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Abnormal Diastolic Flow Patterns in Hypertrophic Cardiomyopathy: Evaluation by Simultaneous Doppler Echocardiography, Cineangiography, and Hemodynamics
Abnormal Diastolic Flow Patterns in Hypertrophic Cardiomyopathy: Evaluation by Simultaneous Doppler Echocardiography, Cineangiography, and Hemodynamics Paul R. Silverman, MD, Folkert J. Ten Cate, MD, Patrick W. Serruys, MD, and Jos R. T. C. Roelandt, MD, Rotterdam) The Netherlands
A 62-year-old woman with an 8-year history of hypertrophic cardiomyopathy and recent septal myotomy and/or myectomy underwent simultaneous hemodynamic and two-dimensional and Doppler echocardiographic evaluation. Evidence of abnormal diastolic relaxation in the absence of obstruction or systolic cavity obliteration was observed. Two abnormal patterns of diastolic blood flow were detected: flow from the left ventricular outflow tract toward the left ventricular body during isovolumetric relaxation, and middiastolic blood flow from the left ventricular body toward the mitral apparatus. This case provides evidence of abnormal diastolic function and two patterns of abnormal diastolic blood flow in a patient with hypertrophic cardiomyopathy but without a systolic gradient or cavity obliteration. These findings support the importance of disturbed diastolic function in the pathogenesis of hypertrophic cardiomyopathy. 0 AM Soc ECHO 1989;2:346-9.)
Hypertrophic cardiomyopathy is a complex disorder in which pathogenesis remains controversial. Recently, increased attention has been focused on ventricular diastolic dysfunction as the primary abnormality in this disease. We report a patient with Doppler echocardiographic, hemodynamic, and cineangiographic evidence of diastolic dysfunction associated with abnormal intraventricular flow patterns.
HISTORY
We studied a 62-year-old woman who had hypertrophic cardiomyopathy for 8 years. In 1981 she underwent cardiac catheterization, and a left ventricular outflow tract gradient of 80 mm Hg at rest was found. However, she declined surgery. In 1988 she had complaints of dizziness and dyspnea. She had catheterization again, and a pressure gradient in the left ventricular outflow tract was 60 mm Hg at provocation with an infusion of isoproterenol. Because she was severely symptomatic (New York Heart AsFrom the Department of Cardiology, Thoraxcenter, Erasmus University Rotterdam, University Hospital Dijkzigt. Reprint requests: Folkett J. Ten Cate, MD, University Hospital Dijkzigt, Thoraxcenter, Room Ba 350, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. 27/1/15059
346
sociation class III), she underwent myotomy and/or myectomy with improvement in her complaints. At the time of her postoperative catheterization, 5 months after operation, she was taking no medication. Physical examination revealed a grade I/VI soft left ventricular outflow tract ejection murmur. There was no murmur audible at the apex of the heart. The electrocardiogram revealed atrial fibrillation with ventricular response of less than 100/min. M-mode and two-dimensional echocardiography revealed a classic example of a postoperative hypertrophic cardiomyopathy patient with a wide left ventricular outflow tract and no abnormal systolic anterior motion of the mitral valve but persistent left ventricular hypertrophy deeper in the left ventricle in the short-axis cross sections. Precordial continuous wave Doppler echocardiography revealed no aortic or mitral insufficiency but showed peculiar diastolic flow patterns in the left ventricular outflow tract and from the mitral position, which could not be explained at that time. Cardiac Catheterization
For postoperative evaluation of the effect of surgery, cardiac catheterization was performed. Right- and left-sided cardiac catheterization was performed with the Seldinger technique. Micromanometer-tipped high fidelity 7F catheters (Millar Instruments, Inc.,
Volume 2 Number 5 September-October 1989
Abnormal diastolic flow in cardiomyopathy 347
Table 1 Hemodynamically derived measurements of diastolic function
HR (beats/min) LVEDP (mm Hg) -dp/dt (mm Hg) Tl (msec) T2 (msec)
Rest
Isoproterenol provocation
75 16 710 75 65
139 10 1450 91 60
n
>950 <37 <32
HR., Heart rate; L VEDP, left ventricular end-diastolic pressure; - lip! tit, negative portion of the first derivative of left ventricular pressure; T 1, time COnstant of relaxation derived from left ventricular pressure curve for 40 msec, after closure of the aortic valve; T2, second part of the time constant of relaxation after 40 msec, from aortic valve closure.
