Br Heart J 1991;65:280-6

Fixed subaortic stenosis: anatomical spectrum andnature of progression

Jung Yun Choi, Ian D Sullivan

AbstractRetrospective echocardiographic reviewidentified 58 consecutive infants andchildren with fixed subaortic stenosis.Mean (SD) age at diagnosis was 4-8 (3-6)years (range two days to 14-7 years), anddiagnosis occurred in infancy in eight.Associated cardiac abnormalities werepresent in 41 (71%) whereas fixedsubaortic stenosis was an isolated lesionin 17 (29%). Four types of fixed subaorticstenosis were identified: short segment(47 (81%)), long segment (7 (12%)), pos-terior displacement of the infundibularseptum with additional discrete narrow-ing of the left ventricular outflow tract (3(5%)), and redundant tissue arising fromthe membranous septum (1 (2%)).Echocardiographic studies had been per-formed before the diagnosis of fixedsubaortic stenosis in nine patients, allwith associated abnormalities. Thesewere performed in infancy in each andshowed a "normal" left ventricularoutflow tract in six-and posterior devia-tion of the infundibular septum in three.In 16 patients serial echocardiographicstudies had been performed after thediagnosis of fixed subaortic stenosis butbefore surgery of the left ventricularoutflow tract. Rapid evolution of shortsegment to long segment narrowing wasseen in one patient, and tethering of theaortic valve or mitral valve developed ina further four patients. Aortic valve ormitral valve involvement was not seenbefore the age of three years but wascommon thereafter (10140 patients,25%).Fixed subaortic stenosis may be an

"acquired" lesion with the potential forchanges in form as well as progression inseverity of left ventricular outflow tractobstruction.

Cardiothoracic Unit,Hospital for SickChildren, LondonJ Y ChoiI D SullivanCorrespondence toDr Ian D Sullivan,Cardiothoracic Unit,Hospital for Sick Children,Great Ormond Street,London WC1N 3JH.Accepted for publication4 January 1991

Fixed subaortic stenosis can occur in isolationor in association with other structural heartdefects but it is rarely diagnosed in infancy.'The subvalvar obstruction is usually a fibrousshelf or a long fibromuscular narrowing.45 Incontrast, when subaortic stenosis occurs ininfancy it is more often the result of a

malalignment ventricular septal defect withposterior deviation of the outlet septum intothe left ventricular outflow tract, usually inassociation with coarctation or interruption ofthe aortic arch.6

Fixed subaortic stenosis progresses inseverity7 and may even present as an"acquired" condition.3 The mechanism ofprogression is unknown. Further knowledgeof the course would be a useful guide tooptimal management, which is controversial.79Cross sectional echocardiography can definethe nature of subaortic stenosis and can easilybe repeated. Consequently, this study wasperformed to detail the echocardiographicfindings of subaortic stenosis at different agesand to identify the nature of progression onserial studies.

Patients and methodsEchocardiographic and surgical records at theHospital for Sick Children between April1981 and December 1986 were reviewed.Fifty eight cases of subaortic stenosis withnormal cardiac connections were diagnosed.The criterion for diagnosis was the demon-stration of a localised subvalvar discrete ridgeor long segment narrowing in the left ven-tricular outflow tract at echocardiographicexamination. This was confirmed by inspec-tion at operation or necropsy whenever possi-ble. Long segment narrowing was diagnosedwhen the length of the obstruction in the leftventricular outflow tract was more than onethird of the aortic valve diameter.'0 Patientswith posterior deviation of the infundibularseptum were excluded unless there wasadditional discrete narrowing in the left ven-tricular outflow tract. Similarly, patients withobstruction of the left ventricular outflowtract caused by hypertrophic cardiomyopathywere excluded. Mitral valve involvement wasdiagnosed when abnormal tissue was attachedto the anterior mitral valve leaflet whichtethered the anterior mitral leaflet during sys-tole. Aortic valve involvement was diagnosedwhen abnormal tissue in the left ventricularoutflow tract seemed to be tethered to the baseof the aortic valve.

All available echocardiograms performedbefore or after the diagnosis of subvalvaraortic stenosis, but before surgical procedureson the left ventricular outflow tract, werereviewed to determine sequential changes.The echocardiograms had been recorded onU-matic or VHS video tape by an ADR SC-2000, ATL mark 5, ATL 600, Ultramark 4, orUltramark 8 machine. During the course ofthe study, operation to the left ventricularoutflow tract was undertaken in 30/58 (52%)patients, twice in three of them. Five patientsdied and a necropsy was performed in three ofthem.

