_.: .* , . Sandto A. Grakam Chtcjc.frdiac 7echnologisr, Cardiac Inuestigarwn Unir, Sr Vincmt's

>AW.&' Al ICISWLIE'.

COFdidagL Fellom; Ow&& hw&&wn U i t , Sr: Vinmnt,i .f;Arpimt Mclborme,. YK: . ' Harpiml, Melhourne, Vic. d . ~ . G M & a I d ' , . . ' D i d r e Tanzer .Dtktor , Grrdioc Invrut&aiwn. Unii, Si Vmcar'r . Hospami, 'Mdteurne, Vie. Hospiral, Melbourne, Vic.

Cardiac. Technologist, Cardiac Invesrigatinn Unir, Sr Vincent's ' . . . . . . k. hCmi.z?: G. ii-?. ~

@mefor, Phjirrd Scmrer,; St. 6ne~nrS,HospIral,.Mel~~bourne, I'ic.

A b s i W : Energyurclmnge h s e d on N e w m i a n principles is t b m o s r appropriate way to express the fuffctiou of pngpuwrp - inctudiq the k&. Using infomwmbn obtained ar cardiac cathereri- ration, we h e measured the total work energv (ET) of rhp It$ ventricle (L V) (mean 1.63 3) iri p"rrclrs with cawre m i r d regurgitarion~ean.rqpusgianrfracrion 0.66). E T was approx- imarefy.CbP4Ai abaw n o d . Of the regorghnr mergy (J#E)-{mm 0.95 J), on average, 314

( 7 3 . g q b f w ~ s 4 i & c {KE)and (23.~)poientipIfPE). Both conrponenrs represent wasred L V r e - ' & &&tic energg assmiPiQd'mith t&dmlemee'~r as heat, rke potenrial energy r&$&ej&a& in LeJz A m a l y L A ) pressure. T k a w w u n t of PE as a percentage of t o t a b q w g & n i h r g y (RE) varied c a s d c m b l y jmm.ahe parient to another (10.5% ro 54.4%) Hence, d m r f k n o mapping which &recisonly KE of rurbulenr jki flow musr una!ercs- rimaro I, K w lbrs and, because ojpuiient to piuiemr variation, cannot consisrenrly refIecr severity of rigurghaiion. Measurernewis o{ PE correlaie e e f l with wedge P-uare heifht. Grrespanding non-inoasive esrimures were nude using sphygmodynamonrerer-calibrated indirecr ca&df&e tracings und echouvdiogrqrhir ntasummenrs. 7'hese were nor signifi- cantly dfjf&m rke invasivf mcasn&mems. E r w m i e ! y , the calculation of PE is indirect nnd:i&s subrracrion, so rhni measrremenr&@ indivadual parients were not accumie.emugkp6c: clinicui use. *Parr of the nnn-inzrasivc calcubrion involved an estimate oflefr Qmid prt%me basedon chc.b!md pswe'rneasrr&enI a d Doppler velociry of regur-

;gIratioq, rhis.ph& be.n useful ineasurement m itself. Mmirrement of E l , an index of borh w h m e ard.pressure a w l o t d freflecri~g pe~pheral resisrance changes), should be resred in wid sncdips as Q prediitor oflejr.oeniricuhrfRiZnr in m e r e mirral regargirarion. NOW invasive &urernmrr d d be ustful ro/d!4w p r i & t r with acure severe mrtrai regurgi- ratio?: Non-invasioe PE meuutremnu p.e,currenr(y mi reliuble enough but an indireci mwqomient 01 &b &rial presswc umld. h verv usefil. (AUSI NZ J hfed 1992; 22: 532-540.) Key & + @ * ~ ~ q w r u x l a z meid, mural ~ p & v u t ; o n + echo iGrdiqvaphy.

