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Congenitally bicuspid aortic valve in multiple family members
go on becausepublished reports provide specific data in this respectin only 2 series.11J2In both, as was our own experience, the amount of radiation measuredwas very low, 0.1 mSv” and 0.5 mSv,12and far lower than that legally admitted for pregnant women subject to radiation exposure (i.e., 5 mSv).rs We have as yet no real certainty with regard to long-term effects,although good indication can be derived from the fact that the 20-year follow-up of 1,000 cases of women irradiated for radiopelvimetry at dosesof 15 to 30 mSv at the samestage of pregnancy,revealed no difference in the incidence of cancer with a control group.19Nonetheless,even if the risk of radiation is low, all the following steps are essential to keep radiation to minimum: shielding of the abdomenby a lead apron, shortening the proceduretime, using fluoroscopy sparingly, and avoiding cineangiography. The last potential complication for the fetus is subsequentthyroid dysfunction resulting from the injection of contrast medium. However, this has not been observed in the caseof dosessimilar to those we administered.20This risk can be avoided by using color Doppler flow imaging instead of cineangiography to evaluate any change in the degree of mitral regurgitation. PMC during pregnancy is thus shown to be efficacious in terms of improving the mother’s hemodynamic status; it is also well tolerated by the fetus. Nonetheless, larger series with longer follow-up are needed to conlirm these findings, particularly with regard to risks and potential long-term side effects of radiation to the fetus. The results obtained in this series suggest that PMC is an attractive procedure for pregnant women who remain symptomatic despite medical therapy.
1. Inoue K, Okawi T. Nakamura T, Kitamura F, Miyamoto N. Clinical application of tramvenous mitral commissurotomy by a new balloon catheter. J Thorax Cardiowsc Sur,q 1984;87:394-402.
2. Vahanian A, Michel PL, Cornier B, Vitoux B,.Michel X, Slama M, Entiquez Sarano L, Trabelsi S, Ben lsmail M, Acar J. Results of percutaneous mitral commissurotomy in 200 patients. Am J Card& 1989;63:847-852. 3. Bemal JM, Mimlles PJ. Cardiac surgery with cardiopulmonary bypass during pregnancy. Obst Gynecol Surv 1986;41:14. 4. Clark SL, Phelan JP, Greenspeon J, Aldahl D, Horenstein J. Labor and delivety in the presence of mitral stenosis: central hemodynamic observations. Am J Obster Gynecol 1985;152:984-988. 5. Lamb Ml’, Ross K, Johnstone AM, Manners JM. Fetal heat monitoring during open heart surgery. Two case reports. Br J Obstet Gynecol 1981;88:66%674. 6. Vosloo S, Reichart 9. The feasibility of closed mitral valvotomy in pregnancy. J Thorac Cardiovasc Surg 1987;93:6%679. 7. Safian RD, Berman AD, Sachs B, Diver DJ, Come PC, Bairn DS, McKay L, Grossman W, McKay RG. Percutaneous balloon mitral valvuloplasty in a pregnant woman with mitral stenosis. Cathet Cardiovasc Diqn 1988;15: 103-108. 8. Palacios IF, Block PC, Wilkins CT, Red&r DE, Daggett WM. Percutaneous mitral balloon valvotomy during pregnancy in a woman with severe mitral stenosis. Cather Cardiovasc Diqn 1988; 15: 109-l 11. 9. Mangione JA, Zuliani MF, Del Castillo JM, Nogueira EA. Arie S. Percutaneous double balloon mitral valvuloplasty in pregnant women. Am J Cardiol 1989; 64:9%102. 10. Smith R, Brenda D, McCredie M. Percutaneous transluminal balloon dilatation of mitral valve in pregnancy. Br Heart J 1989;61:551-553. 11. Esteves CA, Ramos AIO, Braga SLN, Harrison JK, Sousa JE. Effectiveness of percutaneous balloon mitral valvotomy during pregnancy. Am J Cardiol 1991: 68:93&934. 12. Drobinski G, Fraboulet P, Montalescot G, Moussallem N, Coutte R, Artigou JY, Grosgogeat Y. Valvuloplastie mitmle au quatri&me mois de grossesse. F’rotection foetale par un mat&au de plomb. Arch Mal Coeur 199 1;84:249-25 1. 13. Gangbar EW, Watson KR, Howard RJ, Chisholm RJ. Mittal balloon valvuloplasty in pregnancy: advantages of a unique balloon. Cathet Cardiovmc Diqn 1992:25:313-316. 14. Ruzyllo W, Dabrowski M, Woroszylska M, Rydlewska-Sadowska W. Percutaneous mitral commissurotomy with the Inoue balloon for severe mitral stenosis during pregnancy. J Heart Valve Dis 1992; 1:209-2 12. 15. Ben Farhat M, Maatouk F, Betbout F, Ayari M, Brahim H, Souissi M, Sghairi K, Gamra H. Percutaneous balloon mitral valvuloplasty in eight pregnant women with severe mitral stenosis. Eur Heart J 1992;13:1658-1664. 16. Rib&o PA, Fawzi ME, Awad M, Dunn B, Dunn CG. Balloon valvotomy for pregnant patients with severe pliable mitral stenosis using the Inoue technique with total abdominal and pelvic shielding. Am Heart J 1992; 124: 1558-1562. 17. Rib&o PA, Al Zaibag M. Editorial - mitral balloon valvotomy in pregnancy. J Heart I/a/w Dis 1992; 1:20&208. lt3. Wagner LK, Hayman LA. Pregnancy and women radiologists. Radiology 1982: 145:55%562. 19. Griem ML, Meier P, Dobben GD. Analysis of the morbidity and mortality of children irradiated in fetal life. Radiology 1967;88:347-349. 20. Giraud JR, DuguC-Ma&haud M, Fizazi T, De Tounis H, Auben J. Urographie intraveineuse pendant la grossesse et risque d’hypothyroidie foetale. J Gyn Obst Biol Repr 1983;12:4549.
