Mitral-Septal Separation and Ejection Fraction in the Remaining 110

METHODS

MitraI-Septal Separation: New Echocardiographic Index of Left Ventricular Function

BARRY M. MASSIE, MD An echocardiographlc measurement of the minimal separation between NELSON B. SCHILLER, MD, FACC the anterior mitral valve leaflet at its E point and the interventricular ROBERT A. RATSHIN, MD, FACC septum was evaluated as an index of left ventricular function. Mitral-septal WILLIAM W." PARMLEY, MD, FACC separation was found to be easily measured, reproducible and Indepen- San Francisco, California dent of patient position or heart rate changes of up to 32 beats/rain. In a group of 30 normal subjects, E point-septal separation was absenl in 25 and minimal (less than 4 mm) in the remaining 5. The relation of this variable to biplane angiographic ejection fraction was examined In 125 patients with a variety of cardiac diseases. After the 15 patients with mitral stenosis and aortic Insufficiency (conditions that affect anterior leaflet motion) were excluded, a strong negative correlation (r = --0.87, P <0.001) was found between mitral-septal separation and ejection fraction in the remaining 110. The correlation remained high (r = --0,86, P <0.001) when the 60 patients with coronary artery disease were considered separately. When compared with other echographic indexes of ventrlcular function, E point-septal separation correlated more closely with angiographlc ejection fraction and was more useful in discriminating between patients with normal and those with low ejection fraction. This Index appears to be especially useful because of the slrnplicity of its determination and its reliability in patients with coronary artery disease. We hypothesize that mitral-septal separation Is determined by multiple hemodynamic and geometric factors but in most patients reflects an interplay between the amount and rate of early diastolic ventricular filling and ventricular size.

Measurements of left ventricular performance have proved to be important indicators of prognosis in patients with many forms of heart disease. 1 In patients undergoing valve replacement or coronary arterial revascularization, preoperative ejection fraction in particular has been a good predictor of the risks and results of surgery. 2 Consequently, there has been a great deal of interest in the noninvasive evaluation of left ventricular function with echocardiography. 3 Several groups have found correlations between echocardiographically and angiographically determined ejection fraction 4-s and other measures of contractile function. 9 However, other.s have found echographic indexes of ventricu]ar function From the Departmentof Medicine,Cardiovascular to be unreliable in patients with segmental asynergy resulting from Division, and the Cardiovascular Research Insti- coronary artery disease. 1°-13 tute, University of California, San Francisco, We have observed that in normal subjects the anterior mitral valve California. This work was supported in part by Program Project Grant HL 06285 from The Na- leaflet makes contact with or closely approaches the interventricular tional Heart, Lung, and Blood Institute, National septum in early diastole, at the E point in its cycle. In patients with de- Institutes of Health, Bethesda, Maryland. Menu- pressed ventricular function we have noted increased mitral E point- script received August 30, 1976; revised manu- septal separation. Similarly, in patients with papillary muscle dys- script received November 16, 1976, accepted function or congestive cardiomyopathy a pattern of posterior displace- December 14, 1976. Address for reprints: Barry M. Massie, MD, ment of the mitral valve apparatus has been described, 14,15 whereas in Room 1186, Moffitt Hospital, University of Cali- patients with increased contractile function, the mitral valve has been fornia, San Francisco, California 94143. noted to appose the septum in early diastole. 16

