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J Am Coll Cardiol, 1998; 32:1819-1824
© 1998 by the American College of Cardiology Foundation
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CLINICAL STUDIES

The mechanism of decrease in dynamic mitral regurgitation during heart failure treatment: importance of reduction in the regurgitant orifice size

Luis B. Rosario, MDa, Lynne W. Stevenson, MD, FACCa, Scott D. Solomon, MD, FACCa, Richard T. Lee, MD, FACCa and Sharon C. Reimold, MD, FACCa

a Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA

Manuscript received April 10, 1998; revised manuscript received July 27, 1998, accepted August 20, 1998.

Address for correspondence: Dr. Sharon C. Reimold, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St., Boston, Massachusetts 02115
screimold{at}bics.bwh.harvard.edu


   Abstract
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 Abstract
Methods
 Results
 Discussion
 References
 
Objectives. The purpose of this study was to quantify and characterize the regurgitant flow pattern and regurgitant orifice area in patients undergoing therapy for severe heart failure using contemporary echocardiographic techniques.

Background. Mitral regurgitation may be dynamic in patients with heart failure and ultimately correlate with outcome in a group of patients.

Methods. Fourteen patients with severe heart failure felt to require hemodynamic monitoring for the optimization of medical therapy were enrolled. Two-dimensional and Doppler echocardiograms were performed before and following invasively guided therapy. Hemodynamics and standard echocardiographic dimensions were determined as well as regurgitant volume and regurgitant orifice area derived from color M-mode and Doppler measurements.

Results. Invasively guided therapy for heart failure was associated with a reduction in weight, filling pressures of the left and right heart, systemic vascular resistance, and echocardiographic left atrial, left ventricular and mitral annular dimensions. The mitral regurgitant volume decreased from 47 ± 27 ml before therapy to 14 ± 14 ml after therapy; p < 0.001. While therapy for heart failure markedly attenuated the volume of regurgitation, the pattern of regurgitant flow across the mitral valve was not significantly altered. In contrast, there was no difference in the velocity time integral of the continuous-wave Doppler spectra of mitral regurgitation with therapy (128 ± 23 cm to 123 ± 25 cm, p = 0.23). In all patients, the regurgitant orifice area decreased with therapy from 0.55 ± 0.38 cm2 to 0.21 ± 0.20 cm2 (p < 0.001).

Conclusions. Pharmacologic reduction in filling pressure and systemic vascular resistance leads to a reduction in the dynamic mitral regurgitation of heart failure through a reduction in the regurgitant orifice area but not through a change in the gradient across the mitral valve. Reduction of the regurgitant orifice area is likely related to decreased left ventricular volumes and decreased annular distention.

Heart failure is frequently accompanied by dynamic and sometimes severe mitral regurgitation. The presence of mitral regurgitation in patients with heart failure contributes to progression of ventricular dysfunction but also serves as a marker of worse outcome (1). The presence of significant mitral regurgitation may predict a salutory response to intensive vasodilator and diuretic therapy (2,3). Reduction in ventricular filling pressures and systemic vascular resistance may decrease ventricular volumes, increase forward stroke volume and reduce mitral regurgitation in animals with mitral regurgitation and in patients with heart failure (1,3–9).

A postulated mechanism for the development of mitral regulation in heart failure is dilatation of the mitral valve annulus (10). With mitral annular dilatation, mitral leaflet coaptation becomes ineffective and mitral regurgitation ensues (10). The mitral annulus has cyclical changes in diameter including a reduction in annular dimensions in systole (11). The mechanisms behind the development of mitral regurgitation as well as the factors that determine its response to therapy, however, may be more complex than previously assumed. The degree of mitral regurgitation in cardiomyopathy may be influenced not only by dilatation of the mitral annulus but also the geometry and function of the papillary muscles, chordae tendineae and mitral leaflets themselves (12,13). Reduction of mitral regurgitation in heart failure patients may be related to a decrease in afterload, changes in transmitral pressure gradients, reduction in the regurgitant orifice area or some combination of these mechanisms.

