Assessment of diastolic function in normal and hypertrophied hearts: Comparison of Doppler echocardiography and M-mode echocardiography

Assessment of diastOlic furiction iti nor&l and hypertrophied hearts: Corirt)mCsori of Dippier echocardiography and M-Mod6 echocardiography Left ventricular (LV) filling was examined by Doppfer and M-mode e&cardiography in 24 patients with LV hypertrophy (ftve wiffi aWtk stenosis, six with hypertrophic cardlomyopethy, and 13 with LV hypertrophy secondary to systemic hypertension) and ?n 18 normal sub&&s. Patients with LV hypertrophy .had slgniftcently lower Ddppfetietermined peak ftlthig rates (216 + 17 vs 288 + 66 cc/WC, p < O.Ol), but M-mode determined peak rate of chsmber enlargement and normalized peak rate of chamber enlargement did not differ signiff&ntly between groups. Doppler measures of the ratio between early and late filling were rqlgnlficantly depressed in patients with LV hypertrophy and correlated Inversely with age in the normal subjects. The M-mode derived normalized peak rate of chamber enlargement and the Doppler-derived normalized peak ftlling rate correlated.weskly, but stgnlficantly, inhen both groups were combined (I = 0.66, p < 0.61). Thus Doppler measurements can detect abnormalities of LV filling In patients with LV hypertrophy. These abnormalities are present when M-mode filling indices and systolic function are still normal. (AM HEART J lg87;113:1417.)

Anthony C. Pearson, M.D., Arthur J. Labovitz, M.D., Denise Mrosek, George A. Williams, M.D., and Harold L. Kennedy, M.D., M.P.H. St. Louis, MO.

Abnormalities of left ventricular (LV) di.astolic function are well documented in patients with idiopathic hypertrophic cardiomyopathy,‘” with LV hypertrophy secondary to chronic pressure overload,6s8-11 and with coronary artery disease.12* l3Previous studies have analyzed these abnormalities by contrast angiography,3sl4 by radionuclide angiography,b 4,&g,12.13and by echocardiography.** 6,lo.l1 These methods appear to adequately discriminate between abnormal and normal diastolic function but suffer from various limitations. Doppler echocardiography represents a technique that is unique for its ability to simply and noninvasively measure the timing, magnitude, and patterns of blood flow in cardiac chambers during both diastole and systole. Recent report8 ls-18have suggested that Doppler echocardiography may be useful in assessingthe diastolic function of the left ventricle. In light of this, we have analyzed both normal subjects

and

patients

&b

LV

bypertropby

by

From the Department of Medicine, Division of Cardiology, St. Lo& University School of Medicine. Received for publication July 16, 1986; accepted Nov. 21, 1986. Reprint requests: Arthur J. Lebovitz, M.D., St. Louis University Medical Center, 1325 S. Grand Blvd., St. Lade, MO 63104.

Doppler interrogation of the mitral valve in combination with echocardiographic wall motion analysis. Our aims were: (1) to examine Doppler indices of diastolic LV filling in patients with LV hypertrophy in comparison to normals, (2) to com3are Dopplerderived with M-mode-derived indices of diastolic filling, and (3) to determine the clinical and echocardiographic variables that influence diastolic filling in normals and in patients with LV hypertrophy. METHODS Study patients. The study,population (group I) consistedof 24 patients referred for echocardiographicexamination who were found to have LV hypertrophy with high quality M-mode and Doppler echocardiographic reizordings. The causeof the LV hypertrophy in these caseswas one of the following. (1) Aortic.stenosis-six patients with calcified aortic valve and evidence of increased systolic aortic valve gradient hy Doppler echocardiography. (2)

i'i)'/ErtropiIi? Hi~iW~opatpy-rive

~tti!O~

Fyi#

marked LV hypertrophy and no apparent concomitant condition suchas aortic stinosis or hypertension known to cause LV hypertrophy. (3) Concentric LV hypertrophy secondary to hypertension (13 patients). Patients were excluded if they had significant mitral or aortic regurgitation as determined by pulsed Doppler mapping.ln-pIn addition, patients with heart rate 5110 1417

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Fig. 1. ,A, Measurement of the mitral anulus diameter (MALI) from the apical four-chamber view. B, Measurement of mitral rinulus diameter in parasternal long-axis view (MALI, dotted line).

bpm or rhythm other than sinus were excluded. No patients had per&dial diseaseor mitral stenosis, as determined by Doppler echocardiography. There were 11 men and 13 womenpatients, with agesranging from 37 to 69 years (mean = 57). The control population consistedof 18 normal subjectsof a similar agerangewith no history of hypert&ion or cardiovasculardiseaseand no evidence of LV hypertrophy or cardiovascular disorders by echocardiographic, examination (group, II). Only subjects with

5h quality r&xrdigs

were included for analysis.

