Doppler Echocardiographic Estimation of Transmitral Pressure Gradients and Correlations with Micromanometer Gradients in Mitral Stenosis Daniel David, MD, Roberto M. Lang, MD, Richard H. Marcus, FCP(SA), Alex Neumann, 6s. Kirk T. Spencer, MD, Ted Feldman, MD, John D. Carroll, MD, Pinhas Sareli, MD, and Kenneth M. Borow, MD
n vitro studiesusing various flow modelshave shown that the relation between pressure difference and velocity of fluid flow acrossan orike is accurately describedby the modified Bernoulli equation.1-3On the basis of these data, the modified Bernoulli equation has been widely applied in clinical echocardiography to the calculation of transvalvular pressure gradients from Doppler flow velocity data. The accuracy of the modified Bernoulli equation for determination of diastolic transmitral pressuregradients has been assessedpreviously in patients with mitral stenosisby comparing Doppler data with manometric measurements obtained with fluidfilled catheters.4-6In this study, to avoid the inherent inaccuraciesassociatedwith the useof fluid-filled catheters,7-1i direct left atria1 and ventricular micromanometer pressuremeasurementswere usedto reexamine the accuracy of the modified Bernoulli equation for determination of diastolic transmitral gradients from flow velocity data in patients with mitral stenosis.
I
Six patients with rheumatic mitral stenosis, ranging in age from 47 to 71 years (mean f standard deviation 59 f 10) were studied. Exclusion criteria were clinical, echocardiographic or angiographic evidence of occlusive coronary artery disease or significant mitral or tricuspid regurgitation. Mean heart rate was 76 f 14 beatslmin. Five patients were in normal sinus rhythm and 1 was in atria1 fibrillation. Cardiac index and left ventricular end-diastolic pressure were 2.5 f 0.2 liters/min/m2 and 12 f 4 mm Hg, respectively. The mean mitral valve orifice area (Gorlin formula) was 1.O f 0.4 cm2. The experimental protocol was approved by the Clinical Investigation Committee of this institution. All patients were studied during diagnostic left- and right-sided cardiac catheterization. Left ventricular and atria1 pressures were obtained with 7Fr and 6Fr From the Department of Medicine, Sectionof Cardiology, the University of Chicago Medical Center, 5841S. Maryland Avenue, Hospital Box 44, Chicago, Illinois 60637,and the Department of Cardiology, Baragwanath Hospital and University of Witwatersrand, Johannesburg, South Africa. This study was supported in part by Grant AA-006677 and ResearchService Award Training Grant HL-72377 from the National Institutes of Health, Bethesda, Maryland. Additional support was provided by a grant-in-aid from the American Heart Association, Chicago Affiliate, Chicago, Illinois. Manuscript received August 20, 1990;revisedmanuscript receivedand acceptedFebruary 11, 1991.
micromanometer catheters, respectively. The left atrium was accessedfrom the systemic venous system via a Mullin sheath inserted using a transseptal technique. Micromanometers were calibrated after insertion into the vascular system using pressure measurements obtainedfrom juxtaposedfluid-filled catheters connected to strain gauge transducers. After this calibration procedure, both catheters were fluoroscopitally guided into the left ventricle, where pressures were balanced with the catheter tips in close proximity. The left atria1 and ventricular catheter tips were then positioned above the mitral anulus and beneath the mitral leaflets, respectively. Zero balance and internal calibration of the micromanometers were checked periodically during the procedure. Thermodilution cardiac outputs were determined, using Swan-Ganz catheters, as the average of 3 to 5 measurements with an intermeasurement variability of < 10%. Transmittal blood flow velocity recordings were obtained with the transducer positioned at the cardiac apex using continuous wave Doppler (1.9 MHz). Left atria1 and ventricular pressures were recorded simultaneously with the Doppler data using
E, N, A,
&q
FIGUREl.Schemdcikmtmthofbft~rDoppkr infbwvelocitydgMltogetherwltbloftrtrklandwnbieulr (LAP and LVP, m*) *wing dhligclbtoleatwbkbi-micramcmomaarpreesuretmdentswereimparedwithgmdkntscakhtedby themodi%dRemadBequaGon.AtpointsE,N,iandA,flow accelerationiszero;atpointsUandD,ffowisaaakdng mpedhly.Seetextforexphathof ad decekratlnth peinte.
