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Left Ventricular End-Diastolic Pressure Can Be Estimated by Either Changes in Transmitral Inflow Pattern During Valsalva Maneuver or Analysis of Pulmonary Venous Flow
Left Ventricular End-Diastolic Pressure Can Be Estimated by Either Changes in Transmitral Inflow Pattern During Valsalva Maneuver or Analysis of Pulmonary Venous Flow Hans Peter Brunner-La Rocca, MD, Hans Rickli, MD, Christine Helena Attenhofer Jost, MD, and Rolf Jenni, MD, MSEE, Zurich, Switzerland
We directly compared the transmitral inflow pattern during preload reduction and pulmonary venous flow velocities to determine left ventricular end-diastolic pressure (LVEDP) in 78 patients who underwent left heart catheterization. Transmitral inflow indexes (A-wave duration, ratio of peak flow velocity of early diastole [E] to peak flow velocity of late diastole during atrial contraction [A] [E/A ratio]) at rest and during the Valsalva maneuver (30 mm Hg for 15 seconds) and indexes of pulmonary venous flow (velocity and duration of the atrial reversal) were obtained. Fair correlations existed between LVEDP
(mean 15 ± 6 mm Hg) and the percentage decrease in the E/A ratio (r = 0.72), increase in duration of A wave during the Valsalva maneuver (r = 0.60), flow velocity of atrial reversal (r = 0.58), and difference of duration of atrial flow reversal and A wave (r = 0.62) (all P < .001). While sensitivity, specificity, and diagnostic accuracy to detect an elevated LVEDP were comparable, technically adequate Doppler recordings were obtained more often for the mitral inflow during the Valsalva maneuver than for the pulmonary venous flow (72 versus 66 patients, P < 0.05). (J Am Soc Echocardiogr 2000;13:599-607.)
INTRODUCTION Pulsed wave Doppler mitral flow velocities are being used to assess left ventricular diastolic function in cardiac disease.Three different abnormal patterns of mitral filling have been described (impaired relaxation, pseudonormalization, and restriction).1 Diastolic dysfunction leads firstly to a relaxation abnormality with a decreased ratio of peak flow velocity of early diastole (E) to peak flow velocity and duration of late diastole during atrial contraction (A) (E/A ratio) and increased deceleration and isovolumetric relaxation times. Progression of diastolic dysfunction with a successive increase in left-sided filling pressures makes Doppler echocardiography indexes of mitral flow return to “normal” (“pseudonormaliza-
From Echocardiography Laboratory, Division of Cardiology, University Hospital, Zurich, Switzerland. Reprint requests: H. P. Brunner-La Rocca, MD, Division of Cardiology, University Hospital, Rämistrasse 100, 8091 Zurich, Switzerland (E-mail: [email protected]). Copyright © 2000 by the American Society of Echocardiography. 0894-7317/2000 $12.00 + 0 27/1/106077 doi:10.1067/mje.2000.106077
tion”). Further progression of diastolic filling pressure then leads to a restrictive pattern.This inevitably weakens any correlation between Doppler echocardiography indexes of mitral flow and left ventricular end-diastolic pressure (LVEDP).2 Thus, more recent attempts have been made to increase diagnostic accuracy in the prediction of elevated left ventricular pressure and diastolic function. Assessment of pulmonary venous flow velocities has been shown to be useful for predicting elevated leftsided filling pressures and has added to the understanding of diastolic dysfunction.3-5 However, proper recording, especially of atrial flow reversal, may be difficult and time consuming,4 though a recent report suggests that it can be obtained in up to 90% of unselected patients.6 Maneuvers that reduce preload such as the Valsalva maneuver or nitroglycerin have been found to be useful in determining diastolic dysfunction.2,7,8 However, changes in mitral inflow with preload reduction have not been directly compared with pulmonary venous flow velocity for assessing elevated filling pressures. Therefore, the goal of our study was to prospec599
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tively compare the feasibility and accuracy of changes in the transmitral inflow pattern induced by the Valsalva maneuver with measurements of the pulmonary venous flow profile in the diagnosis of elevated left ventricular end diastolic pressure. Furthermore, we hypothesized that an increase in duration of the mitral inflow A wave induced by the Valsalva maneuver may be an additional sign of diastolic dysfunction.
METHODS Study Population Eighty patients (mean age 62 ± 9 years) with stable sinus rhythm who underwent diagnostic cardiac catheterization for suspected coronary artery disease were consecutively evaluated. Seventeen patients (21%) were women and 63 (79%) were men. Excluded from the study were patients with unstable angina or acute myocardial infarction, significant valvular heart disease (moderate to severe regurgitation or stenosis), valve prosthesis, frequent supraventricular or ventricular arrhythmias, severe chronic obstructive lung disease or fusion of the E and A waves (minimal middiastolic flow velocity more than one third of E velocity at baseline). Echocardiography Within 30 minutes before coronary angiography, a complete 2-dimensional (2D) and pulsed wave Doppler echocardiography examination was performed with a Vingmed CFM 750 (Vingmed Sound, Horten, Norway) echocardiographic system with use of standard parasternal and apical views in the fasting patients. From the parasternal long-axis views, M-mode recordings were made and digitally saved on a Macintosh (Apple Computer Inc, Cupertino, Calif) computer. The following measurements were calculated off-line: left ventricular end-systolic and end-diastolic dimensions (LVEDD), left ventricular septal (LVS) and posterior wall (PW) thicknesses, and left atrial dimension.The left ventricular muscle mass index was calculated with the formula muscle mass (in grams per square meter) = 0.8 × 1.04 × [(LVEDD + LVS + PW)3 – (LVEDD)3] / body surface area.9 The pulsed Doppler signal was obtained by placing the sample volume between the tips of the mitral valve leaflets controlled by 2D echocardiography in the apical 4-chamber view. In accordance with recently published guidelines,10 peak flow velocity of early diastole (E) and peak flow velocity and duration of late diastole during atrial contraction (A) were recorded and the E/A ratio calculated. Usually, distinction between the A wave and lowvelocity flow in early systole was possible. However, replacement of the sample volume was necessary in a few
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patients. In addition, deceleration time and isovolumetric relaxation time at baseline were measured.All parameters were digitally recorded and calculated off-line. Mean values were obtained by averaging 4 beats during quiet respiration. Pulmonary venous flow velocities were obtained by placing the sample volume 1 to 2 cm into the upper or lower right pulmonary vein from a slightly anterior angulated 4-chamber view. Velocity filter as well as width and position of the sample volume were set as previously described.10 Velocity and duration of atrial flow reversal were digitally recorded and calculated off-line. Values were obtained by averaging 4 beats during quiet respiration. Finally, E/A ratio and duration of the A wave were measured by averaging the last 2 beats immediately before release of the strain of the Valsalva maneuver.The patients were carefully instructed in the performance of the Valsalva maneuver. Before the measurements, the patients were asked to initiate and maintain the strain 15 to 20 seconds after normal inspiration by forcefully exhaling into a tube connected to a sphygmomanometer. The straining pressure was controlled to be 25 to 35 mm Hg. A tiny air leak was placed in the tube to ensure that airway pressure was produced from the thoracic cavity and not the pharynx. The Doppler sample was repositioned during the Valsalva maneuver by 2D echocardiography control to obtain valid recordings. The maneuver was repeated until 2 satisfactory recordings were obtained. Comparisons between the recordings did not reveal a significant difference. Because of fusion of the E and A waves caused by increased heart rate during the Valsalva maneuver in some patients, particular care was taken to avoid underestimation of A-wave duration by comparing echocardiographic recordings with the electrocardiogram before and during the Valsalva maneuver.Thus the time from the onset of the P wave of the electrocardiogram to the onset of the mitral A wave during the Valsalva maneuver was compared with that at rest. All the echocardiographic examinations were performed and measured by the same examiner (H.P.B.), who was blinded to the results of the catheterization. Coronary Angiography Left ventriculography and coronary angiography were performed from the femoral approach with standard techniques.The LVEDP was recorded on paper with a speed of 200 mm/s and a pressure range of 40 mm Hg before administration of any contrast dye with use of a 6F fluidfilled pigtail catheter connected to a pressure transducer. It was obtained by averaging pre-a (pressure before atrial contraction) and post-a (pressure before ventricular contraction) values throughout a cycle of quiet respiration. A pre-a LVEDP of ≥10 mm Hg and a post-a pressure of ≥15 mm Hg were considered to be elevated.3 In 2 (3%)
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Table 1 Clinical 2-dimensional echocardiography and angiographic characteristics in patients with normal and elevated pre-a and/or post-a LVEDP LVEDP LVEDP normal elevated (42 patients) (36 patients)
Age (y) Men Heart rate at rest (bpm) Difference in heart rate rest to VM (bpm) Body mass index (kg/m2) Ejection fraction End-diastolic volume index (mL/m2) LV muscle mass index (g/m2) Left atrial size (cm) LV end-diastolic diameter (cm) Coronary artery disease Arterial hypertension Previous myocardial infarction
63 ± 9 35 (83%) 57 ± 10 10.4 ± 8.7
59 ± 9 27 (75%) 62 ± 10 6.9 ± 8.2
26.4 ± 3.9 26.5 ± 2.9 0.64 ± 0.10 0.56 ± 0.16 96 ± 27 122 ± 51
P value
.06 >.1 .05 .05 >.1 .01 .007
102 ± 28
113 ± 42
>.1
4.0 ± 0.6 5.2 ± 0.8
4.3 ± 0.6 5.3 ± 1.0
.07 >.1
35 (83%) 7 (17%) 9 (21%)
34 (94%) 5 (14%) 25 (69%)
>.1 >.1 <.001
Numerals indicate number of patients unless otherwise specified. pre-a, Pressure before atrial contraction; post-a, pressure before ventricular contraction; LVEDP, left ventricular end-diastolic pressure; VM, Valsalva maneuver; LV, left ventricular.