Echdc#Qlopr#rMc str#lks. M-mode, two-dimensional echocardiography, and cardiac DoppIer studies were performad with a phased-array echo-Doppler system (Irex Meridian or Hewlett-Packard Series66). (Irex Technology Group, Ramsey, N;J.; Hewlett-Packard Co., Andover, Mass.). Tbeae systems use, either a 2.5 or 3.5 MHz tranadu& for M-mode and two-dimensional echocardiography. M-mode echocardiogramswere recorded in all patient& Recordings of the LV cavity were made at the level just below the mitral leaflets, at a paper speedof 50 or 166 mm/sac. Echoes of the posterior waI1 and septal

endocardium were traced with a digitizing tablet. Data were processed on a Franklin 2609 Cardiac Analysis System (Bruce Franklin, Inc., Woodinville; Wa.) and plots were obtained of the original echocardiographicdata, the instantaneousdimension over time (in milEmet&), and the first derivative and normalized first derivative of dimension over time. From the computei-iied plots the peak rate of increase of dimension during &stole (in millimeters per ,second)and the peak rate of increaseof

dimension divided by instantarieous LV dti.epion (or normalized peak rate of chamber enlargement, in seconds-‘) were determined. The LV end-diastolic volume was calculated as the cube of the end-diastolic diameter. The mitral anulus was measuredfrom the apical fourchamber and the parast&al long-axis views during early di&ole (Fig. 1). Measurementswere taken from the inner edgeof the lateral bright corner of the anulus to the inner edgeof the medial comer just below the insertion of the mitral leaflets, and the mitral anirlus diameter was averaged from the two views. The cross-sectionalarea of the anulus was derived as (3.14) X (mitral annular diametei/

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2. Two-dimensional apical four-chamber view showing position of Doppler beam parallel to presumedmitral inflow and location of Doppler samplevolume at level of mitral anulus.

Fig.

-0

Fig. 3. Doppler signals recorded at mitral anulus showing typical mitral inflow velocity patterns with velocity peaksin the early (EJ and late (A,) diastolic filling periods.The pattern on the left is normal with E, > A, while that on the right is from a group I patient showingreversal of normal pattern.

2)2.LV masswas derived by the method of Woythaler et a1.,23which is a modification of the method of Devereux and R.eichekz4in which mass(grams) = 1.04 x [(posterior wall thickness + septal thickness + LV end-diastolic diameter)s- (LV end-diastolic diameter)3] - 13.6 gm. LV mass index was defined as LV mass divided by body surface area. Shortening fraction was calculated as (LV end-diastolic dimension - LV end-systolic dimension)/ LV end-diastolic dimension. Doppter studies. The Doppler units use frequencies of 2.0 MHz or 2.5 MHz and can be operated either in a pulsedor a continuous wave mode. In the pulsedmode the sample volume is approximately 7 mm in diameter and can be located at various depths between 0 and 15. Transmittal flow was sampled by placing the transducer at the cardiac apex and aligning the Doppler cursor

parallel to flow by means of the two-dimensional image from the four-chamber view (Fig. 2). Recordings were made in the pulsed mode with the sample volume obtained from a position in the LV at the level of the mitral anulus. Doppler analysis. All measurementswere made with a computer interfaced digitizing tablet. The average of at least five consecutive cardiac cycles was taken. The peak early diastolic velocity and peak velocity during atrial contraction were measured as shown in Fig. 3. The velocity integral or under the velocity curve for the early diastolic filling period and the atrial diastolic filling period were derived by digitizing the contour of the darkest portion of the curve (Fig. 4). In casesin which the early filling curve overlapped that of the atrial filling curve, a line dropped from the point that represents the nadir of

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Fig. 4. Doppler-derived mitral inflow velocity with dotted lines showing area measuredas integral of

eGly (Et) and atrial (Ai) diastolic filling periods. 3.030

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Fig. 5. A, Comparisonof rapid filling index (RFZ) between normal controls (group II) and patients with left ventricular hypertrophy (LVH) (seetext). B, Comparisonof early to late integral ratio (E,/A,) between normal controls (group II) and patients with LVH (see text). p < 0.001 for significance of difference between groupsfor both values.

