Alterations in transmitral flow dynamks in patients with early mitral valve closure and aortic regurgitation

Ten patients with severe aortic regurgitation (AR) and early diastdic mitral closure demonstrated by M-mode echocardiography (group I) were compared to 10 age-matched patients with severe AR and normal timing of mitral closure to quantify the accompanying alterations in transmitral flow dynamics assessed by pulsed Doppler echocardiography. Transmitral filling period expressed as a fraction of the time available for diastolic filling was significantly shortened in group I patients relative to group Ii patients (0.50 + 0.10 vs 1.04 + 0.09, p < 0.001) because early mitral cksure truncated trensmitral filling and obliterated the atrial contribution to left ventricular filling. The mpid diastolic filling period normalized for the time availebfe for diastolic filling was also shortened for group I patients relative to group II patients (0.49 +- 0.11 vs 0.64 rt 0.19; p -C 0.05). Early mitral closure in group I patients was functionally incomplete because 9 of the 10 patients had diastolic mitml regurgitation, which was not detected in any patients in group II (P < 0.001). Thus the group I patients with early mitral closure and severe aortic regurgitation had truncated transmitrai inflow and diastolic mitral regurgitation. These patients had higher pulmonary capillary wedge pressures (32 t 6 vs 11 t 9 mm Hg; p < 0.001) and more severe functional limitation (p < 0.001) than group II patients. (AM HEART J 1994;128:941-7.)

Jose Eusebio, MD, Eric K. Louie, MD, Lonnie C. Edwards III, MD, Henry S. Loeb, MD, and Patrick J. Scanlon, MD Maywood and Hines, Ill.

Early diastolic mitral valve closure, which often preempts atrial systole, is a well-recognized sign of acute severe aortic regurgitation.1-3 The rapid rise in left ventricular diastolic pressure as a result of severe aortic regurgitation into a noncompliant left ventri- cle results in reversal of the atrioventricular pressure gradient across the mitral valve,2y 3 premature mitral valve closure and, on occasion, diastolic mitral re- gurgitation.4The echocardiographic detection of such early mitral valve closure is a hallmark of acute severe aortic regurgitation and often requires urgent sur- gical intervention. 5-7 Doppler echocardiographic techniques have demonstrated that early mitral co- aptation in association with acute severe aortic re- gurgitation is incomplete and often associated with diastolic mitral regurgitation.8, g In this study Dop-

From the Division of Cardiology, Loyola University Medical Center, May- wood; and the Veteran’s Administration Medical Center, Hines.

Received for publication Jan. 6, 1994; accepted Feb. 23,1994. Reprint requests: Eric K. Louie, MD, Division of Cardiology, Loyola Uni- versity Medical Center, 2160 S. First Ave., Maywood, IL 60153.

Copyright @J 1994 by Mosby-Year Book, Inc. 0002.8703/94/$3.00 +O 4/l/58135

pler echocardiographic techniques were used to char- acterize transmitral filling dynamics and diastolic mitral regurgitation in patients with severe aortic regurgitation with and without early mitral valve closure.

METHODS Patient selection. All patients referred to the echocar-

diography laboratory for the assessment of aortic regurgi- tation routinely undergo standard two-dimensional echocardiographic imaging, M-mode echocardiographic analysis with detailed interrogation of the mitral valve to evaluate for early mitral leaflet closure, and Doppler echocardiographic mapping of the left ventricular outflow tract to assess the extent of disturbed flow resulting from aortic regurgitation. From our echocardiographic files, 10 consecutive patients with severe isolated aortic regurgita- tion and early mitral valve closure (apparent mitral leaflet apposition before the electrocardiographic R wave) were identified (group I, mean age 40 I 11 years) and age matched to 10 concurrently studied patients with aortic regurgitation of similar severity (group II, mean age 45 ~?r 18 years, difference not significant [NS]). These two groups of patients form the basis for the subsequent comparative analysis of transmitral filling dynamics, diastolic mitral regurgitation, and clinical correlates. All patients had

