Noninvasive Assessment of Pulmonary Hypertension From

Right Ventricular lsovolumic Contraction Time

PETER MILLS, MD INGRID AMARA, MSPH LAMBERT P. McLAURIN, MD, FACC ERNEST CRAIGE, MD, FACC

Chapel Hill, North Carolina

In order to assess a noninvasive method of predicting pulmonary arterial pressure in adults, right ventricular systolic time intervals were determined with echocardiography simultaneously with pulmonary arterial end-dia- stolic pressure measurements. Right ventricular isovolumic contraction time was measured from echographic recordings of the tricuspid and pulmonary valves. Although this interval was found to increase as pul- monary arterial pressure increased, the method cannot be used to predict quantltatlvely the level of pulmonary arterial pressure in adults. However, an echocardiographically determined right ventricular contraction time of less than 25 ms suggests a normal pulmonary arterial pressure. In pa- tients with pulmonary parenchymal diseases, echograms of the tricuspid and pulmonary valves are only rarely of such quality as to permit accurate delineation of the valvular events required for these measurements.

From the Cardiology Division, Department of Medicine, University of North Carolina School of Medicine and the C. V. Richardson Laboratory, North Carolina Memorial Hospital, Chapel Hill, North Carolina. This study was supported by Contract No. l+R-62916 from the National Heart, Lung, and Blood Institute. Bethesda, Maryland. Manuscript received July 16, 1979; revised manuscript received March 3, 1980, accepted March 13. 1980.

Address for reprints: Ernest Craige, MD, 338 Clinical Sciences Building 2291-1, University of North Carolina School of Medicine, Chapel Hill, North Carolina 275 14.

For many years, cardiologists have attempted to anticipate the level of pulmonary arterial pressure on the basis of abnormalities of heart sounds and data from the electrocardiogram and chest X-ray film. However, no more than gross approximations of pulmonary arterial pressure can be made from these methods. The development of echocardiography afforded the opportunity to observe the movements of heart valves, and various abnormalities of pulmonary valve motion, including shallowness of the A wave dip,* diminished E-F slope in diastole and mid systolic closing movement of the valve cusp, have been found to be associated with pulmonary hypertension. However, these findings have been of a qualitative rather than a quantitative nature.

Ability to record the movements of the tricuspid and pulmonary valves permits the noninvasive estimation of right-sided systolic time intervals. Preliminary studies2 from our laboratory had suggested a positive cor- relation between right ventricular isovolumic contraction time obtained echocardiographically and pulmonary arterial end-diastolic pressure. A similar relation was demonstrated by the meticulous hemodynamic investigations of Curtiss et al.,3 who used high fidelity micromanometers to measure right-sided systolic time intervals. Although the highest pulmonary arterial pressures were associated with the longest isovolumic contraction times the relation was not linear. In childrenP7 the echogram of the pulmonary valve is relatively easy to record, permitting estimation of both right ventricular preejection period (RPEP) and right ventricular ejection time (RVET) in this age group. The RPEP/RVET ratio is of some limited value in predicting pulmonary arterial pressure or resis- tance.

The objective of the present study was to see whether echographic tracings of the tricuspid and pulmonary valves could be employed to obtain a quantitative estimate of pulmonary arterial pressure in adults. Specifically, the intention was to measure right ventricular isovolumic contraction time, which was defined as the period from tricuspid valve closure to pulmonary valve opening.

272 August 1980 The American Journal of CARDIOLOGY Volume 46

ASSESSMENT OF PULMONARY HYPERTENSION-MILLS ET AL.

Methods

Patients: Subjects selected for inclusion in this study were drawn from patients referred to our cardiac catheterization laboratory during the period from July 1976 to September 1978. All patients were screened before catheterization to determine whether the tricuspid and pulmonary valves could be adequately visualized with echocardiography. Forty pa- tients form the study group from whom our data are derived (Table I). Their ages ranged from 4 to 63 years, although only five patients were in the pediatric age group, and the average age was 31 years. The predominance of atrial septal defect and mitral stenosis reflects the greater success in recording the tricuspid and pulmonary valves in patients with right ven- tricular dilatation.