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Anomalies associated with subaortic stenosis

Associated anomalies

Nature of Age at diagnosis SVMSsubaortic range (median) + Inf Distalstenosis n (years) VSD Coa/IAA BAV MVS LSVC PDA PS ASD AVSD APW PVS Ao

Short segment 49 0-1-14-7 (4 5) 19 13 6 5 7 6 1 1 2 1 1 0Long segment 8 08-10-4 (4 0) 2 3 3 1 1 2 1 1 0 0 0 1Membranous septum 1 2days 0 0 0 0 1 0 0 0 0 0 0 0

APW, aortopulmonary window; ASD, atrial septal defect; AVSD, atrioventricular septal defect; BAV, bicuspid aortic valve; Coa/IAA, coarctation or interruptionof aortic arch; distal Ao, diffuse narrowing of distal aorta and iliac vessels; Inf PS, infundibular pulmonary stenosis; LSVC, persistent left superior vena cava; PDA,persistent ductus arteriosus; PVS, pulmonary valve stenosis, SVMS + MVS; supravalvar mitral stenosis with or without mitral valve stenosis.

ResultsASSOCIATED ANOMALIESThe table shows the clinical characteristicsand type of subvalvar aortic stenosis. Age atdiagnosis ranged from two days to 14 7 years(mean 48 (3-6) years). There were 35 boysand 23 girls (sex ratio 1-5:1). Associatedanomalies were present in 41 (71%) patients(table), whereas 17 (29%) had "isolated"subaortic stenosis. Common associatedanomalies were ventricular septal defect (21(36%)) and lesions resulting in obstruction toleft heart flow such as coarctation or interrup-tion of the aortic arch (16 (28%)), bicuspidaortic valve (nine (16%)), or supravalvarmitral stenosis (six (10%)). There was a pers-istent left superior vena cava draining tocoronary sinus in 9 (16%) patients.

leaflet of the mitral valve. The extent to whichthe ridge protruded into the left ventricularoutflow tract varied according to the exactplane of the ultrasound beam in parasternallong axis views. The reason was apparent oncareful parasternal short axis scans of the leftventricular outflow tract which showed theextent of the attachment of the subaorticridge. This was sometimes confined to the leftventricular aspect of the infundibular septumbut more often extended from the infun-dibular septum around the margins of the leftventricular outflow tract to the anterior leafletof the mitral valve (fig 2). The ridge came into

Figure 1Echocardiographicfindings at diagnosis ofsubaortic stenosis. Squaresare patients withcoarctation or interruptionof the aortic arch with orwithout a ventricularseptal defect. Circles arepatients with a ventricularseptal defect but withoutobstruction of the aorticarch. A V, aortic valveinvolvement; COA,coarctation; DEV INFSEP, deviation of theinfundibular septum intothe left ventricular outflowtract; IAA, interruptionof the aortic arch; LS,long segment; MEMB,membranous; MV, mitralvalve involvement; SS,short segment; VSD,ventricular septal defect.

NATURE OF SUBAORTIC STENOSISFour types of subaortic stenosis were iden-tified on echocardiographic review. There wasshort segment narrowing in 47 patients, longsegment narrowing in seven patients, dis-placement of the infundibular septum withadditional discrete obstruction in three, andabnormal tissue with a unique appearance inone patient. Figure 1 shows the echocar-diographic findings at diagnosis of subaorticstenosis.

Short segment narrowing, apparently theresult of a fibrous ridge or localised muscularbulging, was usually seen in long axis views.In almost all cases the parastemal long axisallowed better visualisation of the obstructingtissue in the left ventricular outflow tractthan apical or subcostal views. Tilting thetransducer slightly to either side of the trueparasternal long axis plane showed whetherthe fibrous ridge was attached to the anterior

Echo

Short -AAAAAAAAAAA A A A

segment ** A: m*

+MV A AAA

+AV * A A

+MV&AV 0n

Long, ME A A Asegment A

DEV INF SEP-- I+Ss

+LS

MEMBseptum

*

I

1 2 3 4 5 6 7 8 9 10 11 12 1314151617Age (year)

Figure 2 (A) Cross sectional echocardiogram(parasternal long axis view) showing short segmentsubaortic stenosis in a 2 year old boy. (B) Parasternalshort axis view in the same patient showing that theattachment of the obstructing ridge extended around themargins of the left ventricular outflow tract to theanterior mitral valve leaflet so that the lumen of theoutflow tract was reduced to a slit. The curved arrowindicates the base of the anterior mitral valve leaflet. A,anterior; AL, aortic valve leaflets; Ao, ascending aorta;L, left; LA, left atrium; SAS, subaortic stenosis.