the Points
BRIEF REPORTS
1161
a custom-made multichannel physiologic signal recording module (Hewlett-Packard, Inc., Andover, Massachusetts). Manometric and flow velocity data were digitized to allow determination of simultaneous micromanometer and Doppler-derived transmitral pressure gradients throughout the cardiac cycle. Pressure differences were calculated from Doppler flow velocity data (using the modified Bernoulli equation) at 5-ms intervals during diastole. For eachpatient, 3 to 5 endexpiratory beats were analyzed. The time delay between pressure and Doppler data was compensated for by aligning peak early and late diastolic pressure gradients with peak E and A Doppler flow velocity points. Instantaneous micromanometer and Doppler/ modified Bernoulli equation pressure gradients were compared at 5 specific points during diastole (Figure 1): (I) peak early inflow velocity (E); (2) peak atria1 inflow velocity (A); (3) mid-diastolic inflow velocity nadir (N); (4) during the upstroke of early inflow, midway betweenthe onset point and E (U); (5) during the deceleration phase of early inflow, whenflow velocity was similar to that at U(D). At points E, A and
1162
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 67
N, flow acceleration was zero; at U and D, flow acceleration was positive and negative, respectively. Mean diastolic pressure gradients were also compared. Linear regression analysis was used to correlate values for instantaneous and mean transmitral pressure gradients acquired from direct micromanometer pressure recordings and calculated from Doppler data. In addition, the differences between the average valuesfor mean diastolic gradient determined by each method were plotted against the micromanometer value in eachpatient to determine the limits of agreement between the 2 methods.t2 Mean transmitral micromanometer-determined pressure gradients ranged from 9 to 21 mm Hg with corresponding calculated valve areas of 1.4 to 0.5 cm2 (Gorlin formula). Figure 2 is a computer printout of digitized and calculated data in a representative patient. Instantaneous and mean micromanometer pressure gradients correlated well with Doppler-calculated values throughout diastole, with r values ranging from 0.62 to 0.90 (Figure 3). The correlation between micromanometer and Doppler gradients was not influenced significantly by flow acceleration, flow de-
MAY 15, 1991
POINT-U
50~
a -2%
O 0
1-1
/
r = 0.90
/ 4.
/
30.
/
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/
r = 0.62 4.
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50.
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30-
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30.
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10
20
50
MEAN
/
04 0
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30
ii -20% r = 0.77
/ / /
/ /
30.
0
50-
4.
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50
40
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/ /
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PEAK-A
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0
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9
88 . 10
20
30
40
50
PRESSURE GRADIENT - CATH (mmHg) FIGURE 3. hdaths between nom&w (Pmuurs Gradkmt-Cath) and c&dated
(+tshtsf’k&
celeration or absolute velocity ofjlow. However, the Doppler-derived gradients underestimated those determined using micromanometers by 2 to 29%, with the greatest discrepancies occurring in late diastole (points N and A). On average, Doppler underestimated diastolic mean transmitral gradients by 3.0 f 2.7 mm Hg (Figure 4). This represented a negative bias of 18% for the noninvasive measurements and translated into a projected mean difference in calculated mitral orifice area of 9% using the Gorlin formula.
The relation between pressure and flow velocity as expressedby the Bernoulli equation has previously been shown to be applicable to the quantification of mitral transvalvular pressuregradients in patients with mitral stenosis using Doppler-derived flow velocity data.4-6 Moreover, it has been stated that the Bernoulli equation can be simplified without significantly reducing its accuracy by assumingthat the contributions to the gradient of flow acceleration and viscous resistance factors are sma11.4,5 Data from in vivo validation studiesperformed previously in humans are potentially confoundedby the useof fluid-filled catheters and the substitution of pulmonary capillary wedge pressurefor left atria1 pressure.4,6Prior investigations have shown that pulmonary capillary wedge pressurecan overestimatetrue left atria1 pressure by as much as 35%~~-’ l and that phasedelay in the wedge
A) and mean -w-by--
Prassws Gradht-MBE)
in patkmts with mitrd steno&s.
