Doppler mitral flow and pulmonary vein flow

Transcription

1 Mitral Regurgitation and Left Ventricular Diastolic Dysfunction Similarly Affect Mitral and Pulmonary Vein Flow Doppler Parameters: The Advantage of End-Diastolic Markers Andrea Rossi, MD, Mariantonietta Cicoira, MD, Giorgio Golia, MD, Maurizio Anselmi, MD, and Piero Zardini, MD, Verona, Italy Enhanced early mitral flow and reduced systolic pulmonary vein flow may be caused both by increased left ventricular pressure as the result of diastolic dysfunction and by increased transmitral flow as the result of mitral regurgitation. Nevertheless, Doppler parameters are widely used to predict left ventricular filling pressure. We aimed to analyze the interference of mitral regurgitation with Doppler parameters usually used to estimate left ventricular filling pressure and to identify markers independent of mitral regurgitation, which could reliably estimate increased left ventricular filling pressure. Eighty-four patients (age, 62 ± 9 years; 82% men) had a complete echocardiographic Doppler examination. Transmitral E- and A-wave velocity, E deceleration time and A duration, pulmonary vein systolic and diastolic velocities, and reversal flow duration and maximal and minimal left atrial volumes were measured. The difference between the duration of pulmonary vein and mitral A waves was calculated (A -A). Mitral regurgitant volume was quantitatively assessed by echocardiography. Left ventricular end-diastolic pressure was measured invasively. Patients had a wide range of left ventricular ejection fraction (14% to 70%), mitral regurgitant volume (0 to 94 ml), and left ventricular end-diastolic pressure (3 to 37 mm Hg). E velocity, E/A, pulmonary vein systolic and diastolic, and systo-diastolic ratios were significantly and independently correlated with both left ventricular end-diastolic pressure and mitral regurgitant volume. A -A showed a strong correlation with left ventricular end-diastolic pressure (r = 0.70; P <.0001), but the relation with mitral regurgitant volume was not significant (r = 0.19; P =.08). Mitral regurgitation affects the majority of Doppler parameters widely used to predict filling pressure but does not influence Ad -Ad, which proved to be the strongest predictor of left ventricular end-diastolic pressure. (J Am Soc Echocardiogr 2001;14:562-8.) From the Division of Cardiology, University of Verona. Reprint requests: Rossi Andrea, MD, Divisione Clinicizzata di Cardiologia, Universita di Verona, Ospedale Maggiore, P.le Stefani Verona, Italy ( Andrea.Rossi@univr.it). Copyright 2001 by the American Society of Echocardiography /2001/$ /1/ doi: /mje Doppler mitral flow and pulmonary vein flow have been extensively used to evaluate left ventricular diastolic function 1,2 and to estimate left ventricular filling pressure. 3,4 Enhanced early diastolic mitral flow and blunted systolic pulmonary vein flow have been considered hallmarks of increased left ventricular filling pressure. 1 Nevertheless, mitral regurgitation induces comparable modifications to both mitral 5,6 and pulmonary vein flow, 7,8 so much so that it has recently been proposed that mitral regurgitation be quantified by using either the velocity of early mitral flow 9 or the systolic proportion of pulmonary vein flow. 10,11 Therefore the reliability of Doppler parameters in estimating left ventricular diastolic function may be undermined by the presence of mitral regurgitation, whose relation with left ventricular filling pressure is unpredictable The possible interaction between mitral regurgitation, filling pressure, and Doppler has already been considered, 15 but mitral regurgitation was graded by regurgitant jet extension. The wide variability in grading mitral regurgitation that has been demonstrated for semiquantitative methods 16 highlights their low accuracy, leaving the pathophysiologic impact of mitral regurgitation unclear. We undertook the current study (1) to analyze the correlation between Doppler mitral and pulmonary vein parameters and quantitatively assess mitral 562