the two curves (equivalent to the F point of the mitral valve echogram) was used to separate the two integrals. The mean diastolic velocity was determined by planimetering the velocities of the entire diastolic filling period. The following parametersof diastolic function were calculated by meansof the mitral inflow Doppler velocities: (1) Peak filhng rate (in cubic centimeters per second) was determined as the product of the peak early diastolic

velocity and the cross-sectionalarea of the mitral anulus. (2) Normalized peak filhng rate (in seconds-‘)was determined aspeak filling rate divided by the LV end-diastolic volume. (3) Atrial filling rate was determined as the product of the peak atrial velocity and the cross-sectional area of the mitral anulus. As a measure of the balance between early and late diastolic filling, the following ratios were calculated: (1) the ratio of the integral of the early

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Table

Doppler-echo Table

I. Clinical and echocardiographic parameters

Age(yr) R-R interval (msec) % SF LA1 (cm)

Ventricularseptum

LVH (n = 24)

Normals (n = 18)

value ’

56 + 10 798 + 125

53 * 10 a34 * 135

NS

NS

42 + 12 2.0 k 0.4 1.20 * 0.29

37 f a 2.2 f 0.3 0.78 k 0.15

NS NS
1.24 AT 0.50 134 * 51

0.86 f 0.19 90 f 31


101* 29

120+ 36

NS

3.1 f 1.4

3.3 * 1.1

NS

(cm)

Posteriorwall (cm) LVMI (g/M’) MAX DD/DT (mm/set) N-MAX (see-‘)

LVMI = left ventricular mass index; MAX DD/‘DT = peak rate of chamber enlargemen$ N-MAX = normalized peak rate of chamber enlargement; LA1 = left atrial index; SF = shortening fraction.

diastolic filling period to that of the atrial filling period (early to late integral ratio or EJAJ; (2) the ratio of the peak early velocity to the mean velocity, which we have termed the rapid filling index; and (3) the ratio of the peak early to peak atrial velocity (PE/PA). Reproduclbillty. To determine the intraobserver variability of the Doppler measurements,one observer measured the same set of three to five cardiac cycles on 16 mitral flow velocity recordings on two separate occasions. To determine interobserver variability, the samesets of cardiac cycles were measuredindependently by a second observer. The average percent differences (difference in values divided by value for the first observation) for intraand interobserver variability were asfollows: for the total area under the Doppler curve, 3.2 f 3.1% (intraobserver) and 2.7 + 1.7% (interobserver); for the mean velocity, 2.9 + 1.7% (intraobserver) and 3.3 + 1.8% (interobserver); for the area under the early filling curve, 3.0 -t 3.3% (intraobserver) and 3.6 + 2.9% (interobserver); for the area under the atrial filling curve, 4.5 f 3.6% (intraobserver) and 4.9 f 2.9% (interobserver); for the peak early velocity, 1.9 + 2.1% (intraobserver) and 1.2 + 1.4% (interobserver); for the peak atrial velocity 1.5 + 2.3% (intraobserver) and 2.1 + 1.5% (interobserver). Statlstlcs. Statistical comparisons between the two groupswere made by meansof unpaired t tests in the case of normally distributed values. When values were not normally distributed, the Mann-Whitney U test wasused. A two-tailed p value of <0.05 was used to indicate a significant difference between groups. The relation between two variables was assessedby linear regression

‘d d *‘&I

1

ana1ys;s;p -! 0.05 wae cons1 ere a signi cm mre Ation. RESULTS Clinical and echocardlographlc findings. Table I summarizes the clinical and echocardiographic data for groups I and II. There was no significant differ-

and LV diastolic function

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II. Doppler indices of diastolic function

PFR (ml/set) NPFR (set-‘) AFR (ml/set) RF1 EJAi PE/PA

LVH (n = 24)

Normals (n = 18)

P value

218 k 71

288 k 66

0.01

2.9 + 1.6

2.9 f 1.0

328 + 103

229 + a3

1.37* 0.29

2.15f 0.26

NS 0.001 0.001

0.99 + 0.48 0.68 f 0.17

1.71 * 0.43 1.32 k 0.24

0.001 0.001

PFR = peak filling rate; NPFR = normalized filling rate; AFR = atria1 filling rate; RF1 = rapid filling index; E,/A, = early to late integral ratio; PE/PA = ratio of peak early to peak atrial velocity.