tracing can shift the v wave into early diastole, thereby giving the appearanceof a greater early diastolic transmitral gradient than that obtained by direct measurement of left atria1 pressure.Becausemultiple sourcesof error can causeinaccuraciesthat either cancelor amplify one another, the previously reported data require verification. In the current study, these confounding factors
1
I 10
15
20
25
Catheter FIGURE 4. Comparim of trrutunitral maan diastok presswe gradimts msaswad by micromanometer andbyDoppkin dlth3mmbsiwean mmgradiants z=:--(Centrat dashsd hsrizsata/ line) is nsgaiiw, b9flkaSng a consistemtnsgauvebtastsrtbsDoppkrvalues.Tbsss%unlfidsnceblkav&tartha~ lKJtw~the2methods(uppsr ad lowar d&shed hokontal dines) repmml the limii ot zw8emeWbe4weentheme&ds.MGE=mofMiedBefnod equation; SD = standad&viation. BRIEF REPORTS 1163
were eliminated by comparing transmitral gradients derived from Doppler data with gradients determined from simultaneous left atria1 and left ventricular micromanometer pressures. Although there was good correlation between the 2 methods at all sampling intervals, the Doppler-derived instantaneous and mean pressure gradients were consistently lower than those obtained using micromanometers. These results suggestthat the modified Bernoulli equation underestimatestransmitral gradients in mitral stenosis.Similar findings by Holen and Simonsen6 who usedfluid-filled cathetersto measurediastolic gradients between the left atrium and ventricle, were attributed to “overshoot” of manometric pressures.Becausethe problem of overshootis obviated by the useof micromanometers,this could not have accountedfor the differencesobservedin this study. It is unlikely that exclusion from the modified Bernoulli equation of the terms for flow acceleration and viscousresistanceis important since the greatest underestimation of instantaneousgradients occurred when flow accelerationwas zero (N and A, Figure 1) and, at the relatively high flow velocities recorded in mitral stenosis,the contribution of viscous resistanceto the pressuregradient is small. Importantly, the averagedifference betweenthe mean gradient determined by Doppler and that measured invasively was
n vitro studiesusing various flow modelshave shown that the relation between pressure difference and velocity of fluid flow acrossan orike is accurately describedby the modified Bernoulli equation.1-3On the basis of these data, the modified Bernoulli equation has been widely applied in clinical echocardiography to the calculation of transvalvular pressure gradients from Doppler flow velocity data. The accuracy of the modified Bernoulli equation for determination of diastolic transmitral pressuregradients has been assessedpreviously in patients with mitral stenosisby comparing Doppler data with manometric measurements obtained with fluidfilled catheters.4-6In this study, to avoid the inherent inaccuraciesassociatedwith the useof fluid-filled catheters,7-1i direct left atria1 and ventricular micromanometer pressuremeasurementswere usedto reexamine the accuracy of the modified Bernoulli equation for determination of diastolic transmitral gradients from flow velocity data in patients with mitral stenosis.
I
Six patients with rheumatic mitral stenosis, ranging in age from 47 to 71 years (mean f standard deviation 59 f 10) were studied. Exclusion criteria were clinical, echocardiographic or angiographic evidence of occlusive coronary artery disease or significant mitral or tricuspid regurgitation. Mean heart rate was 76 f 14 beatslmin. Five patients were in normal sinus rhythm and 1 was in atria1 fibrillation. Cardiac index and left ventricular end-diastolic pressure were 2.5 f 0.2 liters/min/m2 and 12 f 4 mm Hg, respectively. The mean mitral valve orifice area (Gorlin formula) was 1.O f 0.4 cm2. The experimental protocol was approved by the Clinical Investigation Committee of this institution. All patients were studied during diagnostic left- and right-sided cardiac catheterization. Left ventricular and atria1 pressures were obtained with 7Fr and 6Fr From the Department of Medicine, Sectionof Cardiology, the University of Chicago Medical Center, 5841S. Maryland Avenue, Hospital Box 44, Chicago, Illinois 60637,and the Department of Cardiology, Baragwanath Hospital and University of Witwatersrand, Johannesburg, South Africa. This study was supported in part by Grant AA-006677 and ResearchService Award Training Grant HL-72377 from the National Institutes of Health, Bethesda, Maryland. Additional support was provided by a grant-in-aid from the American Heart Association, Chicago Affiliate, Chicago, Illinois. Manuscript received August 20, 1990;revisedmanuscript receivedand acceptedFebruary 11, 1991.
