MARCH
The American
Journal
1975
of CARDIOLOGY VOLUME NUMBER
CLINICAL
of Left Ventricular
Patients with Obstructive (Idiopathic Hypertrophic
L.
CHESTER JAMES
HENRY,
E. M.
35 3
STUDIES
Mechanism
WALTER
@
CLARK,
MD MD
GRIFFITH
STEPHEN
E.
EPSTEIN,
Bethesda,
Maryland
MD,
FACC
From the Cardiology Branch, National Heart and Lung Institute, and Electrical and Electronic Engineering Section, Biomedical Engineering and Instrumentation Branch, Division of Research Services, National Institutes of Health, Bethesda, Md. Manuscript accepted August 28, 1974. Address for reprints: Walter L. Henry, MD, Cardiology Branch, National Heart and Lung Institute,National Institutes of Health, Building IO, Room 78-15. Bethesda, Md. 20014.
Outflow Obstruction
Asymmetric Subaortic
in
Septal Hypertrophy
Stenosis)
Left ventricular outflow obstruction in patients with idiopathic hypertrophic subaortic stenosis or obstructive asymmetric septal hypertrophy is due to abnormal forward motion during systole of the anterior mitral leaflet. To determine why some patients with this disease have left ventricular outflow obstruction whereas others do not, we studied a large number of patients with asymmetric septal hypertrophy using both one- and two-dimensional echocardiography. In 100 patients with asymmetric septal hypertrophy and 22 normal subjects, mitral valve position at the onset of systole was quantitated by measuring the distance from the ventricular septum to the mitral valve and the distance from the mitral valve to the posterior left ventricular wall. None of the normal subjects and only 3 (6 percent) of 51 patients with nonobstructive asymmetric septal hypertrophy had a septal-mitral valve distance of less than 20 mm compared with 23 (66 percent) of 36 patients with obstructive asymmetric septal hypertrophy. Moreover,, the mitral valve at the onset of systole was actually positioned forward in the left ventricular cavity. Two-dimensional studies in 11 patients with obstructive asymmetric septal hypertrophy revealed that contraction of the malaligned papillary muscles did not cause the abnormal forward mitral valve motion. We propose that the left ventricular outflow obstruction in patients with obstructive asymmetric septal hypertrophy occurs as a result of two factors: (1) narrowing of the left ventricular outflow tract at the onset of systole, and (2) hydrodynamic forces generated by contraction on the left ventricle.
Angiographic and echocardiographic observations in the mid- to late 1960’s suggested that left ventricular outflow obstruction in patients with idiopathic hypertrophic subaortic stenosis1 was due to systolic apposition of the anterior mitral leaflet and the asymmetrically hypertrophied ventricular septum. 2~aDefinitive evidence substantiating this concept was obtained recently by the demonstration of a highly significant correlation between an echocardiographically measured obstruction index (computed from the duration and degree of systolic narrowing of the left ventricular outflow tract between the anterior
March 1975
The American Journal of CARDIOLOGY
Volume 35
337
OBSTRUCTIVE
ASYMMETRIC
SEPTAL HYPERTROPHY-HENRY
ET AL.