ence between the two groups in age or heart rate. Peak rate of chamber enlargement and normalized peak rate of chamber enlargement did not differ significantly between group I and group II (101 + 29 mm/set vs. 120 + 36 mm/set and3.1 + 1.4 vs 3.3 -t 1.1 set-‘). Left ventricular mass index was significantly higher in group I (134 + 51 gm/m”) than in the controls (90 + 31 gm/m”, p < .Ol), whereas shortening fraction was similar between the groups (42 it 12% vs 37 + 8%, p = NS). Doppler

observations

Filling rates. The study patients (groups I, as shown in Table II) had significantly reduced peak filling rate when compared to normals (218 f 17 cc/set vs 288 -t 66 cc/set, p < 0.01). Atrial filling rate was significantly higher in group I (328 t 103 cc/set) than in group II (229 + 83, p < O.OOl), while normalized peak filling rate did not differ between groups (2.87 + 1.6 set-’ vs 2.90 + 1.0 se&, p = NS). Derived values. Marked differences were noted between groups in the values for rapid filling index, early-to-late integral ratio, and peak early/peak late (atrial) mitral velocity, with all three significantly reduced in the patients with hypertrophy. The rapid filling index was 1.37 t- 0.29 in group I vs 2.15 f 0.26 in group II )p < 0.001). Similar differences were seen for early-to-late integral ratio (0.99 zt 0.48 vs 1.71 + 0.43, p < 0.001) and peak early/peak late (atrial) mitral velocity (0.68 + .17 vs 1.3 f 0.24, p < 0.001). Fig. 5, A and B show the separation between the two groups in terms of rapid filling index and early-to-late integral ratio. Only one of

thegroup I patienta hadflrapidfillinQ indelr ueater than 1.8, while only one of the group II patients had a rapid filling index less than 1.8. Subgroup analysis. The means for rapid filling index, early-to-late integral ratio, and peak early/ peak late (atrial) mitral velocity in the subgroups of patients with hypertrophic cardiomyopathy and

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AGE Fig. 6. Regressionanalysiscorrelating early-to-late integral ratio (EiIAJ and age in normals. Coefficient of correlation = -0.80, p < 0.001. Regressionequation; y = -0.055 X 4.6.

Table III. Correlation of age and diastolic function in normals M-mode indices

T&k tion

IV. Relationship of LV mass and diastolic func-

Doppler indices

M-mode indices Doppler indices

MAX Age Abbreviations

DDIDT

-0.49*

N-MAX -0.35

PFR 0.57t

NPFR

E/A,

0.35

-0.80$

RFZ

MAX DDJDT

N-MAX

-0.10

-0.17

PFR NPFR

EJA,

0.15

-0.46

-0.40

0.08

-0.12

RFZ

-0.13

as in Tables I and II.

*p < 0.05. t = p < 0.02.

~=p<0.001.

aortic stenosis were not significantly different from that of the whole group II. Removal of these subsets did not significantly change the statistical significance of the parameters. Effects of age. Table III shows the correlation between age and Doppler echocardiographic measures of diastolic filling in normals. There was a weak but significant (r = 0.49, p < 0.05) correlation between age and MAX DD/DT. Stronger and highly significant correlations existed between age and Doppler measures of diastolic filling-peak filling rate (F = 0.57, p < 0.02) and Ei/Ai (r = -0.80, p < 0.001) (Fit 6). In the patients with LV hypertrophy, age did not correlate significantly with any measure of diastolic function. Effects of left ventricular mass. Table IV shows the relationship between LV mass and both M-mode and Doppler measures of diastolic function in both groups. In normals, the rapid Wing index and the early-to-late integral ratio tended to be lower in those subjects with higher LV mass, but this did not reach statistical significance. In patients with LV

L Normals v M I LVH

0.14

0.18

LVH = left ventricular hypertrophy; other abbreviations II. p = NS for all correlation coefficients.

