Left ventricular end-systolic pressure-volume relation

Left Ventricular End-Systolic Pressure-Volume Relation A Combined Radionuclide and Hemodynamic Study

ABDULMASSIH

S. ISKANDRIAN, MD, A-HAMID HAKKI, MD, CHARLES E. BEMIS, MD,

SALLY A. KANE, RN, BARBARA BOSTON, RN, and ANGELO AMENTA, RT

This study examines the effect of increasing heart rate by atrial pacing on the left ventricular endsystolic pressure-volume relation and determines whether peak pressure can be used instead of end-systolic pressure. Measurements were made of cardiac output (by thermodilution), pulmonary arterial pressure, ejection fraction (by radionuclide angiography), and aortic pressure (by intraarterial catheter). End-systolic pressure was measured at the dicrotic notch. The end-diastolic and end-systolic volumes were determined from the ejection fraction and cardiac output. There was excellent correlation in pressure-volume relation determined by peak pressure and end-systolic pressure (r = 0.95). In 8 normal subjects there was <5 % change in ejection fraction, a decrease in end-systolic volume, 230 % increase in end-systolic pressure/

end-systolic volume, and no change in pulmonary arterial pressure with pacing. Of 20 patients with coronary artery disease, 9 patients had 25% decrease in ejection fraction, 8 had an increase in end-systolic volume, and 14 had <30 % increase in end-systolic pressure/end-systolic volume with pacing (p <0.05). Thus (1) peak systolic pressure can be used reliably instead of end-systolic pressure; (2) atrial pacing has a positive inotropic effect in normal subjects-the minimal increase (30%) in end-systolic pressure/end-systolic volume is similar to the increase (35 % ) reported during exercise; (3) abnormal changes in end-systolic pressure/end-systolic volume in coronary artery disease are more common than changes in either ejection fraction or end-systolic volume with atrial pacing.

Several studies have used radionuclide ventriculography at rest and during exercise to evaluate left ventricular

pressure-volume relation and determines whether peak pressure can be used instead of end-systolic pressure.

(LV) function.‘-s

Atrial

pacing

has also frequently

been

Methods

used to induce myocardial ischemia.4-‘7 In experimental animals, the isolated left ventricle shows a linear endsystolic pressure-volume relation that is not dependent on the preload. l8 The slope of this relation is determined by the contractile state and is increased by positive inotropic interventions 18,1gRecently, radionuclide studies have used the pressure-volume relations as a means of assessing LV function.’ In these studies, peak pressure was used instead of end-systolic pressure, as was origithe effects of nally suggested. ls This study examines increasing heart rate by atria1 pacing on the end-systolic

The patient population

consisted of 8 normal subjects and

20 patients with coronary artery disease (CAD). The normal subjects (6 men and 2 women; age range 37 to 67 years, mean 37) had normal coronary angiograms. The patients with CAD had stable angina pectoris and were found (by coronary arteriography) to have 270% diameter narrowing of 1 vessel (9 patients), 2 vessels (6 patients), or 3 vessels (5 patients). There were 17 men and 3 women, with an age range of 38 to 73 years (mean 55). Nitrates were withheld for at least 2 hours before the study but propranolol, which was prescribed for 12 patients, was not discontinued. There were no complications. The pacing studies were performed with the patient in the supine position. Three catheters were inserted percutaneously with the patient under local anesthesia with lidocaine. First, a 6Fr Gorlin catheter or a 6Fr NBIH catheter was inserted by way of the left antecubital vein and positioned by means of fluoroscopy in the coronary sinus. This catheter was used for pacing. Second, a 7Fr triple-lumen balloon-tipped thermodilution catheter was inserted by way of a femoral vein and

From the Likoff Cardiovascular Institute of Hahnemann University and Hospital, Philadelphia, Pennsylvania. Manuscript received September 30, 1982; revised manuscript received December 13, 1982, accepted December 14. 1982. Address for reprints: Abdulmassih S. Iskandrian, MD, Likoff Cardiovascular Institute. Hahnemann University and Hospital, 230 North Broad Street, Philadelphia, Pennsylvania 19102.