Two additional groups were surveyed echocardiographi- tally to see whether right ventricular isovolumic contraction time could be determined. These consisted of 29 patients with chronic lung disease and 43 patients with chest pain who were being screened prior to cardiac catheterization and coronary arteriography.

Echocardiography: Echocardiograms were recorded with an Irex 101 multichannel recorder (IREX Medical Systems, Upper Saddle River, New Jersey) equipped with two 2.25 megahertz transducers with a diameter of 8 mm. During the course of the investigation, the recorder was modified to permit the simultaneous registration of the output from the two transducers as well as from the electrocardiogram and phonocardiogram.s Thus, in 23 patients the tricuspid and pulmonary valves were recorded sequentially during cathe- terization and in 17 patients these valves were recorded si- multaneously with the technique of dual echocardiography. One transducer was placed in the third or fourth left inter- costal space and angled medially until the anterior leaflet of the tricuspid valve was seen. With further manipulation it, was usually possible to locate the posterior leaflet as well, so that a well defined closure or C point could be determined. Meanwhile, a second operator would locate the echogram of the pulmonary valve by tilting the second transducer to the left and superiorly from a position where the aortic valve had been visualized (Fig. 1). The paper speed of the recorder was set at either 100 or 200 mm/s.

Cardiac catheterization: Diagnostic studies were carried out using standard techniques.g Right-sided pressure deter- minations were obtained with use of fluid-filled catheters. During the registration of pressures from the pulmonary ar- tery, echograms of both right-sided valves were recorded.

Analysis of the data: Right ventricular isovolumic con- traction time was measured from the closure point (C) of the tricuspid valve to the full opening of the pulmonary valve (Fig. 1). In most instances, it was possible to record the coaptation of the tricuspid valve leaflets, thus providing an accurate marker for valve closure. Although the onset of the separation of the cusps of the pulmonary valve would theoretically be the ideal echocardiographic marker for the termination of right ventricular isovolumic contraction time, it is seldom possible to record this event in adults. Therefore, the moment of completed opening of the valve was selected. This definition of the end of right ventricular isovolumic contraction time will be discussed further.

In those patients in whom simultaneous dual echoes of the tricuspid and pulmonary valves could be obtained, the du- ration of echocardiographically determined ventricular iso- volumic contraction time was measured directly from the C point of the tricuspid valve to full opening of the pulmonary valve. It is clear that recording both valves in a single tracing reduces the potential for errors in measurement. In the 23 patients in whom it was necessary to make sequential obser-

vations of the movements of the two valves, time was mea- sured from the Q wave of the electrocardiogram to the re- spective valve landmarks with isovolumic contraction time being the difference between the two measurements. In each patient, the number of cardiac cycles measured was the maximum in which adequate simultaneous echocardiographic and pressure data were available; this number ranged from 5 to 103 cycles (median 21 cycles). A total of 1,296 cardiac cycles was analyzed.

The pulmonary arterial end-diastolic pressure was de- termined at the point immediately preceding the systolic upstroke (Fig. 1).

Results

Relation between pulmonary arterial end-dia- stolic pressure and isovolumic contraction time (Fig. 2): A general trend is demonstrated between these two variables such that as pulmonary arterial pressure

TABLE I

Summary of Results: Relation of Tricuspid Valve Ciosure- Pulmonary Valve Opening Time (RVICT) to Pulmonary Arterial End-Diastolic Pressure (PAedD) and R-R interval

R-R

Age RVICT PAedp interval Case (vr) Diaanosis (ms1 Imm t-kt~ Ims1

CAD AS ASD

znary PH

ZD ASD

I

zap MS

% Postop AR, MS Sarcoid $r$p AR, MR

MS Postop MR

:: MS ASD ASD

z

KD

KD ASD ASD

:: LAM AS ASD

::DS

862 550 520 650 995 810 700 752 550 875 530 777 690

1,150 815 800 555 780 525 850

1,150 825 780 700 380 810 832 800 800 800 575 725 650 785 595 550

1,075 660

1,080 520

AR = aortic regurgitation; ARDS = adult respiratory d/stress syn- drome; AS = aortic stenosis; ASD = atrial septal defect; CAD = cor- onary artery disease; CP = constrictive pericarditis; LAM = left atrial myxoma; MR = mitral regurgitation; MS = mttral stenosis; PH = pul- monary hypertension; Postop = postoperative; RVICT = right ven- tricular isovolumic contraction time.