0.28

-0.36

0.16

as in Tables I and

hypertrophy, there was no relationship between LV mass and diastolic function. M-mode and Doppler correlations in the combined groups. There was no correlation between the M-mode measure of peak rate of chamber enlargement and the Doppler measure of peak filling rate (PFR) (r = 0.01, p = NS). However, when the normalized forms of these parameters were compared, there was a significant correlation between the two \ r = 0.561 p < 0.01). The other Do ppler measuresof diastolic filling, including the rapid filling index and the early-to-late integral ratio, showed no significant correlation with the M-mode measures. D16CtBSlON Doppler echocardiography represents a tool unique in its ability to noninvasively measure flow patterns in the heart. Only a few reports are available on the usefulness of Doppler in measuring

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diastolic event8 and their correlation with previously studied techniques. Rokey et alI5 have shown that peak filling rate as assessed by Doppler correlates well with peak filling rat8 determined by contrast angiography in both normal and diseased ventricles. Several researchers who used Doppler have shown altered LV filling related to aging,16 hypertrophic cardiomyopathy,6* l7 and myocardial infarction.ls Eifeizt of LV hypertrophy. The present study demonstrates marked changes in LV filling as assessed by Doppler echocardiography in patients with LV hypertrophy. In hypertrophied ventricles, the amount of LV filling occurring in later diastole was significantly increased, while that occurring in early diastole was reduced. These findings are in agreement with earlier studies that have used a variety of techniques. Kitabatake et al.,l’ who used Doppler, studied patient8 with hypertension and hypertrophic cardiomyopathy and found a reduced peak early transmitral velocity and reduced ratio of peak early to peak late trarismitral velocity in these two groups in comparison to normals. Fujii et al.25 used M-mode computerized analysis and found reduced LV flliing during the rapid filling period, with a compensatory augmentation of atrial contribution to LV filling in patients with hypertrophic cardiomyopathy, aortic stenosis, and hypertension. Several recent radionuclide studies have similarly found reduced filling in early diastole in hypertrophic cardiomyopathy,’ in secondary LV hypertrophy,b g,26 and in aortic stenosian The determinants of diastolic filling are comp18X28v 2s and include active ventricular relaxation, chamber stiffness, and the atrial driving pressure. All of these may be abnormal in patient8 with LV hypertrophy. Because we did not invasively measure ventricular hemodynamics, we cannot determine which factor may be most important in this group of patients. However, similar abnormalities have been found in patient8 with systemic hypertension in the absence of LV hypertrophy,30 and several studies31*32 have documented normal LV filling in athletes with physiologic hypertrophy. These findings lend support to the concept that factors other than increased LV mass play a more important role in LV diastolic dysfunction in primary and secondary LV hypertro-

normal subjects aged 22 to 69 years (mean $6). Van de Werf et al.% demonstrated an age-related decline in peak rate of chamber enlargement and isovolumic relaxation period that was associated with a reduction in the amplitude of S, and an increase in the time delay of S, after S,. Because aging was associated with increased LV mass in their group of 165 normals, they postulated that the change in diastolic filling dynamics was due to a relative hypertrophy associated with aging. We found some support for this concept, but the correlation between age and LV mass index in our normals (r = 0.37) did not quit8 reach statistical significance. M-mode echocardiography vs Doppler. In thia study, the M-mode echocardiographic indices of diastolic filling were not significantly different between the two groups. These findings are in agreement with a recent study of children with systemic hypertension without overt LV hypertrophy34 that found Doppler LV filling abnormalities but not M-mode abnormalities. Earlier stndies of LV filling that found significant abnormalities in chronic pressure overload states and hypertrophic cardiomyopathy by the use of computerized M-mode wall motion analysis, including those of Gibson et allo and Hanrath et al5 did not appear to control for the variable of age. The discrepancies between the present study and these earlier studies may in part be explained by this factor. In addition, we found only a weak correlation between peak rate of dimension increase by M-mode and the peak filling rate based on Doppler analysis. This is undoubtedly because the behavior of the single LV dimension recorded by M-mode echocardiography may not be representative of the LV cavity as a whole. Comparison of M-mode with cineangiographic volume analysis has revealed significant discrepancies between the two t8chniques,35 with the peak rate of dimension increase preceding the angiographic peak filling rate by 40 to 60 msec. Furthermore, when the ventricle becomes enlarged thereby taking on a more spherical shape, or in the presence of regional asynergy, the relation between the cube of dimension and volume becomes inaccurate.36 Limitations of study. The main limitations of Doppler echocardiography in assessing mitral inflow patterns lie in the assumptions made in order to convert

for LV 6lhn-g also c&related with age in normals. Miyatake et alI6 found a similar strong correlation between a Doppler index of the atrial contribution to diastolic filling (ratio of the peak atrial-to-peak early mitral velocity) and age (r = 0.82) in a group of

and normalized peak filling rate, therefore, may suffer inaccuracy due to technical limitations in measuring mitral annular diameter or end-diastolic dimension. Furthermore, Grmiston et als7 have shown that the mitral anulus area changes signifi-

