Noninvasive quantification of mitral regurgitation in dilated cardiomyopathy: Correlation of two Doppler echocardiographic methods

Noninvasive quantification in dilated cardiomyopathy: Doppler echocardiographic

of mitral regurgitation Correlation of two methods

The presence and severity of functional mitral regurgitation were quantified by Doppler echocardiography in 17 patients with dilated cardiomyopathy and no evidence of primary vaivuiar disease. Mitral regurgitant fraction was greater than 20% in 11 of the 17 patients, and exceeded 40% in four patients. Total stroke volume, calculated from the difference between end-diastolic and end-systotic volumes obtained by two-dimensional echocardiography, correlated well with mitral valve inflow determined by Doppler echocardiography (r = 0.90, p < 0.001). Similarly, mitral regurgitant volume, calculated as the difference between echocardiographic total stroke volume and forward aortic volume obtained by Doppler echocardiography, correlated well with regurgitant volume calculated as the difference between mitral valve inflow and forward aortic flow, both determined by Doppler echocardiography (r = 0.90, p < 0.001). Accordingly, functional mitral regurgitation can be conveniently demonstrated in patients with dilated cardiomyopathy by two different Doppler echocardiography methods, whose results are closely correlated. Mitral regurgitant fraction is greater than 20% in two thirds of the patients with a dilated cardiomyopathy. (AM HEART J 1988; 116:758.)

Gad Keren, MD,* Stuart Katz, MD, Joel Strom, MD, Edmund H. Sonnenblick, MD, and Thierry H. LeJemtel, MD. Bronx, N.Y.

Doppler echocardiography has recently become a convenient and reliable technique for the noninvasive detection of mitral regurgitation (MR),‘-* and has been very useful in demonstrating the high frequency and severity of functional MR in patients with dilated cardiomyopathy.5 Moreover, the amount of MR in a given patient contributes substantially to the hemodynamic response to pharmacologic interventions in these patients,6-g and thus it has become increasingly important to quantify the amount of MR. Two methods that use Doppler echocardiography have been proposed for the quantitative estimation of MR, and have been validated against angiographic methods in patients with primary mitral valve disorders.lOsl1 In both methods, the amount of regurgitation is calculated from the difference between total stroke volume and forward

From the Department of Medicine, Einstein College of Medicine. Dr. Keren Foundation. ILGCGIVW Reprint Medicine, *Current

758

was supported IUI pul~~umuu

in part WIV.

Division

by the G. Harold

Y, lY81;

requests: Thierry H. LeJemtel, 1300 Morris Park Ave., Bronx, address:

Ichilov

Hospital,

of Cardiology,

accepted

and May

MD, Albert NY 10461.

Tel Aviv,

Israel.

Leila

The

Albert

Patient

population.

Twenty

consecutive

patients

with

chronic congestive heart failure, who were admitted to the coronary care unit for invasive hemodynamic monitoring of inotropic or vasodilator therapy, underwent echocardiographic and Doppler studies. An adequate noninvasive examination was obtained in 17 patients. They were in functional classIII to IV accordingto the New York Heart Association classification, despite therapy with digitalis, diuretics, and nitrates. No patient had been previously hydralazine, captopril, or prazosin. Their 63 years and ranged from 52 to 78 years. All patients were in sinusrhythm except one (No. 14) who was in airiai Goriiiation. Left ventricuiar ejection fraction

Y. Mathers

College

METHODS

treated with ages averaged

2, 1988. Einstein

aortic stroke volume; one method derives total stroke volume from Doppler-estimated mitral filling volume,1o while the other obtains total stroke volume by two-dimensional echocardiography.” The present study was undertaken to quantify regurgitation in patients with dilated cardiomyopathy in whom no primary mitral valve abnormality was evident. The ultrasound methods were used and cross-correlated for the estimation of total stroke volume and the amount of MR.

