Peak Left Ventricular Systolic Pressure/End-Systolic Volume Ratio: A Sensitive Detector of Left Ventricular Disease
THASANA STANLEY JAMES
NIVATPUMIN. KATZ, SCHEUER,
Bronx, New York
From the Division of Cardiology, Department of Medicine, Montefiore Hospital and Medical Center, Albert Einstein College of Medicine, Yeshiva University, Bronx, New York. Manuscript received September 5. 1978; revised manuscript received December 20, 1978, accepted December 20, 1978. Address for reprints: Thasana Nivatpumin, MD, FACC, Division of Cardii, Montefbre Hosphal and Mediil Center, 111 East 210th Street, Bronx, New York 10467.
The purpose of this study was to evaluate peak pressure/systolic volume ratio as a detector of cardiac disease. To validate that tracings obtained through fluid-filled catheters were accurate for this purpose, In 35 patients left ventricular pressure-volume loops were constructed from tracings recorded with a micromanometer-tipped angiographic catheter. Comparisons were made between the peak ratio of left ventricular pressure to volume ( Emax)using the micromanometer-tipped angiographic catheter and the ratio between peak left ventricular pressure before anglography and end-systolic volume during angiography (peak pressure/systolic volume ratio) using the fluid-filled lumen of the same catheter. The relations of E,,, and that of peak pressure/systolic volume ratio to ejection fraction were similar and curvilinear. Peak pressure/systolic volume ratio was approximately 10 percent higher than Emsx, with a correlation coefficient between 0.99 of the two ratios. Therefore, peak pressure/ systolic volume ratio, which is easily obtained in clinical practice, can be used instead of E,,,. Retrospective analysis of the peak pressure/systolic volume ratio and ejection fraction was made from routine diagnostic catheterization data obtained uslng fluid-filled catheters in 115 subjects, of whom 17 were normal, 60 had coronary artery disease without asynergy, 23 had aortic valve disease and 15 had mitral valve disease. In subjects wlth a normal ejection fraction (more than 60 percent) the peak pressure/systolic volume ratio separated those groups with a diseased heart from those with a normal heart. Those with a diseased heart had a greater end-systolic volume than normal subjects. Thus, the peak pressure/systolic volume ratio is more sensitive than ejection fraction in detecting subtle changes in myocardial function in human beings.
Studies of isolated heart muscle reveal that during isotonic contraction the peak force generated for any given preload approximates the force generated by an isometric contraction at the same length. The relation of force to initial length appears nearly linear in the physiologic range.‘-:< In the isolated, supported, isovolumically contracting canine left ventricle, pressures generated from different initial volumes also fall along a straight line. Furthermore, in ejecting hearts, the ventricular pressure at end-systole falls along the same isovolumic pressure line.4 The peak ratio of ventricular pressure to volume ( E,,,), which occurs near the end of systole in isolated dog hearts, appears to be independent of afterload and affected minimally by preloads and thus can be used as an index of contractility. Published studies6 have suggested the usefulness of this measurement in human beings. The ejection fraction, which is the ratio of stroke volume to end-diastolic volume, has been useful for sequentially following up ventricular pump function as well as for predicting the outcome of cardiac surgery.7 However, diseased hearts can have an ejection fraction within the normal range. It is possible that E,,,
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or an end-systolic pressure/volume ratio might prove to be more sensitive than ejection fraction for detecting abnormalities in those hearts. The peak systolic pressure/end-systolic volume ratio should be similar to E,,, because peak systolic pressure and the ventricular pressure when ejection ceases are virtually identica1.s The purpose of this investigation was to study the sensitivity of the end-systolic ventricular pressure/ volume relation to determine whether this ratio could separate diseased from normal hearts more clearly than the ejection fraction. To simplify the measurement, we validated that the maximal value for the ratio of left ventricular pressure and volume (E,,,) during systole, which was determined using intracardiac pressure measurements during ventriculography, was similar to the ratio between peak left ventricular pressure measured just before angiography and end-systolic volume measured during angiography (peak pressure/systolic volume ratio). It was then demonstrated that peak pressure/systolic volume ratio was more effective than ejection fraction in separating groups of patients with heart disease from normal subjects. In this study E,,, was not corrected for zero pressure.4 Methods Procedure: After giving fully informed consent, 35 patients underwent left heart catheterization by way of a femoral arterial puncture using a no. 7F PC 471 Millar micromanometer-tipped angiographic catheter (Mikro-Tip Transducer, Millar Instruments, Inc., Houston, Texas). The transducer, which was first submerged in a lukewarm heparinized 5 per-
L F ‘I.
