Assessment of ventricular function by radionuclide angiography: applications and results.
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Biomedical subjects
Publications and source records attributed to M V Green.
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The calcium channel-blocking drugs verapamil, diltiazem, and nifedipine are being used with increasing frequency in patients with angina pectoris due to coronary artery disease. Although each of these agents possesses negative inotropic potential, their relative effects on myocardial function in relation to their vasodilator potencies are unknown. We understood to study this in 20 conscious dogs that had partial occlusions of their circumflex coronary arteries during therapy with placebo, verapamil, nifedipine, or diltiazem. Myocardial blood flow was measured by use of microspheres, and left ventricular function was measured by radionuclide angiography. Drug effects were compared at doses causing equal decreases in mean arterial pressure and coronary vascular resistance of nonischemic myocardium. Global ejection fraction and ejection fraction of the ischemic region were significantly decreased by verapamil (p less than .01) and increased by nifedipine (p less than .001); diltiazem caused no significant changes. Verapamil significantly increased peak diastolic filling rate (p less than .001); nifedipine also increased diastolic filling rate, but only at doses that markedly decreased mean arterial pressure and coronary vascular resistance. The effect of diltiazem on diastolic filling rate was not significantly different than placebo. For doses causing an equal decrease in mean arterial pressure, verapamil decreased heart rate (p less than .001), and diltiazem and nifedipine increased heart rate (p less than .001). We conclude that the relative potencies of these three calcium channel blocking agents on left ventricular systolic and diastolic function during myocardial ischemia are different when compared with their relative vasodilator potencies. These differences may have important clinical implications.
Preoperative left ventricular systolic function is an important predictor of postoperative prognosis in patients with aortic regurgitation. Although left ventricular dysfunction is reversible after aortic valve replacement to a greater extent in patients with good preoperative exercise capacity compared with patients with impaired exercise capacity, not all patients with preserved exercise capacity demonstrate improved left ventricular function after aortic valve replacement. To determine the influence of duration of preoperative left ventricular dysfunction on postoperative reversal of left ventricular dysfunction, we studied 37 patients with aortic regurgitation who preoperatively had left ventricular dysfunction, defined as subnormal echocardiographic fractional shortening (less than 29%), and good preoperative exercise capacity, defined as completion of stage I of the NIH treadmill protocol without limiting symptoms. Eight patients were asymptomatic. In 11 patients left ventricular dysfunction was documented 18 to 57 months preoperatively (prolonged); in 10 patients left ventricular dysfunction developed in an interval of 14 months or less preoperatively (brief); in 16 patients duration of left ventricular dysfunction was unknown. Patients with brief vs those with prolonged left ventricular dysfunction did not differ with respect to severity of preoperative symptoms or exercise tolerance, echocardiographically determined left ventricular dimensions or fractional shortening (25 +/- 3% [SD] vs 25 +/- 3%), or radionuclide angiographic ejection fraction (42 +/- 5% vs 42 +/- 5%).(ABSTRACT TRUNCATED AT 250 WORDS)
To characterize the role of cardiac function in septic shock, serial radionuclide cineangiographic and hemodynamic evaluations were done on 20 patients with documented septic shock. Although all patients had a normal or elevated cardiac index, 10 patients had moderate to severe depression of their ejection fraction with values below 0.40. Thirteen of twenty patients survived their episode. Paradoxically, 10 of 13 survivors, but none of the 7 nonsurvivors, had an initial ejection fraction less than 0.40 (p less than 0.005). The mean initial ejection fraction for the survivors was 0.32 +/- 0.04, and their mean end systolic and end diastolic ventricular volumes were substantially increased with a normal stroke volume. The survivors' serial scans showed a gradual return to normal ejection fraction and ventricular volume by 10 days after the onset of shock. Nonsurvivors had normal initial ejection fractions and ventricular volumes that did not change during serial studies.