August 1980 The American Journal of CARDIOLOGY Volume 48 273

increases, isovolumic contraction time lengthens. However, there is a group of patients in whom a long isovolumic contraction time is found in the presence of a relatively normal pulmonary arterial end-diastolic pressure. The effect of heart rate (R-R interval) on this relation was investigated and found to be only minor. This is indicated by the regression equation linking these three variables: Pulmonary arterial end-diastolic pressure = 23.8 - 0.02 X R-R interval + 0.26 X isovo- lumic contraction time. The correlation coefficient was 0.63 (p <O.OOl).

Application of the regression equation: The re- sults of applying this regression equation are shown in Figure 3, where the observed pulmonary arterial end- diastolic pressure is plotted against the predicted pressure together with the 95 percent confidence limits. Although the majority of the predicted values for pul- monary arterial end-diastolic pressure lie within 5 mm Hg of the observed value, there are several instances,

50 r I .

. . .

FIDURE 2. The points locate the rnedff values of the pulrncnary arterial pressueand echocamiogaphtt rtght ventricular isovolumic contraction time for each of the 40 patients. The total number of cardttc cycles from which these data are derived is 1,296.

FtGURE 1. Dual echocardiographic tracing of the tricuspid valve (top) and pulmonsry valve (bottom) with pulmonary arterial (PA) pressure recorded at cardiac catheterization. The electrocardiogram is displayed in the center. The interval between tricuspid valve closure and complete opening of the pulmonary valve reprqents the echocardio- graphic isovolumic contracticn time (ICT) of 30 ms at a time when pulmonary arterial enddiastolic pressure (PA edp) is 8 mm Hg.

especially in the higher ranges, in which the predicted value deviates unacceptably from the observed value. The limitations of the method for clinical practice are illustrated by the wide band of the 95 percent confi- dence limits.

For clinical use, the method is best applied by means of a double dichotomous model (Fig. 4). When right ventricular isovolumic contraction time is found to be less than or equal to 25 ms, then the pulmonary arterial end-diastolic pressure is equal to or less than 18 mm Hg (p <O.OOS). However, for isovolumic contraction time values greater than 25 ms, no accurate prediction of pulmonary arterial end-diastoljc pressure could be made. The p value for the complete dichotomous table is 0.005, confirming that there is a significant positive association between right ventricular isovolumic con- traction time and pulmonary arterial end-diastolic pressure.

Relation between right ventricular “developed pressure” and isovolumic cpntraction time: The change in pressure during the right ventricular isovo- lumic contraction time is from right ventricular end- diastolic pressure to pulmonary arterial end-diastolic pressure (developed pressure) rather than from 0 to pulmonary arterial end-diastolic pressure. Because right ventricular end-diastolic pressure varies relatively little from one patient to another, changes in pulmonary ar- terial end-diastolic pressure usually reflect changes in developed pressure. However, when right ventricular end-diastolic pressure is elevated, as in right ventricular failure, developed pressure will be relatively lower than pulmonary arterial end-diastolic pressure. Accordingly, we plotted developed pressure against right ventricular isovolumic contraction time to see whether this could account for some of the failure of the latter interval in predicting pulmonary arterial end-diastolic pressure, but the results showed a poorer correlation than that between pulmonary arterial end-diastolic pressure and right ventricular isovolumic contraction time.

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ASSESSMENT OF PULMONARY HYPERTENSION--MILLS ET AL.

Reproducibility of echocardiographic mea- surements: Serial studies were performed in 16 patients in order to determine whether there was any variation in right ventricular isovolumic contraction time mea- sured with echocardiography alone compared with that measured during cardiac catheterization studies. We had expected that in general the echocardiographic isovolumic contraction time might be greater during cardiac catheterization, reflecting an increase in pul- monary arterial pressure, but there was no overall trend in either direction.

Patients with pulmonary and coronary artery disease: Among patients with a diagnosis of chronic pulmonary disease, it was seldom possible to obtain satisfactory echoes from the right-sided valves. Among 18 patients with chronic obstructive pulmonary disease and related problems who were screened before cathe- terization, it was possible to visualize the tricuspid but not the pulmonary valve in 7. In the other 11 of this group, it was impossible to record either valve satis- factorily.