JEtTRODuCTLON '* ' ' . . . terns of energy should therefore be our scientific objective. Are there practical advantages at present in doing so? Measurement of energy might give us

and ihto what our diagnostic tools are acfually

romd the .turn af the century the great ' Ggrman.phpcist mdphitosopherufsriena

crf".phpik.To imA3ure cordkc performance in' Mach's~dlhatOnergy is the currency ' insi&t k t o the mechanics of ventricular overload

- , . ,- /+r@*: Dr .&kw L .Moclsa+, Cardldog). kl low, C a r e ~ Iniestigatlm Unit, Si Vincent's Hospital, hlelbourne, Vic, Australia. *U:Naclsaac is currauly fu& by a Narioid Hear1 Foundation Fellowdup.

I:hTIR'.R(;Y ANI) AtITRAL REGURGIT.ATION . . .

-''Ausk. NZ J Med 1992;: 42

Figitre I : An inwsire study, simultaneous clccrrocardiograni (ECC), srandardised l e f t ventricular (1.V) hl-mode and catheter- tip iiimometer 1.V pressure (P1.v) recording.

pressure wave, its distortion by catheter trans- mission does not, in theory, influence calculation of pressure-volume work. After placement of the catheter in the LV, immediately before angio- graphy, and close to the time of measurement of cardiac output, an M-mode echocardiogram and simultaneous left ventricular pressure were recorded (Figure 1). During the M-mode recording, made by an experienced technician, emphasis was placed on the recording of continuous endocardial echoes, and on a standardisation procedure based on the inter- section of the ultrasonic beam and the tips of the mitral leaflets.' The LV volumes were then estimated from the M-mode dimensions using the Teichholz m e t h ~ d . ~

In six of the patients, and in the four control patients, we also measured the total stroke volume from the LV angiogram, using the single-plane technique of Dodge er al.' This confirmed the good correlations (r = 0.9 1 ) between angiographic and M-mode echocardiography measurements reported previously.'.' We have elected to base our calculations on the echocardiographic method for several reasons. First, steady state conditions are an important requirement for our study. Second, the measurements by echocardiography and angio- graphy showed good agreement, and it would 5 34 .Aust KZ J Med 1992; 22

certainly be unreasonable to attribute all differences to the echocardiographic error. Finally, on practical grounds, angiographic measurements of volume are sometimes not valid, and not even feasible in some patients with severe regurgitation who are in atrial fibrillation.

Itivasive Energy Estiinatioii (Table 2) The basic assumptions behind these measurements are that energy can be calculated according to basic

TABLE 2 Energy Formulae ,

lnvasive Energy Formulae EF = (PAs-~ED) OF ELV = IAPLV dOLV

Non-invasive Energy Formulae

EF = (PAs-~LA) OF ELV = (PAs-~LA) OLV

EK =APLV.LAQR = ' h e OR V R ~

Ep = ELV-EF-EK

EK = ' h e QR VR' Ep = ELV-EF-EK

EF = forward enerqy PAS =mean systolic elecllon a o r k pressure PED = LV end diastolic pressure OF = forward stroke volume E l v = LV energy APLV = systolic ininus diastolic LV prmsure OLV = LV stroke voluine EK = kinetic energy of regur- gitalion APLV LA = systolic left ventricular left atrial pressure gradieni OR = regurgitant volume VR =mean regurgitant jet velocity E p = po'enlial energy of regurg taiion e = density of blood

FNERGY AND M I T R A L REGI'R(;ITATION

Figwe 2: Computer display of the digitised left ventricular volume and pressure, the corresponding pressure-volume

loops and the pressure-volume work (PV Wk).

