Clin. Cardiol. 15,504-512 (1992)

Pulsed Doppler Echocardiographic Indices of Left Ventricular Diastolic Function in Normal Subjects v. K.B m , M.D., T.H.DAVE,M.D., K.R.SUNDAM, M.SC., s. SHRIVASTAVA, M.D. All India Institute of Medical Sciences,New Delhi, India

Summary: To establish the normal limits for various pulsed Doppler echocardiographicindices of left ventricular diastolic function, 92 healthy volunteers aged from 5 to 75 years were prospectively studied. The influence of various variables including age, gender, body surface area, fractional shortening, and left ventricular mass on these parameters was also assessed. Mean (2SD) values for 15 direct and 11 derived parameters were analyzed from transmitral inflow velocity waveform. No statistically significant differences were observed between males and females for any of these parameters. On stepwise multivariate linear regression analysis, age was found to be an independent strong determinant (p < 0.001) of peak velocity of early diastolic filling wave, area of atrial filling period, deceleration slope, normalized peak filling rate, and early filling fraction. There was a significant correlation between heart rate and time to peak early diastolic velocity, total diastolic time period, early diastolic period, atrial filling period, and atrial filling fraction. It was further observed that a significant correlation (p < 0.001)persisted between both age and heart rate with area of early filling period, one-third filling area, one-half filling area, ratio of early to atrial peak velocity and area, atrial filling fraction, and one-third filling fraction. None of the parameters were found to correlate with fractional shortening or left ventricular mass. Thus an effort was made to establish normal limits for various Doppler-derived parameters in healthy volunteers for future comparison in diseased states. Age and heart rate were found to have a significant influence on pattern of diastolic filling and should be taken into account while studying transmitral flow pattern in diseased states.

Key words: Doppler echocardiography, left ventricular diastolic function, transmitral flow velocity

Introduction The importance of left ventricular diastolic dysfunction in the genesis of congestive heart failure has been increasingly recognized in the last Alteration of left ventricular diastolic function, in the presence of normal systolic function, has been well documented in patients with systemic arterial hyperten~ion,~,~ cardiomyopathy,5.6 and coronary artery d i s e a ~ e .Most ~ . ~ of these studies have utilized left ventricular cineangiography,8 radionuclide ~cintigraphy,5.~ or digitized M-mode echocardiography6 for the assessment of left ventricular diastolic function. All of these methods, however, have several important limitation~.~ In the last decade, Doppler echocardiography has been well established as a simple and reliable noninvasive technique to measure intracardiac blood flow. Recently much attention has been focused on utilizing Doppler echocardiography for assessment of diastolic function in patients with various cardiac disorders.lc-14 However, well-established normal values for various diastolic indices are not yet available. Furthermore, few studies have shown that some determinants of left ventricular filling may simply be altered by aging.15J6 The present study was undertaken to determine normal values for different Doppler indices of left ventricular diastolic function in a group of healthy volunteers and to determine the influence of various variables including age, gender, body surface area, fractional shortening, and left ventricular mass on these parameters of left ventricular filling.

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Material and Methods

Dr.V.K.Bah1 Associate Professor of Cardiology All India Institute of Medical Sciences New Delhi 110029, India

Study Population

Received: January 31, 1992 Accepted: February 12,1992

We studied Doppler echocardiographic parameters of left ventricular diastolic function in 92 healthy volunteers. There were 33 males and 59 females with age range of 5 to

V. K. Bahl et al.: Doppler echocardiography for diastolic LV function

75 years (mean k SD: 35f 17). None had symptoms or signs suggesting a cardiac disease and all were normotensives. All had a normal M-mode and cross-sectional echocardiogram, and parameters of systolic function were within normal limits. All subjects were in normal sinus rhythm. These subjects were further separated into seven age groups with 10 subjects aged 5-10 years (Group I), 10 subjects aged 11-20 years (Group 11), 14 subjects aged 21-30 years (Group 111), 23 subjects aged 3 1 4 0 years (Group IV), 15 subjects aged 41-50 years (Group V), 10 subjects aged 51-60 years (Group VI), and 10 subjects aged 61-75 years (Group VII). Cross-Sectionaland Doppler Technique

The ultrasound examination was performed on an Advanced Technology Laboratory (ATL) Ultramark-8 echocardiography system with an imaging cross-sectional/pulsed Doppler 3.015 .O MHz transducer. Recordings were made on videotape or stripchart recorder at a speed of 100 mm/s. First a cross-sectional echocardiographic examination was performed utilizing parasternal and apical positions. Intracardiac anatomy was studied and various measurements were taken. Then the mitral inflow velocity was recorded from an apical four-chamber view that provided optimal visualization of the left ventricular cavity and mitral valve leaflets. The sample volume was placed at the level of the mitral annulus with the cursor oriented in a parallel manner to an imaginary line bisecting the left ventricle from apex to mitral valve. The recordings were considered optimal when a signal of highest audible frequency, maximal velocity, and clearly definable spectral envelope was obtained. As these optimal signals were assumed to be oriented nearly in a parallel manner to the direction of maximal mitral blood flow, no correction was used to compensate for the presumed angle between the direction of Doppler beam and the direction of the maximal mitral blood flow. Doppler and Cross-SectionalEchocardiographic Measurements