2 Volume 14 Number 6 Rossi et al 563 regurgitation and (2) to highlight the interference with left ventricular filling pressure estimation by the presence of mitral regurgitation. METHODS Patients enrolled in the echocardiographic laboratory were chosen from those who had invasive cardiac catheterization.patients were included if their clinical condition was stable and if the invasive evaluation was performed within 2 days of the echocardiographic study.the only exclusion criteria were the presence of mitral stenosis and atrial fibrillation. Echocardiography All patients were examined in left lateral position by precordial M-mode, 2-dimensional, and Doppler echocardiography. Toshiba (Tokyo, Japan) SSH 140 units with 2.5- and 3.75-MHz transducers were used. Images were stored for later playback and analysis. Left ventricular volumes and ejection fraction were measured from the apical 4-chamber view by means of the monoplane area-length method. Mitral flow velocities were recorded in the apical 4- chamber view; a 0.5- to 1.0-cm pulsed wave Doppler sample volume was placed between the tips of the mitral leaflets, where maximal flow velocity was recorded. E- and A-wave velocities, their ratio, and A-wave duration were measured. Deceleration times of E and A waves were measured as the intervals (in milliseconds) from peak early and late mitral filling to an extrapolation of the deceleration to 0 m/s. Pulmonary vein flow velocities were obtained by placing the sampling volume 0.5 to 1 cm into the orifice of the right upper pulmonary vein during the transthoracic examination. Maximal velocity of systolic and diastolic fraction was measured.the duration of pulmonary vein A wave was also determined to analyze the time difference between mitral and pulmonary vein A wave (A -A).The time-velocity integrals of the systolic and diastolic phases were also measured, and the systolic component was expressed as a percentage of the total (systo-diastolic) velocity-time integral (PVs%). If a systolic reversal flow in the pulmonary vein was present, PVs% was considered zero by definition. During the pulsed wave Doppler study, the filter setting was minimized and Doppler velocity curves were recorded at a horizontal sweep speed of 100 mm/s. Left Atrial Volume Left atrial areas were measured at end systole (the largest dimension or the end of the T wave) and end diastole (the smallest dimension or the onset of QRS complex) from the apical 4-chamber (A1) and apical 2-chamber (A2) views,by using the highest frame rate.the left atrial outlines at end systole and end diastole were traced for 3 consecutive beats, then averaged for all calculations. The end-diastolic (minimal volume) and end-systolic (maximal volume) atrial volumes were calculated according to the Dodge method, with a biplane area-length formula: V = 8 A1 A2 3Lπ where L is the common axis pointing from the apex to the base. 17 Left atrial filling (LAfill) volume is the volumetric change from end systole to end diastole. Left atrial ejection fraction was calculated by using the difference between maximal and minimal atrial volume divided by maximal atrial volume. Mitral Regurgitant Volume Mitral regurgitant volume was considered 0 ml if color Doppler or continuous wave Doppler was unable to detect mitral regurgitation. In the presence of mitral insufficiency, regurgitant volume was measured as previously described, 18 by using the volume variation of the left atrium during ventricular systole and the systolic time-velocity integral of pulmonary vein flow, expressed as a percentage of the total (systo-diastolic) time-velocity integral (PVs%) according to the equation Regurgitant volume = (1.01 * LAfill) (0.783 * PVs%) Cardiac Catheterization An invasive hemodynamic evaluation was performed as part of the routine clinical diagnostic procedure. All patients underwent left heart cardiac catheterization from the femoral percutaneous approach with the use of 6F or 7F catheters. The left ventricular pressure curve was recorded with a pigtail catheter before angiography. Measurements were made over a respiratory cycle and averaged.the angiographic severity of mitral regurgitation was classified according to a conventionally accepted grading scheme 19,20 in 4 grades (1, 2, 3, and 4, from mild to severe). The left ventricular angiogram was interpreted at the time of catheterization by an experienced angiographer who did not know that the data would be analyzed for the current study. Interobserver Variability In 20 patients, mitral and pulmonary vein A waves and the difference between their duration were measured independently by two investigators. Interobserver variability was described by linear correlation. Statistics Results are expressed as mean value ± SD. Linear and multiple regression analyses were used to verify the correla-