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Figure 3 Cross sectionalechocardiograms(parasternal long axisviews) in a patient withshort segment subaorticnarrowing and mitralvalve involvement. (A) Indiastole the obstruction inthe left ventricular outflowtract was separate fromthe aortic valve leaflets butattached to the anteriormitral leaflet. (B) Insystole the anterior mitralvalve leaflet was pulledanteriorly at the site ofattachment of the subaorticobstruction (curvedarrow). AL, aortic valveleaflets; LV, left ventricle;LA, left atrium.

and out of the plane of the parasternal shortaxis section very quickly because of heartmovement during the cardiac cycle; frame byframe analysis was necessary to assess itadequately. A localised ridge that did notaffect the mitral or aortic valves was the mostcommon type of subaortic stenosis; it waspresent in 37 (65%) patients (fig 1). Mitralvalve (fig 3) or aortic valve (fig 4) involvementwas confined to patients with short segmentnarrowing and was not seen in any patientaged less than 3 years (fig 1). After that age theaortic or mitral valve or both, were oftenaffected (10/34 (30%)) in patients with shortsegment narrowing and in (10/40 (25%)) theentire group (fig 1). All the patients in whomsubaortic stenosis was diagnosed after infancywho had associated coarctation or interruptionof the aortic arch had undergone previousrepair of the arch abnormality (figs 1 and 5).There was long segment narrowing in seven

(12%) patients (fig 1). The youngest two ofthese had subaortic stenosis diagnosed at 10and 16 months of age and each had coarctationof the aorta without a ventricular septaldefect. The five others were aged 5 to 13 years

at diagnosis (fig 1): one had a ventricularseptal defect and another persistence of thearterial duct but there were otherwise noadditional abnormalities in these patients.There were three patients in whom a pos-

teriorly displaced infundibular septum wascomplicated by an additional discrete subaor-tic lesion (fig 1). All of these had aortic archanomalies (two coarctation, one interruption).The patient with interruption of the aorticarch developed long segment narrowing ininfancy after neonatal repair of the arch andventricular septal defect closure, whereas theremaining two patients developed localisednarrowing that was first apparent beyondinfancy (fig 1). During the period of the studythere were 12 additional patients who hadmalalignment ventricular septal defects withposterior deviation of the infundibular septuminto the left ventricular outflow tract who didnot develop additional discrete subaortic obs-truction.One infant had unusual redundant tissue

obstructing the left ventricular outflow tract.Necropsy confirmed that this was fibrous tis-sue arising from the membranous septum.

Figure 4 Systolicparasternal long axis viewsin different patients withtethering of (A) rightcoronary and (B) leftcoronary cusps of theaortic valve to theadjacent short segmentsubaortic ridge (arrows).R V, right ventricle. Seelegend tofig 3for otherabbreviations.

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Figure S Parasternallong axis view in a I yearold boy with long segmentsubaortic stenosis. Seelegend tofig 2forabbreviations.

SEQUENTIAL CHANGESEchocardiograms had been performed beforethe diagnosis of subaortic stenosis in nine(16%) patients. In six of these the left ven-tricular outflow tract was considered to be"normal" at the time of the first echocar-diogram, performed in infancy in each case (fig6). Each of these infants had clinically evidentassociated cardiac anomalies. Careful retro-spective review with frame by frame analysisshowed subtle irregularity in the location in theleft ventricular outflow tract in two of thesepatients, suggesting that very early ridge for-mation might have been apparent at the initialstudy (undertaken at 3 and 4 weeks of age

respectively). Careful retrospective review ofthe echocardiograms recorded in infancy in theremaining four patients considered to have a

"normal" left ventricular outflow tract did notshow any abnormality (fig 7).The three patients with posterior dis-

placement of the infundibular septum into theleft ventricular outflow tract who subsequentlydeveloped additional discrete subaortic sten-osis (fig 6) have been described above.Ten of the 14 patients who had further

Figure 6Echocardiographicappearances ofsubaorticobstruction in patients whohad more than one study.LVOT, left ventricularoutflow tract. See legendstofigs 1-3for otherabbreviations and symbols.

