DOI 10.1378/chest.96.6.1280 1989;96;1280-1284Chest

 P Mols, C H Huynh, P Dechamps, N Naeije, M Guillaume and H Ham radionuclide ventriculography.chronic obstructive pulmonary disease by Prediction of pulmonary arterial pressure in

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1280 Prediction of Pulmonary Arterial Pressure in COPD (Mo!s St a!)

Prediction of Pulmonary Arterial Pressurein Chronic Obstructive Pulmonary Diseaseby Radionuclide Ventriculography*Pierre Mols, M.D.; Chi-Hoang Huynh, M.D.; Philippe Dechanips, M.D.;

Nicole NaeUe, M. D. ; Marcel Guillaunte, Ph. D. ; and

Hamphrey Hani, M.D. , Ph.D.

Pulmonary arterial hypertension represents an important

parameter for the assessment of the severity of chronic

bronchitis. The measurement of the pulmonary arterial

pressure, however, requires invasive techniques of limitedroutine use because of costs and associated risks. The aim

of this study is to evaluate whether the 81”Kr right ventric-

ular ejection fraction and parameters derived from equilib-

rium �‘Tc red blood cells’ right ventricular curve allow a

better estimation ofPAP than the �Tc RVEF. In 41 patients

with severe chronic bronchitis, the linear correlation be-

tween PAP and �Tc RVEF was - 0.61 (p<O.OOl). None of

the parameters derived from the right ventricular curve

was better correlated to PAP than the �Tc RVEF. In 16

other chronic bronchitis patients, the 8I�(j. RVEF correlated

moderately to PAl?. In conclusion, the alternative isotopic

methods proposed in this work do not provide a reliable

estimation of pulmonary arterial pressure in patients with

chronic bronchitis. (Chest 1989; 96:1280-84

PAP = pulmonary artery pressure; RVEF right ventricularejection fraction; ROl region of interest

C hronic o)bstructive pulmonary disease is one of the

chief causes of disability and death in Europe

and in the United States. Pulmonary hypertension

triggers the development of right ventricular hyper-

trophy which may lead to right ventricular failure with

a high mortality rate.’3 The measurement of PAP

requires right heart catheterization. Although this

technique is widely available, its routine use is limited

by co)sts and associated risks. Therefore, less invasive

methods have been developed to detect and assess

the severity of pulmonary hypertension. One of these

methods is the determination ofRVEF by technetium-

99m radionuclide ventriculography. Studies, however,

show that the ventricular ejection fraction lacks in

specificity and poorly correlates with pulmonary ar-

terial pressure.4’5

During the last few years, however, radionuclide

techniques have improved considerably and some

curve parameters have shown a better sensitivity than

*From the Service of Internal Medicine and of Radio-Isotopes,

Saint-Pierre University I lospital , Brussels, Belgium.Manuscript received April 7; revision accepted May 18.Reprint requests: Dr. Mols, Garde Adults, Hopital Universitaire-St-Pierre, B-1000 Brussels, Belgium

RVEF in assessing pulmonary arterial pressure.6’7 An

improved method for the evaluation of the RVEF by

krypton-8lm (81’�Kr) has also been developed.�’�

The aim ofthis study was to evaluate whether ��mKr

RVEF and parameters derived from equilibrium tech-

netium-99m red blood cells (mmTc RBC) right ventric-

tilar curve allow a better estimation of pulmonary

arterial pressure.

Patients

MATERIAL AND METHODS

Fifty seven patients with stable and severe chronic obstructive

pulmonary disease were subjected to right heart catheterization to

measure pulmonary arterial pressure and estimate right ventricular

function. There were 53 men and four women (group 1: 64 ± 3

years; group 2: 61 ± 1 years). No patient had any clinical or

electrocardiographic evidence of systemic hypertension, valvular

heart disease or coronary artery disease. The patients’ characteris-

tics and lung function data are given in Table 1 . All the patients

have given informed consent to) the study, which was approved by

the Human Investigation Committee of our institution.

Hemodynamic Determination

A triple lumen thermodilution 7F Swan-Ganz catheter was

introdticed into the right internal jugular vein using the Seldinger

technique, and advanced under constant pressure wave and fluor-

Table 1 -Patients’ Characteristics and Lung Function Data

N* Age, yr

Male!