Regional wall motion abnormalities are most often detected visually, and hence subjectively, in gated blood pool studies of the heart. Therefore, an automated method was developed to objectively assess regional left ventricular (LV) function. The method was tested in 26 normal volunteers and 29 patients with angiographically proved coronary artery disease. Fifteen patients with coronary artery disease had a normal LV ejection fraction (EF) at rest, and all had an abnormal EF response with exercise; 23 had visual regional wall motion abnormalities with rest or exercise. The left ventricle was divided into 28 sectors that radiated from the LV center of gravity, with 1 region at the LV center. A time-activity curve was generated for each sector and the EF and Fourier phase were computed from each curve. Rest and exercise sector EF versus sector number plots were superimposed and the area difference between these 2 curves was taken as an index of regional contraction. Similarly, an estimator of sector phase differences, obtained from the plot of phase versus sector number, was taken as an index of wall motion asynchrony. Analysis of the reliability of these 2 indexes suggests that this automated technique has at least the same efficiency as subjective evaluation of gated blood pool studies, but possesses the advantage of objectivity. The technique may also be useful in localizing regional defects and, perhaps, in detecting mild abnormalities not readily perceived visually.
Assessment of left ventricular function may be of value in patients with pressure-loaded, hypertrophied left ventricles for the purpose of characterizing such patients as to prognostic risk. To determine whether left ventricular function is in part independent of loading stresses in such patients, and to assess the effects of removal of loading factors, we have reviewed preliminary data in 60 patients with essential hypertension and in 26 patients with aortic stenosis who were studied with radionuclide cineangiography. Patients with hypertension manifested a poor but statistically significant direct relationship between systolic arterial pressure and left ventricular ejection fraction at rest, and a poor but significant inverse relationship between systolic pressure and the magnitude of change in ejection fraction from rest to exercise. However, a strong correlation existed between echocardiographic systolic fractional shortening and end-systolic wall stress at rest. Nonetheless, many patients with normal fractional shortening-end-systolic wall stress relationships had subnormal ejection fraction responses during exercise; the two patients with subnormal fractional shortening-end-systolic wall stress relationships at rest also had subnormal fractional shortening-end-systolic wall stress relationships during exercise. Arterial pressure alone was not predictive of these functional responses. These data suggest that hypertensive patients can be categorized on the basis of left ventricular function at rest and during exercise, independent of arterial pressure. Among patients with aortic stenosis, ejection fraction at rest averaged 67 percent before valve replacement (normal = 57 percent, p less than 0.01), and changed little after operation (71 percent, not significant). However, potential functional benefits of afterload reduction in the patient with the chronically pressure-loaded, hypertrophied left ventricle was suggested by results during exercise: before surgery the ejection fraction during exercise averaged 56 percent (normal = 71 percent, p less than 0.01), but after valve replacement it rose to 72 percent (not significant versus normal). Thus, our data in patients with aortic stenosis supplement our data in patients with hypertension, indicating that myocardial functional improvement can be achieved by unloading therapy in patients with long-standing left ventricular pressure-loading and hypertrophy.
Many patients with hypertrophic cardiomyopathy (HC) have impaired left ventricular (LV) rapid diastolic filling. To quantitate the contribution of atrial systole to LV filling, we used radionuclide angiography to study 30 normal volunteers and 42 patients with HC before and after oral administration of verapamil (320 to 560 mg/day). LV time-activity curves were constructed by combined forward and reverse gating from the R wave, and the onset of atrial systole was determined by the P-R interval. The percent of LV stroke volume filled during rapid diastolic filling and atrial systole was then computed. Peak LV filling rate during rapid diastolic filling was expressed in end-diastolic volume (EDV)/second. Peak rate of rapid diastolic filling was not different in normal patients and those with HC (3.3 +/- 0.6 versus 3.3 +/- 1.1 EDV/s) and was within the normal range in 34 patients with HC (81%). However, the contribution to LV filling volume by rapid diastolic filling was diminished in patients with HC (83 +/- 7% normal, 67 +/- 17% HC, p less than 0.001) and the contribution of atrial systole was increased (16 +/- 8% normal, 31 +/- 18% HC, p less than 0.001). LV filling volume during atrial systole was above the upper normal limit of 31% in 17 patients (40%), including 13 patients with a normal peak filling rate. After verapamil, peak filling rate increased (to 4.2 +/- 1.2 EDV/s, p less than 0.001), percent LV filling during rapid diastolic filling increased (to 83 +/- 7%, p less than 0.001), and percent LV filling during atrial systole decreased (to 16 +/- 9%, p less than 0.001). Percent LV filling volume during atrial systole was abnormal after verapamil in only 3 patients (7%). Hence, although the peak rate of rapid diastolic filling may be normal in patients with HC, the contribution to LV filling by rapid diastolic filling is reduced and that of atrial systole is thereby increased. Increased rate and magnitude of rapid diastolic filling during verapamil is associated with decrease and normalization of the contribution of atrial systole to LV filling. These data suggest that many patients with HC are at risk of hemodynamic decompensation with the onset of atrial fibrillation or other tachyarrhythmias and loss of the atrial contribution to LV filling. This risk may be reduced during verapamil therapy.
