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Contrasting histoarchitecture of calcified leaflets from stenotic bicuspid versus stenotic tricuspid aortic valves
JACC Vol. IS, No. 5 April IWO: I 104-8
--
JEFFREY
M.
ANTHCNY Bwron,
ISNER, MD, FACC, SAURABH DEFRANCQ,
K. CHOKSHI,
D, JOHN BRAIMEN,
MD, GE
S
Mc1ssnch14setts
we
evaluatedthe his-
Aortic stenosis characterized by extensive calcification of the aortic valve leafletsconstitutes t c most commonform of valvular heart disease in persons older than 40 years (I ). vious studies of stenotic aortic valves examined at netsy G=i-g)or after o~mtive excision ($6) have indicated that c nitdly bicuspid aortic valves account for most cases rtic stenosis in adults under 70 years: in contrast, amou persons beyond the sixth decade of life aortic stenosis most often results from calcification of a congenitally ecuuse of the increased mortality associated with this
St. Elizabeth’s
Hospital. 736
in symptoni~itic piltkfltS (7-9). the onset of sy nerally been conside~d an indication for inte ost commonly, such patients have aortic valve ~p~acement. Alternatively, liab in valvular prostheses have led to re~ewe valvuloplasty procedures ~10-20) designed to preserve the native aortic valve. ~re~in~inaryfindings from clinical trials of both percutaneous /18.21-24 and intraoperative (12,13,20)aortic valvuloplasty have suggestedthat calcified, congenitally bicuspid stenotic aortic valves may be less amenable to such techniques than are calcified stenotic tricuspid aortic valves. A~~~rdi~~ly, the present study was undertaken to investigate the hypothesis that the distribution of calcific deposits in stenotic aortic valves varies according to whether or not the valve is congenitally normal.
!Jkledion of specimens. All operatively excised aortic valves accessioned by our laboratory were reviewed for 073s1097/90/$3.50
( t of the valve could not be accurately class of these IWO types, it was UmS
res~~tat~ve sectwn was
section was then s and stained with ~e~atoxyi~nsa stain for calcium
salts.
iea!I ~~atw~~s. Aortic valves operatively excised fro 40 patients fulfilled the criteria oMtlj~ed and were sub for further pathologic ex ed from 49 to 87 years ( All had doc~me~te regurgitation. Mean aortic 88 (48 L 12) mm Wg. Aorti
genitally
typically enclosed by a collagen envelope, were superimposed on a fibrotic aortic valve leaflet; in type B. calcific deposits were diffusely distributed throughout the body
fibrotic
tricuspid
aortic
valves;
valve
ieatiet
(type
A). In 13 valves
(5?%i),
llQ6
ISNER ET AL. CALCIFIED AORTIC
JACC Vol. April I
VALVES
calcific deposits were diffusely distributed throughout the body (spongiosa) of the aortic valve leaflet (type B). Two valves could not be classified histologically. These histologic subtypes were not randoeily distributed with regard to gross valvu9ar morphology. In each of the 14 valves classified on gross examinaticn as congenitally bicuspid, the distribution of calcific deposits conformed to type 93, as defined. A representative example of the gross ht microscopic findings typical of a heavily calcified, enitally bicuspid aortic valve is illustrated in
15. No.
5
-R
to the histoarcbitecture of a rock-like mass of valvular tissue obstructing left ve~tri~~9~r ou characterized by unavailable interventions ( (before pr~stbetic va9ve re-
In contrast, in I9 (6 aortic VW~VCS,the histo~r~hite~ture was e9 and the distribution of ealcific deposits conformed to
aortic valves has aortic valves are seopie examination. Thr relation between gross vnlvular morphology and light microscopic distribution ofcalc$c deposits is summarized in Figure 4. Chi-square analysis disclosed th portion of type 93histoarchitecture observed a itally bicuspid valves versus type A hist ngenitally tricuspid valves was statistically (p < Q,QI).
