CAHDfOMYOPAlHY
Relation Between Extent of Cardiac Muscle Cell Disorganization and Left Ventricular Wall Thickness in Hypertrophic Cardiomyopathy Barry J. Maron,
MD,
James K. Wolfson,
and William C. Roberts,
MD
ypertrophic cardiomyopathy (HC) is a primary cardiac disease characterized by an asymmetrically hypertrophied but nondilated left ventricle.’ Disorganized arrangement of cardiac muscle cells has been recognized to be an important morphologic feature of the ventricular architecture in this disea~e.~-l~ It has also been generally accepted that in HC the thickest portions of the left ventricular (LV) wall are most likely to contain disordered myocardial cells. However, this relation between the magnitude of LV wall thickness and the degree of cardiac muscle cell disorganization has not been systematically investigated in HC. Therefore, the present investigation was performed using histologic sections obtained at necropsy from 31 patients with HC.
H
The presence of numerous, abnormally arranged, cardiac muscle cells dlstrlbuted widely throughout the hyperkophled left ventricular (LV) wall has been consldered a characterlstk, morphofoglc feature of patients dylng of hypertrophk cardlomyopathy (HC) and also probably a determinant of impaired LV compliance. However, the relation between such reglons of myocardbl cell disarray and the magnitude of wall thkhness in the same areas of the left ventrkle has not been deflned. Therefore, the present study was undertaken in which LV wall thickness and the percent area of myecardlum dlsorganlxed were systematkally compared in the same tissue sectkn. No correlatlon was tdentlfied between wall thkkness and the amount of myocardlum dlsorganlxed In the same tissue sections, either when cakulated separately for the ventrkular septum, and anterolateral and posterior free walls, or when expressed for all 3 regions combined. The&ore, In patlents with HC: (1) dlsorganlzed myocardlal architecture is not confined to greatly thkkened portions of the LV wall, but regions of the left ventrkle wlth normal or only mildly lncreased thkkness may also be disordered; and (2) whereas both LV wall thkkenlng and cellular dlsorganization are manlfestatfons of the prhnary cardlomyopathk process, these 2 morphologk features do not appear to be directly related with regard to their extent and dlstributlon wlthln the LV wall. There observations will potentially enhance understanding of the relation between LV structure and compliance in HC. (Am J Cardlol1992;70:785-790)
ME7HOD3
From the Pathology and Cardiology Branches, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Manuscript received December 27, 1991; revised manuscript received and accepted June 1,1992. Address for reprints: Barry J. Maron, MD, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7B-15, Bethesda, Maryland 20892. DlSORGANlZATlON
MD,
sdactkn of patianW The cardiovascular registry of the National Heart, Lung, and Blood Institute was re viewed, and 31 hearts were included in the present study group. Bach patient fulfilled our basic anatomic definition of HC with an asymmetrically hypertrophied nondilated left ventricle in the absence of another cardiac or systemic disease capable of producing the magnitude of LV hypertrophy present in that patient.’ In 25 of 31 patients, typical clinical, hemodynamic, angiocardiographic and operative findings of HCi4J5 were also present; the other 6 had no cardiovascular evaluation during life, and sudden death was the first definitive manifestation of cardiac disease.i4-l6 The 3 1 study patients ranged in age from 11 to 61 years (mean 34); 16 (51%) were male. Before death, 9 patients were asymptomatic, 9 mildly symptomatic, and 13 severely symptomatic. Nineteen patients had the obstructive form of HC (outflow gradient 130 mm Hg during basal conditions or with provocative maneuvers), 6 were nonobstructive (gradient 30 mm in thickness, the extent of cellular disorganization was similar (range 9 to 59%, mean 36 f 18; p >0.05). In 28 tissue sections with 0.05). RelationbetweenleRvenMcdarwallthkbessand
extenl of A musde eelI di~aniz8ttenr Comparison of LV wall thicknesses and percent area disorganized in the same tissue sections showed no correlation, either when calculated separately for the ventricular
AND HYPERTROPHY
IN HYPERTROPHIC
CARDIOMYOPATHY
787
loo0
. :
80-
.-5 B ‘E m 50.-$
r= -O.Ml r n= 31
0. 0. 0
0
0
00 0
i 40s 20 0
Ia bCO
15
l o 20 SeptalThii
I .I 25 30 (mm)
0 0
0.