mitral leaflet and ventricular septum) and the simultaneously determined outflow gradient measured at cardiac catheterizati0n.m However, it has also become apparent recently that patients with classic idiopathic hypertrophic subaortic stenosis represent only one part of a spectrum of disease that has asymmetric septal hypertrophy as its characteristic feature11-14; most patients with asymmetric septal hypertrophy either do not have left ventricular outflow obstruction or have it only after provocative maneuvers.rl-lg To determine why only some patients have
such obstruction, we studied a large number of patients with asymmetric septal hypertrophy using oneand two-dimensional echocardiography. The results of this investigation, when eombined with previous observations from our laboratory, suggest that outflow obstruction in this disease is a result of hydrodynamic forces and is not, as some have suggested, due to contraction during systole of malaligned papillary muscles. Methods One-Dimensional
Echocardiographic
Studies
Equipment: One-dimensional echocardiograms were ob-
tained with an ultrasonic transducer (Aerotech, 2.25 megahertz, 1.25 cm diameter), an Ekoline 20A ultrasonic receiver and a Honeywell 1856 line scan recorder. The Ekoline receiver and Honeywell recorder were interfaced by way of a custom-built video processor. Signals were recorded on light-sensitive paper. Patient population: One hundred adult patients with asymmetric septal hypertrophy were studied by one-dimensional echocardiography. In every case, the condition was documented echocardiographically and characterized by a ventricular septum at least 1.3 times the thickness of the posterobasal left ventricular free wall. a. Patients with cardiac catheterization studies (classification): Cardiac catheterization data were available in 67 of the 100 patients. In all 67 patients the left ventricular outflow gradient was recorded first when the patient was supine and in a basal condition and then during or after several provocative maneuvers (for example, a premature ventricular contraction, a Valsalva maneuver or infusion of isoproterenol). With use of these data, patients were classified into the following three groups on the basis of the left ventricular outflow pressure gradient: (1) obstructive group (gradient at rest, provocable gradient well in excess of 50 mm Hg); (2) provocable group (no resting gradient, provocable gradient greater than 30 mm Hg and in most instances exceeding 50 mm Hg); and (3) nonobstructiue group (no resting gradient, peak provocable gradient less than 30 mm Hg). Of the 67 patients, 35 were classified in the obstructive, 10 in the provocable and 22 in the nonobstructive group (as determined by cardiac catheterization data alone). The degree of obstruction was estimated echocardiographically lo and compared with catheterization data in each of these 67 patients (nonsimultaneous studies). Thirty-two of 35 patients with resting outflow obstruction had an echocardiographic obstruction index indicating outflow obstruction compared with only 1 of 22 patients with nonobstructive disease and 0 of 10 patients with provocable disease. Thus, in 63 of 67 patients, the echocardiographic
338
March 1975
The American Journal of CARDIOLOGY
and catheterization data were consistent. The four exceptions were patients who had undergone catheterization studies before 1964. In all four cases, physical findings had changed between 1964 and the present and were now compatible with the echocardiographic data.20 As a result, three patients initially classified as having obstructive disease by catheterization data alone were reclassified as having nonobstructive disease; one patient initially classified in the nonobstructive group was reclassified in the obstructive group. Thus, as finally grouped, 33 patients were considered to have obstructive, 10 provocable and 24 nonobstructive disease. Some patients with right ventricular hypertension may have disproportionate septal thickening.lsJl Such patients usually are easily identified on clinical grounds and should not be included in the spectrum of asymmetric septal hypertrophy. In this study, 23 of the 24 patients with catheterization studies and nonobstructive asymmetric septal hypertrophy had a right ventricular systolic pressure of less than 35 mm Hg. Asymmetric septal hypertrophy in these patients therefore cannot be ascribed to right ventricular hypertension. b. Patients with catheterization studies (systolic mitral value motion): As would be expected, all 33 patients with an obstruction index indicating a resting left ventricular gradient had marked systolic anterior motion of the mitral valve leaflets. Ten other patients also had abnormal systolic anterior motion, but this motion was much less prominent than in the patients in the obstructive group and was not sufficient to give an obstruction index compatible with a resting gradient. None of these 10 patients had a resting gradient at cardiac catheterization, but 8 of 10 (80 percent) did have a gradient exceeding 30 mm Hg with provocative maneuvers. Twenty-four patients had no evidence of abnormal systolic motion of the mitral leaflets. In only 2 of the 24 (8 percent) could a gradient greater than 30 mm Hg be provoked at catheterization. Thus, those patients with asymmetric septal hypertrophy who have an obstruction index indicating no resting gradient but an abnormal systolic anterior motion of the mitral leaflets are likely to have a significant gradient provoked at catheterization, whereas those with no abnormal systolic motion are unlikely to have significant provocable gradients. c. Patients without catheterization studies (classification): In the 33 patients with asymmetric septal hypertrophy without catheterization data, classification was based on echocardiographic data alone. Of the total of 100 patients (including those with and without catheterization studies), 51 were in the nonobstructive group, 14 in the provocable group and 35 in the obstructive group. Mitral valve position: The, position of the mitral valve in the ventricular cavity at the onset of systole was assessed in every patient. Mitral valve position was measured with the ultrasonic beam reflected from the tip of the mitral valve. Proper beam orientation was obtained by first visualizing both the anterior and posterior mitral valve leaflets simultaneously and then scanning perpendicular to the left ventricular outflow tract (that is, across the tip of the valve) until the maximal systolic motion of the anterior mitral leaflet was seen. Mitral valve position was quantitated by measuring the distance from the mitral valve (defined as the point of apposition of the anterior and posterior mitral leaflets at the onset of systole) to (1) the ventricular septum, and (2) the left ventricular free wall (Fig. 1). A mitral valve position ratio was computed by dividing the septalmitral valve distance into the mitral valve-posterior wall
Volume 35
OBSTRUCTIVE
NORMAL
ASYMMETRIC
SEPTAL HYPERTROPHY-HENRY
OEISTRUCTIVE
AS Ii
ET AL.
