9-4 r i o t Jet Area for Evaluating c trio itr iRegurgitation: An Animal Study With Quantified Mitral Regurgitation
TAKAHIRO SHIOTA, MD, MICHAEL JONES, MD,* DAG TEIEN, MD, IZUMI YAMADA, MD,*
ARNALDO PASSAFINI, MD, OLE KNUDSON, RDMS, DAVID J . SAHN, MD, FACC
Portland, Oregon and Bethesda, Maryland
Objectives . The purpose of the present study was to rigorouslyevaluate the accuracy of the color Doppler jet area planimetrymethod for quantifying chronic mitral regurgitation.
Background. Although the color Doppler jet area has been widelyused clinically for evaluating the severity of mitral regurgitation,there have been no studies comparing the color jet area with i strictlyquantifiable reference standard for determining regurgitant volume.
Methods. In six sheep with surgically produced chronic mitralregurgitation, 24 hemodynamically different states were obtained .Maximal color Doppler jet area for each state was obtained witha Vingmed 750. Image data were directly transferred in digitalformat to a microcomputer. Mitral regurgitation was quantifiedby the peak and mean regurgitant flow rates, regurgitant strokevolumes and regurgitant fractions determined using mitral andaortic electromagnetic flow probes .
Results. Mean regurgitant volumes varied from 0.19 to 2.4 liters/min (mean [+SD] 1.2 ± 0.59), regurgitant stroke volumes from 1 .8
The color Doppler jet area method has been widely used forassessing the severity of mitral regurgitation (1,2) . This methodhas limitations because of instrumentation variability andhemodynamic and hydrodynamic factors (3-17) . Althoughother methods, including transesophageal echocardiographywith analysis of pulmonary vein flow pattern or the proximalflow convergence methods, or both, have been proposed asbeing useful for evaluating the severity of mitral regurgitation(18-22), color jet planimetry still continues to be used as a firstapproach for evaluating the severity of mitral regurgitationprobably because of its visual simplicity and ease of use .Because only a limited number of studies detailing the capa-bility of this method for determining regurgitation used anadequate quantifiable reference standard to determine mitralregurgitant volume in a model that closely mimics clinical
From the Clinical Care Center for Congenital Heart Disease, Oregon HealthSciences University, Portland, Oregon and *Laboratory of Animal Medicine andSurgery, National Heart, Lung, and Blood Institute, National Institutes ofHealth, Bethesda, Maryland . This study was supported in part by Grant HL43287 from the National Heart, Lung, and Blood Institute, National Institutes ofHealth .
Manuscript received September 17,1993 ; revised manuscript received March2, 1994, accepted March 31, 1994 .
Address for correspondence : Dr . David J . Sahn, The Clinical Care Centerfor Congenital Heart Disease, UHN60, Oregon Health Sciences University,Portland, Oregon 97201-3181 .
Z 1994 by the American College of Cardiology
813
to 29 ml/beat (mean 11 1± 6.2), peak regurgitant volumes from LO to8.1 liters/min (mean 3.5 ± 2.1) and regurgitant fractions from 8.0%to 54% (mean 29 ± 12%) . Twenty-two of 24 jets were eccentric .Simple linear regression analysis between maximal color jet areasand peak and mean regurgitant flow rates, regurgitant stroke vol-umes and regurgitant fractions showed correlation, with r = 0.68(SEE 0.64 ct"2 ), r = 0.63 (SEE 0.67 cm2), r = 0.63 (SEE 0.67 cm2 )and r = 0.58 (SEE 0 .71 cm Z), respectively . Univariate regressioncomparing regurgitant jet area with cardiac output, stroke volume,systolic left ventricular pressure, pressure gradient, left ventricular/left atrial pressure gradient, left atrial mean pressure, left atria) vwave pressure, systemic vascular resistance and maximal jet velocityshowed poor correlation (0.08 < r < 0.53, SEE >0.76 cm2).