Newtonian concepts. Thus, PE can be measured as the product of pressure and volume changes, and KE by multiplying one-half by mass by the square of velocity. The modified Bernoulli equation, the mathematical function relating these variables (AP = 4v2), can be used to transform pressure into an equivalent velocity and vice versa.6

Integrated total LV work energy was calculated as the integral product of instantaneous left ventricular volume (M-mode), and pressure. A pressure-volume loop was constructed using software developed specifically for this purpose (Figure 2). Forward stroke energy was measured as the product of mean aortic pressure during systolic ejection, corrected by subtracting the end-diastolic pressure, and the forward stroke volume measured by thermodilution. Energy of regurgitation was

then calculated by subtracting the forward stroke energy from total L v pressure-volume work. KE of regurgitation was estimated as the product of the regurgitant volume and the mean LV. LA pressure gradient during the period of mitral regurgitation (i.e. systole and isovolumic ventricular relaxation). According to the Bernoulli equation, this pressure measurement is simply an alternative formulation to the more Familiar expression of KE in terms of mass and the square of velocity (Table 2). Allowance was made for delay in transmission of the LA pressure to the wedge pressure. We estimated regur- gitant volume by subtracting the thermodilution forward stroke volume from the total stroke volume measured from the M-mode echocardiogram." The PE of regurgitation was obtained by subtracting the KE from the RE. A sample calculation has been provided in Table 3.

Non-Invasive Studies (Table 2) The non-invasive study was performed immediately before cardiac catheterisation. 12V forward stroke work was derived as the product of an estimate of mean arterial systolic ejection pressure, corrected for atrial pressure, and the forward stroke volume. The forward stroke volume was measured as thc product of the area of the LV outflow tract immedi- ately below the aortic valve (estimated from the two-dimensional echocardiogram in the long axis view) and the mean outflow tract velocity from the Doppler recording.'

The following method was used to correct the arterial pressure so that it yielded an estimate of the pressure developed by the LV over and above LA pressure. The contour of the indirect carotid pulse tracing has been shown to closely resemble that of the pressure tracing in the aortic root." Hence, by measuring blood pressure with an auto-

TABLE 3 Sample Calculation

Sample lnvasive Calculation Sample Non invasive Calculation Therrnodilution Forward Stroke Volume = 38 rnL 2DiDoppler Forward Stroke Volume =43 rnL Mean Systolic Election Aortic Pressure = 100 rnrnHg Mean Systol c Ejection Arterial Pressure

Systolic LA Pressure Corrected Mean Election Arterial Pressure

Corrected Mean Ejection Arterial Pressure

= 103 mmHg

= 15 mmHg = 88

LV End-diastolic Pressure = 17 mmHg Systolic BP =118

Forward Work=38x(100-17)xO 000133=0 42 joule Forward Work = 43 x 88 x 0 000133 = 0 5 0 J LV Stroke Volume = 100 mL LV Stroke Volume = 112 mL

= 88 mmHg LV Pressure-Volume Work = 1 37 joule LV Work = 112 x 88 X O 000133 = I 3 1 J Regurgitant Energy = 1 37-0 42 = 0 95 joules Regurgitant Enerqy = I 31 042 =081 J

Regurgitant Volume = 100 38 = 62 TIL Regurgitant Volume = I 1 7 4 3 =69 mL Mean LV LA Gradient = 64 mmHg Mean Regurgitant Jet Velocity 3 64 mkec Kinetic regurgitant energy = 62 x 64 x 0 00013 = 0 54 J Kinetic regurgitant energy = $ 2 x 69 x 3 642 = 0 50 joule

Poi'ential regurgitant energy = 0 95-0 55 = 0 41 J Potential regurgitant energy = 0 31 joule = 0 81 0 50

ENERGY AND MITRAL REGURGI I rZ I ION Aust NZ J bled 1992, 22 535

Figure 3: A non-invasive study, simultaneous electrocardiogram (ECG), left ventricular (LV) M-mode, phonocardiogram (PCG) and indirecr carotid tracc (ICI’).

matically recording instrument (Dinamap 845@ , Critikon, Tampa, Florida), we calibrated the carotid pulse contour. Mean arterial pressure during systolic ejection was estimated by electronic integration. An estimate of the LA pressure during systole was made from the Doppler recording of the regurgitant jet; the Bernoulli equation was used to translate the peak velocity of the jet into an equivalent LV/LA pressure difference.’ This was then subtracted from the systolic blood pressure to yield a systolic LA pressure. This LA pressure was in turn subtracted from the mean arterial systolic ejection pressure to yield an estimate of the pressure generated by the LV. 536 Ausr K Z J .\Id 1992. 22

