|
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
|
|
|
|||||||||
|
|||||||||||
|
J Am Coll Cardiol, 1999; 33:538-545 © 1999 by the American College of Cardiology Foundation |
* Cardiac Ultrasound Laboratory, Massachusetts General Hospital, Boston, Massachusetts, USA
Heart Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel
Manuscript received April 29, 1998; revised manuscript received August 27, 1998, accepted October 6, 1998.
Reprint requests and correspondence: Judy Hung, MD, Cardiac Ultrasound Laboratory-VBK 508, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114
jhung{at}partners.org
 |
Abstract |
|---|
 Top Abstract MethodsResultsDiscussionReferences |
|---|
We used the Doppler proximal flow convergence technique as a physiologic tool to explore the effects of the time courses of mitral annular area and transmitral pressure on dynamic changes in regurgitant orifice area.
Background
In functional mitral regurgitation (MR), regurgitant flow rate and orifice area display a unique pattern, with peaks in early and late systole and a midsystolic decrease. Phasic changes in both mitral annular area and the transmitral pressure acting to close the leaflets, which equals left ventricular-left atrial pressure, have been proposed to explain this dynamic pattern.
Methods
In 30 patients with functional MR, regurgitant orifice area was obtained as flow (from M-mode proximal flow convergence traces) divided by orifice velocity (v) from the continuous wave Doppler trace of MR, transmitral pressure as 4v2, and mitral annular area from two apical diameters.
Results
All patients had midsystolic decreases in regurgitant orifice area that mirrored increases in transmitral pressure, while mitral annular area changed more gradually. By stepwise multiple regression analysis, both mitral annular area and transmitral pressure significantly affected regurgitant orifice area; however, transmitral pressure made a stronger contribution (r2 = 0.441) than mitral annular area (added r2 = 0.008). Similarly, the rate of change of regurgitant orifice area more strongly related to that of transmitral pressure (r2 = 0.638) than to that of mitral annular area (added r2 = 0.003). A similar regurgitant orifice area time course was observed in four patients with fixed mitral annuli due to Carpentier ring insertion.
Conclusions
In summary, the time course and rate of change of regurgitant orifice area in patients with functional MR are predominantly determined by dynamic changes in the transmitral pressure acting to close the valve. Thus, although mitral annular area helps determine the potential for MR, transmitral pressure appears important in driving the leaflets toward closure, and would be of value to consider in interventions aimed at reducing the severity of MR.
| ||||||||||||||||
Schwammenthal et al. (10), using this PFC technique, noted that the temporal patterns of mitral regurgitant flow and orifice area variation depend on the etiology of the regurgitant lesion, with a constant orifice in some patients with calcific rheumatic heart disease, and a mid to late systolic increase in patients with mitral valve prolapse. A unique biphasic pattern was observed in patients with functional regurgitation in dilated or ischemic left ventricles (LVs) with intrinsically normal mitral leaflets, with early and late systolic peaks and a midsystolic decrease. This initial observation has been confirmed subsequently by Shiota et al. (11) using an independent method with electromagnetic flow meters. This pattern had not been described previously and is of interest because of its potential to provide insights into the mechanism of functional MR and into potential therapeutic targets that would promote or lengthen the midsystolic decrease in orifice area, thereby decreasing the overall severity of regurgitation. Two explanations can be proposed for this pattern: 1) the regurgitant orifice area may vary in parallel with mitral annular area (MAA), which decreases to a minimum in midsystole and then increases in late systole with atrial filling (12); this would be consistent with early concepts relating orifice area to annular dimension (2–5); dilation of the mitral annulus, in fact, has been implicated in the development of functional MR (13), tethering the leaflets apart to limit effective coaptation (14–17); 2) another possibility is that ROA varies in response to phasic changes in the transmitral pressure (TMP), which may act to close the mitral leaflets more effectively when it reaches its peak in midsystole (18,19).