Recently, the echocardiographic proximal flow convergence method has been used to quantify the instantaneous mitral regurgitant flow and instantaneous effective regurgitant orifice area in patients with mitral regurgitation (14,15). Patients who have mitral regurgitation secondary to congestive heart failure have a unique pattern of flow across the mitral valve in systole which consists of early systolic accentuation of mitral regurgitant flow with lesser flow in the latter two-thirds of systole (15). The purpose of this study was to characterize this dynamic regurgitation in patients with severe heart failure and identify components responsible for reduced regurgitant flow during pharmacologic therapy for severe heart failure.


   Methods
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Results
 Discussion
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The echocardiographic protocol was approved by the Human Research Committee of Brigham and Women’s Hospital. Patients admitted to Brigham and Women’s Hospital due to worsening symptoms of heart failure or for evaluation for potential heart transplantation were identified. Patients undergoing hemodynamic monitoring during therapy were prospectively enrolled (14 patients; 13 male, 1 female). Patients were not preselected for the presence of severe mitral regurgitation; however, three additional patients who consented to the study did not have baseline mitral regurgitation and were not included in the study. Heart failure was attributed to ischemic (n = 6) or nonischemic (n = 8) etiologies prior to study enrollment using echocardiography, coronary angiography and/or ventriculography. Patients with heart failure known to be secondary to valvular heart disease were excluded. Hemodynamics were monitored with a pulmonary arterial catheter during the adjustment of therapy. The central venous pressure, pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output and systemic vascular index were determined at least every 4 h and more often during initial titration of medications. Patient weight was recorded daily.

Pharmacologic therapy included intravenous sodium nitroprusside and intravenous furosemide with subsequent uptitration of angiotensin-converting enzyme inhibitors and nitrates with occasional addition or substitution of hydralazine. Low-dose dobutamine was employed to facilitate initial diuresis in three patients. Doses of these medications were adjusted to approach goals of pulmonary capillary wedge pressure ≤ 15 mmHg, right atrial pressure of ≤ 8 mmHg and systemic vascular resistance of 1,000 to 1,200 dynes/s/cm–5 while maintaining systolic blood pressure ≥ 80 mmHg (12,13).

Echocardiographic examination.   Echocardiographic studies were performed using a Hewlett Packard Sonos 2000 imaging device with a 2.5 MHz transducer. Imaging was performed at the beginning and conclusion of invasively guided therapy. The average time between imaging studies was 2.8 ± 1.4 days with a median of 2.5 days. Images were recorded within 30 min of obtaining hemodynamic parameters. Parasternal and apical two-dimensional images were recorded. Doppler pulsed-wave tracings of left ventricular inflow and outflow along with continuous-wave Doppler of the mitral regurgitant jet were also obtained from apical views.

Apical color M-mode recordings were obtained at a depth of 16 to 18 cm and a Nyquist limit of 18 to 25 cm/s (15). Color M-mode recordings were guided by the two-dimensional jet appearance in order to orient the interrogation plane through the zenith of the proximal convergence isovelocity area; this minimizes effects of errors due to the angle between the interrogation axis and the main axis of the jet (15). The gain was adjusted to abolish background noise. The zero shift of the color map was also adjusted in order to have a hemispheric shape of the proximal convergence shell, thus avoiding shape changes caused by the constraints of the atrial walls or the orifice size and shape that may impair the calculations using the proximal isovelocity surface area method (15).

