1-19.

4 Wukasch DC, Deutsch M, Reul GJ, Hallman GL, CooleyDA. Total anomalous pulmonary venous return: review of125 patients treated surgically. Ann Thorac Surg 1975; 19:622-33.

5 Newfeld EA, Wilson A, Paul MH, Reisch JS. Pulmonaryvascular disease in total anomalous pulmonary venousdrainage. Circulation 1980; 61: 103-9.

6 Haworth SG, Reid L. A structural study of the pulmonarycirculation and of the heart in total anomalous pulmonaryvenous return in early infancy. Br Heart J 1977; 39:80-92.

7 Hislop A, Reid L. New pathological findings inemphysema of childhood. I. Polyalveolar lobe withemphysema. Thorax 1970; 25: 682-90.

8 Davies G, Reid L. Growth of the alveoli and pulmonaryarteries in childhood. Thorax 1970; 25: 669-81.

9 Hislop A, Reid L. Fetal and childhood development oftheintrapulmonary veins in man-branching pattern andstructure. Thorax 1973; 28: 3 13-9.

10 Marchand P, Gilroy JC, Wilson VH. An anatomical studyof the bronchial vascular system and its variations indisease. Thorax 1950; 5: 207-2 1.

11 Wagenvoort CA, Wagenvoort N, Becker AE. The effectof obstructed pulmonary venous blood flow on thedevelopment of alternative pathways in the lung.J Pathol1972; 107: 21-5.

12 Wagenvoort CA, Wagenvoort N. Arterial anastomosis,bronchopulmonary arteries and pulmobronchial arteriesin perinatal lungs. Lab Invest 1967: 16: 13-24.

13 Ferencz C, Dammann JF Jr. Significance of thepulmonary vascular bed in congenital heart disease. V.Lesions of the left side of the heart causing obstruction ofthe pulmonary venous return. Circulation 1957; 16: 1046-56.

14 Shinebourne EA, Jones ODH, Denison DM, Lincoln C,Haworth SG. Growth and remodelling of the pulmonarycirculation in congenital heart disease: clinicalimplications. In: Godman M, ed. Paediatric cardiology.vol. 4. Edinburgh, London: Churchill Livingstone, 1981:71-80.

15 Whight CM, Barratt-Boyes BG, Calder AL, Neutze JM,Brandt PWT. Total anomalous pulmonary venousconnection. Long-term results following repair ininfancy. J Thorac Cardiovasc Surg 1978; 75: 52-63.

16 Macartney FJ, Taylor JFN, Graham GR, de Leval M,Stark J. The fate ofsurvivors ofcardiac surgery in infancy.Circulation 1980; 62: 80-91.

17 Fleming WH, Clark EB, Dooley KJ, et al. Latecomplications following surgical repair of total anomalous

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pulmonary venous return below the diaphragm. AnnThorac Surg 1979; 27: 435-9.

18 Friedli B, Davignon A, Stanley P. Infradiaphragmaticanomalous pulmonary venous return. Surgical correctionin a newborn infant. J Thorac Cardiovasc Surg 1971; 62:301-6.

19 Gathman GE, Nadas AS. Total anomalous puhionaryvenous connection: clinical and physiologic observationson 75 pediatric patients. Circulation 1970; 42: 143-54.

20 Lucas RV Jr, Anderson RC, Amplatz K, Adams P Jr,Edwards JE. Congenital causes of pulmonary venousobstruction. Pedlatr Clin North Am 1963; 10: 781-836.

Requests for reprints to Dr S G Haworth, Departmentof Paediatric Cardiology, The Hospital for SickChildren, Great Ormond Street, London WC1N 3JH.



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Totalanomalouspulmonary venous return Prenatal damage ... · 514 Clinicalfeatures All the babies presented withcyanosis duringthefirst six hours oflife. Nonehad a murmursave case