of

averaged 25% and ranged from 17% to 35%. Twelve of the 17 patients demonstrated a holosystolic murmur at the apex, consistent

with

the presence

of mitral

valve

Volum* Number

Table

116 3

Mitral

1. Hemodynamic

Patient

parameters

HR (beatslmin)

regurgitation

in dilated

cardiomyopathy

SV (ml/beat)

(dyne

_..--..~~.-

RAP (mm Hg)

SAP (mm Hg)

PCWP (mm Hg)

CI (Llminlm2)

6

SVR set cm-‘)

1

76

3

77

3.18

69

1127

2 3 4

86 90

a 3 0

80 85 79

20 10 11

2.64 2.3 1.47

42

1578 1853 2488

3 3

85 94

30 36

2.2 2.54

5 0 12

73 94

21 12

9 22

103 88 97

16 19

2.18 2.59 1.56

15 12

75 106

30 26 15

5 6 7 a 9

88 80 92 67 65

10

71 79

11 12 13

100 92 84

14 15 16

85 84 76

9 1 0

99 69 102

17

63 81 +lO

7

98 88 ?12

Mean k SD

759

+6

CI = cardiac index; HR = heart rate; PCWP = mean pulmonary pressure; SV = stroke volume; SVR = systemic vascular resistance.

capillary

regurgitation. The mitral apparatus, tricuspid, and aortic valve were carefully evaluated by Doppler echocardiography to detect any malfunction. None of the patients had primary mitral valve disease or flail mitral leaflet. Nine patients had mild tricuspid regurgitation and none had aortic regurgitation. Left ventricular end-diastolic volume was substantially enlarged in all patients. In nine patients, the etiology of the dilated cardiomyopathy was coronary artery disease that was documented by previous myocardial infarctions and/or abnormal coronary angiograms. No patient had sustained a myocardial infarction within 6 months of the study. The dilated cardiomyopathy was of unknown etiology in five patients and was alcoholic in origin in the remaining three. Long-acting nitrates were discontinued 72 hours prior to admission to the coronary care unit. The nature of the study was explained to all patients, who then gave signed consent. Hemodynamics. Right heart catheterization was performed with a flow-directed, balloon-tipped, thermodilution catheter. Mean pulmonary arterial, pulmonary capillary wedge, and right atria1 pressures were monitored and recorded (Electronics for Medicine/Honeywell Inc., Pleasantville, N.Y.). Cardiac output was determined by the thermodilution technique with iced 5 5% dextrose in water, and was obtained in triplicate with less than 10% variation. Computations of cardiac output were made with a bedside computer (No. 952OA, Baxter Edwards Divisions, Irvine, Calif.). Systemic arterial pressure was obtained by insertion of an indwelling catheter into the radial artery. Derived hemodynamic indices were calculated by standard formulas. In patients who were found by Doppler to

39 29 55

2.25 2.09 1.63 2.74

20 11 4

1.37 2.36 2.07

27 43 61

11 18 *9

1.98 2.17 -t 0.49

53 48 2 -12

pressure;

RAP

= right

1528 1984 2815

58 40 59 37 37 63

wedge

1490 1741

45 53

atria1

pressure;

1350 1639 1437 1426 3157 1494 1770 2192 1827 f 547 SAP

= mean

systemic

arterial

have tricuspid regurgitation, cardiac output was derived from the Fick method with direct measurement of oxygen uptake and arteriovenous oxygen difference, and correlated well with the thermodilution technique (r = 0.90, p < 0.001). Noninvasive studies. A Hewlett-Packard ultrasound imaging system (77020AC, Hewlett-Packard Co., Andover, Mass.) was used for both imaging and Doppler flow studies. The system has a phased-array sector scanner and a movable Doppler cursor that allow sampling directed by two-dimensional echocardiographic imaging in the pulsed Doppler mode. The noninvasive studies were performed simultaneously with cardiac output determination by the thermodilution method. The patient was asked to avoid deep inspiration or Valsalva maneuver. MR volume was calculated as the difference between total left ventricular stroke volume and forward aortic flow. Total left ventricular stroke volume was obtained by two-dimensional echocardiography and by calculation of forward mitral tilling volume over the mitral anulus. Total stroke volume by two-dimensional echocardiography. The apical four-chamber view was used for estimation of volume.6~7~12~13 The patient was positioned in the left lateral decubitus position. Every effort was made to obtain the maximal length and width of both right and left ventricles. Optimal and reproducible transducer angulation was ensured by angling the imaging plane dorsally and ventrally to visualize the mitral and tricuspid valve leaflets and left atrium. Images were accepted for analysis when at least 80% of the endocardium was seen. None of the patients with coronary artery disease had significant left ventricular

