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Dynamic left ventricular outflow tract obstruction and systolic anterior motion of the mitral valve in the absence of asymmetric septal hypertrophy
Dynamic Left Ventricular Outflow Tract Obstruction and Systolic Anterior Motion of the Mitral Valve in the Absence of Asymmetric Septal Hypertrophy
MICHAEL
H. CRAWFORD,
M.D.
BERTRON M. GROVES, M.D. LAWRENCE D. HORWITZ, M.D. San Antonio, Texas
From the Department of Medicine, Division of Cardiology, at The University of Texas Health Science Center, San Antonio, Texas. Requests for reprints should be addressed to Dr. Michael H. Crawford, Non-Invasive Cardiac Diagnostic Laboratories, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284. Manuscript accepted March 29, 1978.
Systolic anterior motion of the anterior mitral valve leaflet and asymmetric septal hypertrophy are the principal components of the dynamic subaortic stenosis in hypertrophic obstructive cardlomyopathy. Mitral valve systolic anterior motion without septal hypertrophy or lefl ventricular outflow tract obstruction has been described, but asymmetric septal hypertrophy is supposedly a consistent feature of dynamic subaortic stenosis. We describe two patients with syncope, chest pain and the typical systolic murmur of hypertrophic subaortic stenosis whose echocardiograms showed mitral valve systolic anterior motion but not asymmetric septal hypertrophy. Normal septal thickness on echo was confirmed by intravenous indocyanine green to identify the right septal endocardium. At catheterization, left ventricular outflow tract gradients were provoked, and neither patient had interventrlcular septal hypertrophy on biventricular cineangiography. These findings in two cases suggest that mitral valve systolic anterlor motion can be the only definable anatomic abnormality associated with symptomatic dynamic left ventricular outflow tract obstruction and that asymmetric septal hypertrophy is not a necessary component of this condition. Abnormal systolic anterior motion of the anterior leaflet of the mitral valve is usually a major component of the dynamic subaortic stenosis that characterizes hypertrophic obstructive cardiomyopathy [ 1,2]. It has been proposed that hypertrophy of the upper portion of the interventricular septum is the primary defect in this disorder and that mitral valve systolic anterior motion is a secondary consequence [3,4]. Patients with hypertrophic subaortic stenosis who do not have systolic anterior motion of the mitral valve have been described [ 1,251. It is also noteworthy that mitral systolic anterior motion alone without associated asymmetric septal hypertrophy or subaortic obstruction has been recorded in other situations [ 6- 121. We here describe two patients with typical symptoms and physical findings of hypertrophic obstructive cardiomyopathy who had systolic anterior motion of the mitral valve and subaortic stenosis on provocation, but who did not have demonstrable septal hypertrophy by contrast echocardiography or biventricular cineangiography. METHODS Echocardiograms were performed with a Picker ultrasonoscope model 80-C utilizing
a 2.25 mHz, 0.5 inch transducer
October 1978
focused at 7.5 cm and recorded on
The American Journal of Medicine
Volume 85
703
krfPERm0~~1c OI~~TRUOTIVE CARDIOMYOPATHY-CRAWF~RO ET AL.
an lrex recorder. the patients transducer
The echocardiograms
in the left lateral in the “standard
were obtained with
decubitus
position
with the
[ 131. Mitral valve
interspace”
motion was recorded near the tip of the anterior leaflet where the posterior leaflet and the left ventricle could be visualized simultaneously
[7]. The interventricular septum was recorded
at the level of the chordae tendineae.
Septal thickness was assessed in diastole prior to the P wave of the electrocardiogram measuring from the leading edge of the right septal endocardium to the leading edge of the left septal endocardium [14]. Right ventricular contrast echocardiography was performed by an antecubital vein injection of 10 mg (2 ml) of indocyanine green followed immediately with 8 ml of normal saline solution. The echocardiographic gain and reject controls were set to obtain a distinct cloud of echoes as a result of the injection to avoid spurious data from reverberations. Catheterization of the left ventricle was accomplished by the retrograde approach employing fluid-filled catheters. Care was taken to carefully position the catheter in the body of the left ventricle to avoid catheter entrapment. Brachial artery pressure was recorded by a Jelco 20 gauge, 1 l/2 inch catheter introduced percutaneously. Simultaneous biventri-
Case 1. Echocardiogram of the right and left ventricles. GD = cloud of echoes in the right ventricle produced by a peripheral venous indocyanine green injection. IVS = interventricular septum, whose diastolic thickness is 0.7 cm.