Congenitally Bicuspid Aortic Valve in Multiple Family Members Brian N. Glick, MD,* and William C. Roberts, MDt he congenitally bicuspid aortic valve has been the subject of numerous publications. Leonardo da Vinci T in the 1400sdrew the valve and provided some reasons
not until the 1950sthat the bicuspid condition was recognized to be a common underlying cause of aortic valve stenosis,and it was not until 1981that it was recwhy it might function abnormally.’ In 1844, Paget ognized to be associatedwith pure aortic regurgitation called attention to the peculiar liability of congenitally unassociatedwith infective endocarditis.5The bicuspid bicuspid aortic valves to disease,but their importance as aortic valve has been the subject, directly or indirectly, something other than a pathologic curiosity was not ap- of 228 publications from this laboratory since 1962.5,c32 preciated. In 1858, Peacock3pointed out that bicuspid Despite the frequency of the congenitally bicuspid aortic valvestendedto become“thick . . . ossilled . . . induc- aortic valve (possibly as high as 1% of the population), ing first obstruction. . . and then incompetency.”Oslefl in its occurrencein >l family memberis extremely uncom1886 lirst described the abnormal liability of the bicus- mon. Only 4 reports have appeareddescribing 4 famipid aortic valve to develop infective endocarditis. It was lies (9 family members)with >l member having a congenitally bicuspid aortic valve (Table I).33-36During the past 27 years, we have encountered6 families (17 famFrom the Pathology Branch, National Heart, Lung, and Blood Instiily members)in whom >l member had aortic valve distute,National Institutes of Health, Bethesda, Maryland 20892. Manuscript received April 16, 1993; revised manuscript received and accepted ease, with bicuspid valve confirmed at operation in 11. June 24, 1993. A description of certain tindings in these 17 family *Cardiology Fellow, Georgetown University Medical Center, membersis the subject of this report. Washington, D.C. The pedigree of the 6 families is shown in Figure 1. Kurrent address: Baylor Cardiovascular Institute, Baylor University Medical Center, 3600 Gaston Avenue, Dallas, Texas 75246. In 3 families (I, II and VI), a parent and 21 child were 400
THE AMERICANJOURNALOF CARDIOLOGY VOLUME73
FEBRUARY15, 1994
affected, and in 3 families (III, IV and V), 21 sibling ly suggestedby aortogram in 1 (number 2). The latter only was affected.In 11 of I7 family members,the con- patient had sign@cant aortic regurgitation by aorgenital bicuspid nature of the aortic valve was con- togram at age 10 years. Patients I1 and 12 were stat$rmed at the time of aortic valve replacement, and the ed to have “aortic valve disease,” but no other inforoperatively excised bicuspid aortic valves in 7 of these mation regarding them was available to us. None of the patients are shown in Figures 2 to 5. Another patient I7 patients apparently had clinical evidence of mitral (number IO, family N, Table II) also had aortic valve valve dysfunction. Pertinent j?ndings in each of the I7 patients are replacement, but the type of valve encountered was unknown to us. In the other 5 patients, the bicuspid na- tabulated in Table II. Of the 17 patients, 10 had cliniture of the aortic valve was demonstrated by echocar- cal evidence of aortic valve stenosis, with or without diogram in 2 (numbers 7 and 17; Table II) and strong- associated aortic regurgitation, including 6 in whom a TABLE I Observations Family
in Nine Previously
Reported
Age Year of Publication
First Author
1972
McKuslck
1977
Patients
(all men) with a Congenitally
Biscuspid
Aortic
Valve in More Than One
Member
Gale
1987
Godden
1989
McDonald
Case
Relation
1 2 3 4 5 6 7 8 9
Father* Son* Brother? Brothert Brothert Brother* Brother Brother Brother
(years) at Death
Age (years) at AVR 44
Type
Year of AVR
AS
-
-
AR Murmur
Calcified AV(O-3) 2+
+
+ + -
+ + t + t +
+ + +
19
61 19
38 44 57 57
1972 1976 1980 1980
23 26
-
3+ 3+ 3+ 3+ -
LV-SA psg (mm Hg) -
-
of AV Prosthesis
(size)
t
S-E
-
+t
40 60 65 -
§ B-S (23) C-E (27) B-S (23) -
80 80
SJM S-E
+ + + t +t + +
*Each had severe cystic medial necrosis of the ascending aorta. The father had dissection involving the entire aorta, which was not dilated: the son had tear of a dilated ascendmg aorta with hemopencardium. Neither had skeletal features of the Marfan syndrome. tBoth have dtlated ascending aortas. Case 4 had medlal cysbc necros15 confirmed by htstologic study of portions of the excised ascending aorta. Neither of the Marfan syndrome. $ldentlcal twins, probably monazygotic. Case 6 had infective endocarditis at 1 bme. §The type of substitute valve used 1s uncertain. AR = aortic regurgitabon; AS = aortic stenosis; AV = aortlc valve: AVR = aotiic valve replacement: BAV = biscuspld aortlc valve; B-S = Bjork-Shirley; LV = leftventncular; psg = peaksystolicgradlent; SA = systemlcartery; s/d = peak systolic/end-dlastollc; S-E = Starr-Edwards; SJM = St. Jude Medical; absent or negative; - = Information not available.
“”
BAV atAVR(+) or Necropsy (++)
a through-and-through
fatal
patlent had skeletal features
C-E = Carpentier-Edwards; + = present orpasitive; 0 =
(57) (60) + WN” M4
El
V FIGURE families member bicuspid
1. The pedllee ef 6 with >l family with a congenitally sortie valve.
0
or H
0 0 or # 0
or or or or
0 = W = H = W = [ 1= ( ) = * =
Female Male Died Known mrtic stanasia or pure aortic regurgitation Age (years) at aortic valve replacement Aw@an)atdeath 8iispid aortic valve confirmed at operation
L BRIEFREPORTS 401
peak systolic pressure gradient ranging from 38 to 100 mm Hg was recorded at cardiac catheterization. Of the latter 6 patients, 5 had aortic valve replacement within 1 month of cardiac catheterization. The remaining patient (number 14, Table II) had a cardiac catheterization when she was aged 70 years, and now (April 1993), 9 months later, she has still not had aortic valve replacement, primarily because of noncardiac problems. Four of the 17 patients had pure aortic regurgitation, and 3 of them have had aortic valve replacement. In 3 patients (numbers 10, 11 and 12; Table II), the type of aortic valve dysfinction was unknown to us. Of the 6 families, all affectedmembersin 3 families had aortic stenosis (with or without associated aortic regurgitation); in 2 families (numbers I and II, Table II), the father in each had aortic stenosis, and the child (1 daughter and 1 son) had pure aortic regurgitation, and in 1 family (number IV), it is likely but not proven that some family members had aortic stenosis and others pure aortic regurgitation.