tally tricuspid Volvos,
tive rnan~~9 or u9 r-tie vdve resultin
it as the “bicuspid condition” and ~~ognized that “clinically this is a very important congenital defect, owing to th liability of the combined valve [conjoined leaflet] to s (26) subsequently attributed de~ene~tive effects associated t opning and closing of two asymmetric (9-4). in a series of classic studies. defined ity gQsed by the ~on~~nital9y bicuspid aortic valve in terms of valvular stenosis. valvular insufficiency Iy little information has histologic characteristics of the aortie valve. ~~icMl~9~ once it has ed. Studies are similariy limited with ic features of heavily calcified. It is perhaps understandable that little attention was paid
most tricuspid valves will prove appropriate for intraoperative debridement. there will be some in which debridement will not be possible. A second ~~~~n~~u~implication of the present findings is the possibility that the ;lattern by which the calcific deposits are dist~b~t~d within the valve leaflet determines whether or not such a valve will prove a plasty. It is possible, but as calcific deposits (17,29,22) may be more readily accomplished when the calcium is deposited in nodular form on an underiying leaflet rather than thickness of the leaflet. Perhaps this explains the apparent increased refractoriness of the bicuspid valve to balloon dilation.
the ventricularaspects.
scopic biding in an operatively itallytricuspidaorticvalve. Gross
1108
JACC Vol. IS. No. 5 : I104-8 April I
ISNER ET AL. CALClFtED AORTIC VALVES
w
r
81
?,I
9. Turina J. Hess 0. Sepulcri F, Krayenbuehl HP. S~nta~leo~s course of aortic valve disease. Eur Heart J 1987:83471-83.
HISTOLOGIC EXA
a 0 11
14 3
IO. Kirklin JW. The replacement of cardiac valves (editorial). N E 1981:304:291-2.
oltho? 0
i I. lsner JM, Michlewitz H. Clarke RN. Donaldson RF,
2
assisted debridement of aortic valve calcium. Am 448-52.
?!I?ij art .i
12. King RM. Pluth JR, Giuliani ER, Piehler JM. Mechanical dcca~cifica?io~ l~;4~:26~-7~. of the aortic valve. Ann Thorac S Relation of gross valvular morphology and light microscopic dktribution of calcific dewsits for specimens studied. Chisquare an@sis disclosed that the dis chiteeture
The basis for the differi erved in this study rema tee pat One possible explanation relates to the duration of the ess. Because the bicus has been subject to accelerated tion as a posed by asym:zetric leaflet mc’ion (26). calcification at a relatively earlier age may ultimately lead to more thorough leaflet involvement than in the case of a normally functicning tricuspid valve. Alternatively, these two patterns could conceivably be related to sites of maximal stress. For example, a heter~mer~us bileadet valve in the aortic position may open and clsse in such a manner that all aspects of the leaflet are stressed te an abnormal and equivalent degree. In a normal valve the of calcium distributed ~rima~ly on ulnar)surface of the valve leaflet su may be predominant alo periods to the closing pressure of the systemic ~i~ul~ti~n.
13. Mindich BP. Guarino T. Goldman aortic stenosis. Circulation IBSb;74@tppl J):Ct30-5. 14. Worlcy SJ, shock wave intraoperative studies. J Am Colt awlak IS, Freeman WK, Scha~ HV, King valve dec~i~ci~cation: J Am Coil Cnrdiol ~~~~~~ltsuppl Ak229A.
_
vatves: TA. ~~tr~so~ic aortic
16, Cribier A, Saoudi N, Berland J, Savin I”, Rochu P, Lelac B. ~e~~~ta~~o~ls transl~mim~lvalvuleptasty dfacyuired aortic stenosis in elderly ~~~tic~is~ an alternative to valve replucement’! Lancer l~8~~:6~7. 17. McKay RG, Satlan RD. Lock JE. et al. Balloon d~iatat~l~aofca~c~~caordc stenosis in elderly patients: ~stmo~em, int 18. lsner SM. Salem DN. 19. 2% Chokshi SK. Slovenkai GA. lsner JM. valve calcium is elective for three-cusp aortic valves tabstrt. Clin Res l9~;3~25lA.
deb~~dea~~atof uortic c~n~enita~~yhicu~~~d,
21. Kennedy KD. Hauck AJ. E Nishimura RA. ~~ecb~ais~ of ~ed~~ct~o~~ of aortic valvular stenosis h percutaneous t~ns~~rni~al balloo review of thr literature. 22. lsner JM. Aortic valvu~oplas~y: are bal “cracked” up to be’! Mayo Clin Proe 19 23.
olland K. Santinga J, Lee f.. a’Neill WW of valve type predicts h~m~ynamic res aortic valvuloplasty (abstr~, Circulation I
24. lsner JM. Mansfield IDE lnvestig of halloun aortic valvul~p~asty. J Am Coil CardioI (in press) I*
Valvuhr, kabms.
2.
subvrlvulrr and supravalvular aortic Cardiovasc Clint 19735:97-I 16.
SltXWk
The structure of the aortic valve in clinically isolated aortic stenosis: an autopsy study of 162 patients over IS years of ape. Circulation I :42%-J.