1008 June 1977 The Amerlcan Journal of CARDIOLOGY Volume 39 MITRAL-SEPTAL SEPARATION--MASSIE ET AL.

This study was undertaken to determine (1) whether TABLE I measurements of mitral-septal separation provide a Patient Diagnoses useful measure of ventricular function in a large and diverse group of patients undergoing cardiac catheter- Coronary artery disease 60 Valvular heart disease 39 ization, and (2) whether they remain reliable in patients Aortic stenosis 12 with coronary artery disease. Aortic insufficiency 7 Mitral stenosis 6 Methods Mitral insufficiency 7 Mixed valvular disease 7 Patient population: A total of 160 patients underwent Cardiomyopathy 11 echocardiographic examination and biplane left ventricu- Congestive 6 Hypertrophic 4 lography within an interval of 5 days (within 48 hours in 146 Restrictive 1 patients) over a 15 month period at our institution. No patient Congenital heart disease 9 who manifested a significant change in clinical status between Atrial septal defect 4 Ventricular septal defect, 3 the two studies was included. Thirty-five patients were ex- Other 2 cluded because angiographic (15 cases) or echocardiographic No heart disease 6 (20 cases) studies were technically inadequate for analysis. The remaining 125 patients form the basis for this report. The primary cardiac diagnoses, established with hemodynamic measurements, oximetry, ventriculography and selective EDD - ESD coronary arteriography, are listed in Table I. In addition, 30 %S= normal subjects without clinical, historical or electrocardio- EDD graphic evidence of heart disease were studied echocardi- An echocardiographic ejection fraction was computed ographically. using the formulae for end-systolic volume (ESV) and end- Eehocardiographic measurements: Echocardiograms diastolic volume (EDV) developed by Teichholz et al.12: were performed using commercially available 0.5 inch (1.27 7.0 cm), 2.25 megahertz transducers with repetition rates of 1,000 ESV - (ESD) '~ cycles/sec, nominally focused at 7.5 or 10 cm, and Picker 2.4 + ESD Echoview 10 ultrasonoscopes. The time-motion output was 7.0 EDV = (EDD) s recorded on either a Honeywell model 1856 or an Irex strip 2.4 + EDD chart recorder. The patients were positioned in semirecum- EDV - ESV bent posture (with 15 to 30 ° oftruncal elevation) in various EF- degrees of left lateral decubitus rotation. The interspace from EDV which one or both mitral valve leaflets could be well visualized Determination of mitral-septal separation: The amount while the transducer was held perpendicularly to the chest of mitral-septal separation was defined as the perpendicular wall (usually the fourth) was determined, and a sweep from distance between the E point of the anterior mitral leaflet and that area was recorded between the aortic valve and apex of a tangent drawn to the most posterior point reached by the the left ventricle. interventricular septum within the same cycle. This method The left ventricular dimensions were determined at a level of measuring mitral-septal separation allowed the inclusion just below the anterior mitral valve leaflet, where chordal of five patients with paradoxical septal motion (four with an echoes were still visible. The end-diastolic dimension (EDD) atria[ septal defect, one with septal infarction) and others with was measured at the peak of the simultaneously recorded flat or reduced septal motion. Mitral-septal separation was electrocardiographic R wave, and the end-systolic dimension measured in the view in which it was minimized, usually ator (ESD} was defined as the closest approximation of the inter- just below the junction of the left atrial and left ventricular ventricular septum to the posterior wall endocardium during posterior walls, at a level in which both mitral leaflets were the same cardiac cycle. well seen (Fig. 1). A normalized index of E point separation The percent shortening of the echographic minor axis (%S) was computed by dividing the measured amount of mitral- was calculated using the formula: septal separation by the echographic end-diastolic dimension.

FIGURE 1. M mode echographic sweep from the left ventricular apex to the aortfc valve in a normal subject, demonstrating the normal close approximation between the anterior mitral valve (MV) leaflet at its E point and the interventricular septum (Sept). The arrowhead Indicates the level at which E point-septal separation (EPSS) is measured, at or just below the left atrial-left ventricular junction where both mitral valve leaflets are well visualized, In this case no separation is present. AoV = aortic valve; LA = left atrium; PW = posterior wall.

June 1977 The American Journal of CARDIOLOGY Volume 39 1009 MITRAL-SEPTAL SEPARATION--MASSIEET AL.