Houston) were advanced to the left ventricular apex and to the ascending aorta. A 7F fluid-filled catheter (Cordis Corp., Miami) was advanced to the right ventricle. Simultaneous two-dimensional and Doppler (continuous, pulsed wave, and color flow) echocardiographic imaging were recorded during cardiac catheterization from the apical position with a 3 MHz duplex transducer and commercially available apparatus (Vingmed GFM 700, Diasonics, Inc., San Francisco). Two-dimensional echocardiographic four-chamber views were obtained. Doppler flow in the left ventricular outflow tract and mitral inflow were assessed with standard techniques.1 Hemodynamic assessment was made with the high fidelity catheters in the aorta and left ventricle. Calculation of peak negative qp/dt, Tl, and T2 were perfonned with a previouslY. described on-line computer based system. Biplane cineventriculography and biventricular cineangiocardiography in the left superior oblique position were perfonned.
Findings There was no resting gradient. After an infusion of isoproterenol (dosage 1 fJ.g/min) a peak left ventricular apex to ascending aortic gradient of 31 mm Hg was provoked. The hemodynamic indexes of diastolic function at rest and during provocation are shown in Table l. Biplane ventriculography did not reveal systolic anterior motion of the mitral valve. However, two abnormal patterns of diastolic flow were revealed by Doppler tracings and cineangiography. Doppler tracings in the left ventricular outflow tract revealed early diastolic flow from the left ventricular outflow tract toward the ventricular apex (Figure 1, A). This was seen cineangiographically as the flow of dye from the left ventricular outflow tract toward the ventricular body during isovolumetric relaxation (Figure 2, A).
a Figure 1 A, Doppler flow velocity profile in left ventricular outflow tract and simultaneous left ventricular pressure (LVP). Left ventricular systolic outflow (1). Early diastolic flow reversal (2). B, Doppler flow velocity profile in mitral valve region. Early rapid filling profile (1). Middiastolic flow reversal (2) . Late diastolic filling (3). Note small increase in left ventricular pressure (LVP) immediately preceding flow reversal (2), which decreases before late diastolic filling (3).
The second diastolic flow abnonnality involved mitral inflow. Doppler examination revealed middiastolic flow reversal immediately after the early rapid filling phase of diastole. This was seen consistendy and was followed by continued filling in late diastole (Figure 1, B). The simultaneous left ventricle pressure curve reveals a small increase in pressure immediately before the flow reversal. Inspection of the left ventriculogram also demonstrated middiastolic dye reversal toward the mitral apparatus from the body of the left ventricle (Figure 2, B). During infusion of isoproterenol, neither the hemodynamic recordings nor Doppler echotracings revealed this abnormality . DISCUSSION
Recendy, much attention has been focused on diastolic function in hypertrophic cardiomyopathy.2-3 Doppler-derived indexes of diastolic function have correlated with hemodynamic and cineangiographic assessment of diastolic function in patients with heart disease but without hypertrophic cardiomyopathy. In our patient abnormal hemodynamic indexes of diastolic function were accompanied by Doppler and cineangiographic evidence of abnormal intraventric-
348
8.
Silverman et al.
Jouma! of the American Society of Echocardiography
1.
b. Figure 2 A, Left ventriculography (left anterior oblique view) . End systole (1). Early diastole (2). Several frames later showing movement of contrast dye from left ventricular outflow tract toward left ventricular apex (3). Lar,ge arrows indicate position of aortic valve. Small arrows
indicate movement of dye. B, Biventriculography (left superior oblique view). Early diastole demonstrating opening of mitral valve (lar,ge arrows) and contrast dye immediately below mitral valve orifice (small arrows) (1). Rapid diastolic filling demonstrating clearance of dye from mitral valve orifice (2). Middiastolic flow reversal with dye obscuring mitral valve orifice (3) . Open arrows outline left ventricular cavity and demonstrate diastolic chamber enlargement.