cent glucose solution for balancing and calibration, was connected to a Millar model TC 160 transducer control unit and an Electronics for Medicine pressure amplifier, model V2203. The fluid-filled lumen of the PC 471 catheter was connected with a Statham P23db transducer and an Electronics for Medicine pressure amplifier, model V2203. The Mikro-Tip and P23db transducers were calibrated, using a mercury manometer, to have the same sensitivity. Using a Phillips cesium iodide 9 inch image (23 cm) intensifier, cineventriculography at 50 frames/set was performed in the 30’ right anterior oblique view using Renografin-7@ dye (40 to 45 ml) injected at 36.3 kg/cm2 at 12 to 15 ml/set. In some patients a second angiogram was performed after sublingual nitroglycerin. During cineventriculography, left ventricular pressure and each tine frame number were recorded on photographic paper at 100 mm/set using 0.02 second time lines (Electronics for Medicine VR 12 multichannel recorder). The pressure tracing and each tine frame number were also recorded on the tine film (Electronics for Medicine model V4290) for each angiographic frame. In these 35 patients peak systolic pressure was recorded through the fluid-filled lumen of the Millar PC 471 catheter immediately before angiography, and it averaged 0.7 percent higher than the peak ventricular pressure recorded during angiography using the Mikro-Tip transducer. This measured difference was not statistically significant. The pressure values before angiography were 125 f 42 mm Hg (mean f standard deviation) and 126 f 40 for peak pressure during angiography. Measurements: Frame by frame ventricular volumes were determined by the area-length method with the aid of a light-pen tracer (Conrac) and an Electronics for Medicine computer system, model CLC-1, VVC mode.9 After identifying the tine frame number from the pressure recording, the ventricular pressure corresponding to the particular tine frame volume was measured and the ventricular pressurevolume loop constructed. In these hearts we calculated the ratio of peak left ventricular pressure before ventriculography to end-systolic volume (peak pressure/systolic volume ratio), the highest value for the ratio of ventricular pressure to systolic volume (E,,,) during ventriculography and the ejection fraction. Retrospective analyses: An additional retrospective analysis of peak pressure/systolic volume ratio and ejection fraction was carried out in three groups of patients from our catheterization laboratory. The ventricular pressures were determined from the fluid-filled catheters. The groups consisted of 60 patients with coronary artery disease, 23 patients with aortic regurgitation or aortic stenosis plus regurgitation and 15 patients with mitral valve disease. The control subjects consisted of 17 patients who had a normal electrocardiogram, normal left ventricular end-diastolic pressure, normal coronary arteriogram and normal ejection fraction. Patients who had ventricular dyskinesia or severe hypokinesia were excluded from all analyses. Comparisons between individual groups were made using a Student’s t test. Results
VOLUME ml FIGURE 1. The left ventricular pressure/volume relation in one patient with three different loading conditions-the control state and after administration of methoxamine (METHOX) and nitroglycerin (NTG). E F = ejection fraction; E. MAX = peak ratio of ventricular pressure to volume.