FlBBRE 2. Patients 3 and 4 (Table II). operatively excised aortii valves of patients WN (NIH# 5873152) and WN Jr (NIH# S71-3019). lhe father, who was 44 years old at the time of aortic valve replacement, had aortic valve stenosis and a heavily calcified valve; the son, who was 26 years old had pure aortic re@rgitation and a at valve replacement, noncalcified valve.
FtBURE 3. Paweats 5 and 6 (Table II)., Bperatively excised aortlc valves of patients LB (NIN# S78-43) and PB (NIl+# ~).Patientffiwas53yearsokl,andffiwas72atthe ~Bothpatlmtshrxlstsmticvalves, tineal’dve hut the older brother (PB) had considerrmly more calcilic deposits in the valve than dii the younger sister (LB).
402
THE AMERICAN JOURNAL OF CARDIOLOGY
VOLUME 73
In 2 families (numbers II and V, Table II), all affected memberswere men, in 1 family (number VI), all 3 affected memberswere women, and in 3 families (numbers I, III and IV; Table II), 21 affected member was male and 21 was female. Infective endocarditis occurred in only 1 (number 8, Table II) of the 17 patients, and in this case, it caused severeaortic regurgitation and necessitatedaortic valve replacement. The hitherto described observations indicate that the bicuspid aortic valve may occur in >l family member. Although approximately 75% of subjects with congenitally bicuspid aortic valves are male, female members of families are not immune to this congenital malformation. Of our 17 patients, only 9 (53%) were male; in 1 family (number VI), all 3 affected members were female. The type of valve dysfunction resulting from the bicuspid condition was variable. In some families, all affected members had aortic stenosis (with or without associated regurgitation), in some, all affected members
FlBURE 4. PatJents 8 and 9 (Table II). Operatively excised aortic valves of patients FA (NBl# S7939) and BA (NIN# 80 174). The valve of FA is focally calcified and was partially destroyed by actiie infective endccardiiis approximately 1.5 at age 21 years. The valve years before valve replacement of patient BA is devoid of calcium, and it was purely re&~. aant*
ORE 5. Patient 2.4 (Table II). Operatively excised aortii valve of patient LB (NIN# SB9-50) who had valve replace merit for aortic stenosis at aBe 69 years One of the 2 cusps is heavily calcified, and the other one is devoid of calcium. The operatively excised valve weiighed 4 g.
FEBRUARY 15,1994
Patient’s Initials Relation at Death
Age (years)
21 26 -
at AVR
Age (years)
Ill
IV
44 26 53 72
70 69 78 65 -t
Year AR Mumur
+ + -
+
AS
+ 0 + + + 0 0 -
~ ~ 0 0
of AVR 1966 -0 1967 1971 1978 1984 1979 1980 _ + t t t +
0 + + + 0 + -
~ 1981 1989 1982 1989 -
SA (s/d) (mmHg)
85 08 50 0 55 60
LV-SA Psg (mm Hg)
2+
0 3+§ 3+ 3+
AR by AA Angiogram (O-4+)
2.6 4.94 3.3 4.0 2.7 2.2
Cl
0.6 0.5 -
(cm”)
Hancock (23) S-E (9A) t*
S-E (8A) S-E (12A) S-E (11A) B-S (19) B-S (19)
Type (we) of AV Prosthesis
LV b/d) (mm Hg)
120155 135/55§ 130/52 145165 80155 180/70
-
0.6
+ll C-E(21)
+/I SJM (25)
AVA
3+
Calcified AV (O-3+)
20518 135159 180/20 145126 135130 240137
2.4 3.4
~
-
4t 4f -
38 -
-
142180
100 50
-
0
180/18
180/90 140170
-
120/40 140/60
3+
190/16
3+ 0 3+ 3+ 3+ l+ 0
3t 3t
as I” Table I.
2.3
140/13
TABLE II Clinical Findings in the Six Families in Whom More Than One Member Had a Congenitally Bicuspid Aortic Valve
Case 58 58 26 60 70 26 -
V VI
-
58
I
Family Father Daughter Father Son Sister Brother Sister Brother Brother Sister* Sistert Brother7 Brother Brother Mother Daughter Daughter
II
WB LB WN WN Jr LG PG JG FA BA RB LB ED EBD LGD 80 73
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
*This patient died at the time of aortlc valve replacement. The type of valve dysfunction. and the number of aorbc valve cusps are unknown to US tThe only mformatlon wallable I” these 2 subjects IS that each was described in the medlcal records of FA and BA as having “aorbc valve dwase.” $Thls woman was aged 70 years at cardiac catheterization, and by publlcatlon, she will be 7 1. $These data were collected when the patent was 10 years old (1966). Aorw valve replacement was performed. The typeof substitute valve used IS unknown 1 Coronary artery bypass surgery. AA = ascending aorta; AVA = aort!c valve area; CAD = coronary artery disease; Cl = cardtac Index (Llmlnlm2); TC = total cholesterol; other abbrevlatlons
CAD by Angiogram
-
+ll + -
0 -
+ 0
BAV Confirmed at AVR
181 189 253 236 122 201
Serum TC (mg/dl)
232 207
262
+ 0 + + + + 0 + +
-
t t t + 0
had pure aortic regurgitation (no element of stenosis), and in others, 21 family member had aortic stenosisand 21 had pure aortic regurgitation. The frequency in which a congenitally bicuspid aortic valve occurs in >l family member is unclear. Although our study includes a relatively large number of families in which >l family memberhad a bicuspid aortic valve found at the time of aortic valve replacement, we do not know how many other operatively excised congenitally bicuspid aortic valves we have seen in which only 1 family member had a congenitally bicuspid aortic valve. Some information regarding this frequency question, however, has been provided by Emanuel and associates.37These authors examined 188 living, first-degree relatives of 41 patients (41 different families) who had malfunctioning congenitally bicuspid aortic valves excised at operation. By precordial examination, chest radiograph and electrocardiogramin all 188 relatives, and by M-mode echocardiogramin 52 (28%), 8 of the 188 relatives (4%) from 7 of the 41 families (17%) had evidence of “aortic valve disease.” Thus, of 229 family membersexamined in 41 families, 49 (21%) had clinical or operative evidence of aortic valve disease (the bicuspid condition probably in all of them). Of the 71 family membersin our 6 families, 17 (24%) had evidence of aortic valve disease (most likely a bicuspid aortic valve in all of them). This high percentageis not surprising, becauseeach of the 6 families that provided the 71 family members had 22 members with aortic valve disease.Of the 71 family membersin our 6 families, aortic valve diseasewas present in 8 of 46 living members(17%) and in 9 of 25 dead members(36%). In the study by Emanuel and colleagues,37only 2 of 229 patients were stated to be dead (assuming that each of the 41 patients having aortic valve replacement are alive), and both of them had aortic valve disease;of the 227 presumably living patients, 47 (21%) had evidence of aortic valve disease. In conclusion, the bicuspid aortic valve is clear ly more common in first&ree relatives of sub Jects with a bicuspid aortic Valve than in those of subjects with a tricuspid aortic valve. lt appears reasonable to recommend a good precordial examinat@n and possibly an echocardiogram in firstdegree relatives of subjects clearly identified as having a congenitally bicuspid aortic valve.