ular flow patterns. The left ventricular outflow tract abnormality resembles an abnormality previously noted at ventriculography in a patient with hypertrophic cardiomyopathy and a resting outflow gradient. 4 The patient we present had undergone septal myotomy and/ or myectomy and did not have a resting gradient. Therefore the abnormal flow pattern observed presumably resulted from delayed relaxation in the left ventricular outflow tract compared with the left ventricular body. Recently a group of patients with hyperdynamic left ventricular function has been reported to have similar Doppler findings during isovolumetric relaxation. 5 This was attributed to cavity obliteration and asynchronous relaxation, as seen on cineangiography. In the patient we present, flow during isovolumetric relaxation was present in the absence of cavity obliteration. This observation, along with the simultaneous hemodynamic data, support the primary role of abnormal diastolic relaxation in the genesis of this phenomenon. Although aortic insufficiency could have produced a similar flow pattern, careful examination of the angiogram did not reveal aortic insufficiency, and the patients' preoperative Doppler and cineangiocardio-
graphic examinations revealed no evidence of aortic insufficiency. Also the Doppler findings were seen before cardiac catheterization so that artifactual findings resulting from catheter placement were excluded. The abnormal left ventricular diastolic inflow pattern by two independent methods has not been reported as yet. We hypothesize that asynchronous and delayed relaxation results in an elevated ventricular pressure after early filling, which causes a brief flow reversal toward the mitral anulus. The small increase in pressure is seen on the simultaneous left ventricular pressure tracing in Figure 1, B. Because the patient had atrial fibrillation, the late diastolic filling could not result from atrial contraction but must have resulted from ventricular relaxation and/ or atrial filling during diastole. Although the elevation in left ventricular pressure and the mitral flow reversal could conceivably result from the early diastolic left ventricular outflow tract abnormality, the simultaneous left ventricle pressure curves do not reveal an increase in pressure associated with the left ventricular outflow tract flow reversal (Figure 1, A) . Therefore we believe that these were independent phenomena. Recent work has shown that diastolic abnormali-
Volume 2 Number 5 September-October 1989
ties are present in the majority of patients with hypertrophic cardiomyopathy.6 It has been postulated that diastolic dysfunction is of primary importance in the genesis of the symptoms of the disease. 2 Asynchronous relaxation of the ventricle has been demonstrated in normal and in diseased hearts. 7 The abnormal mitral flow pattern was not observed during infusion of isoproterenol. This may reflect more rapid or uniform ventricular relaxation at a faster heart rate as evidenced by a higher - dp / dt and lower left ventricular end-diastolic pressure (Table 1). However, the T1 and T2 during isoproterenol infusion were increased. This paradox raises interesting questions about the effect of isoproterenol on overall diastolic function in hypertrophic cardiomyopathy. Unfortunately, Doppler evaluation of the left ventricular outflow tract was not obtained during infusion of isoproterenol. The findings described in this study are not attributable to the previous surgery for the following reasons: 1. Review of the cineangiograms of patients at our institution who had surgery revealed this finding both before and after operation. 2. More experience with one other patient who recently had surgery at our institution with symptomatic hypertrophic cardiomyopathy confirmed the Doppler echocardiographic and angiographic findings described in the present study. This article demonstrates Doppler and cineangiographic evidence of abnormal intraventricular diastolic flow along with simultaneous hemodynamic evidence of diastolic dysfunction. To our knowledge the mitral flow pattern has not been reported previously by two separate, independent methods. The left ventricular outflow tract abnormality has only
Abnormal diastolic flow in cardiomyopathy 349
been reported in a patient with a resting gradient and in patients with cavity obliteration, which were not present in our patient. This article supports the recent emphasis on abnormal diastolic function and segmental relaxation as important contributors to the pathogenesis of hypertrophic cardiomyopathy. Furthermore, combined hemodynamic and Doppler studies might give more insight into abnormal diastolic flow patterns. REFERENCES 1. Hatle L, Angelsen B. Doppler ultrasound in cardiology: physical principles and clinical applications. Philadelphia: Lea & Febiger, 1985:78-81. 2. Maron BJ, Bonow RO. Cannon RO, Leon MB, Epstein SE. Hypertrophic cardiomyopathy: interrelations of clinical manifestations, pathophysiology and management (part I). N Eng! J Med 1987;316:780-9. 3. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity parterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coli CardioI1988;12:426-40. 4. Tronman RG, Palomo AR, Nguyen NX, Myerburg RJ, Kessler KM. Reversal of left ventricular intracavitary gradient with intracavitary diastolic regurgitation in hypertrophic obstrUctive cardiomyopathy. J Am Coli CardioI1986;8:703-5. 5. Sasson Z, Hatle L, Appleton CP, Jewett M, Alderman EL, Popp RL. Intraventricular flow during isovolumetric relaxation: description and characterization by Doppler echocardiography. J Am Coli Cardiol 1987;10:539-46. 6. Maron BJ, Spirito P, Green KJ, Wesley YE, Bonow RO, Arce J. Noninvasive assessment ofleft ventricular diastolic function by pulsed Doppler echocardiography in patients with hypertrophic cardiomyopathy. J Am Coli Cardiol 1987;10:733-42. 7. Rokey R, Kuo LC, Zoghbi WA, Limacher MC, Ouinones MA. Determination of parameters of left ventricular diastolic filling with pulsed Doppler echocardiography: comparison with cineangiography. Circulation 1985;71:543-50.