Figure 2. I
-.
I
.
I
I
--
cular cineangiography was performed in the left anterior oblique position utilizing a power injection of 40 ml of contrast material (Renograffin@ 76) into the left ventricle, and a forceful hand injection of 36 ml into the right ventricle. Positioning of the patient to view the intetventricular septum “on end” was accomplished by rotating the patient during small test injections of contrast material. Interventricular septal thickness was measured as the largest dimension in the upper half of the septum in mid-diastole. CASE REPORTS
Figure 1. Case 1. Mitral valve echogram. Arrow points to anterior leaflet systolic anterior motion. AL = anterior leaflet. ECG = electrocardiogram. PL = posterior leaflet.
704
October 1978
The American Journal of Medicine
Case 1. A 34 year old man with 10 years of progressive exertional weakness associated with diaphoresis and excessive tachycardia was evaluated because of a recent episode of dizziness and near syncope. No family member was known to have heart disease or sudden death. On physical examination the major finding was a systolic ejection murmur, loudest at the left sternal border, which increased during the Valsalva maneuver and decreased upon squatting. A fourth heart sound was present. The electrocardiogram and chest film were within normal limits. The echocardiogram showed systolic anterior motion of the mitral valve (Figure I), however, the interventricular septal thickness was within normal limits; proper identification of the right side of the septum was confirmed by indocyanine green injection (Figure 2). At cardiac catheterization left ventricular pressures at rest were
Volume 85
HYPERTROPHIC OBSTRUCTIVE
CARDIOMYOPATHY-CRAWFORD
ET AL.
aortic valve leaflets (Figure 5) and normal septal thickness. The absence of septal hypertrophy was confirmed by indocyanine green injection (Figure 6). At cardiac catheterization left ventricular pressure was normal at rest without an outflow tract gradient. No gradient appeared during the Valsalva maneuver or after amyl nitrite inhalation. However, in the beat following a ventricular premature contraction after amyl nitrite inhalation and with sinus tachycardia during an infusion of isoproterenol (2 pg/min intravenously), outflow tract peak systolic pressure gradients of 140 mm Hg appeared. During the isoproterenol infusion, when the heart rate reached 150 beats/min, the patient complained of dizziness and her typical chest pain. Biventricular cineangiography demonstrated normal septal thickness (Figure 7). Also, a left ventricular ejection fraction of 77 per cent was calculated from a right anterior oblique ventriculogram. The patient was discharged on propranolol therapy but has been lost to follow-up. COMMENTS
Case 1. Diastolic biventricular cineangiogram frame taken in the left anterior oblique position. The arrows point to the inter-ventricular septum which measures 0.7 cm. LV = left ventricular cavity. Figure
3.
within normal limits without an outflow tract gradient. Outflow tract systolic pressure gradients were recorded during the following maneuvers: Valsalva = 20 mm Hg, amyl nitrite inhalation = 50 mm Hg, isoproterenol infusion = 80 mm Hg. The postpremature beat response in the left ventricular and brachial arterial pressures was normal at rest and during the Valsalva maneuver. Biventricular cineangiography demonstrated normal thickness of the interventricular septum (Figure 3) and a left ventricular ejection fraction of 83 per cent. On coronary arteriography there was an anomalous origin of the left circumflex from the right coronary artery. The patient was treated with propranolol, 40 mg orally four times a day, and has improved symptomatically. The murmur is now absent and systolic anterior motion of the mitral valve is no longer demonstrable at rest by echocardiography. No first degree relatives are available for examination. A 2 1 year old woman known to have a heart murmur since two years of age had episodes of palpitation, dizziness and syncope for several years. In recent months she had experienced numerous episodes of dyspnea and crushing substernal chest pain that radiated to the neck and both arms. The pain was precipitated by exertion and emotional stress, was aggrevated by cold weather and was relieved within 5 minutes by rest. There was no family history of heart disease or sudden death. On physical examination there was a moderate pectus excavatum, a fourth heart sound and a systolic ejection murmur heard best at the lower left sternal border. The murmur increased during the Valsalva maneuver or upon standing and decreased during squatting. On the chest film there was a moderate pectus deformity, but the anteroposterior diameter of the chest was adequate and heart size was normal. An electrocardiogram was within normal limits. Echocardiography revealed systolic anterior motion of the mitral valve at rest (Figure 4), mid-systolic closure of the
In all previously reported cases of hypertrophic obstructive cardiomyopathy with documented dynamic left ventricular outflow tract obstruction, asymmetric septal hypertrophy has been present whether or not systolic anterior motion of the mitral valve was present. There have been reports of mitral valve systolic anterior motion without septal hypertrophy in a variety of conditions including mitral stenosis, cleft mitral valve, atrial septal defect and apparently normal persons [6-121. However, there was no evidence of outflow tract obstruction in these cases and in few have the patients had symptoms consistent with left ventricular obstruction.