The purpose of this study, therefore, was to use the proximal flow convergence technique as a noninvasive tool to examine whether the dynamic variation of ROA in functional MR is related primarily to temporal changes in MAA, TMP or both. One potential hypothesis, for example, is that the dynamic variation of ROA in functional MR is influenced by both TMP and MAA. This question is important because it may provide insights into the fundamental mechanism of functional MR and potentially improve our therapeutic approach to this problem in patients.
|
Methods |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
30% and at least mild functional MR without intrinsic valvular disease, who had been referred for two-dimensional Doppler echocardiography and had images suitable for quantitative analysis. To determine the temporal pattern of ROA in the presence of a fixed annulus, we were able to include in this group four patients with Carpentier-Edwards mitral annular rings and persistent functional MR. Echocardiographic studies. All studies were performed with a scanner (Hewlett-Packard SONOS 2500) equipped with a 2.5-MHz transducer. Two-dimensional echocardiography was performed in the standard apical four- and two-chamber views to visualize the mitral annulus in two orthogonal planes (20). The region of the mitral valve was magnified and the frame rate maximized by narrowing the sector angle to optimize measurement of mitral annular dimensions. The MR orifice velocity profile was obtained by continuous-wave Doppler with the beam aligned parallel to the regurgitant flow, and it was recorded digitally onto a magneto-optical disk for subsequent analysis.
PFC technique.
The PFC technique has been validated as a quantitative Doppler method to calculate regurgitant flow rate and orifice area (6–9). As flow approaches an orifice, it forms concentric isovelocity shells of decreasing surface area and increasing velocity. By conservation of mass, flow through any shell must pass through the orifice. Doppler color flow mapping can depict such shells based on a selected velocity or provide a range of isovelocity contours as a digital map. The flow through any such shell equals its surface area times the velocity that defines the shell (2
r2 x [velocity]) for a hemispheric shape of the isovelocity shell (6–9).
The PFC region was imaged in the apical four-chamber view with the Doppler color gain adjusted to maximize signal without random noise velocities. The sector angle was narrowed and depth decreased to maximize the pulse repetition frequency for optimal velocity resolution. An M-mode cursor was aligned along the maximal diameter of the PFC region to obtain a color Doppler M-mode of the PFC region (tracing of color coded velocities vs time, Fig. 1), which was then digitally recorded.
|
(a/2)(b/2) for an ellipse with a the diameter measured in the four-chamber view and b measured in the two-chamber view (20).
Regurgitant orifice area.
Customized software developed on a work station (Silicon Graphics) was used to measure instantaneous mitral regurgitant flow rates and orifice areas from the digitized color M-mode images of the PFC region. To calculate regurgitant flow rate, the PFC technique requires measurement of the distance from the level of the leaflet orifice to the location at which a given velocity occurs. First, the LV edge of the mitral leaflet was traced to establish the location of the orifice. The definition of the mitral leaflets was facilitated by removal of the color signal from the display generated from the digital image. Then, the velocity contour defined by 
x Nyquist velocity was traced at each point in time from the digitized image. This velocity was chosen because studies in our laboratory have shown that digital color flow mapping in a converging calibration flow phantom designed by the American Society of Echocardiography accurately measures velocity from 0.5 to 1.5 times the Nyquist velocity, which is determined by the fundamental sampling frequency (pulse repetition frequency) of the Doppler technique. One-half the Nyquist velocity was chosen to maximize the size of the distance measured from the orifice to provide greatest accuracy. The traced contours were typically at a velocity of 25–35 cm/s. Finally, the instantaneous radii of the PFC were measured as the distance at each point in time between the velocity and leaflet contours, thus accounting for the axial motion of the mitral orifice during systole. Figure 2A shows a digital image of a color M-mode of the PFC region. The longer arrows point in the direction of flow from LV to LA, and the shorter arrows point to the leaflet edge. Figure 2B shows the contour of the PFC region with the velocity set at Nyquist. Figure 2C shows the instantaneous radii obtained throughout the systolic time period. Mitral regurgitant flow rate (Q) was calculated as: 
(velocity) where 2r2 is equal to the surface area of the hemisphere with its apex at a given distance r from the mitral orifice and velocity is equal to Nyquist. The ROA was calculated as follows:
 |
|
Comparison of time course. The time courses of MAA, TMP and ROA were obtained for each patient by plotting the instantaneous values over systole, beginning with the peak of the QRS of the common electrocardiographic signal. Values for each variable were normalized to the maximum value for each patient to permit comparison of their time courses. Because the purpose of this study was to examine the midsystolic decrease in ROA and its subsequent rise, we analyzed the time course of all three variables during the interval between the early and late peaks of the ROA. This had the advantage of avoiding the intervals in early and in late systole during which both regurgitant flow rate and TMP were low, thereby avoiding the uncertainty in the calculated ratio of regurgitant flow rate and orifice velocity (orifice area) that comes from dividing two numbers close to zero, and avoiding the additional potential for flow rate underestimation by the Doppler technique (see "Discussion" section) (23,24). For the rates of change of these three variables, standard statistical software (Statview 4.5, 1996, Abacus Concepts, Inc., Berkeley, CA) was used to fit each time course to a polynomial equation, from which a first derivative or slope was calculated.