8
I 35
I 4c
0
0
I
r= -0.026 n- 31
I FmJRE2.ReMionbetween~wntrkukwaDtMdawes(im3sites)andextentel mdiacmudecemdrorgrJutknin smetksuesedionhwn31~wilh bP-wk--
I
0
20
I
30
25
35
I
40
Anterolateral FreeWall Thickness(mm) lOO-
0
,s 80! E 8 5
HI-
L--Y r=-O.lsB n= 31
0
l * :
g
40-
0 : 0
5 3 ; 2o 0
788
0
.*mrl
10
THE AMERICAN
0
m
I
15 20 25 30 PosteriorFreeWall Thickness(mm) JOURNAL
OF CARDIOLOGY
VOLUME
70
I
I
35
40
SEPTEMBER
15, 1992
TABLE I Relation Between Cardiac Muscle Thickness in 3 1 Patients with Hypertrophic
LV Site
No. of Pts.
Ventricular septum Anterolateral free wall Posterior free wall All combined
31 31 31 93
Cell Disorganization Cardiomyopathy
and Left Ventricular
Wall Thickness (mm)
% Area Disorganized
40 f 30 (O-95) 33 k 36 (O-94) 19 -t 23 (O-81)
22 2 6 (14-40) 18 + 5 (10-30)
31 f 31 (O-95)
19 2 5 (10-40)
17 2 4 (1 l-27)
Wall
r Value
Slope
-0.021 -0.026 -0.159 -0.063
-0.101 -0.188 -0.863 -0.342
LV = left ventricular.
septum, and anterolateral and posterior free walls (Figure 2), or when expressed for all 3 regions combined (Table I); correlation coefficients ranged from -0.021 to -0.159. Furthermore, no correlation was evident between LV wall thickness and either type I or II disorganization when assessed separately. No correlation was evident between total percent cellular disorganization and basal LV outflow gradient in the 25 patients with hemodynamic studies (r = -0.08). DlSCUSSlON We previously demonstrated that in patients dying of HC, disorganization of cardiac muscle cells is usually widely distributed throughout the LV wa11.6-10The findings of the present study extend those observations and show that disordered myocardial architecture is not confined to greatly thickened portions of the ventricular myocardium, and that conversely, regions of normal or only mildly increased wall thickness also may be disorganized. For the overall group of patients studied, there was absolutely no statistical relation between the magnitude of LV wall thickness and the extent to which cardiac muscle cells within the same tissue section were disorganized, regardless of the particular region of the LV wall assessed (i.e., ventricular septum, or anterolatera1 or posterior free wall). The clear inference of the data is that whereas both LV wall thickening and cellular disorganization appear to be manifestations of the primary cardiomyopathic process in HC,15 these 2 morphologic features are not linked with respect to their extent and distribution. Our observation that LV segments of normal or only mildly increased thickness may have substantial regions of disorganization demonstrates that even the least hypertrophied portions of the LV wall may also be considered part of the primary myopathic process. This finding deviates from the previous morphologic perception that it is primarily the greatly hypertrophied portions of hearts with HC that show abnormal myocardial architecture.19q20 The significance of the disordered myocardial architecture characteristic of HC is uncertain, although it has been suggested that it may have an important role in producing increased ventricular chamber stiffness and impaired relaxation. 14,15,21If myocardial disorganization has such pathophysiologic significance, then the present data would suggest that abnormalities in compliance may involve normal or relatively thin segments of the wall (as well as those with greater wall thickDISORGANIZATION