There was no change in mitral-septal separation in several whose echocardiogram is shown in Figure 1, had no subjects who were examined in different degrees of left lateral mitral-septal separation, and each of the remaining 5 decubitus positioning. In 25 patients, two independent ob- had less than 4 mm separation. E point separation was servers obtained echocardiograms and measured the amount also less than 4 mm in the six patients who had no evi- of mitral-septal separation. The differences between the two dence of cardiac disease at the time of catheterization determinations were small, ranging from 0 to 2 mm in patients and angiography. with little E point separation (less than 10 mm) and 0 to 4 mm in those with greater separation (10 to 28 mm). The mean of Relation of mitral-septal separation to heart rate the absolute differences between the two sets of measurements and rhythm: Echocardiograms from l 0 patients who was 1 mm, which was proportionally 10 percent of the mean manifested spontaneous changes in sinus rate of 14 to amount (10 ram) of mitral-septal separation in these 25 pa- 32 beats/min (mean 22 beats) during the examination tients. were analyzed to determine whether there was any Cardiac catheterization and angiographic measure- rate-dependent variation in E point separation. No ments: These were performed in the postabsorptive state after difference in the magnitude of mitral-septal separation premedication with diazepam (Valium®), 10 mg given intra- was present from cycle to cycle in these patients. Only muscularly. Biplane left ventricular cineangiograms were two patients in the final study group did not have sinus taken in 30 ° right anterior oblique and 60 ° left anterior rhythm, and both had atrial fibrillation with relatively oblique projections after an injection of 45 cc of a 66 percent meglumine diatrizoate, 10 percent sodium diatrizoate solution regular ventricular responses (less than 25 percent (Renografin 76®) over 3 seconds. Left ventricular volumes at variation in cycle length). In these two patients, the end-diastole and end-systole were obtained by the modified magnitude of mitral-septal separation remained almost Simpson's rule method of Goerke and Carlsson. ]7 The ven- constant (with a maximum of 2 ram), as did the ejection tricular ejection fraction was calculated as the ratio of anglo- fraction, which was determined for several different graphic stroke volume to end-diastolic volume. An ejection cycles of the ventriculogram. fraction of 55 percent was arbitrarily taken as the lower limit Relation of mitral-septal separation to ventric- of the normal range. Segmental wall motion was assessed ulographic ejection fraction: Fifteen of the 125 pa- qualitatively by an experienced angiographer. Stroke volume tients had mitral stenosis or at least moderate aortic was determined both angiographically and by the Fick regurgitation, conditions in which normal mitral ante- method. rior leaflet motion is restricted. In these patients, no Results consistent relation between the degree of E point sep- Mitral-septa] separation in normal subjects: aration and other echographic or angiographic indexes Twenty-five of the 30 normal subjects, including the one of ventricular function was present. However, among

30 ~1 [ x ~' I I I I I \\ ~\\m. \\ • CAD \ \\ .\ • Others 25 \\

\k \ " \ \~'\ \'\ \\ \-_ - \\ a \~\ • • x\ 20

EPSS 15 - "\\ -\-~\ • \ \ EP$S=--.51 EF + 33.6 \ • \\~ \ R=--.87 \\ \\3\ \% p< .OO1

10 - \\ • e"~%e~e \\\ \\\• mm'~m~¢ ~\

FIGURE 2. Correlation between E point- \\ • • "-~\ \\ septal separation (EPSS) and biplane angiographic ejection fraction (EF). Inner and \~ • ••'1~°"i,.}= u \\ outer pairs of interrupted lines are 95 percent confidence limits for the regres- 0 -- i i 1 i 18- ell". -- lUL~t .~tonl~'Jq, oe.,ot ona • - ooe -- sion line and for the points, respectively. 0 20 40 60 80 100 Patients with coronary artery disease (CAD) are indicated by squares, p = probability; BIPLANE ANGIOGRAPHIC EJECTION FRACTION R = correlation coefficient.

1010 June 1977 The American Journal of CARDIOLOGY Volume 39 MITRAL-SEPTAL SEPARATION--MASSIE ET AL.

RV . Sept " ~ys

FIGURE 3. Echocardiogram and right anterior oblique ventriculographic outlines from a patient with alcoholic cardlomyopathy, demonstrating considerable E polnt-septal separation (EPSS) and a (ow ejection fraction (EF). Dia = diastole; ECG = electrocardio: gram; EDV and ESV = end-diastolic and end-systolic volumes, respectively; MV = mitral valve; RV = right ventricle; Sept = Interventricular septum; Sys = systole.