760

Keren

Table

II. Echo-Doppler measurementsand derived parameters

Patient No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17

Mean +SD ASV = volume RFb = *For a

et al.

American

MR Vu

SwWnber Hemi

1988 Journal

EDV

ESV

TSV

ASV

MFV

(ml)

(ml)

(ml)

(ml)

(ml)

(ml)

MR Vb (ml)

RFa

RFb

EFa

EFb

202 179 217 252 308 235 232 248 175 297 178 245 354 285 274 299 228 248 251

129 125 162 200 242 183 193 179 116 228 130 175 278 233 193 241 142 185 &48

73 54 55 52 66 52 39 69 59 69 48 70 75 52 81 58 86 62 +-13

64 46 37 30 57 39 37 54 56 52 37 40 69 33 38 62 66 48 *13

70 62 51 54 67 53 37 61 59 63 58 70 67 59 81 64 84 62 *11

9 8 18 22 9 13 2 15 3 17 11 30 6 19 43 0 20 14 *12

6 16 14 24 10 14 0 7 3 11 21 30 0 26 43 2 18 14 *11

12 14 33 42 14 25 5 22 5 25 23 43 8 36 53 0 23 23 &15

9 25 27 44 15 26 0 11 5 17 36 43 0 44 53 3 21 22 +16

36 30 25 20 21 22 17 27 33 27 27 28 21 18 29 19 37 26

35 34 23 16 21 22 16 24 33 21 33 28 18 21 29 21 35 25

?6

k7

aortic forward stroke volume; EDV = end-diastolic volume; ESV = end-systolic volume; MFV = mitral filling volume; MRVa = mitral regurgitation by method a*; MRVb = mitral regurgitation volume by method b*; TSV = total stroke volume; RFa = regurgitation fraction by method a*; regurgitation fraction by method b*; EFa = ejection fraction by method a*; EFb = ejection fraction by method h*. description of methods a and b, see Methods section of the report.

asynergy. Endocardial echocardiogramswere traced with an integrated Echo-Doppler analyzer (Microsonics-Datavue, Indianapolis, Ind.) programmed for single-planearea, length, and volume computation by means of Simpson’s rule, as previously described.6r7Left ventricular volumes were measuredat end diastole (i.e., largest dimension or onset of the QRS complex) and at end systole (i.e., smallest dimension or one frame prior to opening of the mitral valve). Total stroke volume was calculated from end-diastolic and end-systolic volumes. Three to five cardiac cycles were analyzed when patients were in sinus rhythm (<5 % variation per cycle) and seven cycles were analyzed in one patient who was in atria1 fibrillation. Left ventricular ejection fraction was calculated by two methods: a, the ratio of total stroke volume obtained by echocardiography to end-diastolic volume and b, the ratio of total stroke volume obtained by Doppler study of forward mitral flow to end-diastolic volume obtained by echocardiography. Forward stroke volume by pulsed Doppler cardiography. Left ventricular outflow was recorded from the apical position at the level of the aortic anulus, as described previously.6*7The samplevolume wasplaced in the middle of the left ventricular outflow tract, immediately proximal to the leaflets of the aortic valve. Slight adjustments were required to optimize the orientation between the sample volume and flow. Pnr.,7nmJ ---L!ti.\r ZUVYVU~UIU~was determined as the _- -- . UuI product of the integrated velocity of aortic outflow relative to time, and the cross-sectional area of the aortic

