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Severe systemic hypertension and muscular subaortic stenosis
Severe systemic hypertension subaortic stenosis
and muscular
Luis E. Alday, M.D. Henry R. Wagner, M.D. Peter Vlad, M.D. Bu$trlo, N. Y.
B
rock’s1 description of muscular subaortic stenosis considered systemic hypertension to be a possible etiologic factor of the disease, but coexistence is probably coincidental since subsequent surveys2-s failed to find a significant correlation. Hypertension in patients with muscular subaortic stenosis is infrequent and usually mild8-I0 but rarely severe.1*11~12 The case herein reported is an example of this unusual association. Case report D. M., a 1.5year-old girl, was born with a neurogenie bladder, bilateral hydronephrosis, hydrometer, and an imperforate anus. Several surgical procedures were performed during infancy and childhood (suprapubic cystostomy, cutaneous ureterostomy, total cystectomy, bilateral ureteroileostomy, and pyelotomy for renal calculi). A moderately loud, systolic murmur, maximal at the left lower sternal border and accompanied by a systolic thrill, was heard first when she was 3 years old; a clinical diagnosis of ventricular septal defect was made and repeatedly maintained. Chronic renal failure with hypertension developed at 13 years. Antihypertensive therapy (reserpine, Apresoline, methyldopa, guanethidine, and thiazides) elicited only intermittent response; blood pressure measurements varied between 130/95 and 180/120 mm. Hg. Chest x-ray and electrocardiogram (ECG) showed progressive hypertrophy of the left
ventricle. The systolic murmur became louder and an early diastolic murmur developed. The clinical diagnosis was changed to aortic valve disease when renal function deteriorated at the age of 14%. years. At this time, a kidney transplant was considered and cardiac catheterization was performed. The hemodynamic and cineangiographic findings were consistent with severe muscular subaortic stenosis (Table I and Fig. 1) and mild mitral and aortic regurgitation. The patient’s twenty-fifth hospital admission was made 6 weeks after cardiac catheterization, because of frequent, severe headaches. Although she was taking guanethidine, her blood pressure was 210/130 mm. Hg in the supine position and 170/115 mm. Hg while standing. Grade 2 fundoscopic changes were present. The apical impulse was in the anterior axillary line in the sixth intercostal space. A Grade 2/6 harsh systolic ejection murmur was present along the left sternal border. A Grade l/6 early diastolic murmur could also be heard in the aortic area. The second heart sound was normal in intensity. Heart rate was 84 beats per minute. Clinically, there was no evidence of heart failure. Laboratory data reflected severe renal impairment and anemia. The x-ray showed a cardiothoracic ratio of 60 per cent and normal pulmonary markings. The ECG, as shown in Fig. 2, was compatible with left atria1 enlargement and severe left ventricular hypertrophy. Prominent delta waves were evident. A striking feature of this examination was the decrease in intensity of the systolic murmur, which in previous examinations had been considered to be Grade 4/6. This decrease occurred when the patient’s blood pressure was uncontrolled with read-
Supported in part by Research Grant HE 09474.04 from the National Heart and Lung Institute, National Institutes of Health, Bethesda, Md. Work was done during Dr. Alday’s tenure of a cardiac fellowship from the National Heart Institute. Received for publication Sept. 21. 1970. Reprint requests to: Henry R. Wagner. M.D., Children’s Hospital, 219 Bryant St., Buffalo, N. Y. 14222.
Vol. 83, No. 3, fib. 395-400
March, 1972
American Heart Journal
395
396
Alday,
Wagner, and I/lad
Fig. 1. Pull-back pressure 80 mm. Hg at subvalvar
Table I. Hemodynamic
tracing level.
from
left ventricular
body
to ascending
aorta
showing
pressure
gradient
of
Jina%ngs* Pressures
(mm.