Female

FEV

mI-s �

FEV1/FEV1,

%

PaO�,

mm Hg

PaCO2,

mm Hg

Groupi 16 64±3 16-0 953±122 40±3 64±4 44±2

Group 2 41 61 ± 1 37!4 912 ± 63 39 ± 6 64 ± 2 43 ± 1

*N, number O)fpatients; values are expressed as mean ± SEM.

 © 1989 American College of Chest Physicians by guest on July 11, 2011chestjournal.chestpubs.orgDownloaded from

TINE

U-LU>

E

0?

a

a

60

50

40

30

a a

aa a

y - 54.8317 . O.6127x R = 0.76

a

aa

CHEST I 96 I 6 I DECEMBER, 1989 1281

C)0Cz-I

z

-�

m

FIGURE 1 . Parameters calculated from the right ventricular curve

during the systolic and diastolic phases. For the signification of the

abbreviations, see methods.

oscopic control in the right pulmonary artery. Pulmonary pressure

was measured using a physiologic pressure transducer and recorded

on a thermal writing recorder. The zero reference was placed at

midchest level and values for pressures were averaged for three

successive respiratory cycles. Heart rate was derived from a

continuously monitored ECG lead. Cardiac output was measured

in triplicate by the thermodilution method using a computer. The

following formulae were used for hemodynamic calculations: cardiac

index (l/min/m2) = cardiac output (L/min) ! body surface area (rn2);

pulmonary vascular resistance index (dyne.s.cm -��m2) 80 X (mean

pulmonary arterial pressure - pulmonary wedge pressure)!cardiac

index.

Right Ventricular Ejection Fraction Techniques

In 16 patients (group 1), RVEF was determined using TM1”Krwithin

the seven days following right heart catheterization. The detailed

procedure of the 5”Kr right ventricular study has been described

previously.� Briefly, the patient was studied supine, in a 30� right

anterior oblique projection. The ‘�“Kr was continuously infused and

16 ECG-gated frames were acquired. Background activity was

corrected using �‘Tc MAA lung perfusion scintigraphy acquired in

the same position immediately after the completion of the gated

study. End-diastolic and end-systolic right ventricular ROIs were

carefully delineated on the background corrected images taking

into account isocount lines and the phase and amplitude images of

the first and second Fourier harmonics constnicted from the original

70

gated data. In 41 patients (group 2), ECG-gated equilil)rlum �“Tc

RBC ventriculography was performed simultaneously with right

heart catheterization. The patient was studied supine in 45#{176}left

anterior oblique projection and 16 ECG-gated frames were ac-

quired. End-diastolic right ventricular ROI was delineated following

the limits o)f the ventricular phase area. For background correction,

50 percent o)f the maximum activity in the right ventricular area in

the end-diastolic frame was subtracted o�n each pixel of the 16

gated-frames. The end-systolic right ventricular ROI was therefore

automatically defined. The RVEF was calculated using the classical

end-diastolic mintis end-systolic over end-diastolic count rates. A

three-harmonics Fourier curve fitting was then applied on the

corrected right ventricular volume curve;1#{176}#{176}and the following

parameters were calculated (Fig 1): pre-ejection period, ms; time

to the first third of the systole, ms; time to peak ejection rate, ms;

total ejection time, ms; first third ejection rate, countss ‘; peak

ejection rate, co)unts-s ‘; mean ejection rate, counts-s ‘; first third

ejection on total ejection, VFEITE; rapid filing time, ms; slow filing

time, Ins; time to the first third diastole, ms; time to peak filing

rate, ms; total filing time, ms; first third filing rate, counts-s ‘; peakfiling rate, counts-s � mean filing rate, co)unts-s ‘; and first third

filing on total filing, FTFIFF.

Study Protocol

In group 1 , ‘1”Kr RVEF was measured at rest and correlated to)

the pulmonary hemodynamic measurements performed during the

same week.

In group 2, ‘#{176}“TcRVEF and the other noninvasive parameters

were correlated to) pulmonary arterial pressures and resistances

measured simultaneousl�:

Statistics

These co)nsisted oflinear, logarithmic and exponential correlations

between no)ninvasive parameters and pulmonary hemodynarnics.