Total LV work energy was calculated as the product of the corrected arterial pressure and the total LV stroke volume measured from the M-mode echocardiogram (Figure 3). Initial attempts to use a biplane echocardiographic methodlo were thwarted by the unreliability of measurements made from single frames in patients with suboptimal image quality. The difference between total and forward stroke volumes was used to calculate the RE. KE of regurgitation was calculated from the mean regurgitant Doppler regurgitant velocity and the regurgitant volume. The regurgitant volume was calculated as the difference between the M- mode total stroke volume and the LV outflow tract

ENERGY AND MITRAI. REGURGITATIOK

TABLE 4 Energy Estimates 1

Initials Total LV Work (ET) Forward Work (EF)

Cath Echo Cath Echo

1 AK 2. DC 3. JC 4. EG 5. JW 6. WS 7 MS Mean

sd

~

1 4 8 115 0 5 2 0 6 0 1 4 5 1 0 2 044 0 4 3 0 9 9 1 3 5 0 3 2 0 3 4 1.37 1.31 0.42 0.50 2.51 2.20 0.79 0.79 2 26 1 9 8 0 4 9 0 3 2 1 4 5 1 3 4 0 5 0 0 3 3 1 6 4 1 4 8 0 5 0 0 4 7 0 5 4 0 4 4 0 1 5 0 1 7

p = 0 2 9 p = 0 3 8

Regurgitant Energy (ER) Regurgitant KE (EK) Regurgitant PE (Ep) Cath Echo Cath Echo Cath Echo

0 96 0 56 0 7 7 0 4 1 0 1 9 0 1 4 1 0 1 0 59 0 4 6 0 4 3 0 5 5 0 16

0 1 4 0 3 7 0 67 101 0 5 3 0 6 4 0 4 1 031 0 95 0 81 0 5 4 050

1 7 2 141 135 1 0 0 0 3 6 0 4 1 1.77 1.65 1 24 1.03 0 5 4 0 6 2 0.95 1.01 0.85 0.63 0.10 0.37 1.15 1.01 0.82 0.66 0.33 0.34 0.42 0.41 0.35 0.26 0.19 0.16

p = 0 2 8 p=o.19 p=0.46

All measurement in loule I

forward stroke volume. The mean regurgitant jet velocity was measured from the Doppler recording. As for invasive measurement, PE was the difference between total L V work energy and KE.

In each patient the number of measurements used to obtain an average value for each variable reflected the difficulty of measurement and its handling in calculations. For example, at least ten estimates were made of the diameter of the LV outflow tract, a measurement which is squared in the calculation of flow. Interobserver variability was measured for key variables. Pearson's correlation coefficient was used to test the relationship between variables mean values and the regression line to detect systematic differences, and the paired t-test to assess significance of differences between mean values.

2'o 1

V." . 1 2 3 4 5 6 7

Patients Figure 4: T h e relationship between the potential (Cath PE) and kinetic (Cath KE) components of regurgitant

energy, measured invasively, in individual patients.

ENERGY AND MITRAL REGURGITATION

50 1 R = 0.92

G 40 I E E - 30 z

a

a

: $ 20

3 > 10 3 a a

0.0 0.1 0.2 0.3 0.4 0.5 0.6

Cath PE (Joule) Figure 5: Potential energy of regurgitation (PE) and the

pulmonary artery wedge (PAW) V-wave peak.