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To investigate the effects of verapamil on left ventricular systolic and diastolic function in patients with hypertrophic cardiomyopathy, we studied 14 patients at catheterization with a nonimaging scintillation probe before and after serial intravenous infusions of low-, medium-, and high-dose verapamil (total dose 0.17 to 0.72 mg/kg). Percent change in radionuclide stroke counts after verapamil correlated well with percent change in thermodilution stroke volume (r = .87), and changes in diastolic and systolic counts were used to assess relative changes in left ventricular volumes after verapamil. Verapamil produced dose-related increases in end-diastolic counts (19 +/- 9% increase; p less than .001), end-systolic counts (91 +/- 54% increase; p less than .001), and stroke counts (7 +/- 10% increase; p less than .02). This was associated with a decrease in ejection fraction (83 +/- 8% control, 73 +/- 10% verapamil; p less than .001) and, in the 10 patients with left ventricular outflow tract gradients, a reduction in gradient (62 +/- 27 mm Hg control, 32 +/- 35 mm Hg verapamil; p less than .01). The end-systolic pressure-volume relation was shifted downward and rightward in all patients, suggesting a negative inotropic effect. In 10 patients, left ventricular pressure-volume loops were constructed with simultaneous micromanometer pressure recordings and the radionuclide time-activity curve. In five patients, verapamil shifted the diastolic pressure-volume curve downward and rightward, demonstrating improved pressure-volume relations despite the negative inotropic effect, and also increased the peak rate of rapid diastolic filling. In the other five patients, the diastolic pressure-volume relation was unaltered by verapamil, and increased end-diastolic volumes occurred at higher end-diastolic pressures; in these patients, the peak rate of left ventricular diastolic filling was not changed by verapamil. The negative inotropic effects of intravenous verapamil are potentially beneficial in patients with hypertrophic cardiomyopathy by decreasing left ventricular contractile function and increasing left ventricular volume. Verapamil also enhances left ventricular diastolic filling and improves diastolic pressure-volume relations in some patients despite its negative inotropic effect.
Random fluctuations limit the accuracy of quantities derived from cardiac time-activity curves (TACs). To overcome this problem, TACs are often fitted with a truncated Fourier series giving rise to two sources of error: (a) the truncated series may not adequately describe the TAC shape, causing errors in parameters calculated from the fit: and (b) successive TACs acquired from the same subject under identical circumstances will fluctuate due to limited counts, causing the Fourier fits (and parameters derived from them) to fluctuate. These two errors, respectively, decrease and increase as the number of harmonics increases, suggesting the existence of a minimum in total error. This number of harmonics for minimum error (NHME) was calculated for each of six common parameters used to describe LV TACs. The "true" value of each parameter was determined from TACs of very high statistical precision. Poisson noise was added to simulate lower count rates. For low-count TACs, use of either a smaller or a larger number of harmonics resulted in significantly greater error. NHME was found to occur at two harmonics for the systolic parameters studied, regardless of the noise level present in the TAC. For diastolic parameters, however, NHME was a strong function of the noise present in the TAC, varying from three harmonics for noise levels typical of regional TACs, to five or six harmonics for high-count global TACs.