Case 2.
Case 2. Mitral valve echogram. Arrow points to systolic anterior motion.
Figure 4.
1979
The American Journal of Medicine
Volume 65
705
HYPERTROPHIC OBSTRUCTIVE
CARDIOMYOPATHY-CRAWFORD
El
AL.
the anterior mitral valve leaflet echo does not return to a posterior position prior to the end of systole, which is the case with true systolic anterior motion. In our cases, care was taken to record the tip of the anterior leaflet from the “standard interspace.” Also, the mitral valve systolic anterior motion we observed was typical of that usually seen in hypertrophic obstructive cardiomyopathy in that it began immediately after the onset of systole, peaked in mid-systole and receded prior to the onset of diastole [3,6]. Accurate measurements of interventricular septal thickness depend upon identification of the right septal endocardium. This can be difficult because of its close association with the trabeculated free wall of the right ventricle anteriorly, the opposition of tricuspid chordae tendineae and poor near-field resolution with some echocardiographic transducers. We used indocyanine green dye injections [ 17,181 to confirm that we had accurately identified the right septal endocardium, but because of the potential pitfalls in echocardiographic estimates of septal thickness, we also confirmed that no septal hypertrophy was present in our two subjects by the performance of biventricular cineangiograms [19,20]. The mechanism of mitral valve systolic anterior motion is poorly understood. On the basis of cineangiographic and necropsy studies of patients with hypertrophic obstructive cardiomyopathy, Simon et al. [l] Case 2. Echocardiogram of the aortic root. Arrow indicates mid-systolic closing movement of an aortic leaf-
Figure 5.
let. The unique feature of our two symptomatic cases is the presence of dynamic outflow tract obstruction with systolic anterior motion of the mitral valve, but without septal hypertrophy. Considerable care must be taken to ensure that an echocardiographic diagnosis of mitral valve systolic anterior motion is not factitious due to technical error. Since the anterior leaflet of the mitral valve is attached to the mitral annulus, movement of the annulus may be accompanied by movement of the leaflet (5,6]. During systole, the mitral annulus usually moves anteriorly. If the echocardiographic transducer is positioned too low on the chest and directed superiorly, normal systolic movement of the entire mitral apparatus may be falsely assumed to be mitral valve systolic anterior motion. In addition, in certain states with a high left ventricular stroke output, i.e. aortic regurgitation, or in the presence of a large pericardial effusion, movement of the mitral annulus may be exaggerated resulting in false or “pseudo” systolic anterior motion of the mitral valve even when the recording is performed from the “standard interspace” [ 15,161. However, in these conditions
706
October 1978
The American Journal of Medicine
Case 2. Echocardiogram of the right and left ventricles during the injection of indocyanine green (GD). The interventricular septum (06) measures 0.8 cm in diastole.
Figure 6.
Volume 65
HYPERTROPHICOBSTRUCTIVE CARDIOMYQPATHY-CRAWFORD ET AL.