3 564 Rossi et al June 2001 Table 1 Correlation of echocardiographic and Doppler parameters and left ventricular end-diastolic pressure and mitral regurgitant volume Correlation with left ventricular end-diastolic pressure Correlation with mitral regurgitant volume r value P value r value P value E-wave maximal velocity 0.54 < A-wave maximal velocity E/A ratio 0.60 < E-wave deceleration time 0.55 < A-wave deceleration time 0.50 < Pulmonary vein systolic velocity <.0001 Pulmonary vein diastolic velocity 0.49 < Pulmonary vein systo-diastolic ratio 0.50 < <.0001 Left ventricular diastolic volume Left ventricular systolic volume Left ventricular ejection fraction Left atrial maximal volume <.0001 Left atrial minimal volume <.0001 Left atrial ejection fraction Not significant Left atrial filling volume 0.04 Not significant 0.58 <.0001 A -A 0.70 < PVs% <.0001 Left ventricular end-diastolic pressure tion between Doppler parameters and left ventricular enddiastolic pressure. Multivariate models were constructed with each Doppler parameter used as a dependent variable and left ventricular filling pressure and mitral regurgitant volume as independent variables to verify the common effect of the two pathophysiologic variables on each Doppler parameter. RESULTS The population comprised 84 patients (mean age, 62 ± 12 years; 82% men). Forty-one patients had left ventricular systolic dysfunction (ejection fraction < 50%) and 43 had normal left ventricular systolic function. In the overall population, a broad range of hemodynamic, functional, and clinical parameters was present: left ventricular ejection fraction: range, 14% to 70% (47% ± 14%); left ventricular end-diastolic pressure: range, 3 to 37 mm Hg (19 ± 8); and mitral regurgitant volume: range, 0 to 94 ml (15 ± 25). The method of quantitatively grading mitral regurgitation was further validated in the current study by analyzing the correlation between the estimated mitral regurgitant volume and the semiquantitative evaluation during left ventriculography (r = 0.72; P <.0001). The majority of Doppler and echocardiographic parameters commonly used to predict left ventricular filling pressure were univariately correlated with both left ventricular end-diastolic pressure and mitral regurgitant volume (Table 1). Multivariate models showed that E-wave velocity, E/A ratio, E-wave deceleration time, systolic pulmonary vein velocity and systo-diastolic ratio, and maximal and minimal atrial volumes were independently associated with both mitral regurgitant volume and left ventricular end-diastolic pressure (Table 2). Neither mitral regurgitant volume nor the semiquantitative grading of mitral regurgitation during left ventriculography correlated significantly with left ventricular end-diastolic pressure (respectively, r = 0.19, P =.08; r = 0.22, P =.1). In patients with left ventricular systolic dysfunction, E-wave deceleration time was an accurate predictor of left ventricular end-diastolic pressure (r = 0.68; P <.0001). However, in 22 patients with mitral regurgitation, the correlation decreased substantially (r = 0.50; P =.02) compared with 19 patients without mitral insufficiency (r = 0.76; P =.0002).A deceleration time less than 200 ms had a specificity of 40% in detecting a left ventricular end-diastolic pressure more than 20 mm Hg in patients with left ventricular systolic dysfunction and mitral regurgitation, whereas it had a specificity of 89% in patients without mitral regurgitation. In the overall population, multivariate analysis was run by using those variables more closely correlated (P <.0001) to left ventricular end-diastolic pressure at the univariate analysis. Table 3 shows that A-A is the most powerful predictor of left ventricular enddiastolic pressure.