A 62-year-old woman with an 8-year history of hypertrophic cardiomyopathy and recent septal myotomy and/or myectomy underwent simultaneous hemodynamic and two-dimensional and Doppler echocardiographic evaluation. Evidence of abnormal diastolic relaxation in the absence of obstruction or systolic cavity obliteration was observed. Two abnormal patterns of diastolic blood flow were detected: flow from the left ventricular outflow tract toward the left ventricular body during isovolumetric relaxation, and middiastolic blood flow from the left ventricular body toward the mitral apparatus. This case provides evidence of abnormal diastolic function and two patterns of abnormal diastolic blood flow in a patient with hypertrophic cardiomyopathy but without a systolic gradient or cavity obliteration. These findings support the importance of disturbed diastolic function in the pathogenesis of hypertrophic cardiomyopathy. 0 AM Soc ECHO 1989;2:346-9.)
Hypertrophic cardiomyopathy is a complex disorder in which pathogenesis remains controversial. Recently, increased attention has been focused on ventricular diastolic dysfunction as the primary abnormality in this disease. We report a patient with Doppler echocardiographic, hemodynamic, and cineangiographic evidence of diastolic dysfunction associated with abnormal intraventricular flow patterns.
HISTORY
We studied a 62-year-old woman who had hypertrophic cardiomyopathy for 8 years. In 1981 she underwent cardiac catheterization, and a left ventricular outflow tract gradient of 80 mm Hg at rest was found. However, she declined surgery. In 1988 she had complaints of dizziness and dyspnea. She had catheterization again, and a pressure gradient in the left ventricular outflow tract was 60 mm Hg at provocation with an infusion of isoproterenol. Because she was severely symptomatic (New York Heart AsFrom the Department of Cardiology, Thoraxcenter, Erasmus University Rotterdam, University Hospital Dijkzigt. Reprint requests: Folkett J. Ten Cate, MD, University Hospital Dijkzigt, Thoraxcenter, Room Ba 350, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. 27/1/15059
346
sociation class III), she underwent myotomy and/or myectomy with improvement in her complaints. At the time of her postoperative catheterization, 5 months after operation, she was taking no medication. Physical examination revealed a grade I/VI soft left ventricular outflow tract ejection murmur. There was no murmur audible at the apex of the heart. The electrocardiogram revealed atrial fibrillation with ventricular response of less than 100/min. M-mode and two-dimensional echocardiography revealed a classic example of a postoperative hypertrophic cardiomyopathy patient with a wide left ventricular outflow tract and no abnormal systolic anterior motion of the mitral valve but persistent left ventricular hypertrophy deeper in the left ventricle in the short-axis cross sections. Precordial continuous wave Doppler echocardiography revealed no aortic or mitral insufficiency but showed peculiar diastolic flow patterns in the left ventricular outflow tract and from the mitral position, which could not be explained at that time. Cardiac Catheterization
For postoperative evaluation of the effect of surgery, cardiac catheterization was performed. Right- and left-sided cardiac catheterization was performed with the Seldinger technique. Micromanometer-tipped high fidelity 7F catheters (Millar Instruments, Inc.,
Volume 2 Number 5 September-October 1989
Abnormal diastolic flow in cardiomyopathy 347
Table 1 Hemodynamically derived measurements of diastolic function
HR (beats/min) LVEDP (mm Hg) -dp/dt (mm Hg) Tl (msec) T2 (msec)
Rest
Isoproterenol provocation
75 16 710 75 65
139 10 1450 91 60
n
>950 <37 <32
HR., Heart rate; L VEDP, left ventricular end-diastolic pressure; - lip! tit, negative portion of the first derivative of left ventricular pressure; T 1, time COnstant of relaxation derived from left ventricular pressure curve for 40 msec, after closure of the aortic valve; T2, second part of the time constant of relaxation after 40 msec, from aortic valve closure.