1. O’Malley CD, Saunders CM. Leonardo da Vinci on the Human Body. New York: H. Wolff Company, 1952:X%. 2. Paget J. On obstruction of the branches of the pulmonwy artery. Mrd-Chir Tnmans 1884;27:162-188. 3. Peacock TB. On Malformations of the Human Heat. 2nd ed. London: Churchill, 1858:204. 4. Osler W. The bicuspid condition of the amtic valves. Tram Assoc Am Physicians 1886;2:185-192. 5. Roberts WC, Morrow AG, McIntosh CL, Jones M, Epstein SE. Congenitally bicuspid sonic valve causing severe, pure a&c regurgitation without superimposed
404
THE AMERICANJOURNALOF CARDIOLOGY VOLUME73
infective endccarditis. Analysis of 13 patents requiring aortic valve replacement. 198 1;47:2C%209. 2. Roberts WC, Momw AC, Braunwald E. Complete intetnption of the aortic arch. Circularion 1962;26:39-59. 7. Roberts WC, Morrow AC. Cardiac valves and the surgical pathologist. A&I fat/d 1966$2:309-313. 2. Robens WC, Elliott L. Lesions complicating the congenitally bicuspid aortic valve. Anatomic and radiographic features. Radio/ C/m Nmfh Am 1968;6:40842 I 9. Roberts WC. The structure of the aortic valve in clinically-isolated aortic stenosis. An autopsy study of 162 patients over I5 years of age. C~wulahon 1970,42:9 l-97. 10. Roberts WC. The congenitally bicuspid sonic valve. A study of 85 cakes. Am J Cardiol 1970:26:72-83. 11. Robat? WC. Anatomically isolated aortic valvulx disease. The case agamst its being of rheumatic etiology. Am J Mrd 1970:49:151-159. 12. Roberts WC, Perloff JK, Costantino T. Severe valvular aortic stenosis in patients over 65 years of age. A clinicopathologic study. Am J Cardiol 1971:27:497,506. 13. Buchbinder NA, Roberts WC. Left-sided valvular active infective endocatdtis. A study of forty-five necropsy patients. Am J Med 1972:53:2&35. 14. Roberts WC. Valvular, subvalvular, and supravalvular aortic stenosis: marphologic features. Cardiol C/in 1973:5:97-126. 15. Roberts WC, Dangel JC. Bulkley BH. Non-rheumatic valvular cardiac disease: a clinicopathologic survey of 27 different conditions causing valvular dysfunction. Car-dial C/in 1973;5:333446. 16. Amett EN, Robetts WC. Valve ring abscess in active infective endocarditis. Frequency, location, and clues to clinical diagnosis from the study of 95 necropsy patients. Circulrrion 197654: 14&145. 17. McReynolds RA, Ali NO, Cuadra M, Roberts WC. Combined acute rheumatic fever and congenitally bicuspid aottic valve. A hitheno unconfirmed combination. Chest 1976:70:98-100. 16. Amett EN, Roberts WC. Active infective endocarditis: a clinicopathology analysis of 137 necropsy patients. Cuw Pro/~/ Cuvdiol 1976:l:l-76. 19. Roberts WC, Buchbinder NA. Healed left-sided infective endocarditis: a clinicopathologic study of 59 patients. Am J Cardiol 1977:40:87&888. 20. Shemin RJ, Kent KM, Roberts WC. Syndrome of valvular pulmonary stenosis and valvular aottic stenosis with atrial septal defect. Br Heart J 1979;42:442-446. 21. Roberts WC. Aortic dtssection: anatomy, consequences, and causes. Am Hmrr J 1981;101:195-214. 22. Roberts WC, Amett EA. Cabin HS. McIntosh CL, Aisner SC. Documented development of severe stenoses of previous confirmed normally functioning aortic valves. Am Han J 1982: 104~306-308. 23. Amett EA, Robens WC. Pathology of active infective endocarditis: a necropsy analysis of 192 patients. Thomc Cordiovasc Surg 1982;30:327-335. 24. Glancy DL, Morrow AG, Simon AL, Robau WC. Juxtaductal aortic coarctation. Analysis of 84 patients studied hemodynamically, angiographically and marphologically after age I year. Am J Cardiol 1983;51:537-55 I. 21. Roberts WC. Congenital cardiovascular abnormalities usually silent until adulthood. In: Roberts WC, ed. Adult Congenital Heart Diseases. Philadelphia: FA Davis, 1987:631-691. 26. Roberts WC, McIntosh CL, Wallace RB. Aortic valve perforation with calcific aortic valve stenosis and without infective endocarditis or significant aonic regurgitation. Am J Cardrol 1987;59:476+78. 27. Robens WC. Examining operative excised cardiac valves. Am J Cardiol 1987: 59:1434-1436. 28. Mann JM, McIntosh CL, Katz NM, Roberts WC. Cardiac valve replacement for stenotic bicuspid aortic valve in husband and for purely regurgitant pmlapsed mitral valve in wife. Am J Curdiol 1987;60:401402. 29. Kalan JM, McIntosh CL, Bonow RO, Roberts WC. Development of severe stenosis in a previously purely regurgitant, congenitally bicuspid sonic wlvc. Am J Cmdml 1988;62:98&989. 20. Dressier FA, R&ens WC. Infective endocarditis in opiate addicts: analysis of 80 cases studied at necropsy. Am J Cwdiol 1989;63: 124&1257. 31. Roberts WC. Living with a congenitally bicuspid aortic valve. Am .I Car-dial 1989;64:1408-1409. 32. Brown PS Jr, Roberts CS, Mclnto$h CL, Roberts WC, Clark RE. Combtned obstructive hypertrophic cardiomyopathy and stenotic congenitally bicuspid axtic valve. Am J Co,-dial 1990;66: 1368-1372. 22. McKusick V. Association of congenital bicuspid sonic valve and Erdheim’a cystic medial necrosis. Lunwt 1972; I: 1026-1027. 34. Gale AN, McKusick VA, Hutchins GH, Gott VL. Familial congenital bicuspid aortic valve. Chest 1977:72:5:668-670. 25. Godden DJ, Sandhu PS, Kerr F. Stenosed bicuspid aorttc valves in twins. Eur Heart J 1987;8:31&318. 36. McDonald K, Maurer BJ. Familial aortic valve disease: evidence for a genetic influence? Eur Heart J 1989; 10:676*77. 37. Emanuel R, Withers R, O’Brien K, Ross P, Feizi 0. Congenitally bicuspid aorttc valve. Clinicogenetic study of 41 families. Br Heart .I 1978% 1402-1407. Am J Cardiol
FEBRUARY15,1994
1. Inoue K, Okawi T. Nakamura T, Kitamura F, Miyamoto N. Clinical application of tramvenous mitral commissurotomy by a new balloon catheter. J Thorax Cardiowsc Sur,q 1984;87:394-402.
