Coexisting Right and Left Hypertrophic Subvalvular Stenosis and Fixed Left Ventricular Outflow Obstruction Due to Aortic Valve Stenosis ERIC E . HARRISON, MD, FACC SHELDON S . SBAR, MD, FACC HUGH MARTIN, MD DENNIS F . PUPELLO, MD Tampa, Florida
A case of fixed left ventricular outflow tract obstruction due to aortic valve stenosis coexisting with right- and left-sided subvalvular hypertrophic stenosis is documented with hemodynamic data, angiograms, echocardiograms and findings at surgery . Histologic examination of the septal muscle with light and electron microscopy revealed hypertrophy of the muscle but none of the characteristics of Idiopathic hypertrophic subaortic stenosis . Septal hypertrophy with subvalvular obstruction can occur secondary to left ventricular pressure overload due to fixed left ventricular outflow tract obstruction and is not always the chance occurrence of two separate diseases .
Cases of well documented fixed aortic valve obstruction in association with a subvalvular gradient are unusual . Because of the characteristic cell architecture of idiopathic hypertrophic subaortic stenosis, it has been postulated that these cases represent the coincidental coexistence of two separate disease entities . The following report presents a patient who had valve obstruction without the characteristic cell changes of idiopathic hypertrophic subaortic stenosis .
Case History
From the Divisions of Cardiology and Cardiovascular Surgery, The Cardiology Center, Tampa General Hospital, Tampa, Florida . Manuscript received November 3, 1976, accepted December
24, 1977 . Address for reprints : Eric E . Harrison MD, The Cardiology Center, Tampa General Hospital, Davis Island, Tampa, Florida 33606 .
The patient, a 70 year old woman, had a 20 year history of a heart murmur with a recent history of fatigue and dyspnea on exertion . She had been having melena for 1 month and was admitted to another hospital for evaluation . Her hematocrit was 20 percent. She was given blood replacement . Contrast studies revealed diverticulosis of the colon . Because of a grade 4/6 systolic ejection murmur and cardiomegaly, she was transferred to this center for further evaluation . Prior medications were propranolol, 20 mg twice daily, and digitoxin, 0 .2 mg daily . On the day of transfer, the patient was lethargic and her medical history was difficult to obtain . She complained of fatigue, two pillow orthopnea and frequent palpitations accompanied by chest discomfort . There was no family history of cardiovascular disease . Physical examination revealed a blood pressure of 90/60 mm Hg with decreased central pulse amplitude and pulse pressure but no delay in pulses . The jugular venous pressure was not increased . The point of maximal impulse was deviated to the left of the mid clavicular line and thrusting ; a fourth sound gallop could he palpated . A grade 4/6 harsh systolic murmur at the cardiac apex radiated to the left sternal border and to both carotid vessels . No diastolic murmurs were heard . Laboratory data revealed a normal hematocrit and a blood urea nitrogen of 25 mg/100 ml . The chest roentgenogram showed cardiomegaly with left ventricular prominence, prominence of the ascending aorta and clear lung fields . The electrocardiogram revealed first degree atrioventricular (A-V) block and left ventricular hypertrophy with strain . The echocardiogram disclosed left ventricular hypertrophy, a calcified aortic valve, a decreased E to F slope (46 mm/sec), systolic anterior motion of the anterior leaflet of the mitral valve, and a septal to posterior wall thickness ratio of 1 .4 to 1 (Fig . 1) . Cardiac catheterization: The patient continued to do poorly, and cardiac catheterization was performed . There was a pressure gradient of 120 mm Hg across the aortic valve, and an additional subvalvular gradient of 90 mm Hg . In the right ventricle there was a 15 mm Hg subpulmonary gradient . The cardiac output was reduced as calculated by both the Fick and the green dye methods . Cardiac fluoroscopy revealed heavy calcification of the aortic valve . A left ventriculogram in the right anterior oblique projection revealed almost complete
July 1977
The American Journal
of
CARDIOLOGY Volume
40
133
OUTFLOW OBSTRUCTION IN AORTIC VALVE STENOSIS-HARRISON ET AL.