25. Grossman W. Aortic stenosis. In: Grossman W. ed. tion and Angiopraphy. Philadelphia: WE Saunders,
~at~eter~za-
26. Edwards JE. The co~enital bicuspid aortic valve. 485-K
1961;23:
3. Roberts WC. The congenitally bicuspid aortic valve: a study of 85 autopsy cases. Am J Cardiol 1970:26:72-83.
21. Wailer BF. Carter 38. Williams HJ Jr. Wang K. Edwards SE. Bicuspid aortic VdVe: comparison of congenital and acquired types. Circulation 1973:48:I 140-50.
4. Roberts WC. Anatomically isolated aortic valvular disease: the case in9 ef rheumatic etiology. Am J Med 1970:49:151-9.
28. Fenoglio JJ, McAllister HA. HeCastro CM. The congenital bicuspid aorlic valve after ape 20. Am J Cardiol 1977:39: 164-9.
5 ., So~~lial~ R, Olson LJ. Edwards WD. Surgical pathology of pure aortic stcr&s: a study of 374 cases. Mayo Clis Proc I~:~~~.~~.
29.
6.
ssik CS. Acke~an D uth JR. Edwards WI). ‘fernpond changes in ic stenosis: a s~r&ul pathologic study of 646 cases.
3. Prank S. J&BXI A. ROSSJ Jr. Natural history of valvular aurtic stenosis. Br dcprt J 1973%:41-6. 8. o’K~f% JH Jr. Vfitstra RE. Bailey KR. Holmes DR Jr. Natural history es for balloon aortic valvuloplasty. Mayo Clin Pmc F&7:62:
Thr Principles and Practice of Me~icioe. New York: D. Appleton
30. Rickrtdson L. Richardson’s combination of Verhoeff s elastic and Gomori’s trichmme stains with modifications. Lab 31.
orrow AG. McIntosh CL. Jones Eps:ein SE. Congenital!y bicuspid aortic valve causing severe, pure aortic regurgitatiun without superimposed infective ea~ocar~~tis: anatysis of 13 patients requiring aortir valve replacement. Am J Cardiol 1981:47:2&9.
32. Robefis WC. Buchbinder NA. Healed left-sided infective endocarditis: a clinicopathologic study of 59 patients. Am J Cardiol 1977;40:876-88.
--
JEFFREY
M.
ANTHCNY Bwron,
ISNER, MD, FACC, SAURABH DEFRANCQ,
K. CHOKSHI,
D, JOHN BRAIMEN,
MD, GE
S
Mc1ssnch14setts
we
evaluatedthe his-
Aortic stenosis characterized by extensive calcification of the aortic valve leafletsconstitutes t c most commonform of valvular heart disease in persons older than 40 years (I ). vious studies of stenotic aortic valves examined at netsy G=i-g)or after o~mtive excision ($6) have indicated that c nitdly bicuspid aortic valves account for most cases rtic stenosis in adults under 70 years: in contrast, amou persons beyond the sixth decade of life aortic stenosis most often results from calcification of a congenitally ecuuse of the increased mortality associated with this
St. Elizabeth’s
Hospital. 736
in symptoni~itic piltkfltS (7-9). the onset of sy nerally been conside~d an indication for inte ost commonly, such patients have aortic valve ~p~acement. Alternatively, liab in valvular prostheses have led to re~ewe valvuloplasty procedures ~10-20) designed to preserve the native aortic valve. ~re~in~inaryfindings from clinical trials of both percutaneous /18.21-24 and intraoperative (12,13,20)aortic valvuloplasty have suggestedthat calcified, congenitally bicuspid stenotic aortic valves may be less amenable to such techniques than are calcified stenotic tricuspid aortic valves. A~~~rdi~~ly, the present study was undertaken to investigate the hypothesis that the distribution of calcific deposits in stenotic aortic valves varies according to whether or not the valve is congenitally normal.