941

942 Eusebio et al. November 1994

American Heart Journal

ECG f

Fig. 1. M-mode echocardiographic measurements of mitral valve motion. Left, M-mode echocardiogram of mitral valve obtained from left parasternal transducer position. Electrocardiogram (ECG) is at top, su- perimposed on anterior thoracic structures. Ordinate: calibrations at 1.0 cm intervals measuring depth from anterior chest wall. Abscissa: minor calibrations at 200 msec intervals. Right, Diagram of M-mode echocar- diogram at left. Mitral valve opens at point D, when anterior and posterior leaflets separate, and closes at point C, when anterior and posterior leaflets appose. Early mitral valve closure occurs when C point is in- scribed before peak of R wave of ECG. Available diastolic filling period (DIP) is time interval from D point to peak of R wave of ECG. Duration of mitral valve opening (MVO) is time interval between D and C points.

structurally normal mitral valves and were in normal sinus rhythm with PR interval <200 ms at the time of the echocardiographic study.

Doppler echocardiographic studies. While breathing quietly in the left lateral decubitus position all patients were studied with a Diasonics CV-400 (Milpitas, Calif.), Sonos 1000 (Hewlett-Packard, Andover, Mass.) or ACU- SON XP-10 (Mountain View, Calif.) echocardiograph. Re- al-time two-dimensional echocardiographic studies were recorded on 1.27 cm VHS videotape for subsequent play- back and review. M-mode echocardiographic studies tar- geted by two-dimensional imaging were recorded at 100 mm/set, and pulsed Doppler spectra were recorded at 100 mm/set with a simultaneous limb lead II electrocardio- gram. M-mode echocardiographic studies were obtained with the transducer positioned in the left parasternal win- dow. The mitral leaflets were extensively interrogated to determine the timing of the closing motion and apparent coaptation of the anterior and posterior leaflets relative to the electrocardiogram. All dimensions measured from the M-mode echocardiogram were performed according to the conventions of the American Society of Echocardiogra- phy.1°

Pulsed Doppler mapping of the spatial extent of the flow disturbance of aortic regurgitation was performed from an apical window in the four-chamber plane with anterior an- gulation to image the left ventricular outflow tract and in the two-chamber plane rotated to include the left ventric- ular outflow tract. The left ventricular outflow tract was also interrogated from the left parasternal window. Pulsed Doppler spectra recorded from the left ventricular outflow tract met criteria for the presence of disturbed flow repre- senting aortic regurgitation when (1) the diastolic flow ve-

locity signal showed spectral broadening from the zero baseline to the peak recorded velocity; (2) the peak veloc- ity was >l m/set, resulting in signal aliasing; (3) the dura- tion of the flow disturbance was >200 msec; and (4) there was no evidence for a spectral envelope resembling the transmitral flow velocities characteristic for the particular patient. The flow disturbance of aortic regurgitation was judged as representing severe aortic incompetence in every study patient based on the detection of an abnormal dias- tolic flow disturbance, which occupied greater than half the diameter of the left ventricular outflow tract and extended beyond the tips of the anterior mitral leaflet.ll, l2 Pulsed Doppler measurement of transmitral flow velocities was obtained from the apical four-chamber view with the Dop- pler cursor aligned parallel to the left ventricular inflow tract along a line running from the left ventricular apex to the midpoint of the mitral annulus. The pulsed Doppler sample volume was positioned at the level of the mitral an- nulus to measure transmitral flow velocities uncontami- nated by the flow disturbance of aortic regurgitation. To achieve optimal flow velocity spectra, we required that (1) the spectrum be highly reproducible; (2) peak velocities be maximized; (3) a high-pitched, pure-tone audio signal ac- company the Doppler signal; and (4) spectral broadening of the flow velocity envelope be minimaLl After transmitral flow velocity spectra were recorded, the pulsed Doppler sample volume was systematically positioned to interro- gate the left atrial aspect of the mitral valve for the pres- ence of a flow disturbance signifying mitral incompetence. Diastolic mitral regurgitation was considered to be present when a pulsed Doppler sample volume positioned on the left atrial side of the mitral leaflets recorded a signal before the inscription of the electrocardiographic R wave, which