patients, assessment of LVEDP was inaccurate because of inadequate pressure tracings; these patients were excluded from further analysis. Left ventricular end-diastolic and end-systolic volumes were obtained, and the ejection fraction was calculated with the biplane area-length method. All these measurements were performed by one examiner who was blinded to the echocardiographic results (H.R.). Statistical Analysis Data are presented as frequencies or means ± standard deviations or standard error as indicated. Doppler echocardiography parameters were correlated to LVEDP with the Spearman rank correlation. Comparison between groups were made with the chi-square test, the student t test, or Mann-Whitney U test as appropriate. Sensitivity, specificity, positive and negative predictive values, as well as diagnostic accuracy (percentage of correct classification) to detect an elevated LVEDP (either pre-a or post-a) were assessed with use of cut-off points previously found to be good indicators of an elevated LVEDP. In addition, area under curve was calculated by receiver operating characteristic curves (sensitivity versus 1-specificity) to compare Doppler echocardiography parameters detecting an elevated LVEDP.11 A P value of less than .05 was considered statistically significant. All calculations were performed with a commercially available statistical package (SPSS for Windows 6.0, Cary, NC).
Figure 1 Relation between post-a LVEDP and decrease in the E/A ratio and duration of A wave during Valsalva maneuver. E/a ratio, Ratio of peak flow velocity of early diastole to peak flow velocity and duration of late diastole during atrial contraction; post-a, pressure before ventricular contraction; LVEDP, left ventricular end-diastolic pressure.
RESULTS Table 1 lists the clinical, 2D echocardiography, and angiographic data of the 78 patients with normal and elevated post-a LVEDP. Mean pre-a LVEDP was 8.1 ± 3.5 mm Hg (range 2 to 22 mm Hg) and mean post-a LVEDP was 14.6 ± 5.8 mm Hg (range 4 to 31 mm Hg). Pre-a LVEDP was elevated in 22 (30%) patients and post-a in 34 (44%). Pre-a and/or post-a LVEDP was elevated in 36 patients (46%); in these patients, ejection fraction was significantly lower, left ventricular end-diastolic volume index increased, and heart rate at rest higher. In addition, they more often had a history of myocardial infarction. Of the 78 patients, 5 (6%) had technically inadequate recordings of both transmitral inflow during the Valsalva maneuver and pulmonary venous flow, 1 (1%) had technically inadequate recordings of transmitral inflow pattern during the Valsalva maneuver only, and 7 (9%) had technically inadequate recordings of atrial flow reversal in the pulmonary vein only. Thus 72 of 78 (92%) patients had adequate recordings of mitral flow before and during the Valsalva maneuver, and 66 patients (85%) had adequate recordings of pulmonary venous flow (P < .05). There were fairly weak correlations of LVEDP with the isovolumetric relaxation time (pre-a: r = –0.32, P < .01; post-a: r = –0.29, P < .05), the deceleration time (pre-a: r = –0.43, P < .001; post-a: r = –0.34, P < .01), and the E/A ratio (pre-a: r = 0.33, P < .01; posta: r = 0.30, P < .05).
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Figure 2 Transmitral flow velocity profiles at baseline (A) and during Valsalva maneuver (B) and pulmonary venous flow profile (C) in a patient with normal LVEDP (pre-a 4 mm Hg, post-a 5 mm Hg; upper panel) and in a patient with elevated LVEDP (pre-a 13 mm Hg, post-a 22 mm Hg) and pseudonormal transmitral inflow pattern at rest (lower panel). Duration of A wave and atrial reversal in ms; flow velocity in m/s. E/A, Ratio of peak flow velocity of early diastole to peak flow velocity and duration of late diastole during atrial contraction; LVEDP, left ventricular end-diastolic pressure; pre-a, pressure before atrial contraction; post-a, pressure before ventricular contraction.
As shown in Table 2, the correlations between post-a LVEDP and atrial reversal in the pulmonary vein as well as the extent of changes in transmitral inflow pattern during the Valsalva maneuver were moderately good, whereas correlations between prea LVEDP and the Doppler echocardiographic indexes were generally weaker. Reanalysis of the data after accounting for the mitral inflow velocity at the onset of atrial contraction (E at A) did not significantly change the correlation between percentage decrease of E/A ratio during the Valsalva maneuver and pre-a (r = 0.56, P < .001) and post-a LVEDP (r = 0.74, P < .001). Figure 1 depicts the good correlation between the post-a LVEDP and the changes of the E/A ratio and the duration of the A wave during the Valsalva maneuver. The comparison of the absolute mean values of the Doppler indexes of mitral inflow and pulmonary venous flow in patients with normal and elevated pre-a and/or post-a LVEDP are shown in Table 3. Sensitivity, specificity, positive and negative pre-
dictive values, as well as diagnostic accuracy of atrial reversal and transmitral inflow during the Valsalva maneuver to detect an elevation of pre-a and/or post-a LVEDP are shown in Table 4 (all P < .001).The area under the receiver operating characteristic curves (±SE) of the changes in E/A ratio (0.89 ± 0.04) and duration of A wave (0.83 ± 0.05) during the Valsalva maneuver were comparable to the flow velocity of atrial reversal in the pulmonary vein (0.85 ± 0.05) and the difference between the duration of A wave at rest and atrial reversal (0.85 ± 0.05). Sensitivity, specificity, and diagnostic accuracy of all 4 Doppler echocardiography indexes were separately analyzed in patients with an E/A ratio within the normal range of 1.0 to 2.0 (n = 35, 47%) and in those with a possible impaired relaxation pattern (with an arbitrary threshold of E/A ratio < 1.0, n = 35, 47%). Of those with a normal E/A ratio, 15 (43%, Figure 2, upper panel) had a normal and 20 (57%, Figure 2, lower panel) a pseudonormal (elevation of pre-a and/or post-a LVEDP) transmitral inflow pat-
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Table 2 Spearman rank correlation (r) between Doppler echocardiography indexes and post-a LVEDP
Pre-a Post-a
%↓ in E (n = 72)
%↓ in A (n = 72)
%↓ in E/A (n = 72)
↑ of A (n = 72)
AR in PV (n = 66)
∆AR-A (n = 66)
0.34* 0.53†
–0.46† –0.37*
0.57† 0.72†
0.46† 0.60†
0.33* 0.58†
0.43† 0.62†
post-a, Pressure before ventricular contraction; LVEDP, left ventricular end-diastolic pressure; pre-a, Pressure before atrial contraction; %↓, percentage of decrease during the Valsalva maneuver; E, E wave; A, A wave; ↑, increase in duration during the Valsalva maneuver; E/A, ratio of peak flow velocity of early diastole to peak flow velocity and duration of late diastole during atrial contraction; AR, flow velocity of atrial reversal; PV, right lower pulmonary vein; ∆ARA, difference in duration of atrial reversal and A wave. *P < .01. †P < .001.
Table 3 Doppler echocardiography indexes in patients with normal and elevated pre-a and/or post-a LVEDP LVEDP Normal, n = 39 (PV n = 36)
E/A ratio Deceleration time (ms) Isovolumetric relaxation time (ms) Change in E wave during VM (%) Change in A wave during VM (%) Change in E/A ratio during VM (%) Change in corr E/A ratio during VM (%) Change in duration of A wave from rest to VM (ms) Flow velocity of atrial reversal in PV (cm/s) Difference between duration of atrial reversal in PV and A wave at rest (ms)
1.0 237 96 –33 –10 –23 –15 –4 29 –19
± ± ± ± ± ± ± ± ± ±
0.4* 84† 22* 10‡ 21* 15‡ 19‡ 14‡ 5‡ 22‡
Elevated, n = 33 (PV n = 30)
1.3 186 85 –46 2 –46 –43 12 37 9
± ± ± ± ± ± ± ± ± ±
0.7 77 19 13 19 13 14 12 6 20
Numbers are mean ± SD. pre-a, Pressure before atrial contraction; post-a, pressure before ventricular contraction; LVEDP, left ventricular end-diastolic pressure; corr, denotes corrected for mitral flow velocity at the onset of atrial contraction (E at A); PV, right upper pulmonary vein; VM, Valsalva maneuver. *P < .05. †P < .01. ‡P < .001.