Conclusions . This study demonstrates that color Doppler jetarea has limited use for evaluating the severity of mitral regurgi-tation with eccentric jets .
(J Am Coil Cardiol 1994;24:813-9)
disease, the present study using regurgitant volumes quantifiedby electromagnetic flow probes was performed to assess theapplicability of color Doppler jet area method for evaluatingthe severity of mitral regurgitation .
MethodsExperimental preparation. Six sheep weighing 31 to 36 kg
were studied . Four to 5 months before hemodynamic andultrasound studies, two or three secondary chordae to theanterior leaflet (three sheep) or posterior leaflet (three sheep)of the mitral valve were severed under direct vision usingcardiopulmonary bypass . All operative and animal manage-ment procedures were approved by the Animal Care and UseCommittee of the National Heart, Lung, and Blood Institute .Preoperative, intraoperative and postoperative animal man-agement and husbandry methods are described in detail else-where (23). After surgery the sheep were maintained ondigoxin and furosemide .
Four to 5 months later the sheep were returned to theanimal surgery facility for the physiologic studies that are thesubject of this report . Anesthesia was induced with intravenoussodium pentobarbital (25 mg/kg body weight) and maintainedwith 1% to 2% isoflurane with oxygen, and the animals were
0735-1097/94/$7 .(H)
814 SHIOTA ET AL.COLOR MITRAL REGURGITANT JET AREA
ise
Flgure 1 . Recording of left ventricular (LV) and left atrial (LA)pressures and simultaneous electromagnetic flow data . ECG = elec-trocardiogram; QAO (QMV) = aortic (mitral) flow by the electro-magnetic flow meter; the smallest y-axis unit of flow is I liter/min .
ventilated by means of an endotracheal tube using a volume-cycled ventilator.
Cardiac catheterization and electromagnetic flow meters.A Swan-Ganz catheter was positioned in the main pulmonaryartery through the femoral vein, and another catheter waspositioned in the right common femoral artery for monitoringsystemic arterial pressure and arterial blood gases . Thesecatheters were interfaced with a physiologic recorder (ES 1000,Gould Inc.) using fluid-filled pressure transducers (modelPD23 ID, Gould Statham) . Arterial blood gases and pH weremaintained within physiologic ranges . A bilateral transversethoracotomy was performed. After institution of cardiopulmo-nary bypass, an electromagnetic flow probe (model EP455c,Carolina Medical Electronics, Inc .) was sutured into the leftatrium above the mitral annulus . The left atrium was closed,and the sheep was weaned from cardiopulmonary bypass.Another electromagnetic flow probe (Model EP455, CarolinaMedical Electronics) was placed snugly around the skeleton-ized ascending aorta distal to the coronary ostia and proximalto the brachiocephalic trunk. Both flow probes were connectedto flow meters (Model FM501, Carolina Medical Electronics),and these were connected to the same physiologic recorders(ES 1000, Gould Inc.) used for hemodynamic pressure record-ings. Left atrial and left ventricular pressures were obtainedfrom intracavitary catheter-tipped transducers (model SPC-350, Millar Instruments, Inc.) positioned transmurally . Allhemodynamic data were recorded at paper speeds of 250 mm/s(Fig. 1). Four consecutive cardiac cycles were analyzed foreach hemodynamic determination .