Echocardiographic image analysis.   All images were acquired in video format and analyzed with a custom-made post-processing program by an observer blinded to the identity and timing of each test. For each measurement and tracing, a minimum of three cardiac cycles were used. M-mode left ventricular chamber dimensions were measured from parasternal long-axis views according to specifications of the American Society of Echocardiography. Mitral annulus diameter was measured from the apical four chamber view at end-diastole and end-systole. Pulsed-wave Doppler measurements of E and A wave maximal velocity as well as E wave deceleration time and velocity time integrals of left ventricular inflow and outflow were performed using the modal velocity. Color M-mode recordings of mitral regurgitation were traced (15). The distance between the aliasing boundary and the mitral valve over time was measured and the aliasing velocity recorded.

Theoretical background.   As flow converges toward an orifice, the theory of conservation of mass predicts that velocity should increase, creating a hemispheric geometry of flow with increasing velocities and decreasing surface areas as blood approaches the orifice. Using the appropriate settings for color Doppler echocardiography, it is possible to visualize and record the hemispheric acceleration zone. Color Doppler M-mode has the temporal and spatial resolution to record the changes in the radius of the shell during the cardiac cycle. Assuming that the blood passing through the hemispheric shell is the same as that passing through the orifice, the flow through the orifice can be calculated from the formula: In the color Doppler M-mode tracings, the distance from the valve to the first aliasing boundary was digitized over time and used to calculate the instantaneous volumetric flow across the mitral valve during systole (15). The regurgitant volume was calculated by integrating over systole the instantaneous volumetric curve according to the formula: The effective mitral regurgitant orifice area was calculated as

Instantaneous flow rates and regurgitant orifice area were calculated for each patient and comparisons were made before and after therapy. In addition, the proportion of regurgitant flow occurring in the first third of systole was assessed to determine if aggressive therapy for heart failure altered the temporal pattern of blood flow through the mitral orifice.

Statistics.   Paired Student’s t tests were used to compare hemodynamic parameters and echocardiographic characteristics before and after therapy. A p value of <0.05 was considered to be statistically significant.


   Results
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Discussion
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Patient hemodynamics.   Between initiation and conclusion of therapy, there were significant reductions in weight, central venous pressure, pulmonary capillary wedge pressure, systemic vascular resistance, pulmonary vascular resistance and pulmonary capillary wedge pressure in these patients and an increase in cardiac output (Table 1). There were no significant changes in heart rate during the study. Despite these dramatic hemodynamic changes, there was no significant change during therapy in the pressure difference between the systolic blood pressure and the mean capillary wedge pressure, a surrogate for the systolic pressure difference across the mitral valve (75.3 ± 12.2 mmHg to 71.1 ± 12.8 mmHg, p = 0.16). These changes reflected primarily vasodilation and diuresis because inotropic support was used in only three patients.


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  		Table 1 Individual and Group Hemodynamics

 
Echocardiographic and Doppler parameters.   Patients had marked left ventricular dilatation with initial end-diastolic dimensions of 7.4 ± 1.0 cm. End-diastolic dimensions decreased significantly with therapy (Table 2). The left atrium decreased in size. There was a small but significant decrease in the diameter of the mitral annulus. The left ventricular inflow pattern demonstrated a decrease in peak E wave velocity but no substantial changes in mitral valve deceleration time. The velocity time integral of antegrade flow through the mitral valve also decreased from 13.8 ± 3.9 cm to 11.9 ± 4.2 cm.


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  		Table 2 Echocardiographic and Doppler Variables Before and After Therapy

 
The mitral regurgitant volume decreased from 47 ± 27 ml prior to therapy to 14 ± 14 ml after therapy, p < 0.001 (Fig. 1). The regurgitant orifice area decreased significantly with therapy from 0.55 ± 0.38 cm2 to 0.21 ± 0.20 cm2 (p < 0.001, Fig. 2). The regurgitant fraction fell from 50.3 ± 13.1% to 14.9 ± 15.0%, p < 0.001. These findings were uniformly consistent; 14/14 (100%) of patients had a decrease in the echocardiographically determined regurgitant volume and effective regurgitant orifice area with therapy. Individual changes in Doppler-derived flow and orifice area are shown in Table 3. The velocity time integral of the continuous-wave Doppler spectra of mitral regurgitation did not change with therapy in the ten patients in whom it could be recorded before and after therapy (128.3 ± 22.6 cm before therapy to 123.0 ± 25.0 cm after therapy, p = 0.23).