Statistical analysis. Univariate and multivariate stepwise regression analysis (Statview 4.5, 1996, Abacus Concepts, Inc., Berkeley, CA) was performed to examine the contribution of MAA and TMP to the values of ROA at individual time points. A similar analysis was performed to relate the rates of change of these three variables. Variables were entered in the order suggested by the regression model based on the F to enter or remove. Results were considered statistically significant for p value <0.05.
Observer variability. Interobserver variability was calculated as the SD of the differences in measurements by two independent observers over 25 traces for both ROA and TMP.
|
Results |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
Temporal pattern of MAA, TMP and ROA. Figure 3 shows the normalized time courses of MAA, TMP and ROA in four representative patients. In all patients, ROA decreased rapidly from its early systolic peak and, in late systole, increased rapidly toward its second peak. Although MAA also peaked in early and late systole, its changes were far more gradual. In contrast, TMP showed similarly wide and rapid changes in early and late systole, mirroring the time course of ROA variations. This is also shown in Figure 4, in which ROA is seen to vary inversely with TMP over its full range in the upper two panels, in contrast to the wide variation of ROA over a narrow range of MAA values in the lower panels. A pattern similar to that of ROA was also observed for regurgitant flow rate itself, although the midsystolic decrease was less prominent in those with more severe MR.
|
|
|
Interobserver variability. Interobserver variability for instantaneous ROAs and TMPs were 4.9% and 4.8% of the respective mean values.
|
Discussion |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
Mechanistic insights. Prior studies have emphasized the role of geometric factors (13,25–30), particularly mitral annular dilatation with insufficient leaflet area to cover the annulus (13), in determining the potential for functional MR. This study demonstrates that there is also an important contribution of the transmitral force required to drive the leaflets toward effective closure, consistent with the concepts derived from the models of global LV dysfunction studied by Kaul et al. (18) and Dent et al. (19). The importance of a closing force provided by TMP acting on leaflets that are tethered apart is compatible with the mechanism for functional MR illustrated schematically in Figure 6. The strong dependence of ROA on TMP, in fact, suggests the presence of opposing tethering forces in a dilated LV. In other words, it is precisely when tethering forces are increased, such as in functional MR, that variations in TMP can lead to important changes in ROA. Leaflet tethering can be considered to delay effective coaptation until LV pressure has risen sufficiently to close the leaflets, in contrast to the rapid leaflet closure observed normally when the leaflets are not subject to increased tethering forces; this delayed closure may also reflect LV dysfunction with delayed pressure development (18,19). Similar findings of delayed leaflet closure, early and late systolic peaks of ROA and a midsystolic decrease mirroring the rise in LV pressure have also been observed in vitro in a model of tethered mitral leaflets subjected to physiologic pulsatile flow (31).
|
In evaluating the effects of such therapies, the results of the present study imply that standard measures of peak MR, such as maximal jet area, are insufficient because of the variable temporal pattern of regurgitant flow rate. This is the case in other conditions as well such as mitral valve prolapse (10,34), so that a large jet occurring only briefly during systole should not be overinterpreted in terms of the severity of regurgitation (35). The M-mode PFC method takes into account the temporal variation to determine total regurgitant stroke volume per beat (10).