concluded that the hypertrophied septum causes malalignment of the papillary muscles which in turn permits anterior displacement of the anterior mitral valve leaflet during systole. Wigle et al. [21] have suggested that a Venturi effect may be operative in hypertrophic obstructive cardiomyopathy whereby the stream of blood being rapidly ejected through the left ventricular outflow tract draws the anterior mitral valve leaflet forward. Henry et al. [22] studied patients with hypertrophic obstructive cardiomyopathy with two dimensional echocardiography and noted frequent narrowing of the outflow tract with reduced septum to mitral valve distance at the onset of systole. It was suggested that this outflow tract change might enhance the venturi effect or other hydrodynamic forces which tend to cause systolic anterior motion of the mitral valve. Recently, Come and associates [ 121 described four patients with physical findings suggestive of hypertrophic obstructive cardiomyopathy in whom echocardiograms had mitral valve systolic anterior motion but in whom there was no evidence of asymmetric septal hypertrophy either in the echocardiograms (three patients), in scintiphotograms (three patients) or at autopsy (one patient). One patient had symptoms suggestive of left ventricular obstruction. This patient was the only one
in whom cardiac catheterization was performed, and no evidence of any outflow tract gradient at rest was identified. All four patients had left ventricular ejection fractions (three by gated blood pool imaging and one by catheterization) which were on the high side of normal (67 to 80 per cent). They suggested that this hyperkinetic left ventricular wall movement may create a Venturi effect which causes systolic anterior motion of the mitral valve. Also, they proposed that hypercontractile cardiac action may be the common denominator of a heterogeneous group of disorders which includes cases such as those they described and more typical hypertrophic obstructive cardiomyopathy with asymmetric septal enlargement. Bjork et al. [ 231 reported an abnormal anatomic insertion of the anterior mitral valve leaflet in two patients with hypertrophic subaortic stenosis. The leaflet was attached below the right sinus of Valsalva instead of in the usual position below the posterior sinus of Valsalva. Wigle [ 241 has observed a similar case. An abnormal rightward insertion could make the valve leaflet more susceptible to being pushed forward by the stream of blood as well as offering greater susceptibility to a Venturi effect. Which of these mechanisms are responsible for the mitral valve systolic anterior motion and dynamic outflow tract obstruction observed in our cases is speculative. One of our subjects had a reduced septum to mitral valve distance at the onset of systole (22 mm) of the type reported by Henry et al. [ 221, and both had left ventricular ejection fractions on the high side of normal. Whether or not the abnormal insertion of the mitral valve reported in some cases of classic hypertrophic obstructive cardiomyopathy may also occur in the absence of septal hypertrophy is unknown. The young age of our two patients raises the possibility that they represent an early phase of the more typical hypertrophic obstructive cardiomyopathy in which interventricular septal hypertrophy has not developed. Only further follow-up will determine whether features more like typical hypertrophic obstructive cardiomyopathy will develop or whether these patients will remain in a distinct variant condition. ACKNOWLEDGMENT We wish to thank Dr. Robert A. O’Rourke for his advice and enthusiastic support of these studies.
REFERENCES 1.
2.
3.
Simon AL, Ross J Jr, Gault JH: Angiographic anatomy of the ventricle and mitral valve in idiopathic hypertrophic subaortic stenosis. Circulation 36: 852, 1967. Henry WL, Clark GE, Glancy DL, et al.: Echocardiographic measurement of the left ventricular outflow gradient in idiopathic hypertrophic subaortic stenosis. N Engl J Med 288: 989, 1973. Shah PM, Gramiak R, Kramer DH: Ultrasound localization
4.
5.
October 1976
of left ventricular outflow obstruction in hypertrophic obstructive cardiomyopathy. Circulation 40: 3, 1969. Henry WL, Clark CE, Epstein SE: Asymmetric septal hypertrophy (ASH): the unifying link in the IHSS disease spectrum. Observations regarding its pathogenesis, pathophysiology, and course. Circulation 47: 827, 1973. King JF, DeMaria AN, Reis RL, et al.: Echocardiographic
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6.
7.
8.
9.
10. 11. 12.
13.
14.
15.
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CARDIOMYOPATHY-CRAWFORD
ET AL
assessment of idiopathic hypertrophic subaortic stenosis. Chest 64: 723, 1973. Popp RL, Harrison DC: Ultrasound in the diagnosis and evaluation of therapy of idiopathic hypertrophic subaortic stenosis. Circulation 40: 905, 1969. Shah PM, Gramiak R, Adelman AG, et al.: Role of echocardiography in diagnostic and hemodynamic assessment of hypertrophic subaortic stenosis. Circulation 44: 89 1, 1971. King JF. DeMaria AN, Miller RR, et al.: Markedly abnormal mitral valve motion without simultaneous intraventricular pressure gradient due to uneven mitral-septal contact in idiopathic hypertrophic subaortic stenosis. Am J Cardiol 34: 360, 1974. Rossen RM, Goodman DJ, lngham RE, et al.: Echocardiographic criteria in the diagnosis of idiopathic hypertrophic subaortic stenosis. Circulation 50: 747. 1974. Criley JM, Blaufuss AH, Abbasi AS: Nonobstructive IHSS (letter to editor). Circulation 52: 963, 1975. Feigenbaum H: Echocardiography. Philadelphia, Lea & Fe’ biger, 1976, p 137. Come CC, Bulkley BH, Goodman ZD, et al.: Hypercontractile cardiac states simulating hypertrophic cardiomyopathy. Circulation 55: 901, 1977. Popp RL, Filly K, Brown OR, et al.: Effect of transducer placement on echocardiographic measurement of left ventricular dimensions. Am J Cardiol 35: 537, 1975. Henry WL, Clark CE, Epstein SE: Asymmetric septal hypertrophy. Echocardiographic identification of the pathognomonic anatomic abnormality of IHSS. Circulation 47: 225, 1973. Pridie RB, Oakley CM: Mechanism of mitral regurgitation in
October 1979
The American Journal of Medlclne
16.