(IHSS)
FIGURE 1. Unretouched echocardiograms from a normal subject (left) and a patient with obstructive asymmetric septal hypertrophy (ASH) (right). Compared with findings in the normal subject, septal-mitral valve distance (S-MV) is decreased in obstructive asymmetric septal hypertrophy whereas mitral valve-posterior wall distance (MV-PW) is increased, indicating that the mitral valve, at the onset of systole, is positioned forward in the left ventricular cavity. IHSS = idiopathic hypertrophic subaortic stenosis.
distance. In many patients, multiple echoes were recorded from the mitral valve during systole (Fig. 1). When this occurred, mitral valve position was defined from the point midway between the anterior and posterior mitral valve echoes at onset of systole. Two-Dimensional
Echocardiographic
Studies
Equipment: Two-dimensional echocardiographic studies were obtained in real time using a custom-built mechanical sector-scanner consisting of a standard ultrasonic transducer (2.25 megahertz, 1.25 cm diameter, Aerotech transducer), an angle indicator and a small motor. The details of this system have been described previously. The transducer directs the ultrasonic beam into the chest and is angled rapidly through either a 30’ or 45’ arc at a rate of 15 cycles/sec. Each complete cycle results in the generation of two separate sectors (that is, one sector is produced as the transducer moves from left to right and another as it moves from right to left). Thus, 30 separate frames (or sectors) are produced per second, each one containing 100 individual ultrasonic data lines. The ultrasonic signals obtained by the scanner are electronically processed by an ultrasonic receiver (Ekoline 2OA) and specially designed electronic circuits and displayed on a cathode ray tube. The two-dimensional images are recorded permanently with a closedcircuit television system. In this system, a television camera is focused on the cathode ray tube and the camera output recorded by a videotape unit. The videotapes obtained in this manner are used for subsequent analysis. Patient selection: Eleven patients with obstructive asymmetric septal hypertrophy were studied by two-dimensional echocardiography. In every case, the condition had been demonstrated previously by one-dimensional echocardiography, and the degree of obstruction had been
determined by both cardiac catheterization and one-dimensional echocardiography. Study procedure: In each study, the sector scanner was oriented in two ways: (1) parallel to the left ventricular long axis, and (2) perpendicular to the left ventricular long axis. With both parallel and perpendicular orientation, particular care was used so that the papillary muscles, mitral valve, left ventricular outflow tract and ventricular septum were visualized.
Results One-Dimensional
Echocardiography
The mean septal-mitral valve distance was 34.6 mm in normal subjects, 19.6 mm in those with obstructive asymmetric septal hypertrophy, 22.0 mm in those with provocable and 27.4 mm in those with nonobstructive asymmetric septal hypertrophy (Fig. 2). The mean distances in the patients with asymmetric septal hypertrophy were significantly less than the distance in normal subjects (P
The American
Journal
1975
of CARDIOLOGY VOLUME NUMBER
CLINICAL
of Left Ventricular
Patients with Obstructive (Idiopathic Hypertrophic
L.