!Jkledion of specimens. All operatively excised aortic valves accessioned by our laboratory were reviewed for 073s1097/90/$3.50
( t of the valve could not be accurately class of these IWO types, it was UmS
res~~tat~ve sectwn was
section was then s and stained with ~e~atoxyi~nsa stain for calcium
salts.
iea!I ~~atw~~s. Aortic valves operatively excised fro 40 patients fulfilled the criteria oMtlj~ed and were sub for further pathologic ex ed from 49 to 87 years ( All had doc~me~te regurgitation. Mean aortic 88 (48 L 12) mm Wg. Aorti
genitally
typically enclosed by a collagen envelope, were superimposed on a fibrotic aortic valve leaflet; in type B. calcific deposits were diffusely distributed throughout the body
fibrotic
tricuspid
aortic
valves;
valve
ieatiet
(type
A). In 13 valves
(5?%i),
llQ6
ISNER ET AL. CALCIFIED AORTIC
JACC Vol. April I
VALVES
calcific deposits were diffusely distributed throughout the body (spongiosa) of the aortic valve leaflet (type B). Two valves could not be classified histologically. These histologic subtypes were not randoeily distributed with regard to gross valvu9ar morphology. In each of the 14 valves classified on gross examinaticn as congenitally bicuspid, the distribution of calcific deposits conformed to type 93, as defined. A representative example of the gross ht microscopic findings typical of a heavily calcified, enitally bicuspid aortic valve is illustrated in
15. No.
5
-R
to the histoarcbitecture of a rock-like mass of valvular tissue obstructing left ve~tri~~9~r ou characterized by unavailable interventions ( (before pr~stbetic va9ve re-
In contrast, in I9 (6 aortic VW~VCS,the histo~r~hite~ture was e9 and the distribution of ealcific deposits conformed to
aortic valves has aortic valves are seopie examination. Thr relation between gross vnlvular morphology and light microscopic distribution ofcalc$c deposits is summarized in Figure 4. Chi-square analysis disclosed th portion of type 93histoarchitecture observed a itally bicuspid valves versus type A hist ngenitally tricuspid valves was statistically (p < Q,QI).
tally tricuspid Volvos,
tive rnan~~9 or u9 r-tie vdve resultin
it as the “bicuspid condition” and ~~ognized that “clinically this is a very important congenital defect, owing to th liability of the combined valve [conjoined leaflet] to s (26) subsequently attributed de~ene~tive effects associated t opning and closing of two asymmetric (9-4). in a series of classic studies. defined ity gQsed by the ~on~~nital9y bicuspid aortic valve in terms of valvular stenosis. valvular insufficiency Iy little information has histologic characteristics of the aortie valve. ~~icMl~9~ once it has ed. Studies are similariy limited with ic features of heavily calcified. It is perhaps understandable that little attention was paid
most tricuspid valves will prove appropriate for intraoperative debridement. there will be some in which debridement will not be possible. A second ~~~~n~~u~implication of the present findings is the possibility that the ;lattern by which the calcific deposits are dist~b~t~d within the valve leaflet determines whether or not such a valve will prove a plasty. It is possible, but as calcific deposits (17,29,22) may be more readily accomplished when the calcium is deposited in nodular form on an underiying leaflet rather than thickness of the leaflet. Perhaps this explains the apparent increased refractoriness of the bicuspid valve to balloon dilation.
the ventricularaspects.
scopic biding in an operatively itallytricuspidaorticvalve. Gross
1108
JACC Vol. IS. No. 5 : I104-8 April I
ISNER ET AL. CALClFtED AORTIC VALVES
w
r
81
?,I
9. Turina J. Hess 0. Sepulcri F, Krayenbuehl HP. S~nta~leo~s course of aortic valve disease. Eur Heart J 1987:83471-83.
HISTOLOGIC EXA
a 0 11
14 3
IO. Kirklin JW. The replacement of cardiac valves (editorial). N E 1981:304:291-2.
oltho? 0
i I. lsner JM, Michlewitz H. Clarke RN. Donaldson RF,
2
assisted debridement of aortic valve calcium. Am 448-52.
?!I?ij art .i
12. King RM. Pluth JR, Giuliani ER, Piehler JM. Mechanical dcca~cifica?io~ l~;4~:26~-7~. of the aortic valve. Ann Thorac S Relation of gross valvular morphology and light microscopic dktribution of calcific dewsits for specimens studied. Chisquare an@sis disclosed that the dis chiteeture
The basis for the differi erved in this study rema tee pat One possible explanation relates to the duration of the ess. Because the bicus has been subject to accelerated tion as a posed by asym:zetric leaflet mc’ion (26). calcification at a relatively earlier age may ultimately lead to more thorough leaflet involvement than in the case of a normally functicning tricuspid valve. Alternatively, these two patterns could conceivably be related to sites of maximal stress. For example, a heter~mer~us bileadet valve in the aortic position may open and clsse in such a manner that all aspects of the leaflet are stressed te an abnormal and equivalent degree. In a normal valve the of calcium distributed ~rima~ly on ulnar)surface of the valve leaflet su may be predominant alo periods to the closing pressure of the systemic ~i~ul~ti~n.