17.
18.
19.
20.
21.
22.
23.
24.
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hypertrophic obstructive cardiomyopathy. Br Heart J 32: 203, 1970. Nanda NC, Gramiak R, Gross CM: Echocardiography of cardiac valves in pericardial effusion. Circulation 54: 500, 1976. Gramiak R, Shah PM, Kramer DH: Ultrasound cardiography: Contrast studies in anatomy and function. Radiology 92: 939, 1969. Feigenbaum H, Stone JM, Lee DA, et al.: Identification of ultrasound echoes from the left ventricle by use of intracardiac injections of indocyanine green. Circulation 41: 615, 1970. Desilets DT, Kadell BM, Ruttenburg HD, et al.: Angiographic demonstration of the ventricular septum. A new technique. Radiology 91: 329, 1968. Redwood DR, Scherer JL, Epstein SE: Biventricular cineagnigraphy in the evaluation of patients with asymmetric septal hypertrophy. Circulation 49: 1116, 1974. Wigle ED, Adelman AG, Silver MD: Pathophysiological considerations in muscular subaortic stenosis. Hypertrophic Obstructive Cardiomyopathy (Wolstenholme GEW, O’Connor M, ed). London, Longman Group Ltd., 1971. Henry WL, Clark CE, Griffith JM, et al.: Mechanism of left ventricular outflow obstruction in patients with obstructive asymmetric septal hypertrophy (idiopathic hypertrophic subaortic stenosis). Am J Cardio135: 337, 1975. Bjork VO, Hultquist G, Lodin H: Subaortic stenosis produced by an abnormally placed anterior mitral leaflet. J Thorac Cardiovasc Surg 4 1: 659, 196 1. Wigle ED: Discussion comment. Cardiomyopathies (Wolstenholme GEW, O’Connor M, ed). Boston, Little, Brown & Company, 1965, p 19.
MICHAEL
H. CRAWFORD,
M.D.
BERTRON M. GROVES, M.D. LAWRENCE D. HORWITZ, M.D. San Antonio, Texas
From the Department of Medicine, Division of Cardiology, at The University of Texas Health Science Center, San Antonio, Texas. Requests for reprints should be addressed to Dr. Michael H. Crawford, Non-Invasive Cardiac Diagnostic Laboratories, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78284. Manuscript accepted March 29, 1978.
Systolic anterior motion of the anterior mitral valve leaflet and asymmetric septal hypertrophy are the principal components of the dynamic subaortic stenosis in hypertrophic obstructive cardlomyopathy. Mitral valve systolic anterior motion without septal hypertrophy or lefl ventricular outflow tract obstruction has been described, but asymmetric septal hypertrophy is supposedly a consistent feature of dynamic subaortic stenosis. We describe two patients with syncope, chest pain and the typical systolic murmur of hypertrophic subaortic stenosis whose echocardiograms showed mitral valve systolic anterior motion but not asymmetric septal hypertrophy. Normal septal thickness on echo was confirmed by intravenous indocyanine green to identify the right septal endocardium. At catheterization, left ventricular outflow tract gradients were provoked, and neither patient had interventrlcular septal hypertrophy on biventricular cineangiography. These findings in two cases suggest that mitral valve systolic anterlor motion can be the only definable anatomic abnormality associated with symptomatic dynamic left ventricular outflow tract obstruction and that asymmetric septal hypertrophy is not a necessary component of this condition. Abnormal systolic anterior motion of the anterior leaflet of the mitral valve is usually a major component of the dynamic subaortic stenosis that characterizes hypertrophic obstructive cardiomyopathy [ 1,2]. It has been proposed that hypertrophy of the upper portion of the interventricular septum is the primary defect in this disorder and that mitral valve systolic anterior motion is a secondary consequence [3,4]. Patients with hypertrophic subaortic stenosis who do not have systolic anterior motion of the mitral valve have been described [ 1,251. It is also noteworthy that mitral systolic anterior motion alone without associated asymmetric septal hypertrophy or subaortic obstruction has been recorded in other situations [ 6- 121. We here describe two patients with typical symptoms and physical findings of hypertrophic obstructive cardiomyopathy who had systolic anterior motion of the mitral valve and subaortic stenosis on provocation, but who did not have demonstrable septal hypertrophy by contrast echocardiography or biventricular cineangiography. METHODS Echocardiograms were performed with a Picker ultrasonoscope model 80-C utilizing
a 2.25 mHz, 0.5 inch transducer
October 1978
focused at 7.5 cm and recorded on
The American Journal of Medicine
Volume 85
703
krfPERm0~~1c OI~~TRUOTIVE CARDIOMYOPATHY-CRAWF~RO ET AL.