CHESTER JAMES
HENRY,
E. M.
35 3
STUDIES
Mechanism
WALTER
@
CLARK,
MD MD
GRIFFITH
STEPHEN
E.
EPSTEIN,
Bethesda,
Maryland
MD,
FACC
From the Cardiology Branch, National Heart and Lung Institute, and Electrical and Electronic Engineering Section, Biomedical Engineering and Instrumentation Branch, Division of Research Services, National Institutes of Health, Bethesda, Md. Manuscript accepted August 28, 1974. Address for reprints: Walter L. Henry, MD, Cardiology Branch, National Heart and Lung Institute,National Institutes of Health, Building IO, Room 78-15. Bethesda, Md. 20014.
Outflow Obstruction
Asymmetric Subaortic
in
Septal Hypertrophy
Stenosis)
Left ventricular outflow obstruction in patients with idiopathic hypertrophic subaortic stenosis or obstructive asymmetric septal hypertrophy is due to abnormal forward motion during systole of the anterior mitral leaflet. To determine why some patients with this disease have left ventricular outflow obstruction whereas others do not, we studied a large number of patients with asymmetric septal hypertrophy using both one- and two-dimensional echocardiography. In 100 patients with asymmetric septal hypertrophy and 22 normal subjects, mitral valve position at the onset of systole was quantitated by measuring the distance from the ventricular septum to the mitral valve and the distance from the mitral valve to the posterior left ventricular wall. None of the normal subjects and only 3 (6 percent) of 51 patients with nonobstructive asymmetric septal hypertrophy had a septal-mitral valve distance of less than 20 mm compared with 23 (66 percent) of 36 patients with obstructive asymmetric septal hypertrophy. Moreover,, the mitral valve at the onset of systole was actually positioned forward in the left ventricular cavity. Two-dimensional studies in 11 patients with obstructive asymmetric septal hypertrophy revealed that contraction of the malaligned papillary muscles did not cause the abnormal forward mitral valve motion. We propose that the left ventricular outflow obstruction in patients with obstructive asymmetric septal hypertrophy occurs as a result of two factors: (1) narrowing of the left ventricular outflow tract at the onset of systole, and (2) hydrodynamic forces generated by contraction on the left ventricle.
Angiographic and echocardiographic observations in the mid- to late 1960’s suggested that left ventricular outflow obstruction in patients with idiopathic hypertrophic subaortic stenosis1 was due to systolic apposition of the anterior mitral leaflet and the asymmetrically hypertrophied ventricular septum. 2~aDefinitive evidence substantiating this concept was obtained recently by the demonstration of a highly significant correlation between an echocardiographically measured obstruction index (computed from the duration and degree of systolic narrowing of the left ventricular outflow tract between the anterior
March 1975
The American Journal of CARDIOLOGY
Volume 35
337
OBSTRUCTIVE
ASYMMETRIC
SEPTAL HYPERTROPHY-HENRY
ET AL.
