Assessment of Diastolic Function of the Heart: Background and Current Applications of Doppler Echocardiography. Part II.

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1 ΐ 3' "i 11 is f s 4 f, i;:»^ i ^ ^ ^ > Assessment of Diastolic Function of the Heart: Background and Current Applications of Doppler Echocardiography. Part II. Clinical Studies RICK A. NISHIMURA, M.D., Division of Cardiovascular Diseases and Internal Medicine; MARTIN D. ABEL, M.D., Department of Anesthesiology; LIV K. HATLE, M.D., Section of Cardiology, Regional Hospital, Trondheim, Norway; A. JAMIL TAJIK, M.D, Division of Cardiovascular Diseases and Internal Medicine Evaluation of diastolic filling of the heart has been difficult because of its complexity and the numerous interrelated contributing factors. Previous determinations have depended on high-fidelity, invasive measurements of instantaneous pressure, volume, mass, and wall stress, which could not be done on a routine clinical basis. With the advent of Doppler echocardiography, intracardiac blood flow velocities can now be noninvasively assessed. For application of this technique to evaluation of diastolic function in patients with heart disease, it is necessary to understand what the Dopplerderived variables represent. It is also necessary to know how they are affected by changes in loading conditions and changes in myocardial relaxation. In this review, we provide an interpretation of the mitral valve, tricuspid valve, and systemic and pulmonary venous inflow velocities in the normal patient and in various disease states. In the first part of this review (see the January issue of the Proceedings), we presented current concepts of diastole based on complex analyses of high-fidelity pressure measurements and pressurevolume relationships. Although these studies have added to our understanding of the diastolic properties of the heart, these measurements cannot be performed on a routine clinical basis. Therefore, other methods have been proposed for analysis of diastolic function based on volumetric-filling rates of the left ventricle. A variety of techniques, including radionuclide angiography, left ventriculography, and digitized M-mode echocardiography, This work was supported in part by Grant GM from the National Institutes of Health, Public Health Service. Address reprint requests to Dr. R. A. Nishimura, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN Mayo Clin Proc 64: , have been used. Doppler echocardiography was initially used as another method for examining filling rates. Because of its ability to measure blood flow velocity directly, however, it has become a unique technique for evaluation of diastolic function. 1,2 In this section, we discuss the previous findings with use of these different modalities in various disease entities; then we present the current clinical applications of Doppler echocardiography in the assessment of diastole. VOLUMETRIC-FILLING RATES Previous Studies Cardiac Catheterization, Radionuclide Angiography, and M-Mode Echocardiography. The first description of volumetric-filling rates was based on analysis of high-resolution cineangiographic volume changes of the left ventricle during diastole. 3-5 Shortly thereafter, published reports described other modalities in which sequential changes in left

2 182 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE Mayo Clin Proc, February 1989, Vol 64 ventricular volume could be analyzed, including digitized M-mode echocardiography 6-10 and radionuclide angiography A typical graph of volume changes over time is shown in Figure 1, which could be derived from any of the aforementioned methods. A rapidfilling phase occurs in early diastole, during which time the volume rapidly increases; this phase is followed by a slower rate of filling through middiastole and finally a rapid increase in volume at the end of diastole from atrial contraction. Also shown in Figure 1 is the first derivative of the changes in volume, or rates of filling. The highest rate normally occurs during early diastole, midway through the rapid-filling phase, and is followed by a rapid decline in rate. At end-diastole, atrial contraction results in an increase in filling rate. The highest early filling rate, termed the "peak filling rate," has been the most widely evaluated variable in clinical studies. Other variables have included the time to half-peak filling rate, the percentage of filling at middiastole, and the ratio of early-to-late filling. Previous studies in which these filling rates were used have demonstrated abnormal peak filling rates in various disease entities (Table 1). Changes in peak filling rates during interventions have also been reported. In patients with coronary artery disease, abnormally low peak filling rates decrease during ischemia evoked by Fig. 1. Graph of left ventricular volume (top) and first derivative of the volume (bottom) over time. Dotted lines (from left to right) represent the following: (1) end-systole, (2) mitral valve opening, (3) peak diastolic filling, (4) onset of atrial contraction, and (5) end-diastole. (See text for details.) Table 1. Peak Left Ventricular Filling Rates in Various Diseases Disease Coronary disease 3 6 7' Aortic stenosis 9,18,19 Mitral stenosis 3 Amyloid heart disease 20 Hypertension 9,21 " 23 Aortic régurgitation 3 Mitral régurgitation 24 Constructive pericarditis 20 Hypertrophie cardiomyopathy 3,5 9, ' 26 Dilated cardiomyopathy 7 Filling rates * 1 t exercise ' and with balloon inflation during percutaneous transluminal coronary angioplasty. 28,29 Investigators have described an increase toward normalization of abnormal peak filling rates when patients with various disease entities (such as hypertension, 22 hypertrophie cardiomyopathy, 26 or dilated cardiomyopathy 27 ) undergo treatment with medications. The peak filling rates seem to decrease with advancing age. 30,31 Previous Studies Doppler Echocardiography. With the advent of pulsed Doppler echocardiography, blood flow velocity could be measured across cardiac valves and in the cardiac chambers. When a pulsed-wave sample volume was placed at the level of the mitral valve, a characteristic velocity curve was observed. 32 This observed velocity curve resembled the firstderivative curve of the volumetric-filling studies (Fig. 1), as assessed by other modalities. The mitral flow velocity was proposed to reflect rates of changes of volume flowing into the left ventricle. Subsequent studies in which the mitral flow velocity curve was compared with the first derivative of the volume changes by cardiac catheterization, 32 ' 33 radionuclide angiography; 34,35 and digitized M-mode echocardiography 36 demonstrated a fair correlation. As with the other modalities, Doppler echocardiographic measurements of peak filling velocities were shown to be abnormal in patients with various disease entities. Because the contribution from atrial contraction was readily measurable, many studies also examined the ratio of earlyto-late diastolic velocity (E:A ratio). A lower peak filling velocity and a decreased E:A ratio were found in Doppler inflow patterns in patients with coronary artery disease, 29,32,37,38 aortic stenosis, 36 hypertension, 32,39 and dilated cardiomyopathy. 40