Echo

'Normal'LVOT

Shortsegment w* **

+MV

+AV

+MV&AV

Longsegment

DEV INF SEP %E

+55+SS \ +CO or IAAl

+LS o+VSD

1 2 3 4 5 6 7 8 9 10 11 12 13141516Age (year)

echocardiograms after the diagnosis of subaor-tic stenosis had persistence of short segmentnarrowing (fig 6). In one infant who hadundergone coarctation repair there was rapidevolution of short segment to long segmentnarrowing (figs 6 and 8). The long segmentnarrowing was confirmed at operation.Acquired valve involvement was seen in fourpatients. Short segment narrowing evolved toinclude tethering of the mitral valve (twopatients) or aortic valve (two patients, fig 6).Ages at diagnosis of new valve involvementranged from 5 to 16 years (fig 6).

In three patients with repaired coarctation,short segment narrowing with aortic or mitralvalve involvement was diagnosed at 3-5 yearsofage (fig 1). In another, long segment narrow-ing was diagnosed at 16 months of age (fig 1).Subaortic stenosis had not been diagnosed atthe time of coarctation repair in infancy in anyof these patients but, because echocardiogramsfrom that time were not available, serialchanges in the shape of the left ventricularoutflow tract could not be described.

DiscussionCLASSIFICATION OF SUBAORTIC STENOSISAt least nine mechanisms for subaortic obs-truction have been described." Almost allcases, however, are examples of "fibrous dia-phragm" or "fibromuscular" narrowing ifpos-terior displacement of the infundibular septumand hypertrophic cardiomyopathy areexcluded." These categories inevitably overlapbecause "fibrous diaphragm" refers to narrow-ing over a short but unspecified length whereas"fibromuscular" narrowing occurs over a lon-ger but variable length. Our classification ofsubaortic lesions into short segment, long seg-ment, and displaced infundibular septum withadditional localised narrowing was basedpurely on echocardiographic appearanceswithout inferring the composition of thesubaortic tissue. In one infant we described anunusual appearance as "aberrant tissue"; thiswas shown at necropsy to be an extension offibrous tissue from the membranous septum.The distinction between short segment nar-rowing and long segment narrowing was basedon previous work'0 but was neverthelessarbitrary. In practice, there was little difficultyclassifying the appearances in individual cases."Fixed subaortic stenosis" may be thepreferred term to encompass these lesions.'

PROGRESSION OF SUBAORTIC STENOSISSubaortic stenosis may cause progressivelymore severe obstruction of the left ventricularoutflow tract.7 Significant obstruction hasdeveloped even in the absence of a systolicpressure difference between left ventricle andaorta at a previous catheterisation,37 showingthat lesions can present as an "acquired"disorder that increases in haemodynamicseverity, presumably when there is a pre-existing anatomical substrate.3 Most patients inthese studies37 were first seen before crosssectional echocardiography became available.We used echocardiography in an attempt to

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Figure 7 (A)Parasternal long axis viewin systole in a neonate withcoarctation of the aorta.The left ventricle wassmall but there was noevidence of obstruction inthe left ventricular outflowtract. The arrows indicatethe aortic valve leaflets.(B) Parasternal long axisview in systole in the samepatient at age 3 years.Short segment subaorticstenosis had developed. Seelegends to figs 3 and 4forabbreviations.

assess the anatomical range of fixed subaorticstenosis and the nature of its progression in aconsecutive unselected series of infants andchildren.Our data confirmed that short segment narr-

owing is by far the most common form of fixedsubaortic stenosis and that most cases areassociated with congenital heart defects,typically ventricular septal defect and obstruc-tive lesions of the left heart. The associationbetween obstructive lesions ofthe left heart andfixed subaortic stenosis was recognised as longago as 1963.12 Persistence of the left sidedsuperior vena cava was a notable feature, whichwe found in nine (16%) of our patients. Wepreviously noted a similar association betweenpersistence of the left superior vena cava andsupravalvar mitral stenosis (6/16 patients,38%) but not in patients with cor triatriatum(0/6 patients) or with congenital mitral stenosiswithout a supravalvar membrane (1/16patients, 6%).3 14 This suggests that persis-tence of the left superior vena cava with con-sequent enlargement of the coronary sinus mayrestrict left ventricular filling during prenatallife and that the diminished flow may con-