FIGURE 1 . Preoperative echocardiogram disclosing asymmetric septal hypertrophy, and systolic anterior motion and diminished E to F slope of the anterior mitral valve leaflet . AMVL = anterior metral valve leaflet ; IVS = interventricular septum .
obliteration of the left ventricular cavity during systole and an ejection fraction of 87 percent. There was a puff of mitral insufficiency. Simultaneous right and left ventriculograms revealed an extremely large septum with systolic narrowing of both the left and right outflow tracts . Aortic root injection revealed a puff of aortic insufficiency, a distorted aortic valve with a small anulus and poststenotic dilatation of the aortic root. Coronary angiograms were normal .
Surgical and histologic findings : Because of these findings and the clinical history, the patient underwent aortic valve replacement with a no . 21 porcine heterograftt as well as excision of subaortic hypertrophied muscle . Observations at surgery were marked hypertrophy of the left ventricle, an ascending aorta two times normal size, an aortic valve with an opening 3 to 4 mm in diameter and subaortic outflow tract obstruction . Segments in the muscle were cut from the septum
FIGURE 2 . Light photomicrograph of septal muscle tissue showing hypertrophied muscle fibers in an orderly arrangement without evidence of the disarray seen in idiopathic hypertrophic subaortic stenosis . (Hematoxylin-eosin X40, reduced by 24 percent .)
134
July
1977
The American Journal
of
CARDIOLOGY
Volume 40
OUTFLOW OBSTRUCTION IN AORTIC VALVE STENOSIS-HARRISON ET AL .
FIGURE 3. Electron photomicrograph of septal muscle tissue showing muscle fibers arranged in parallel without evidence of whorls or abnormal myocytic size or shape . (osmium-uranil acetate lead citrate X98,600, reduced by 23 percent .)
and left lateral wall in a circumferential area between the right and left coronary arteries. Myectomy was performed according to the technique of Morrow et al? Two samples of muscle were preserved in formalin and glutaraldehyde for preparation for light and electron microscopy. Light microscopy disclosed mild myocardial hypertrophy and focal fibrosis (Fig . 2) . Electron microscopy revealed that the fibers were arranged in parallel without evidence of whorls or disarray . The myofibrils showed minimal irregularity of the Z bands, and the myocytes appeared to have a normal number of mitochondria . Glycogen was present. The intercalated discs were intact (Fig. 3) .
when the patient's condition failed to improve after aortic valve replacement . Histologic examination of septal tissue was performed in only two of the reported cases . Both demonstrated many of the findings of idiopathic hypertrophic aortic stenosis with hypertrophy and disorderly array of the myocardial fibers, which branched and changed direction, forming loops and whorls ." These data provided supportive evidence for the coexistence of two distinct diseases . Our patient had none of the histologic characteristics of idiopathic hypertrophic subaortic stenosis on either light or electron microscopy . This finding supports the hypothesis that in our patient the subvalvular obstruction on both the right and left sides was secondary to hypertrophy of the septum as a response to pressure overload due to aortic valve obstruction . Sufficient data are not available at this time to determine the frequency of occurrence of the two lesions independently and that of aortic stenosis with secondary subvalvular stenosis . The probability that the two lesions will occur simultaneously is the multiple of the probabilities of the independent occurrence of each disease, thus making the former an uncommon accident of nature . However, secondary hypertrophy with subvalvular obstruction commonly occurs in right-sided valvular lesions (pulmonary valve stenosis) . That it could also occur on the left side is not unlikely because the same hemodynamics are involved .
Discussion The clinical presentation, hemodynamic findings and noninvasive observations of asymmetric septal hypertrophy and idiopathic hypertrophic subaortic stenosis have been well described . 36 Abnormalities of celland myocardial architecture have been found in septal muscle and have been recognized as a microscopic indicator of this disease . 7-10 The muscle cells, which are in disarray, are found focally in the myocardium and are arranged in whorls or randomly . The cells themselves are irregular and of different sizes and shapes . The coexistence of hypertrophic subaortic stenosis and fixed left ventricular outflow obstruction due to aortic valve stenosis is uncommon. Twenty-six cases have been reported, 11-19 many of them in children . In our patient the hemodynamically fixed and subvalvular obstructions were nicely demonstrated without provocative pharmacologic agents . The diagnosis was suspected before cardiac catheterization because of the asymmetric septal hypertrophy and systolic anterior motion of the anterior leaflet of the mitral valve in the echocardiogram . In most reported cases, the diagnosis was made operatively or suspected postoperatively
Acknowledgment W e are indebted to Charles K . Donegan, MD and Richard Conner, MD for allowing us to present their patient . We acknowledge the technical assistance of Mrs . Denise King and Mrs . Susie Sharp.