Table 4 Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of Doppler echocardiography indexes in the detection of an elevated pre-a and/or post-a LVEDP
Sensitivity Specificity Positive predictive value Negative predictive value Diagnostic accuracy
↓ of E/A ratio ≥40% during VM (n = 72)
Any ↑ in dur of A during VM (n = 72)
Flow ≥0.35 m/s of AR in PV (n = 66)
Dur AR > dur A (n = 66)
76% 92% 89% 81% 85%
88% 84% 83% 84% 86%
67% 94% 91% 77% 82%
70% 89% 84% 81% 80%
All values shown are percentages. pre-a, Pressure before atrial contraction; post-a, pressure before ventricular contraction; LVEDP, left ventricular end-diastolic pressure; ↓, decrease; E/A ratio, ratio of peak flow velocity of early diastole to peak flow velocity and duration of late diastole during atrial contraction; VM, Valsalva maneuver; ↑, increase; AR, atrial reversal; PV, pulmonary vein; dur, duration; A, A wave.
tern. Separation of patients with a pseudonormal transmitral inflow pattern from those with a normal pattern was possible with an acceptable diagnostic accuracy by all Doppler echocardiography indexes (decrease of E/A ratio ≥40% [sensitivity, specificity, and diagnostic accuracy: 80%, 87%, 83%, respectively] and increased A wave during the Valsalva maneuver [80%, 71%, 76%], velocity of atrial flow reversal ≥0.35
m/s [77%, 86%, 81%], duration of atrial flow reversal > duration A wave [78%, 86%, 82%], P > 0.1 between different Doppler echocardiography parameters). Given the past literature on the subject,7 we further assessed the use of a decrease in the E/A ratio of < 1.0 during the Valsalva maneuver as an indicator of a pseudonormal pattern (ie, elevated LVEDP). Whereas sensitivity was good (ie, 90%), specificity
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was only 27% (diagnostic accuracy 63%). Finally, in the patients with a baseline E/A ratio of < 1.0, an elevated pre-a and/or post-a LVEDP (n = 11, 31%) was detected with an acceptable diagnostic accuracy. In this group, sensitivity, specificity, and diagnostic accuracy tended to be higher for changes in transmitral inflow pattern during the Valsalva maneuver (decrease of E/A ratio ≥40%: 73%, 96%, 88%, respectively; increased A wave during the Valsalva maneuver: 100%, 91%, 94%, respectively) than for atrial flow reversal in the pulmonary vein (velocity of atrial flow reversal ≥0.35 m/s: 46%, 100%, 81%, respectively; duration of atrial flow reversal > duration A wave: 55%, 90%, 77%, respectively) (P = .08).
DISCUSSION In our prospective and direct comparison of echocardiographic estimation of LVEDP, the diagnostic accuracy of changes of transmitral inflow pattern induced by the Valsalva maneuver was found to be comparable to that obtained by analysis of atrial flow reversal in the pulmonary vein. Both methods were equally useful in the differentiation of patients with normal and elevated LVEDP, with a diagnostic accuracy ranging from 80% to 86%. In addition, it was possible to distinguish patients with a normal transmitral inflow pattern from those with a pseudonormal pattern with a diagnostic accuracy of > 80%. However, feasibility was significantly higher for the assessment of the transmitral inflow pattern during the Valsalva maneuver than for the obtainment of an adequate recording of atrial flow reversal in the pulmonary veins in our patient group. Knowledge of left ventricular filling pressures is important for diagnosis, prognosis, and treatment of patients with cardiac disease.12,13 Because one third of patients with congestive heart failure have normal systolic left ventricular function,14 assessment of diastolic function is extremely important. Pulsed wave Doppler variables of the transmitral inflow have been proposed as a noninvasive method for assessing left ventricular diastolic function.The ratio of transmitral flow velocities (E/A ratio), deceleration time, and isovolumetric relaxation time have all been reported to accurately predict elevated left ventricular filling pressure in patients with decreased ejection fraction.1,15 In patients with a normal or only slightly reduced ejection fraction, however, these parameters are of less value,15 as shown in the current study group, in which only 12% of patients had an ejection fraction below 0.45. In addition to methods such as color M-mode flow
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propagation velocity from base to apex16,17 and 2D echocardiography determination of left atrial size,18 assessment of pulmonary venous flow was proposed to overcome limitations related to the reliance on only the transmitral inflow pattern.3,5 A longer duration of atrial flow reversal in the pulmonary vein compared to the A wave of mitral inflow and a peak velocity of atrial flow reversal of ≥0.35 m/s were found to be good indicators of an elevated LVEDP. Thus inclusion of these parameters in the routine Doppler echocardiography study is generally recommended.19,20 In our study, both indexes were found to be good discriminators of a normal or elevated post-a LVEDP, whereas pre-a LVEDP correlated less well to atrial flow reversal, which is in good agreement with previous findings.3 However, an adequate pulmonary venous flow recording is sometimes difficult to obtain (as it was in 12 of our 78 subjects). In addition, alterations of preload by drugs or various maneuvers have been reported to increase diagnostic accuracy of echocardiography in the assessment of left ventricular filling pressure and diastolic function. However, though useful to investigate pathophysiology of diastolic dysfunction, application of drugs like nitroglycerin21 or nitroprusside22 and negative body pressure23 are hardly suitable for use in routine clinical practice. In contrast, the Valsalva maneuver is a simple and easily applicable method of reducing venous return and, consequently, of reducing the pressure gradient between the left atrium and ventricle. It has been shown that an elevated filling pressure can be unmasked by a lack of normal response of blood pressure and heart rate to the Valsalva maneuver.24,25 The utility of the technique in the diagnosis of diastolic dysfunction has been demonstrated in recent studies that have described the use of the Valsalva maneuver in the reduction of preload while obtaining a Doppler echocardiography transmitral inflow pattern.2,7,8,26 Changes of the transmitral inflow pattern during the Valsalvan maneuver were found to be useful in the diagnosis of coronary heart disease and arterial hypertension in patients with a normal E/A ratio.7,26 However, an E/A ratio cutoff point of < 1.0 was used irrespectively of the E/A ratio at rest, and the extent of change of the transmitral inflow pattern was not taken into account. Obviously, patients with an E/A ratio close to 1.0 at baseline have a much higher probability of reaching that cutoff point after the Valsalva maneuver, independently of the underlying mechanism. Thus specificity to detect pseudonormal inflow pattern was very low in our study population. In addition, this cutoff point of 1.0 is of no use in patients with a baseline E/A ratio < 1.0.
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Therefore a decrease in the E/A ratio independent of the E/A ratio at rest seems to be more promising. Recently, it was found that a relationship exists between LVEDP and the extent of change of the E/A ratio during performance of the Valsalva maneuver.2,8 It was shown that the extent of decrease in the E/A ratio was higher in patients with a pre-a LVEDP > 15 mm Hg.2 However, correlation and diagnostic accuracy were not assessed in that study, making a direct comparison with our results difficult. Besides, mean pre-a LVEDP was considerably higher than in our population, further complicating a direct comparison. Nevertheless, an overlap of change in the E/A ratio was present in patients with pre-a LVEDP < 15 mm Hg and ≥ 15 mm Hg.This is in agreement with our results, indicating a closer relationship of changes of the E/A ratio with post-a than with pre-a LVEDP.2 To our knowledge, this study shows for the first time that an increase in the duration of the A wave during the Valsalva maneuver compared to baseline may be an additional and easily obtainable parameter that can help accurately predict an elevated LVEDP. In fact, it was the most powerful parameter for the detection of an elevated LVEDP in patients with an impaired relaxation pattern. In patients with elevated filling pressures, the venous return to the left ventricle and stroke volume should still be adequate to prevent a decrease of the systolic blood pressure or an increase in heart rate during the Valsalva maneuver.27 Because the duration of the A wave actually increased during the Valsalva maneuver in most of our patients with an elevated LVEDP, the left ventricular stiffness seemed to decrease as the end-diastolic volume fell.This would allow the maintenance of stroke volume, even though the atrial preload is reduced. In addition, reduced diastolic pressure is synonymous with lower left atrial afterload and facilitates atrial ejection. However, because the decreased preload leads to a reduced early diastolic filling of the left ventricle, diastolic filling during atrial contraction would become more important, and reduced operating stiffness would allow a relatively larger amount of blood to pass the mitral valve during that phase of diastolic filling. This would explain the increase in duration and relative height of the A wave induced by the Valsalva maneuver in patients with an elevated LVEDP. In addition, the atrium might be on the descending part of its Starling curve at high pre-a pressures,28 which could further contribute to the increased flow during atrial systole in patients with elevated LVEDP. Finally, variations in the change of heart rate during the Valsalva maneuver accompanied by changes of the PR interval could further con-
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tribute to differences in the A-wave duration in patients with normal and elevated LVEDP. Likelihood of Obtaining High-Quality Recordings It has been reported that transmitral inflow pattern during the Valsalva maneuver may be obtained in nearly all patients.7,26 It is, however, more difficult to obtain high-quality signals in the pulmonary vein. Initially, a rather low success rate of obtaining highquality signals of atrial reversal flow was reported.29 However, with increasing experience and the new generation of ultrasonographic equipment, diagnostic information can be obtained in up to 90% of the patients.3,6 Our data are in agreement with this finding, though the success rate of obtaining acceptable pulmonary flow reversal was slightly less (85%), leading to a significant difference between the successful acquisition of a transmitral inflow pattern during the Valsalva maneuver (92%) and the atrial flow reversal. In addition, we found it less time consuming to obtain changes of transmitral inflow pattern during the Valsalva maneuver than to obtain pulmonary venous flow at baseline, though we did not quantitatively assess this time difference in our study. Study Limitations The echocardiographic data were not obtained simultaneously with the angiographic measurements of LVEDP but within 30 minutes before catheterization.All patients were in stable condition, fasting, and without any medication.Thus the possible impact on our results seems to be negligible. Because we examined consecutive patients with suspected coronary artery disease, LVEDP in our patients was relatively low. Thus, our data are not transferable to a patient population with advanced heart failure and a very high LVEDP. It has recently been shown that a restrictive transmitral inflow pattern may fail to revert after preload reduction induced by nitroprusside, nitroglycerin, or the Valsalva maneuver.2,22 These patients seem to have a particularly high risk for bad outcome.22 Whether irreversibility of restrictive inflow pattern after preload reduction by the Valsalva maneuver also predicts a clinically adverse outcome remains to be determined. Patients with fusion of the E and A waves at baseline were not included in our study. Assessment of transmitral inflow pattern either at rest or during the Valsalva maneuver may be difficult or even impossible in these patients. However, pulmonary venous flow may still provide useful information in these patients.Thus, depending on the patient population,
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the likelihood of obtaining pulmonary venous flow as compared with transmitral inflow pattern during the Valsalva maneuver may be higher than in our study. Finally, LVEDP was measured by use of a fluid-filled catheter. High-velocity catheters may have provided slightly different results. However, patients with inadequate recordings of LVEDP were excluded from the study.Thus it is unlikely that this has flawed our findings.
