Left ventricular filling at elevated diastolic pressures: Relationship between transmitral Doppler flow velocities and atrial contribution The relationship between transmitral Doppler blood flow velocities and atrial contribution to left ventricular (LV) filling was investigated in seven open-chest dogs. At LV filling pressures greater than 15 to 20 mm Hg, LV volume approaches a maximum. Thus we hypothesized that when LV pressure before the onset of atrial systole exceeds this level, the atrial contribution would decrease and the ratio between peak early (E) and atrial-induced (A) mitral velocities would increase. Atrial contribution w a s measured as LV diameter increase during atrial contraction expressed as a percentage of the total LV diameter change during diastole (sonomicrometry). When left ventricular end-diastolic pressure (LVEDP) was progressively increased from 10 • 1 (mean • standard deviation) to 28 • 3 mm Hg by intravenous saline solution, the atrial contribution decreased from 3 4 • 1 4 % to 8 • 1 0 % (p < 0.001). Concomitantly the A velocity decreased from 39 • 7 to 24 • 8 cm 9 sec -1 (p < 0.01), and the E / A ratio increased from 1.8 • 0.3 to 3.6 • 1.5 (p < 0 . 0 0 1 ) . The E / A ratio and the atrial contribution were constant until LVEDP e x c e e d e d 17 to 20 mm Hg, at which level marked changes in both parameters were noted. Thus when LV filling pressure was increased, the E / A ratio increased, indicating a filling shift towards early diastole. The reduced atrial contribution during increased preload was explained by the curvilinear shape of the LV pressure-volume curve. At markedly elevated filling pressures, near-maximum LV diameter was achieved before atrial contraction; hence the atrial contribution decreased and the E / A ratio increased. Caution should therefore be exercised when the E / A ratio is used to evaluate diastolic performance at elevated filling pressures. (AM HEART J 1990; 1 1 9 : 6 2 0 . )

Yngvar Myreng, MD, Otto A. Smiseth, MD, PhD, and Cecilie Ris~te, MD.

Oslo, Norway There has been increasing interest in the use of Doppler echocardiographic indices of transmitral blood flow for evaluation of left ventricular (LV) diastolic function. In particular, the ratio between early (E) and atrial-induced (A) peak velocities (E/A ratio) has been used to assess the relative magnitude of early and late LV filling. In a wide variety of cardiac disease states the E/A ratio deviates from that found in normal individuals. 1-6 Such abnormalities of the E/A ratio have been ascribed to underlying abnormalities in LV diastolic function. 2, 7, SAn increased E/A ratio, reflecting decreased LV filling during atrial systole, has been proposed to indicate elevated LV diastolic From the Institute for Surgical Research and Medical Department B, Rikshospitalet, University of Oslo. Supported by a research fellowship from the Norwegian Council on Cardiovascular Research (Dr. Myreng). Received for publication June 20, 1989, accepted Oct. 10, 1989. Reprint requests: Yngvar Myreng, MD, Medical Department B, Rikshospitalet, N-0027 Oslo 1, Norway. 4/1/17964

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pressure,9,10 although the data are conflicting. 11, 12 A priori it seems reasonable to expect that the E/A ratio will be influenced by altered LV diastolic chamber stiffness (dp/dv). Changes in chamber stiffness may reflect changes in the diastolic pressurevolume relationship resulting from changes in intrinsic myocardial properties or in extraventricular pressure. However, because of the curvilinear shape of the LV pressure-volume curve, chamber stiffness increases with increasing LV volume. 13 Accordingly, it seems possible that the E/A ratio may be influenced by changes in preload, per se, in the absence of changes in the LV pressure-volume curve. Results of a study by Boettcher et al. 13 showed in a chronic canine preparation that LV volume approached maximum levels at moderately elevated filling pressures. The present study investigated the hypothesis that the atrial contribution to LV filling depends on the LV pressure before the onset of atrial contraction (pre-A wave pressure) and that the atrial contribution will decrease when the steep portion of

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Fig. 1. Examples of Doppler spectra of transmittal flow velocities at LVEDP values 12 and 24 mm Hi. E and A depict early and atrially induced velocity peaks, respectively.