an lrex recorder. the patients transducer
The echocardiograms
in the left lateral in the “standard
were obtained with
decubitus
position
with the
[ 131. Mitral valve
interspace”
motion was recorded near the tip of the anterior leaflet where the posterior leaflet and the left ventricle could be visualized simultaneously
[7]. The interventricular septum was recorded
at the level of the chordae tendineae.
Septal thickness was assessed in diastole prior to the P wave of the electrocardiogram measuring from the leading edge of the right septal endocardium to the leading edge of the left septal endocardium [14]. Right ventricular contrast echocardiography was performed by an antecubital vein injection of 10 mg (2 ml) of indocyanine green followed immediately with 8 ml of normal saline solution. The echocardiographic gain and reject controls were set to obtain a distinct cloud of echoes as a result of the injection to avoid spurious data from reverberations. Catheterization of the left ventricle was accomplished by the retrograde approach employing fluid-filled catheters. Care was taken to carefully position the catheter in the body of the left ventricle to avoid catheter entrapment. Brachial artery pressure was recorded by a Jelco 20 gauge, 1 l/2 inch catheter introduced percutaneously. Simultaneous biventri-
Case 1. Echocardiogram of the right and left ventricles. GD = cloud of echoes in the right ventricle produced by a peripheral venous indocyanine green injection. IVS = interventricular septum, whose diastolic thickness is 0.7 cm.
Figure 2. I
-.
I
.
I
I
--
cular cineangiography was performed in the left anterior oblique position utilizing a power injection of 40 ml of contrast material (Renograffin@ 76) into the left ventricle, and a forceful hand injection of 36 ml into the right ventricle. Positioning of the patient to view the intetventricular septum “on end” was accomplished by rotating the patient during small test injections of contrast material. Interventricular septal thickness was measured as the largest dimension in the upper half of the septum in mid-diastole. CASE REPORTS
Figure 1. Case 1. Mitral valve echogram. Arrow points to anterior leaflet systolic anterior motion. AL = anterior leaflet. ECG = electrocardiogram. PL = posterior leaflet.
704
October 1978
The American Journal of Medicine
Case 1. A 34 year old man with 10 years of progressive exertional weakness associated with diaphoresis and excessive tachycardia was evaluated because of a recent episode of dizziness and near syncope. No family member was known to have heart disease or sudden death. On physical examination the major finding was a systolic ejection murmur, loudest at the left sternal border, which increased during the Valsalva maneuver and decreased upon squatting. A fourth heart sound was present. The electrocardiogram and chest film were within normal limits. The echocardiogram showed systolic anterior motion of the mitral valve (Figure I), however, the interventricular septal thickness was within normal limits; proper identification of the right side of the septum was confirmed by indocyanine green injection (Figure 2). At cardiac catheterization left ventricular pressures at rest were
Volume 85
HYPERTROPHIC OBSTRUCTIVE
CARDIOMYOPATHY-CRAWFORD
ET AL.