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Occlusive zeros for the aortic and mitral flow probes wereconfirmed on cardiopulmonary bypass. Calibration factors forthe flow probes were corrected for the sheep's hematocritsaccording to the manufacturer's specification . The integrals ofinstantaneous flows over time were determined by planimetryof the flow signal recordings . The problem of zero baselinedrift was managed by the techniques described by Dent et al .(24) . The aortic flow zero-level baseline was adjusted accord-ing to the contour of its electromagnetic flow probe signal ; thisbaseline was confirmed by the occlusive zeros . No sheep hadphysiologically important aortic regurgitation . For the purposeof this study, coronary artery blood flow during ventricularsystole was considered to be negligible . The baseline for themitral flow w is adjusted until the forward minus the backwardmitral flow volumes equaled the aortic flow volumes . Thecorrelation coefficient for the regression of aortic forward flowversus mitral forward minus mitral regurgitant flow was 0 .97(SEE 0.116 liter/min) . Regurgitant fraction was calculated asbackward mitral flow volume per minute divided by forwardmitral flow volume per minute . A hydrostatic standard wasused for calibration of all pressure recordings . Left ventricularand left atrial pressures were recorded simultaneously . Allhemodynamic recordings were performed simultaneously intandem with the echocardiographic studies . After baselinemeasurements, varying degrees of severity of mitral regurgita-tion were produced by altering preload or afterload, or both,using blood transfusion or angiotensin infusion, or both . Atotal of 24 stable hemodynamic states (3 to 5 sheep) wereobtained. Systolic stroke volume was obtained from the aorticflow meter and was multiplied by the heart rate to obtaincardiac output. Left ventricular systolic and left atrial meanand peak v wave pressures were obiainee from the pressuretracings. The data were averaged over at least four measure-ments for each determination.
Color Doppler echocardiography. Color Doppler flowmapping was performed with a Vingmed 750 system (VingmedSound, AIS, Oslo, Norway) using a 5-MHz transducer placedepicardially . Pulse repetition frequency was 4 .0 kHz for colorDoppler scanning. Color gain was adjusted to eliminate ran-dom color in areas without flow . The typical aliasing velocityfor imaging the color jet area was 72 cm/s . Color sector size waslimited to 45° to allow frame rates up to 45 frames/s and tomaximize angular line density for color Doppler interrogation .The color Doppler filter was held constant and set with a rolloffto minimize velocities <8 cm/s . From various approaches,including the apical and basal positions on the heart, themaximal color jet areas of mitral regurgitation were sought byslight modifications of the transducer positions (Fig . 2) . Allcolor Doppler flow images were transferred as digital cineloops to a Macintosh computer (Iici) for later analysis. In viewsthat showed the regurgitant jets going away from the trans-ducer and parallel to the direction of interrogation, continuouswave Doppler velocities were obtained under imaging guid-ance .
The maximal jet area was obtained using frame-by-frameanalysis of the cine loops with a computer software program
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Figure 2. Apical color Doppler image of an eccentric mitral regurgi-tant jet at peak systole (heart rate 119 heats/min, area 1 .91 cm -,circumference 9 .21 cm). LA = left atrium ; LV = left ventricle .
(Echo Disp) . The jet area was measured by planimetry of theouter border of clearly definable maximal color-encoded jetarea using the variance-encoded central jet with and withoutthe contiguous less turbulent velocities moving in the samedirection as the central jet (3,5) . Left atrial size was alsomeasured by the computer-assisted planimetry system in thesame frame in which the maximal color jet area was observed .Continuous wave Doppler velocities were available in digitalfiles matched to the hemodynamic states and the color jetimages. Maximal color jet areas, the ratio of the maximal jetarea to the size of left atrium and the maximal jet velocity weremeasured and averaged (for at least 3 beats) on the computer .
To evaluate interobserver variability, all of the color jetareas were measured by two independent observers who hadno knowledge of electromagnetic flow data or the otherobserver's data .
Statistical analysis. Simple linear regression analysis wasused for obtaining correlation coefficients for the referenceelectromagnetic flow data and other hemodynamic data withcolor regurgitant jet area and the ratio of the jet size to the leftatrial size . In addition, because multiple points were obtainedin the same animals, a multivariate regression analysis wasused to examine the relation of data between sheep . To do this,we created the design matrix in a spreadsheet of a statisticalcomputer program (Stat View 1988, Abacus Concepts, Inc.)using dummy variables as columns to encode the differentsheep (25) and used the multiple regression function of Stat
SHIOTA ET AL . 815COLOR MITRAL REGURGITANT JET AREA
View. A probability value < 0.05 was considered statisticallysignificant .