tribute to the development of the various"downstream" fixed obstructive lesions.The classification of the fixed subaortic

lesion did not change in most infants andchildren in this study, but follow up beforesurgical procedures on the left ventricularoutflow tract was short (maximum six years).Short segment narrowing, however, causedprogressively more important obstruction ofthe left ventricular outflow tract.3Tethering of the mitral valve or aortic valve

or both, was not seen before the age of 3 yearsbut developed or was present in most children(7/13, 54%) who had at least one serial assess-ment at age 5 years or more. The developmentof aortic regurgitation when fixed subaorticstenosis is present is almost certainly the resultboth of tethering of the aortic valve and thetrauma to the valve from the turbulent ejectionjet during left ventricular systole.'0

In rare cases, however, long segment subaor-tic stenosis can rapidly develop in infancy. Aninfant in whom severe long segment narrowingdeveloped within four months of repair ofaortic coarctation has been reported. The leftventricular outflow tract had been considered

Figure 8 (A)Parasternal long axis viewin systole in an infant aged6 months, showing shortsegment subaorticnarrowing. Coarctationwas repaired at that time.(B) Parasternal long axisview in the same patientaged 20 months. Longsegment subaortic stenosishad evolved and dysplasiaof the mitral valve wasevident. See legends to figs3 and 4for abbreviations.

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normal on initial echocardiographic andangiocardiographic assessment at age 7weeks.'5 In the two patients in this study whofollowed a similar course after repair ofcoarcta-tion, the "substrate" in the left ventricularoutflow tract was short segment narrowing inone and displacement of the infundibular sep-tum in the other. In two additional children, wesaw the development of a localised ridgesuperimposed on a posteriorly displaced infun-dibular septum after repair of coarctation ininfancy.

Consequently, the potential for changes inform as well as for progression in haemodyn-amic severity of left ventricular outflow tractobstruction exists. Reports of long segmentsubaortic stenosis described patients who weremuch older than those in our series.'° 1617Perhaps short segment narrowing would haveevolved into long segment narrowing in moreof our patients during a longer prospectivefollow up. The term "transitional" was used todescribe a form of subaortic stenosis inter-mediate between "discrete" and "tunnel"types in a study that included young adults.'8

In infants with coarctation or interruption ofthe aortic arch the left ventricular outflow tractis narrow even in the absence of an aortic valveabnormality or of a malalignment ventricularseptal defect with posterior deviation of theinfundibular septum. Reduced aortic valvediameter and increased mitral aortic separationwere identified in a pathological study ofpatients with isolated subaortic stenosis.'8 Itwas suggested that the altered flow characteris-tics in a narrow and elongated left ventricularoutflow tract during early heart developmentcould cause embryonic cells near the crest ofthe ventricular septum to accumulate and laterdifferentiate into a ridge or band of tissue.'8When subaortic stenosis occurs in associationwith a ventricular septal defect but withoutother abnormality, the obstruction in the leftventricular outflow tract is typically at thelower margin of a perimembranous defect."Maximum turbulence at this site in thepresence of a left to right shunt through theventricular septal defect might explain this andalso the tendency for subaortic stenosis to beespecially associated with malalignment ven-tricular septal defects in which there is anteriordeviation of the outlet septum9 20 where theflow disturbance at the lower margin of aperimembranous defect is likely to be evengreater.

CLINICAL IMPLICATIONSWe studied infants with clinically evident con-

genital heart defects. Subaortic stenosis wasseen in six young children who had had an

apparently normal left ventricular outflow tractin infancy; this accords with the contention thatfixed subaortic stenosis is a lesion acquiredbecause of flow disturbance in the left yen-tricular outflow tract.'8"2 A review of theechocardiographic studies to examine the leftventricular outflow tract showed that very early"ridge" development in the outflow tract mayhave been present in two patients. A similarappearance was described in an infant, but it

was not stated whether subaortic stenosisdeveloped subsequently.7The sequential changes that we saw emphas-

ise the need for careful serial echocardiographicassessment of the left ventricular outflow tractin infants with other obstructive lesions of theleft heart, especially if physical signs of leftventricular outflow tract obstruction mightbe obscured by coexisting abnormalities.Similarly, patients about to undergo ven-tricular septal defect closure should have adetailed echocardiographic assessment todetect possible incipient subaortic stenosisbecause surgical removal of any fibrous tissuewith the potential to cause subsequent leftventricular outflow tract obstruction is advisa-ble, even when this is only an "echodense areaat the crest of the ventricular septum" seenduring preoperative echocardiographic assess-ment.20When fixed subaortic stenosis is "isolated",