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Clinical Implications Atrial flow reversal and the extent of changes of the transmitral inflow pattern induced by the Valsalva maneuver are both suitable methods for noninvasive estimation of LVEDP.Whereas a restrictive transmitral inflow pattern does not need further assessment,19,20 both methods are equally useful in the differentiation of a normal transmitral inflow pattern from a pseudonormal pattern and in the detection of an elevated LVEDP in patients with an impaired relaxation pattern. An increase in the duration of the A wave induced by the Valsalva maneuver may be an additional tool in the assessment of diastolic function although reproducibility still needs to be demonstrated. The feasibility of obtaining high-quality recordings, however, is significantly higher when using changes of the transmitral inflow pattern induced by the Valsalva maneuver rather than those of atrial flow reversal in the pulmonary vein. Even though our findings need to be tested in different patient populations and by other investigators, the pulsed wave Doppler echocardiography assessment of mitral inflow during the Valsalva maneuver may be useful in the assessment of diastolic function by echocardiography.
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REFERENCES 16. 1. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol 1988;12:426-40. 2. Hurrell DG, Nishimura RA, Ilstrup DM, Appleton CP. Utility of preload alteration in assessment of left ventricular filling pressure by Doppler echocardiography: a simultaneous catheterization and Doppler echocardiographic study. J Am Coll Cardiol 1997;30:459-67. 3. Rossvoll O, Hatle LK. Pulmonary venous flow velocities recorded by transthoracic Doppler ultrasound: relation to left ventricular diastolic pressures. J Am Coll Cardiol 1993;21: 1687-96. 4. Brunazzi MC, Chirillo F, Pasqualini M, et al. Estimation of left ventricular diastolic pressures from precordial pulsed-
17.
18.
Doppler analysis of pulmonary venous and mitral flow. Am Heart J 1994;128:293-300. Nagano R, Masuyama T, Lee JM, et al. Transthoracic Doppler assessment of pattern of left ventricular dysfunction in hypertensive heart disease: combined analysis of mitral and pulmonary venous flow velocity patterns. J Am Soc Echocardiogr 1994;7:493-505. Jensen JL, Williams FE, Beilby BJ, et al. Feasibility of obtaining pulmonary venous flow velocity in cardiac patients using transthoracic pulsed wave Doppler technique. J Am Soc Echocardiogr 1997;10:60-6. Dumesnil JG, Gaudreault G, Honos GN, Kingma JG. Use of Valsalva maneuver to unmask left ventricular diastolic function abnormalities by Doppler-echocardiography in patients with coronary artery disease or systemic hypertension. Am J Cardiol 1991;68:515-9. Brunner-La Rocca HP, Attenhofer CH, Jenni R. Can the extent of change of the left ventricular Doppler inflow pattern during the Valsalva maneuver predict an elevated left ventricular end-diastolic pressure? Echocardiography 1998;15:2118. Devereux RB, Alonso DR, Lutas EM, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison with necropsy findings. Am J Cardiol 1991;57:450-8. Appleton CP, Jensen JL, Hatle LK, Oh JK. Doppler evaluation of left and right ventricular diastolic function: a technical guide for obtaining optimal flow velocity recordings. J Am Soc Echocardiogr 1997;10:271-92. Hanley JA, McNeil JJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 1993;148:839-43. Gilbert JC, Glantz SA. Determinants of left ventricular filling and of the diastolic pressure-volume curve. Circ Res 1989;64: 827-52. Stevenson LW, Tillisch JH, Hamilton M, et al. Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or nonischemic dilated cardiomyopathy. Am J Cardiol 1990;66:1348-54. Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol 1995;26:565-74. Nishimura RA, Appleton CP, Redfield MM, Ilstrup DM, Holmes DR, Tajik AJ. Noninvasive Doppler echocardiographic evaluation of left ventricular filling pressures in patients with cardiomyopathies: a simultaneous Doppler echocardiographic and cardiac catheterization study. J Am Coll Cardiol 1996;28:1226-33. Brun P, Tribouilloy C, Duval AM, al. Left ventricular flow propagation during early filling is related to wall relaxation: a color M-mode Doppler analysis. J Am Coll Cardiol 1992;20: 420-32. Takatsuji H, Mikami T, Urasawa K, et al. A new approach for evaluation of left ventricular diastolic function: spatial and temporal analysis of left ventricular filling flow propagation by color M-mode Doppler echocardiography. J Am Coll Cardiol 1996;27:365-71. Appleton CP, Galloway JM, Gonzalez MS, Gaballa M, Basnight MA. Estimation of left ventricular filling pressure using two-dimensional and Doppler echocardiography in adult patients with cardiac disease: additional value of analyzing left atrial size, left atrial ejection fraction and the difference in duration of pulmonary venous and mitral flow velocity at atrial contraction. J Am Coll Cardiol 1993;22:1972-82.
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19. Rakowski H, Appleton CP, Chan KL, et al. Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography. J Am Soc Echocardiogr 1996;9:736-60. 20. Oh JK, Appleton CP, Hatle LK, Nishimura RA, Seward JB, Tajik AJ. The noninvasive assessment of left ventricular diastolic function with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 1997;10:246-70. 21. Choong CY, Herrmann HC, Weyman AE, Fifer MA. Preload dependence of Doppler-derived indexes of left ventricular diastolic function in humans. J Am Coll Cardiol 1987;10: 800-8. 22. Pozzoli M, Traversi E, Cioffi G, Stenner R, Sanarico M, Tavazzi L. Loading manipulations improve the prognostic value of Doppler evaluation of mitral flow in patients with chronic heart failure. Circulation 1997;95:1222-30. 23. Berk MR, Xie GY, Kwan OL, et al. Reduction of left ventricular preload by lower body negative pressure alters Doppler transmitral filling patterns. J Am Coll Cardiol 1990;16:138792.
24. McIntyre KM, Vita JA, Lambrew CT, Freeman J, Loscalzo J. A noninvasive method of predicting pulmonary-capillary wedge pressure. N Engl J Med 1992;327:1715-20. 25. Schmidt DE, Shah PK. Accurate detection of elevated left ventricular filling pressure by a simplified bedside application of the Valsalva maneuver. Am J Cardiol 1993;71:462-5. 26. Demeule E, Dumesnil JG, Coulombe D, LeBlanc MH. Comparison of Valsalva Maneuver and pulmonary venous recordings in diastolic function evaluation by Doppler echocardiography. [abstract] J Am Coll Cardiol 1996;27:174A. 27. Little WC, Barr WK, Crawford MH. Altered effect of the Valsalva maneuver on left ventricular volume in patients with cardiomyopathy. Circulation 1985;71:227-33. 28. Payne RM, Stone HL, Engelken EJ. Atrial function during volume loading. J Appl Physiol 1971;31:326-31. 29. Masuyama T, Lee J, Tamai M, Tanouchi J, Kitabatake A, Kamada T. Pulmonary venous flow velocity pattern as assessed with transthoracic pulsed Doppler echocardiography in subjects without cardiac disease. Am J Cardiol 1991;67: 1396-1404.