Results
Measurable color Doppler jets were recorded for all 24hemodynamic conditions and ranged from 0 .23 to 3 .66 cm' inarea (mean [± SD] 1 .99 ± 0 .85). Heart rates ranged from 84 to142 beats/min (mean 110 ± 13) . Twenty-two of 24 regurgitantjets were eccentric, veering toward a left atrial wall . Theremaining two regurgitant jets were free or central in the leftatrial cavity (5,6) .
Severity of mitral regurgitation . Quantitation of the regur-gitation with the electromagnetic flow probes indicated clini-cally relevant severities of regurgitation: Peak regurgitant flowrates ranged from 1 .0 to 8 .1 liters/min (mean 3 .5 ± 2 .1), meanregurgitant flow rates from 0 .19 to 2.4 liters/min (mean 1 .2 ±0.59), regurgitant stroke volumes from 1 .8 to 29 ml/beat (mean11 ± 6.2) and regurgitant fraction from 8.0°Ir% to 54% (mean29 + I2`4% .
Relation between color jet areas and severity of mitralregurgitation. Simple linear regression analysis between themaximal color jet areas, including the contiguous, less turbu-lent velocities moving in the same direction as the central jet,and the peak and mean regurgitant flow rates, regurgitantstroke volumes and regurgitant fractions showed only moder-ately good correlation (r = 0 .68 (SEE 0.64 cm), r = 0.63 (SEE0.67 cm'), r = 0.63 (SEE 0.67 cm') and r = 0.58 (SEE0.71 cm), respectively, Fig . 3] . When the ratio of color jet sizeto left atrial size was used, the correlations improved somewhat(r = 0.70, 0 .65, 0 .68 and 0.65, respectively), but significantscatter in the data still existed, resulting in a limited ability ofthe color Doppler jet planimetry method to predict the severityof mitral regurgitation . The relation between the maximalcolor jet areas excluding the contiguous, less turbulent veloc-ities moving in the same direction as the central jet and thepeak regurgitant flow rates was similar to that between the jetarea with the less turbulent flow and the peak regurgitant flowrate (r = 0.64, SEE 0.63 cm`, p < 0 .01) . When a multiple-regression model was used to eliminate associations based ondata from within one sheep, a decreased relation between themaximal color jet areas and the peak regurgitant flow rates wasobtained. (The slope of the regression was 0 .19, which was<0.26, the slope of the simple regression analysis, and thestandard error of estimate was 0 .07, which was larger than 0 .05,the standard error of estimate by the simple regression analy-sis, p < 0 .05 .) In addition, there was no significant relationbetween the color jet area and the mean regurgitant flow rate,the regurgitant stroke volume or the regurgitant fraction, allp > 0 .05, when accounting for variability between sheep in thelinear regression .
Relations to other variables . Univariate regression for thejet areas compared with cardiac output, systolic volume, leftventricular systolic pressure, left ventricular and left atrialpressure gradients, systemic vascular resistance and maximaljet velocity showed poorer correlation (r = 0 .22, 0 .16, 0.O;,,
816
NvaO
SHIOTA ET AL .COLOR MITRAL REGURGITANT JET AREA
C Regurgitant Faction
FlRure 3. Regression analysis between maximal color jet area andpeak mitral regurgitation (MR) flow rate (A), mean mitral regurgita-tion flow rate (B), regurgitant fraction (C) and regurgitant strokevolume (D) .
0.14, 0.11, 0 .30, respectively, none of which was statisticallysignificant) . For all hemodynamic indexes, statistical signifi-cance was obtained only between jet area and left atrial meanand maximal v wave pressures (r = 0.46, SEE 0.77 cm 2 ; r0.53, SEE 0 .74 cm 2, respectively, p < 0 .02) (Fig. 4). When themultivariate analysis was used to focus on predictability be-tween sheep and to eliminate data tracking induced by serialmeasurements within the same animal, no significant relationwas found between the color jet area and left atrial mean ormaximal iP wave pressures (p > 0.05) .