the patients with aortic insufficiency, mitral-septal relations at E point separation with end-diastolic di- separation was always larger (greater than 8 mm) in mension and angiographic ejection fraction are com- those with more severe regurgitation or with concomi- pared in these 110 patients, mitral-septal separation tantly reduced ejection fraction, is correlates more closely with ejection fraction than with The relation between mitral-septal separation and echographic end-diastolic dimension (P <0.01) (Fig. 4). biplane angiographic ejection fraction in the remaining Indeed, there were five patients (one with acute mitral 110 patients is shown in Figure 2. In this, and in suc- regurgitation, two with chronic mitral regurgitation and ceeding graphs, data from the patients without mi- two with ventricular septal defect) with a volume- tral-septal separation were plotted but were excluded overloaded normally functioning left ventricle. Each of from the linear regression analysis because the measured separation cannot be less than zero. There was a highly significant negative correlation between the magnitude of E point separation and ejection fraction 30 (r = -0.87, P <0.001) which held over a wide range. =CAD Ira/ Figure 3, taken from the echocardiogram of a patient ° Others with severe alcoholic cardiomyopathy and a consider- 25 ably depressed ejection fraction, demonstrates the large R= .62 amount of mitral-septal separation in patients with poor p< .001 ventricular function in contrast to that in normal subjects (Fig. 1). 20 @ ° Relation of mitral-septal separation to left ventricular size and stroke volume: The possibility that the magnitude of mitral-septal separation was deter- ° • / EPSS 15 mined primarily by stroke volume or ventricular size (ram) rather than by ventricular function was evaluated. Among the 90 patients with less than 10 percent difference in heart rate between the echographic and an- 10 giographic studies, no relation was detected between the E point separation and stroke volume, as determined either angiographically or with the Fick method (r = I 0.24, P :>0.05 and r = 0.22, P >0.05, respectively). Because many patients with ventricular enlargement //=I • ,,= t=,° also manifested reduced ventricular function, some ,Ira ° Ii ° degree of correlation between mitral-septal separation 0 L----L-L---.Zlhk~IIIII~I~D..°. lz__~. and ventricular size was expected even if ventricular 20 30 40 50 60 70 80 dimensions were not a major determinant of this variable. However, the correlations between E point sepa- ECHOGRAPHIC END-DIASTOLIC ration and both angiographic end-diastolic volume (r DIMENSION (ram) = 0.51) and echographic end-diastolic dimension (r = FIGURE 4. Relation between E point-septal separation (EPSS) and 0.62) were surprisingly poor. When the respective cot- echographic end-diastolic dimension. Abbreviations as in Figure 2.

June 1977 The American Journal of CARDIOLOGY Volume 39 1011 MITRAL-SEPTAL SEPARATION--MASSIE ET AL.

" ECG " ,, t

• EDD -'~,EPS~S \.J' j 57m , =0 :

FIGURE 5. Echocardlogram and ventriculogram from a patient with ruptured chordae tendineae and acute volume overload. Despite Increased end-diastolic dimension ESV=64cc (EDD) at this level (and at the chordal level not iJlustrated here) and chamber dilatation, there is no E polnt-septal separation (EPSS), consistent with normal ejection fraction (EF). Abbreviations as in Figure 3.

the five had an increased echographic diastolic dimen- tral-septal separation in the face of a small left ventricle sion and only a small amount of E point separation. (end-diastolic dimension - 45 ram; angiographic end- Conversely, there were 15 patients with normal end- diastolic volume = 88 cc) suggested the presence of diastolic dimension and reduced angiographic ejection depressed contractile function, which was eventually fraction, and 12 of these had increased E point separa- confirmed during cardiac catheterization. tion (more than 5 mm). In 11 of these, the other echo- Figure 7 demonstrates the relation between mitral- cardiographic indexes of ventricular function were septal separation normalized for echographic end-dia- normal. stolic dimension and angiographic ejection fraction. Figure 5 reproduces the echocardiogram and ven- Again, a highly significant negative correlation is triculographic outlines from a patient with acute mitral present (r = -0.86, P <0.001), indicating that this index regurgitation and volume overload. Despite ventricular is a useful indicator of ventricular function independent dilatation (echographic end-diastolic dimension = 57 of chamber size. A ratio of 0.1 provides an excellent mm; angiographic end-diastolic volume = 220 cc), there demarcation between patients with normal (55 percent is no mitral-septal separation, thus indicating preserved and greater) and reduced ejection fraction. Only one ventricular function. The studies illustrated in Figure patient with a normal ejection fraction and four with a 6 are taken from a patient who presented in severe bi- low ejection fraction had normalized E point separation ventricular failure with a normal cardiac silhouette on inappropriately above or below 0.1. Because the relation chest X-ray examination. The finding of 10 mm of mi- between the normalized index and ejection fraction is

,sept

FIGURE 6. Echocardiogram and ventrlculographlc EOV=88...... outlines from a patient with restrictive cardiomy- ESV=52cc " " opathy. Echographic dimensions at the mitral valve (MV) and chordal levels and angiographio volumes are small, but E polnt-septal separation (EPSS) Is increased and ejection fraction (EF) reduced. Abbreviations as in Figure 3.