aortic valve leaflets (Figure 5) and normal septal thickness. The absence of septal hypertrophy was confirmed by indocyanine green injection (Figure 6). At cardiac catheterization left ventricular pressure was normal at rest without an outflow tract gradient. No gradient appeared during the Valsalva maneuver or after amyl nitrite inhalation. However, in the beat following a ventricular premature contraction after amyl nitrite inhalation and with sinus tachycardia during an infusion of isoproterenol (2 pg/min intravenously), outflow tract peak systolic pressure gradients of 140 mm Hg appeared. During the isoproterenol infusion, when the heart rate reached 150 beats/min, the patient complained of dizziness and her typical chest pain. Biventricular cineangiography demonstrated normal septal thickness (Figure 7). Also, a left ventricular ejection fraction of 77 per cent was calculated from a right anterior oblique ventriculogram. The patient was discharged on propranolol therapy but has been lost to follow-up. COMMENTS
Case 1. Diastolic biventricular cineangiogram frame taken in the left anterior oblique position. The arrows point to the inter-ventricular septum which measures 0.7 cm. LV = left ventricular cavity. Figure
3.
within normal limits without an outflow tract gradient. Outflow tract systolic pressure gradients were recorded during the following maneuvers: Valsalva = 20 mm Hg, amyl nitrite inhalation = 50 mm Hg, isoproterenol infusion = 80 mm Hg. The postpremature beat response in the left ventricular and brachial arterial pressures was normal at rest and during the Valsalva maneuver. Biventricular cineangiography demonstrated normal thickness of the interventricular septum (Figure 3) and a left ventricular ejection fraction of 83 per cent. On coronary arteriography there was an anomalous origin of the left circumflex from the right coronary artery. The patient was treated with propranolol, 40 mg orally four times a day, and has improved symptomatically. The murmur is now absent and systolic anterior motion of the mitral valve is no longer demonstrable at rest by echocardiography. No first degree relatives are available for examination. A 2 1 year old woman known to have a heart murmur since two years of age had episodes of palpitation, dizziness and syncope for several years. In recent months she had experienced numerous episodes of dyspnea and crushing substernal chest pain that radiated to the neck and both arms. The pain was precipitated by exertion and emotional stress, was aggrevated by cold weather and was relieved within 5 minutes by rest. There was no family history of heart disease or sudden death. On physical examination there was a moderate pectus excavatum, a fourth heart sound and a systolic ejection murmur heard best at the lower left sternal border. The murmur increased during the Valsalva maneuver or upon standing and decreased during squatting. On the chest film there was a moderate pectus deformity, but the anteroposterior diameter of the chest was adequate and heart size was normal. An electrocardiogram was within normal limits. Echocardiography revealed systolic anterior motion of the mitral valve at rest (Figure 4), mid-systolic closure of the
In all previously reported cases of hypertrophic obstructive cardiomyopathy with documented dynamic left ventricular outflow tract obstruction, asymmetric septal hypertrophy has been present whether or not systolic anterior motion of the mitral valve was present. There have been reports of mitral valve systolic anterior motion without septal hypertrophy in a variety of conditions including mitral stenosis, cleft mitral valve, atrial septal defect and apparently normal persons [6-121. However, there was no evidence of outflow tract obstruction in these cases and in few have the patients had symptoms consistent with left ventricular obstruction.
Case 2.
Case 2. Mitral valve echogram. Arrow points to systolic anterior motion.
Figure 4.
1979
The American Journal of Medicine
Volume 65
705
HYPERTROPHIC OBSTRUCTIVE
CARDIOMYOPATHY-CRAWFORD
El
AL.
the anterior mitral valve leaflet echo does not return to a posterior position prior to the end of systole, which is the case with true systolic anterior motion. In our cases, care was taken to record the tip of the anterior leaflet from the “standard interspace.” Also, the mitral valve systolic anterior motion we observed was typical of that usually seen in hypertrophic obstructive cardiomyopathy in that it began immediately after the onset of systole, peaked in mid-systole and receded prior to the onset of diastole [3,6]. Accurate measurements of interventricular septal thickness depend upon identification of the right septal endocardium. This can be difficult because of its close association with the trabeculated free wall of the right ventricle anteriorly, the opposition of tricuspid chordae tendineae and poor near-field resolution with some echocardiographic transducers. We used indocyanine green dye injections [ 17,181 to confirm that we had accurately identified the right septal endocardium, but because of the potential pitfalls in echocardiographic estimates of septal thickness, we also confirmed that no septal hypertrophy was present in our two subjects by the performance of biventricular cineangiograms [19,20]. The mechanism of mitral valve systolic anterior motion is poorly understood. On the basis of cineangiographic and necropsy studies of patients with hypertrophic obstructive cardiomyopathy, Simon et al. [l] Case 2. Echocardiogram of the aortic root. Arrow indicates mid-systolic closing movement of an aortic leaf-
Figure 5.