the likelihood of increasing left ventricularoutflow tract obstruction, tethering of the aor-tic and mitral valves, and the risk of endocar-ditis argue in favour of early operation.89However, recurrent or residual postoperativeleft ventricular outflow tract obstruction is animportant complication of operation,2' andsome children with fixed subaortic stenosis donot develop increasingly severe left ventricularoutflow tract obstruction or other complica-tions during follow up for many years. Surgicalresults are probably satisfactory for at least adecade provided the obstruction of left ven-tricular outflow tract is effectively relieved atthe initial operation.22 The postoperative prog-nosis of patients with short segment subaorticstenosis was better than those with long seg-ment narrowing.'7 It might therefore be arguedthat indications for operation should includeevidence of important or increasing left ven-tricular outflow tract obstruction, the develop-ment of mitral or aortic valve tethering, orevidence of possible transition from short seg-ment to long segment narrowing on serialstudies. Certainly, serial echocardiographicassessment of the left ventricular outflow tractis mandatory for medical management.

JYC was supported by the British Council.

1 Wright GB, Keane JF, Nadas AS, Bernhard WF, CastanedaAR. Fixed subaortic stenosis in the young: medical andsurgical course in 83 patients. Am J Cardiol 1983;52:830-5.

2 Newfeld EA, Muster AJ, Paul MH, Idriss FS, Riker WL.Discrete subvalvular aortic stenosis in childhood. Study of51 patients. Am J Cardiol 1976;38:53-61.

3 Leichter DA, Sullivan ID, Gersony WM. "Acquired"discrete subvalvular aortic stenosis: natural history andhemodynamics. J Am Coll Cardiol 1989;14:1539-44.

4 Maron BJ, Redwood DR, RobertsWC, Henry WL, MorrowAG, Epstein SE. Tunnel subaortic stenosis. Left ven-tricular outflow tract obstruction produced by fibromus-cular tubular narrowing. Circulation 1976;54:404-16.

5 Reis RL, Peterson LM, Mason DT, Simon AL, MorrowAG. Congenital fixed subvalvular aortic stenosis. Ananatomical classification and correlations with operativeresults. Circulation 1971;33 & 34 (suppl 1):11-8.

6 Smallhorn JF, Anderson RH, Macartney FJ. Morphologicalcharacterisation of ventricular septal defects associatedwith coarctation of aorta by cross-sectional echo-cardiography. Br Heart J 1983;49:485-92.

7 Freedom RM, Pelech A, Brand A, et al. The progressivenature ofsubaortic stenosis in congenital heart disease. IntJ Cardiol 1985;8:137-43.

8 Somerville J. Fixed subaortic stenosis-a frequently misun-derstood lesion. Int J Cardiol 1985;8:145-8.

9 Somerville J. Aortic stenosis and incompetance. In:Anderson RH, Macartney FJ, Shinebourne EA, Tynan

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M, eds. Paediatric cardiology. London: Churchill Living-stone, 1987:987-92.

10 Feigl A, Feigl D, Lucas RV Jr, Edwards JE. Involvement ofthe aortic valve cusps in discrete subaortic stenosis.Pediatr Cardiol 1984;5:185-90.

11 Vogel M, Freedom RM, Brand A, Trusler GA, WilliamsWG, Rowe RD. Ventricular septal defect and subaorticstenosis: an analysis of 41 patients. Am J Cardiol1983;52: 1258-63.

12 Shone JD, Sellers RD, Anderson RC, Adams P Jr, LilleheiCW, Edwards JE. The developmental complex of "para-chute mitral valve", supravalvular ring of left atrium,subaortic stenosis, and coarctation of aorta. Am J Cardiol1963;11:714-25.

13 Sullivan ID, Robinson PJ, de Leval M, Graham TP Jr.Membranous supravalvular mitral stenosis: a treatableform of congenital heart disease. J Am Coll Cardiol1986;8:159-64.

14 Sethia B, Sullivan ID, Elliott MJ, de Leval M, Stark J.Congenital left ventricular inflow obstruction: Is theoutcome related to the site of the obstruction? Eur JCardiothorac Surg 1988;2:312-7.