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  		Figure 1 The regurgitant volume calculated using proximal isovelocity surface area methods is shown before and after therapy. The mitral regurgitant volume decreased from 47 ± 27 ml prior to therapy to 14 ± 14 ml after therapy, p < 0.001. The fall in regurgitant volume was noted for all patients enrolled in the study.

 


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  		Figure 2 The regurgitant orifice area is shown before and after therapy. The regurgitant orifice area decreased significantly from 0.55 ± 0.38 cm2 to 0.21 ± 0.20 cm2 (p < 0.001, Fig. 2). There was a decrease in the regurgitant orifice area in all patients.

 

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  		Table 3 Individual Changes in Mitral Regurgitation Associated with Heart Failure Therapy

 
The temporal pattern of mitral regurgitant flow in these heart failure patients prior to therapy consisted of slightly more regurgitant flow in the first two-thirds of systole. The proportion of regurgitant flow occurring in each third of systole was 36.8 ± 7.4%, 36.0 ± 4.6%, and 27.0 ± 5.4% prior to therapy. While therapy for heart failure markedly attenuated the volume of regurgitation, the timing of flow across the valve was not significantly altered. Following therapy, the proportion of regurgitant flow in each third of systole was 35.5 ± 7.9%, 33.1 ± 3.7%, and 31.4 ± 7.0%. The regurgitant orifice area was not constant and was largest in early systole, decreasing throughout the remainder of systole. In the first third of systole, the orifice area was 50% larger than the average orifice area (0.55 ± 0.38 cm2 average area, 0.84 ± 0.61 cm2 in the first third of systole). The relationship was similar after therapy (0.21 ± 0.20 cm2 average area, 0.31 ± 0.31 cm2 in the first third of systole). An example of changes in orifice area before and after therapy in one patient is shown in Figure 3.



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  		Figure 3 Changes in the regurgitant orifice area over time are shown for one patient prior to therapy (solid line) and after therapy (dotted line). While there is a decrease in regurgitant orifice area throughout systole, the orifice remains the largest early in systole.

 

   Discussion
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 Methods
 Results
 Discussion
References
 
Intensive therapy for heart failure is accompanied by a marked reduction in mitral regurgitant volume and regurgitant orifice area. This reduction in orifice area appears to result from a decrease in left ventricular end-diastolic dimensions, left atrial dimensions and mitral annular dimensions consistent with a decrease in the volume load on the left atrium and left ventricle. The major change in hemodynamics is related to a decrease in left ventricular filling pressures and a decrease in systemic vascular resistance with augmented forward output.

Several studies performed in the 1970s and 1980s investigated the hemodynamic effects of exercise and various inotropic and vasodilator agents in patients with heart failure and mitral regurgitation (3,7–9,16–20). Keren et al. (3) noted that isometric exercise resulted in a decrease in forward stroke volume and an increase in mitral regurgitant volume in patients with heart failure. Nitroglycerin and dobutamine therapy each led to a reduction in mitral regurgitation and an increase in stroke volume in one study (3). This pharmacologic effect was most apparent in patients with the greatest amounts of mitral regurgitation (3). Other investigators have described divergent responses to nitroprusside and dobutamine therapy (18). Nitroprusside led to increased cardiac output, reduced filling pressure and a decrease in mitral regurgitation while dobutamine led to increased cardiac output with a variable effect on the degree of mitral regurgitation by color Doppler echocardiography (18). Nitroglycerin may result in improved hemodynamics when administered topically as well as intravenously (3,19). Both sodium nitroprusside and hydralazine result in a decrease in mitral regurgitation and an increase in forward cardiac output by decreasing systemic vascular resistance but sodium nitroprusside may result in a greater reduction in left ventricular diastolic volumes (20).