anulus. Curves exhibiting the highest peak velocities of flow were selectedfor analysis. The cross-sectionalarea of the aortic anulus was calculated asAr*, where r represents half of the maximal annular diameter measured in the parasternal long-axis view, immediately proximal to the points of insertion of the aortic leaflets. Measurementsof aortic anulus were made from leading edgeto leadingedge at mid-systole. Mitral flow study. The presenceof mitral insufficiency was thoroughly searched for by scanning the atrium near the mitral valve for regurgitating flow. Mitral flows at the levels of the tips of the mitral leaflets and at the mitral anulus were recorded. Mitral flow and left ventricular outflow velocities were recorded on video (PanasonicAG6300, PanasonicInternational, Secaucus, N.J.) and on a hard copy recorder (Hewlett-Packard 77500B) at a paper speed of 100 mm/ sec. Three to five Doppler flow tracings were analyzed in the patients with sinus rhythm and seven tracings were made in the patient in atria1 fibrillation. Mitral inflow was determined from the product of the integrated mitral flow velocity curve over time, and mitral anulus area.‘0*14The diameter of the mitral anulus was measuredasthe distance from the lateral inner edgeto the medial inner edgeof the anulusjust below the insertion of the mitral leaflets, with the apical four-chamber view. Measurements were made two or three frames after the maximal opening of the anterior leaflet. Cross-sectional areaswere obtained assuminga circular geometry, i.e., 1rr2, where r represents half of the annular diameter.

Volume Numbor

116 3

Mitral

y=o.a4x+a r =o.ao p< 0.001 SEE= 7.6

80-

100

-

/

/

P@ / - / / J I

0

cardiomyopathy

761

y=O.BX+13 r = 0.90 p < 0.001

80

7%

L

?

20

in dilated

0 a/

40

a/

. t”

60

regurgitation

/

,/’

/

//

/A

/

/ / I

I

I

I

I

I

I

0

I

20 40 60 80 forward stroke volume by thermodilution(FSV, ml)

Fig. 1. Correlation between stroke volume obtained thermodilution and aortic stroke volume measured Doppler echocardiography at the aortic anulus.

by by

The regurgitant volume and regurgitation fraction were derived by two methods: In method a, regurgitant volume (MRVa) was measured as the difference between total stroke volume obtained by two-dimensional echocardiography (TSVe) and forward aortic stroke volume obtained by Doppler (ASVd). The mitral regurgitant fraction (MRFa) was calculated as the ratio of the regurgitant volume (MRVa) to the total stroke volume by echocardiography (TSVe). Thus MRVa = TSVe-ASVd and MRFa = MRVa/TSVe. In method b, mitral regurgitant volume (MRVb) was derived from the difference between forward mitral filling volume (MFVd) and aortic stroke volume (ASVd), both obtained by Doppler. Mitral regurgitation fraction (MRFb) was calculated as the ratio of MRVb to MFVd. Statistical analysis. The data were expressed as mean + SD. Differences between means were determined by Student’s t test. A regression analysis was performed to determine the relationship between volumes and fractions derived by the different methods. The correlation coefficient (r) was determined for each regression analysis. Statistical significance was accepted at a 95% confidence level. RESULTS

The hemodynamic measurements for all 1’7 patients are detailed in Table I, while noninvasive measurements are shown in Table II. Left ventricular performance was compromised in all patients, as evidenced by a reduced cardiac index averaging

I

I

I

I

20 40 60 80 100 total stroke volume by echocardiography (TSV, ml)

Fig. 2. Correlation between total stroke volume derived from left ventricular end-diastolic and systolic volumes measured by two-dimensional echocardiography and transmitral filling volume measured by Doppler echocardiography at the mitral anulus.