Methods and limitations. The advantage of using the PFC method is that it is a noninvasive technique applied to increase our understanding of the mechanism of functional MR. Its limitation is that the isovelocity shells may not be strictly hemispheric, causing underestimation or overestimation of the flow rate (23,24). However, 1) throughout most of systole, the error of the flow calculation, as determined by the selected velocity for surface area calculation relative to the orifice velocity, was at most 5% based on the data of Rodriguez et al. (39), suggesting only mild estimation error; 2) overestimation of flow rates far from the orifice occurs primarily when the ventricular walls confine the PFC region and cause it to merge, in part, with vigorous aortic flow (23,36); because the patients studied had dilated LVs and low ejection fractions, such overestimation should be minimal and flow rate calculations accurate (36); 3) a similar technique used by Schwammenthal et al. (10) accurately integrated flow rate to give regurgitant stroke volume compared with both pulsed Doppler and quantitative angiographic techniques in patients, as well as in an in vivo model with implanted regurgitant orifices of known size; 4) it should be emphasized that our primary goal was not to obtain a more accurate determination of regurgitant flow and orifice area, but rather to describe the temporal pattern of the ROA, which should not be greatly affected by minor variations in quantification of regurgitant flow.
Calculating instantaneous regurgitant flow rates from color M-mode recordings of the PFC region also faces the potential limitation that the position of the regurgitant orifice and associated PFC zone can change due to translational movements of the heart while the M-mode beam is fixed. Therefore, the color M-mode cursor may not always pass exactly through both the zenith of the PFC region and the regurgitant orifice. However, at a depth of 16 cm and using a 2.5-MHz transducer, the finite ultrasound beam width results in a lateral resolution of 6 mm. The ultrasound beam therefore covers the whole pole rather than only the zenith of the isovelocity hemisphere, so that small translational movements should not affect measurements importantly. Thus, for the purpose of this method, the problem of the limited lateral resolution actually becomes an advantage, as validated and applied in clinical and experimental studies (10,34). Moreover, these patients with functional MR showed markedly reduced translational motion caused by impaired LV function, thereby minimizing any such potential effect.
The maximal value for r2 explaining the variation in ROA is 0.449 using the normalized values of TMP and MAA, and is 0.64 using the rates of change of these variables, which are more likely to influence dynamic changes in ROA; other factors that could potentially explain the remaining variability include patient-to-patient variation in the absolute values and rates of change of TMP, MAA, mitral leaflet length and ventricular size, geometry and function.
The possibility can also be raised that the ROA might vary in patients with functional MR because of phasic changes not only in the mitral annulus but also in the tethering distances between the papillary muscles and the mitral annulus (37). To evaluate whether such an effect is likely, we measured the papillary muscle tethering distances to the anterior mitral annulus using three-dimensional echocardiography (37) in early systole, midsystole and late systole in four of the patients in this study. The tethering distances of both medial and lateral papillary muscles to the mitral annulus were measured at these time points and were not statistically different throughout systole by two-way analysis of variance (p = 0.52). Thus, there do not appear to be important phasic changes that could contribute to the observed and extensive variations in ROA. This is consistent as well with the observations of Sanfillipo et al. (38), who showed no significant variation in papillary muscle tip-to-annulus distance in patients without mitral valve prolapse, consistent with the concept that papillary muscle shortening offsets the systolic apex-to-base contraction of the heart.
Conclusions. In summary, the time course and rate of change of ROA in patients with functional MR are predominantly determined by dynamic changes in the TMP acting to close the valve. Thus, although MAA helps determine the potential for MR, TMP appears important in driving the leaflets toward closure, and would be of value to consider in interventions aimed at reducing the severity of MR.