15 Freedom RM, Fowler RS, Duncan WJ. Rapid evolutionfrom "normal" left ventricular outflow tract to fatalsubaortic stenosis in infancy. Br Heart J 1981;45:605-9.

16 Wilcox WD, Seward JB, Hagler DJ, Mair DD, Tajik AJ.

Discrete subaortic stenosis. Two-dimensional echocar-diographic features with angiographic and surgicalcorrelation. Mayo Clin Proc 1980;55:425-33.

17 Moses RD, Barnhart GR, Jones M. The late prognosis afterlocalized resection for fixed (discrete and tunnel) leftventricular outflow tract obstruction. J Thorac CardiovascSurg 1984;87:410-20.

18 Rosenquist GC, Clark EB, McAllister HA, Bharati S,Edwards JE. Increased mitral aortic separation in discretesubaortic stenosis. Circulation 1979;60:70-4.

19 Zielinsky P, Rossi M, Haertel JC, Vitola D, Lucchese FA,Rodrigues R. Subaortic fibrous ridge and ventricularseptal defect: role of septal malalignment. Circulation1987;75:1 124-9.

20 Vogel M, Smallhorn JF, Freedom RM, Coles J, WilliamsWG, Trusler GA. An echocardiographic study of theassociation of ventricular septal defect and right ven-tricular muscle bundles with a fixed aubaortic abnor-mality. Am J Cardiol 1988;61:857-60.

21 Somerville J, Stone S, Ross D. Fate of patients with fixedsubaortic stenosis after surgical removal. Br Heart J1980;43:629-47.

22 Kirklin JW, Barratt-Boyes BG. Congenital discretesubvalvular aortic stenosis. In: Kirklin JW, Barratt-BoyesBG, eds. Cardiac surgery. New York: John Wiley andSons, 1986:988-1001.

Veratrum alkaloidsThe Veratrum species (Liliaceae) contain over20 alkaloids with important cardiovascular,neuromuscular, and respiratory actions. Theylower the blood pressure by an unusualmechanism first elucidated in 1867 by A vonBezold. Stimulation of vagal afferent fibres inthe left ventricle causes the vasomotor centre toreset homoeostatic control at a lower level and

Veratrum viride Ait. Bentley R, Trimen H. Medicinal plants. vol 4.London: Churchill, 1880: 286.

to reduce the peripheral vascular resistancethrough the sympathetic nervous system.When pure alkaloids became available theywere shown by A E Doyle and F H Smirk(British Heart Journal 1953;15:439-49) and byothers to reduce considerably the blood pres-sure in hypertensive patients. But toxicity,especially nausea and vomiting also caused byvagal action, made treatment difficult and theiruse stopped despite their attractive vasodilatormode of action. Veratrum was used in eclamp-sia before its pharmacology was studied. It hadbeen given for mania and epilepsy early in thenineteenth century and prompted Dr P de LBaker of Eufala, Alabama, to prescribeVeratrum viride, the American or greenhellebore, with success in 1859 for a lady witheclamptic fits. This was well before the associa-tion between eclampsia and hypertension wasrecognised. The plant and its alkaloids wereused with good effect in toxaemia of pregnancyand eclampsia for the next 100 years.The Veratrum species are handsome peren-

nial plants with large -pleated leaves and tallspikes of flowers-well worth growing in thegarden. The two European species, V albumand V nigrum, are common on alpine meadows.There are 43 other species, the best knownbeing V viride and V sabadilla. The alkaloidscome from the rhizome and root, or occasion-ally from the seed. Their common name, fromantiquity, is hellebore but they are quite dif-ferent from the genus Helleborus-the Christ-mas and Lenten roses. Veratrum has alwaysbeen known as a highly poisonous plant causingvomiting, substernal constriction, faintnesswith a weak pulse, convulsions, and death. In1985 a Frenchman made wine from it, believ-ing it to be gentian, and developed completeatrioventricular block. It is also known as astrong teratogen; ewes that eat it can havelambs with a central eye.Other medicinal members of the Lily family

include those that contain cardiac glycosides,such as squill (Drimia maritima) and lily of thevalley (Convallaria majalis). Colchicine isfound in the meadow saffron ("autumncrocus") Colchicum autumnale while sisalAgave sisalana provides the starting materialfor steroid synthesis.

A HOLLMAN

PLANTS IN CARDIOLOGY

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