1424

Pearson et al.

cantly in size during diastole, thereby introducing further error into the determination of the Doppler peak filling rate, which is based on an assumed constant mitral annular cross-sectional area throughout diastole. It should be noted, however, in this regard, that in the study of Rokey et al.,15 a good correlation was noted between peak filling rate by Doppler and angiographic techniques when this assumption was employed. Assuming constant mitral annular diameter over time in adult patients should make serial measurements of these parameters helpful in assessing changes in diastolic function in the same patient or in a group of patients over time. A second consideration is the assumption that the Doppler beam interrogates the mitral flow jet in parallel fashion. From the apical four-chamber view, the assumption is made that mitral inflow is directed toward the apex and thus is parallel to flow. The error is less than 3% if the angle between the Doppler beam and the blood flow direction is less than 10 degrees. The Doppler values that assess the atrial contribution to total diastolic filling, earlyto-late integral ratio, rapid filling index, and peak early/peak late (atrial) mitral velocity, however, are not dependent on two-dimensional echocardiographit measurements for their determination. In the presence of nonparallel interrogation, furthermore, these values would not be expected to change. Consequently, these values may prove to be most reliable when making intergroup comparisons of diastolic function. Finally, although we used a heterogeneous population for our study group, we feel this is justified because of previous echocardiographic and radionuelide studies1-3s5*7-12,I4 that showed similar changes in LV filling occurring in all three types of LV hypertrophy that we studied. The results of our study would appear to confirm this similarity in LV diastolic function. The indices of LV filling were indistinguishable in this study among the three types of LV hypertrophy. Further subset analysis was not deemed feasible due to the small size of each

NbgFVUpl Measurement of the mitral valve Doppler pattern has revealed abnormalities of LV filling in the majority of patients with LV hypertrophy in this study. These abnormalities better separated hypertrophied from normal ventricles than did M-mode echocardiographic indices. The reduction in the ratio of early (rapid) filling-to-late (atrial) filling of the LV as assessed by Doppler not only occurs in LV hypertrophy but also correlates strongly with age in normal subjects. This Doppler techConclusions.

June 1987 Heart Journal

Ametlcsn

nique may prove useful in the noninvasive, serial assessment of patients with coronary artery disease, LV hypertrophy, and other myocardial diseases that impair diastolic function. We wish to gratefully acknowledge the secretarial assistance of Susan Buenger and Paris 0. Luster and the technical assistance of Terry Evans, Kathleen Habermehl, and Jeanne Nelson. REFERENCES

1. Bonow RO, Frederick TM, Bacharach SL, Green MV, Goose PW, Maron BJ, Rosing DR. Atria1 systole and left ventricular filling in liypertrophic cardiomyopathy: Effect of verapamil. Am J Cardiol 1983;51:1386. 2. Sanderson JE, Trail1 TA, St. John Sutton MG, Brown DJ, Gibson DG, Goodwin JF. Left ventricular relaxation and filling in hypertrophic cardiomyopathy: An echocardiographit study. Br Heart J 1978;40:596. 3. Sanderson JE, Gibson DG, Brown DJ, Goodwin JF. Left ventricular filling in hypertrophic cardiomyopathy: An anaiographic study. Br Heart J 1977;39:661-670. 4. Bonow RO. Effects of calcium-channel blockinn aaents on left ventricular diastolic function in hypertrophic cardiomyopathy and in coronary artery disease. Am J Cardiol 1985; 553172B. 5. Hanrath P, Mathey DG, Siegert R, Bleifeld W. Left ventricular relaxation and filling pattern in different forms of left ventricular hypertrophy: An echocardiographic study. Am J Cardiol 1980;45:15. 6. Maron BJ, Arce J, Bonow RO, Wesley Y. Noninvasive assessment of left ventricular relaxation and filling by pulsed Doppler echocardiography in hypertrophic cardiomyopathy. Circulation 1984;7O(supplII):18. 7. Spirit0 P, Maron BJ, Chiarella F, Bellotti P, Tramarin R, Pozzoli M, Vecchio C. Diastolic abnormalities in patients with hypertrophic cardiomyopathy: Relation to magnitude of left ventricular hypertrophy.Circulation 1985;72:310-316. 8. Smith V-E, Schulman P. Karimeddini MK. White MB. Meeran MK, Katz AM. ‘Rapid ventricular filling in left ventricular hypertropy. II. Pathologic hypertrophy. J Am Co11 Cardiol 1985;5:869. 9. Inouye I, Massie B, Loge D, Topic N, Silverstein D, Simpson P, Tubau J. Abnormal left ventricular filling: An early finding in mild to moderate systemic hypertension. Am J Cardiol 1984;53:120. 10. Gibson DG, Trail1 TA, Hall RJC, Brown DJ. Echocardiographit features of secondary left ventricular hypertrophy. Br Heart J 1979;41:54. 11. Top01 EJ, Trail1 TA, Fortuin NJ. Hypertensive hypertrophic cardiomvonathv of the elderlv. N Enal J Med 1985:312:227. 12. Bonow RO; Bacharach SL, Green. MV: Kent KM, Rdsing DR, Lipson LC, Leon MB? Epstein SE. Impaired left ventricular diastolic filling in patients with coronary artery disease: Assessment with radionuclide angiography. Circulation 1981;64:315. .