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Figure 1 shows representative pressure-volume loops from one normal subject. Three ventriculograms were obtained at different levels of preload and afterload. Methoxamine was used to increase and nitroglycerin to decrease preload and afterload. In this patient the peak left ventricular systolic pressures during the control state and after nitroglycerin were slightly higher than the end-systolic ventricular pressure. After methoxa-
ratio may be more practical for use in clinical practice. Peak pressure/systolic volume ratio versus ejection fraction: Figure 4 shows the plot of peak pressure/systolic volume ratio versus ejection fraction in the patients subjected to retrospective analysis. As predicted, the relation was curvilinear. When ejection fraction was less than 40 percent, the value for peak pressure/systolic volume ratio was less than 1. In patients with an ejection fraction greater than 60 percent, peak pressure/systolic volume ratio ranged between 1 and 5. Normal hearts tended to have higher values for peak pressure/systolic volume ratio. This basic relation was not altered when end-systolic volumes were normalized for body surface area. To test the sensitivity of peak pressure/systolic volume ratio in detecting disease, hearts with ejection fractions over 60 percent in each disease category were analyzed and compared with findings in the normal group. This sub group consisted of 17 normal subjects, 30 patients with coronary artery disease, 5 with mitral valve disease and 10 with aortic stenosis and aortic regurgitation, 5 of whom had predominant aortic stenosis and 5 who had predominant aortic regurgitation. In patients with aortic stenosis the mean gradient across the aortic valve was 38 f 20 mm Hg (standard deviation).
mine, peak and end-systolic pressures were the same. This figure demonstrates that the peak ratios of ventricular pressure to volume (E,,,) were relatively stable under the three different loads. Peak pressure/systolic volume ratio versus Emax: Peak systolic pressure with the fluid-filled catheter just before angiography averaged 111 f 4 mm Hg and the end-systolic pressure during angiography was 103 f 4 (mean f standard error) (P >0.05; no. = 50). This finding suggests that the peak pressure/systolic volume ratio should be close to E,,,. Figure 2 shows the values for the peak pressure/systolic volume ratio compared with E,,, in 50 examinations. The relation is positive and linear, with a correlation coefficient of 0.99. The value of peak pressure/systolic volume ratio is approximately 10 percent higher than E,,,. Figure 3 shows both E,,, and the peak pressure/ systolic volume ratio plotted against ejection fraction. The two curves are similar. When ejection fraction is within the normal range of greater than 60 percent, E,,, and peak pressure/systolic volume ratio vary widely. Therefore, similar information can be derived from the peak pressure/systolic volume ratio and E,,,. To obtain E max in human hearts a high fidelity catheter-tipped micromanometer angiographic catheter or two catheters are necessary as well as construction of the pressurevolume loop. Therefore, peak pressure/systolic volume
% f P 4.0 N
r =o.aa w 2.0
FIGURE 2. Relationof peak left ventricular systolic pressure/end-systolic volume (PLVSPIESV) ratio to E,x in a group of 50 patients. N = number of patients; r = correlation coefficient.
= 0.07 +l.ll
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FIGURE 3. Relationof ejection fraction (E F) to E,,
Figure 5 shows the similarity of the ejection fraction in each patient category. Peak pressure/systolic volume ratio was significantly higher in the normal subjects than in those with a diseased heart (P 4 &
CAD AVD MVD
: NL CAD AVD MVD
FIGURE 5. Ejection fraction (E F) and peak left ventricular systolic pressure/end-systolic volume (PLVSPIESV) ratio in patients with a normal heart (NL), coronary artery disease (CAD), aortic valve disease (AVD) and mitral valvular disease (MVD). Results are mean f SE. Numbers in the bars denote number of patients.
volume (E,,,), which is thought to be an index of contractility.4-6J0 Our study shows that the peak systolic pressure just before angiography is not significantly different from the peak systolic pressure during angiography and is similar to the pressure at the time ejection of blood ceases, that is, when the systolic volume is minimal. This finding is similar to those of Rushmer and West in dogs.s Also E,,, and the peak pressure/ systolic volume ratio correlate very closely, the latter being 10 percent higher then E,,,. Therefore, data from a routine catheterization can be used for this measurement. The assumption that E,,, can be used as an index of contractility is based on the work of Suga and Sagawa and their co-workers4~5J0 demonstrating that this index is relatively independent of preload and afterload in the isolated dog heart, yet is sensitive to change in the contractile state. Grossman et aL6 recently reported that the end-systolic pressure/volume relation is sensitive to inotropic interventions in human hearts. Our findings suggest that it is insensitive to preload and afterload in human subjects. However, further validation of these findings need to be carried out. One potential drawback of both the peak pressure/ systolic volume ratio and the E,,, measurement in human hearts is that the accuracy of measuring endsystolic volume is uncertain. At this phase of the cardiac cycle, the ventricular geometry deviates most from the ellipsoidal assumption, and the contrast at the bloodwall interface may not be sharp. Nevertheless, this same error is present in other angiographic evaluations of ventricular function such as ejection fraction and analysis of segmental shortening. Our finding that the relation of E,,, to ejection fraction in human beings is curvilinear agrees with the theoretical model proposed by Sagawa et al.1° in which
NL CAD AVD MVD
FIGURE 6. Peak left ventricular systolic pressure (PLVSP) and endsystolic volume (ESV) in normal subjects and patients with coronary artery disease (CAD), aortic valve disease (AVD) and mitral valve disease (MVD).