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END-SYSTOLIC

PRESSURE-VOLUME

RELATION

advanced into the pulmonary artery. This catheter was used to measure pulmonary artery pressure and cardiac output. Third, a short (6 inch) 6Fr Teflon@ catheter was inserted into a femoral artery to monitor systemic pressure. After the catheters were in position, we obtained baseline measurements of the pulmonary artery and the aortic pressures. End-systolic pressure was measured at the level of the dicrotic notch. Pacing was then begun with gradual increments of heart rate by 10 beats/min. Pacing was continued for a minimum of 2 minutes to assure hemodynamic stability, and then the measurements were repeated. In the first 10 patients with CAD (Group I), pacing was done at 1 rate. The endpoints of pacing in these patients were the development of Wenckebach atrioventricular block, or severe angina pectoris, or at least 2 mm S-T segment depression. In the last 10 patients, pacing studies were performed at 2 different rates (Group II). During the first study, the heart rate was increased by at least 20 beats/min above the control rate; during the second pacing study, the pacing rate was determined by 1 or more of the pacing endpoints described above. Radionuclide angiograms were obtained in the control state and during pacing. All radionuclide angiography studies were performed in the anterior projection by the first-pass method with a computerized multicrystal camera (Baird-Atomic System-77). Radionuclide angiograms were processed to measure LV ejection fraction, end-diastolic volume, and end-systolic volume using the computer software incorporated into the Baird-Atomic System.20J1 The reliability and reproducibility of the method have been previously reported.2J,20 The LV end-diastolic volume and end-systolic volume were derived as follows by an independent method using the cardiac output determined by the thermodilution method, and the ejection fraction determined by the radionuclide angiogram: Stroke volume (milliliters by thermodilution) = cardiac output (milliliters/minute by thermodilution)/heart rate (beats/ minute) (Equation 1). This stroke volume was then used in the next 2 equations: End-diastolic volume (milliliters) = stroke volume (milliliters)/ejection fraction (%) (Equation 2); and End-systolic volume (milliliters) = end-diastolic volume (milliliters) - stroke volume (milliliters) (Equation 3). Statistical analysis: The results are expressed as mean f standard deviation (SD) when appropriate. Differences between the rest and pacing studies were analyzed by the paired t test or analysis of variance. Comparison of volume measurements by different methods was performed by linear correlation analysis.

Results Clinical, electrocardiographic, and hemodynamic changes during pacing: No normal subject had angina or S-T depression during pacing. In 11 patients (55%) with CAD, angina or S-T depression (or both) developed during pacing. The hemodynamic data in normal subjects and in patients with CAD at rest and during pacing are shown in Table I. Changes in ventricular function and volumes during pacing: In normal subjects, there were significant decreases in end-diastolic and end-systolic volumes during pacing (Fig. 1 and 2), while the change in the ejection fraction was 0 to 4% (Fig. 3). In the 10 patients with CAD who had 1 pacing study (Group I), 2 patients had 25% decrease in ejection fraction with pacing while among the remaining 10 patients who had studies at, 2 pacing rates (Group II), 8 patients showed 25% decrease in the ejection fraction at the final pacing rate compared

April 1983

THE AMERICAN JOURNAL OF CARDIOLOGY

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1. Changes in end-diastolic volume index during pacing in normal subjects and patients with coronary artery disease. C = control: CAD = coronary artery disease; P = pacing. Means f standard deviations are shown.

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FIGURE 3. Changes in ejection fraction during pacing. C = control; CAD = coronary artery disease; P = pacing. Means f standard deviations are shown.

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with measurements at the first pacing rate (Fig. 3). The end-systolic volume increased during pacing in 2 patients in Group I and in 4 patients in Group II (Fig. 2). The end-diastolic volume decreased during pacing in both groups (Fig. 1). The end-systolic pressure-volume relation was determined in the normal subjects and in patients with CAD by using either peak systolic pressure or end-systolic pressure. The correlation between peak pressure-to-end-systolic volume ratio and the endsystolic pressure-to-end-systolic volume ratio was excellent (r = 0.95) (Fig. 4). The end-systolic pressure to end-systolic volume ratio increased by 130% in normal subjects. On the other hand, 6 patients with CAD in Group I and 8 patients in Group II had <30% increase (Fig. 5). An abnormal increase in the end-systolic pressure/end-systolic volume ratio was more common than an abnormal response to the ejection fraction or an increase in end-systolic volume during pacing (70% versus 50% versus 30%, respectively) (p <0.05, change in end-systolic pressure to volume ratio compared with increase in end-systolic volume). An abnormal response of the ejection fraction to pacing was found in 4 of 9 patients with l-vessel disease