”

131 Green MV, Epstein.SE. I&roved ieft ventricular diastolic filling in patients with coronary artery disease after percutaneous transluminal coronary angioplasty. Circulation 1982; 661159. 14. Gibson DG, Brown DJ. Measurement of peak rates of left ventricular wall movement in man: Comnarison of echocardiography with angiography. Br Heart J i975;37:677. 15. Rokev R. Kuo LC. Zoahibi WA. Limacher MC. Quinones MA. De&n&ion of pa&meters’ of left ventricular diastolic filling with pulsed Doppler echocardiography: Comparison with cineangiography. Circulation 1985;71:543. 16. Miyatake K, Okamoto M, Kinoshita N, Owa M, Nakasone I, Sakakibara H, Nimura Y. Augmentation of atrial contribu-

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22. 23.

24. 25. 26.

tion to left ventricular inflow with aging as assessed by intracardiac Doppler flowmetry. Am J Cardiol 19&4,53:586. Kitabatake A, Inoue M, Asao M, Tanouchi J, Masuyama T, Abe H, Morita H, Senda S, Matsuo H. Transmit& blood flow reflecting diastolic behavior of the left ventricle in health and disease-a study of pulsed Doppler technique. Jpn Circ J 1982;46:92. Fujii J, Yaxaki Y, Sawada H, Aizawa T, Watanabe H, Kato K. Noninvasive assessment of left and right ventricular filling in myocardial infarction with a two-dimensional Doppler echocardiographic method. J Am Coll Cardiol 1985;5:1155. Ciobanu M, Abbasi AS, Allen M, Hermar A, Spellberg R. Pulsed Doppler echocardiography in the diagnosis and estimation of severity of aortic insufficiency. Am J Cardiol 1982;49:339. Quinones MA, Young JB, Waggoner AD, Ostojic MC, Ribelro LGT, Miller RR. Assessment of pulsed Doppler echocardiography in detection and quantification of aortic and mitral reaureitation. Br Heart J 1980:44:612. - . Abbasi AS, Allen MW, DeCristofaro D, Ungar I. Detection and estimation of the degree of mitral regurgitation by range-gated pulsed Doppler echocardiography. Circulation 1980;61:143. Labovitz AJ, Williams GA. Doppler echocardography: Quantitative methods of pulsed and continuous-wave cardiac Doppler. Philadelphia: Lea & Febiger, 1985~38-62. Woythaler JN, Singer SL, Kwan 0, Meltzer RS, Reubner B, Bommer W, DeMaria A. Accuracy of echocardiography versus electrocardiography in detecting left ventricular hypertrophy: Comparison with postmortem mass measurements. J Am Co11 Cardiol 1983;2:305. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man. Circulation 1977;55:613. Fujii J, Watanabe H, Koyama S, Kato K. Echocardiographic study on diastolic posterior wall movement and left ventricular filling by disease category. AM HEART J 1976;98:144. Fouad FM, Slominski JM, Taraxi RC. Left ventricular dia-

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