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We directly compared the transmitral inflow pattern during preload reduction and pulmonary venous flow velocities to determine left ventricular end-diastolic pressure (LVEDP) in 78 patients who underwent left heart catheterization. Transmitral inflow indexes (A-wave duration, ratio of peak flow velocity of early diastole [E] to peak flow velocity of late diastole during atrial contraction [A] [E/A ratio]) at rest and during the Valsalva maneuver (30 mm Hg for 15 seconds) and indexes of pulmonary venous flow (velocity and duration of the atrial reversal) were obtained. Fair correlations existed between LVEDP
(mean 15 ± 6 mm Hg) and the percentage decrease in the E/A ratio (r = 0.72), increase in duration of A wave during the Valsalva maneuver (r = 0.60), flow velocity of atrial reversal (r = 0.58), and difference of duration of atrial flow reversal and A wave (r = 0.62) (all P < .001). While sensitivity, specificity, and diagnostic accuracy to detect an elevated LVEDP were comparable, technically adequate Doppler recordings were obtained more often for the mitral inflow during the Valsalva maneuver than for the pulmonary venous flow (72 versus 66 patients, P < 0.05). (J Am Soc Echocardiogr 2000;13:599-607.)
INTRODUCTION Pulsed wave Doppler mitral flow velocities are being used to assess left ventricular diastolic function in cardiac disease.Three different abnormal patterns of mitral filling have been described (impaired relaxation, pseudonormalization, and restriction).1 Diastolic dysfunction leads firstly to a relaxation abnormality with a decreased ratio of peak flow velocity of early diastole (E) to peak flow velocity and duration of late diastole during atrial contraction (A) (E/A ratio) and increased deceleration and isovolumetric relaxation times. Progression of diastolic dysfunction with a successive increase in left-sided filling pressures makes Doppler echocardiography indexes of mitral flow return to “normal” (“pseudonormaliza-
From Echocardiography Laboratory, Division of Cardiology, University Hospital, Zurich, Switzerland. Reprint requests: H. P. Brunner-La Rocca, MD, Division of Cardiology, University Hospital, Rämistrasse 100, 8091 Zurich, Switzerland (E-mail: [email protected]). Copyright © 2000 by the American Society of Echocardiography. 0894-7317/2000 $12.00 + 0 27/1/106077 doi:10.1067/mje.2000.106077
tion”). Further progression of diastolic filling pressure then leads to a restrictive pattern.This inevitably weakens any correlation between Doppler echocardiography indexes of mitral flow and left ventricular end-diastolic pressure (LVEDP).2 Thus, more recent attempts have been made to increase diagnostic accuracy in the prediction of elevated left ventricular pressure and diastolic function. Assessment of pulmonary venous flow velocities has been shown to be useful for predicting elevated leftsided filling pressures and has added to the understanding of diastolic dysfunction.3-5 However, proper recording, especially of atrial flow reversal, may be difficult and time consuming,4 though a recent report suggests that it can be obtained in up to 90% of unselected patients.6 Maneuvers that reduce preload such as the Valsalva maneuver or nitroglycerin have been found to be useful in determining diastolic dysfunction.2,7,8 However, changes in mitral inflow with preload reduction have not been directly compared with pulmonary venous flow velocity for assessing elevated filling pressures. Therefore, the goal of our study was to prospec599
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tively compare the feasibility and accuracy of changes in the transmitral inflow pattern induced by the Valsalva maneuver with measurements of the pulmonary venous flow profile in the diagnosis of elevated left ventricular end diastolic pressure. Furthermore, we hypothesized that an increase in duration of the mitral inflow A wave induced by the Valsalva maneuver may be an additional sign of diastolic dysfunction.
METHODS Study Population Eighty patients (mean age 62 ± 9 years) with stable sinus rhythm who underwent diagnostic cardiac catheterization for suspected coronary artery disease were consecutively evaluated. Seventeen patients (21%) were women and 63 (79%) were men. Excluded from the study were patients with unstable angina or acute myocardial infarction, significant valvular heart disease (moderate to severe regurgitation or stenosis), valve prosthesis, frequent supraventricular or ventricular arrhythmias, severe chronic obstructive lung disease or fusion of the E and A waves (minimal middiastolic flow velocity more than one third of E velocity at baseline). Echocardiography Within 30 minutes before coronary angiography, a complete 2-dimensional (2D) and pulsed wave Doppler echocardiography examination was performed with a Vingmed CFM 750 (Vingmed Sound, Horten, Norway) echocardiographic system with use of standard parasternal and apical views in the fasting patients. From the parasternal long-axis views, M-mode recordings were made and digitally saved on a Macintosh (Apple Computer Inc, Cupertino, Calif) computer. The following measurements were calculated off-line: left ventricular end-systolic and end-diastolic dimensions (LVEDD), left ventricular septal (LVS) and posterior wall (PW) thicknesses, and left atrial dimension.The left ventricular muscle mass index was calculated with the formula muscle mass (in grams per square meter) = 0.8 × 1.04 × [(LVEDD + LVS + PW)3 – (LVEDD)3] / body surface area.9 The pulsed Doppler signal was obtained by placing the sample volume between the tips of the mitral valve leaflets controlled by 2D echocardiography in the apical 4-chamber view. In accordance with recently published guidelines,10 peak flow velocity of early diastole (E) and peak flow velocity and duration of late diastole during atrial contraction (A) were recorded and the E/A ratio calculated. Usually, distinction between the A wave and lowvelocity flow in early systole was possible. However, replacement of the sample volume was necessary in a few
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patients. In addition, deceleration time and isovolumetric relaxation time at baseline were measured.All parameters were digitally recorded and calculated off-line. Mean values were obtained by averaging 4 beats during quiet respiration. Pulmonary venous flow velocities were obtained by placing the sample volume 1 to 2 cm into the upper or lower right pulmonary vein from a slightly anterior angulated 4-chamber view. Velocity filter as well as width and position of the sample volume were set as previously described.10 Velocity and duration of atrial flow reversal were digitally recorded and calculated off-line. Values were obtained by averaging 4 beats during quiet respiration. Finally, E/A ratio and duration of the A wave were measured by averaging the last 2 beats immediately before release of the strain of the Valsalva maneuver.The patients were carefully instructed in the performance of the Valsalva maneuver. Before the measurements, the patients were asked to initiate and maintain the strain 15 to 20 seconds after normal inspiration by forcefully exhaling into a tube connected to a sphygmomanometer. The straining pressure was controlled to be 25 to 35 mm Hg. A tiny air leak was placed in the tube to ensure that airway pressure was produced from the thoracic cavity and not the pharynx. The Doppler sample was repositioned during the Valsalva maneuver by 2D echocardiography control to obtain valid recordings. The maneuver was repeated until 2 satisfactory recordings were obtained. Comparisons between the recordings did not reveal a significant difference. Because of fusion of the E and A waves caused by increased heart rate during the Valsalva maneuver in some patients, particular care was taken to avoid underestimation of A-wave duration by comparing echocardiographic recordings with the electrocardiogram before and during the Valsalva maneuver.Thus the time from the onset of the P wave of the electrocardiogram to the onset of the mitral A wave during the Valsalva maneuver was compared with that at rest. All the echocardiographic examinations were performed and measured by the same examiner (H.P.B.), who was blinded to the results of the catheterization. Coronary Angiography Left ventriculography and coronary angiography were performed from the femoral approach with standard techniques.The LVEDP was recorded on paper with a speed of 200 mm/s and a pressure range of 40 mm Hg before administration of any contrast dye with use of a 6F fluidfilled pigtail catheter connected to a pressure transducer. It was obtained by averaging pre-a (pressure before atrial contraction) and post-a (pressure before ventricular contraction) values throughout a cycle of quiet respiration. A pre-a LVEDP of ≥10 mm Hg and a post-a pressure of ≥15 mm Hg were considered to be elevated.3 In 2 (3%)
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Table 1 Clinical 2-dimensional echocardiography and angiographic characteristics in patients with normal and elevated pre-a and/or post-a LVEDP LVEDP LVEDP normal elevated (42 patients) (36 patients)
Age (y) Men Heart rate at rest (bpm) Difference in heart rate rest to VM (bpm) Body mass index (kg/m2) Ejection fraction End-diastolic volume index (mL/m2) LV muscle mass index (g/m2) Left atrial size (cm) LV end-diastolic diameter (cm) Coronary artery disease Arterial hypertension Previous myocardial infarction
63 ± 9 35 (83%) 57 ± 10 10.4 ± 8.7
59 ± 9 27 (75%) 62 ± 10 6.9 ± 8.2
26.4 ± 3.9 26.5 ± 2.9 0.64 ± 0.10 0.56 ± 0.16 96 ± 27 122 ± 51
P value
.06 >.1 .05 .05 >.1 .01 .007
102 ± 28
113 ± 42
>.1
4.0 ± 0.6 5.2 ± 0.8
4.3 ± 0.6 5.3 ± 1.0
.07 >.1
35 (83%) 7 (17%) 9 (21%)
34 (94%) 5 (14%) 25 (69%)
>.1 >.1 <.001
Numerals indicate number of patients unless otherwise specified. pre-a, Pressure before atrial contraction; post-a, pressure before ventricular contraction; LVEDP, left ventricular end-diastolic pressure; VM, Valsalva maneuver; LV, left ventricular.