mitral leaflet and ventricular septum) and the simultaneously determined outflow gradient measured at cardiac catheterizati0n.m However, it has also become apparent recently that patients with classic idiopathic hypertrophic subaortic stenosis represent only one part of a spectrum of disease that has asymmetric septal hypertrophy as its characteristic feature11-14; most patients with asymmetric septal hypertrophy either do not have left ventricular outflow obstruction or have it only after provocative maneuvers.rl-lg To determine why only some patients have
such obstruction, we studied a large number of patients with asymmetric septal hypertrophy using oneand two-dimensional echocardiography. The results of this investigation, when eombined with previous observations from our laboratory, suggest that outflow obstruction in this disease is a result of hydrodynamic forces and is not, as some have suggested, due to contraction during systole of malaligned papillary muscles. Methods One-Dimensional
Echocardiographic
Studies
Equipment: One-dimensional echocardiograms were ob-
tained with an ultrasonic transducer (Aerotech, 2.25 megahertz, 1.25 cm diameter), an Ekoline 20A ultrasonic receiver and a Honeywell 1856 line scan recorder. The Ekoline receiver and Honeywell recorder were interfaced by way of a custom-built video processor. Signals were recorded on light-sensitive paper. Patient population: One hundred adult patients with asymmetric septal hypertrophy were studied by one-dimensional echocardiography. In every case, the condition was documented echocardiographically and characterized by a ventricular septum at least 1.3 times the thickness of the posterobasal left ventricular free wall. a. Patients with cardiac catheterization studies (classification): Cardiac catheterization data were available in 67 of the 100 patients. In all 67 patients the left ventricular outflow gradient was recorded first when the patient was supine and in a basal condition and then during or after several provocative maneuvers (for example, a premature ventricular contraction, a Valsalva maneuver or infusion of isoproterenol). With use of these data, patients were classified into the following three groups on the basis of the left ventricular outflow pressure gradient: (1) obstructive group (gradient at rest, provocable gradient well in excess of 50 mm Hg); (2) provocable group (no resting gradient, provocable gradient greater than 30 mm Hg and in most instances exceeding 50 mm Hg); and (3) nonobstructiue group (no resting gradient, peak provocable gradient less than 30 mm Hg). Of the 67 patients, 35 were classified in the obstructive, 10 in the provocable and 22 in the nonobstructive group (as determined by cardiac catheterization data alone). The degree of obstruction was estimated echocardiographically lo and compared with catheterization data in each of these 67 patients (nonsimultaneous studies). Thirty-two of 35 patients with resting outflow obstruction had an echocardiographic obstruction index indicating outflow obstruction compared with only 1 of 22 patients with nonobstructive disease and 0 of 10 patients with provocable disease. Thus, in 63 of 67 patients, the echocardiographic
338
March 1975
The American Journal of CARDIOLOGY
and catheterization data were consistent. The four exceptions were patients who had undergone catheterization studies before 1964. In all four cases, physical findings had changed between 1964 and the present and were now compatible with the echocardiographic data.20 As a result, three patients initially classified as having obstructive disease by catheterization data alone were reclassified as having nonobstructive disease; one patient initially classified in the nonobstructive group was reclassified in the obstructive group. Thus, as finally grouped, 33 patients were considered to have obstructive, 10 provocable and 24 nonobstructive disease. Some patients with right ventricular hypertension may have disproportionate septal thickening.lsJl Such patients usually are easily identified on clinical grounds and should not be included in the spectrum of asymmetric septal hypertrophy. In this study, 23 of the 24 patients with catheterization studies and nonobstructive asymmetric septal hypertrophy had a right ventricular systolic pressure of less than 35 mm Hg. Asymmetric septal hypertrophy in these patients therefore cannot be ascribed to right ventricular hypertension. b. Patients with catheterization studies (systolic mitral value motion): As would be expected, all 33 patients with an obstruction index indicating a resting left ventricular gradient had marked systolic anterior motion of the mitral valve leaflets. Ten other patients also had abnormal systolic anterior motion, but this motion was much less prominent than in the patients in the obstructive group and was not sufficient to give an obstruction index compatible with a resting gradient. None of these 10 patients had a resting gradient at cardiac catheterization, but 8 of 10 (80 percent) did have a gradient exceeding 30 mm Hg with provocative maneuvers. Twenty-four patients had no evidence of abnormal systolic motion of the mitral leaflets. In only 2 of the 24 (8 percent) could a gradient greater than 30 mm Hg be provoked at catheterization. Thus, those patients with asymmetric septal hypertrophy who have an obstruction index indicating no resting gradient but an abnormal systolic anterior motion of the mitral leaflets are likely to have a significant gradient provoked at catheterization, whereas those with no abnormal systolic motion are unlikely to have significant provocable gradients. c. Patients without catheterization studies (classification): In the 33 patients with asymmetric septal hypertrophy without catheterization data, classification was based on echocardiographic data alone. Of the total of 100 patients (including those with and without catheterization studies), 51 were in the nonobstructive group, 14 in the provocable group and 35 in the obstructive group. Mitral valve position: The, position of the mitral valve in the ventricular cavity at the onset of systole was assessed in every patient. Mitral valve position was measured with the ultrasonic beam reflected from the tip of the mitral valve. Proper beam orientation was obtained by first visualizing both the anterior and posterior mitral valve leaflets simultaneously and then scanning perpendicular to the left ventricular outflow tract (that is, across the tip of the valve) until the maximal systolic motion of the anterior mitral leaflet was seen. Mitral valve position was quantitated by measuring the distance from the mitral valve (defined as the point of apposition of the anterior and posterior mitral leaflets at the onset of systole) to (1) the ventricular septum, and (2) the left ventricular free wall (Fig. 1). A mitral valve position ratio was computed by dividing the septalmitral valve distance into the mitral valve-posterior wall
Volume 35
OBSTRUCTIVE
NORMAL
ASYMMETRIC
SEPTAL HYPERTROPHY-HENRY
OEISTRUCTIVE
AS Ii
ET AL.