micromanometer catheters, respectively. The left atrium was accessedfrom the systemic venous system via a Mullin sheath inserted using a transseptal technique. Micromanometers were calibrated after insertion into the vascular system using pressure measurements obtainedfrom juxtaposedfluid-filled catheters connected to strain gauge transducers. After this calibration procedure, both catheters were fluoroscopitally guided into the left ventricle, where pressures were balanced with the catheter tips in close proximity. The left atria1 and ventricular catheter tips were then positioned above the mitral anulus and beneath the mitral leaflets, respectively. Zero balance and internal calibration of the micromanometers were checked periodically during the procedure. Thermodilution cardiac outputs were determined, using Swan-Ganz catheters, as the average of 3 to 5 measurements with an intermeasurement variability of < 10%. Transmittal blood flow velocity recordings were obtained with the transducer positioned at the cardiac apex using continuous wave Doppler (1.9 MHz). Left atria1 and ventricular pressures were recorded simultaneously with the Doppler data using
E, N, A,
&q
FIGUREl.Schemdcikmtmthofbft~rDoppkr infbwvelocitydgMltogetherwltbloftrtrklandwnbieulr (LAP and LVP, m*) *wing dhligclbtoleatwbkbi-micramcmomaarpreesuretmdentswereimparedwithgmdkntscakhtedby themodi%dRemadBequaGon.AtpointsE,N,iandA,flow accelerationiszero;atpointsUandD,ffowisaaakdng mpedhly.Seetextforexphathof ad decekratlnth peinte.
the Points
BRIEF REPORTS
1161
a custom-made multichannel physiologic signal recording module (Hewlett-Packard, Inc., Andover, Massachusetts). Manometric and flow velocity data were digitized to allow determination of simultaneous micromanometer and Doppler-derived transmitral pressure gradients throughout the cardiac cycle. Pressure differences were calculated from Doppler flow velocity data (using the modified Bernoulli equation) at 5-ms intervals during diastole. For eachpatient, 3 to 5 endexpiratory beats were analyzed. The time delay between pressure and Doppler data was compensated for by aligning peak early and late diastolic pressure gradients with peak E and A Doppler flow velocity points. Instantaneous micromanometer and Doppler/ modified Bernoulli equation pressure gradients were compared at 5 specific points during diastole (Figure 1): (I) peak early inflow velocity (E); (2) peak atria1 inflow velocity (A); (3) mid-diastolic inflow velocity nadir (N); (4) during the upstroke of early inflow, midway betweenthe onset point and E (U); (5) during the deceleration phase of early inflow, whenflow velocity was similar to that at U(D). At points E, A and
1162
THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 67
N, flow acceleration was zero; at U and D, flow acceleration was positive and negative, respectively. Mean diastolic pressure gradients were also compared. Linear regression analysis was used to correlate values for instantaneous and mean transmitral pressure gradients acquired from direct micromanometer pressure recordings and calculated from Doppler data. In addition, the differences between the average valuesfor mean diastolic gradient determined by each method were plotted against the micromanometer value in eachpatient to determine the limits of agreement between the 2 methods.t2 Mean transmitral micromanometer-determined pressure gradients ranged from 9 to 21 mm Hg with corresponding calculated valve areas of 1.4 to 0.5 cm2 (Gorlin formula). Figure 2 is a computer printout of digitized and calculated data in a representative patient. Instantaneous and mean micromanometer pressure gradients correlated well with Doppler-calculated values throughout diastole, with r values ranging from 0.62 to 0.90 (Figure 3). The correlation between micromanometer and Doppler gradients was not influenced significantly by flow acceleration, flow de-
MAY 15, 1991
POINT-U
50~
a -2%
O 0
1-1
/
r = 0.90
/ 4.