ejection fraction is a complex function of E,,,, endsystolic pressure and end-diastolic volume. Ejection fraction is preload- and afterload-dependent.lcJ1 Thus, it is predictable that ejection fraction would not detect subtle changes in myocardial contractile state and that there might be a high degree of overlap between values in diseased and normal hearts. Because E,,, and peak pressure/systolic volume ratio are relatively independent of load, they might logically be more sensitive to such subtle changes in contractility. Clinical implications: The depressed peak pressure/systolic volume ratio in diseased hearts with a normal ejection fraction was found to be largely due to increased end-systolic volume. Grossman et al.” also noted that diseased hearts tended to have a larger end-systolic volume. Patients with pure aortic stenosis also might have higher values for peak pressure/systolic volume ratio than normal subjects, but we did not evaluate that condition in our study. Because patients with coronary disease and abnormal wall motion (asynergy or dyskinesia) were excluded from our study, the application of the peak pressure/systolic volume ratio to this group of patients remains to be investigated. Our study demonstrates increased sensitivity for the peak pressure/systolic volume ratio in detecting heart disease in patients other than those with pure aortic stenosis. The significance of this abnormality relative to the prognostic power of ejection fraction is not known. Also, whether sequential changes in peak pressure/systolic volume ratio will be useful in monitoring the course of patients with heart disease remains to be evaluated. Acknowledgment We acknowledge the secretarial skills of Robin Orlansky.
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References 1. Brutsaert DL, Sonnenbiick EH: Cardiac muscle mechanics in the evaluation of myocardial contractility and pump functions: problems, concepts and directions. Prog Cardiovasc Dis 16:337-361. 1973 2. Downing SE, Sonnenbiick EH: Cardiac muscle mechanics and ventricular performance: force and time parameters. Am J Physiol 207:704-715, 1964 3. Taylor RR: Active length-tension relations in isometric, afterload and isotonic contractions of cat papillary muscle. Circ Res 26: 279-266, 1970 4. Suga H, Sagawa K: Instantaneous pressure-volume relationships and their ratio in the excised, supported canine left ventricle. Circ Res 35:117-126, 1974 5. Suga H, Sagawa K, Shonkas AA: Load independence of the instantaneous pressure-volume ratio of the canine left ventricle and effects of epinephrine and heart rate on the ratio. Circ Res 32: 314-322, 1973 6. Grossman W, Braunwaid E, Mann T, McLaurin LP, Green LH:
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Contractile state of the left ventricle in man as evaluated from end-systolic pressure-volume relation. Circulation 56:645-652, 1977 Cohn PF: Left ventricular ejection fraction as a prognostic guide in surgical treatment of coronary and valvular heart disease. Am J Cardioi 34:136-141. 1974 Rushmer RF, West TC: Role of autonomic hormones on left ventricular performance continuously analyzed by electronic computers, Circ Res 5:240-246, 1957 Rackiey CE: Quantitative evaluation of left ventricular function by radiographic techniques. Circulation 54:862-879, 1976 Sagawa K, Suga H, Shoukas AA, Bakaiar KM: End-systolic pressure/volume ratio: a new index of ventricular contractility. Am J Cardiol 40:748-753, 1977 Mitchell JH, Wlidenthai K, Muiiins CB: Geometrical studies of the left ventricle utilizing biplane cinefiuorography. Fed Proc 28: 1334-1343, 1969