Eusebil) et al. 943

Fig. 2. Pulsed Doppler echocardiographic measurements of transmitral flow velocities. Left, Pulsed Dop- pler spectrum of transmitral flow velocities obtained with transducer positioned at left ventricular apex and sample volume at level of mitral annulus. Electrocardiogram (ECG) is at top of spectrum. Ordinate: cal- ibrations 1 m/set intervals measuring flow velocity directed toward the transducer. Abscissa: minor cali- brations at 200 msec intervals. Right, Diagram of pulsed Doppler spectrum at left. Early diastolic trans- mitral flow begins at D point and reaches its peak velocity (VE) at E point before decelerating to zero-flow baseline at point F. Peak velocity of atrial systolic component of left ventricular filling occurs at point A. Available diastolic filling period (DFP) is time interval from point D to peak of R wave of ECG. Trans- mitral filling period (MFP) is time interval from point D to end of transmitral flow profile (in this case, point C). Duration of early diastolic filling is time interval from point D to point F. Deceleration time is time interval from point E to point F.

demonstrated abnormal disturbed flow velocities with spectral broadening from the zero baseline to the peak re- corded velocity.‘4“5

Quantitation of Doppler and M-mode echocardio- graphic parameters (Figs. 1 and 2). Measurements were performed from stripchart recordings or videotaped trac- ings with a dedicated microcomputer, bit-pad digitizer, and customized software. For M-mode echocardiographic mea- surements, the time interval available for diastolic filling (available DFP) was defined as beginning with the opening of the mitral valve (D point) and ending with the peak of the subsequent electrocardiographic R wave. Similarly, for pulsed Doppler measurements the available DFP was de- fined as beginning with the onset of transmitral forward flow and ending with the peak of the subsequent electro- cardiographic R wave. The duration of mitral valve open- ing (MVO) was measured from the M-mode echocardio- gram from the mitral opening point (D point) to that point in the cardiac cycle when the mitral leaflets moved toward coaptation and achieved a position of apparent closure that persisted through ventricular systole. The transmitral fill- ing period (MFP) was measured from the pulsed Doppler spectrum of transmitral flow velocities from the onset of transmitral forward flow to the end of the flow velocity spectrum. Both the duration of mitral valve opening and the transmitral filling period were expressed as a fraction of the available diastolic filling period: Fractional mitral valve opening (MVOf) = MVO/available DFP and Frac-

tional transmitral filling period (MFPf) = MFP/Available DFP. The duration of the aortic regurgitation (AR) signal recorded by pulsed wave Doppler just proximal to the aor- tic cusps was also expressed as a fraction of the available diastolic filling period: Fractional duration of aortic regur- gitation (ARf) = AR/available DFP.

The dynamics of transmitral left ventricular filling were characterized by digitizing the envelope of the transmitral flow velocity spectrum that represented the instantaneous modal transmitral flow velocities. The maximal velocity of early diastolic filling (VE) and the duration of the rapid di- astolic filling period (the interval between points D and F, Fig. 2) were measured. The acceleration and deceleration limbs of the early diastolic filling velocities were extrapo- lated when necessary to intersect the zero velocity baseline to make these measurements. The rate of early diastolic deceleration was characterized by two parameters: (1) the deceleration time (time interval between the E and F points; Fig. 2) and deceleration time normalized for the available diastolic filling period (fractional deceleration time), and (2) the average deceleration rate = Vg/deceler- ation time.

Statistical analysis. Data are presented as mean + SD. Intergroup comparisons were analyzed with the Student unpaired t test or the chi-squared test with Yates correc- tion for continuity, with a two-tailed p < 0.05 considered statistically significant. Linear regression analysis was used to establish the correlation between two variables.