4 Volume 14 Number 6 Rossi et al 565 Table 2 Multivariate models relating mitral regurgitant volume and left ventricular end-diastolic pressure to each Doppler parameter Linear correlation of mitral, PV A waves, and A-A measured by the two investigators showed good agreement (mitral A wave: r = 0.90; SEE, 7.6 ms; P <.0001; PV A wave: r = 0.89; SEE, 12.7 ms; P <.0001;A- A : r = 0.95; SEE, 11.7 ms; P <.0001). DISCUSSION Independent variables Left Mitral ventricular regurgitant end-diastolic Dependent variable volume pressure Model 1 E-wave velocity (m/s) <.002 <.0001 Model 2 E/A ratio.004 <.0001 Model 3 E-wave deceleration time (ms).004 <.0001 Model 4 PVs% < Model 5 Pulmonary vein diastolic.02 <.0001 velocity (m/s) Model 6 A -A (ms).3 <.0001 Model 7 Left atrial maximal volume (ml) < The current study shows that mitral regurgitation strongly affects both mitral and pulmonary vein flow and that only end-diastolic Doppler parameters (A- A, A-wave deceleration time, and left atrial ejection fraction) resulted independent of mitral regurgitation. Diastolic Mitral Flow Parameters It is widely accepted that increased early diastolic mitral velocity (E wave), reduced atrial contribution (A wave),and increased E/A ratio are reliable markers of increased filling pressure, 1 particularly in patients with reduced ejection fraction. Mitral regurgitation, which affects up to 68% 15 of those patients, influences mitral inflow pattern in the same direction as left ventricular diastolic dysfunction. 6,21 It has been proposed that mitral regurgitation affects early left ventricular filling by increasing left atrial pressure rather than through the volumetric importance of the regurgitation. 22 However, in our study, mitral regurgitant volume did not significantly correlate Table 3 Multivariate Doppler predictors of left ventricular end-diastolic pressure P value A-A (ms) <.0001 E-wave deceleration time (ms).3 E/A ratio.3 A-wave deceleration time (ms).3 Pulmonary vein diastolic velocity (m/s).8 Pulmonary vein systo-diastolic ratio.6 E-wave velocity (m/s).001 with left ventricular end-diastolic pressure, confirming the unpredictable atrial pressure level in mitral regurgitation Furthermore, multivariate analysis showed that E-wave velocity is independently predicted both by left ventricular end-diastolic pressure and by mitral regurgitant volume.the determinants of early left ventricular diastolic filling (E wave) are the interaction between the pushing atrial pressure and sucking ventricular restoring forces, which generate negative pressures within the ventricle that are difficult to document because they are dissipated by the filling. However, the increased early diastolic flow in mitral regurgitation is associated with enhanced restorative forces and elastic recoil. 23 This emphasizes the fact that mitral regurgitation might enhance the E wave without interfering with left ventricular filling pressure. E-wave deceleration time very accurately predicts filling pressure in patients with left ventricular systolic dysfunction, 3 although in patients with normal ejection fraction the correlation disappears completely, 21a,22a which undermines its clinical utility. A regression equation, constructed with the use of deceleration time, can consistently predict filling pressure in patients with left ventricular dysfunction, but its reliability is reduced in the presence of mitral regurgitation. 15 The lack of quantitative grading of mitral regurgitation leaves unclear the real impact of this limitation on estimates of filling pressure. In accordance with previous observations, 24 our data showed that deceleration time correlates with the degree of mitral regurgitation.furthermore, mitral regurgitant volume and left ventricular enddiastolic pressure proved to be independently correlated with deceleration time. Pulmonary Vein Flow A linear correlation has been described between systolic pulmonary vein velocity and systo-diastolic ratio with left ventricular filling pressure, suggesting that pulmonary vein flow might be used for noninvasive quantitative estimation. 25 However, the pat-

5 566 Rossi et al June 2001 tern of pulmonary vein flow is influenced by several factors, including left atrial pressure and stiffness, left ventricular systolic and diastolic function, right ventricular systolic function, systolic blood pressure, peripheral vascular resistance, age, and cardiac rhythm. In patients with mitral regurgitation, regurgitant volume is a major determinant of pulmonary vein pattern, and indeed, some studies recently proposed the use of PV flow to quantify mitral regurgitant volume. 10,11 The relation between systolic pulmonary vein flow, regurgitant volume, and atrial pressure has recently been evaluated. Pulmonary vein systolic velocity was progressively reduced by increasingly severe mitral regurgitation, and the effect on pulmonary vein flow was not mediated through atrial pressure elevation. 26 End-Diastolic Parameters Early diastolic parameters such as E-wave velocity and deceleration time have been widely used to predict end-diastolic events (chamber stiffness or pressure), especially in patients with left ventricular dysfunction, assuming homogeneous ventricular relaxation impairment. 