Hg)
Site Rest RA (mean) RV MPA PCW (mean) LV A0 PSG CO CI
4 2516 22113 14 150/16 86/60 64 6.9 L./min. 4.5 L./min./M.2
Isoproterend
PropranoEol
Iso~roierenol~
210/20 80/S 130
150/16 87/58 63
140/16 82/56 58
*Abbreviations: RA, right atrium; RV, right ventricle; MPA, main pulmonary artery; PCW. ventricle; AO, central aorta; PSG. peak systolic gradient; CO, cardiac output; CI. cardiac tAfter propranolol infusion.
ings of 210/130 mm. Hg. A phonocardiogram (Fig. 3) revealed marked increase in the intensity of the systolic murmur after amyl nitrite inhalation. A presystolic murmur appeared after the pharmacologic test. The second heart sound in the resting phonocardiogram was paradoxically split. A late systolic bulge which increased after inhalation of amyl nitrite was seen in the apexcardiogram. The carotid pulse tracing showed a bifid contour. The patient received methyldopa, propranolol (40 to 80 mg. daily), chlorothiazide, and calcium carbonate, but blood pressure fluctuated considerably, ranging from 170/11.5 mm. Hg in the supine position to 90/60 mm. Hg while standing. Dizziness and substernal discomfort were present when she was in the latter position. Changes in the intensity of the systolic murmur were noticed: the lower the blood pressure, the louder the murmur and vice versa. After 6 weeks of unsuccessful medical treatment congestive heart failure occurred. Blood pressure readings were 230/140 mm. Hg in the supine position and 220/140 mm. Hg while standing. Rena1 function deteriorated. Propranolol was discontinued. The congestive heart failure did not improve with therapy. A hemodialysis was performed 3 weeks
pulmonary index.
capillary
wedge;
later. The patient subsequently developed cardial effusion, 300 C.C. of bloody fluid moved from the pericardium. Shortly after patient had a cardiac arrest.
Autopsy
LV,
left
a periwere rethat the
findings
The principal findings from the autopsy were severe, chronic pyelonephritis due to obstructive uropathy, severe hypertrophy of the left ventricle producing narrowing of the outflow tract, and uremic pericardial effusion of 1,100 ml. Heart. The weight of the heart was 580 grams. The epicardium appeared cloudy and granular. The left ventricle (Fig. 4) was concentrically hypertrophied but the thickening of the myocardium was maximal at the upper muscular septum, which measured 25 mm. in diameter compared to 20 mm. at the left ventricular free wall. The diameter of the outflow tract measured 9 mm. in the autopsy specimen. The mus-
Volume Number
Fig.
83 3
2. The
Severe systemic hypertension
12-lead
ECG
showing
left ventricular
397
strain.
cular septum opposite to the anterior leaflet of the mitral valve was covered by a thickened, fibrous endocardium (Fig. 5). The left atrium was enlarged, its wall up to 4 mm. thick. Both mitral valve leaflets were thickened but no signs of endocarditis were present. The papillary muscles were extremely hypertrophied, the anterior one measuring 16 mm. in diameter. The aortic valve was normal, tricuspid; the aortic annulus diameter measured 19 mm. The coronary ostia were placed normally and the coronary arteries were patent and smooth. The ascending aorta was slightly dilated. Discussion Following detailed clinical, hemodynamic, angiocardiographic, and anatomic description of muscular subaortic stenosis,3-8 it was evident that the degree of obstruction of the left ventricular outflow tract could be altered, by a number of circumstances. Extrasystoles,13 exercise,‘*J5 the Valsalva maneuver,16 upright tilt,l’ bleeding,‘* administration of the nitrites,16Jg-21 digitalis glycosides,22 and isoproterenol,14J8*23 acting by different ways, augment the severity of the obstruction. Conversely, amelioration of the stenosis can be obtained with general anesthesia,g transfusion,18 changes in body position, i.e., head-down tilt” or squatting,z* and the administration of several pharmacologic agents as methox-
Fig. 3. Phonocardiogram (PCG) at lower left sternal border, apexcardiogram (A CC), and electrocardiogram (ECG). After inhalation of amyl nitrite the systolic murmur intensified and a presystolic murmur appeared. SI, first heart sound; AS, aortic closure; P2, pulmonic closure; SM, systolic murmur; PSM, presystolic murmur.