1012 June 1977 The American Journal of CARDIOLOGY Volume 39 MITRAL-SEPTAL SEPARATION--MASSlE ET AL. similar to that between E point separation itself and index of less than 0.1 in patients with normal ventricular ejection fraction, normalization is not routinely per- dimensions. formed in our laboratory. The normal range for un- Mitral-septa! separation in patients with coro- normalized mitral-septal separation is defined as less nary artery disease: The utility of this index was ex- than 5 mm, a value that corresponds to a normalized amined more closely in the patients with coronary artery

0.6 ~,- \ I I I I \ \ \ \ \ \ • CAD \ \ • Others 0.5

0.4 \\ "=~== \\ \\_ \ "x \ -\ \ \a k \ \ \. \\ \ ~'\Q ~'\ EPSS/EDD=--.OO76EF+.54 EPSS (mm) 0.3 EDD (mm)

0.2 -- % ei" ~%ii % --

% \era% ~, • ,, • • \ 0.1

FIGURE 7. Relation between E 1 • |\ %% • • ~-- point-septal separation (EPSS), normalized for echographlc end- 0 diastolic dimension (EDD), and an- 0 20 40 60 80 100 giographic ejection fraction (EF). Abbreviations as in Figure 2. BIPLANE ANGIOGRAPHIC EJECTION FRACTION

30 \ 1 u,, ? I I I I I Segmental Wall Motion Abnormality _ \ 25 a None • Generalized \ \ o Anterior, 5eptal \ 20 \ ,\ \~'\ "~ • Inferior, Posterior % ', "\N k. % A Aplca|, Lateral ",, N\\ o % EPSS • % 15 "\. \_\\ % (ram) % \\\ • A\~ \ EPSS=--.49 EF + 32.6 R = -.86 XX% \\'~ \ \ p<.O01 10 e& % \ \ \ \ Aoe\ \ \ \ \ \ ' 5 \ A \ \ \X \ \ ~ ,--o N FIGURE 8. Relation between E point-septal \ [] X separation (EPSS) and angiographic ejection % X fraction (EF) in patients with coronary artery 0 t I I I L._ , disease. Symbols indicate areas of major 0 20 40 60 80 100 segmental asynergy. Abbreviations as in Fig- ure 2. BIPLANE ANGIOGRAPHIC EJECTION FRACTION

June 1977 The American Journal of CARDIOLOGY Volume 39 1013 MITRAL-SEPTAL SEPARATION--MASSIE El" AL.

TABLE II Superiority of E Point-Septal Separation (EPSS) Over Othel 4& : ...~.",= ." .. Echocardiographic Indexes of Ventricular Function in Discriminating Between Patients With Normal and Reduced • -~ .... . Sept . Angiographic Ejection Fractions

• • . Sept ~~'~ Patients With Coronary All Patients (no. = 110) Disease (no. = 60)

EF > 55% EF < 55% EF > 55% EF < 85%

EPSS <5 mm 66 6 28 3 ~5 mm 2 36 1 28 X a= 78.7* X2= 45.3* Echo EF ~65% 59 15 5 11 <65% 9 27 4 20 ×~ = 30.7* X 2 = 29.4 4 %S ~35 60 14 25 10 <35 8 28 4 21 ×~ = 35.5 ~ X a = 32.8*

"The chi square value for each four quadrant analysis is given. For all of these x 2,P less than 0.001. Echo EF =echocardiographic ejection fraction; EF = biplane angiographic ejection fraction; %S = percent shortening of the echographic minor axis,