3 Mayo Clin Proc, February 1989, Vol 64 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE 183 Variable peak filling velocity was observed in patients with hypertrophie cardiomyopathy. 32,36,41-45 High peak filling rates were found in patients with constrictive pericarditis 46 and mitral régurgitation. 33 Of interest was the finding that athletes had a normal-appearing mitral valve inflow pattern 47 " 51 despite an increase in left ventricular size and mass. CURRENT CONCEPTS OF MITRAL FLOW VELOCITIES Although many investigators have described mitral velocity measurements in various disease states, understanding what these velocities represent is essential for describing the filling characteristics of the left ventricle. Substantial changes in the mitral flow velocities have been noted with changes in loading conditions, 52,53 differing heart rates, 54,55 and the left ventricular contractile state. Previous studies in which flow rates derived by Doppler echocardiography were compared with those of other modalities have demonstrated a reasonable, but not perfect, correlation Some studies have suggested that the Doppler flow velocities are more sensitive than those from other modalities. 36,41 Left ventriculography, radionuclide angiography, and M-mode echocardiography all have inherent limitations for determination of left ventricular volume. Several assumptions made in the Doppler determination of volumetric flow, however, may account for these discrepancies. Volumetric flow analysis assumes a completely laminar flow through a constant cross-sectional area. Although the mitral flow velocity profile has been assumed to be flat, recent work has shown lack of a flat profile, both at the annulus and between the leaflets in normal subjects. 56 Temporally, the flow is directed centrally into the left ventricle in early diastole but then becomes directed posterolaterally during end-diastole. 57 The annulus area itself changes from 10 to 35% throughout diastole, the greatest change occurring during atrial contraction. 58,59 In addition, the annulus moves longitudinally in relationship to the Doppler beam. 58 Therefore, pulsed-doppler recording of the flow velocity through the mitral valve annulus may not accurately reflect instantaneous volumetric flow. An advantage of Doppler echocardiography is the ability to measure the velocity of intracardiac blood flow. Because the flow velocity is determined in part by the pressure gradient across the valves, the mitral flow velocity can be considered as representing the driving force across the mitral valve. A direct application of the modified Bernoulli equation (pressure gradient = 4 χ velocity 2 ) cannot be made for transmitrai velocity because of the contributions of blood flow acceleration, inertial forces, and viscous forces. The relative changes in left atrial and ventricular pressure relationships, however, are reflected by the transmitral velocities The normal mitral flow velocities and the corresponding left atrial and left ventricular pressure contours are shown in Figures 2 and 3. The initial early diastolic velocity begins at a point of pressure crossover as the left ventricular pressure decreases below the left atrial pressure because of continued myocardial relaxation and diastolic suction of the left ventricle. 60,61,63 The pressure gradient generates a "driving pressure" across the mitral valve, rapidly accelerating transmitrai velocity. 53,63,64 The left ventricular pressure increases because of the viscoelastic forces of the u myocardium, pericardial restraint, and ventricular interaction. This increasing left ventricular pressure will approximate or may ex- ΔΑ Fig. 2. Diagram of left ventricular and left atrial pressure contours in normal heart (top), with corresponding mitral flow velocity curve (bottom).

4 184 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE Mayo Clin Proc, February 1989, Vol 64 A2 S, PHONO " l -E / \ -A IVR AT DT IVR<40y.o. 69±12msec IVR >40 y.o. 76 ± 13 msec DT (age 20-60) = 199 ± 32 msec E = 0.85±0.16 m/sec A = 0.56±0.13 m/sec Fig. 3. Diagram of a normal mitral flow velocity curve, demonstrating Doppler-derived determinations. A = velocity at time of atrial contraction; A 2 = aortic valve closure; AT = acceleration time; DT = deceleration time; E = initial peak velocity; IVR = isovolumic-relaxation period; phono = phonocardiogram; Si = first heart sound. ceed the left atrial pressure, and the transmitrai velocity will decelerate. 61,63 The rate of decline in the mitral velocity can be measured by the deceleration time, which is the time from the peak filling to an extrapolation of the rate of decline of the velocity to baseline (Fig. 3). In middiastole, continued forward flow with low velocities may be seen in the absence of a measurable pressure gradient, possibly because of inertia. During atrial contraction, the left atrial pressure increases relative to the left ventricular pressure and results in a late acceleration of mitral flow velocity. It is apparent how changes in the relationship between the left ventricular and the left atrial pressures can result in changes in the mitral flow velocity curves. This concept can be used to explain the various effects of altered myocardial relaxation and loading conditions on the mitral flow velocities. The time constant of relaxation (tau) has previously been demonstrated to be inversely related to the peak filling rate. 15,53,65 " 69 A prolongation of relaxation, or increase in tau, will result in a lower peak early gradient between the left atrium and the left ventricle. In addition, the decrease of the left atrial-left ventricular gradient in middiastole is prolonged because of continued delayed myocardial relaxation (Fig. 4). 70 Figure 5 demonstrates the actual changes in a mitral flow velocity pattern in a patient with increased afterload and thus prolonged myocardial relaxation. These factors resulted in a decrease in the peak velocity and also a slower rate of decline of the velocity; hence, the deceleration time was lengthened. With increases in filling pressures, these relationships may no longer be seen. 71 A change in the compliance of the left ventricle may result in substantial changes in the deceleration time and in the contribution from atrial contraction. Patients who demonstrate a decrease in compliance (large change in pressure per unit change in volume) may have a rapid increase in left ventricular pressure early in diastole (that is, an increase in the height of the rapid-filling wave). The rapid increase in left ventricular diastolic pressure will result in considerable shortening of the deceleration time as the left atrial-left ventricular pressure gradient decreases more rapidly. 71 There may be less filling during atrial contraction when the left ventricular pressure is high before atrial contraction. This decrease in compliance can be due to either (1) a true shift of the pressure-volume curve upward and lefti I I I I U Fig. 4. Diagram of prolongation of myocardial relaxation on left ventricular and left atrial pressure contours (top). There is a slower rate of decline of left ventricular pressure, which continues into middiastole. Resultant mitral flow velocities are shown below, with decrease in initial peak velocity, prolongation of deceleration time, and a low E:A ratio. i