Houston) were advanced to the left ventricular apex and to the ascending aorta. A 7F fluid-filled catheter (Cordis Corp., Miami) was advanced to the right ventricle. Simultaneous two-dimensional and Doppler (continuous, pulsed wave, and color flow) echocardiographic imaging were recorded during cardiac catheterization from the apical position with a 3 MHz duplex transducer and commercially available apparatus (Vingmed GFM 700, Diasonics, Inc., San Francisco). Two-dimensional echocardiographic four-chamber views were obtained. Doppler flow in the left ventricular outflow tract and mitral inflow were assessed with standard techniques.1 Hemodynamic assessment was made with the high fidelity catheters in the aorta and left ventricle. Calculation of peak negative qp/dt, Tl, and T2 were perfonned with a previouslY. described on-line computer based system. Biplane cineventriculography and biventricular cineangiocardiography in the left superior oblique position were perfonned.
Findings There was no resting gradient. After an infusion of isoproterenol (dosage 1 fJ.g/min) a peak left ventricular apex to ascending aortic gradient of 31 mm Hg was provoked. The hemodynamic indexes of diastolic function at rest and during provocation are shown in Table l. Biplane ventriculography did not reveal systolic anterior motion of the mitral valve. However, two abnormal patterns of diastolic flow were revealed by Doppler tracings and cineangiography. Doppler tracings in the left ventricular outflow tract revealed early diastolic flow from the left ventricular outflow tract toward the ventricular apex (Figure 1, A). This was seen cineangiographically as the flow of dye from the left ventricular outflow tract toward the ventricular body during isovolumetric relaxation (Figure 2, A).
a Figure 1 A, Doppler flow velocity profile in left ventricular outflow tract and simultaneous left ventricular pressure (LVP). Left ventricular systolic outflow (1). Early diastolic flow reversal (2). B, Doppler flow velocity profile in mitral valve region. Early rapid filling profile (1). Middiastolic flow reversal (2) . Late diastolic filling (3). Note small increase in left ventricular pressure (LVP) immediately preceding flow reversal (2), which decreases before late diastolic filling (3).
The second diastolic flow abnonnality involved mitral inflow. Doppler examination revealed middiastolic flow reversal immediately after the early rapid filling phase of diastole. This was seen consistendy and was followed by continued filling in late diastole (Figure 1, B). The simultaneous left ventricle pressure curve reveals a small increase in pressure immediately before the flow reversal. Inspection of the left ventriculogram also demonstrated middiastolic dye reversal toward the mitral apparatus from the body of the left ventricle (Figure 2, B). During infusion of isoproterenol, neither the hemodynamic recordings nor Doppler echotracings revealed this abnormality . DISCUSSION
Recendy, much attention has been focused on diastolic function in hypertrophic cardiomyopathy.2-3 Doppler-derived indexes of diastolic function have correlated with hemodynamic and cineangiographic assessment of diastolic function in patients with heart disease but without hypertrophic cardiomyopathy. In our patient abnormal hemodynamic indexes of diastolic function were accompanied by Doppler and cineangiographic evidence of abnormal intraventric-
348
8.
Silverman et al.
Jouma! of the American Society of Echocardiography
1.
b. Figure 2 A, Left ventriculography (left anterior oblique view) . End systole (1). Early diastole (2). Several frames later showing movement of contrast dye from left ventricular outflow tract toward left ventricular apex (3). Lar,ge arrows indicate position of aortic valve. Small arrows
indicate movement of dye. B, Biventriculography (left superior oblique view). Early diastole demonstrating opening of mitral valve (lar,ge arrows) and contrast dye immediately below mitral valve orifice (small arrows) (1). Rapid diastolic filling demonstrating clearance of dye from mitral valve orifice (2). Middiastolic flow reversal with dye obscuring mitral valve orifice (3) . Open arrows outline left ventricular cavity and demonstrate diastolic chamber enlargement.