/
30.
/
T -2%
/
r = 0.62 4.
POINT-D
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50.
0
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W
m
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50
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MEAN
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/ / /
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30.
0
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50
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/ /
4.
20
PEAK-A
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h -29% r = 0.72
0
I 10
30
40
50
0
10
20
JO
40
04 0
50
/
9
88 . 10
20
30
40
50
PRESSURE GRADIENT - CATH (mmHg) FIGURE 3. hdaths between nom&w (Pmuurs Gradkmt-Cath) and c&dated
(+tshtsf’k&
celeration or absolute velocity ofjlow. However, the Doppler-derived gradients underestimated those determined using micromanometers by 2 to 29%, with the greatest discrepancies occurring in late diastole (points N and A). On average, Doppler underestimated diastolic mean transmitral gradients by 3.0 f 2.7 mm Hg (Figure 4). This represented a negative bias of 18% for the noninvasive measurements and translated into a projected mean difference in calculated mitral orifice area of 9% using the Gorlin formula.
The relation between pressure and flow velocity as expressedby the Bernoulli equation has previously been shown to be applicable to the quantification of mitral transvalvular pressuregradients in patients with mitral stenosis using Doppler-derived flow velocity data.4-6 Moreover, it has been stated that the Bernoulli equation can be simplified without significantly reducing its accuracy by assumingthat the contributions to the gradient of flow acceleration and viscous resistance factors are sma11.4,5 Data from in vivo validation studiesperformed previously in humans are potentially confoundedby the useof fluid-filled catheters and the substitution of pulmonary capillary wedge pressurefor left atria1 pressure.4,6Prior investigations have shown that pulmonary capillary wedge pressurecan overestimatetrue left atria1 pressure by as much as 35%~~-’ l and that phasedelay in the wedge
A) and mean -w-by--
Prassws Gradht-MBE)
in patkmts with mitrd steno&s.
tracing can shift the v wave into early diastole, thereby giving the appearanceof a greater early diastolic transmitral gradient than that obtained by direct measurement of left atria1 pressure.Becausemultiple sourcesof error can causeinaccuraciesthat either cancelor amplify one another, the previously reported data require verification. In the current study, these confounding factors
1
I 10
15
20
25
Catheter FIGURE 4. Comparim of trrutunitral maan diastok presswe gradimts msaswad by micromanometer andbyDoppkin dlth3mmbsiwean mmgradiants z=:--(Centrat dashsd hsrizsata/ line) is nsgaiiw, b9flkaSng a consistemtnsgauvebtastsrtbsDoppkrvalues.Tbsss%unlfidsnceblkav&tartha~ lKJtw~the2methods(uppsr ad lowar d&shed hokontal dines) repmml the limii ot zw8emeWbe4weentheme&ds.MGE=mofMiedBefnod equation; SD = standad&viation. BRIEF REPORTS 1163
were eliminated by comparing transmitral gradients derived from Doppler data with gradients determined from simultaneous left atria1 and left ventricular micromanometer pressures. Although there was good correlation between the 2 methods at all sampling intervals, the Doppler-derived instantaneous and mean pressure gradients were consistently lower than those obtained using micromanometers. These results suggestthat the modified Bernoulli equation underestimatestransmitral gradients in mitral stenosis.Similar findings by Holen and Simonsen6 who usedfluid-filled cathetersto measurediastolic gradients between the left atrium and ventricle, were attributed to “overshoot” of manometric pressures.Becausethe problem of overshootis obviated by the useof micromanometers,this could not have accountedfor the differencesobservedin this study. It is unlikely that exclusion from the modified Bernoulli equation of the terms for flow acceleration and viscousresistanceis important since the greatest underestimation of instantaneousgradients occurred when flow accelerationwas zero (N and A, Figure 1) and, at the relatively high flow velocities recorded in mitral stenosis,the contribution of viscous resistanceto the pressuregradient is small. Importantly, the averagedifference betweenthe mean gradient determined by Doppler and that measured invasively was