ness), in sharp contrast to the widely held concept that impaired compliance in HC is closely related to particularly substantial LV wall thickening.14,21 However, the observations in the percent morphologic study are also consistent with previous Doppler echocardiographic lindings22 that LV diastolic filling abnormalities in HC are largely independent of the magnitude of LV hypertrophy, and are also frequent in patients with only mild and localized hypertrophy. We could not assesswith precision the impact that connective tissue formation had on the relation between LV wall thickness and the extent of cellular disorganization in the same tissue section. First, by necessity, sections with substantial scarring23-25 were excluded from the present analysis (because assessment of cardiac muscle cell arrangement was precluded), and second, a detailed quantitative assessment of the magnitude of interstitial, perivascular and replacement fibrosis was not part of the study design. REFERENCE!3 1. Maron BJ, Epstein SE. Hypwtrophic cardiomyopathy: a discussion of nomenclature. Am J Cardiol 1919;43:1242-1244. 2. Teare D. Asymmetrical hypertrophy of the heart in young adults. Br Hew? J 1958;20:1-8. 3. Olsen EG. Anatomic and light microscopic characterization of hypertrophic obstructive and non-obstructive cardiomyopathy. Eur Heart J 1983;4(suppl F):l-8. 4. Ferrans VJ, Morrow AG, Roberts WC. Myocardial ultrastructure in idiopathic hypertrophic subaortic stenosis: a study of operatively excised left ventricular outflow tract muscle in 14 patients. Circulafion 1972;45:769-792. 5. Sutton MSJ, Lie JT, Anderson KR, O’Brien PC, Frye RL. Histopathological specificity of hypertrophic obstructive cardiomyopathy. Myocardial libre disarray and myocardial fibrosis. Br Heart J 1980;44:433-443. 6. Maron BJ, Roberts WC. Hypertrophic cardiomyopathy and cardiac muscle cell disorganization revisited: relation between the two and significance. Am Heart J 1981;102:95-110. 7. Maron BJ, Anan TJ, Roberts WC. Quantitative analysis of the distribution of cardiac muscle cell disorganization in the left ventricular wall of patients with hypertrophic cardiomyopathy. Circulation 1981;63:882-894. 8. Maron BJ, Sato N, Roberts WC, Edwards JE, Chandra RS. Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum: mmparison of fetuses and infants with and without congenital heart disease and patients with hypertrophic cardiomyopathy. Circulnfion 1979;60:685-696. 9. Maron BJ, Roberts WC. Quantitative analysis of cardiac muscle cell disorganiration in the ventricular septum of patients with hypertrophic cardiomyopathy. Circulation 1979;59:689-706. 10. Maron BJ, Epstein SE. Hypertrophic cardiomyopathy. Recent observations regarding the specificity of three hallmarks of the disease: asymmetric septal hypertrophy, septal disorganization, and systolic anterior motion of the anterior mitral leaflet. Am J Cordial 1980;45:141-154. 11. Isner JM, Maron BJ, Roberts WC. Comparison of amount of cardiacmuscle-cell disorganization in operatively-excised septectomy specimens to amount observed at necropsy in 18 patients with hypertmphic cardiomyopathy. Am J Cardiol 1980;46:42-41. 12. Fujiwara H, Kawai C, Hamashima Y. Myocardial fascicle and fiber disarray in 25 p-thick sections. Cireulotion 1979;59:1293-1298. 13. Van Noorden S, Olsen EGJ, Pearse AGE. Hypertrophic obstructive cardio
AND HYPERTROPHY
IN HYPERTROPHIC
CARDIOMYOPATHY
789
myopathy, a hiitological, hiitochemical, and ultrastructural rial.
Cu~diouusc
study of biopsy mate-
Res 1971;5:118-131.
14. Wigle ED, Sasson 2, Henderson MA, Ruddy TD, Fulop J, Rakowski H, Williams WG. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Ccudiovaw Dis 1985;28:1-83. 1% Maron BJ, Bonow RO, Cannon RO, Leon MB, Epstein SE. Hypertrophic cardiomyopathy: Interrelation of clinical manifestations, pathophysiology and therapy. N Engl J Med 1987;780-789 and 844-852. 16. McKenna WJ, Camm AJ. Sudden death in hypertrophic cardiomyopathy: assessment of patients at high risk. Circulation 1989;80:1489-1492. 17. Roberts CS, Roberts WC. Morphologic features. In: Zipes DP, Rowlands DJ, eds. Progress in Cardiology 2/2. Philadelphia: Lea & Febiger, 19893-22. 18. Maron BJ, Epstein SE, Roberts WC. Hypertrophic cardiomyopathy and transmural myocardial infarction without significant atherosclerosis of the extramural coronary arteries. Am J CardioI 1979;43:1086-1102. 19. Henry WL, Clark CE, Epstein SE. Asymmetric septal hypertrophy (ASH): echocardiographic identification of the pathognomonic anatomic abnormality of IHSS. Circulation 1973;4?:225-233.