2. Vahanian A, Michel PL, Cornier B, Vitoux B,.Michel X, Slama M, Entiquez Sarano L, Trabelsi S, Ben lsmail M, Acar J. Results of percutaneous mitral commissurotomy in 200 patients. Am J Card& 1989;63:847-852. 3. Bemal JM, Mimlles PJ. Cardiac surgery with cardiopulmonary bypass during pregnancy. Obst Gynecol Surv 1986;41:14. 4. Clark SL, Phelan JP, Greenspeon J, Aldahl D, Horenstein J. Labor and delivety in the presence of mitral stenosis: central hemodynamic observations. Am J Obster Gynecol 1985;152:984-988. 5. Lamb Ml’, Ross K, Johnstone AM, Manners JM. Fetal heat monitoring during open heart surgery. Two case reports. Br J Obstet Gynecol 1981;88:66%674. 6. Vosloo S, Reichart 9. The feasibility of closed mitral valvotomy in pregnancy. J Thorac Cardiovasc Surg 1987;93:6%679. 7. Safian RD, Berman AD, Sachs B, Diver DJ, Come PC, Bairn DS, McKay L, Grossman W, McKay RG. Percutaneous balloon mitral valvuloplasty in a pregnant woman with mitral stenosis. Cathet Cardiovasc Diqn 1988;15: 103-108. 8. Palacios IF, Block PC, Wilkins CT, Red&r DE, Daggett WM. Percutaneous mitral balloon valvotomy during pregnancy in a woman with severe mitral stenosis. Cather Cardiovasc Diqn 1988; 15: 109-l 11. 9. Mangione JA, Zuliani MF, Del Castillo JM, Nogueira EA. Arie S. Percutaneous double balloon mitral valvuloplasty in pregnant women. Am J Cardiol 1989; 64:9%102. 10. Smith R, Brenda D, McCredie M. Percutaneous transluminal balloon dilatation of mitral valve in pregnancy. Br Heart J 1989;61:551-553. 11. Esteves CA, Ramos AIO, Braga SLN, Harrison JK, Sousa JE. Effectiveness of percutaneous balloon mitral valvotomy during pregnancy. Am J Cardiol 1991: 68:93&934. 12. Drobinski G, Fraboulet P, Montalescot G, Moussallem N, Coutte R, Artigou JY, Grosgogeat Y. Valvuloplastie mitmle au quatri&me mois de grossesse. F’rotection foetale par un mat&au de plomb. Arch Mal Coeur 199 1;84:249-25 1. 13. Gangbar EW, Watson KR, Howard RJ, Chisholm RJ. Mittal balloon valvuloplasty in pregnancy: advantages of a unique balloon. Cathet Cardiovmc Diqn 1992:25:313-316. 14. Ruzyllo W, Dabrowski M, Woroszylska M, Rydlewska-Sadowska W. Percutaneous mitral commissurotomy with the Inoue balloon for severe mitral stenosis during pregnancy. J Heart Valve Dis 1992; 1:209-2 12. 15. Ben Farhat M, Maatouk F, Betbout F, Ayari M, Brahim H, Souissi M, Sghairi K, Gamra H. Percutaneous balloon mitral valvuloplasty in eight pregnant women with severe mitral stenosis. Eur Heart J 1992;13:1658-1664. 16. Rib&o PA, Fawzi ME, Awad M, Dunn B, Dunn CG. Balloon valvotomy for pregnant patients with severe pliable mitral stenosis using the Inoue technique with total abdominal and pelvic shielding. Am Heart J 1992; 124: 1558-1562. 17. Rib&o PA, Al Zaibag M. Editorial - mitral balloon valvotomy in pregnancy. J Heart I/a/w Dis 1992; 1:20&208. lt3. Wagner LK, Hayman LA. Pregnancy and women radiologists. Radiology 1982: 145:55%562. 19. Griem ML, Meier P, Dobben GD. Analysis of the morbidity and mortality of children irradiated in fetal life. Radiology 1967;88:347-349. 20. Giraud JR, DuguC-Ma&haud M, Fizazi T, De Tounis H, Auben J. Urographie intraveineuse pendant la grossesse et risque d’hypothyroidie foetale. J Gyn Obst Biol Repr 1983;12:4549.