Although prior studies have described a reduction in the color jet area of mitral regurgitation in patients treated for heart failure, our study more precisely quantifies the magnitude of this change and helps to elucidate the mechanism (16). The decrease in regurgitant volume and orifice area, a uniform finding in all study participants, was not associated with any significant changes in the systolic blood pressure to pulmonary capillary wedge pressure difference or in the mitral regurgitant Doppler continuous-wave velocity time integral, suggesting that the mechanism for a reduction in the orifice area is related predominantly to alterations in the mitral apparatus geometry as opposed to altered pressure gradients across the mitral apparatus. These results correspond well with the observation of a decrease in the regurgitant orifice area using nitroglycerin (7). The bulk of mitral regurgitation occurs during aortic ejection (21). The timing of regurgitant flow does not change significantly with therapy, suggesting that the intrinsic mechanisms responsible for producing mitral regurgitation in this heart failure population remain operative following intensive therapy.

It is likely that leaflet coaptation is improved at smaller left ventricular volumes due to a small decrease in mitral annular distention. For instance, a reduction in the mitral annulus diameter from 3.5 cm to 3.3 cm observed in our population would result in a decrease in the effective annular area (assuming a circular annulus) from 9.6 cm2 to 8.6 cm2, a difference that far exceeds the average change in orifice area of 0.34 cm2 in the population. In addition, reduction in left ventricular volumes may improve the relationship between the subvalvar apparatus and valve leaflets and decrease ischemia in those individuals with coronary artery disease. Because the mechanisms underlying mitral regurgitation are complex, it is difficult to determine the relative contributions of changes in the annulus and the subvalvar apparatus to this effect. A decrease in left atrial size and pressure may contribute to reduced stress on the annular apparatus.

Doppler echocardiographic mitral flow velocity patterns have been shown to be useful in estimation of left ventricular filling pressures and predicting the risk of death (22,23). Administration of vasodilators is also associated with a decrease in Doppler echocardiographic mitral valve Doppler E wave velocities and a decrease in the antegrade velocity time integral consistent with a decrease in mitral regurgitation (24,25). Our results are consistent with these prior observations. Mitral inflow deceleration times did not change in our study. This is possibly related to the advanced degree of heart failure in our patients.

Limitations.   Calculation of mitral regurgitant transvalvar flow as described in this study makes several assumptions regarding uniformity of flow through the mitral valve and to the technique of the proximal isovelocity surface area as previously described (15,26,27). These limitations were minimized because the study was designed as a comparison of regurgitant flow before and after therapy in individual patients. Regurgitant flow following therapy may be difficult to determine when flow falls below a critical level. The assumption that regurgitant flow is zero in these instances may lead to a slight overestimation of the size of treatment effect, but this small difference would not influence the statistical significance of these findings. Since heart failure treatment was aimed at reaching predetermined treatment goals, therapy was not randomized and it would not be possible to attribute the effects to a specific drug. It should also be recognized that the hemodynamic and mechanistic changes in this study may not apply to patients with other etiologies of mitral regurgitation such as rheumatic valvular disease.

Clinical implications.   The use of vasodilators and diuretics leads to a reduction in the dynamic mitral regurgitation of heart failure through a reduction in the regurgitant orifice area. Much of the benefit of therapy for decreasing pulmonary congestion and improving forward output is from the redistribution of mitral regurgitant flow to forward flow. This study suggests that serial measurement of mitral regurgitation may provide important guidance for acute and chronic adjustment of vasodilators and diuretics in heart failure.


   Footnotes
 
Dr. Rosario was supported by the Fundacao Luso-Americana para o Desenvolvimento. Dr. Solomon was supported by a Clinician Scientist Award from the American Heart Association. Dr. Reimold was supported by a Clinical Investigator Development Award from the NHLBI (HL-02758).