790
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
70
20. Epstein SE, Henry WL, Clark CE, Roberts WC, Maron BJ, Ferrans VJ, Redwood DR. Morrow AG. Asymmetric septal hypertrophy. Ann Intern Med 1974;81:650-680. 21. Goodwin JF. Congestive and hypertrophic cardiomyopathiea: a decade of study. Lmcet 1970;1:731-739. 22. Spirit0 P, Maron BJ. Relation between extent of left ventricular hypertrophy and diastolic tilling abnormalities in hypertrophic cardiomyopathy. J Am Coil Cordiof 1990;15:808-813. 23. Factor SM, Butany J, Sole MJ, Wigle ED, Williams WC, Rojkind M. Pathologic fibrosis and matrix connective tissue in the subaortic myocardium of patients with hypertrophic cardiomyopathy. J Am Coil Cordial 1991;17: 1343-1351. 24. Tanaka M, Fujiwara H, Onodera T, Wu D-J, Hamashima Y, Kawai C. Quantitative analysis of myocardial fibrosis in normals, hypertensive hearts, and hypertrophic cardiomyopathy. Br Hem J 1986;55:575-581. 25. Maron BJ, Wolfson JK, Epstein SE, Roberts WC. Intramural (“small yesset”) coronary artery disease in hypertrophic cardiomyopathy. J Am Co11 Cardiol 1986;8:545-557.
SEPTEMBER
15. 1992
Relation Between Extent of Cardiac Muscle Cell Disorganization and Left Ventricular Wall Thickness in Hypertrophic Cardiomyopathy Barry J. Maron,
MD,
James K. Wolfson,
and William C. Roberts,
MD
ypertrophic cardiomyopathy (HC) is a primary cardiac disease characterized by an asymmetrically hypertrophied but nondilated left ventricle.’ Disorganized arrangement of cardiac muscle cells has been recognized to be an important morphologic feature of the ventricular architecture in this disea~e.~-l~ It has also been generally accepted that in HC the thickest portions of the left ventricular (LV) wall are most likely to contain disordered myocardial cells. However, this relation between the magnitude of LV wall thickness and the degree of cardiac muscle cell disorganization has not been systematically investigated in HC. Therefore, the present investigation was performed using histologic sections obtained at necropsy from 31 patients with HC.
H
The presence of numerous, abnormally arranged, cardiac muscle cells dlstrlbuted widely throughout the hyperkophled left ventricular (LV) wall has been consldered a characterlstk, morphofoglc feature of patients dylng of hypertrophk cardlomyopathy (HC) and also probably a determinant of impaired LV compliance. However, the relation between such reglons of myocardbl cell disarray and the magnitude of wall thkhness in the same areas of the left ventrkle has not been deflned. Therefore, the present study was undertaken in which LV wall thickness and the percent area of myecardlum dlsorganlxed were systematkally compared in the same tissue sectkn. No correlatlon was tdentlfied between wall thkkness and the amount of myocardlum dlsorganlxed In the same tissue sections, either when cakulated separately for the ventrkular septum, and anterolateral and posterior free walls, or when expressed for all 3 regions combined. The&ore, In patlents with HC: (1) dlsorganlzed myocardlal architecture is not confined to greatly thkkened portions of the LV wall, but regions of the left ventrkle wlth normal or only mildly lncreased thkkness may also be disordered; and (2) whereas both LV wall thkkenlng and cellular dlsorganization are manlfestatfons of the prhnary cardlomyopathk process, these 2 morphologk features do not appear to be directly related with regard to their extent and dlstributlon wlthln the LV wall. There observations will potentially enhance understanding of the relation between LV structure and compliance in HC. (Am J Cardlol1992;70:785-790)