Congenitally Bicuspid Aortic Valve in Multiple Family Members Brian N. Glick, MD,* and William C. Roberts, MDt he congenitally bicuspid aortic valve has been the subject of numerous publications. Leonardo da Vinci T in the 1400sdrew the valve and provided some reasons
not until the 1950sthat the bicuspid condition was recognized to be a common underlying cause of aortic valve stenosis,and it was not until 1981that it was recwhy it might function abnormally.’ In 1844, Paget ognized to be associatedwith pure aortic regurgitation called attention to the peculiar liability of congenitally unassociatedwith infective endocarditis.5The bicuspid bicuspid aortic valves to disease,but their importance as aortic valve has been the subject, directly or indirectly, something other than a pathologic curiosity was not ap- of 228 publications from this laboratory since 1962.5,c32 preciated. In 1858, Peacock3pointed out that bicuspid Despite the frequency of the congenitally bicuspid aortic valvestendedto become“thick . . . ossilled . . . induc- aortic valve (possibly as high as 1% of the population), ing first obstruction. . . and then incompetency.”Oslefl in its occurrencein >l family memberis extremely uncom1886 lirst described the abnormal liability of the bicus- mon. Only 4 reports have appeareddescribing 4 famipid aortic valve to develop infective endocarditis. It was lies (9 family members)with >l member having a congenitally bicuspid aortic valve (Table I).33-36During the past 27 years, we have encountered6 families (17 famFrom the Pathology Branch, National Heart, Lung, and Blood Instiily members)in whom >l member had aortic valve distute,National Institutes of Health, Bethesda, Maryland 20892. Manuscript received April 16, 1993; revised manuscript received and accepted ease, with bicuspid valve confirmed at operation in 11. June 24, 1993. A description of certain tindings in these 17 family *Cardiology Fellow, Georgetown University Medical Center, membersis the subject of this report. Washington, D.C. The pedigree of the 6 families is shown in Figure 1. Kurrent address: Baylor Cardiovascular Institute, Baylor University Medical Center, 3600 Gaston Avenue, Dallas, Texas 75246. In 3 families (I, II and VI), a parent and 21 child were 400
THE AMERICANJOURNALOF CARDIOLOGY VOLUME73
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affected, and in 3 families (III, IV and V), 21 sibling ly suggestedby aortogram in 1 (number 2). The latter only was affected.In 11 of I7 family members,the con- patient had sign@cant aortic regurgitation by aorgenital bicuspid nature of the aortic valve was con- togram at age 10 years. Patients I1 and 12 were stat$rmed at the time of aortic valve replacement, and the ed to have “aortic valve disease,” but no other inforoperatively excised bicuspid aortic valves in 7 of these mation regarding them was available to us. None of the patients are shown in Figures 2 to 5. Another patient I7 patients apparently had clinical evidence of mitral (number IO, family N, Table II) also had aortic valve valve dysfunction. Pertinent j?ndings in each of the I7 patients are replacement, but the type of valve encountered was unknown to us. In the other 5 patients, the bicuspid na- tabulated in Table II. Of the 17 patients, 10 had cliniture of the aortic valve was demonstrated by echocar- cal evidence of aortic valve stenosis, with or without diogram in 2 (numbers 7 and 17; Table II) and strong- associated aortic regurgitation, including 6 in whom a TABLE I Observations Family
in Nine Previously
Reported
Age Year of Publication
First Author
1972
McKuslck
1977
Patients
(all men) with a Congenitally
Biscuspid
Aortic
Valve in More Than One
Member
Gale
1987
Godden
1989
McDonald
Case
Relation
1 2 3 4 5 6 7 8 9
Father* Son* Brother? Brothert Brothert Brother* Brother Brother Brother
(years) at Death
Age (years) at AVR 44
Type
Year of AVR
AS
-
-
AR Murmur
Calcified AV(O-3) 2+
+
+ + -
+ + t + t +
+ + +
19
61 19
38 44 57 57
1972 1976 1980 1980
23 26
-
3+ 3+ 3+ 3+ -
LV-SA psg (mm Hg) -
-
of AV Prosthesis
(size)
t
S-E
-
+t
40 60 65 -
§ B-S (23) C-E (27) B-S (23) -
80 80
SJM S-E
+ + + t +t + +
*Each had severe cystic medial necrosis of the ascending aorta. The father had dissection involving the entire aorta, which was not dilated: the son had tear of a dilated ascendmg aorta with hemopencardium. Neither had skeletal features of the Marfan syndrome. tBoth have dtlated ascending aortas. Case 4 had medlal cysbc necros15 confirmed by htstologic study of portions of the excised ascending aorta. Neither of the Marfan syndrome. $ldentlcal twins, probably monazygotic. Case 6 had infective endocarditis at 1 bme. §The type of substitute valve used 1s uncertain. AR = aortic regurgitabon; AS = aortic stenosis; AV = aortlc valve: AVR = aotiic valve replacement: BAV = biscuspld aortlc valve; B-S = Bjork-Shirley; LV = leftventncular; psg = peaksystolicgradlent; SA = systemlcartery; s/d = peak systolic/end-dlastollc; S-E = Starr-Edwards; SJM = St. Jude Medical; absent or negative; - = Information not available.
“”
BAV atAVR(+) or Necropsy (++)
a through-and-through
fatal
patlent had skeletal features
C-E = Carpentier-Edwards; + = present orpasitive; 0 =
(57) (60) + WN” M4
El
V FIGURE families member bicuspid
1. The pedllee ef 6 with >l family with a congenitally sortie valve.
0
or H
0 0 or # 0
or or or or
0 = W = H = W = [ 1= ( ) = * =
Female Male Died Known mrtic stanasia or pure aortic regurgitation Age (years) at aortic valve replacement Aw@an)atdeath 8iispid aortic valve confirmed at operation
L BRIEFREPORTS 401
peak systolic pressure gradient ranging from 38 to 100 mm Hg was recorded at cardiac catheterization. Of the latter 6 patients, 5 had aortic valve replacement within 1 month of cardiac catheterization. The remaining patient (number 14, Table II) had a cardiac catheterization when she was aged 70 years, and now (April 1993), 9 months later, she has still not had aortic valve replacement, primarily because of noncardiac problems. Four of the 17 patients had pure aortic regurgitation, and 3 of them have had aortic valve replacement. In 3 patients (numbers 10, 11 and 12; Table II), the type of aortic valve dysfinction was unknown to us. Of the 6 families, all affectedmembersin 3 families had aortic stenosis (with or without associated aortic regurgitation); in 2 families (numbers I and II, Table II), the father in each had aortic stenosis, and the child (1 daughter and 1 son) had pure aortic regurgitation, and in 1 family (number IV), it is likely but not proven that some family members had aortic stenosis and others pure aortic regurgitation.
FlBBRE 2. Patients 3 and 4 (Table II). operatively excised aortii valves of patients WN (NIH# 5873152) and WN Jr (NIH# S71-3019). lhe father, who was 44 years old at the time of aortic valve replacement, had aortic valve stenosis and a heavily calcified valve; the son, who was 26 years old had pure aortic re@rgitation and a at valve replacement, noncalcified valve.
FtBURE 3. Paweats 5 and 6 (Table II)., Bperatively excised aortlc valves of patients LB (NIN# S78-43) and PB (NIl+# ~).Patientffiwas53yearsokl,andffiwas72atthe ~Bothpatlmtshrxlstsmticvalves, tineal’dve hut the older brother (PB) had considerrmly more calcilic deposits in the valve than dii the younger sister (LB).