July
1977
The American Journal
of
CARDIOLOGY Volume
40
13 5
OUTFLOW OBSTRUCTION IN AORTIC VALVE STENOSIS-HARRISON ET AL .
References 1 . Pupello OF, Blank RH, Seasons LN, of al : Local deep hypothermia for combined valvular and coronary heart disease . Ann Thorac Surg 21 :508-512, 1976 2 . Morrow AG, Fogarty TJ, Hannah H, at al : Operative treatment in idiopathic hypertrophic subaortic stenosis . Circulation 38 :589-596, 1968 3 . Frank S, Braunwald E: Idiopathic hypertrophic subaortic stenosis . Circulation 37 :759-788, 1968 4 . Simon A: Angiographic diagnosis of idiopathic hypertrophic subaortic stenosis . Radiol Clin North Am 6 :423-435, 1969 5 . Simons AL, Ross J Jr, Gault JH : Angiographic anatomy of the left ventricle and mitral valve in idiopathic subaortic stenosis . Circulation 36:852-867, 1967 6 . Popp RL, Harrison DC: Ultrasound in the diagnosis and evaluation of therapy of idiopathic hypertrophic subaortic stenosis . Circulation 40 :905-914, 1969 7 . Tears D : Asymmetrical hypertrophy of the heart in young adults . Br Heart J 20 :1-18, 1958 8 . Epstein SE, Henry WL, Clark CE, at al : Asymmetric septet hypertrophy . Ann Intern Med 81 :650-680, 1974 9 . Maron BJ, Ferrans VJ, Henry WL, at al: Differences in distribution of myocardial abnormalities in patients with obstructive and nonobstructive asymmetric septal hypertrophy . Circulation 50 : 436-446,1974 10 . Ferrans VJ, Morrow AG, Roberts WC : Myocardial ultrastructure in idiopathic hypertrophic subaortic stenosis . Circulation 45 : 769-797,1972
136
July 1977
The American Journal of CARDIOLOGY
Volume 40
11 . Gordon AS : Surgical management of congenital supravalvular, valvular and subvalvular aortic stenosis using deep hypothermia . J Thorac Cardiovasc Surg 43 :141-156, 1962 12 . Davies H: Hypertrophic subaortic stenosis as a complication of fixed obstruction to left ventricular outflow . Guys Hosp Rep 119 : 35-45 . 1970 13 . Hancock EW: Differentiation of valvar, subvalvar, and supravalvar aortic stenosis . Guys Hosp Rep 110 :1-30, 1961 14 . Morgan JR : Idiopathic hypertrophic subaortic stenosis : variability of obstruction associated with mild aortic valvular stenosis . Milit Med 137 :238-240, 1972 15 . Benchimol A, Legler JF, Dimond EG : Carotid tracing and apexcardiogram in subaortic stenosis and idiopathic myocardial hypertrophy . Am J Cardiol 11 :427-435, 1963 16 . Parker DP, Kaplan MA, Connelley JE : Coexistent aortic valvular and functional hypertrophic subaortic stenosis . Clinical, physiologic and angiographic aspects . Am J Cardiol 24 :307-317, 1969 17 . Block PC, Powell JW, Dinsmore RE, at al : Coexistent fixed congenital and idiopathic hypertrophic subaortic stenosis . Am J Cardiol 31 :523-526, 1973 18 . Chung KJ, Manning JA, Gramiak R : Echocardiography in coexisting hypertrophic subaortic stenosis and fixed left ventricular outflow obstruction . Circulation 49 :673-677, 1974 19. Stewart S, Nanda N, DeWese J : Simultaneous operative correction of aortic valve stenosis and idiopathic subaortic stenosis . Circulation 51, 52 :Suppl 1 :1-35-1-39, 1975
A case of fixed left ventricular outflow tract obstruction due to aortic valve stenosis coexisting with right- and left-sided subvalvular hypertrophic stenosis is documented with hemodynamic data, angiograms, echocardiograms and findings at surgery . Histologic examination of the septal muscle with light and electron microscopy revealed hypertrophy of the muscle but none of the characteristics of Idiopathic hypertrophic subaortic stenosis . Septal hypertrophy with subvalvular obstruction can occur secondary to left ventricular pressure overload due to fixed left ventricular outflow tract obstruction and is not always the chance occurrence of two separate diseases .