Similarly, in a group of 43 patients with coronary artery disease who were screened before catheterization and’coronary arteriography, it was possible to record both valves in only 2 patients. In this group of patients, a large number had a long history of smoking and may have had an element of chronic bronchopulmonary disease.

Discussion

Theoretical background: The basic hypothesis that we have investigated is that right ventricular isovolumic contraction time can usefully reflect changes in right ventricular afterload. The preejection period has been shown to lengthen as pulmonary arterial pressure in- creases.3 Echocardiography not only affords the op- portunity of measuring right-sided events of the cardiac cycle with considerable accuracy, but also allows dis- section of the preejection period into its two compo- nents, the electromechanical interval and isovolumic contraction time. Previous author@ investigating the noninvasive assessment of pulmonary hypertension by echocardiography in children have found the ratio of right-sided preejection period divided by the ejection time (RPEPRVET) to be useful in anticipating the level of pulmonary arterial pressure. Although a ratio of less than 0.30 could be used to predict a pulmonary arterial end-diastolic pressure of less than 30 mm Hg, intermediate and higher ratios could not be used to quantitate reliably changes in pulmonary pressure.

Because the end of right ventricular ejection, as marked by closure of the pulmonary valve, is very rarely recorded in adults, the methods mentioned earlier cannot be a plied to an adult population. We therefore investigate : the relation of early right ventricular sys- tolic time intervals to changes in pulmonary arterial end-diastolic pressure. We chose the right ventricular isovolumic contraction time rather than the preejection period because the latter includes both the electrome- chanical interval and the isovolumic contraction time. Of these two constituents of the preejection period only the isovolumic contraction time would be expected to

40

b Y a 20

9 & ; IO

$

0

-10 1 I I 1 0 IO 20 30 40

PREDICTED PAEDP ImmHg)

FIGURE 3. Predicted pulmonary arterial enddiitolic pressure (PAEDP) values with 95 percent confidence limits for each patient plotted against observed values (see text).

reflect alterations in pulmonary arterial diastolic pressure. The simultaneity of pulmonary arterial pressure measurement and the recording of echocar- diographic intervals in our investigation restricted the number of patients available for study, but eliminated a possible source of inaccuracy that might result from fluctuations in pressure between the registrations of the systolic time intervals and the hemodynamic mea- surements.

Echocardiographic measurement of right ven- tricular contraction time: Right ventricular isovo- lumic contraction time, when measured echocardi- ographically, is slightly different from that determined according to the conventional hemodynamic definition. The start of isovolumic contraction may be considered to be either the onset of right ventricular pressure up- stroke or the moment of tricuspid valve closure. In pa- tients with normal sinus rhythm, the tricuspid valve opens and then starts to close after atria1 systole. The

PAedp h Hs)

> 18

5 18

1 18

10 13

J

5 25 > 25

ICT (ms)

FlGURE 4. The double dichotomy model relating isovolumic contraction time (KIT) to pulmonary arterial end-diastolic oressure (PAedo): numbers of patients are seen in each quadrant. Fish& p value again& positive association = 0.005.

August lgg0 The American Journal of CARDIOLOGY Volume 46 275

ASSESSMENT OF PULMONARY HYPERTENSION-MILLS ET AL.

rapid closing motion imparted by the onset of ventric- ular contraction is not generally seen. However, in pa- tients with atria1 fibrillation, the onset of ventricular contraction is refl e&d in the tricuspid valve echogram by a rapid closing motion after a pause of approximately 25 ms.s Thus, the moment of tricuspid valve closure can more readily be recorded than the onset of right ven- tricular contraction and we have therefore elected to use this event to define the onset of isovolumic contrac- tion.