Transmitral flow velocities were measured during early and late diastole (Fig.1). All measurements were obtained during quiet respiration with the subject in a lateral recumbent position. At least three cardiac cycles were analyzed. The real-time mitral flow was reviewed frame by frame to determine the frame that showed maximal left ventricular filling in early and late diastole. The model peak velocity was chosen for digitization of the traces. This is defined as the most dense area of the waveform produced by spectral analysis.I2 The following measurements and calculations were performed:

(1) Peak velocity of early diastolic filling wave (E): measured as the height of maximal deflection during the first half of diastole

505

E

-.

*

OE

I

OF

FC

oc

L

FIG.1 Schematic drawing of normal transmitral flow-velocity wave form showing various measurement points and intervals. O= beginning of mitral flow; E=peak of early diastolic filling; F= beginning of atrial filling; A = peak of atrial filling; C =end of mital flow: other abbreviations as in Table I.

Peak velocity of the atrial filling wave (A): measured as the height of maximal deflection after the plateau phase of the early filling period Total diastolic integrated velocity or area (TA): derived by digitizing the velocity curve for the total diastolic period Integrated velocity or area of early filling period (EA): derived by digitizing the velocity curve for the early filling period. In case the contour of the flow velocity waveform showed a wide spectral spread at the end of the early flow velocity, the descent point was identified as intersection between the line of descent of early flow velocity and baseline'* Integrated velocity or area of atrial filling period (AA): derived by digitizing the velocity curve for the atrial filling period One third filling area (OC/3 area): derived by digitizing the first one third of the velocity curve for the total diastolic period One half filling area (OC/2) area): derived by digitizing the first half of the curve for the total diastolic period Time to peak early diastolic velocity (OE): measured from beginning of diastolic flow to the peak velocity of the early diastolic filling wave Time to peak early diastolic velocity (CE): measured also from the termination of diastolic flow of the previous cycle to the peak velocity of the early diastolic filling waveI9 Acceleration half-time (Ez-E): defined as time interval between a point at half peak velocity on the ascending limb of the early filling velocity curve to the peak of early filling velocity

Clin. Cardiol. Vol. 15, July 1992 Deceleration half-time (E-Ez):defined as time interval between the peak of early filling velocity to a point at half peak velocity on the descending limb of the early filling velocity curve Total diastolic time period (OC): defined as the interval from mitral valve opening to mitral valve closure as determined by Doppler recording The early diastolic (OF) and atrial (FC) filling periods were empirically divided at the onset of atrial flow velocity (initial increase in velocity after the plateau phase of the early filling period). As our study population did not have very rapid heart rates, all flow velocity curves returned to baseline at point F Deceleration slope (EF)or rate of decrease of flow velocity in early diastole was measured by constructing a straight line corresponding to the descent of the early diastolic filling curve. When the slope EF was curved rather than straight, EF was constructed as the line that identified the maximal incline of the slope.

(4)

(5)

(6)

(7)

(8)

(9) (10)

M-mode and cross-sectionalechocardiographicstudies were also analyzed specifically for the measurementof the following parameters: (1) Cross-sectionalarea of the mitral annulus: calculated assuming a circular geometry by the formula nXrZ,where r represents half of the diameter. The diameter of the mitral annulus was measured in the four-chamber view, from the inner edge of the lateral bright comer of the annulus to the inner edge of the medial comer just below the insertion of the mitral leaflets (2) Long axis of the left ventricle (La): measured in the four-chamber view from the outer margin of the apex to the lateral corner of the mitral annulus (3) Largest minor axis of the left ventricle (D-): obtained as the largest internal diameter measured from either the parasternal long axis or the apical view. All these measurements were taken at end diastole. The following indices of diastolic function were calculated from the data obtained by cross-sectional and Doppler echocardiographic measurements: (1) Ratio of early to atrial peak velocity P A ) : defined as peak velocity of the early diastolic filling wave divided by peak velocity of atrial filling wave (2) Peak filling rate (PFR): determined as the peak early diastolic velocity times the cross-sectional area of the mitral annulus20 (3) Normalized peak filling rate (NPFR):determined as the peak filling rate divided by the left ventricular end-diastolic volume. End-diastolic volume

(11)

was calculated by the formula: EDV = (3.42 Lmax X Dma)-6.44z1 Atrial filling rate (AFR):determined as the peak atrial velocity times the cross-sectionalarea of the mitral annulus Normalized atrial filling rate (NAFR): determined as atrial filling rate divided by the left ventricular end-diastolic volume Ratio of early to atrial filling area (ENAA): defined as integrated velocity or area of the early filling period divided by integrated velocity or area of the atrial filling period Early filling fraction (EFF): defined as integrated velocity or area during early filling (EA) divided by total diastolic area (TA) Atrial filling fraction (AFF):defined as integrated velocity or area during atrial filling (AA) divided by total diastolic area (TA) One third filling fraction (1/3 FF): determined as ratio of frst one third filling area (OC/3) to total diastolic area (TA) One half filling fraction (1/2 FF): determined as ratio of first half of diastolic area (OC/2) to total diastolic area (TA) Ratio of early diastolic (OF) and atrial (FC) filling periods (OFFC).