patients, assessment of LVEDP was inaccurate because of inadequate pressure tracings; these patients were excluded from further analysis. Left ventricular end-diastolic and end-systolic volumes were obtained, and the ejection fraction was calculated with the biplane area-length method. All these measurements were performed by one examiner who was blinded to the echocardiographic results (H.R.). Statistical Analysis Data are presented as frequencies or means ± standard deviations or standard error as indicated. Doppler echocardiography parameters were correlated to LVEDP with the Spearman rank correlation. Comparison between groups were made with the chi-square test, the student t test, or Mann-Whitney U test as appropriate. Sensitivity, specificity, positive and negative predictive values, as well as diagnostic accuracy (percentage of correct classification) to detect an elevated LVEDP (either pre-a or post-a) were assessed with use of cut-off points previously found to be good indicators of an elevated LVEDP. In addition, area under curve was calculated by receiver operating characteristic curves (sensitivity versus 1-specificity) to compare Doppler echocardiography parameters detecting an elevated LVEDP.11 A P value of less than .05 was considered statistically significant. All calculations were performed with a commercially available statistical package (SPSS for Windows 6.0, Cary, NC).
Figure 1 Relation between post-a LVEDP and decrease in the E/A ratio and duration of A wave during Valsalva maneuver. E/a ratio, Ratio of peak flow velocity of early diastole to peak flow velocity and duration of late diastole during atrial contraction; post-a, pressure before ventricular contraction; LVEDP, left ventricular end-diastolic pressure.
RESULTS Table 1 lists the clinical, 2D echocardiography, and angiographic data of the 78 patients with normal and elevated post-a LVEDP. Mean pre-a LVEDP was 8.1 ± 3.5 mm Hg (range 2 to 22 mm Hg) and mean post-a LVEDP was 14.6 ± 5.8 mm Hg (range 4 to 31 mm Hg). Pre-a LVEDP was elevated in 22 (30%) patients and post-a in 34 (44%). Pre-a and/or post-a LVEDP was elevated in 36 patients (46%); in these patients, ejection fraction was significantly lower, left ventricular end-diastolic volume index increased, and heart rate at rest higher. In addition, they more often had a history of myocardial infarction. Of the 78 patients, 5 (6%) had technically inadequate recordings of both transmitral inflow during the Valsalva maneuver and pulmonary venous flow, 1 (1%) had technically inadequate recordings of transmitral inflow pattern during the Valsalva maneuver only, and 7 (9%) had technically inadequate recordings of atrial flow reversal in the pulmonary vein only. Thus 72 of 78 (92%) patients had adequate recordings of mitral flow before and during the Valsalva maneuver, and 66 patients (85%) had adequate recordings of pulmonary venous flow (P < .05). There were fairly weak correlations of LVEDP with the isovolumetric relaxation time (pre-a: r = –0.32, P < .01; post-a: r = –0.29, P < .05), the deceleration time (pre-a: r = –0.43, P < .001; post-a: r = –0.34, P < .01), and the E/A ratio (pre-a: r = 0.33, P < .01; posta: r = 0.30, P < .05).
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Figure 2 Transmitral flow velocity profiles at baseline (A) and during Valsalva maneuver (B) and pulmonary venous flow profile (C) in a patient with normal LVEDP (pre-a 4 mm Hg, post-a 5 mm Hg; upper panel) and in a patient with elevated LVEDP (pre-a 13 mm Hg, post-a 22 mm Hg) and pseudonormal transmitral inflow pattern at rest (lower panel). Duration of A wave and atrial reversal in ms; flow velocity in m/s. E/A, Ratio of peak flow velocity of early diastole to peak flow velocity and duration of late diastole during atrial contraction; LVEDP, left ventricular end-diastolic pressure; pre-a, pressure before atrial contraction; post-a, pressure before ventricular contraction.
As shown in Table 2, the correlations between post-a LVEDP and atrial reversal in the pulmonary vein as well as the extent of changes in transmitral inflow pattern during the Valsalva maneuver were moderately good, whereas correlations between prea LVEDP and the Doppler echocardiographic indexes were generally weaker. Reanalysis of the data after accounting for the mitral inflow velocity at the onset of atrial contraction (E at A) did not significantly change the correlation between percentage decrease of E/A ratio during the Valsalva maneuver and pre-a (r = 0.56, P < .001) and post-a LVEDP (r = 0.74, P < .001). Figure 1 depicts the good correlation between the post-a LVEDP and the changes of the E/A ratio and the duration of the A wave during the Valsalva maneuver. The comparison of the absolute mean values of the Doppler indexes of mitral inflow and pulmonary venous flow in patients with normal and elevated pre-a and/or post-a LVEDP are shown in Table 3. Sensitivity, specificity, positive and negative pre-
dictive values, as well as diagnostic accuracy of atrial reversal and transmitral inflow during the Valsalva maneuver to detect an elevation of pre-a and/or post-a LVEDP are shown in Table 4 (all P < .001).The area under the receiver operating characteristic curves (±SE) of the changes in E/A ratio (0.89 ± 0.04) and duration of A wave (0.83 ± 0.05) during the Valsalva maneuver were comparable to the flow velocity of atrial reversal in the pulmonary vein (0.85 ± 0.05) and the difference between the duration of A wave at rest and atrial reversal (0.85 ± 0.05). Sensitivity, specificity, and diagnostic accuracy of all 4 Doppler echocardiography indexes were separately analyzed in patients with an E/A ratio within the normal range of 1.0 to 2.0 (n = 35, 47%) and in those with a possible impaired relaxation pattern (with an arbitrary threshold of E/A ratio < 1.0, n = 35, 47%). Of those with a normal E/A ratio, 15 (43%, Figure 2, upper panel) had a normal and 20 (57%, Figure 2, lower panel) a pseudonormal (elevation of pre-a and/or post-a LVEDP) transmitral inflow pat-
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Table 2 Spearman rank correlation (r) between Doppler echocardiography indexes and post-a LVEDP
Pre-a Post-a
%↓ in E (n = 72)
%↓ in A (n = 72)
%↓ in E/A (n = 72)
↑ of A (n = 72)
AR in PV (n = 66)
∆AR-A (n = 66)
0.34* 0.53†
–0.46† –0.37*
0.57† 0.72†
0.46† 0.60†
0.33* 0.58†
0.43† 0.62†
post-a, Pressure before ventricular contraction; LVEDP, left ventricular end-diastolic pressure; pre-a, Pressure before atrial contraction; %↓, percentage of decrease during the Valsalva maneuver; E, E wave; A, A wave; ↑, increase in duration during the Valsalva maneuver; E/A, ratio of peak flow velocity of early diastole to peak flow velocity and duration of late diastole during atrial contraction; AR, flow velocity of atrial reversal; PV, right lower pulmonary vein; ∆ARA, difference in duration of atrial reversal and A wave. *P < .01. †P < .001.
Table 3 Doppler echocardiography indexes in patients with normal and elevated pre-a and/or post-a LVEDP LVEDP Normal, n = 39 (PV n = 36)
E/A ratio Deceleration time (ms) Isovolumetric relaxation time (ms) Change in E wave during VM (%) Change in A wave during VM (%) Change in E/A ratio during VM (%) Change in corr E/A ratio during VM (%) Change in duration of A wave from rest to VM (ms) Flow velocity of atrial reversal in PV (cm/s) Difference between duration of atrial reversal in PV and A wave at rest (ms)
1.0 237 96 –33 –10 –23 –15 –4 29 –19
± ± ± ± ± ± ± ± ± ±
0.4* 84† 22* 10‡ 21* 15‡ 19‡ 14‡ 5‡ 22‡
Elevated, n = 33 (PV n = 30)
1.3 186 85 –46 2 –46 –43 12 37 9
± ± ± ± ± ± ± ± ± ±
0.7 77 19 13 19 13 14 12 6 20
Numbers are mean ± SD. pre-a, Pressure before atrial contraction; post-a, pressure before ventricular contraction; LVEDP, left ventricular end-diastolic pressure; corr, denotes corrected for mitral flow velocity at the onset of atrial contraction (E at A); PV, right upper pulmonary vein; VM, Valsalva maneuver. *P < .05. †P < .01. ‡P < .001.