13. Mindich BP. Guarino T. Goldman aortic stenosis. Circulation IBSb;74@tppl J):Ct30-5. 14. Worlcy SJ, shock wave intraoperative studies. J Am Colt awlak IS, Freeman WK, Scha~ HV, King valve dec~i~ci~cation: J Am Coil Cnrdiol ~~~~~~ltsuppl Ak229A.
_
vatves: TA. ~~tr~so~ic aortic
16, Cribier A, Saoudi N, Berland J, Savin I”, Rochu P, Lelac B. ~e~~~ta~~o~ls transl~mim~lvalvuleptasty dfacyuired aortic stenosis in elderly ~~~tic~is~ an alternative to valve replucement’! Lancer l~8~~:6~7. 17. McKay RG, Satlan RD. Lock JE. et al. Balloon d~iatat~l~aofca~c~~caordc stenosis in elderly patients: ~stmo~em, int 18. lsner SM. Salem DN. 19. 2% Chokshi SK. Slovenkai GA. lsner JM. valve calcium is elective for three-cusp aortic valves tabstrt. Clin Res l9~;3~25lA.
deb~~dea~~atof uortic c~n~enita~~yhicu~~~d,
21. Kennedy KD. Hauck AJ. E Nishimura RA. ~~ecb~ais~ of ~ed~~ct~o~~ of aortic valvular stenosis h percutaneous t~ns~~rni~al balloo review of thr literature. 22. lsner JM. Aortic valvu~oplas~y: are bal “cracked” up to be’! Mayo Clin Proe 19 23.
olland K. Santinga J, Lee f.. a’Neill WW of valve type predicts h~m~ynamic res aortic valvuloplasty (abstr~, Circulation I
24. lsner JM. Mansfield IDE lnvestig of halloun aortic valvul~p~asty. J Am Coil CardioI (in press) I*
Valvuhr, kabms.
2.
subvrlvulrr and supravalvular aortic Cardiovasc Clint 19735:97-I 16.
SltXWk
The structure of the aortic valve in clinically isolated aortic stenosis: an autopsy study of 162 patients over IS years of ape. Circulation I :42%-J.
25. Grossman W. Aortic stenosis. In: Grossman W. ed. tion and Angiopraphy. Philadelphia: WE Saunders,
~at~eter~za-
26. Edwards JE. The co~enital bicuspid aortic valve. 485-K
1961;23:
3. Roberts WC. The congenitally bicuspid aortic valve: a study of 85 autopsy cases. Am J Cardiol 1970:26:72-83.
21. Wailer BF. Carter 38. Williams HJ Jr. Wang K. Edwards SE. Bicuspid aortic VdVe: comparison of congenital and acquired types. Circulation 1973:48:I 140-50.
4. Roberts WC. Anatomically isolated aortic valvular disease: the case in9 ef rheumatic etiology. Am J Med 1970:49:151-9.
28. Fenoglio JJ, McAllister HA. HeCastro CM. The congenital bicuspid aorlic valve after ape 20. Am J Cardiol 1977:39: 164-9.
5 ., So~~lial~ R, Olson LJ. Edwards WD. Surgical pathology of pure aortic stcr&s: a study of 374 cases. Mayo Clis Proc I~:~~~.~~.
29.
6.
ssik CS. Acke~an D uth JR. Edwards WI). ‘fernpond changes in ic stenosis: a s~r&ul pathologic study of 646 cases.
3. Prank S. J&BXI A. ROSSJ Jr. Natural history of valvular aurtic stenosis. Br dcprt J 1973%:41-6. 8. o’K~f% JH Jr. Vfitstra RE. Bailey KR. Holmes DR Jr. Natural history es for balloon aortic valvuloplasty. Mayo Clin Pmc F&7:62:
Thr Principles and Practice of Me~icioe. New York: D. Appleton
30. Rickrtdson L. Richardson’s combination of Verhoeff s elastic and Gomori’s trichmme stains with modifications. Lab 31.
orrow AG. McIntosh CL. Jones Eps:ein SE. Congenital!y bicuspid aortic valve causing severe, pure aortic regurgitatiun without superimposed infective ea~ocar~~tis: anatysis of 13 patients requiring aortir valve replacement. Am J Cardiol 1981:47:2&9.
32. Robefis WC. Buchbinder NA. Healed left-sided infective endocarditis: a clinicopathologic study of 59 patients. Am J Cardiol 1977;40:876-88.