5 Mayo Clin Proc, February 1989, Vol 64 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE 185 ward or (2) a shift to the right on a normal curvilinear pressure-volume curve. In patients with less abnormal compliance, the abnormal pressure response may occur only late in diastole at the time of atrial contraction. Early mitral flow Fig. 5. Mitral flow velocity curves in the same patient during various loading conditions. Top Left, Control state. Top Right, During pharmacologie increase in afterload, resulting in decrease in peak velocity and prolongation of deceleration time (DT). Bottom Left, During preload reduction with intravenously administered nitroglycerin (NTG), resulting in decrease in peak velocity and prolongation of deceleration time. Bottom Right, During fluid loading, resulting in increase in peak velocity and shortening of deceleration time. BP = blood pressure; PCW= pulmonary capillary wedge pressure. velocity and the velocity at the time of atrial contraction may then be normal, but the increased pressure may result in a larger reversal in the pulmonary veins during atrial contraction. Changes in preload do not directly affect the time constant of relaxation 72 but have a major effect on passive compliance (because of the curvilinear nature of the diastolic pressure-volume curve). For larger preloads, there will be a greater change in pressure per a given change in volume. In addition, a higher preload will increase the left atrial pressure relative to the left ventricular pressure in early diastole. This effect results in a higher initial driving pressure across the mitral valve, 53 ' 65-68,73 as shown in Figure 6. If there is a larger and more rapid increase in left ventricular early diastolic pressure, this pressure gradient will decline more rapidly and the deceleration time will shorten. Conversely, a decrease in preload results in a lower driving pressure across the mitral valve and consequently a lower initial velocity, and the deceleration time may lengthen. Figure 5 demonstrates the actual changes of a decrease in initial velocity and prolongation of the deceleration time in a patient who underwent preload reduction by intravenous administration of nitroglycerin. The increase in preload by administration of fluids causes the opposite effect an increase in early peak velocity and a shortening of the deceleration time (Fig. 5). This conceptual framework demonstrates that the mitral flow velocities are dependent on many factors that must all be considered for interpretation of abnormalities of diastolic function. Myocardial relaxation, passive compliance, and left atrial pressure all play important roles in determining the mitral flow velocities. When myocardial relaxation is prolonged, a decrease in peak velocity and a lengthening of the deceleration time will be noted if the left atrial pressure is not clearly increased. In the presence of decreased compliance, deceleration time can shorten and the velocity at the time of atrial contraction may decrease. The filling pressure affects all variables because an increase in the left atrial pressure will increase the driving pressure across the mitral valve and also shift the diastolic pressure-volume curve upward and to the right. In addition, nonuniformity of relaxation dramatically affects any measurement of diastolic function. In normal persons, different segments of the left ventricle may undergo relaxation at varied rates. In var-

6 186 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE Mayo Clin Proc, February 1989, Vol 64 LÌ u y ^± J\j± A^. \ preload Control t preload Fig. 6. Diagram showing left ventricular and left atrial pressure tracings (top) and resultant mitral flow velocities (bottom) at different preload conditions. Center example depicts a patient with normal hemodynamics. Lower preload will result in example on the left. Higher preload will cause changes observed in example on the right. (See text for details.) ious disease states, the rates of relaxation of the different segments may demonstrate wider variations 26 ' 74 " 77 and may affect the mitral flow velocities. The deceleration time is a measure of how rapidly the early diastolic filling stops. It is influenced by myocardial relaxation, passive filling, and left atrial and left ventricular pressures. The isovolumic-relaxation period reflects the rate of myocardial relaxation but is also dependent on the magnitude of the decrease in left ventricular pressure as well as the height and contour of the left atrial pressure. 78 A combination of the deceleration time and a measure of the isovolumicrelaxation period, as well as the relationship between early and late filling, is currently used to assess overall diastolic function. In addition to evaluation of the filling of the left ventricle, Doppler echocardiography can be used to assess the filling of the right ventricle and the venous inflow patterns. In the subsequent material, we will discuss current clinical applications of Doppler echocardiography. MITRAL FLOW VELOCITIES Normal. The mitral flow velocity curve provides a considerable amount of information about the diastolic-filling characteristics of the left ventricle. A pulsed-wave sample volume may be recorded at different levels within the inflow region. For obtaining volumetric flow, placing the sample volume at the level of the mitral valve annulùs has the advantage of less change in flow area during diastole; however, in order to determine the highest velocities, the sample volume should be placed between the tips of the mitral valve leaflets. 71,79 These highest velocities best reflect the driving force across the mitral valve. The normal mitral flow velocity curve is shown in Figures 2 and 3. The onset of flow reflects mitral valve opening. A high initial velocity ("E" velocity) represents early rapid filling. The acceleration time is the time interval from mitral valve opening to the peak velocity. During this period, the left ventricular pressure decreases more rapidly than the left atrial pressure because of continued myocardial relaxation. The peak E velocity is followed by a decrease in velocity that initially is linear. The deceleration time can be measured as the time from peak filling (E velocity) to an extrapolation of this negative slope to the baseline. In middiastole, there is continued forward flow with a low velocity. At times, the velocity may increase again in middiastole, partly because of pulmonary venous flow. During late diastole, in patients with normal sinus rhythm, the velocity ("A" velocity) increases rapidly because of atrial contraction. The height of the A velocity, as well as the E:A ratio, is dependent on the absolute-filling volume, loading conditions, contractility of the left atrium itself, and ventricular compliance. The isovolumic-relaxation period, or the time from aortic valve closure to mitral valve opening, can be measured by Doppler echocardiography. The most accurate method is to superimpose a simultaneous phonocardiogram on the mitral valve inflow signal (Fig. 7). The first highfrequency component of the second heart sound usually represents aortic valve closure and can be verified by superimposing the phonocardiogram on an aortic valve Doppler signal. One can then measure the time interval from aortic valve closure on the phonocardiogram to mitral valve opening (onset of the mitral valve velocity profile). If a phonocardiogram is not available, a continuous-wave Doppler signal, which intersects both the left ventricular outflow velocity and the mitral valve motion, can be used to derive this interval (Fig. 8). Investigators have observed that changes may occur in some of these measurements during different phases of respiration. Therefore, recording of respiration when the Doppler measurements

7 Mayo Clin Proc, February 1989, Vol 64 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE 187 " '!""i""l""r Fig. 7. Measurement of isovolumic-relaxation period with use of phonocardiogram. Left, Phonocardiogram superimposed on pulsed-wave Doppler tracing of aortic valve, verifying that the first high-frequency component of the second heart sound (S2) represents aortic valve closure (ave). Right, Phonocardiogram superimposed on pulsed-wave Doppler tracing of mitral flow velocity. Isovolumicrelaxation period is time from aortic valve closure to mitral valve opening (mvo). Si = first heart sound. are obtained is a useful procedure (Fig. 9). A practical method is to use a nasal respirometer that can be clipped onto a nostril. This device measures the changes in respiration by means of a heat-sensitive probe, and the tracing can be superimposed directly onto the Doppler tracing. An upward deflection in the respirometer tracing represents the onset of inspiration, and a downward deflection represents the onset of expiration. Normal values for some of these measurements are shown in Table 2. Some of these variables are dependent on the age of the subject, presumably because of changing diastolic properties of the myocardium with aging. 57,80-82 Left ventricular mass will increase with advancing age, 83,84 a factor that may increase myocardial stiffness. 80,85 Nonuniformity of myocardial relaxation may be present to a higher degree with increasing age; thus, diastolic variables may also be affected. 75 With increasing age, the isovolumic-relaxation period is prolonged, 86 the E velocity is decreased, and the A velocity is increased. 57,80 " 82 The Doppler variables will also depend on the loading conditions, the heart rate, and the contractile state of the heart. Therefore, all these factors must be considered when the Doppler findings are compared with "normal" values. Abnormal Relaxation. One of the first observations made when the mitral flow velocities were examined in various disease states was the presence of a low initial peak velocity in patients with abnormal myocardial relaxation. This finding has been noted in patients with hypertrophie cardiomyopathy, hypertension, and coronary artery disease. 32,36,37,44 The characteristic mitral flow velocity curve is shown in Figure 10. This velocity curve may be explained by a slower rate of decline of the left ventricular pressure caused by an abnormality of myocardial relaxation (Fig. 4). In such patients, tau (or the time constant of relaxation) is prolonged, and the result is a "flattening" of the left ventricular pressure during early diastole and middiastole. Because flow into the left ventricle is dependent