The end of isovolumic contraction is marked by the opening of the pulmonary valve. We have found that the moment of initial cusp separation cannot be regularly recorded echocardiographically and is seen only occa- sionally in patients with dilatation of the pulmonary artery.‘O It has been suggested that initial pulmonary valve opening can be estimated by the point at which the echogram of the valve cusp thins.5 However, because thinning is a gradual process, we found this method to be subject to the opinion of the observer and therefore we chose the point of full opening of the pulmonary valve to mark the end of isovolumic contraction. An inevitable disadvantage of this definition is that varia- tions in the rate of opening of the pulmonary cusps will affect echocardiographic isovolumic contraction time. Recent experimental studiesll suggest that there is a complex relation between rate of opening of the pul- monary cusps and the individual component.s of the right heart hemodynamics.

The use of two transducers simultaneously in a system of dual echocardiography permits direct measurement of the interval between the tricuspid C point and full opening of the pulmonary valve in the same cardiac cycle. In view of the potentially critical effect of brief differences in temporal measurements, this method has distinct advantages over sequential

measurements of the interval from the Q wave in the electrocardiogram to the respective valvular events with subtraction as a second step in arriving at the right ventricular isovolumic contraction time.

Clinical value of the metbsd: With these factors in mind we examined the relation between right ventric- ular isovolumic contraction time measured directly from the movements of the tricuspid and pulmonary valves and pulmonary arterial end-diastolic pressure. Our observations confirm those of Curtiss et a1.,3 who, in measuring right ventricular isovolumic contraction time from hemodynamic data, found that the relation be- tween the two variables is not linear. In particular, a long isovolumic contraction time may be found with both elevated and normal pulmonary arterial pressures and the 95 percent confidence limits for predicting pulmo- nary arterial pressure are too great for the method to be of clinical value. These findings cannot be accounted for either by the effect of heart rate or by the postulation that right ventricular isovolumic contraction time would be a better predictor of right ventricular developed pressure. However, the method may be of limited clin- ical use in that a right ventricular isovolumic contraction time of less than 25 ms was found only with a normal pulmonary arterial pressure. Unfortunately, in patients with chronic lung disease, in whom it would be partic- ularly helpful to know the pulmonary arterial pressure, the method has limited application because of the dif- ficulties in visualizing the right-sided valves. Therefore, in view of both the wide range of pressures occurring with right ventricular isovolumic contraction times of longer duration and the technical problems associated with the method, the echocardiographic estimation of right ventricular systolic time intervals cannot be rec- ommended as a routine method for the prediction of pulmonary arterial pressure in adults.

References

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2. Mlllo P, Leech G, Leatham A, Glnks W. Non-invasive evaluation pulmonary/systemic resistance ratios from echocardiographic of pulmonary artery end-diastolic pressure (abstr). Circulation systolic time intervals in young patiits with congenital or acquired 1975;52:Suppl ll:ll-50. heart disease. Am J Cardiol 1978;42:810-16.

3. Curtlss El, Reddy PS, O’Toele JD, Shaver JA. Alterations 01 right 8. Mills PG, Chamusco RF, Moos S, Cralge E. Echophonocardi- ventricular systolic time intervals by chronic pressure and volume ographic studies of the contribution of the atrioventricular valves overloading. Circulation 1976;53:997-1003. to the first heart sound. Circulation 1976;54:944-51.

4. Hfrscbfefd S, Meyer R, Sphwartz DC, Korfhagen J, Kaplan S. The 9. Grossman W. Cardiac Catheterization and Angfography. Phila- echocamiographic assessment of pulmonary artery pressure and delphia: Lea 8 Febiger, 1974235-50. pulmonary resistance. Circulation 1975;52:642-50. 10. Mills PG. Brocfie 6, Molaurln L, Sohall S, Crafge E. Echocardio-

5. Rtggs T, HfrsoMeM S, Borkaf 0. Knoke J, Lfebman J. Assessment graphic and hemodynamlc relationships of ejection sounds. Cir- of the pulmonary vascular bed by echocardiographic right ven- culatlon 1977;56:430-6. tricular systolic time intervals. Circulation 1978;57:939-47. 11. Kcwbw RE, MartIns JB, Bamee R, Manuel WJ, Maxlmov M. Effects

6. Johnson GL, Meyer RA, Kerfhagen J, Schwartz DC, Kaplan S. of acute hemodynamic alteratlons on pulmonic valve motion. Echocardlographic assessment of pulmonary arterial pressure in Circulation 1979;60:1074-81.

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