amine,23 neosynephrine,25 and angiotensin.26p27 Beta-adrenergic blocker agents prevent, or greatly reduce, the induced gradient across the obstruction, but they do not affect the resting gradient significantly.15 In an attempt to explain the variability of the stenosis in patients with muscular subaortic stenosis, Wigle and associates26 proposed that the severity of the obstruction was regulated by a number of inter-
39s
Alduy,
Am. Heart I. 1972 March,
Wagner, and L’lad
Fig. 5. Close-up view of the left ventricular outflow tract. M‘v, mitral valve; A V, aortic valve; AO, aorta; Llr, left ventricle.
Fig. 4. View aorta (AO).
of the opened
left
ventricle
(Lv)
and
related variables, namely, the distending pressure of the left ventricular outflow tract, the circumferential wall tension of this tract, and the volume of the left ventricle. The distending pressure of the left ventricular outflow tract, or pressure distal to the stenosis, is equal to the aortic pressure; the circumferential wall tension is the result of the tension developed by the contraction of the bulbospiral muscles of the left ventricular outflow tract. A decrease in the distending pressure, an increase in the contractility of the left ventricle, or a reduction of the left ventricular size, would be followed by worsening of the obstruction. A reduction of the gradient between the inflow and outflow tracts of the left ventricle would be provoked by increasing the distending pressure or the ventricular volume, or by decreasing the contractility of the muscle fibers of the left ventricular outflow tract. The administration of vasoconstricting agents, such as neosynephrine, methoxamine, and angiotensin, is followed by an increase of the systemic pressure or left ventricular afterload, thus augmenting the distending pressure of the outflow tract and reducing the obstruction.26s27 A hemody-
namic situation closely resembling this acute phenomenon is seen when sustained severe hypertension is associated with muscular subaortic stenosis. The difficulties encountered in treating these patients have recently been stressed by others.12 There is no question that muscular subaortic stenosis in our patient long preceded the development of hypertension. She was misdiagnosed as having a ventricular septal defect at the age of 3 years. Systemic hypertension was first recorded when she was 13 and subsequently a cardiac catheterization proved that she had muscular subaortic stenosis. Aortic insufficiency may be associated with muscular subaortic stenosisgs24s2* or with systemic hypertension due to a distended aortic valve ring.24 Changes in the physical findings, similar to those appearing after provocative maneuvers, were noticed during the patient’s last two admissions. Significant elevation of the patient’s blood pressure by augmenting the distending pressure of the left ventricular outflow tract was accompanied by marked attenuation of the systolic murmur. On the other hand, orthostatic hypotension resulted in a much louder systolic murmur, substernal discomfort, and dizziness. These signs and symptoms were also produced by inhalation of amyl nitrite. At this stage, it was very difficult to offer this patient any form of palliation. A kidney transplant had been
Volwne Nwmber
83 3
considered, but this possibility was discarded because of the severe cardiac disease. Open heart surgery could not be performed, in view of the renal failure. A combined treatment with antihypertensive drugs and propranolol was unsuccessful. Congestive heart failure developed, the renal function deteriorated, and the patient died. Contradictory long-term results with this form of therapy have been reported.2g-33 The cause of this patient’s death was a combination of renal failure and severe heart disease. It is likely, although it cannot be proved, that the antihypertensive therapy aggravated the muscular subaortic stenosis. It has been suggested that when this disease is associated with severe systemic hypertension, surgical relief of the outflow tract obstruction should be tried first.12 Summary The case of a 15year-old girl with severe systemic hypertension secondary to chronic pyelonephritis and muscular subaortic stenosis is reported. The severity of the obstruction of the left ventricular outflow tract varied according to the blood pressure levels. Uncontrolled hypertension attenuated the auscultatory signs indicative of stenosis. Augmentation of the obstruction, evidenced by intensification of the murmur, was present when antihypertensive drugs produced orthostatic hypotension. No adequate form of palliation could be offered to this patient because of the coexistence of end-stage renal failure and the severe cardiac disease which led to her death.