2.17 -+ 0.49 L/min/m2, and an increased pulmonary capillary wedge pressure of 18 ? 9 mm Hg. Left ventricular end-diastolic volume was increased to 248 -+ 51 ml, with an average ejection fraction of 25 +- 6%. Left ventricular end-diastolic volume tended to be greater in patients with nonischemic cardiomyopathy than in those with ischemic cardiomyopathy, although it did not reach statistical significance: 256 & 38 vs 239 +- 60 ml (NS). MR was detected in all but one patient. The regurgitant volume was greater than 10 ml in 11 of the 17 patients, which corresponded to a regurgitant fraction of more than 20%. Overall, the MR fraction ranged from 0% to 53%. MR volume was correlated with mitral annular area (r = 0.53, p < 0.05), but not with end-diastolic volume. MR volume was greater in patients with nonischemic cardiomyopathy than in those with ischemic cardiomyopathy: 17 -+ 7 vs 12 + 12 ml (p < 0.05). Similarly, the area of the mitral anulus tended to be greater in patients with nonischemic cardiomyopathy than in those with ischemic cardiomyopathy: 8.1 r+ 1.7 vs 7.4 + 1.9 cm*. Forward stroke volume measured by the thermodilution technique averaged 48 f 12 ml and correlated well with aortic stroke volume obtained by Doppler echocardiographic methods (Fig. 1; r = 0.80, p < 0.001). Total stroke volume, as calcu-

762

Keren

et al.

American

y= 0.99x r =0.90

50-

+ 0.22

60 r

p
September 1988 Heart Journal

y =1.03x - 1.02 r ~0.92 p
ki 402 c c SE 305 _ .z >” $g zoc-3 t.-

lo-

E I

I

I

- 10 20 30 40 mitral regurgitation volume (MRVa, ml)

I

50

Fig. 3. Correlation between mitral regurgitant volume (MRVa) obtained from the difference between echocardiographic total stroke volume and Doppler-derived aortic stroke volume and (MRVb) mitral regurgitant volume obtained from the difference between Doppler-derived transmitral filling volume and aortic stroke volume.

lated by two-dimensional echocardiography, averaged 62 + 13 ml and was highly correlated with the mitral filling volume obtained by Doppler cardiographic measurements of flow past the mitral valve anulus (Fig. 2; r = 0.90, p < 0.001). As a consequence of the close correlation of total stroke volume measured by either echocardiographic or Doppler techniques, MR volume derived by both techniques was identical (14 f 11 vs 14 + 12 ml) and was closely correlated (Fig. 3; r = 0.90, p < 0.001). Similarly, MR fraction derived by both techniques was highly correlated: r = 0.92; p < 0.001 (Fig. 4). Left ventricular ejection fraction derived from ventricular volumes measured by echocardiography correlated well with that calculated from the ratio of mitral valve filling volume derived by Doppler technique (Table II): r = 0.9, p < 0.001. DISCUSSION

With Doppler echocardiography, previous investigator&8, g,l5 have documented the high frequency of funct,ional

MR

in

patipptg

with ~ __--

rli1atm-l --rL.I"U

,-nd:n-*rhU.AL urvll‘y

up-

athy. Our present data not only confirm the high incidence of MR in this patient population, but also quantify the severity of the functional MR. The

10 20 30 40 50 regurgitation fraction by Doppler(MRF, , %)

J 60

Fig. 4. Correlation between regurgitant fraction calculated by two methods: MRFa, as the ratio of regurgitant volume to total stroke volume obtained by two-dimensional echocardiography and (MRFb, as the ratio of regurgitant volume to total stroke volume obtained by Doppler study of forward mitral flow.