Interobserver variability. There was good agreement be-tween measurements of the color jet areas by two independentobservers (r = 0.89, SEE 0.02 cm-, p < 0.0001) (Fig. 5).
0
0 0
0
1 2 3Mean MR Flow Rate (Ilmin)
10 20
JACC Vol . 24, No . 3September 1994:813-9
Regurgitant Volumelbeat (cc)
DiscussionThis study, in an animal model using quantified mitral
regurgitant volume, demonstrates that the color Doppler jetplanimetry method has limited utility for estimating severity ofregurgitation .
Previous studies . Early reports on the color Doppler jetarea method for evaluating the severity of mitral regurgitationused angiographic data as a reference for grading the severityof mitral regurgitation and proposed a clinical applicability ofthis method (1,2) . Other experimental and clinical studies,however, have raised questions with regard to the accuracy ofthe color Doppler jet area method for grading the severity ofmitral regurgitation (3-17). Our laboratory and others havereported that jet-wall interactions (the Coanda effect) altercolor Doppler flow mapping of regurgitant jets (11,13,15) .Chen et al . (5) and Sarano et al . (6) confirmed these in vitrofindings, reporting that eccentric regurgitant jets were signifi-cantly smaller than free regurgitant jets and that the correla-tion with Doppler-derived regurgitant volume was poorer with
30
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NE0
V wave (mmHg)
Figure 4. Regression analysis of maximal color jet area versus leftaerial (LA) mean pressure (A) and left atrial ,'wave pressure (a) .
surface jets than with free or central jets. The Doppler-derivedregurgitant fraction or regurgitant volume that was used inthese studies as a reference standard may be hampered by thepotential inaccuracy of Doppler itself for flow volume calcula-tion (8) .
Advantage of our study. Compared with the previouslyreported clinical or in vivo studies, our present study offers asignificant advantage : The mitral regurgitant volume was quan-tified using electromagnetic flow probes. Grading mitral regur-gitation by invasive left ventriculography is the conventionaland most widely accepted standard for evaluating the severityof mitral regurgitation (1,2) . However, this method is subjec-tive and semiquantitative at best . It is affected by manyvariables, such as arrhythmia, catheter position, amount of dyeinjected, left atrial size and X-ray film setting . Actual calcula-tion of regurgitant volume from left ventriculography, derived
NE
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aud
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y m 1.13 + 0.05xr = 0.46p < 0 .02SEE 0.77 cm2
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Mean LA pressure (mmHg)
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SHIOTA ET AL . 817COLOR MITRAL REGURGITANT JET AREA
1 2
Observer 1Figure 5. lnterobserver variability, Maximal color Doppler regurgitantareas (cm') obtained by one observer are compared with those by asecond independent observer.
by subtracting effective forward stroke volume (from thermodi-lution) from total left ventricular stroke volume, has beenwidely used for determining the severity of mitral regurgita-tion, but this method is limited by the problems of derivingquantitated left ventricular volume measurements from planarangiograms and the error in thermodilution determinations(2,3,8) .
Considering the excellent correlation coefficient for theregression of aortic forward flow versus mitral forward minusmitral regurgitant flow (r = 0 .97), the electromagnetic flowreference for the regurgitant volume appears more accurateand reliable than the left ventricular cineangiographic or theDoppler methods for determining the severity of regurgitation(2,3,8,26,27). Importantly, the synchronous on-line nature ofthe electromagnetic flow recordings allows peak regurgitantflow rates as well as mean regurgitant flow rates, regurgitantfractions and regurgitant stroke volumes to be available forcomparison with maximal color Doppler jet areas . The com-parison between the peak regurgitant flow rate and the colorDoppler jet area has rarely been investigated. The colorDoppler planimetry method is based on a single still frameshowing the maximal jet area . Only the peak regurgitant flowrate should be expected to correlate with the maximal color jetarea. Therefore, it is not surprising that the peak regurgitantflow rate showed the highest correlation coefficient with themaximal color jet area and with the ratio of maximal jet area toleft atrial size . Despite intermediate-range correlation coeffi-cients, the wide ranges of the standard error of the estimatedeterminations for the linear regression preclude using thesefor prediction. Because multiple points were obtained in thesame sheep, a multiple-regression analysis was used to examinedifferences between sheep. This showed an even weaker rela-tion between maximal jet area and peak regurgitant flow rate .