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and in 5 of 11 patients with multivessel disease (p = not significant [NS]). An abnormal change in end-systolic pressure-to-end-systolic volume ratio was found in 4 of 9 patients with l-vessel disease and in 10 of 11 patients with multivessel disease (p <0.05). In evaluating the results in relation to resting LV function, an abnormal ejection fraction response was noted in 3 of 6 patients with normal function and in 6 of 14 patients with abnormal function, and abnormal pressure-volume relation was noted in 4 of 6 patients with normal function and in 10 of 14 patients with abnormal function (p = NS). An abnormal response in ejection fraction was noted in 3 of 8 patients not receiving propranolol therapy and in 6 of 12 patients receiving propranolol therapy (p = NS), and an abnormal change in pressure-volume relation was noted in 5 patients not receiving propran0101 therapy and in 9 patients receiving such therapy (p = NS). The mean normalized systolic ejection rate (ejection fraction/ejection time) decreased in the normal subjects (0.32 f 0.03 control versus 0.26 f 0.02 s-l pacing, p
END-SYSTOLIC PRESSURE-VOLUME RELATION

1060

TABLE

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EDV = enddiastolic volume (milliliters); ESV = end-systolic volume (milliliters); RNA = radionuclide angiography.

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20

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4.0

Correlation Between Control and PacingDerived Volumes With Similar Measurements Obtained From Thermodllution Stroke Volume and Radionuclide Ejection Fraction

Normal subjects EDV (using Equation 2) = 25 -I- 0.68 X EDV (by RNA), r = 0.80 ESV (usina Eauation 3) = 4.1 -I 1.0 X ESV (bv RNA). r = 0.86 Patients withcoronary artery disease . . ‘. EDV (using Equation 2) = 43 + 0.62 X EDV (by RNA), r = 0.80 ESV (using Equation 3) = 18 -I- 0.74 X ESV (by RNA), r = 0.85

0 NL, Control . NL, Pacing 0 CAD, Control - CAD, Pacing

30

II

landmark study, Dwyer,5 cognizant of this problem, obtained the ejection fraction from the end-diastolic volume measured by contrast angiography and the stroke volume measured by the dye dilution method. Ten patients with CAD were studied by pacing. Dwyer found that end-diastolic volume decreased in 9 patients and the ejection fraction decreased in 8 patients. Other investigators have similarly shown a decrease in ejection fraction during pacing-induced ischemia.6J5,1s Our results showed that atria1 pacing resulted in a significant decrease in end-diastolic volume in patients with CAD (Table I, Fig. 1). The decrease in end-diastolic volume was a continuous one, as demonstrated in 10 patients who had measurements at 2 pacing rates. In some patients there was a marked elevation in pulmonary artery pressure despite a decrease in end-diastolic volume during pacing-induced ischemia, indicating an alteration in LV compliance as reported by other investigators.22s23 Our results in normal subjects showed no significant change in the ejection fraction despite a decrease in end-diastolic volume during pacing (Fig. 1 and 3). The end-systolic pressure-to-end-systolic volume ratio increased in all. These results may suggest increased inotropicity with pacing, and therefore they support the findings of other investigators.17J4-26 There was excellent correlation between peak systolic pressure-toend-systolic volume ratio and the end-systolic pressure-to-end-systolic volume ratio (r = 0.95) (Fig. 4), thus indicating that the peak pressure can be used reliably instead of the end-systolic pressure. Although the dierotic pressure and the end-systolic pressure are not identical, they are usually very similar.27 We also found

m ‘50

ESP/ESV Ratio FIGURE 4. Correlation between the peak systolic pressure to endsystolic volume (PSP/ESV) ratio and the end-systolic pressure to end-systolic volume (ESP/ESV) ratio. CAD = patients with coronary artery disease.