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THE AMERICAN JOURNAL OF CARDIOLOGY
VOLUME 73
In 2 families (numbers II and V, Table II), all affected memberswere men, in 1 family (number VI), all 3 affected memberswere women, and in 3 families (numbers I, III and IV; Table II), 21 affected member was male and 21 was female. Infective endocarditis occurred in only 1 (number 8, Table II) of the 17 patients, and in this case, it caused severeaortic regurgitation and necessitatedaortic valve replacement. The hitherto described observations indicate that the bicuspid aortic valve may occur in >l family member. Although approximately 75% of subjects with congenitally bicuspid aortic valves are male, female members of families are not immune to this congenital malformation. Of our 17 patients, only 9 (53%) were male; in 1 family (number VI), all 3 affected members were female. The type of valve dysfunction resulting from the bicuspid condition was variable. In some families, all affected members had aortic stenosis (with or without associated regurgitation), in some, all affected members
FlBURE 4. PatJents 8 and 9 (Table II). Operatively excised aortic valves of patients FA (NBl# S7939) and BA (NIN# 80 174). The valve of FA is focally calcified and was partially destroyed by actiie infective endccardiiis approximately 1.5 at age 21 years. The valve years before valve replacement of patient BA is devoid of calcium, and it was purely re&~. aant*
ORE 5. Patient 2.4 (Table II). Operatively excised aortii valve of patient LB (NIN# SB9-50) who had valve replace merit for aortic stenosis at aBe 69 years One of the 2 cusps is heavily calcified, and the other one is devoid of calcium. The operatively excised valve weiighed 4 g.
FEBRUARY 15,1994
Patient’s Initials Relation at Death
Age (years)
21 26 -
at AVR
Age (years)
Ill
IV
44 26 53 72
70 69 78 65 -t
Year AR Mumur
+ + -
+
AS
+ 0 + + + 0 0 -
~ ~ 0 0
of AVR 1966 -0 1967 1971 1978 1984 1979 1980 _ + t t t +
0 + + + 0 + -
~ 1981 1989 1982 1989 -
SA (s/d) (mmHg)
85 08 50 0 55 60
LV-SA Psg (mm Hg)
2+
0 3+§ 3+ 3+
AR by AA Angiogram (O-4+)
2.6 4.94 3.3 4.0 2.7 2.2
Cl
0.6 0.5 -
(cm”)
Hancock (23) S-E (9A) t*
S-E (8A) S-E (12A) S-E (11A) B-S (19) B-S (19)
Type (we) of AV Prosthesis
LV b/d) (mm Hg)
120155 135/55§ 130/52 145165 80155 180/70
-
0.6
+ll C-E(21)
+/I SJM (25)
AVA
3+
Calcified AV (O-3+)
20518 135159 180/20 145126 135130 240137
2.4 3.4
~
-
4t 4f -
38 -
-
142180
100 50
-
0
180/18
180/90 140170
-
120/40 140/60
3+
190/16
3+ 0 3+ 3+ 3+ l+ 0
3t 3t
as I” Table I.
2.3
140/13
TABLE II Clinical Findings in the Six Families in Whom More Than One Member Had a Congenitally Bicuspid Aortic Valve
Case 58 58 26 60 70 26 -
V VI
-
58
I
Family Father Daughter Father Son Sister Brother Sister Brother Brother Sister* Sistert Brother7 Brother Brother Mother Daughter Daughter
II
WB LB WN WN Jr LG PG JG FA BA RB LB ED EBD LGD 80 73
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17
*This patient died at the time of aortlc valve replacement. The type of valve dysfunction. and the number of aorbc valve cusps are unknown to US tThe only mformatlon wallable I” these 2 subjects IS that each was described in the medlcal records of FA and BA as having “aorbc valve dwase.” $Thls woman was aged 70 years at cardiac catheterization, and by publlcatlon, she will be 7 1. $These data were collected when the patent was 10 years old (1966). Aorw valve replacement was performed. The typeof substitute valve used IS unknown 1 Coronary artery bypass surgery. AA = ascending aorta; AVA = aort!c valve area; CAD = coronary artery disease; Cl = cardtac Index (Llmlnlm2); TC = total cholesterol; other abbrevlatlons
CAD by Angiogram
-
+ll + -
0 -
+ 0
BAV Confirmed at AVR
181 189 253 236 122 201
Serum TC (mg/dl)
232 207
262
+ 0 + + + + 0 + +
-
t t t + 0
had pure aortic regurgitation (no element of stenosis), and in others, 21 family member had aortic stenosisand 21 had pure aortic regurgitation. The frequency in which a congenitally bicuspid aortic valve occurs in >l family member is unclear. Although our study includes a relatively large number of families in which >l family memberhad a bicuspid aortic valve found at the time of aortic valve replacement, we do not know how many other operatively excised congenitally bicuspid aortic valves we have seen in which only 1 family member had a congenitally bicuspid aortic valve. Some information regarding this frequency question, however, has been provided by Emanuel and associates.37These authors examined 188 living, first-degree relatives of 41 patients (41 different families) who had malfunctioning congenitally bicuspid aortic valves excised at operation. By precordial examination, chest radiograph and electrocardiogramin all 188 relatives, and by M-mode echocardiogramin 52 (28%), 8 of the 188 relatives (4%) from 7 of the 41 families (17%) had evidence of “aortic valve disease.” Thus, of 229 family membersexamined in 41 families, 49 (21%) had clinical or operative evidence of aortic valve disease (the bicuspid condition probably in all of them). Of the 71 family membersin our 6 families, 17 (24%) had evidence of aortic valve disease (most likely a bicuspid aortic valve in all of them). This high percentageis not surprising, becauseeach of the 6 families that provided the 71 family members had 22 members with aortic valve disease.Of the 71 family membersin our 6 families, aortic valve diseasewas present in 8 of 46 living members(17%) and in 9 of 25 dead members(36%). In the study by Emanuel and colleagues,37only 2 of 229 patients were stated to be dead (assuming that each of the 41 patients having aortic valve replacement are alive), and both of them had aortic valve disease;of the 227 presumably living patients, 47 (21%) had evidence of aortic valve disease. In conclusion, the bicuspid aortic valve is clear ly more common in first&ree relatives of sub Jects with a bicuspid aortic Valve than in those of subjects with a tricuspid aortic valve. lt appears reasonable to recommend a good precordial examinat@n and possibly an echocardiogram in firstdegree relatives of subjects clearly identified as having a congenitally bicuspid aortic valve.