944 Eusebio et al. November 1994

American Heart Journal

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0.0 i

p<0.001 p<o.o5

I

T

q AR with Early Mitral

Closure

[7 AR with Normal Mitral

Closure

-rL L Fractional Fractional

Transmitral Early Diastolic Filling Period Filling Period

Fig. 3. Fractional left ventricular transmitral filling period and fractional left ventricular early diastolic filling period in patients with severe aortic regurgitation (AR) with and without early mitral valve closure. Patients with severe aortic regurgitation and early mitral valve closure have alterations in both early and late transmitral filling dynamics. In these patients late diastolic contribution to left ventricular filling of atria1 systole is preempted and total duration of transmitral filling is truncated. In addition, early diastolic filling period is shortened relative to measurements in patients with severe aortic regurgitation who do not exhibit early mitral valve closure.

RESULTS Apparent early mitral valve closure and diastolic mitral

regurgitation. For the 10 patients with severe aortic regurgitation (AR) and early mitral closure (group I, MVOf = 0.59 _+ 0.09), transmitral flow was truncated (with elimination of the atria1 contribution to trans- mitral filling) compared to measurements in the 10 patients with severe AR and normal timing of mitral closure (group II, MVOf = 1.00 _t 0.04). Thus frac- tional transmitral filling period (MFPf) for patients with early mitral closure (0.50 + 0.10) was signifi- cantly less than MFPf (1.04 + 0.09, p < 0.001) for patients with normal timing of mitral valve motion (Fig. 3). The timing of mitral valve closure accurately predicted the degree of truncation of transmitral filling as reflected in the linear correlation between MVOr and MFPf (r = 0.92). Despite apparent early closure of the mitral valve in group I patients, such mitral leaflet apposition was ineffective because all but one of these 10 patients had Doppler echocardio- graphic evidence for diastolic mitral regurgitation. In contrast, none of the group II patients had Doppler echocardiographic evidence for diastolic mitral re- gurgitation. (xc2 = 12.929, p < 0,001). Aortic regurgi- tation was detected throughout the available dias- tolic filling period for both group I and group II patients, and no significant difference was found for the fractional duration of aortic regurgitation (1.01 -t 0.07 vs 1.07 +- 0.08, NS).

Transmitral left ventricular filling dynamics. Group I patients with severe aortic regurgitation and early mitral closure tended to have slightly higher maximal early diastolic transmitral velocities (VE = 55 + 13 cm/set) compared to group II patients with severe aortic regurgitation and normal timing of mitral valve closure (VE = 44 -t 11 cm/set, p < 0.08), but this difference did not achieve statistical significance. The duration of the rapid diastolic filling period was significantly shorter in group I patients compared to group II patients (143 + 32 vs 267 +- 84 msec, p < 0.001); this difference persisted after normaliza- tion for the duration of the time available for diastolic filling (0.49 + 0.11 vs 0.64 + 0.19, p < 0.05, Fig. 3). This abbreviation of the rapid diastolic filling period in patients with early mitral closure is the result of more rapid deceleration of transmitral filling at the end of the rapid diastolic filling period (993 -+ 412 cm/sec2) compared to patients with normal timing of mitral closure (284 -+ 147 cm/sec2, p < 0.001; Fig. 4) and is accompanied by shortening of the deceleration time (60 k 17 vs 194 +- 95 msec; p < 0.001). When deceleration time is normalized for the time available for diastolic filling, the resulting fractional duration of the deceleration period is also significantly less for group I patients than for group II patients (0.21 -+ 0.08 vs 0.46 t 0.20, p < 0.002).