8 188 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE Mayo Clin Proc, February 1989, Vol 64 l i l l l t M l I t I I I t I M I t I t «r - -a~~ Table 2. Doppler Measurements of Mitral and Tricuspid Velocities in Normal Subjects* Measurement Mitral Tricuspid Velocities (cm/s) E A 86 ±16 56 ±13 57 ±8 39 ±6 E:A 1.6 ± ±0.3 AT (ms) 73 ±10 83 ±14 DT (ms) 199 ± ± 28 DT, insp (ms) 221 ± 31 IVR (ms) <40 yr old >40 yr old 69 ±12 76 ±13 *Values are reported as means ± 1 SD. A = velocity at time of atrial contraction; AT = acceleration time; DT = deceleration time; E = peak initial velocity; insp = during inspiration; IVR = isovolumic-relaxation time. Data from Appleton and associates. 79 Fig. 8. Continuous-wave Doppler tracing intersecting left ventricular outflow velocity and mitral valve motion. Isovolumicrelaxation period is time from aortic valve closure (ave) to mitral valve opening (mvo). on the left atrial-left ventricular pressure gradient, the filling early in diastole is slower. Therefore, a greater proportion of filling occurs later in diastole, and atrial contraction may result in a higher velocity of blood flow into a ventricle when relaxation now is complete. Whether this larger volume of blood will result in an abnormal increase in the left ventricular pressure at the time of atrial contraction depends on the compliance of the ventricle. 71 When compliance is normal, filling will increase without an abnormal increase in pressure during atrial contraction. If compliance is decreased, an abnormal increase in pressure will accompany the increase in filling. Abnormal relaxation can be indicated by the presence of a prolonged isovolumic-relaxation Fig. 9. Respirometer tracing superimposed on mitral flow velocity curve, indicating onset of inspiration (insp) and expiration (exp). There is a 200-ms delay inherent in the respiratory tracing. Measurement of deceleration time (DT), initial peak velocity (E), and velocity at time of atrial contraction (A) are shown.

9 Mayo Clin Proc, February 1989, Vol 64 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE 189 B,,...,...,. l,j*l\0*s*'"**"" r ~"'~' f DT380» IVR 140 ave mvo 4 I r i fp.v;* «r i wmwif- τ^ρ Mir Vp*wPfe, I Fig. 10. Mitral flow velocity curve of a patient with abnormal myocardial relaxation. A, Deceleration time (DT) is prolonged, and E:A ratio is low (see text). B, Isovolumic-relaxation period (IVR) is substantially prolonged to 140 ms. ave = aortic valve closure; mvo = mitral valve opening. I i #f period, low E velocity, and prolonged deceleration time. Of these, the isovolumic-relaxation period is probably the most sensitive measurement, as it is the first to become abnormal. All these variables will be influenced by changes in the filling pressure. A low filling pressure will exaggerate the degree of any abnormalities. If left atrial pressure is increased in a patient with abnormal myocardial relaxation, the mitral valve will open earlier and the driving pressure across the mitral valve will be higher. The result will be a decrease in the isovolumic-relaxation period and an increase in the height of the E wave. The increase in early filling may lead to a more rapid increase in left ventricular diastolic pressure and a resultant decrease in deceleration time. Thus, the mitral flow velocity curve may undergo a "pseudonormalization," in which the velocity curve appears to be similar to that of a patient with normal diastolic function (Fig. 11). It may be possible to distinguish this pattern from normal by examining the pulmonary venous inflow velocity. The degree of atrial reversal on the pulmonary venous velocity may be increased if the left ventricular pressure is abnormally increased during atrial contraction. Restriction to Filling. Another abnormality of the mitral flow velocity consists of a high, early diastolic velocity, a short deceleration time, and a relatively small A velocity (and thus a high E:A ratio) (Fig. 12). This type of abnormality occurs when there is a large increase in pressure per unit volume during the early diastolic-filling phase and is seen in restriction to filling. This type of pattern is evident in patients with restrictive cardiomyopathy 79 and also in dilated, hypertrophie, or ischemie cardiomyopathy with high filling pressures. The hemodynamic abnormality in these patients consists of a high left atrial pressure and a rapid increase in left ventricular diastolic pressure during rapid filling; thus, a "dip and plateau" is created (Fig. 13). The major pathophysiologic problem is a decrease in compliance in early

10 190 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE Mayo Clin Proc, February 1989, Vol 64 in the presence of high left ventricular diastolic pressures. 79 Restriction to filling may occur in patients with normal or abnormal myocardial relaxation. The deceleration time is likely a result of the relative contribution of passive ventricular compliance and myocardial relaxation. Thus, one may have considerable prolongation of tau yet still have a short deceleration time if the effect of an abnormality of compliance outweighs the effect of abnormal relaxation. Valvular Abnormalities. In the presence of various left-sided valvular abnormalities, the mitral flow velocities can be profoundly affected. Therefore, the presence or absence of valvular disease must be established. In patients with severe aortic régurgitation, the left ventricular diastolic pressure may rapidly increase early in diastole, and the result will be Fig. 11. Diagram depicting left atrial and left ventricular pressure tracings and mitral flow velocity curve in a patient who initially demonstrated abnormal myocardial relaxation (solid lines). With increase in preload, left atrial pressure increased relative to left ventricular pressure in early diastole. Thus, driving force across mitral valve will be higher, and "pseudonormalization" pattern will appear (dotted lines). I tl tl l# I I f t tl ll I I I * I I I, t, f,,, ) ^ff^i^^^ diastole, in which the pressure is considerably increased for small changes in volume. This decrease in compliance may be due to (1) a shift of volume on a pressure-volume curve to the far right in the presence of a normal modulus of chamber stiffness (dilated ventricle) or (2) a displacement of the entire diastolic curve upward and leftward (restrictive cardiomyopathy). Most of the filling occurs during the rapid-filling phase. The contribution of atrial contraction depends on the left ventricular diastolic pressure before atrial contraction. 87 " 89 When the left ventricular diastolic pressure is substantially elevated, the A velocity begins to decrease. 88 Atrial function may still be normal, and a corresponding increase in atrial reversal velocity would be evident in the pulmonary veins. A low A velocity may also be due to failure of left atrial contraction. Diastolic mitral régurgitation may be seen f Ύ.Γ l ' I ί Fig. 12. Mitral flow velocity curve of a patient with restriction to filling. Note high initial peak velocity, shortened deceleration time (DT), and low velocity at time of atrial contraction.