   References
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 Abstract
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 Discussion
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  1. Conti JB, Mills RM. Mitral regurgitation and death while awaiting cardiac transplantation. Am J Cardiol. 1993;71:617–618[CrossRef][Medline]
  2. Evangelista-Masip A, Bruguera-Cortada J, Serrat-Serradell R, et al. Influence of mitral regurgitation on the response to captopril therapy for congestive heart failure caused by idiopathic dilated cardiomyopathy. Am J Cardiol. 1992;69:373–376[CrossRef][Medline]
  3. Keren G, Katz S, Strom J, Sonnenblick EH, LeJemtel TH. Dynamic mitral regurgitation. An important determinant of the hemodynamic response to load alterations and inotropic therapy in severe heart failure. Circulation. 1989;80:306–313[Abstract/Free Full Text]
  4. Borgenhagen DM, Serur JR, Gorlin R, Adams D, Sonnenblick EH. The effects of left ventricular load and contractility on mitral regurgitant orifice size and flow in the dog. Circulation. 1977;56:106–118[Abstract/Free Full Text]
  5. Yoran C, Yellin EL, Becker RM, Gabbay S, Frater RWM, Sonnenblick EH. Dynamic aspects of acute mitral regurgitation: effects of ventricular volume, pressure and contractility on the effective regurgitation orifice area. Circulation. 1979;60:170–176[Abstract/Free Full Text]
  6. Yellin EL, Yoran C, Sonnenblick EH, Gabbay S, Frater RWM. Dynamic changes in the canine mitral regurgitant orifice area during ventricular ejection. Circ Res. 1979;45:677–683[Abstract/Free Full Text]
  7. Keren G, Bier A, Strom JA, Laniado S, Sonnenblick EH, LeJemtel TH. Dynamics of mitral regurgitation during nitroglycerin therapy. Am Heart J. 1986;112:517–525[CrossRef][Medline]
  8. Stevenson LW, Bell D, Grover-Mickey M, Brunched R, Schwaiger M, Tillisch J, et al. Effects of afterload reduction (diuretics and vasodilators) on left ventricular volume and mitral regurgitation in severe congestive heart failure secondary to ischemic or idiopathic cardiomyopathy. Am J Cardiol. 1987;60:654–658[CrossRef][Medline]
  9. Keren G, Laniado S, Sonnenblick EH, Lejemtel TH. Dynamics of functional mitral regurgitation during dobutamine therapy in patients with severe congestive heart failure: a Doppler echocardiographic study. Am Heart J. 1989;118:748–754[CrossRef][Medline]
  10. Boltwood CM, Tei C, Wong M, Shah PM. Quantitative echocardiography of the mitral complex in dilated cardiomyopathy: the mechanism of functional mitral regurgitation. Circulation. 1983;68:498–508[Free Full Text]
  11. Ormiston JA, Shah PM, Tei C, Wong M. Size and motion of the mitral valve annulus in man. I. A two-dimensional echocardiographic method and findings in normal subjects. Circulation. 1981;64:113–120[Abstract/Free Full Text]
  12. Izumi S, Miyatake K, Beppu S, et al. Mechanism of mitral regurgitation in patients with myocardial infarction: a study using real-time two-dimensional Doppler flow imaging and echocardiography. Circulation. 1987;76:777–785[Abstract/Free Full Text]
  13. Kaul S, Spotnitz WD, Glasheen WP, Touchstone DA. Mechanism of ischemic mitral regurgitation. Circulation. 1991;84:2167–2180[Abstract/Free Full Text]
  14. Enriquez-Sarano M, Sinak LJ, Tajik AM, Bailey KR, Seward JB. Changes in effective regurgitant orifice throughout systole in patients with mitral valve prolapse. Circulation. 1995;92:2951–2958[Abstract/Free Full Text]