function: Fairly good correlations were present between echographic and angiographic ejection fractions (r -- 0.73, all patients; r = 0.71, patients with coronary disease) and between percent minor axis shortening and EDV=96cc ESV =64cc EDV=lO6cc ESV=64cc angiographic ejection fraction (r = 0.72, all patients; r FIGURE 9. Echocardiograms and ventrlculograms performed 1 year = 0.69, patients with coronary disease). However, when apart In a patient who had an inferior wall myocardial infarction 6 weeks the correlations between these two indexes and anglo- before the second study (right), demonstrating interval appearance of abnormal E polnt-septal separation (EPSS) and decreased in ejection graphic ejection fraction were compared with that be- fraction (EF). Abbreviations as in previous figures. tween E point separation and angiographic ejection fraction for both patient groups, the latter was superior to each (P <0.025). disease because other echocardiographic measures of Mitral-septal separation also proved to be more ventricular function are less reliable in this setting. useful in discriminating between patients with normal Figure 8 is a graph of mitral-septal separation versus and abnormal ventriculographic ejection fractions. If ejection fraction in the patients with coronary disease. normal mitral-septal separation is defined as less than The correlation (r = -0.86, P <0.001) is similar to that 5 mm, there were only two patients with a normal recorded for the entire patient group, and indeed the ejection fraction and increased mitral-septal separation, regression equations are nearly identical for both and only six with normal separation and a low ejection groups. When the region of abnormal wall motion is fraction (four of whom had an ejection fraction of 50 to considered, there was some tendency for E point sepa- 55 percent). Table II demonstrates that although each ration to be less than expected for the observed reduc- of the echographic indexes was useful in predicting tion in ejection fraction in patients with predominant which patients had a normal and which a low ejection apical-lateral asynergy. It was also greater than ex- fraction, mitral-septal separation was more reliable in pected in two patients with anteroseptal asynergy (one separating these groups, particularly in the patients with paradoxical and another with flat septal motion). with coronary disease. This finding is especially note- Nonetheless, mitral-septal separation remained a good worthy because the values for echographic ejection predictor of reduced ventricular function and continued fraction and percent minor axis shortening (65 and 35 to correlate closely with ejection fraction in most of the percent, respectively) chosen for this comparison were patients with these segmental disorders. Figure 9 il- those that best separated the patients into those with lustrates serial echocardiograms and ventriculograms a ventriculographic ejection fraction above or below 55 from a patient who had normal ventricular function and percent. no E point separation when first seen and who then, after an inferior wall myocardial infarction, had a con- Discussion siderably lower ejection fraction and 13 mm of separa- Assessment of left ventricular function has become tion. an important part of the echocardiographic examina- Comparison of mitral-septal separation with tion. '~ Angiographic ejection fraction has been demon- other echocardiographic indexes of ventricular strated to be a useful measure of cardiac contractile