ME7HOD3
From the Pathology and Cardiology Branches, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Manuscript received December 27, 1991; revised manuscript received and accepted June 1,1992. Address for reprints: Barry J. Maron, MD, National Heart, Lung, and Blood Institute, National Institutes of Health, Building 10, Room 7B-15, Bethesda, Maryland 20892. DlSORGANlZATlON
MD,
sdactkn of patianW The cardiovascular registry of the National Heart, Lung, and Blood Institute was re viewed, and 31 hearts were included in the present study group. Bach patient fulfilled our basic anatomic definition of HC with an asymmetrically hypertrophied nondilated left ventricle in the absence of another cardiac or systemic disease capable of producing the magnitude of LV hypertrophy present in that patient.’ In 25 of 31 patients, typical clinical, hemodynamic, angiocardiographic and operative findings of HCi4J5 were also present; the other 6 had no cardiovascular evaluation during life, and sudden death was the first definitive manifestation of cardiac disease.i4-l6 The 3 1 study patients ranged in age from 11 to 61 years (mean 34); 16 (51%) were male. Before death, 9 patients were asymptomatic, 9 mildly symptomatic, and 13 severely symptomatic. Nineteen patients had the obstructive form of HC (outflow gradient 130 mm Hg during basal conditions or with provocative maneuvers), 6 were nonobstructive (gradient 30 mm in thickness, the extent of cellular disorganization was similar (range 9 to 59%, mean 36 f 18; p >0.05). In 28 tissue sections with 0.05). RelationbetweenleRvenMcdarwallthkbessand
extenl of A musde eelI di~aniz8ttenr Comparison of LV wall thicknesses and percent area disorganized in the same tissue sections showed no correlation, either when calculated separately for the ventricular
AND HYPERTROPHY
IN HYPERTROPHIC
CARDIOMYOPATHY
787
loo0
. :
80-
.-5 B ‘E m 50.-$
r= -O.Ml r n= 31
0. 0. 0
0
0
00 0
i 40s 20 0
Ia bCO
15
l o 20 SeptalThii
I .I 25 30 (mm)
0 0
0.
8
I 35
I 4c
0
0
I
r= -0.026 n- 31
I FmJRE2.ReMionbetween~wntrkukwaDtMdawes(im3sites)andextentel mdiacmudecemdrorgrJutknin smetksuesedionhwn31~wilh bP-wk--
I
0
20
I
30
25
35
I
40
Anterolateral FreeWall Thickness(mm) lOO-
0
,s 80! E 8 5
HI-
L--Y r=-O.lsB n= 31
0
l * :
g
40-
0 : 0
5 3 ; 2o 0
788
0
.*mrl
10
THE AMERICAN
0
m
I
15 20 25 30 PosteriorFreeWall Thickness(mm) JOURNAL
OF CARDIOLOGY
VOLUME
70
I
I
35
40
SEPTEMBER
15, 1992
TABLE I Relation Between Cardiac Muscle Thickness in 3 1 Patients with Hypertrophic
LV Site
No. of Pts.
Ventricular septum Anterolateral free wall Posterior free wall All combined
31 31 31 93
Cell Disorganization Cardiomyopathy
and Left Ventricular
Wall Thickness (mm)
% Area Disorganized
40 f 30 (O-95) 33 k 36 (O-94) 19 -t 23 (O-81)
22 2 6 (14-40) 18 + 5 (10-30)
31 f 31 (O-95)
19 2 5 (10-40)
17 2 4 (1 l-27)
Wall
r Value
Slope
-0.021 -0.026 -0.159 -0.063
-0.101 -0.188 -0.863 -0.342
LV = left ventricular.