Clinical, hemodynamic, and echocardiographic com- parisons. M-mode echocardiographic indexes of left

Volume 128, Number 5 American Heart Journal Ei:sehio et al. 945

Fig. 4. Deceleration of early diastolic left ventricular filling. Early diastolic left ventricular filling decel- erates more rapidly in patients with aortic regurgitation (AR) and early mitral valve closure than in pa- tients with aortic regurgitation and normal timing of mitral valve closure, resulting in shorter early dias- tolic left ventricular filling period in patients with early mitral valve closure (see Fig. 3).

ventricular size, wall thickness, and systolic shorten- ing were similar between patients in groups I and II (Table I). In general, the left ventricles were dilated but systolic shortening was preserved, and the left ventricular walls were mildly hypertrophied or nor- mal in thickness. Systemic arterial pulse pressure tended to be narrower in group I patients than in group II patients (64 ? 17 vs 74 t 30 mm Hg, p 0.39) but this difference was not statistically significant. Group I patients had more tachycardia than group II patients (93 + 16 vs 70 + 9 beats/min, p < 0.001) and had more functional limitation from dyspnea (New York Heart Association functional class (FC) 3.5 * 0.5 vs 2.1 + 0.7,~ < 0.001). All group I patients had acute aortic regurgitation (8 from recent-onset infective endocarditis and 2 from the sudden onset of symptoms associated with the surgical findings of primary myxomatous degeneration of the aortic valve) resulting in severe functional limitation (4 pa- tients were FC III and 6 were FC IV), whereas all group II patients had chronic aortic regurgitation and were relatively less symptomatic (2 patients were FC I, 5 FC II, and 3 FC III). The left atrium was signif- icantly larger in group I patients than in group II pa- tients (55 -t 6 vs 44 k 9 mm, p < 0.005). Pulmonary capillary wedge pressure was measured in 6 patients from each group and was significantly higher in group I patients (32 + 6 mm Hg) than in group II patients (11 + 9 mm Hg, p < 0.001).

Table I. M-mode echocardiographic dimensions

Left ventricle EDD (mm) ESD (mm) EPSS (mm) VS (mm) PW (mm) FS (‘3,)

Left atria1 diameter (mm)

Group I Group II p Value

72 + 14 72 i 9 NS 44 f 10 47 i 11 NS 22 t 9 19 It 9 NS 12 + 3 12 L 3 NS 12 _+ 2 12 1- 3 NS 39 f 10 35 rt 9 NS 55 +- 6 44 T! 9 p < 0.005

EDD, End-diastolic dimension; EPSS, mitral valve E point to ventricular septal separation; ESD, end-systolic dimension; FS, minor axis fractional shortening; PW, diastolic posterior wall thickness: VS. diastolic ventricular septal thickness.

DISCUSSION

The early mitral valve closure demonstrated in group I patients with aortic regurgitation resulted in functionally incompetent mitral leaflet coaptation because 9 of the 10 patients with early mitral closure had Doppler echocardiographic evidence for diastolic mitral regurgitation. Pulsed Doppler assessment of transmitral flow dynamics demonstrated the impact of severe aortic regurgitation associated with early mitral closure on transmitral filling and the rapid di- astolic transmitral filling period of the left ventricle. In group I patients with early mitral closure, the transmitral filling period was shortened to approxi-