Cases of well documented fixed aortic valve obstruction in association with a subvalvular gradient are unusual . Because of the characteristic cell architecture of idiopathic hypertrophic subaortic stenosis, it has been postulated that these cases represent the coincidental coexistence of two separate disease entities . The following report presents a patient who had valve obstruction without the characteristic cell changes of idiopathic hypertrophic subaortic stenosis .
Case History
From the Divisions of Cardiology and Cardiovascular Surgery, The Cardiology Center, Tampa General Hospital, Tampa, Florida . Manuscript received November 3, 1976, accepted December
24, 1977 . Address for reprints : Eric E . Harrison MD, The Cardiology Center, Tampa General Hospital, Davis Island, Tampa, Florida 33606 .
The patient, a 70 year old woman, had a 20 year history of a heart murmur with a recent history of fatigue and dyspnea on exertion . She had been having melena for 1 month and was admitted to another hospital for evaluation . Her hematocrit was 20 percent. She was given blood replacement . Contrast studies revealed diverticulosis of the colon . Because of a grade 4/6 systolic ejection murmur and cardiomegaly, she was transferred to this center for further evaluation . Prior medications were propranolol, 20 mg twice daily, and digitoxin, 0 .2 mg daily . On the day of transfer, the patient was lethargic and her medical history was difficult to obtain . She complained of fatigue, two pillow orthopnea and frequent palpitations accompanied by chest discomfort . There was no family history of cardiovascular disease . Physical examination revealed a blood pressure of 90/60 mm Hg with decreased central pulse amplitude and pulse pressure but no delay in pulses . The jugular venous pressure was not increased . The point of maximal impulse was deviated to the left of the mid clavicular line and thrusting ; a fourth sound gallop could he palpated . A grade 4/6 harsh systolic murmur at the cardiac apex radiated to the left sternal border and to both carotid vessels . No diastolic murmurs were heard . Laboratory data revealed a normal hematocrit and a blood urea nitrogen of 25 mg/100 ml . The chest roentgenogram showed cardiomegaly with left ventricular prominence, prominence of the ascending aorta and clear lung fields . The electrocardiogram revealed first degree atrioventricular (A-V) block and left ventricular hypertrophy with strain . The echocardiogram disclosed left ventricular hypertrophy, a calcified aortic valve, a decreased E to F slope (46 mm/sec), systolic anterior motion of the anterior leaflet of the mitral valve, and a septal to posterior wall thickness ratio of 1 .4 to 1 (Fig . 1) . Cardiac catheterization: The patient continued to do poorly, and cardiac catheterization was performed . There was a pressure gradient of 120 mm Hg across the aortic valve, and an additional subvalvular gradient of 90 mm Hg . In the right ventricle there was a 15 mm Hg subpulmonary gradient . The cardiac output was reduced as calculated by both the Fick and the green dye methods . Cardiac fluoroscopy revealed heavy calcification of the aortic valve . A left ventriculogram in the right anterior oblique projection revealed almost complete
July 1977
The American Journal
of
CARDIOLOGY Volume
40
133
OUTFLOW OBSTRUCTION IN AORTIC VALVE STENOSIS-HARRISON ET AL.