1 The presence of mitral regurgitation might confound the assessment of relaxation because the rate of isovolumic pressure decline is difficult to measure; this decline does not occur during a totally isovolumic period, and contrasting data have been published. 27,28 Early diastolic mitral flow also may be influenced by regional nonuniformity, 29 which is not a diastolic anomaly but may still alter the ventricular pressure decline during isovolumic relaxation and therefore affect mitral Doppler pattern. Uncertainties regarding these early diastolic phenomena, especially in the presence of mitral regurgitation, argue against the use of early mitral flow parameters to investigate end-diastolic function. The use of end-diastolic parameters is advantageous because they directly reflect this phase for temporal reasons. 30 Furthermore, end-diastolic events may be more predictable because they are closely related to ventricular stiffness, because ventricular relaxation and suction have already been completed. It has been demonstrated that the difference between the duration of pulmonary vein and mitral A waves is a useful marker of increased left ventricular end-diastolic pressure, 31 because it expresses the change in left atrial systolic pressure waveform in relation to diastolic ventricular pressure. 32 In the current study,a -A was found to be the best predictor of end-diastolic pressure; in contrast to other widely used Doppler parameters, it is independent of both left ventricular systolic function 22a and mitral regurgitant volume. Another limitation of using early mitral flow and forward pulmonary vein parameters is their strong age dependency. 33 A young person without any cardiac disorder may have the same mitral and forward pulmonary vein pattern as a patient with restrictive ventricular disease. The high correlation coefficients shown in several studies might be greatly decreased by introducing normal young people into those populations. A -A has been shown to be independent of age 34 ; therefore it can be applied in the majority of patients. Limitations The current study was carried out in a routine clinical diagnostic setting, so that echocardiography and invasive hemodynamic assessment were not simultaneous. However, an inclusion criterion was a stable hemodynamic and ischemic condition, and medication was not modified or withheld before the invasive procedure. A nonsignificant difference between heart rate and blood pressure during the two diagnostic procedures (performed within 48 hours of each other) suggests a similar hemodynamic background. Left ventricular end-diastolic pressure was used as a measure of filling pressure. Right heart catheterization was not performed routinely, so data about mean atrial pressure and atrial v wave were not available. There is an intriguing relation between ventricular diastolic function and atrial systolic function; increased ventricular filling pressure decreases atrial function, which may contribute to an alteration of diastolic filling, but primary atrial dysfunction (ie, after recovering from atrial fibrillation cardioversion) can modify ventricular filling, which may cause misinterpretation of left ventricular diastolic function. However, the difference between pulmonary vein and mitral A-wave duration is not influenced by atrial function because both flows are determined by the same phenomenon, and in our study, A -A did not correlate with left atrial ejection fraction. The methodology used to quantify mitral regurgitation has previously been shown to correlate very strongly with the gold standard Doppler technique, but it has not been validated by other researchers yet. However, the extent of correlation (r = 0.72; P <.0001) between the estimated regurgitant volume and the invasive mitral regurgitation grading during left ventriculography is very close to that described by Dujardin et al 35 between mitral regurgitant volume (quantitatively measured by Doppler) and invasive grading. Pulmonary vein flow is still difficult to measure

6 Volume 14 Number 6 Rossi et al 567 with the echocardiographic transthoracic approach. However, in the current study, pulmonary vein A- wave flow could not be recorded in only 9% of patients; other groups had better results. In our opinion, because pulmonary vein flow gives fundamental information for hemodynamic assessment, the use of new contrast agents that have been shown to significantly enhance pulmonary vein Doppler recordings 36 may be warranted in clinical practice. Conclusions Mitral regurgitation and left ventricular diastolic dysfunction similarly modify both mitral inflow and pulmonary vein Doppler parameters. Consequently, the noninvasive evaluation of diastolic function is confounded by the presence of mitral regurgitation. Opposite to other widely used Doppler parameters, end-diastolic variables are not affected by volume overload induced by mitral regurgitation and might be more reliable markers of diastolic function. REFERENCES 1. Nishimura RA, Tajik AJ. 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