ular flow patterns. The left ventricular outflow tract abnormality resembles an abnormality previously noted at ventriculography in a patient with hypertrophic cardiomyopathy and a resting outflow gradient. 4 The patient we present had undergone septal myotomy and/ or myectomy and did not have a resting gradient. Therefore the abnormal flow pattern observed presumably resulted from delayed relaxation in the left ventricular outflow tract compared with the left ventricular body. Recently a group of patients with hyperdynamic left ventricular function has been reported to have similar Doppler findings during isovolumetric relaxation. 5 This was attributed to cavity obliteration and asynchronous relaxation, as seen on cineangiography. In the patient we present, flow during isovolumetric relaxation was present in the absence of cavity obliteration. This observation, along with the simultaneous hemodynamic data, support the primary role of abnormal diastolic relaxation in the genesis of this phenomenon. Although aortic insufficiency could have produced a similar flow pattern, careful examination of the angiogram did not reveal aortic insufficiency, and the patients' preoperative Doppler and cineangiocardio-
graphic examinations revealed no evidence of aortic insufficiency. Also the Doppler findings were seen before cardiac catheterization so that artifactual findings resulting from catheter placement were excluded. The abnormal left ventricular diastolic inflow pattern by two independent methods has not been reported as yet. We hypothesize that asynchronous and delayed relaxation results in an elevated ventricular pressure after early filling, which causes a brief flow reversal toward the mitral anulus. The small increase in pressure is seen on the simultaneous left ventricular pressure tracing in Figure 1, B. Because the patient had atrial fibrillation, the late diastolic filling could not result from atrial contraction but must have resulted from ventricular relaxation and/ or atrial filling during diastole. Although the elevation in left ventricular pressure and the mitral flow reversal could conceivably result from the early diastolic left ventricular outflow tract abnormality, the simultaneous left ventricle pressure curves do not reveal an increase in pressure associated with the left ventricular outflow tract flow reversal (Figure 1, A) . Therefore we believe that these were independent phenomena. Recent work has shown that diastolic abnormali-
Volume 2 Number 5 September-October 1989
ties are present in the majority of patients with hypertrophic cardiomyopathy.6 It has been postulated that diastolic dysfunction is of primary importance in the genesis of the symptoms of the disease. 2 Asynchronous relaxation of the ventricle has been demonstrated in normal and in diseased hearts. 7 The abnormal mitral flow pattern was not observed during infusion of isoproterenol. This may reflect more rapid or uniform ventricular relaxation at a faster heart rate as evidenced by a higher - dp / dt and lower left ventricular end-diastolic pressure (Table 1). However, the T1 and T2 during isoproterenol infusion were increased. This paradox raises interesting questions about the effect of isoproterenol on overall diastolic function in hypertrophic cardiomyopathy. Unfortunately, Doppler evaluation of the left ventricular outflow tract was not obtained during infusion of isoproterenol. The findings described in this study are not attributable to the previous surgery for the following reasons: 1. Review of the cineangiograms of patients at our institution who had surgery revealed this finding both before and after operation. 2. More experience with one other patient who recently had surgery at our institution with symptomatic hypertrophic cardiomyopathy confirmed the Doppler echocardiographic and angiographic findings described in the present study. This article demonstrates Doppler and cineangiographic evidence of abnormal intraventricular diastolic flow along with simultaneous hemodynamic evidence of diastolic dysfunction. To our knowledge the mitral flow pattern has not been reported previously by two separate, independent methods. The left ventricular outflow tract abnormality has only
Abnormal diastolic flow in cardiomyopathy 349
been reported in a patient with a resting gradient and in patients with cavity obliteration, which were not present in our patient. This article supports the recent emphasis on abnormal diastolic function and segmental relaxation as important contributors to the pathogenesis of hypertrophic cardiomyopathy. Furthermore, combined hemodynamic and Doppler studies might give more insight into abnormal diastolic flow patterns. REFERENCES 1. Hatle L, Angelsen B. Doppler ultrasound in cardiology: physical principles and clinical applications. Philadelphia: Lea & Febiger, 1985:78-81. 2. Maron BJ, Bonow RO. Cannon RO, Leon MB, Epstein SE. Hypertrophic cardiomyopathy: interrelations of clinical manifestations, pathophysiology and management (part I). N Eng! J Med 1987;316:780-9. 3. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity parterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coli CardioI1988;12:426-40. 4. Tronman RG, Palomo AR, Nguyen NX, Myerburg RJ, Kessler KM. Reversal of left ventricular intracavitary gradient with intracavitary diastolic regurgitation in hypertrophic obstrUctive cardiomyopathy. J Am Coli CardioI1986;8:703-5. 5. Sasson Z, Hatle L, Appleton CP, Jewett M, Alderman EL, Popp RL. Intraventricular flow during isovolumetric relaxation: description and characterization by Doppler echocardiography. J Am Coli Cardiol 1987;10:539-46. 6. Maron BJ, Spirito P, Green KJ, Wesley YE, Bonow RO, Arce J. Noninvasive assessment ofleft ventricular diastolic function by pulsed Doppler echocardiography in patients with hypertrophic cardiomyopathy. J Am Coli Cardiol 1987;10:733-42. 7. Rokey R, Kuo LC, Zoghbi WA, Limacher MC, Ouinones MA. Determination of parameters of left ventricular diastolic filling with pulsed Doppler echocardiography: comparison with cineangiography. Circulation 1985;71:543-50.