FIGURE 1 . Preoperative echocardiogram disclosing asymmetric septal hypertrophy, and systolic anterior motion and diminished E to F slope of the anterior mitral valve leaflet . AMVL = anterior metral valve leaflet ; IVS = interventricular septum .
obliteration of the left ventricular cavity during systole and an ejection fraction of 87 percent. There was a puff of mitral insufficiency. Simultaneous right and left ventriculograms revealed an extremely large septum with systolic narrowing of both the left and right outflow tracts . Aortic root injection revealed a puff of aortic insufficiency, a distorted aortic valve with a small anulus and poststenotic dilatation of the aortic root. Coronary angiograms were normal .
Surgical and histologic findings : Because of these findings and the clinical history, the patient underwent aortic valve replacement with a no . 21 porcine heterograftt as well as excision of subaortic hypertrophied muscle . Observations at surgery were marked hypertrophy of the left ventricle, an ascending aorta two times normal size, an aortic valve with an opening 3 to 4 mm in diameter and subaortic outflow tract obstruction . Segments in the muscle were cut from the septum
FIGURE 2 . Light photomicrograph of septal muscle tissue showing hypertrophied muscle fibers in an orderly arrangement without evidence of the disarray seen in idiopathic hypertrophic subaortic stenosis . (Hematoxylin-eosin X40, reduced by 24 percent .)
134
July
1977
The American Journal
of
CARDIOLOGY
Volume 40
OUTFLOW OBSTRUCTION IN AORTIC VALVE STENOSIS-HARRISON ET AL .
FIGURE 3. Electron photomicrograph of septal muscle tissue showing muscle fibers arranged in parallel without evidence of whorls or abnormal myocytic size or shape . (osmium-uranil acetate lead citrate X98,600, reduced by 23 percent .)
and left lateral wall in a circumferential area between the right and left coronary arteries. Myectomy was performed according to the technique of Morrow et al? Two samples of muscle were preserved in formalin and glutaraldehyde for preparation for light and electron microscopy. Light microscopy disclosed mild myocardial hypertrophy and focal fibrosis (Fig . 2) . Electron microscopy revealed that the fibers were arranged in parallel without evidence of whorls or disarray . The myofibrils showed minimal irregularity of the Z bands, and the myocytes appeared to have a normal number of mitochondria . Glycogen was present. The intercalated discs were intact (Fig. 3) .
when the patient's condition failed to improve after aortic valve replacement . Histologic examination of septal tissue was performed in only two of the reported cases . Both demonstrated many of the findings of idiopathic hypertrophic aortic stenosis with hypertrophy and disorderly array of the myocardial fibers, which branched and changed direction, forming loops and whorls ." These data provided supportive evidence for the coexistence of two distinct diseases . Our patient had none of the histologic characteristics of idiopathic hypertrophic subaortic stenosis on either light or electron microscopy . This finding supports the hypothesis that in our patient the subvalvular obstruction on both the right and left sides was secondary to hypertrophy of the septum as a response to pressure overload due to aortic valve obstruction . Sufficient data are not available at this time to determine the frequency of occurrence of the two lesions independently and that of aortic stenosis with secondary subvalvular stenosis . The probability that the two lesions will occur simultaneously is the multiple of the probabilities of the independent occurrence of each disease, thus making the former an uncommon accident of nature . However, secondary hypertrophy with subvalvular obstruction commonly occurs in right-sided valvular lesions (pulmonary valve stenosis) . That it could also occur on the left side is not unlikely because the same hemodynamics are involved .
Discussion The clinical presentation, hemodynamic findings and noninvasive observations of asymmetric septal hypertrophy and idiopathic hypertrophic subaortic stenosis have been well described . 36 Abnormalities of celland myocardial architecture have been found in septal muscle and have been recognized as a microscopic indicator of this disease . 7-10 The muscle cells, which are in disarray, are found focally in the myocardium and are arranged in whorls or randomly . The cells themselves are irregular and of different sizes and shapes . The coexistence of hypertrophic subaortic stenosis and fixed left ventricular outflow obstruction due to aortic valve stenosis is uncommon. Twenty-six cases have been reported, 11-19 many of them in children . In our patient the hemodynamically fixed and subvalvular obstructions were nicely demonstrated without provocative pharmacologic agents . The diagnosis was suspected before cardiac catheterization because of the asymmetric septal hypertrophy and systolic anterior motion of the anterior leaflet of the mitral valve in the echocardiogram . In most reported cases, the diagnosis was made operatively or suspected postoperatively
Acknowledgment W e are indebted to Charles K . Donegan, MD and Richard Conner, MD for allowing us to present their patient . We acknowledge the technical assistance of Mrs . Denise King and Mrs . Susie Sharp.