0.38 control versus 1.69 f 0.47 s-l pacing, p <0.05). All 8 normal subjects had a decrease while 14 of 20 patients with CAD had an increase (p <0.02). Finally, we found a good correlation between radionuclide derived end-diastolic and end-systolic LV volumes and similar volumes determined from thermodilution stroke volume and radionuclide ejection fraction (Equations 2 and 3) (Table II). Discussion We evaluated ventricular function by means of atrial pacing in normal subjects and in patients with CAD. We measured LV volumes by 2 methods: first, by radionuelide angiography, and second, by using the stroke volume derived from the thermodilution cardiac output and the ejection fraction derived from the radionuclide angiogram. This second method is not entirely independent from the first, but it is based on data derived by 2 reliable methods. This report, therefore, combines the best available methods for accurate measurement of ventricular volumes and has advantage over volume measurement by contrast angiography, since segmental wall-motion abnormalities during ischemia and changes in the shape of the ventricle may affect the reliability of geometric methods for volume measurements. In a

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FIGURE 5. Changes in end-systolic Pressure to endsystolic volume &SP/ESV) ratio during pacing. C = control; CAD = coronary artery disease; P = pacing. Means f standard deviations are shown.

April 1983

that LV end-diastolic and end-systolic volumes can be reliably measured noninvasively by radionuclide angiography not only at rest but also during pacing-induced ischemia. These findings are important since the LV end-systolic pressure-volume relation can be determined by noninvasive measurements of the peak systemic pressure (by the cuff method) and the end-systolic volume (by radionuclide angiography). The minimal increase (30%) in the end-systolic pressure-to-endsystolic volume ratio in the normal subjects during pacing is similar to the minimal increase (35%) reported during exercise.l Finally, an abnormal increase in end-systolic pressure-to-end-systolic volume ratio was seen in 14 patients (70%) with CAD, while only 6 patients (30%) had an increase in end-systolic volume (p <0.05) and 10 patients (50%) had 25% decrease in the ejection fraction with pacing. The normal subjects had a decrease in the mean normalized systolic ejection rate with pacing while patients with CAD had an increase. Since most patients had abnormal resting ejection fractions, the pacing studies were not done to diagnose CAD but rather to evaluate the pressure-volume changes. Thus, peak pressure can be used reliably instead of end-systolic pressure; pacing has a positive inotropic effect in normal subjects; the minimal increase (30%) in end-systolic pressure-to-end-systolic volume ratio is similar to the increase (35%) reported during exercise; and abnormal changes in end-systolic pressure-volume relation are more frequent than changes in the ejection fraction or end-systolic volume during pacing. Acknowledgment: We thank Wanda Klein for secretarial assistance and Edith Schwager for editorial assistance. References 1. Dehmer GJ, Lewis SE, Hillis LD, Corbett J, Parkey RW, WilIerson JT. Exercise-induced alterations in left ventricular volumes and the pressurevolume relationship: a sensitive indicator of left ventricular dysfunction in patients with coronary artery disease. Circulation 1981;63:1008-1018. 2. Rerych SK, Scholr PM, Newman GE, Sabidon Jr DE, Sones RH. Cardiac function at rest and during exercise in normals and in patients with cwonary heart disease: evaluation by radionuclide angiocardiography. Ann Surg 1978;303:1404-1416. 3. lskandrlan AS, Hakkl AH, Kane SA, Segal BL. Evaluation of left ventricular function bv radionuclide anoioqraphv: (1) comparison of radionuclide derived measurements in the detection bf coidnary heart disease and (2) effect of basal left ventricular function on exercise oerformance. J Cardiac Rehab. in press. 4. Sowton E, Balcon R, Cross D, Krick MH. Measurement of the angina1 threshold using atrial pacing: a new technique for the study of angina pec-