Severe systemic hypertension
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
REFERENCES 18. 1. Brock, R. C.: Functional obstruction of the left ventricle, Guy Hosp. Rep. 106:221, 1957. R. C.: Functional obstruction of the left 2. Brock. ventricle, Guy Hosp. Rep. 108:126, 1959. 3. Brachfeld, N., and Gorlin, R.: Subaortic stenosis: A revised concept of the disease, Medicine 38:415, 1959. 4. Goodwin, J. I., Hollman, A., Cleland, W. P., et al.: Obstructive cardiomyopathy simulating aortic stenosis. Brit. Heart 1. 22:403. 1960. .5 . Braunwald, E:, Morrow, A:G., Cornell, W. P., et al.: Idiopathic hypertrophic subaortic stenosis. Clinical, hemodynamic and angiographic manifestations, Amer. J. Med. 29:924, 1960. 6. Menges, H., Jr., Brandenburg, R. O., and Brown, A. L.: The clinical, hemodynamic and
19.
20.
21.
22.
399
pathologic diagnosis of muscular subvalvar aortic stenosis, Circulation 24:1126, 1961. Wigle, E. D., Heimbecker, R. O., and Gunton, R. W.: Idiopathic ventricular septal hypertrophy causing muscular subaortic stenosis, Circulation 26:325, 1962. Burchell, H. B.: Hypertrophic obstructive type of cardiomyopathy: Clinical syndrome, in Wolstenholme, G. E. W., and O’Connor, M., editors: Cardiomyopathies, London, 1964, J. & A. Churchill Ltd.; p. 29. Braunwald. E.. Lambrew. C. T.. Rockoff. S. D., et al:: Idiopathic hypertrophic subaortid stenosis. I. A description of the disease based upon an analysis of 64 patients, Circulation 30 (Suppl. 4):3, 1964. Cohen, J., Effat, H., Goodwin, J. F., et al.: Hypertrophic obstructive cardiomyopathy, Brit. Heart-J. 26:16, 1964. Ewv. G. A.. Marcus. F. I.. Bohaialian. 0.. et al.: Mu’scular subaortic stenosis, clinical and pathological observations in an elderly patient, Amer. J. Cardiol. 22:126, 1968. Moreyra, E., Knibbe, P., and Brest, A.: Hypertension and muscular subaortic stenosis, Chest 57:87, 1970. Brockenbrough, E. C., Braunwald, E., and Morrow, A. G.: A hemodynamic technic for the detection of hypertrophic subaortic stenosis, Circulation 23:189, 1961. Whalen, R. E., Cohen, A. I., Sumner, R. G., et al.: Demonstration of the dynamic nature of idiopathic hypertrophic subaortic stenosis, Amer. J. Cardiol. 11:8, 1963. Harrison, D. C., Braunwald, E., Glick, G., et al.: Effects of beta adrenergic blockade on the circulation, with particular reference to observations in patients with hypertrophic subaortic stenosis, Circulation 29:84, 1964. Braunwald, E., Oldham, H. N., Jr., Ross, J., Jr., et al. : The circulatory response of patients with idiopathic hypertrophic subaortic stenosis to nitroglycerin and to the Valsalva maneuver, Circulation 29:422, 1964. Mason, D. T., Braunwald, E., and Ross, J., Jr.: Effects of changes in body position on the severity of obstruction to left ventricular outflow in idiopathic hypertrophic subaortic stenosis, Circulation 33:374, 1966. Krasnow, N., Rolett, E., Hood, W. B., Jr., et al.: Reversible obstruction of the ventricular outflow tract. Amer. T. Cardiol. 11:l. 1963. Wigle, E.‘D., Lenkei, S. C. M., Chrysohou, A., et al.: Muscular subaortic stenosis: The effect of peripheral vasodilatation, Canad. Med. Ass. J. 89:896, 1963. Marcus, F. I., Perloff, J. K., and De Leon, A. C.: The use of amyl nitrite in the hemodynamic assessment of aortic valvular and muscular subaortic stenosis, AMER. HEART J. 68:468, 1964. Hancock, E. W., and Fowkes, W. C.: Effects of amyl nitrite in aortic valvular and muscular subaortic stenosis, Circulation 33:383, 1966. Braunwald, E., Brockenbrough, E. C., and Frye, R. L.: Studies on digitalis. V. Comparison of the effects of ouabain on left ventricular
400
23.