regurgitant fraction was greater than 20% in approximately two thirds of our patients, and even exceeded 40% in one fifth of them. Of importance, the hemodynamic benefits of hydralazine in patients with chronic heart failure, which are predicated on reducing the amount of MR, are not observed in the absence of functional MR.16 The intensity of the Doppler signal, its extension into the left atrium, and the increase in forward flow across the mitral valve were initially used to assess the severity of MR by echocardiography.l-* Twodimensional, color-coded Doppler cardiography further extends these methods,17s I* but does not require the tedious atrial interrogation needed with the routine pulsed Doppler technique. More recently, Doppler echocardiographic techniques have been used to quantify MR volume as the difference between total stroke volume and forward stroke vo1ume.1ov 11,lg During cardiac catheterization, forward stroke volume is measured by the Fick principle and total stroke volume is obtained by left ventriculography.20-23 With Doppler echocardiography, forward stroke volume, i.e., aortic blood flow, is the product of aortic area measured by echocardiography and the velocity of blood flow integrated over time. Total stroke volume is obtained either by determination of ventricular volumes by two-dimen-

Vobme Number

116 3

sional echocardiography or by mitral valve inflow determined by Doppler echocardiography techniques, similar to the method used for aortic blood flow. The various methods for measuring mitral filling volume and aortic stroke volume differ mainly in the sampling site and in calculation of the orifice of flow, The area derived from echocardiography generally assumes a circular shape of the orifice. This assumption is marred by potential error in the radius measurement, which may result in marked differences in the area calculated. In a dog model, Ascah et all9 calculated MR from the difference between Doppler-derived forward mitral filling volume and aortic stroke volume. As suggested by Fisher et a1.,24 the sampling volume was positioned at the tips of the mitral leaflets. This method has proven accurate in experimental preparations” but not in clinical use.25 Alternatively, left ventricular filling can be determined by positioning the sampling volume at the mitral anulus.13s l4 The mitral annular area is assumed to be circular and in calculated from the four-chamber view, taken two to three frames after the initial maximal opening of the anterior mitral leaflet. However, the mitral anulus is ellipsoid rather than circular, and in normal subjects the annular area varies during the cardiac cyclez6 as the maximal diameter occurs just before the onset of atrial systole.27s28These inherent methodologic problems are of less importance in patients with dilated cardiomyopathies, where mitral anuli are dilated, are presumably more circular, and are less dynamic.*5 In contrast to the dynamic nature of the mitral valve anulus, the aortic root is nonmuscular, and its diameter does not change substantially during the cardiac cycle, except in aortic insufficiency.29*30 Consequently, Doppler echocardiography allows an accurate measurement of aortic stroke volume and has been validated relative to other techniques.‘,6,‘4 The close correlation found in our study between forward stroke volume obtained by thermodilution and by doppler echocardiography confirms the accuracy of the Doppler echocardiographic method. Total stroke volume can be determined from left ventricular diastolic and systolic volumes measured by two-dimensional echocardiography.12* 13,31-33Echocardiography tends to underestimate volumes when compared to cineangiography, primarily when the inner edge instead of the leading edge tracing method is used. To be accurate, this method requires visualization of most of the endocardial surface.12* l3 Blumlein et al.” used this approach to quantify MR. Forward stroke volume was calculated from the