1014 June 1977 The American Journal of CARDIOLOGY Volume 39 MITRAL-SEPTAL SEPARATION--MASSIE ET AL. function 1,2 and is an accepted standard for echocardi- shown to correlate with transvalvular blood flow20,23 and ographic measurements of ventricular function. Our to reflect alterations in indexes of the left ventricular results, in agreement with those of others, 4-s indicate pressure-volume relations. 23-25 that there is a reasonably close correlation between The magnitude of mitral-septal separation is deter- echographic indexes of pump function and the anglo- mined by multiple geometric and hemodynamic factors, graphic ejection fraction in most patients. However, the including the degree of mitral valve mobility, inter- decreased reliability of these unidimensional mea- ventricular septal motion, ventricular size and geometry surements in patients with segmental asynergy has been and the pattern of early diastolic filling. If patients with repeatedly demonstrated, l°-ls and our lower overall conditions that restrict mitral valve mobility (such as correlation probably reflects the large number of pa- mitral stenosis, congenital deformities of the mitral tients with coronary artery disease in this series. valve or aortic regurgitation) are excluded, this factor Our results indicate that the amount of mitral-septal is probably not an important determinant in most pa- separation in early diastole correlates well with ven- tients. In the five patients with mitral valve prolapse, triculographic ejection fraction in a large series of pa- a condition that may be associated with the increased tients with a variety of cardiac diseases. This relation valve mobility, E point separation correlated well with persists over a wide range of ventricular dimensions and ejection fraction. ejection fractions. Mitral-septal separation appears to Mitral-septal separation and abnormal septal be invalid as an index of ventricular function only in motion: By defining the amount of mitral-septal sep- patients with mitral stenosis or at least moderate aortic aration as described, we have been able to measure it regurgitation. reproducibly in patients with abnormal septal motion. The reliability of this index in patients with coronary Four patients with paradoxical septal motion due to artery disease is noteworthy. Although the index has atrial septal defect had a normal ejection fraction and some tendency to overestimate ejection fraction in pa- no E point separation. Because we have not studied tients with predominant apical-lateral synergy, and to other patients with paradoxical septal motion and right underestimate it in those with anteroseptal asynergy, ventricular volume overload, with or without accom- E point separation remains a generally applicable panying left ventricular failure, we are unable to com- echographic index of ventricular function in the setting ment on the reliability of this index in such patients. of ischemic heart disease. Further studies will be needed The one patient with paradoxical septal motion sec- to determine the true frequency and magnitude of the ondary to ischemic heart disease did manifest more discrepancies between the amount of mitral-septal mitral-septat separation than expected for the observed separation and the ejection fraction in patients with reduction in ejection fraction, and another patient with segmental asynergy. flat septal motion also displayed disproportionately The utility of this variable is enhanced by the relative increased separation. Thus, although this index con- simplicity of obtaining simultaneous echoes from the tinues to correlate well with ejection traction in most anterior mitral leaflet and the interventricular septum patients with coronary artery disease and segmental at the required level without needing to define clearly anteroseptal asynergy, focal septal motion abnormali- the posterior wall endocardium. In addition, E point ties will occasionally result in increased amounts of separation can be measured rapidly and no further mitral-septal separation. computation is required, thus allowing a rapid estima- Mitral-septal separation, ventricular filling and tion of ventricular function from an almost qualitative ventrieular size: Our data suggest that, although there inspection of the echocardiogram. is a weak correlation between ventricular size and the Factors determining magnitude of mitral-septal magnitude of mitral-septal separation, ventricular di- separation: The relation of several indexes of mitral mensions are not the sole determinant of the index. diastolic motion to blood flow, ventricular pressure and Rather, in most patients, mitral-septal separation ventricular compliance has been investigated pre- probably reflects the interplay between early diastolic viously. However, no attempt has been made to relate ventricular filling and ventricular size. Separation would systematically any aspect of diastolic mitral movement thus increase as: (1) the ventricle enlarges without a to a measure of systolic function such as ejection frac- proportional increment in early diastolic transmitral tion. Hemodynamic variables affecting mitral valve flow, or (2) the amount of early diastolic filling is re- motion in early diastole would be expected to have the duced in a ventricle of a given size, either as a result of most bearing on the magnitude of mitral-septal sepa- a decrease in overall stroke volume or in the fraction of ration. Fischer et al. 19 found a good correlation between filling occurring in early diastole. Recent evidence 23,2s,27 an index of mitral valve diastolic opening and s~roke has demonstrated the decreased fraction of ventricular volume, but others 2° have not been able to demonstrate filling that occurs in early diastole in patients with a close relation between valve opening and blood flow coronary artery disease and other forms of heart disease. experimentally. Decreases in anterior leaflet opening In patients with a mildly reduced ejection fraction in excursion (between the D and E points of its cycle) and whom other echographic indexes of ventricular function in the rate of early diastolic opening have been described remain normal, this shift of filling to later in diastole in patients with poor ventricular function or elevated may be an early phenomenon and could explain the initial diastolic pressure, respectively. 14,zl,22 In patients sensitivity of this index of ventricular function. without mitral valve disease, the early diastolic closing In conclusion, we have demonstrated that an easily velocity (E to F slope) of the mitral valve has also been performed measurement of the minimal separation

June 1977 The American Journal of CARDIOLOGY Volume 39 1015 MITRAL-SEPTAL SEPARATION--MASRIE ET AL.

between the anterior mitral leaflet and the interven- Acknowledgment tricular septum is a useful index of ventricu/ar function. We express our appreciation to Mrs. GaiJ Davis and Ms. Yin It correlates well with angiographic ejection fraction, Yee for technical assistance, to Dr. Julien I. J~. Hoffman £o~ regardless of chamber size, and appears to be useful in crifical review o£ this manuscript, to Mrs. Kathleen Hecker patients with coronary artery disease, in whom other for editorial assistance and to Mrs. Marfiyn Baram for typ. echocardiographic indexes are less reliable. Jng.