septum, and anterolateral and posterior free walls (Figure 2), or when expressed for all 3 regions combined (Table I); correlation coefficients ranged from -0.021 to -0.159. Furthermore, no correlation was evident between LV wall thickness and either type I or II disorganization when assessed separately. No correlation was evident between total percent cellular disorganization and basal LV outflow gradient in the 25 patients with hemodynamic studies (r = -0.08). DlSCUSSlON We previously demonstrated that in patients dying of HC, disorganization of cardiac muscle cells is usually widely distributed throughout the LV wa11.6-10The findings of the present study extend those observations and show that disordered myocardial architecture is not confined to greatly thickened portions of the ventricular myocardium, and that conversely, regions of normal or only mildly increased wall thickness also may be disorganized. For the overall group of patients studied, there was absolutely no statistical relation between the magnitude of LV wall thickness and the extent to which cardiac muscle cells within the same tissue section were disorganized, regardless of the particular region of the LV wall assessed (i.e., ventricular septum, or anterolatera1 or posterior free wall). The clear inference of the data is that whereas both LV wall thickening and cellular disorganization appear to be manifestations of the primary cardiomyopathic process in HC,15 these 2 morphologic features are not linked with respect to their extent and distribution. Our observation that LV segments of normal or only mildly increased thickness may have substantial regions of disorganization demonstrates that even the least hypertrophied portions of the LV wall may also be considered part of the primary myopathic process. This finding deviates from the previous morphologic perception that it is primarily the greatly hypertrophied portions of hearts with HC that show abnormal myocardial architecture.19q20 The significance of the disordered myocardial architecture characteristic of HC is uncertain, although it has been suggested that it may have an important role in producing increased ventricular chamber stiffness and impaired relaxation. 14,15,21If myocardial disorganization has such pathophysiologic significance, then the present data would suggest that abnormalities in compliance may involve normal or relatively thin segments of the wall (as well as those with greater wall thickDISORGANIZATION
ness), in sharp contrast to the widely held concept that impaired compliance in HC is closely related to particularly substantial LV wall thickening.14,21 However, the observations in the percent morphologic study are also consistent with previous Doppler echocardiographic lindings22 that LV diastolic filling abnormalities in HC are largely independent of the magnitude of LV hypertrophy, and are also frequent in patients with only mild and localized hypertrophy. We could not assesswith precision the impact that connective tissue formation had on the relation between LV wall thickness and the extent of cellular disorganization in the same tissue section. First, by necessity, sections with substantial scarring23-25 were excluded from the present analysis (because assessment of cardiac muscle cell arrangement was precluded), and second, a detailed quantitative assessment of the magnitude of interstitial, perivascular and replacement fibrosis was not part of the study design. REFERENCE!3 1. Maron BJ, Epstein SE. Hypwtrophic cardiomyopathy: a discussion of nomenclature. Am J Cardiol 1919;43:1242-1244. 2. Teare D. Asymmetrical hypertrophy of the heart in young adults. Br Hew? J 1958;20:1-8. 3. Olsen EG. Anatomic and light microscopic characterization of hypertrophic obstructive and non-obstructive cardiomyopathy. Eur Heart J 1983;4(suppl F):l-8. 4. Ferrans VJ, Morrow AG, Roberts WC. Myocardial ultrastructure in idiopathic hypertrophic subaortic stenosis: a study of operatively excised left ventricular outflow tract muscle in 14 patients. Circulafion 1972;45:769-792. 