1. O’Malley CD, Saunders CM. Leonardo da Vinci on the Human Body. New York: H. Wolff Company, 1952:X%. 2. Paget J. On obstruction of the branches of the pulmonwy artery. Mrd-Chir Tnmans 1884;27:162-188. 3. Peacock TB. On Malformations of the Human Heat. 2nd ed. London: Churchill, 1858:204. 4. Osler W. The bicuspid condition of the amtic valves. Tram Assoc Am Physicians 1886;2:185-192. 5. Roberts WC, Morrow AG, McIntosh CL, Jones M, Epstein SE. Congenitally bicuspid sonic valve causing severe, pure a&c regurgitation without superimposed
404
THE AMERICANJOURNALOF CARDIOLOGY VOLUME73
infective endccarditis. Analysis of 13 patents requiring aortic valve replacement. 198 1;47:2C%209. 2. Roberts WC, Momw AC, Braunwald E. Complete intetnption of the aortic arch. Circularion 1962;26:39-59. 7. Roberts WC, Morrow AC. Cardiac valves and the surgical pathologist. A&I fat/d 1966$2:309-313. 2. Robens WC, Elliott L. Lesions complicating the congenitally bicuspid aortic valve. Anatomic and radiographic features. Radio/ C/m Nmfh Am 1968;6:40842 I 9. Roberts WC. The structure of the aortic valve in clinically-isolated aortic stenosis. An autopsy study of 162 patients over I5 years of age. C~wulahon 1970,42:9 l-97. 10. Roberts WC. The congenitally bicuspid sonic valve. A study of 85 cakes. Am J Cardiol 1970:26:72-83. 11. Robat? WC. Anatomically isolated aortic valvulx disease. The case agamst its being of rheumatic etiology. Am J Mrd 1970:49:151-159. 12. Roberts WC, Perloff JK, Costantino T. Severe valvular aortic stenosis in patients over 65 years of age. A clinicopathologic study. Am J Cardiol 1971:27:497,506. 13. Buchbinder NA, Roberts WC. Left-sided valvular active infective endocatdtis. A study of forty-five necropsy patients. Am J Med 1972:53:2&35. 14. Roberts WC. Valvular, subvalvular, and supravalvular aortic stenosis: marphologic features. Cardiol C/in 1973:5:97-126. 15. Roberts WC, Dangel JC. Bulkley BH. Non-rheumatic valvular cardiac disease: a clinicopathologic survey of 27 different conditions causing valvular dysfunction. Car-dial C/in 1973;5:333446. 16. Amett EN, Robetts WC. Valve ring abscess in active infective endocarditis. Frequency, location, and clues to clinical diagnosis from the study of 95 necropsy patients. Circulrrion 197654: 14&145. 17. McReynolds RA, Ali NO, Cuadra M, Roberts WC. Combined acute rheumatic fever and congenitally bicuspid aottic valve. A hitheno unconfirmed combination. Chest 1976:70:98-100. 16. Amett EN, Roberts WC. Active infective endocarditis: a clinicopathology analysis of 137 necropsy patients. Cuw Pro/~/ Cuvdiol 1976:l:l-76. 19. Roberts WC, Buchbinder NA. Healed left-sided infective endocarditis: a clinicopathologic study of 59 patients. Am J Cardiol 1977:40:87&888. 20. Shemin RJ, Kent KM, Roberts WC. Syndrome of valvular pulmonary stenosis and valvular aottic stenosis with atrial septal defect. Br Heart J 1979;42:442-446. 21. Roberts WC. Aortic dtssection: anatomy, consequences, and causes. Am Hmrr J 1981;101:195-214. 22. Roberts WC, Amett EA. Cabin HS. McIntosh CL, Aisner SC. Documented development of severe stenoses of previous confirmed normally functioning aortic valves. Am Han J 1982: 104~306-308. 23. Amett EA, Robens WC. Pathology of active infective endocarditis: a necropsy analysis of 192 patients. Thomc Cordiovasc Surg 1982;30:327-335. 24. Glancy DL, Morrow AG, Simon AL, Robau WC. Juxtaductal aortic coarctation. Analysis of 84 patients studied hemodynamically, angiographically and marphologically after age I year. Am J Cardiol 1983;51:537-55 I. 21. Roberts WC. Congenital cardiovascular abnormalities usually silent until adulthood. In: Roberts WC, ed. Adult Congenital Heart Diseases. Philadelphia: FA Davis, 1987:631-691. 26. Roberts WC, McIntosh CL, Wallace RB. Aortic valve perforation with calcific aortic valve stenosis and without infective endocarditis or significant aonic regurgitation. Am J Cardrol 1987;59:476+78. 27. Robens WC. Examining operative excised cardiac valves. Am J Cardiol 1987: 59:1434-1436. 28. Mann JM, McIntosh CL, Katz NM, Roberts WC. Cardiac valve replacement for stenotic bicuspid aortic valve in husband and for purely regurgitant pmlapsed mitral valve in wife. Am J Curdiol 1987;60:401402. 29. Kalan JM, McIntosh CL, Bonow RO, Roberts WC. Development of severe stenosis in a previously purely regurgitant, congenitally bicuspid sonic wlvc. Am J Cmdml 1988;62:98&989. 20. Dressier FA, R&ens WC. Infective endocarditis in opiate addicts: analysis of 80 cases studied at necropsy. Am J Cwdiol 1989;63: 124&1257. 31. Roberts WC. Living with a congenitally bicuspid aortic valve. Am .I Car-dial 1989;64:1408-1409. 32. Brown PS Jr, Roberts CS, Mclnto$h CL, Roberts WC, Clark RE. Combtned obstructive hypertrophic cardiomyopathy and stenotic congenitally bicuspid axtic valve. Am J Co,-dial 1990;66: 1368-1372. 22. McKusick V. Association of congenital bicuspid sonic valve and Erdheim’a cystic medial necrosis. Lunwt 1972; I: 1026-1027. 34. Gale AN, McKusick VA, Hutchins GH, Gott VL. Familial congenital bicuspid aortic valve. Chest 1977:72:5:668-670. 25. Godden DJ, Sandhu PS, Kerr F. Stenosed bicuspid aorttc valves in twins. Eur Heart J 1987;8:31&318. 36. McDonald K, Maurer BJ. Familial aortic valve disease: evidence for a genetic influence? Eur Heart J 1989; 10:676*77. 37. Emanuel R, Withers R, O’Brien K, Ross P, Feizi 0. Congenitally bicuspid aorttc valve. Clinicogenetic study of 41 families. Br Heart .I 1978% 1402-1407. Am J Cardiol
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