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractMethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  S. Buchner, K. Debl, F. Poschenrieder, S. Feuerbach, G. A.J. Riegger, A. Luchner, and B. Djavidani Cardiovascular Magnetic Resonance for Direct Assessment of Anatomic Regurgitant Orifice in Mitral Regurgitation Circ Cardiovasc Imaging, September 1, 2008; 1(2): 148 - 155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Buck, B. Plicht, P. Kahlert, I. M. Schenk, P. Hunold, and R. Erbel Effect of Dynamic Flow Rate and Orifice Area on Mitral Regurgitant Stroke Volume Quantification Using the Proximal Isovelocity Surface Area Method J. Am. Coll. Cardiol., August 26, 2008; 52(9): 767 - 778. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J-M Song, M-J Kim, Y-J Kim, S-H Kang, J-J Kim, D-H Kang, and J-K Song Three-dimensional characteristics of functional mitral regurgitation in patients with severe left ventricular dysfunction: a real-time three-dimensional colour Doppler echocardiography study Heart, May 1, 2008; 94(5): 590 - 596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Savage and S. Konstadt CON: Proximal Isovelocity Surface Area Should Not Be Measured Routinely in All Patients with Mitral Regurgitation Anesth. Analg., October 1, 2007; 105(4): 944 - 946. [Full Text] [PDF]
|
|
|
|
|
|
S. Fukuda, R. Grimm, J.-M. Song, T. Kihara, M. Daimon, D. A. Agler, B. L. Wilkoff, A. Natale, J. D. Thomas, and T. Shiota Electrical Conduction Disturbance Effects on Dynamic Changes of Functional Mitral Regurgitation J. Am. Coll. Cardiol., December 20, 2005; 46(12): 2270 - 2276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Levine and E. Schwammenthal Ischemic Mitral Regurgitation on the Threshold of a Solution: From Paradoxes to Unifying Concepts Circulation, August 2, 2005; 112(5): 745 - 758. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Schwammenthal and R. A. Levine The non-ischaemic dynamics of ischaemic mitral regurgitation: solving the paradox Eur. Heart J., August 1, 2005; 26(15): 1454 - 1455. [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Pierard and P. Lancellotti The Role of Ischemic Mitral Regurgitation in the Pathogenesis of Acute Pulmonary Edema N. Engl. J. Med., October 14, 2004; 351(16): 1627 - 1634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Levine and J. Hung Ischemic mitral regurgitation, the dynamic lesion: clues to the cure J. Am. Coll. Cardiol., December 3, 2003; 42(11): 1929 - 1932. [Full Text] [PDF]
|
|
|
|
|
|
O. A. Breithardt, A. M. Sinha, E. Schwammenthal, N. Bidaoui, K. U. Markus, A. Franke, and C. Stellbrink Acute effects of cardiac resynchronization therapy on functional mitral regurgitation in advanced systolic heart failure J. Am. Coll. Cardiol., March 5, 2003; 41(5): 765 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Kwan, T. Shiota, D. A. Agler, Z. B. Popovic, J. X. Qin, M. A. Gillinov, W. J. Stewart, D. M. Cosgrove, P. M. McCarthy, and J. D. Thomas Geometric Differences of the Mitral Apparatus Between Ischemic and Dilated Cardiomyopathy With Significant Mitral Regurgitation: Real-Time Three-Dimensional Echocardiography Study Circulation, March 4, 2003; 107(8): 1135 - 1140. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kumanohoso, Y. Otsuji, S. Yoshifuku, K. Matsukida, C. Koriyama, A. Kisanuki, S. Minagoe, R. A. Levine, and C. Tei Mechanism of higher incidence of ischemic mitral regurgitation in patients with inferior myocardial infarction: Quantitative analysis of left ventricular and mitral valve geometry in 103 patients with prior myocardial infarction J. Thorac. Cardiovasc. Surg., January 1, 2003; 125(1): 135 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hung, J. L. Guerrero, M. D. Handschumacher, G. Supple, S. Sullivan, and R. A. Levine Reverse Ventricular Remodeling Reduces Ischemic Mitral Regurgitation: Echo-Guided Device Application in the Beating Heart Circulation, November 12, 2002; 106(20): 2594 - 2600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Otsuji, T. Kumanohoso, S. Yoshifuku, K. Matsukida, C. Koriyama, A. Kisanuki, S. Minagoe, R. A. Levine, and C. Tei Isolated annular dilation does not usually cause important functional mitral regurgitation: Comparison between patients with lone atrial fibrillation and those with idiopathic or ischemic cardiomyopathy J. Am. Coll. Cardiol., May 15, 2002; 39(10): 1651 - 1656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Lebrun, P. Lancellotti, and L. A. Pierard Quantitation of functional mitral regurgitation during bicycle exercise in patients with heart failure J. Am. Coll. Cardiol., November 15, 2001; 38(6): 1685 - 1692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A. Timek and D. C. Miller Experimental and clinical assessment of mitral annular area and dynamics: what are we actually measuring? Ann. Thorac. Surg., September 1, 2001; 72(3): 966 - 974. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. DAVIES and D. SAHN Detection and significance of subclinical mitral regurgitation by colour Doppler techniques Heart, April 1, 2001; 85(4): 369 - 370. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | SUBSCRIPTIONS | CURRENT ISSUE | PAST ISSUES | CARDIOSOURCE | SEARCH | HELP | FEEDBACK |