let. The unique feature of our two symptomatic cases is the presence of dynamic outflow tract obstruction with systolic anterior motion of the mitral valve, but without septal hypertrophy. Considerable care must be taken to ensure that an echocardiographic diagnosis of mitral valve systolic anterior motion is not factitious due to technical error. Since the anterior leaflet of the mitral valve is attached to the mitral annulus, movement of the annulus may be accompanied by movement of the leaflet (5,6]. During systole, the mitral annulus usually moves anteriorly. If the echocardiographic transducer is positioned too low on the chest and directed superiorly, normal systolic movement of the entire mitral apparatus may be falsely assumed to be mitral valve systolic anterior motion. In addition, in certain states with a high left ventricular stroke output, i.e. aortic regurgitation, or in the presence of a large pericardial effusion, movement of the mitral annulus may be exaggerated resulting in false or “pseudo” systolic anterior motion of the mitral valve even when the recording is performed from the “standard interspace” [ 15,161. However, in these conditions
706
October 1978
The American Journal of Medicine
Case 2. Echocardiogram of the right and left ventricles during the injection of indocyanine green (GD). The interventricular septum (06) measures 0.8 cm in diastole.
Figure 6.
Volume 65
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concluded that the hypertrophied septum causes malalignment of the papillary muscles which in turn permits anterior displacement of the anterior mitral valve leaflet during systole. Wigle et al. [21] have suggested that a Venturi effect may be operative in hypertrophic obstructive cardiomyopathy whereby the stream of blood being rapidly ejected through the left ventricular outflow tract draws the anterior mitral valve leaflet forward. Henry et al. [22] studied patients with hypertrophic obstructive cardiomyopathy with two dimensional echocardiography and noted frequent narrowing of the outflow tract with reduced septum to mitral valve distance at the onset of systole. It was suggested that this outflow tract change might enhance the venturi effect or other hydrodynamic forces which tend to cause systolic anterior motion of the mitral valve. Recently, Come and associates [ 121 described four patients with physical findings suggestive of hypertrophic obstructive cardiomyopathy in whom echocardiograms had mitral valve systolic anterior motion but in whom there was no evidence of asymmetric septal hypertrophy either in the echocardiograms (three patients), in scintiphotograms (three patients) or at autopsy (one patient). One patient had symptoms suggestive of left ventricular obstruction. This patient was the only one
in whom cardiac catheterization was performed, and no evidence of any outflow tract gradient at rest was identified. All four patients had left ventricular ejection fractions (three by gated blood pool imaging and one by catheterization) which were on the high side of normal (67 to 80 per cent). They suggested that this hyperkinetic left ventricular wall movement may create a Venturi effect which causes systolic anterior motion of the mitral valve. Also, they proposed that hypercontractile cardiac action may be the common denominator of a heterogeneous group of disorders which includes cases such as those they described and more typical hypertrophic obstructive cardiomyopathy with asymmetric septal enlargement. Bjork et al. [ 231 reported an abnormal anatomic insertion of the anterior mitral valve leaflet in two patients with hypertrophic subaortic stenosis. The leaflet was attached below the right sinus of Valsalva instead of in the usual position below the posterior sinus of Valsalva. Wigle [ 241 has observed a similar case. An abnormal rightward insertion could make the valve leaflet more susceptible to being pushed forward by the stream of blood as well as offering greater susceptibility to a Venturi effect. Which of these mechanisms are responsible for the mitral valve systolic anterior motion and dynamic outflow tract obstruction observed in our cases is speculative. One of our subjects had a reduced septum to mitral valve distance at the onset of systole (22 mm) of the type reported by Henry et al. [ 221, and both had left ventricular ejection fractions on the high side of normal. Whether or not the abnormal insertion of the mitral valve reported in some cases of classic hypertrophic obstructive cardiomyopathy may also occur in the absence of septal hypertrophy is unknown. The young age of our two patients raises the possibility that they represent an early phase of the more typical hypertrophic obstructive cardiomyopathy in which interventricular septal hypertrophy has not developed. Only further follow-up will determine whether features more like typical hypertrophic obstructive cardiomyopathy will develop or whether these patients will remain in a distinct variant condition. ACKNOWLEDGMENT We wish to thank Dr. Robert A. O’Rourke for his advice and enthusiastic support of these studies.
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