11 Mayo Clin Proc, February 1989, Vol 64 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE 191 L Fig. 13. Diagram depicting left atrial and left ventricular pressure tracings (top) and mitral flow velocity curve (bottom) in restriction to filling. Initial gradient is high during early diastole, and left ventricular pressure shows "dip-and-plateau" pattern. The result is shortening of deceleration time and high E:A ratio on mitral flow velocity curve (see text). a rapid equalization of left atrial and left ventricular pressures and a pronounced increase in the overall rate of left ventricular filling (with contributions from both mitral valve inflow and aortic régurgitation). Therefore, the gradient between the left atrium and the left ventricle will sharply decrease and the deceleration time will be shortened. 90 A short deceleration time has been shown to normalize in patients who have undergone aortic valve replacement for severe aortic régurgitation. The presence of severe mitral régurgitation may also affect the mitral flow velocity curve. When mitral régurgitation causes a large "V" wave in the left atrial pressure, the left atrial-left ventricular gradient and the initial peak velocity will be high. During percutaneous aortic balloon valvuloplasty, an appreciable increase in the initial peak velocity in the presence of severe mitral régurgitation has been demonstrated. 90 The presence or absence of severe mitral régurgitation might be one of the reasons for the variability in peak filling rates noted in patients with hypertrophic cardiomyopathy 44,45 or dilated cardiomyopathy. 40 Coexistent mitral stenosis or a mitral valve prosthesis obviates any interpretation of diastolic function because of the intrinsic left atrial-left ventricular gradient. The common occurrence of trivial mitral régurgitation probably does not affect the mitral flow velocity inasmuch as it has a minimal effect on the left atrial pressure. Caveats. Sample Volume Position. The highest velocities across the mitral valve are usually recorded with the sample volume at or between the tips of the mitral valve leaflets as they open during diastole. In this region, one should detect the opening click of the mitral valve, and the closing click should be inaudible or just barely audible. If no clicks are heard, the sample volume may be too far into the left ventricular cavity. If a loud closing click or mitral régurgitation is present, the sample volume may be too close to the mitral valve annulus. The position is important because the velocity curve changes with alterations in position (Fig. 14). 91 As the sample volume is placed further superiorly, the E velocity lessens in conjunction with relatively smaller change in the A velocity. Therefore, the relationship between E and A can change substantially by movement of the sample volume. The deceleration time decreases when the sample volume is moved into the left atrium. These changes with the position of the sample volume can be greater in patients with abnormalities of diastolic filling in comparison with normal subjects. If the sample volume is placed at the level of the mitral valve annulus, small changes in position of the sample volume relative to the heart (because of respiratory or cardiac movements) may result in changes in the velocity curve. As the sample volume is placed superiorly into the left atrium, diastolic mitral régurgitation may become evident in the presence of high left ventricular diastolic pressure. 79 The sample volume should be superior to the mitral valve annulus when a patient is examined for diastolic mitral régurgitation in order to avoid eddies on the ventricular side of the mitral valve. Diastolic mitral régurgitation may also be seen during atrial relaxation in the presence of first-degree atrioventricular block or other atrial arrhythmias. 92

12 192 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE Mayo Clin Proc, February 1989, Vol 64 τ ρ τ,.,, ^., ^. ρ.,., τ, τ ^ ^, ρ».,,,,,,. MVI ANNULUS 3p VV\-*W^NkWiAV*\**>c'W'/*^ IA Fig. 14. Mitral flow velocities in a normal patient when sample volume is placed at mitral valve leaflet tips (top), 5 mm inferior to level of mitral annulus (middle), and into the left atrium (LA) (bottom). Opening click of mitral valve is shown in top panel, and closing click of mitral valve is shown in middle and bottom panels. Changes in E:A ratio and deceleration time are more pronounced in patients with abnormalities of mitral flow velocity curves (see text). MVI = mitral valve inflow. A continuous-wave Doppler tracing across the mitral valve will sum all the velocities along the Doppler beam. The resultant mitral flow velocity curve will be different from a pulsed-wave flow velocity curve; thus, continuous-wave Doppler echocardiography should not be used in assessment of diastolic function (Fig. 15). Heart Rate. The heart rate may influence the relative height of the E and A velocities, although it has little effect on the deceleration time. 55 With an increased heart rate, the A velocity will be increased relative to the E velocity. 54 The isovolumic-relaxation period is also dependent on the heart rate the duration increases as the cycle length increases. 86 Therefore, the heart rate must be taken into consideration when Doppler measurements are obtained. The presence of multiple ventricular ectopie beats may complicate assessment of diastolic function, as changes in contractility resulting from the ectopie beats may influence the subsequent diastole. With an increase in heart rate or prolongation of the PQ interval (or both), the E and A velocities may merge to form a single diastolic signal. In these instances, a maneuver such as carotid sinus massage may be performed to decrease the heart rate and thereby allow the E and A velocities to emerge separately. Heart Rhythm. In the presence of atrial flutter, organized atrial contraction occurs at a rate of 300 beats/min. Depending on the atrial function and the left ventricular compliance, the contribution by atrial contraction may be variable. The diastolic measurements cannot be determined in this situation, as the repeated atrial contraction will be superimposed on the rapidfilling phase. When atrioventricular dissociation is present, the mitral flow velocity will vary, depending on the timing of atrial contraction. 93 This occurrence can be associated with complete heart block, VVI (ventricular demand) pacing, or blocked supraventricular ectopie beats. If atrial contraction occurs during rapid diastolic filling, the velocity curve will represent the summation of both; thus, the usual variables cannot be measured accurately. In the presence of sinus rhythm with varied PQ intervals, the rapid-filling velocity is unaffected. 94 Right ventricular pacing will affect filling of the left ventricle by producing asynchronous myocardial relaxation. Therefore, there will be a direct effect on regional and global indices