RESULTS

The plotting of sih1lKr RVEF and mean pulmonary

arterial pressure, presented in Figure 2, shows that

both parameters are correlated (r - 0.75) though not

perfectly.

Correlations between curve parameters derived

from the ECG-gated right volume curve and mean

pulmonary arterial pressure are presented in Table 2.

None ofthese curve parameters correlates better with

mean pulmonary arterial pressure than RVEF even

when using a logarithmic or exponential correlation

10 20 30

Mean pulmonary arterial pressure, mmHg.

, FIGuRE 2. Linear correlation between 81”Kr right yen-

4 0 tricular ejection fraction and mean pulmonary arterial

pressure in 16 patients with COPD.

 © 1989 American College of Chest Physicians by guest on July 11, 2011chestjournal.chestpubs.orgDownloaded from

Cs

U

fC

. ,�

:s�!:�/�!

: :� R-049 �

�: �#{176} H:

:,‘H .� �.

�B #{149}�

U g #{149}� #{149}�

y - 1.873 ‘0.0278x R - 0.34

40 50 ‘o ‘ i’s ‘ 20 ‘ 30 ‘ 40 50

pressure, mmHg. Mean pulmonary arterial pressure, mmHg.

third ejection rate

patients with COPD.

and FIGURE 4. Linear correlation between first third filling rate and

mean pulmonary arterial pressure in 41 patients with COPD.

Table 2-Linear Correlation Between Radionuclide and HeInOd*JnamiC Parameters.

1282 Prediction of Pulmonary Arterial Pressure in COPD (Mo!s St a!)

PAP PAPS PVRI

Systolic phase

Pre-ejection period ms + 0. 10 + 0.05 + 0.14

Time to peak ejection rate ms + 0.24� + 0.26* + 0.30t

lime to first third systole ms +0.24k +0.23� +0.28t

Totalejectiontime ms +0.04 +0.09 +0.14

First third ejection rate count-s ‘ - 0.49� - 0.52� - 0.38�

Peak ejection rate count-s’ - 0.29t - 0.351 - 0.28�

Mean ejection rate co - 0.43� - 0.461 - 0.414

First third/total ejection rate count-s ‘ + 0. 17 + 0. 10 + 0.13

TPER-PEP� ms +0.14 +0.19 +0.15

Diastolic phase

Rapidfillingtime ms -0.06 -0.04 -0.07

Slow filling time ms �0.23�

Time to peak filling rate ms +0.01 +0.01 -0.01

‘Lime to first third diastole ms + 0.02 + 0.06 + 0.05

Total filling time ms -0.2&#{176} -0.24k �0.22�

Peak filling rate count-s’ - 0. 13 - 0.19 - 0.15

First third filling rate count-s’ -0.34� -0.35t

Mean filling rate count-s’ -0.23� -0.27t -0.22�

First third to total filling rate -0.15 -0.19 �0.22�

RV ejection fraction % - 0.61t -0.631 -0.54�

�0 = p<O.O5.

tp<0.01.

:tp<0.001.

§TPER-PEP, time to peak ejection-rate pre-ejection period.

instead of a linear correlation. Figures 3 and 4 show

the calculated parameters of the systolic and diastolic

phases which correlate best with mean pulmonary

arterial pressure, respectively first third ejection and

filing rate.

The same results have been observed with the

systolic pulmonary arterial pressure and the pulmo-

nary vascular resistance index (Table 2).

DISCUSSION

In chronic obstructive pulmonary disease, pulmo-

nary arterial hypertension frequently induces cor

pulmonale and symptomatic right congestive heart

failure with poor �3 The higher the pulmo-

nary arterial pressure, the worse the prognosis. There-

fore, the determination ofthis parameter seems inter-

esting for both the evaluation and the follow-up of

COPD patients. Since measuring pulmonary arterial

pressure requires right heart catheterization, a trau-

matic and expensive procedure, a variety of other

techniques have been proposed, including chest roent-

genography, echocardiography, radionuclide angiog-

raphy and others.’2’7 Unfortunately, up to now, none

ofthem has yielded accurate estimations of pulmonary

arterial pressure.