Previous studies have shown that these Doppler diastolic indices have satisfactory reproducibility with a relatively low intraobserver and interobserver variabilityF2 Statistical Analysis

Data were expressed as mean (2SD) and examined by linear correlation analysis. Statisticalsignificanceof differences in various Doppler diastolic indices between sexes were determined by the Student’s unpaired t test and those among seven age groups by the one-way analysis of variance. Correlations between age, body surface area, heart rate, fractional shortening, and left ventricular mass with Doppler indices of left ventricular diastolic performance were assessed by stepwise multivariate regression analysis. All values were taken as significant only if p c 0.001.

Results The instantaneous transmitral inflow velocity revealed a biphasic pattern including an early diastolic filling wave followedby a late atrial filling wave. Mean ( f 2 SD) values for 15 direct and 11 derived parameters were analyzed from this inflow velocity wave form (Tables I and II). No statistically significant (p c 0.01) differences were observed between males and females for any of these parameters. Age was found to have a positive linear correlation with area of atrial filling period (AA), early diastolic period (OF), time to peak early diastolic period (CE), atrial

430 f 94 44f 17 72 f 28

462 f 224 249 f 34

7. 8.

9. 10. 11.

12.

465 f 190

163f 80 458 f 194

235 f 88

485 f 244

430 f 96 43 f 16 74 f 27

164f68 478 f 182

419 f 150 237 f 82

430 f 92 4 5 f 19 69 f 28

94 f 38

0.08 f 0.04

0.04 f 0.02 0.06 f 0.04

0.09 f 0.03 94 f 25

0.09 f 0.04

0.04 f 0.02 0.07 f 0.04

340f 132 203 f 56 136f 98 541 f 137

39f9 68 f 39

376 f 77

0.09 f 0.04 0.04 f 0.01 0.06 f 0.04 0.08 f 0.04 81 f 16

0.12 f 0.04

58 f 16

91 f 2 4

I (n=10)

II

148 f 56 536 f 143

230 f 58

438 k 224

430 f 66 4 6 f 12 7 2 f 18

0.09 f 0.04 0.04 f 0.02 0.08 f 0.04 0.10 f 0.04 97 f 23

53 k 16 0.14 f 0.04

88 f 24

(n=10)

0.04 f 0.02 0.08 f 0.06 0.10 f 0.04 102 f 26 428 f 82 51 f 2 1 69 f 26 474 f 268 245 f 64 165 f 82 510f 168

0.10 f 0.04

5 2 f 16 0.14 f 0.06

+ 16

+ +

0.09 f 0.04 0.04 f 0.02 0.07 f 0.04 0.09 f 0.04 96 f 23 425 f 108 42+ 14 71 +34 490 f 176 262 f 68 176 80 476 152

0.14 f 0.06

51

79 +- 22

86 +- 36

N (n=23)

(n=14)

m

Age group

176 f 55 430 f 127"

272 f 76

501 f 192

0.09 f 0.04 0.05 f 0.02 0.07 f 0.04 0.09 f 0.04 100f28 447f91 4 5 f 15 7 4 f 16

5 6 f 18 0.14 f 0.06

78 26

*

V (n=15)

VI

264f 139

476 f 235

43f 14 77 f 32

455 f 76

0.07 f 0.06 89 f 24

0.06 f 0.04

0.05 f 0.02

0.08 f 0.04

0.13 f 0.06

57 k 16

62 f 28ebsc

VII (n=10)

162 f 68 157 f 65 382 f 184ab 368 f 1W"'

236 f 95

451 f 227

447 f 58 3 9 f 17 76 f 27

0.08 f 0.04 0.04 f 0.02 0.06 f 0.04 0.07 f 0.03 82 f 26ac

0.12 f 0.04

5 6 f 15

67 f 24ab

(n=lO)

compared with age group N. Abbreviath~:E = peak velocity of early diastolic filling wave; A =peak velocity of atrial filling wave; TA = total diastolic area; EA = area of early fillingperiod, AA = m a of atrial fillhg period; oU3 =One-thirdfilling area; OCT;! = one-half fillingarea; OEBECE= time to peak early diastolic velocity; E a = acceleration half time; EE2= deceleration half time; OC =total diastolic time period,OF =early diastolic period,FC = atrial filling period, EF =deceleration slope.

ap

Values are expresed as meauf2 SD.

Pulsed Doppler echocardiographic indices of left ventricular diastolic function in normal subjects.

To establish the normal limits for various pulsed Doppler echocardiographic indices of left ventricular diastolic function, 92 healthy volunteers aged...
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