Table 4 Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of Doppler echocardiography indexes in the detection of an elevated pre-a and/or post-a LVEDP
Sensitivity Specificity Positive predictive value Negative predictive value Diagnostic accuracy
↓ of E/A ratio ≥40% during VM (n = 72)
Any ↑ in dur of A during VM (n = 72)
Flow ≥0.35 m/s of AR in PV (n = 66)
Dur AR > dur A (n = 66)
76% 92% 89% 81% 85%
88% 84% 83% 84% 86%
67% 94% 91% 77% 82%
70% 89% 84% 81% 80%
All values shown are percentages. pre-a, Pressure before atrial contraction; post-a, pressure before ventricular contraction; LVEDP, left ventricular end-diastolic pressure; ↓, decrease; E/A ratio, ratio of peak flow velocity of early diastole to peak flow velocity and duration of late diastole during atrial contraction; VM, Valsalva maneuver; ↑, increase; AR, atrial reversal; PV, pulmonary vein; dur, duration; A, A wave.
tern. Separation of patients with a pseudonormal transmitral inflow pattern from those with a normal pattern was possible with an acceptable diagnostic accuracy by all Doppler echocardiography indexes (decrease of E/A ratio ≥40% [sensitivity, specificity, and diagnostic accuracy: 80%, 87%, 83%, respectively] and increased A wave during the Valsalva maneuver [80%, 71%, 76%], velocity of atrial flow reversal ≥0.35
m/s [77%, 86%, 81%], duration of atrial flow reversal > duration A wave [78%, 86%, 82%], P > 0.1 between different Doppler echocardiography parameters). Given the past literature on the subject,7 we further assessed the use of a decrease in the E/A ratio of < 1.0 during the Valsalva maneuver as an indicator of a pseudonormal pattern (ie, elevated LVEDP). Whereas sensitivity was good (ie, 90%), specificity
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was only 27% (diagnostic accuracy 63%). Finally, in the patients with a baseline E/A ratio of < 1.0, an elevated pre-a and/or post-a LVEDP (n = 11, 31%) was detected with an acceptable diagnostic accuracy. In this group, sensitivity, specificity, and diagnostic accuracy tended to be higher for changes in transmitral inflow pattern during the Valsalva maneuver (decrease of E/A ratio ≥40%: 73%, 96%, 88%, respectively; increased A wave during the Valsalva maneuver: 100%, 91%, 94%, respectively) than for atrial flow reversal in the pulmonary vein (velocity of atrial flow reversal ≥0.35 m/s: 46%, 100%, 81%, respectively; duration of atrial flow reversal > duration A wave: 55%, 90%, 77%, respectively) (P = .08).
DISCUSSION In our prospective and direct comparison of echocardiographic estimation of LVEDP, the diagnostic accuracy of changes of transmitral inflow pattern induced by the Valsalva maneuver was found to be comparable to that obtained by analysis of atrial flow reversal in the pulmonary vein. Both methods were equally useful in the differentiation of patients with normal and elevated LVEDP, with a diagnostic accuracy ranging from 80% to 86%. In addition, it was possible to distinguish patients with a normal transmitral inflow pattern from those with a pseudonormal pattern with a diagnostic accuracy of > 80%. However, feasibility was significantly higher for the assessment of the transmitral inflow pattern during the Valsalva maneuver than for the obtainment of an adequate recording of atrial flow reversal in the pulmonary veins in our patient group. Knowledge of left ventricular filling pressures is important for diagnosis, prognosis, and treatment of patients with cardiac disease.12,13 Because one third of patients with congestive heart failure have normal systolic left ventricular function,14 assessment of diastolic function is extremely important. Pulsed wave Doppler variables of the transmitral inflow have been proposed as a noninvasive method for assessing left ventricular diastolic function.The ratio of transmitral flow velocities (E/A ratio), deceleration time, and isovolumetric relaxation time have all been reported to accurately predict elevated left ventricular filling pressure in patients with decreased ejection fraction.1,15 In patients with a normal or only slightly reduced ejection fraction, however, these parameters are of less value,15 as shown in the current study group, in which only 12% of patients had an ejection fraction below 0.45. In addition to methods such as color M-mode flow
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propagation velocity from base to apex16,17 and 2D echocardiography determination of left atrial size,18 assessment of pulmonary venous flow was proposed to overcome limitations related to the reliance on only the transmitral inflow pattern.3,5 A longer duration of atrial flow reversal in the pulmonary vein compared to the A wave of mitral inflow and a peak velocity of atrial flow reversal of ≥0.35 m/s were found to be good indicators of an elevated LVEDP. Thus inclusion of these parameters in the routine Doppler echocardiography study is generally recommended.19,20 In our study, both indexes were found to be good discriminators of a normal or elevated post-a LVEDP, whereas pre-a LVEDP correlated less well to atrial flow reversal, which is in good agreement with previous findings.3 However, an adequate pulmonary venous flow recording is sometimes difficult to obtain (as it was in 12 of our 78 subjects). In addition, alterations of preload by drugs or various maneuvers have been reported to increase diagnostic accuracy of echocardiography in the assessment of left ventricular filling pressure and diastolic function. However, though useful to investigate pathophysiology of diastolic dysfunction, application of drugs like nitroglycerin21 or nitroprusside22 and negative body pressure23 are hardly suitable for use in routine clinical practice. In contrast, the Valsalva maneuver is a simple and easily applicable method of reducing venous return and, consequently, of reducing the pressure gradient between the left atrium and ventricle. It has been shown that an elevated filling pressure can be unmasked by a lack of normal response of blood pressure and heart rate to the Valsalva maneuver.24,25 The utility of the technique in the diagnosis of diastolic dysfunction has been demonstrated in recent studies that have described the use of the Valsalva maneuver in the reduction of preload while obtaining a Doppler echocardiography transmitral inflow pattern.2,7,8,26 Changes of the transmitral inflow pattern during the Valsalvan maneuver were found to be useful in the diagnosis of coronary heart disease and arterial hypertension in patients with a normal E/A ratio.7,26 However, an E/A ratio cutoff point of < 1.0 was used irrespectively of the E/A ratio at rest, and the extent of change of the transmitral inflow pattern was not taken into account. Obviously, patients with an E/A ratio close to 1.0 at baseline have a much higher probability of reaching that cutoff point after the Valsalva maneuver, independently of the underlying mechanism. Thus specificity to detect pseudonormal inflow pattern was very low in our study population. In addition, this cutoff point of 1.0 is of no use in patients with a baseline E/A ratio < 1.0.
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Therefore a decrease in the E/A ratio independent of the E/A ratio at rest seems to be more promising. Recently, it was found that a relationship exists between LVEDP and the extent of change of the E/A ratio during performance of the Valsalva maneuver.2,8 It was shown that the extent of decrease in the E/A ratio was higher in patients with a pre-a LVEDP > 15 mm Hg.2 However, correlation and diagnostic accuracy were not assessed in that study, making a direct comparison with our results difficult. Besides, mean pre-a LVEDP was considerably higher than in our population, further complicating a direct comparison. Nevertheless, an overlap of change in the E/A ratio was present in patients with pre-a LVEDP < 15 mm Hg and ≥ 15 mm Hg.This is in agreement with our results, indicating a closer relationship of changes of the E/A ratio with post-a than with pre-a LVEDP.2 To our knowledge, this study shows for the first time that an increase in the duration of the A wave during the Valsalva maneuver compared to baseline may be an additional and easily obtainable parameter that can help accurately predict an elevated LVEDP. In fact, it was the most powerful parameter for the detection of an elevated LVEDP in patients with an impaired relaxation pattern. In patients with elevated filling pressures, the venous return to the left ventricle and stroke volume should still be adequate to prevent a decrease of the systolic blood pressure or an increase in heart rate during the Valsalva maneuver.27 Because the duration of the A wave actually increased during the Valsalva maneuver in most of our patients with an elevated LVEDP, the left ventricular stiffness seemed to decrease as the end-diastolic volume fell.This would allow the maintenance of stroke volume, even though the atrial preload is reduced. In addition, reduced diastolic pressure is synonymous with lower left atrial afterload and facilitates atrial ejection. However, because the decreased preload leads to a reduced early diastolic filling of the left ventricle, diastolic filling during atrial contraction would become more important, and reduced operating stiffness would allow a relatively larger amount of blood to pass the mitral valve during that phase of diastolic filling. This would explain the increase in duration and relative height of the A wave induced by the Valsalva maneuver in patients with an elevated LVEDP. In addition, the atrium might be on the descending part of its Starling curve at high pre-a pressures,28 which could further contribute to the increased flow during atrial systole in patients with elevated LVEDP. Finally, variations in the change of heart rate during the Valsalva maneuver accompanied by changes of the PR interval could further con-
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tribute to differences in the A-wave duration in patients with normal and elevated LVEDP. Likelihood of Obtaining High-Quality Recordings It has been reported that transmitral inflow pattern during the Valsalva maneuver may be obtained in nearly all patients.7,26 It is, however, more difficult to obtain high-quality signals in the pulmonary vein. Initially, a rather low success rate of obtaining highquality signals of atrial reversal flow was reported.29 However, with increasing experience and the new generation of ultrasonographic equipment, diagnostic information can be obtained in up to 90% of the patients.3,6 Our data are in agreement with this finding, though the success rate of obtaining acceptable pulmonary flow reversal was slightly less (85%), leading to a significant difference between the successful acquisition of a transmitral inflow pattern during the Valsalva maneuver (92%) and the atrial flow reversal. In addition, we found it less time consuming to obtain changes of transmitral inflow pattern during the Valsalva maneuver than to obtain pulmonary venous flow at baseline, though we did not quantitatively assess this time difference in our study. Study Limitations The echocardiographic data were not obtained simultaneously with the angiographic measurements of LVEDP but within 30 minutes before catheterization.All patients were in stable condition, fasting, and without any medication.Thus the possible impact on our results seems to be negligible. Because we examined consecutive patients with suspected coronary artery disease, LVEDP in our patients was relatively low. Thus, our data are not transferable to a patient population with advanced heart failure and a very high LVEDP. It has recently been shown that a restrictive transmitral inflow pattern may fail to revert after preload reduction induced by nitroprusside, nitroglycerin, or the Valsalva maneuver.2,22 These patients seem to have a particularly high risk for bad outcome.22 Whether irreversibility of restrictive inflow pattern after preload reduction by the Valsalva maneuver also predicts a clinically adverse outcome remains to be determined. Patients with fusion of the E and A waves at baseline were not included in our study. Assessment of transmitral inflow pattern either at rest or during the Valsalva maneuver may be difficult or even impossible in these patients. However, pulmonary venous flow may still provide useful information in these patients.Thus, depending on the patient population,
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the likelihood of obtaining pulmonary venous flow as compared with transmitral inflow pattern during the Valsalva maneuver may be higher than in our study. Finally, LVEDP was measured by use of a fluid-filled catheter. High-velocity catheters may have provided slightly different results. However, patients with inadequate recordings of LVEDP were excluded from the study.Thus it is unlikely that this has flawed our findings.