13 Mayo Clin Proc, February 1989, Vol 64 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE 193 Fig. 15. Mitral flow velocities, illustrating differences in deceleration time (DT) and E:A ratio (see text) when pulsed-wave Doppler (PW) (left) is used in comparison with continuous-wave Doppier (CW) (right). of relaxation unrelated to loading conditions or contractility. 95 Because myocardial relaxation is prolonged and the peak filling rate is depressed, the isovolumic-relaxation period will be prolonged and the E velocity will be decreased. Isovolumic Flow. In patients with a hypertrophied, nondilated left ventricle or a hyperdynamic heart, flow may be recorded toward the left ventricular apex during the isovolumicrelaxation period when both mitral and aortic valves are closed (Fig. 16). This flow pattern may be due to asynchronous myocardial relaxation, with the apex relaxing before the base of the heart, which creates an intraventricular pressure gradient favoring flow toward the apex. 96 This isovolumic flow is usually recorded toward the transducer before mitral valve opening and can occasionally merge with early diastolic filling. It should be distinguished from true filling, however, as it occurs before mitral valve opening. TRICUSPID FLOW VELOCITIES Normal. The tricuspid flow velocity curve is a valuable adjunct to the interpretation of the mitral flow velocities because it reflects the filling characteristics of the right side of the heart. The diastolic velocities are slightly lower than those of the mitral valve. The normal tricuspid flow velocity curve, similar to the mitral flow velocity curve, consists of an early diastolic velocity that denotes rapid filling, a rapid descent during middiastole, and an increase in velocity during atrial contraction. As opposed to the normal mitral flow velocity curve, the peak velocity in normal persons changes during the respiratory cycle, with an increase during inspiration and a decrease during expiration. Normal values for the tricuspid flow velocities are shown in Table 2. The pitfalls that can occur in the assessment of the mitral flow velocities are also present in the assessment of the tricuspid flow velocities. Therefore, close attention must be paid to the heart rate and rhythm and the position of the sample volume. Abnormalities. Abnormalities of tricuspid flow velocity curves are similar to those of the mitral flow velocities. Patients with abnormal relaxation of the right ventricle may show a prolongation of the deceleration time and a decrease in the E:A ratio. This pattern has been shown to be present in patients with right ventricular infarction. 38,97 Similar changes are present in patients with right ventricular hypertrophy due to pressure overload. Patients with abnormally decreased compliance of the right ventricle will demonstrate findings

14 194 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE Mayo Clin Proc, February 1989, Vol 64 of restriction to filling. One element will be a shortened deceleration time, which will further decrease during inspiration when the increase in filling produces a volume loading. Diastolic tricuspid régurgitation can also be seen as the right ventricular diastolic pressure becomes elevated and exceeds that of the right atrium. By recording both the mitral and the tricuspid flow velocities in association with respiration, conditions with increased ventricular interactions can be diagnosed. VENOUS INFLOW PATTERNS Normal. Doppler echocardiography is useful for examining venous inflow patterns, including flow through the superior and inferior venae cavae, hepatic veins, and pulmonary veins (Table w IVR.2m/s f mài M f:m ' MVO * Fig. 16. Flow toward left ventricular apex (small arrowheads) occurring during isovolumic relaxation (IVR). This pattern should not be mistaken for true peak filling velocity (large arrowheads) starting at mitral valve opening (MVO). 3). The velocity curve in the inferior and superior venae cavae resembles the pressure waveforms seen clinically in the jugular veins or at catheterization. Flow in the inferior vena cava can be recorded from the apical or low-left parasternal window when a reasonable angle of incidence can be obtained. The angle of incidence is usually large when the inferior vena cava is examined from the subcostal position. In most patients, the Doppler beam can be placed in the hepatic vein flow from the subcostal position; thus, a low angle of incidence is achieved. Because of the small diameter of the hepatic vein in patients with low rightsided pressures, keeping the sample volume within the vein during respiration may be difficult. A normal hepatic vein velocity curve is shown in Figure Usually, a negative velocity (antegrade flow) is present during both systole and diastole, the systolic velocity being higher than the diastolic velocity. A small degree of positive velocity (retrograde flow), called a "reversal" of flow, may be seen during end-systole and during atrial contraction. The superior vena cava can be imaged from the suprasternal or right supraclavicular position with a sample volume placed at a depth of 5 to 7 cm in the superior vena cava. The normal flow velocity in the superior vena cava is similar to that in the hepatic vein except for a relatively smaller degree of reversal (Fig. 17). 98 In most adults, pulmonary vein velocities can be recorded from the apical four-chamber view. Color flow imaging may be used to guide the placement of the sample volume at the junction of the pulmonary vein and the left atrium. In patients in whom the parasternal windows provide an excellent view, pulmonary vein flow can sometimes be recorded from the parasternal short-axis view. The normal pulmonary vein flow is biphasic and consists of both a systolic and a diastolic antegrade signal (Fig. 18). 99 ' 100 Lowvelocity atrial reversal is commonly seen. Major respiratory changes can be seen in the right-sided venous flow patterns in normal subjects and in patients with various disease entities. Therefore, a simultaneous respiratory tracing is helpful in interpretation of these flow curves. Normal values of both forward and reverse flow velocities during respiration are shown in Table 3. During inspiration, forward flow velocity is increased and reversal is diminished. With the onset of expiration, increased reversal can be

15 Mayo Clin Proc, February 1989, Vol 64 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE 195 V^-^V^ T.2m/s Ï.2m/s» ^ f * 1 ^Ρ^Ι ^WP> ":fv]f v * -Ψ SVC n * i fm Hepatic Vein B* Fig. 17. Velocity curves of normal superior vena cava (SVC) (A) and hepatic vein ( ). Antegrade flow is evident during both systole and diastole (systolic flow is greater than diastolic flow). There is a small reversal at time of atrial contraction; reversal is relatively higher in hepatic vein, where reversal at end-systole may be seen. seen and forward flow velocity is slightly lower than during apnea. Abnormalities. Abnormalities of the venous flow patterns occur in various disease states, as discussed in the subsequent paragraphs. Atrial Fibrillation. In the presence of atrial fibrillation, the reversal of flow normally seen during atrial contraction will be absent. Systolic forward flow may be decreased because it is partially due to atrial relaxation; however, movement of the atrioventricular annulus during systole causing enlargement of both atria also may contribute to systolic forward flow. Therefore, systolic forward flow may still be present, albeit decreased, in patients with atrial fibrillation. 101 Tricuspid Régurgitation. One of the contributions provided by the right-sided venous flow velocity pattern is in the quantitation of tricuspid régurgitation. 101 " 103 It complements color flow imaging and should be an integral part of the assessment of patients with tricuspid régurgitation. Patients with severe tricuspid régurgitation usually have dilated hepatic veins, a factor that technically facilitates the recording. In severe tricuspid régurgitation, there is a large retrograde blood volume from the right ventricle into the right atrium and often into the cavae during systole. As a result, an appreciable systolic reversal will appear in the venous flow velocity ομγνβ, similar to the large V wave seen on the jugular venous pulse tracing (Fig. 19). All forward flow occurs during diastole, and with the additional systolic régurgitant volume, the early diastolic velocity may be increased. Patients with lesser degrees of tricuspid régurgitation have little or no systolic reversal and lower diastolic forward velocity. They may have only a reduction in, or a cessation of, systolic forward flow velocity. The velocity flow pattern in the hepatic vein and superior vena cava, however, is dependent not only on the degree of tricuspid régurgitation but also on the size and the compliance of the right atrium, as well as right atrial and ventricular function. Therefore, a patient with a large and compliant right atrium will not manifest the same degree of abnormality as a patient with a less compliant atrium and a similar degree of tricuspid régurgitation. In patients with atrial