(IHSS)
FIGURE 1. Unretouched echocardiograms from a normal subject (left) and a patient with obstructive asymmetric septal hypertrophy (ASH) (right). Compared with findings in the normal subject, septal-mitral valve distance (S-MV) is decreased in obstructive asymmetric septal hypertrophy whereas mitral valve-posterior wall distance (MV-PW) is increased, indicating that the mitral valve, at the onset of systole, is positioned forward in the left ventricular cavity. IHSS = idiopathic hypertrophic subaortic stenosis.
distance. In many patients, multiple echoes were recorded from the mitral valve during systole (Fig. 1). When this occurred, mitral valve position was defined from the point midway between the anterior and posterior mitral valve echoes at onset of systole. Two-Dimensional
Echocardiographic
Studies
Equipment: Two-dimensional echocardiographic studies were obtained in real time using a custom-built mechanical sector-scanner consisting of a standard ultrasonic transducer (2.25 megahertz, 1.25 cm diameter, Aerotech transducer), an angle indicator and a small motor. The details of this system have been described previously. The transducer directs the ultrasonic beam into the chest and is angled rapidly through either a 30’ or 45’ arc at a rate of 15 cycles/sec. Each complete cycle results in the generation of two separate sectors (that is, one sector is produced as the transducer moves from left to right and another as it moves from right to left). Thus, 30 separate frames (or sectors) are produced per second, each one containing 100 individual ultrasonic data lines. The ultrasonic signals obtained by the scanner are electronically processed by an ultrasonic receiver (Ekoline 2OA) and specially designed electronic circuits and displayed on a cathode ray tube. The two-dimensional images are recorded permanently with a closedcircuit television system. In this system, a television camera is focused on the cathode ray tube and the camera output recorded by a videotape unit. The videotapes obtained in this manner are used for subsequent analysis. Patient selection: Eleven patients with obstructive asymmetric septal hypertrophy were studied by two-dimensional echocardiography. In every case, the condition had been demonstrated previously by one-dimensional echocardiography, and the degree of obstruction had been
determined by both cardiac catheterization and one-dimensional echocardiography. Study procedure: In each study, the sector scanner was oriented in two ways: (1) parallel to the left ventricular long axis, and (2) perpendicular to the left ventricular long axis. With both parallel and perpendicular orientation, particular care was used so that the papillary muscles, mitral valve, left ventricular outflow tract and ventricular septum were visualized.
Results One-Dimensional
Echocardiography
The mean septal-mitral valve distance was 34.6 mm in normal subjects, 19.6 mm in those with obstructive asymmetric septal hypertrophy, 22.0 mm in those with provocable and 27.4 mm in those with nonobstructive asymmetric septal hypertrophy (Fig. 2). The mean distances in the patients with asymmetric septal hypertrophy were significantly less than the distance in normal subjects (P