24.
25.
26.
27.
Alday,
Wagner, and Wad
dynamics in valvular aortic stenosis and hypertrophic subaortic stenosis, Circulation 26:166. 1962. Braunwald, E., and Ebert, P. A.: Hemodynamic alterations in idiopathic hypertrophic subaortic stenosis induced by sympathomimetic drugs, Amer. J. Cardiol. 103489, i962. Nellen. M.. Gotsman. M. S.. and Schrire. V.: The influence of certain drugs and of prompt squatting on the systolic murmur in hypertrophic obstructive cardiomyopathy, AMER. HEART J. 76:295, 1968. Goodwin, J. F., Shah, P. M., Oakley, C. M., et al.: The clinical pharmacology of hypertrophic obstructive cardiomyopathy, in Wolstenholme. G. E. W.. and O’Connor. M.. editors: Cardiomyopathies, London, 1964,’ J. & A. Churchill, Ltd., p. 189. Wigle, E. D., David, P. R., Labrosse, C. J., et al.: The interrelation of wall tension, outflow tract “distending pressure” and orifice radius, Amer. J. Cardiol. 15:761, 1965. Wigle, E. D.: Cardiovascular drugs in muscular subaortic stenosis, Fed. Proc. 24:1279, 1965.
Am. Heart 3. March, 1972
28. Frank, S., and Braunwald, E.: Idiopathic hypertrophic subaortic stenosis: Clinical analysis of 126 patients with emphasis on the natural history, Circulation 37r7.59, 1968. 29. Cherian, G., Brokington, I. F., Shah, P. M., et al.: Beta adrenergic blockade in hypertrophic obstructive cardiomyopathy, Amer. J. Cardiol. 18:481, 1966. 30. Cohen, L. S., and Braunwald, E.: Amelioration of exercise-induced angina pectoris in idiopathic hypertrophic subaortic stenosis with betaadrenereic blockade. Circulation 35:847. 1967. 31. Bliss, H’. A., Moffat, J. E., and Gantt, ‘C. L.: Effects of chronic oral propranolol therapy in idiopathic hypertrophic subaortic stenosis, Circulation 35-36 (Suppl. 2):72, 1967. (Abst.) 32. Rosenblum, R., Frieden, J., Delman, A. J., et al.: Long-term propranolol therapy in patients with idiopathic hypertrophic subaortic stenosis, Circulation 35-36 (Suppl. 2):226, 1967. (Abst.) 33. Flamm, M. D., Harrison, D. C., and Hancock, E. W.: Muscular subaortic stenosis: Prevention of outflow obstruction with propranoloi, Circulation 38:846, 1968.
and muscular
Luis E. Alday, M.D. Henry R. Wagner, M.D. Peter Vlad, M.D. Bu$trlo, N. Y.