the LV pressure-volume curve is reached. Accordingly we would expect the A velocity to decrease a n d the E / A ratio to increase when filling pressure was m a r k e d l y elevated. T h e experiments were done in acutely i n s t r u m e n t e d anesthetized dogs. METHODS Animal preparation. The experiments were done in

seven dogs weighing 26 _~ 3 kg (range 21 ~o 30 kg). Anesthesia was induced with thiopental and continued with intravenous injections of morphine (50 to 100 mg/hr) supplemented with sodium pentobarbital as needed. The lungs were ventilated with room air by means of a Servo Ventilator 900B (Siemens Elema, Stockholm, Sweden). Blood gases and body temperature were kept within physiologic limits. The chest was opened through a median sternotomy, and the pericardium was left open and the lungs held away from the heart during the recordings. The subendocardial anteroposterior LV diameter was measured by sonomicrometry (Sonomicrometer 120, Triton Technology, Inc., San Diego, Calif.). To achieve a faceto-face position of the crystals, they were positioned with a steel spear (2 mm in diameter) that was pierced through the anterior and posterior LV walls. The spear was introduced just to the left of the left anterior descending artery and traversed the assumed greatest LV diameter at the level of the papillary muscles. In one dog the septum-free wall diameter was also measured, which allowed calculation of the LV cross-sectional area index by multiplication of the two diameters. At the end of the experiment proper positioning of the crystals was verified by autopsy. Through peripheral vessel incisions a high-fidelity catheter (Millar Instruments, Houston, Tex.) and a fluid-filled

reference catheter were placed in the left ventricle. A fluid-filled catheter was advanced to the ascending aorta. The fluid-filled catheters were Connected to AE 840 transducers (SensoNor, Horten, Norway). Left atrial pressure was recorded with a high-fidelity catheter (Millar Instruments, Houston, Tex.) that was inserted through the left atrial appendage and referenced against LV pressure such that the pressure curves overlapped during long diastases. Both external jugular veins were cannulated to allow for rapid volume infusion. The pressure tracings and ECGs were printed on paper at a speed of 200 m m . sec -1 by means of a Gould recorder 2600 S (Gould, Inc., Test & Msmt. Rec. Syst. Div., Cleveland, Ohio). Doppler echocardiography. A dedicated Doppler instrument (SD-100, Vingmed Sound, Horten, Norway) with

a 3 MHz probe was used for Doppler measurements. During acquisition of data the dog was placed in the semilateral left decubitus position. The Doppler probe was applied manually directly on the apex. Continuous-wave mode was used to locate the highest velocities and thus align the ultrasound beam parallel to the flow direction, whereas pulsed-wave mode was used for recording the signals. The sample volume was cylindrically shaped and measured approximately 7 mm in diameter and 7 mm in length in the measuring depth (40 to 60 mm). The sample volume was placed in the depth at which the spikes produced by mitral opening were most distinctly seen in the Doppler spectrum and amplitude tracing: this corresponds to the tip of the mitral valve. 14 Position and angulation of the probe were adjusted to optimize the signals as judged from the spectral display and the audible Doppler shift. Care was taken to display a narrow-band spectrum with distinct velocity peaks at early inflow and at atrial contraction (Fig. 1). We have previously reported that reproducible measurements

March 1990

622

Myreng, Smiseth, and Risc~e

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LVP ( m m H g ) Fig. 2. Left ventricular (LV) dimensions and E/A ratios at various levels of LV diastolic pressures in representative dog. Lower panel shows relationship between LV diameter and LV pressure (LVP) before atrial contraction (pre-A wave P) and at end diastole (LVEDP). Upperpanel shows E/A ratio at corresponding LVEDP.

of transmittal filling indices can be achieved by this technique in patients} 5 In a similar dog preparation no significant difference between paired measurements of Doppler indices was found at baseline, the percentage difference ranging from 6 + 4 % to 12 z 7 % .16 All Doppler recordings were videotaped. P r o c e d u r e . To reduce reflex-mediated changes in cardiac contractility during volume loading, propranolol, 1 m g . kg -1, was injected intravenously. Then, at least 10 minutes after the injection of propranolol, left ventricular end-diastolic pressure (LVEDP) was progressively increased by several steps of rapid infusion of saline solution. Pressures, sonomicrometry, and Doppler signals were recorded at four to eight increasing levels of LVEDP. All data were acquired during suspension of ventilation for 15 to 30 seconds. LV pressure was recorded continuously to ensure that LVEDP remained constant throughout each recording session. Doppler and sonomicrometry data had to be acquired separately because of acoustic interference. First, pressures and Doppler signals were recorded. Then the Doppler probe was removed, and pressures and sonomicrometry data were recorded immediately thereafter. The time inerval between Doppler and sonomicrometry recordings was less than 5 seconds. Only data obtained during unchanged LVEDP were used for further analysis. D a t a analysis and calculation