The most commonly used radionuclide parameter

is the RVEF. Indeed, correlations have been found

between pulmonary arterial pressure and RVEF, but

within both the normal and abnormal range, the

variability of estimated pulmonary arterial pressure is

important and small changes in RVEF may reflect

large variations in pulmonary pressure . Therefore,

more reliable radionuclide parameters have been

sought. Friedman and Holman6 used regional RVEF

 © 1989 American College of Chest Physicians by guest on July 11, 2011chestjournal.chestpubs.orgDownloaded from

CHEST I 96 I 6 I DECEMBER, 1989 1283

during the second half of systole and noted that this

improved accuracy in evaluating pulmonary arterial

hypertension as compared to the global ejection

fraction. However, in their report, accurate and repro-

ducible results were said to require a high degree of

proficiency. Marmor et al� proposed another index

composed by RVEF and right atrial emptying rate. In

their hands, this parameter seems to evaluate the

severity of pulmonary arterial hypertension very pre-

cisely.

We were interested in other radionuclide ap-

proaches. First, we used sImKr radionuclide ventricu-

lography because it solves most of the technical

problems posed by classical methods: the surimposi-

tion ofthe heart chambers for equilibrium techniques,

the low count rate or low resolution for first pass study,

for instance. But the correlation between 8�’Kr RVEF

and pulmonary arterial pressure hardly improved and

the range of pulmonary arterial values corresponding

to each RVEF was still too large. The use of 81”Kr

RVEF as an accurate pulmonary arterial pressure

predictor index was thus questioned.

Second, the use of right ventricular curve parame-

ters derived from a Y9mTc red blood cells ECG gated

equilibrium study. Indeed, systolic or diastolic delays,

right ventricular ejection or filling speed have not yet

been tested as indices evaluating pulmonary arterial

pressure. But neither systolic nor diastolic delays

could be correlated with pulmonary arterial pressure

in our work.

In contrast, Marchandise et al’� found a correlation

between the acceleration time measured by Doppler

echocardiography and PAP in patients with COPD.

In our study, the time between the onset and peak

pulmonary flow velocity is reflected by the difference

between time to peak ejection rate and pre-ejection

period. This parameter has not allowed an accurate

evaluation of pulmonary arterial pressure. The dis-

crepancies between our results and Marchandise’s

suggest that the measurement of systolic and diastolic

delays might be less accurate by the isotopic method

than by the Doppler technique. This is probably due

to the surimposition of the right auricle and the right

ventricle. Moreover, the evaluation of mean pulmo-

nary arterial pressure by parameters derived from a

right ventricular equilibrium curve rather than the

evaluation of pulmonary arterial pressure values dur-

ing one heart cycle implies less precise measurements

because of chest movements and a variability in

duration of the heart cycles.

The speed ofright ventricular emptying at different

moments of the systolic phase decreases when pul-

monary hypertension increases in our work. Since the

right ventricular contractility either does not change

or increases with deteriorating pulmonary fu’8

the decrease ofright ventricular emptying speed might

be caused by an increase of RV afterload, and thus, o)f

pulmonary arterial pressure. Unfortunately, in our

work, those indices correlate to) 20 to 25 percent of

measured pulmonary arterial pressure and are of no

clinical interest fur evaluating pulmonary arterial

pressure.

Finally, our findings sugj�est a slightly negative

correlation between pulmonary arterial pressure and

right ventricular filling speed during the first third of

diastole. This slower early filling speed of the right

ventricle is probably to be ascribed to a decreased

compliance secondary to both muscular hypertrophy

and chamber dilation observed in COPD with pt’1-

monary yp’9

In conclusion, our findings show that pulmonary

hypertension in patients with COPD affects both the

systolic and diastolic phase of the right ventricular

function. The isotopic methods proposed do not yet

provide a reliable estimation of pulmonary arterial

pressure in our patients.

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American Board of Internal Medicine,Subspecialty Examination in Pulmonary Disease

The 1990 subspecialty examination in pulmonary disease has been announced by the ABIM.

The registration period is January 1-April 1, 1990 and the examination date is November 6,1990. For information, contact the Registration Section, ABIM, 3624 Market Street, Philadel-phia 19104 (800:441-ABIM).

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DOI 10.1378/chest.96.6.1280 1989;96; 1280-1284Chest

P Mols, C H Huynh, P Dechamps, N Naeije, M Guillaume and H Hamdisease by radionuclide ventriculography.

Prediction of pulmonary arterial pressure in chronic obstructive pulmonary

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