16 196 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE Mayo Clin Proc, February 1989, Vol 64,....,....,....,....,....,...!... PULMONARY VEIN Ί Ι< Ψ# '. ψ *"}*Τ.'^ψ^ Fig. 18. Normal pulmonary vein flow, consisting of both systolic (S) and diastolic (D) antegrade signals and atrial reversal (A). fibrillation and tricuspid régurgitation, systolic reversals will be greater than in patients who have a decrease in forward flow during systole because of loss of atrial contraction. As in normal patients, those with tricuspid régurgitation have more prominent reversals in the hepatic veins than in the superior vena cava. With severe tricuspid régurgitation, however, this difference can be pronounced. Abnormal Relaxation. Patients who have myocardial disease that involves the right side of the heart or right ventricular hypertrophy from pressure overload may demonstrate abnormalities of relaxation in the venous inflow velocities (Fig. 20). If the abnormal relaxation is moderate, the forward flow during diastole may be less than usual. With more severe abnormalities of relaxation, diastolic forward flow may be completely absent (Fig. 21). The atrial reversal velocity will be increased if there is a coexistent decrease in compliance of the right ventricle. Decreased Compliance. In patients with restrictive cardiomyopathy or myocardial disease associated with decreased compliance, abnormalities occur in the venous inflow velocities. 79 In the early stage, first atrial reversal increases and then systolic forward flow decreases. In the later stages, systolic filling can be completely lost, and all forward flow may occur during diastole (Fig. 22). With a substantial decrease in compliance, rapid cessation of filling is evident, and reversal of flow occurs before the onset of atrial contraction. The determinant of when diastolic filling becomes predominant over systolic filling depends on atrial contractility, as well as right ventricular diastolic pressure, right ventricular systolic function, and coexistent tricuspid régurgitation. When atrial function deteriorates, predominant diastolic filling will occur. Characteristic changes in the velocity curves during respiration are noted in patients who have restriction to filling (Fig. 22). As in normal subjects, such patients have an increase in forward flow velocity during inspiration. In contrast to normal subjects, however, they have a greater degree of reversal occurring both at the time of atrial contraction and during systole. One may even see holosystolic flow reversal during inspiration because of a blending of these reversals. This increase in reversal seen in conjunction with an increase in forward flow during inspiration is a good marker for the presence of physiologic restriction. Table 3. Doppler Measurements of Superior Vena Cava and Hepatic Vein Velocities in Normal Subjects* Measurement Forward flow (cm/s) Systole Apnea Inspiration Expiration Diastole Apnea Inspiration Expiration Reverse flow (cm/s) Atrial Apnea Inspiration Expiration Ventricular Apnea Inspiration Expiration Superior vena cava 45.7 ± ± ± ± ± ± ± ± ± ±2.1 *Values are reported as means ± SD. Data from Appleton and associates. 98 Hepatic vein ± ± ±

17 Mayo Clin Proc, February 1989, Vol 64 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE 197 Normal Mild-mod Severe Fig. 19. A, Hepatic vein velocity curve from a patient with severe tricuspid régurgitation. Because of régurgitation, holosystolic reversal is present. All antegrade flow occurs during diastole. B, Diagram of spectrum of venous inflow patterns occurring with various degrees of tricuspid régurgitation, mod = moderate. The presence of coexistent tricuspid régurgitation complicates the analysis of systolic filling and restriction because the tricuspid régurgitation itself may cause systolic reversal and an increase in diastolic forward flow velocity. If severe tricuspid régurgitation is present, a pronounced inspiratory increase in reversal flow A Normal Relaxation (mild) Relaxation (severe) *=- Restriction Fig. 20. Diagram of wide spectrum of venous inflow abnormalities occurring in patients with myocardial disease of right side of heart. may still indicate the presence of restriction to filling. A short tricuspid deceleration time with further shortening during inspiration will also be seen if restriction to filling is present. DISEASE ENTITIES Constrictive Pericarditis. Previous studies have attempted to diagnose constrictive pericarditis on the basis of the presence of rapid, early diastolic filling. 20 ' 46 Rapid, early diastolic filling, however, is also a characteristic finding in patients with restrictive cardiomyopathy. A more diagnostic finding in constrictive pericarditis is the change in velocity curves that occurs during the different phases of respiration. These changes are due to abnormal pressure relationships and increased ventricular interdependence that result from the constrictive process. 104 In constrictive pericarditis, dissociation of the intrathoracic and intracardiac pressures during the various phases of respiration may be present. With the onset of inspiration, the wedge pressure is lowered in association with less change in the left ventricular diastolic pressure. Thus, the diastolic gradient between the wedge and the left ventricular pressure decreases, and the result is a delay in mitral valve opening and a decrease in the E velocity on the mitral valve inflow tracing. Similarly, with the onset of expiration, the gradient between the wedge and the left ventricular pressure is increased in association with an early opening of the mitral valve and an increase

18 198 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE Mayo Clin Proc, February 1989, Vol 64.2irVsT Fig. 21. Hepatic vein velocity curve of a normal patient (left), showing characteristic systolic (syst) and diastolic (diasi) patterns, and of a patient with right ventricular hypertrophy (right) in whom all forward flow is during systole and diastolic flow is completely absent (vertical arrowhead). Flow reversal is increased (horizontal arrowhead) with onset of a trial contraction (a). in the E velocity (Fig. 23 A). In patients with constructive pericarditis, the mitral flow velocity curve may have a shorter deceleration time than normal. The normal pericardium enhances diastolic interaction between the two ventricles. 105 In the presence of constrictive pericarditis, ventricular interaction is increased. 104 Changes in filling of the left side of the heart will therefore result in reciprocal changes in filling of the right side of the heart on a beat-to-beat basis. Although the inspiratory increase in tricuspid flow velocity may not differ from normal, this reciprocal beatto-beat relationship results in a considerable decrease in the tricuspid velocity as the mitral velocity increases at the onset of expiration (Fig. 23 B). In patients with constriction in normal sinus rhythm, the systolic flow velocity is greater than or equal to diastolic forward flow velocity in the systemic veins. With the onset of expiration, however, diastolic forward flow decreases, often in conjunction with substantial flow reversals. This pattern corresponds to the decrease in diastolic flow through the tricuspid valve that occurs during the onset of expiration (Fig. 23 C). During inspiration, a moderate increase in forward flow velocity may be recorded in the hepatic vein. The superior vena cava may show no increase, or even a decrease, in forward flow velocity during inspiration, possibly because of an increase in the diameter of this vessel. If a patient with constrictive pericarditis is in atrial fibrillation, there may be loss of systolic filling, and forward flow may occur only during diastole. This pattern will resemble the changes seen in restrictive cardiomyopathy during apnea. In these two entities, however, changes with respiration differ. Patients with constriction will have an appreciable decrease in forward flow and an increase in reversal with the onset of expiration. In restriction to filling, the increase in reversal occurs at the time of increase in forward flow during inspiration. Respiratory changes in the mitral flow velocity curve resembling those seen in constrictive pericarditis may be seen in other conditions as well for example, conditions in which the depth of respiration is increased (chronic obstructive pulmonary disease and obesity) or conditions in which ventricular interaction is increased (acute right ventricular infarction or acute pulmonary embolus that produces acute right ventricular dilatation). In patients early after a cardiac sur-