Mitral

regurgitation

in dilated

cardiomyopathy

763

product of M-mode-derived aortic valve area, and the integral of ascending aortic flow velocity assessed by continuous wave Doppler, while left ventricular stroke volume was determined from two-dimensional echocardiographic diastolic and systolic volumes. In the present study, an excellent correlation was found between total stroke volume calculated by echocardiography and by Doppler cardiography. MR volume, derived from these two methods, correlated closely. Thus these two techniques can be used interchangeably to estimate MR. The combined echocardiography-Doppler method can be used when a good outline of the endocardial surface is obtained and when there is no significant ventricular asynergy. The second method, the use of the Doppler flow technique, should be used in patients in whom mitral annular area can be accurately calculated and mitral Doppler velocity flow can be precisely traced. A substantial amount of MR is frequently observed in patients with dilated cardiomyopathies. MR, which is highly dependent on the mitral valve regurgitant area, has been attributed to dilatation of the mitral anulus.6*34-37 As demonstrated with nitroglycerin63 8,9,l6 noninvasive quantification of MR should improve our understanding of the mechanisms involved and/of the effects of other pharmacologic interventions. REFERENCES Hatle L, Angelsen B. Doppler ultrasound in cardiology. Phvsical principles and clinical annlications. 2nd ed. Philadeiphia: Lea &Febiger, 1985:176,-306. 3-. Abbasi AS, Allen MW, Decristofaro D, Ungar 1. Detection and estimation of the degree of mitral regurgitation by range gated pulsed Doppler echocardiography. Circulation 1981; 61:143. ?I Quinones MA, Young JB, Waggoner AD, Ostojic MC, Ribeiro LGT, Miller RR. Assessment of pulsed Doppler echocardiography in detection and quantification of aortic and mitral regurgitation. Br Heart J 1980;44:612. Feigenbaum H. Echocardiography. 4th ed. Philadelphia: Lea and Febiger, 1986262. Strauss RH, Stevenson LW, Dadourian HA, (:hild JS. Predictability of mitral regurgitation detected by Doppler echocardiography in patients referred for cardiac transplantation. Am J Cardiol 1987;59:892. 6. Keren G, Bier A, Strom JA, Laniado S, Sonnenblick EH, LeJemtel TH. Dynamics of mitral regurgitation during nitroglycerin therapy: a Doppler echocardiography study. AM HEART J 1986;112:517. 7. Keren G, LeJemtel TH, Zelcer A, Meisner JS, Bier A, Yellin EL. Time variation of mitral regurgitant flow in patients with dilated cardiomyopathy. Circulation 1986:74:684. 8. Stevenson LW, Bellil -D, Grover McKay M, Brunken RC, Schwaiger M, Tillisch JH, Schelbert HR. Effects of afterload reduction (diuretics and vasodilators) on left ventricular volume and mitral regurgitation in severe congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 1987;60:654. 1.

764

Keren

et al.

American

9. Weiland

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

DS, Konstam MA, Salem DN, Martin TT, Cohen SR, Zile MR, Dhirenda DAS. Contribution of reduced mitral regurgitant volume to vasodilator effect in severe left ventricular failure secondary to coronary artery disease or idiopathic dilated cardiomyopathy. Am J Cardio11986;58:1046. Rockev R. Sterling LL, Zoshbi WA. et al. Determination of regurgitant fraction in isolated mitral or aortic regurgitation by pulsed Doppler two-dimensional echocardiography. J Am Co11 Cardiol 1986;7:1273. Blumlein S, Bouchard A, Schiller NB, et al. Quantitation of mitral regurgitation by Doppler echocardiography. Circulation 1986;74:306. Schnittger I, Fitzgerald PJ, Daughters GH, Ingels NB, Kantrowitz WE, Schwarzkoph A, Mead CW, Popp RL. Limitations of comparing left ventricular volumes by two-dimensional echocardiography, myocardial markers and cineangiography. Am J Card&-1982;503512. Gordon EP. Schnitteer I. Fitzgerald PJ. Williams P. PODD RL. Reproducibilityof left ventricular volumes by twodimensional echocardiography. J Am Co11 Cardiol 1983; 2:5lx-. Lewis JF, Kuo LC, Nelson JC, Limacher MC, Quinones MA. Pulsed Doppler echocardiographic determination of stroke volume and cardiac output: clinical validation of two new methods using the apical window. Circulation 1984;70:425. B&wood CM, Chuwa T, Wong M, Shah PM. Quantitative echocardiography in the mitral complex in dilated cardiomyopathy. The mechanism of functional mitral regurgitation. Circulation 1983;68:498. Packer M, Kessler DD, Lee WH. Does the presence of a prosthetic mitral valve prevent hydralazine from exerting its beneficial effects in patients with congestive heart failure? Circulation 1986;74(Suppl II):II-56. Helmke F, Nanda N, Hsiung MC, Soto B, Adey CK, Goyal RG, Gatewood RP. Color Doppler assessment of mitral regurgitation with orthogonal planes. Circulation 1987; 75:175. Izumi S, Miyatake K, Beppu S, Park YD, Nagata S, Kinoshita N, Sakakibara H, Nimura Y. 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. Ascah KJ, Stewart WJ, Jiang L, et al. A Doppler twodimensional echocardiographic method for quantitation of mitral regurgitation. Circulation 1985;72:377. Yang SS, Bontivoglio LG, Maranhao V, Goldberg H. Assessment of valvular regurgitation. In: From cardiac catheterixation data to hemodynamic parameters. Philadelphia: F.A. Davis Co., 1978189. Barry WH. Invasive investigation for the diagnosis of mitral valve disease. In: Ionescu MI, Cohn LH, eds. Mitral valve disease. London: Butterworths, 1985:87. Grossman W, Dexter L. Profiles in valvular heart disease. In: Grossman W, ed. Cardiac catheterization and angiography. Philadelphia: Lea & Febiger, 1985:364-g. Dodge HT, Kennedy JW, Petersen JL. Quantitative angio-