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Clinical Implications Atrial flow reversal and the extent of changes of the transmitral inflow pattern induced by the Valsalva maneuver are both suitable methods for noninvasive estimation of LVEDP.Whereas a restrictive transmitral inflow pattern does not need further assessment,19,20 both methods are equally useful in the differentiation of a normal transmitral inflow pattern from a pseudonormal pattern and in the detection of an elevated LVEDP in patients with an impaired relaxation pattern. An increase in the duration of the A wave induced by the Valsalva maneuver may be an additional tool in the assessment of diastolic function although reproducibility still needs to be demonstrated. The feasibility of obtaining high-quality recordings, however, is significantly higher when using changes of the transmitral inflow pattern induced by the Valsalva maneuver rather than those of atrial flow reversal in the pulmonary vein. Even though our findings need to be tested in different patient populations and by other investigators, the pulsed wave Doppler echocardiography assessment of mitral inflow during the Valsalva maneuver may be useful in the assessment of diastolic function by echocardiography.
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REFERENCES 16. 1. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol 1988;12:426-40. 2. Hurrell DG, Nishimura RA, Ilstrup DM, Appleton CP. Utility of preload alteration in assessment of left ventricular filling pressure by Doppler echocardiography: a simultaneous catheterization and Doppler echocardiographic study. J Am Coll Cardiol 1997;30:459-67. 3. Rossvoll O, Hatle LK. Pulmonary venous flow velocities recorded by transthoracic Doppler ultrasound: relation to left ventricular diastolic pressures. J Am Coll Cardiol 1993;21: 1687-96. 4. Brunazzi MC, Chirillo F, Pasqualini M, et al. Estimation of left ventricular diastolic pressures from precordial pulsed-
17.
18.
Doppler analysis of pulmonary venous and mitral flow. Am Heart J 1994;128:293-300. Nagano R, Masuyama T, Lee JM, et al. Transthoracic Doppler assessment of pattern of left ventricular dysfunction in hypertensive heart disease: combined analysis of mitral and pulmonary venous flow velocity patterns. J Am Soc Echocardiogr 1994;7:493-505. Jensen JL, Williams FE, Beilby BJ, et al. Feasibility of obtaining pulmonary venous flow velocity in cardiac patients using transthoracic pulsed wave Doppler technique. J Am Soc Echocardiogr 1997;10:60-6. Dumesnil JG, Gaudreault G, Honos GN, Kingma JG. Use of Valsalva maneuver to unmask left ventricular diastolic function abnormalities by Doppler-echocardiography in patients with coronary artery disease or systemic hypertension. Am J Cardiol 1991;68:515-9. Brunner-La Rocca HP, Attenhofer CH, Jenni R. Can the extent of change of the left ventricular Doppler inflow pattern during the Valsalva maneuver predict an elevated left ventricular end-diastolic pressure? Echocardiography 1998;15:2118. Devereux RB, Alonso DR, Lutas EM, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison with necropsy findings. Am J Cardiol 1991;57:450-8. Appleton CP, Jensen JL, Hatle LK, Oh JK. Doppler evaluation of left and right ventricular diastolic function: a technical guide for obtaining optimal flow velocity recordings. J Am Soc Echocardiogr 1997;10:271-92. Hanley JA, McNeil JJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology 1993;148:839-43. Gilbert JC, Glantz SA. Determinants of left ventricular filling and of the diastolic pressure-volume curve. Circ Res 1989;64: 827-52. Stevenson LW, Tillisch JH, Hamilton M, et al. Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or nonischemic dilated cardiomyopathy. Am J Cardiol 1990;66:1348-54. Vasan RS, Benjamin EJ, Levy D. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol 1995;26:565-74. Nishimura RA, Appleton CP, Redfield MM, Ilstrup DM, Holmes DR, Tajik AJ. Noninvasive Doppler echocardiographic evaluation of left ventricular filling pressures in patients with cardiomyopathies: a simultaneous Doppler echocardiographic and cardiac catheterization study. J Am Coll Cardiol 1996;28:1226-33. Brun P, Tribouilloy C, Duval AM, al. Left ventricular flow propagation during early filling is related to wall relaxation: a color M-mode Doppler analysis. J Am Coll Cardiol 1992;20: 420-32. Takatsuji H, Mikami T, Urasawa K, et al. A new approach for evaluation of left ventricular diastolic function: spatial and temporal analysis of left ventricular filling flow propagation by color M-mode Doppler echocardiography. J Am Coll Cardiol 1996;27:365-71. Appleton CP, Galloway JM, Gonzalez MS, Gaballa M, Basnight MA. Estimation of left ventricular filling pressure using two-dimensional and Doppler echocardiography in adult patients with cardiac disease: additional value of analyzing left atrial size, left atrial ejection fraction and the difference in duration of pulmonary venous and mitral flow velocity at atrial contraction. J Am Coll Cardiol 1993;22:1972-82.
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19. Rakowski H, Appleton CP, Chan KL, et al. Canadian consensus recommendations for the measurement and reporting of diastolic dysfunction by echocardiography. J Am Soc Echocardiogr 1996;9:736-60. 20. Oh JK, Appleton CP, Hatle LK, Nishimura RA, Seward JB, Tajik AJ. The noninvasive assessment of left ventricular diastolic function with two-dimensional and Doppler echocardiography. J Am Soc Echocardiogr 1997;10:246-70. 21. Choong CY, Herrmann HC, Weyman AE, Fifer MA. Preload dependence of Doppler-derived indexes of left ventricular diastolic function in humans. J Am Coll Cardiol 1987;10: 800-8. 22. Pozzoli M, Traversi E, Cioffi G, Stenner R, Sanarico M, Tavazzi L. Loading manipulations improve the prognostic value of Doppler evaluation of mitral flow in patients with chronic heart failure. Circulation 1997;95:1222-30. 23. Berk MR, Xie GY, Kwan OL, et al. Reduction of left ventricular preload by lower body negative pressure alters Doppler transmitral filling patterns. J Am Coll Cardiol 1990;16:138792.
24. McIntyre KM, Vita JA, Lambrew CT, Freeman J, Loscalzo J. A noninvasive method of predicting pulmonary-capillary wedge pressure. N Engl J Med 1992;327:1715-20. 25. Schmidt DE, Shah PK. Accurate detection of elevated left ventricular filling pressure by a simplified bedside application of the Valsalva maneuver. Am J Cardiol 1993;71:462-5. 26. Demeule E, Dumesnil JG, Coulombe D, LeBlanc MH. Comparison of Valsalva Maneuver and pulmonary venous recordings in diastolic function evaluation by Doppler echocardiography. [abstract] J Am Coll Cardiol 1996;27:174A. 27. Little WC, Barr WK, Crawford MH. Altered effect of the Valsalva maneuver on left ventricular volume in patients with cardiomyopathy. Circulation 1985;71:227-33. 28. Payne RM, Stone HL, Engelken EJ. Atrial function during volume loading. J Appl Physiol 1971;31:326-31. 29. Masuyama T, Lee J, Tamai M, Tanouchi J, Kitabatake A, Kamada T. Pulmonary venous flow velocity pattern as assessed with transthoracic pulsed Doppler echocardiography in subjects without cardiac disease. Am J Cardiol 1991;67: 1396-1404.
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