3
818 SHIOTA ET Al .COLOR MITRAL REGLJRGITANT JET AREA
(The slope of the regression was 0 .19, which was <0.26, the
slope of the simple regression analysis .) Other variables, such
as mean regurgitant flow rate and regurgitant fraction, showedno significant relation with the color jet area when the multipleanalysis was used . In contrast, in a preliminary extension of thepresent study, instantaneous mitral regurgitant flow rates
obtained by the electromagnetic flow probes and meters
divided by the corresponding instantaneous Doppler velocityprovided instantaneous orifice areas during systole . The aver-
age of instantaneous orifice areas during systole was closelyrelated (r = 0.87, p < 0.0001) to mean regurgitant flow ratesand therefore to severity of mitral regurgitation (28). Thus,methods providing the regurgitant orifice size (such as dividing
flow convergence calculated flows divided by the appropriatecontinuous wave Doppler vel(cities) may prove more usefulthan the jet area method for evaluating mitral regurgitation .
Smith et al . (29) recently reported temporal variability of themaximal development of color Doppler jet area in patients withmitral regurgitation . In the present study, we compared the timeperiod from the (0 wave of the electrocardiogram with themaximal color Doppler jet area and with the peak flow rateobtained by the electromagnetic flow meters A close relation(r = 0.89) was found between the two peak timings, with asignificant delay (average 24 ms) of maximal • olor jet appearancecompared with the electromagnetic peak flow rate . This could beimportant for understanding the temporal relation of color jetarea as computed and displayed by "real-time" Doppler flowmapping and the pathophysiology of mitral regurgitation .
Relation between left atrial pressure and color jet area .Hemodynamic indexes, including systolic stroke volume andcardiac output, (lid not correlate with maximal jet area . Of theindexes studied, only mean atrial pressure and size of the vwave showed any relation to maximal jet area ; in addition, therelations were weak, with standard errors precluding clinicalusefulness. In vitro studies (12,14) have indicated that high leftatrial pressures produce minor tdtftereences in color jet areas . Arecent clinical stuffy (alt) has demonstrated the development ofhigher left atrial pressures with more severe degrees of mitralregurgitation as graded by color Doppler jet size .
Study limitations . The majority of the jets (22 of 24) in thisstudy were eccentric, impinging on the atrial wall. Only two ofthe jets were central and could therefore be expected toexpand symmetrically: this small number was not consideredsufficient for independent analysis . Therefore, our conclusionmay be overly pessimistic, applying mainly to eccentric mitralregurgitant jets, Nonetheless, the type of mitral regurgitationthat we studied, in terms of leaflet pathology and jet type,mimics common clinical findings .
Finally, the mean body weight of the animals in our studywas 33 ± 2 .0 kg, and the ranges of volumes of forward flows aswell as regurgitant flows reflected these body weights . Thus, foranimals of larger size, one might anticipate proportionatelylarger absolute regurgitant volumes.
Coaclasiions. Our study of chronic mitral regurgitationquantified in an animal model indicates that the color Dopplerjet planimetry method has limited use for determining regur-
JACC Vol. 24, No.September 1994 :813-')
gitant flow rates. Although our observations were limited toeccentric jets associated with flail leaflets as a result ofdisrupted chordae tendineae, the observation may also haveimplications for other types of mitral regurgitation encoun-tered in clinical practice .
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