24.

25.

26.

27.

28.

29.

30

31.

32.

33.

34.

35.

36.

37.

8eptembsr 1988 Heart Journal

graphic methods in the evaluation of valvular heart disease. Prog Cardiovasc Dis 1973;16:1. Fisher DC, Sahn DJ, Friedman JM, et al. The mitral valve orifice method for non-invasive two-dimensional Doppler determination of cardiac output. Circulation 1983;67:872. Loeber CP, Goldberg SJ, Allen HD. Doppler echocardiographic comparison of flows distal to the four cardiac valves. J Am Co11 Cardiol 1984;4:268. Vijayaraghavan G, Boltwood CM, Tei C, Wong M, Shah PM. Simplified echocardiographic measurement of the mitral anulus. AM HEART J 1986;112:985. Tsakiris AG, Von Bernuth G, Rastelli GC, Bourgeois MJ, Titus JL, Wood EH. Size and motion of the mitral annulus in anesthetized intact dogs. J Appl Physiol 1971;30:611. 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. Christie J, Sheldahl LM, Tristani FE, Sagar B, Ptacin MJ, Warm S. Determination of stroke volume and cardiac output during exercise: comparison of two-dimensional and Doppler echocardiography, Fick oximetry and thermodilution. Cifculation 1987;76:539. Touche T, Prasquier R, Nitenberg A, Zuttere DD, Gourgon R. Assessment and follow up of patients with aortic regurgitation by an updated Doppler echocardiographic measurement of regurgitant fraction in the aortic arch. Circulation 1985;72:819. Wyatt HL, Haendchen RV, Meerbaum S, Corday E. Assessment of quantitative methods for two-dimensional echocardiography. Am J Cardiol 1983;52:396. Quinones MA, Waggoner AD, Reduto LA, et al. A new, simplified and accurate method for determining ejection fraction with two-dimensional echocariography. Circulation 1981;64:744. Tortoledo FA, Quinones MA, Fernandez GC, Waggoner, AD, Winters WL. Quantificative of left ventricular volumes by two-dimesional echocardiography: a simplified and accurate approach. Circulation 1983;67:579. Bdrgenhagen 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. Yoran C,.Yellin EL, Becker R, Gabbay S, Frater R, Sonnenblick EH. Dynamic aspects of acute mitral regurgitation: effects of ventricular volume, pressure and contractility on the effective regurgitant orifice area. Circulation 1979; 60:170. Yoran C, Yellin EL, Becker RM, Gabbay S, Frater RWM, Sonnenblick EH. Mechanism of reduction in mitral regurgitation with vasodilator therapy. Am J Cardiol 1979;43:773. Keren G, Bier A, LeJemtel TH. Improvement in forward cardiac output without a change in ejection fraction during nitroglycerin therapy in patients with functional mitral regurgitation. Can J Cardiol 1986;2:206.