November 1994 946 Eusebio et al. American Heart Journal

mately half of the time available for diastolic filling. In contrast, transmitral filling in group II patients with equivalent severity of aortic regurgitation per- sisted throughout the available diastolic filling pe- riod. Not only was late diastolic filling (in particular the atria1 contribution to diastolic left ventricular filling) truncated in group I patients, but rapid dias- tolic filling dynamics were also significantly altered. Group I patients had a reduction of the rapid diastolic transmitral filling period to 49 % of the time available for diastolic filling, whereas in group II pa- tients rapid diastolic transmitral filling comprised approximately 64% of the available diastolic filling period. This disproportionate shortening of the rapid diastolic transmitral filling phase results from a more abrupt deceleration of early diastolic filling and most likely results from the exaggerated rise in left ven- tricular diastolic pressure resulting from acute seuere volume overload of a noncompliant left ventricular chamber. In contrast, group II patients with chronic seuere aortic regurgitation probably have greater ef- fective left ventricular chamber compliance and hence demonstrated less volumetric competition be- tween the regurgitant filling of the ventricle from the aorta and the early phase of transmitral filling. These findings are consistent with the observations from the study of Oh et al., 16, l7 which compared patients with severe aortic regurgitation (a minority of whom had early mitral valve closure) to normal control subjects. In that study the 11 patients with severe symptomatic aortic regurgitation had shorter decel- eration times for early transmit& filling than aged- matched normal subjects. I6 The patients with severe aortic regurgitation reported by Oh et al. were some- what older (mean age 53 years) than the patients in our study making direct comparisons with our data speculative. It is interesting to note, however, that the average deceleration time (117 msec) found in their patients with severe aortic regurgitation are in- termediate between the measurements for patients in groups I and II of our study. These findings sug- gest that the patients with acute severe aortic regur- gitation and early mitral valve closure represent one end of a continuous spectrum of progressively greater competition between regurgitant and transmitral ventricular filling that is most marked in patients with acute aortic regurgitation.17

This study has demonstrated that acute aortic re- gurgitation with early mitral closure is associated with premature termination of early diastolic trans- mitral filling of the left ventricle resulting from uol- umetric competition between the two sources for left ventricular filling. Previously, we reported a different kind of interaction between aortic regurgitation and

mitral inflow in patients who demonstrate anterior mitral leaflet fluttering. l2 In our earlier study of pa- tients with chronic aortic regurgitation, anterior mi- tral leaflet fluttering marked interaction between the regurgitant stream directed on the anterior mitral leaflet and transmitral inflow, which resulted in pro- longation of early diastolic filling, suggesting relative obstruction to inflow. In contrast, in the current study the abnormality of mitral valve motion in acute severe aortic regurgitation is not the governing factor influencing transmitral dynamics; instead, it is a passive reflection of the rapid rise in left ventricular diastolic pressure from aortic regurgitation, which results in early reversal of the mitral atrioventricular pressure difference. The result is early apparent clo- sure of the mitral valve and truncation of transmitral filling with obliteration of the atria1 contribution to transmitral left ventricular filling. In addition, this premature coaptation of the mitral valve leaflets appears to be functionally ineffective because 9 of our 10 patients in group I had diastolic mitral regur- gitation despite early mitral valve closure. These im- pediments to early and late transmitral filling in association with diastolic mitral regurgitation are associated with greater elevations in pulmonary cap- illary wedge pressure and more left atria1 enlarge- ment in group I patients by comparison to group II patients.

One uncontrolled difference between group I and group II patients is that the heart rate is significantly higher in group I patients, presumably a reflection of the greater functional limitation and more acute symptomatic state of these patients. In this regard it can be argued that the observed differences in trans- mitral flow dynamics are largely a reflection of this increase in heart rate (on average 23 beats/min). It is worth noting, however, that the significant shorten- ing of the total transmit& filling period, the rapid diastolic transmitral filling period, and the decelera- tion time in group I patients relative to group II pa- tients persists after normalization by the time avail- able for diastolic filling. Thus even after correction for the relative decrease in time available for diastolic filling expected with increasing heart rates, the group I patients exhibit a significant shortening of the frac- tional transmitral filling period, fractional rapid di- astolic transmitral filling period, and fractional de- celeration time of left ventricular filling.

Conclusions. Early mitral closure is a marker for severe acute aortic regurgitation, which is character- ized by (1) volumetric competition for early diastolic filling between the regurgitant stream and transmi- tral inflow; (2) truncation of late diastolic transmitral filling with elimination of the atria1 contribution to

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American Heart Journal Eusehio et nl. 947

transmitral filling; and (3) early but functionally in- complete closure of the mitral valve with accompa- nying diastolic mitral regurgitation.

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