July
1977
The American Journal
of
CARDIOLOGY Volume
40
13 5
OUTFLOW OBSTRUCTION IN AORTIC VALVE STENOSIS-HARRISON ET AL .
References 1 . Pupello OF, Blank RH, Seasons LN, of al : Local deep hypothermia for combined valvular and coronary heart disease . Ann Thorac Surg 21 :508-512, 1976 2 . Morrow AG, Fogarty TJ, Hannah H, at al : Operative treatment in idiopathic hypertrophic subaortic stenosis . Circulation 38 :589-596, 1968 3 . Frank S, Braunwald E: Idiopathic hypertrophic subaortic stenosis . Circulation 37 :759-788, 1968 4 . Simon A: Angiographic diagnosis of idiopathic hypertrophic subaortic stenosis . Radiol Clin North Am 6 :423-435, 1969 5 . Simons AL, Ross J Jr, Gault JH : Angiographic anatomy of the left ventricle and mitral valve in idiopathic subaortic stenosis . Circulation 36:852-867, 1967 6 . Popp RL, Harrison DC: Ultrasound in the diagnosis and evaluation of therapy of idiopathic hypertrophic subaortic stenosis . Circulation 40 :905-914, 1969 7 . Tears D : Asymmetrical hypertrophy of the heart in young adults . Br Heart J 20 :1-18, 1958 8 . Epstein SE, Henry WL, Clark CE, at al : Asymmetric septet hypertrophy . Ann Intern Med 81 :650-680, 1974 9 . Maron BJ, Ferrans VJ, Henry WL, at al: Differences in distribution of myocardial abnormalities in patients with obstructive and nonobstructive asymmetric septal hypertrophy . Circulation 50 : 436-446,1974 10 . Ferrans VJ, Morrow AG, Roberts WC : Myocardial ultrastructure in idiopathic hypertrophic subaortic stenosis . Circulation 45 : 769-797,1972
136
July 1977
The American Journal of CARDIOLOGY
Volume 40
11 . Gordon AS : Surgical management of congenital supravalvular, valvular and subvalvular aortic stenosis using deep hypothermia . J Thorac Cardiovasc Surg 43 :141-156, 1962 12 . Davies H: Hypertrophic subaortic stenosis as a complication of fixed obstruction to left ventricular outflow . Guys Hosp Rep 119 : 35-45 . 1970 13 . Hancock EW: Differentiation of valvar, subvalvar, and supravalvar aortic stenosis . Guys Hosp Rep 110 :1-30, 1961 14 . Morgan JR : Idiopathic hypertrophic subaortic stenosis : variability of obstruction associated with mild aortic valvular stenosis . Milit Med 137 :238-240, 1972 15 . Benchimol A, Legler JF, Dimond EG : Carotid tracing and apexcardiogram in subaortic stenosis and idiopathic myocardial hypertrophy . Am J Cardiol 11 :427-435, 1963 16 . Parker DP, Kaplan MA, Connelley JE : Coexistent aortic valvular and functional hypertrophic subaortic stenosis . Clinical, physiologic and angiographic aspects . Am J Cardiol 24 :307-317, 1969 17 . Block PC, Powell JW, Dinsmore RE, at al : Coexistent fixed congenital and idiopathic hypertrophic subaortic stenosis . Am J Cardiol 31 :523-526, 1973 18 . Chung KJ, Manning JA, Gramiak R : Echocardiography in coexisting hypertrophic subaortic stenosis and fixed left ventricular outflow obstruction . Circulation 49 :673-677, 1974 19. Stewart S, Nanda N, DeWese J : Simultaneous operative correction of aortic valve stenosis and idiopathic subaortic stenosis . Circulation 51, 52 :Suppl 1 :1-35-1-39, 1975