B
rock’s1 description of muscular subaortic stenosis considered systemic hypertension to be a possible etiologic factor of the disease, but coexistence is probably coincidental since subsequent surveys2-s failed to find a significant correlation. Hypertension in patients with muscular subaortic stenosis is infrequent and usually mild8-I0 but rarely severe.1*11~12 The case herein reported is an example of this unusual association. Case report D. M., a 1.5year-old girl, was born with a neurogenie bladder, bilateral hydronephrosis, hydrometer, and an imperforate anus. Several surgical procedures were performed during infancy and childhood (suprapubic cystostomy, cutaneous ureterostomy, total cystectomy, bilateral ureteroileostomy, and pyelotomy for renal calculi). A moderately loud, systolic murmur, maximal at the left lower sternal border and accompanied by a systolic thrill, was heard first when she was 3 years old; a clinical diagnosis of ventricular septal defect was made and repeatedly maintained. Chronic renal failure with hypertension developed at 13 years. Antihypertensive therapy (reserpine, Apresoline, methyldopa, guanethidine, and thiazides) elicited only intermittent response; blood pressure measurements varied between 130/95 and 180/120 mm. Hg. Chest x-ray and electrocardiogram (ECG) showed progressive hypertrophy of the left
ventricle. The systolic murmur became louder and an early diastolic murmur developed. The clinical diagnosis was changed to aortic valve disease when renal function deteriorated at the age of 14%. years. At this time, a kidney transplant was considered and cardiac catheterization was performed. The hemodynamic and cineangiographic findings were consistent with severe muscular subaortic stenosis (Table I and Fig. 1) and mild mitral and aortic regurgitation. The patient’s twenty-fifth hospital admission was made 6 weeks after cardiac catheterization, because of frequent, severe headaches. Although she was taking guanethidine, her blood pressure was 210/130 mm. Hg in the supine position and 170/115 mm. Hg while standing. Grade 2 fundoscopic changes were present. The apical impulse was in the anterior axillary line in the sixth intercostal space. A Grade 2/6 harsh systolic ejection murmur was present along the left sternal border. A Grade l/6 early diastolic murmur could also be heard in the aortic area. The second heart sound was normal in intensity. Heart rate was 84 beats per minute. Clinically, there was no evidence of heart failure. Laboratory data reflected severe renal impairment and anemia. The x-ray showed a cardiothoracic ratio of 60 per cent and normal pulmonary markings. The ECG, as shown in Fig. 2, was compatible with left atria1 enlargement and severe left ventricular hypertrophy. Prominent delta waves were evident. A striking feature of this examination was the decrease in intensity of the systolic murmur, which in previous examinations had been considered to be Grade 4/6. This decrease occurred when the patient’s blood pressure was uncontrolled with read-
Supported in part by Research Grant HE 09474.04 from the National Heart and Lung Institute, National Institutes of Health, Bethesda, Md. Work was done during Dr. Alday’s tenure of a cardiac fellowship from the National Heart Institute. Received for publication Sept. 21. 1970. Reprint requests to: Henry R. Wagner. M.D., Children’s Hospital, 219 Bryant St., Buffalo, N. Y. 14222.
Vol. 83, No. 3, fib. 395-400
March, 1972
American Heart Journal
395
396
Alday,
Wagner, and I/lad
Fig. 1. Pull-back pressure 80 mm. Hg at subvalvar
Table I. Hemodynamic
tracing level.
from
left ventricular
body
to ascending
aorta
showing
pressure
gradient
of
Jina%ngs* Pressures
(mm.
Hg)
Site Rest RA (mean) RV MPA PCW (mean) LV A0 PSG CO CI
4 2516 22113 14 150/16 86/60 64 6.9 L./min. 4.5 L./min./M.2
Isoproterend
PropranoEol
Iso~roierenol~
210/20 80/S 130
150/16 87/58 63
140/16 82/56 58
*Abbreviations: RA, right atrium; RV, right ventricle; MPA, main pulmonary artery; PCW. ventricle; AO, central aorta; PSG. peak systolic gradient; CO, cardiac output; CI. cardiac tAfter propranolol infusion.
ings of 210/130 mm. Hg. A phonocardiogram (Fig. 3) revealed marked increase in the intensity of the systolic murmur after amyl nitrite inhalation. A presystolic murmur appeared after the pharmacologic test. The second heart sound in the resting phonocardiogram was paradoxically split. A late systolic bulge which increased after inhalation of amyl nitrite was seen in the apexcardiogram. The carotid pulse tracing showed a bifid contour. The patient received methyldopa, propranolol (40 to 80 mg. daily), chlorothiazide, and calcium carbonate, but blood pressure fluctuated considerably, ranging from 170/11.5 mm. Hg in the supine position to 90/60 mm. Hg while standing. Dizziness and substernal discomfort were present when she was in the latter position. Changes in the intensity of the systolic murmur were noticed: the lower the blood pressure, the louder the murmur and vice versa. After 6 weeks of unsuccessful medical treatment congestive heart failure occurred. Blood pressure readings were 230/140 mm. Hg in the supine position and 220/140 mm. Hg while standing. Rena1 function deteriorated. Propranolol was discontinued. The congestive heart failure did not improve with therapy. A hemodialysis was performed 3 weeks
pulmonary index.