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toris. Cardiovasc Res 1967;1:301-307. 5. Dwyer EM. Left ventricular pressure-volume alterations and regional disorders of contraction during myocardial ischemia induced by atrial pacing. Circulation 1970;42:111 l-l 122. 6. Paslernac A, Gorlin R, Sonnenbllck EH, Haft JI, Kemp HG. Abnormalities of ventricular motion induced by atrial pacing in coronary artery disease. Circulation 1972;45:1195-1205. 7. Parker JO, Ledwlch JR, West RO, Case RB. Reversible cardiac failure during angina pectoris: hemodynamic effects of atrial pacing in coronary artery disease. Circulation 1969;39:745-753. 8. Parker JO, Chiong MA, West RO, Case RB. Sequential alterations in myocardial lactate metabolism, ST segments, left ventricular function during angina induced by atrial pacing. Circulation 1969;40: 113-131. 9. DeSanctls RW. Diagnostic and therapeutic uses of atrial pacing. Circulation 1971;43:748-761. 10. Bahler RC, Macleod CA. Atrial pacing and exercise in the evaluation of patients with angina pectoris. Circulation 1971;43:407-419, 11. O’Brien KP, Higgs LM, Glancy DL, Epstein SE. Hemodynamic accompaniments of angina: a comparison during angina induced by exercise and by atrial pacing. Circulation 1969;39:735-744. 12. Linharf JW. Myocardial function in coronary artery disease determined by atrial pacing. Circulation 1971;44:203-212, 13. Kelemen MH, Gillilan RE, Bouchard JR, Heppner RL, Warbasse JR. Diagnosis of obstructive coronary disease by maximal exercise and atrial pacing. Circulation 1973;48:1227-1233. 14. Ross J Jr, Linharl JW, Braunwald E. Effects of changing heart rate in man by electrical stimulation of the right atrium: studies at rest, during exercise and with isoproteronol. Circulation 1965;32:549-558. 15. Stone D, Dymond D, Elliott AT, Brltton KE, Spurrell RAJ, Banlm SO. Use of first-pass radionuclide ventriculography in assessment of wall motion abnormalities induced bv incremental atrial oacina with coronarv. artetv. disease. Br Heart J 1986;43:369-375. 16. Sltisky R, Watkins J, Peterson K, Karllner J. The response of left ventricular function and size to atrial pacing, volume loading and afterload stress in patients with coronary artery disease. Circulation 1981;83:864-870. 17. Hung J, Kelly DT, Hutton BF, Uther JB, Baird DK. Influence of heart rate and strial transport on left ventricular volume and function: relation to hemodvnamic chanaes orcxfuced bv_ suoraventricular tachvcardia. Am J Cardiol 198i;48:632-63-i. 18. Suga H, Sagawa K, Shoukas AA. Loud independence of the instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ Res 1973;32:314-321. 19. Mehmel HC, Stockins B, Ruffman K, Olshausen KV, Schuler G, Kubler W. The linearitv of the end-svstolic oressure-volume relationshio in man and its sensitiviiy for asses&g of l&I ventricular function. Circilation 1981; 63:1216-1222. 20. lskandrian AS, Hakki AH, Kane SA, Segal BL. Quantitative radionuclide angiography in assessment of hemodynamic changes during upright exercise: observations in normal subjects, patients with coronary artery disease and patients with aortic regurgitation. Am J Cardiol 1981;48;239246. 21. Dodge HT, Hay RE, Sandler H. An angiocardiographic method for directly determining left ventricular stroke volume in man. Circ Res 1982;ll: 739-745. 22. Mann T, Brodie BR, Grossman W, McLaurin LP. Effect of angina on the lefl ventricular diastolic pressure-volume relationship. Circulation 1977;55: 761-766. 23. Grossman W, McLaurin LP. Diastolic properties of the left ventricle. Ann Intern Med 1976;84:316-326. 24. Ricci D, Orlick A, Alderman E, lngels N, Daughters G, Kusnick C, ReRz 8, Stinson E. Role of tachycardia as an inotropic stimulus in man. J Clin Invest 1979;63:695-703. 25. DeMarla A, Neuman A, Schubarf P, Lee G, Mason D. Systematic correlation of cardiac chamber size and ventricular performance determined with echocardiography and alterations in heart rate in normal persons. Am J Cardiol 1979;43:1-9. 26. Mahler F, Yoran C, Ross J Jr. lnotropic effect of tachycardia and poststimulation potentiation in the conscious dog. Am J Physiol 1974;227: 569-575. 27. Grose R, Nivatpumin T, Katz S, Yipintsoi T, Scheuer J. Mechanism of nitroglycerin effect in vatvular aortic stenosis. Am J Cardiol 1979;44: 1371-1379.