  15. Schwammenthal E, Chen C, Benning F, Block M, Breithardt G, Levine RA. Dynamics of mitral regurgitant flow and orifice area. Circulation. 1994;90:307–322[Abstract/Free Full Text]
  16. Hamilton MA, Stevenson LW, Child JS, Moriguchi JD, Woo M. Acute reduction of atrial overload during vasodilator therapy in advanced congestive heart failure. Am J Cardiol. 1990;65:1209–1221[CrossRef][Medline]
  17. Chatterjee K, Parmley WW, Swan HJC, Berman G, Forrester J, Marcus HS. Beneficial effects of vasodilator agents in severe mitral regurgitation due to dysfunction of subvalvar apparatus. Circulation. 1973;48:684–690[Abstract/Free Full Text]
  18. Capomolla S, Pozzoli M, Opasich C, et al. Dobutamine and nitroprusside infusion in patients with severe congestive heart failure: hemodynamic improvement by discordant effects on mitral regurgitation, left atrial function, and ventricular function. Am Heart J. 1997;134:1089–1098[CrossRef][Medline]
  19. Taylor WR, Forrester JS, Magnusson P, Takano T, Chatterjee K, Swan HJ. Hemodynamic effects of nitroglycerin ointment in congestive heart failure. Am J Cardiol. 1976;38:469–473[CrossRef][Medline]
  20. Greenberg BH, Massie BM, Brundage BH, Botvinick EH, Parmley WW, Chatterjee K. Beneficial effects of hydralazine in severe mitral regurgitation. Circulation. 1978;58:273–279[Abstract/Free Full Text]
  21. Keren G, LeJemtel TH, Zelcer AA, Meisner JS, Bier A, Yellin EL. Time variation of mitral regurgitant flow in patients with dilated cardiomyopathy. Circulation. 1986;74:684–692[Abstract/Free Full Text]
  22. Nishimura RA, Appleton CP, Redfield MM, Ilstrup DM, Holmes DR, Tajik AJ. Noninvasive Doppler echocardiographic evaluation of left ventricular filling pressures in patients with cardiomyopathies: a simultaneous Doppler echocardiographic and cardiac catheterization study. J Am Coll Cardiol. 1996;28:1226–1233[Abstract]
  23. Xie GY, Berk MR, Smith MD, Gurley JC, DeMaria AN. Prognostic value of Doppler transmitral flow patterns in patients with congestive heart failure. J Am Coll Cardiol. 1994;24:132–139[Abstract]
  24. Lee JM, Masuyama T, Nagano R, et al. Effects of vasodilators on pulmonary venous and mitral flow velocity patterns in patients with congestive heart failure. Jpn Circ J. 1993;57:935–946[Medline]
  25. Keren G, Pardes A, Eschar Y, Hansch E, Scherez J, Laniado S. Left ventricular filling dynamics by Doppler echocardiography in dilated cardiomyopathy: one-year follow-up in patients treated with captopril compared to placebo. Cardiology. 1992;81:196–206[Medline]
  26. Enriquez-Sarano M, Miller FA, Hayes SN, Bailey KR, Tajik J, Seward JB. Effective mitral regurgitant orifice area: clinical use and pitfalls of the proximal isovelocity surface area method. J Am Coll Cardiol. 1995;25:703–709[Abstract]
  27. Vandervoort PM, Rivera JM, Mele D, et al. Application of color Doppler flow mapping to calculate effective regurgitant orifice area. Circulation. 1993;88:1150–1156[Abstract/Free Full Text]



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S. F. Yiu, M. Enriquez-Sarano, C. Tribouilloy, J. B. Seward, and A. J. Tajik
Determinants of the Degree of Functional Mitral Regurgitation in Patients With Systolic Left Ventricular Dysfunction : A Quantitative Clinical Study
Circulation, September 19, 2000; 102(12): 1400 - 1406.
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