capillary
wedge;
later. The patient subsequently developed cardial effusion, 300 C.C. of bloody fluid moved from the pericardium. Shortly after patient had a cardiac arrest.
Autopsy
LV,
left
a periwere rethat the
findings
The principal findings from the autopsy were severe, chronic pyelonephritis due to obstructive uropathy, severe hypertrophy of the left ventricle producing narrowing of the outflow tract, and uremic pericardial effusion of 1,100 ml. Heart. The weight of the heart was 580 grams. The epicardium appeared cloudy and granular. The left ventricle (Fig. 4) was concentrically hypertrophied but the thickening of the myocardium was maximal at the upper muscular septum, which measured 25 mm. in diameter compared to 20 mm. at the left ventricular free wall. The diameter of the outflow tract measured 9 mm. in the autopsy specimen. The mus-
Volume Number
Fig.
83 3
2. The
Severe systemic hypertension
12-lead
ECG
showing
left ventricular
397
strain.
cular septum opposite to the anterior leaflet of the mitral valve was covered by a thickened, fibrous endocardium (Fig. 5). The left atrium was enlarged, its wall up to 4 mm. thick. Both mitral valve leaflets were thickened but no signs of endocarditis were present. The papillary muscles were extremely hypertrophied, the anterior one measuring 16 mm. in diameter. The aortic valve was normal, tricuspid; the aortic annulus diameter measured 19 mm. The coronary ostia were placed normally and the coronary arteries were patent and smooth. The ascending aorta was slightly dilated. Discussion Following detailed clinical, hemodynamic, angiocardiographic, and anatomic description of muscular subaortic stenosis,3-8 it was evident that the degree of obstruction of the left ventricular outflow tract could be altered, by a number of circumstances. Extrasystoles,13 exercise,‘*J5 the Valsalva maneuver,16 upright tilt,l’ bleeding,‘* administration of the nitrites,16Jg-21 digitalis glycosides,22 and isoproterenol,14J8*23 acting by different ways, augment the severity of the obstruction. Conversely, amelioration of the stenosis can be obtained with general anesthesia,g transfusion,18 changes in body position, i.e., head-down tilt” or squatting,z* and the administration of several pharmacologic agents as methox-
Fig. 3. Phonocardiogram (PCG) at lower left sternal border, apexcardiogram (A CC), and electrocardiogram (ECG). After inhalation of amyl nitrite the systolic murmur intensified and a presystolic murmur appeared. SI, first heart sound; AS, aortic closure; P2, pulmonic closure; SM, systolic murmur; PSM, presystolic murmur.
amine,23 neosynephrine,25 and angiotensin.26p27 Beta-adrenergic blocker agents prevent, or greatly reduce, the induced gradient across the obstruction, but they do not affect the resting gradient significantly.15 In an attempt to explain the variability of the stenosis in patients with muscular subaortic stenosis, Wigle and associates26 proposed that the severity of the obstruction was regulated by a number of inter-
39s
Alduy,
Am. Heart I. 1972 March,
Wagner, and L’lad
Fig. 5. Close-up view of the left ventricular outflow tract. M‘v, mitral valve; A V, aortic valve; AO, aorta; Llr, left ventricle.