RESULTS Invasive Study (Table 4) For the eight patients with mitral regurgitation, the mean total LV stroke work energy was 1.64 joule, range 0.99 to 2.51 J. This was 84% greater than that measured in the four control patients 0.89 J (0.78 to 0.98 J). For patients with mitral regurgi- tation, mean RE was 1.1 5 J (0.67-1.77 J), to which KE contributed 0.82 J (0.46-1.35 J) and PE 0.33 J (0.10-0.55 J). Thus, approximately three-quarters (73.6%) of the RE was KE. However, this was not a constant proportion in different patients (Figure 4). The PE component of RE ranged from 10.5% to 54.4% in individual patients. Since the quantity of regurgitant potential energy (RPE) and the energy capacitance of the L A and pulmonary veins

537 Aust NZ J Med 1992; 22

TABLE 5 I Correlation of lnvasive and Non-invasive Estimates 30 1

R = 0.34

A A

A AA A

A 0'

0.0 0.4 0.8 1.2

Cath KE (Joule) Figure 6: Kinetic energy of regurgitation (KE) and Doppler colour flow mapping (CFM) regurgitant jet area

in square centimcrres (sq cm).

will determine the LA pressure during systole, we would expect some relationship between our measurement of RPE and the pulmonary arterial wedge pressure. The pulmonary artery wedge v- wave peak pressure was closely related to the estimate of RPE at cardiac catheterisation (Figure 5) . Given that the proportion of the RE which is PE varies from patient to patient, a close relation- ship between the jet area measured in the colour flow map and total RE would not be expected; this was found to be the case. On the other hand, unless other technical factors intervened, we would expect good correlation between our measurement of KE and colour flow map jet area but this was not so (Figure 6).

Since our estimate of PE is an indirect one based on subtraction of the KE from the RE, we sought independent data on directly measured pressure- volume work in the LA. Unfortunately, no such measurements have been published. However, a crude estimate of PE of regurgitation can be derived from an early study of LA atrial pressure-volume relations." We selected from this study the three patients with mitral regurgitation and atrial fibril- lation. In atrial fibrillation, there is obviously no contribution of atrial systole to pressure and volume fluctuations. T h e LA volume change then reflects mainly the LV regurgitant volume, and the height of the atrial v-wave reflects the pressure change attributable to regurgitation. Hence, we can make a direct estimate of the LA PE energy. The average height of the v-wave in these patients was 538 Aust NZ J Med 1992; 22

Variables Pearson's r QLV " 0.93

PLA 0.83 ET* 0.87 EF' 0.79 ER 0.79 EK 0.88

QF 0.89

EP 0.18

P-value (<0.005) (<0.01) (<0.05) (<0.02) (<0.05) (< 0.05) (<0.01)

(-1 'Includes data from 4 control sublects. Abbreviations - see Table 2

21.3 mmHg, and the atrial volume fluctuation was 106.7 mL. The estimate of PE is therefore 0.30 J, a value close to our mean value of 0.33 J.

The relationship between PE and the atrial v- wave pressure and the correspondence of our indirect measurement with a more direct one suggest that our estimate of PE is of the right order of magnitude.

Non-invasive Study (Table 4) Differences between invasive and non-invasive measurements of LV ventricular work energy will result from absence of a steady state during the two measurements, from systematic differences in measurement technique and random error in all measurements. In addition, it should be noted that by using catheterisation data as a 'gold-standard', we tend to consign arbitrarily all errors to the non- invasive measurements which, of course, was not likely to be the case. There was good correlation between heart rate for the two studies with no systemic variation but blood pressure tended to be lower under sedation during catheterisation so that correlation of mean systolic blood pressure for the two procedures was only fair. The relationships between key measurements made at cardiac catheterisation, which we take as our gold standard, and those made non-invasively have been summar- ised in Table 5.

For patients with mitral regurgitation, the non- invasively measured mean values of total LV work energy (1.48 J), of forward stroke work (0.47 J), and of KE of regurgitation (0.82 J) were not signifi- cantly different, and correlation between values for individuals was good in each case (Table 5 ) . The mean value for regurgitant work (1.01 J) was not significantly different but the correlation of individ- ual values was fair only. The difference between mean values of RE (0.34 J) measured invasively and non-invasively was not significant either but here the correlation for individuals was poor. This

ENERGY AND MITRAL REGURGITATION

phenomenon of good agreement between mean but not individual values is due to the additive effects of errors in individual patients created by two consecutive calculations involving subtraction. Thus, the errors in estimating RE produced by the subtraction of forward from LV work were then compounded by the subtraction of K E from RE to obtain PE. We therefore concluded that the accurate non-invasive measurement of PE in individual patients will probably require a more direct estimate of some kind.