Doppler measurements. The Doppler measurements

were done with the analysis system of SD-100 by replaying the sound track from the videotape. This yields highquality Doppler signals identical to the real-time recordings. The velocities during the early transmitral flow (E) and during atrial contraction (A) were measured at the peaks (Fig. 1). Deceleration time was measured as the interval from E to the zero line crossing of the straight line through E and a point halfway down the following slope. At least four consecutive beats were averaged. Pressures. LV diastolic pressures were measured immediately before the rapid upstroke in the LV pressure tracing (LVEDP) and immediately before the pressure increase caused by the atrial contraction (pre-A wave pressure). Left atrial pressure was measured at the time of pressure crossover (PCO) between the LV and left atrial pressure tracings. Furthermore, the maximum atrioventricular pressure gradient was measured during early inflow and during atrial contraction. Systolic and diastolic blood pressures were measured from the aortic pressure tracing. Sonomicrometry. LV diameter was measured at minimum dimension (Drain), at the start of the atrially induced pressure increase in the LV pressure tracing (DpreA), and at end diastole (Ded). Atrial contribution (AC) to LV filling was calculated as the diameter increase during atrial contraction expressed as a percentage of the total diameter change during LV filling according to the formula: AC = (Ded - DpreA) / (Ded - Dmin) " 100%. S t a t i s t i c s . The results are presented as mean + 1 standard deviation. Data from the various experiments were grouped according to the level of LVEDP, and differences between groups were analyzed by two-way analysis of variance. Individual data were analyzed by linear regression analysis (least squares). A p value less than 0.05 was considered statistically significant. RESULTS

A total of 10 separate loading experiments were performed. T h e Doppler and h e m o d y n a m i c variables within the various groups of L V E D P are s u m m a r i z e d in Table I. A representative single experiment is shown in Fig. 2. Transmitral velocities. During increasing L V diastolic pressures caused by the saline infusion, the E velocity increased and A velocity decreased (Table I). As a result the E / A ratio increased exponentially with the progressively increasing p r e - A wave LV pressure: logE/A = 0.15 + 0 . 0 2 . P (r = 0.66; p < 0.001) (Fig. 3). Only minor changes in the E / A ratio were seen at n o r m a l and m o d e r a t e l y elevated L V E D P s . However, when L V E D P and the p r e - A wave pressure exceeded 17 to 20 m m Hg a n d 13 to 17 m m Hg, respectively, the E / A ratio increased m a r k e d l y (Fig. 4). Deceleration time decreased progressively with increasing L V E D P (Table I). Atrial contribution t o LV filling. W h e n L V E D P was progressively increased within the normal a n d moderately elevated range, the atrial contribution mea-

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Table I. Doppler parameters and hemodynamic data during volume loading L V E D P range (ram Hg) 9-12 (n = 9) E(cm s e c -1) A ( c m s e c -1) E/A ratio Deceleration time (msec) AC (%) LVEDD (mm) LVEDP (mm Hg) Pre-A wave P (mm Hg) PCO (ram Hg) APE (mm Hg) APA(mmHg) SBP (mm Hg) DBP (mm Hg) H R ( b e a t s 9 m i n -1)

70z 5 39z 7 1.8 z 0.3 116 z 9 34 _ 14 4 2 _+ 11 10 z 1 7 _~ 1 13 z 2 7 z 2 3 z 2 1 1 0 ~- 17 63 _~ 7 1 0 6 z 12

13-16 (n = 10) 74 z 37_~ 2.1 _~ 113 z 31 ~43 z 14 _~ 10 _~ 18 _+ 8 _~ 4_~ 113 z 64 z 111 _

14 11 0.3 24 13 8 1 2 3 2 2 15 9 14

17-20 (n = 10) 7 9 - ~ 18 4 0 z 10 2.0 z 0.5 103 z 14 36 z 19 4 4 ~- 10 19 z 1 13 ~- 2 2 3 _+ 4 8 -~ 3 2_~ 1 109 _~ 24 6 6 z 15 1 1 0 z 17

21-24 (n = 9) 88 29 3.3 99 15 46 23 17 32 12 3 125 71 118

z 11 z 10 z 1.2 • 32 _~ 7 _* 13 • 1 z 2 z 6 z 5 z 1 z 6 z 11 z 4

>25 (n = 8)

F ratio

p Val u e

8 0 _ ~ 16 24z 8 3.6 + 1.5 91 ___ 26 8 _~ 10 4 6 _ 15 2 8 _~ 3 23 _~ 3 36 _~ 4 10 _ 5 2 z 1 1 0 6 _~ 22 67 z 14 107 _~ 23

4.3 4.9 8.8 4.9 7.7 0.2 187.2 75.5 44.1 5.8 2.4 0.9 0.4 1.l

Left ventricular filling at elevated diastolic pressures: relationship between transmitral Doppler flow velocities and atrial contribution.

The relationship between transmitral Doppler blood flow velocities and atrial contribution to left ventricular (LV) filling was investigated in seven ...
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