Fig. 4. View aorta (AO).
of the opened
left
ventricle
(Lv)
and
related variables, namely, the distending pressure of the left ventricular outflow tract, the circumferential wall tension of this tract, and the volume of the left ventricle. The distending pressure of the left ventricular outflow tract, or pressure distal to the stenosis, is equal to the aortic pressure; the circumferential wall tension is the result of the tension developed by the contraction of the bulbospiral muscles of the left ventricular outflow tract. A decrease in the distending pressure, an increase in the contractility of the left ventricle, or a reduction of the left ventricular size, would be followed by worsening of the obstruction. A reduction of the gradient between the inflow and outflow tracts of the left ventricle would be provoked by increasing the distending pressure or the ventricular volume, or by decreasing the contractility of the muscle fibers of the left ventricular outflow tract. The administration of vasoconstricting agents, such as neosynephrine, methoxamine, and angiotensin, is followed by an increase of the systemic pressure or left ventricular afterload, thus augmenting the distending pressure of the outflow tract and reducing the obstruction.26s27 A hemody-
namic situation closely resembling this acute phenomenon is seen when sustained severe hypertension is associated with muscular subaortic stenosis. The difficulties encountered in treating these patients have recently been stressed by others.12 There is no question that muscular subaortic stenosis in our patient long preceded the development of hypertension. She was misdiagnosed as having a ventricular septal defect at the age of 3 years. Systemic hypertension was first recorded when she was 13 and subsequently a cardiac catheterization proved that she had muscular subaortic stenosis. Aortic insufficiency may be associated with muscular subaortic stenosisgs24s2* or with systemic hypertension due to a distended aortic valve ring.24 Changes in the physical findings, similar to those appearing after provocative maneuvers, were noticed during the patient’s last two admissions. Significant elevation of the patient’s blood pressure by augmenting the distending pressure of the left ventricular outflow tract was accompanied by marked attenuation of the systolic murmur. On the other hand, orthostatic hypotension resulted in a much louder systolic murmur, substernal discomfort, and dizziness. These signs and symptoms were also produced by inhalation of amyl nitrite. At this stage, it was very difficult to offer this patient any form of palliation. A kidney transplant had been
Volwne Nwmber
83 3
considered, but this possibility was discarded because of the severe cardiac disease. Open heart surgery could not be performed, in view of the renal failure. A combined treatment with antihypertensive drugs and propranolol was unsuccessful. Congestive heart failure developed, the renal function deteriorated, and the patient died. Contradictory long-term results with this form of therapy have been reported.2g-33 The cause of this patient’s death was a combination of renal failure and severe heart disease. It is likely, although it cannot be proved, that the antihypertensive therapy aggravated the muscular subaortic stenosis. It has been suggested that when this disease is associated with severe systemic hypertension, surgical relief of the outflow tract obstruction should be tried first.12 Summary The case of a 15year-old girl with severe systemic hypertension secondary to chronic pyelonephritis and muscular subaortic stenosis is reported. The severity of the obstruction of the left ventricular outflow tract varied according to the blood pressure levels. Uncontrolled hypertension attenuated the auscultatory signs indicative of stenosis. Augmentation of the obstruction, evidenced by intensification of the murmur, was present when antihypertensive drugs produced orthostatic hypotension. No adequate form of palliation could be offered to this patient because of the coexistence of end-stage renal failure and the severe cardiac disease which led to her death.
Severe systemic hypertension
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
REFERENCES 18. 1. Brock, R. C.: Functional obstruction of the left ventricle, Guy Hosp. Rep. 106:221, 1957. R. C.: Functional obstruction of the left 2. Brock. ventricle, Guy Hosp. Rep. 108:126, 1959. 3. Brachfeld, N., and Gorlin, R.: Subaortic stenosis: A revised concept of the disease, Medicine 38:415, 1959. 4. Goodwin, J. I., Hollman, A., Cleland, W. P., et al.: Obstructive cardiomyopathy simulating aortic stenosis. Brit. Heart 1. 22:403. 1960. .5 . Braunwald, E:, Morrow, A:G., Cornell, W. P., et al.: Idiopathic hypertrophic subaortic stenosis. Clinical, hemodynamic and angiographic manifestations, Amer. J. Med. 29:924, 1960. 6. Menges, H., Jr., Brandenburg, R. O., and Brown, A. L.: The clinical, hemodynamic and
19.
20.
21.
22.
399
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