5. Sutton MSJ, Lie JT, Anderson KR, O’Brien PC, Frye RL. Histopathological specificity of hypertrophic obstructive cardiomyopathy. Myocardial libre disarray and myocardial fibrosis. Br Heart J 1980;44:433-443. 6. Maron BJ, Roberts WC. Hypertrophic cardiomyopathy and cardiac muscle cell disorganization revisited: relation between the two and significance. Am Heart J 1981;102:95-110. 7. Maron BJ, Anan TJ, Roberts WC. Quantitative analysis of the distribution of cardiac muscle cell disorganization in the left ventricular wall of patients with hypertrophic cardiomyopathy. Circulation 1981;63:882-894. 8. Maron BJ, Sato N, Roberts WC, Edwards JE, Chandra RS. Quantitative analysis of cardiac muscle cell disorganization in the ventricular septum: mmparison of fetuses and infants with and without congenital heart disease and patients with hypertrophic cardiomyopathy. Circulnfion 1979;60:685-696. 9. Maron BJ, Roberts WC. Quantitative analysis of cardiac muscle cell disorganiration in the ventricular septum of patients with hypertrophic cardiomyopathy. Circulation 1979;59:689-706. 10. Maron BJ, Epstein SE. Hypertrophic cardiomyopathy. Recent observations regarding the specificity of three hallmarks of the disease: asymmetric septal hypertrophy, septal disorganization, and systolic anterior motion of the anterior mitral leaflet. Am J Cordial 1980;45:141-154. 11. Isner JM, Maron BJ, Roberts WC. Comparison of amount of cardiacmuscle-cell disorganization in operatively-excised septectomy specimens to amount observed at necropsy in 18 patients with hypertmphic cardiomyopathy. Am J Cardiol 1980;46:42-41. 12. Fujiwara H, Kawai C, Hamashima Y. Myocardial fascicle and fiber disarray in 25 p-thick sections. Cireulotion 1979;59:1293-1298. 13. Van Noorden S, Olsen EGJ, Pearse AGE. Hypertrophic obstructive cardio
AND HYPERTROPHY
IN HYPERTROPHIC
CARDIOMYOPATHY
789
myopathy, a hiitological, hiitochemical, and ultrastructural rial.
Cu~diouusc
study of biopsy mate-
Res 1971;5:118-131.
14. Wigle ED, Sasson 2, Henderson MA, Ruddy TD, Fulop J, Rakowski H, Williams WG. Hypertrophic cardiomyopathy. The importance of the site and the extent of hypertrophy. A review. Prog Ccudiovaw Dis 1985;28:1-83. 1% Maron BJ, Bonow RO, Cannon RO, Leon MB, Epstein SE. Hypertrophic cardiomyopathy: Interrelation of clinical manifestations, pathophysiology and therapy. N Engl J Med 1987;780-789 and 844-852. 16. McKenna WJ, Camm AJ. Sudden death in hypertrophic cardiomyopathy: assessment of patients at high risk. Circulation 1989;80:1489-1492. 17. Roberts CS, Roberts WC. Morphologic features. In: Zipes DP, Rowlands DJ, eds. Progress in Cardiology 2/2. Philadelphia: Lea & Febiger, 19893-22. 18. Maron BJ, Epstein SE, Roberts WC. Hypertrophic cardiomyopathy and transmural myocardial infarction without significant atherosclerosis of the extramural coronary arteries. Am J CardioI 1979;43:1086-1102. 19. Henry WL, Clark CE, Epstein SE. Asymmetric septal hypertrophy (ASH): echocardiographic identification of the pathognomonic anatomic abnormality of IHSS. Circulation 1973;4?:225-233.
790
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUME
70
20. Epstein SE, Henry WL, Clark CE, Roberts WC, Maron BJ, Ferrans VJ, Redwood DR. Morrow AG. Asymmetric septal hypertrophy. Ann Intern Med 1974;81:650-680. 21. Goodwin JF. Congestive and hypertrophic cardiomyopathiea: a decade of study. Lmcet 1970;1:731-739. 22. Spirit0 P, Maron BJ. Relation between extent of left ventricular hypertrophy and diastolic tilling abnormalities in hypertrophic cardiomyopathy. J Am Coil Cordiof 1990;15:808-813. 23. Factor SM, Butany J, Sole MJ, Wigle ED, Williams WC, Rojkind M. Pathologic fibrosis and matrix connective tissue in the subaortic myocardium of patients with hypertrophic cardiomyopathy. J Am Coil Cordial 1991;17: 1343-1351. 24. Tanaka M, Fujiwara H, Onodera T, Wu D-J, Hamashima Y, Kawai C. Quantitative analysis of myocardial fibrosis in normals, hypertensive hearts, and hypertrophic cardiomyopathy. Br Hem J 1986;55:575-581. 25. Maron BJ, Wolfson JK, Epstein SE, Roberts WC. Intramural (“small yesset”) coronary artery disease in hypertrophic cardiomyopathy. J Am Co11 Cardiol 1986;8:545-557.
SEPTEMBER
15. 1992