DISCUSSION Regurgitant volume is a commonsense measure of severity of a valve leak, hallowed by long usage in the angiographic laboratory. Before the advent of colour flow mapping, attempts had been made to use conventional Doppler mapping to estimate the severity of regurgitation. However, subsequent attempts to relate jet area measured by colour flow mapping to regurgitant volume were disap- pointing.IJ This is scarcely surprising when we consider that these maps are representations of velocity which is only indirectly related to volume. However, the discovery that the size of the colour flow jet and the pixel velocities could be used to estimate KE' was a conceptual advance. At some point, however, we appear to have lost sight of the fact that RE has components of both KE and PE. Colour flow jet area could therefore be taken to represent total energy only if the magnitudes of the two forms of energy remain in a fixed relationship to each other. We have shown, however, that they can vary independently of one another (Figure 4).

On the other hand, we anticipated that our measurement of K E would be related to jet area. However, it was not. Clinical experience suggests that the explanation for this was probably that poor transthoracic transmission of the backscattered Doppler ultrasonic signal in some patients reduced the area of the jet. This results in underestimation of the severity of regurgitation. Thus, there are both theoretical and practical reasons to exercise caution when using colour flow mapping as the sole or major means of assessing severity of mitral regurgitation.

Measurements of total LV stroke work, forward work, and regurgitant work all provide slightly different perspectives on LV overload in mitral regurgitation. The total LV work energy can be used as a measure of the load on the LV which takes account of both volume and pressure overload. Evidence that it is important to do so comes from both animal studies and from experience with afterload r e d u ~ t i o n . ' ~ Regurgitant work is wasted ENERGY AND MITRAL REGURGITAI'ION

work from the point of view of the LV. These indices should therefore be put to test as predictors of declining LV function or onset of LV failure in patients with mitral regurgitation. If we could measure PE more accurately in individuals, this should provide interesting insights into acute severe mitral regurgitation. For example, low blood pressure and high LA pressure at presentation with much PE might be replaced by more KE and less PE as the blood pressure rises and the LA pressure falls with treatment. This would be a useful way to follow such patients non-invasively. A direct method for measuring PE may be required to accomplish this, rather than using a method which depends on subtraction of the directly estimated KE. However interesting the measurement of PE might be in its relation to the genesis of the LA pressure, from the practical point of view our non- invasive measure of LA pressure would suffice.

In summary, we have demonstrated that in patients with mitral regurgitation, that regurgitant LV energy has both K E and PE components, both of which must be taken into account. Our evidence suggests that variation in the relative amounts of K E and PE could account for some discrepancies between the overall assessment of severity of mitral regurgitation and the colour flow mapping assessment. Another important factor is likely to be variation in the intensity of back-scattered ultra- sound associated with variations in image quality. Estimations of total LV stroke work, regurgitant stroke work and RE fraction, are all measurements sensitive to both pressure and volume load on the LV; they should be tested as serial measures which might assist in the prediction of the need for mitral valve replacement. Although the relationship between RPE and wedge pressure v-wave indicates that PE reflects the haemodynamic severity of heart failure, unfortunately the non-invasive estimate in individual patients is not sufficiently accurate to allow its use in serial studies in individuals. However, our non-invasive estimate of LA pressure should be useful in serial studies to monitor haemodynamic changes, including response to treatment. rn

Acknowledgments T h e authors would like to thank I l r J. Gutman for his assistance and support and Dr J. Santamaria for his help in the preparation of the figures.

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ENERGY AND MITRAL REGURGITATION