References 1. Cohn PF, Gorlln R" Dynamic ventriculography and the role of the 1973 ejection fraction. Am J Cardiol 36:529-531, 1975 15. Skunk BL, Guss SB, Hicks RE, et el-- Echocardlographl¢ recog- 2. Cohn PF, Gorlin R, Cohn I.H, et el: Left ven~icular ejection fraction nition of the mitral valve-posterior aortic wall relationship. Circu- as a prognostic guide In surgical treatment of coronary and valvular lation 51:594-598, 1975 heart disease. Am J Cardlol 34:136-141, 1974 16. Shah PM, Gramlak R, Kramer OH: Ultrasound localization of le~t 3. Fei~mbaum H: Echocardiographicexamination of the left ventricle. ventricular outflow obstruction in hypertrophic obstructive oar- Circulation 51:1-7, 1975 diomyopathy. Circulation 40:3-11, 1969 4. Pombo JF, Troy BL, Russell RO: Left ventricular volumes and 17. Goarka RJ, Carluon E: Calculat~o~ of right and left ventrlcular ejection fraction by echocardiography. Circulation 43:480-490, volumes. Methods using standard computer equipment and biplane 1971 angiograms. Invest Radlol 2:360-367, 1967 5. Forluln NJ, Hood WP, Cralge E: Evaluation of left ventricular 18. Botvlnlck EH, Schiller NB, Wlckramasekaran R, et ah Echocar- function by echocardiography. Circulation 46:26-35, 1972 diographic demonstration of early mitral valve olosure In severe 6. ~ ~ Es~mationof left ventricular size by e~diography. aortic insufficiency. Circulation 51:836-847, 197 5 Br Heart J 35:128-134, 1973 19. Fischer JC, Chang S, Konecke LL, at el: EchocardlographIG de- 7. Ludbrook P, Karliner JS, Paterson K, at ah Comparison of ultra- termination of mltral valve flow (abstr). Am J Cardlol 29:262, sound and oineangiographlc measurements of left ventrlcular 1972 performance in patients with and without wall motion abnormalities. 20. Lanlado S, Yellln E, Kotler M, el ah A study of the dynamic relations Br Heart J 35:1026-1032, 1973 between the mltral valve echogram and phasic mltral flow. Cir- 8. Belenkle I, Nuttsr DO, Clark DW, et ah Assessment of left van. culation 51:104-113, 1973 tric~Jlardimensions and function by echocardiography.Am J Cardlol 21. MIIIward DK, McLaurln LP, Cralge E: Eohocardiographlo studies 31:755-762, 1973 of the mltral valve motion in patients with congestive cardlomy- 9. Cooper RH, O'Rourke RA, Karliner JS, at ai: Comparison of ul- opathy and mitral regurgitation. Am Heart J 85:413-431, 1973 trasound and clneangiographio measurements of the mean rate 22. Konecke LL, Falgtmbaum H, Chang S, el ah Abnormal mttral valve of circumferential fiber shortening In man. Circulation 46:914-923, motion in patients with elevated left ventrlcular dlastoUc pressures. 1972 Circulation 47:989-996, 1973 10. Popp RL, Alderman EL, Brown OR, et ah Sources of error in cal- 23. DeMarla AN, Miller RR, Amsterdam EA, et al: Mitral valve carry culation of left ventrioular volumes by echocardiography (abstr). diastolic closing velocity in the echocardiogram: relationship to Am J Cardlol 31:152, 1973 sequential diastolic flow and ventrlcular compliance. Am J Cardlol 11. IJnhad JW, Mlntz GS, Segai BL, et el: Left ventricular volume 37:693-700, 1976 measurement by echocardiography: fact or fiction? Am J Cardlol 24. Layton C, Gent G, Prldla R, et el: Diastolic closure rate of normal 36:114-118, 1975 mitral valve. Br Heart J 35:1066-1074, 1973 12. Taichholz LE, Krauian T, Herman MV, at ah Problems in echo- 25. Qulnonas MA, Gaasch WH, Walsser E, et el: Reduction in the rate cardlographic volume determinations: echocardiographlc.anglo- of diastolic descent of the mitral valve echogram in patients with graphic correlations In the presence or absence of asynergy. Am altered left ventricular diastolic pressure-volume relations, Cir- J Cardlol 37:7-11, 1975 culation 49:246-254, 1974. 13. Harming H, Schelbart H, Crawford MH, at ah Left vantrlcular 26. SIIverman B, Fortuln N: Diastolic filling in cardiac disease (abstr). performance assessed by radlonuclide angiography a n~l echo- Clin Res 20:398, 1972 cardiography in patients with previous myocardial Infarction. Cir- 27. Decoodt PR, Mathey DG, Swan HJC: Abnormal raft ventrlcular culation 52:1069-1075, 1975 filling in coronary artery disease (abstr). Circulation 52:Suppt li:ll 14. Burgelm J, Clark R, Kamakl M, at el: Echooardiographic findings 133, 1975 In different types of mltral regurgitation. Circulation 48:97-106,

1016 June 1977 The Amarlcan Journal of CARDIOLOGY Volume 39