19 Mayo Clin Proc, February 1989, Vol 64 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE 199 j^r.hv'y «Fig. 22. Hepatic vein velocity curve (HV) of a patient with restriction to filling. There is complete loss of forward systolic flow, and all antegrade flow occurred during diastole. With inspiration, diastolic forward flow increased, and a greater degree of reversal resulted. Simultaneous right atrial (RA) pressure waveform is displayed, which is similar to hepatic vein velocity curve. Note rapid "y" descent, particularly during inspiration. Asc. Ao = ascending aortic pressure; Resp. = respiratory tracing. gical procedure, these respiratory changes may be present because of pericardial or pulmonary changes from the operation. Patients with chronic obstructive pulmonary disease have a large decrease in intrathoracic pressure and a decrease in the initial mitral flow velocity during inspiration. 106 The timing of this change, however, differs from that in constrictive pericarditis, with a further decrease in velocity on the second and third beats during inspiration. Similarly, during expiration, the initial mitral flow velocity increases, but it is not highest on the first beat of expiration as in constriction. Respiratory changes in the isovolumic-relaxation period can be less pronounced in patients with chronic obstructive pulmonary disease. These patients are most easily distinguished from patients with constriction by the tricuspid and right-sided venous velocities. Because right-sided filling is not limited, the tricuspid inflow and right-sided veins show increased forward flow velocities throughout inspiration. Another setting in which a change in the initial mitral flow velocity may be seen is when the sample volume is placed too close to the mitral valve annulus. In this region, small changes in the position of the sample volume can result in major changes in the E:A ratio. The changes in position of the heart relative to the sample volume caused by respiration can artifactually result in changes in the mitral flow velocity. The isovolumic-relaxation period, however, does not change with respiration in this situation. Pericardial Tamponade. The pathophysiologic changes that occur in pericardial tamponade resemble those in constrictive pericarditis. When the pericardial pressure is high, the intrathoracic, intrapericardial, and intracardiac pressures are dissociated during inspiration. During inspiration, the flow through the left side of the heart is decreased and the flow through the right side of the heart is increased Conversely, during expiration, the flow across the left side of the heart is increased and the flow across the right

20 200 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE Mayo Clin Proc, February 1989, Vol 64 side of the heart is decreased. The respiratorychanges seen in pericardial tamponade are similar to those seen in constrictive pericarditis: (1) a decrease in the mitral E velocity during onset of inspiration, (2) a loss of diastolic filling on the venous inflow with onset of expiration, and (3) ^ > ^_ MITRAL!.% hi JrLiiü'il > *? P'i*tk. TRICUSPID > te>. I»»<4» tee*"-, j ^. *> 4 1 '* ^»- i ' -<<* I A a decrease in the tricuspid E velocity with onset of expiration. 110 As the pericardial pressure increases, it will vary less with respiration. If the inspiratory intrathoracic pressure is less than the intrapericardial pressure, early mitral filling may not occur. In this instance, the mitral valve will open only with atrial contraction. In pericardial tamponade, diastolic filling may be completely absent on the venous inflow patterns. 109 This pattern may simulate venous filling patterns seen in abnormalities of myocardial relaxation, such as right ventricular hypertrophy and right ventricular infarction. Restrictive Cardiomyopathy. The changes seen in patients with restrictive cardiomyopathy are those of a decrease in ventricular compliance. 79 The characteristic mitral flow velocity curve in restrictive cardiomyopathy consists of a short deceleration time and a high E:A ratio. In contradistinction to constrictive pericarditis, no inspiratory decrease in velocities occurs. The tricuspid flow velocities will also have a short deceleration time in patients with restrictive cardiomyopathy. The venous flow patterns will be abnormal, depending on the rhythm and the degree of myocardial abnormality present. These changes can vary from partial to complete loss of systolic forward flow. In addition, there can be increases in systolic, diastolic, or atrial reversals, which will further increase on inspiration. f.t.t...,.,..,,,,.,,.. HEPATIC VSIN i >pr^ ' ^ V ν^ ψφφ Mj Fig. 23. Pulsed-wave Doppler recordings of a patient with constrictive pericarditis. A, Mitral flow velocity curve, demonstrating pronounced decrease in initial velocity during inspiration (arrowheads). B, Tricuspid flow velocity curve, demonstrating appreciable decrease in initial velocity during expiration (arrowheads). C, Hepatic vein velocity curve, demonstrating approximately equal forward flow in systole and diastole. During inspiration, there is an increase in forward flow without an increase in reversal. Notable reversal and loss of diastolic filling occur with expiration (double arrowheads), a = apnea; e = expiration; i = inspiration. CONCLUSION Abnormalities of diastolic function occur in most patients with cardiac disease. Doppler echocardiography may provide the means by which specific abnormalities of diastolic function can be noninvasively assessed in these patients. Diastolic function is a complex process consisting of numerous interrelated contributing factors. It is highly dependent on the loading conditions, heart rate, and contractility. Therefore, any measurement of diastolic function will change as the hemodynamic milieu changes. This interdependence must be taken into consideration in both the initial and the serial assessment of a patient by Doppler echocardiography. A change in a Doppler determination after any intervention may be due to the intervention itself, the effect of changes in loading conditions, changes in heart rate, or a combination of these factors.

21 Mayo Clin Proc, February 1989, Vol 64 DOPPLER ECHOCARDIOGRAPHIC ASSESSMENT OF DIASTOLE 201 Further understanding of what influences these Doppler determinations is necessary before routine interpretations of diastolic function can be made in the assessment of an individual patient, including responses to interventions. Nonetheless, future investigations, with application of these measurements in a large number of patients, should prove to be of clinical benefit in distinguishing various disease processes, assessing the prognosis, and evaluating the effect of treatment. REFERENCES 1. DeMaria AN, Wisenbaugh T: Identification and treatment of diastolic dysfunction: role of transmitrai Doppler recordings (editorial). J Am Coll Cardiol 9: , Labovitz AJ, Pearson AC: Evaluation of left ventricular diastolic function: clinical relevance and recent Doppler echocardiographic insights. Am Heart J 114: , Hammermeister KE, Warbasse JR: The rate of change of left ventricular volume in man. II. 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