To determine the effects of verapamil on left ventricular (LV) systolic function and diastolic filling in patients with coronary artery disease (CAD), we performed gated radionuclide angiography at rest and during exercise in 16 symptomatic patients before and during oral verapamil therapy (480 mg/day). Twelve patients were also studied during oral propranolol (160--320 mg/day). LV ejection fraction at rest was normal in 13 patients, but abnormal diastolic filling at rest, defined as peak filling rate (PFR) less than 2.5 end-diastolic volumes (EDV)/sec or time to PFR greater than 180 msec, was present in 15. During verapamil, resting ejection fraction decreased (control 50 +/- 10% [+/- SD), verapamil 45 +/- 12%, p less than 0.005), but resting diastolic filling improved: PFR increased (control 1.9 +/- 0.6 EDV/sec, verapamil 2.3 +/- 0.9 ECV/sec, p less than 0.005) and time to PFR decreased (control 185 +/- 38 msec, verapamil 161 +/- 27 msec, p less than 0.05). Exercise ejection fraction did not change during verapamil (control 42 +/- 13%, verapamil 43 +/- 12%, NS), but exercise PFR increased (control 3.1 +/- 0.9 EDV/sec, verapamil 3.6 +/- 1.1 EDV/sec, p less than 0.05) and exercise time to PFR decreased (control 108 +/- 30 msec, verapamil 91 +/- 17 msec, p less than 0.05). In contrast, propranolol did not alter ejection fraction, PFR, or time to PFR at rest or during exercise. Thus, LV ejection fraction is decreased by verapamil at rest but is unchanged during exercise. While LV systolic function is not improved by verapamil, LV diastolic filling is enhanced by verapamil, both at rest and during exercise. These mechanisms may account in part for the symptomatic improvement in many patients during verapamil therapy.
Left ventricular (LV) diastolic filling is abnormal at rest in many patients with coronary artery disease (CAD), even in the presence of normal resting LV systolic function. To determine the effects of improved myocardial perfusion on impaired. LV diastolic filling, we studied 25 patients with one-vessel CAD by high-temporal-resolution radionuclide angiography before and after percutaneous transluminal coronary angioplasty (PTCA). No patient had ECG evidence of previous myocardial infarction. Despite normal regional and global LV systolic function at rest in all patents, LV diastolic filling was abnormal (peak LV filling rate [PFR] less than 2.5 end-diastolic volumes (EDV)/sec or time to PFR greater than 180 msec) in 17 of 25 patients. Twenty-three patients had abnormal LV systolic function during exercise. After successful PTCA, LV ejection fraction and heart rate at rest were unchanged, but LV ejection fraction during exercise increased, from 52 +/- 8% (+/- SD) to 63 +/- 5% (p less than 0.001). LV diastolic filling at rest improved: PFR increased from 2.3 +/- 0.6 to 2.8 +/- 0.5 EDV/sec (p less than 0.001) and time to PFR decreased from 181 +/- 22 to 160 +/- 18 msec (p less than 0.001). Thus, a reduction in exercise-induced LV systolic dysfunction after PTCA, reflecting a reduction in reversible ischemia, was associated with improved LV diastolic filling at rest. These data suggest that in many CAD patients with normal resting LV systolic function and without previous infarction, abnormalities of resting LV diastolic filling are not fixed, but appear to be reversible manifestations of impaired coronary flow.
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A method is described for characterizing functional maps by means of a frequency distribution function (DF) of pixels. The method makes use of a map of the standard deviation of the functional parameter. By use of this map the method (a) becomes less sensitive to imprecise definition of the organ borders, (b) compensates for random fluctuations in the functional map, and (most importantly) (c) permits spatial information to be included in the DF. This spatial information is included by performing spatial cluster weighting--a procedure that emphasizes regional dysfunction over global dysfunction. The method is illustrated by applying it to phase maps of the left ventricle. In this example, it is shown that analysis of the DF permits detection of regional abnormalities of LV wall motion and that an improvement in detectability is obtained with cluster weighting.
Abnormalities of left ventricular contraction in patients with mitral valve prolapse have suggested a myocardial factor in this disease. To determine systolic left ventricular function in mitral valve prolapse, technetium-99m gated equilibrium radionuclide cineangiography was performed in 47 patients with this diagnosis. In 39 patients without mitral regurgitation the average ejection fraction was normal at rest (average [+/- standard error of the mean] 57 +/- 3 percent, normal 57 +/- 1 percent, difference not significant) and exceeded the lower limits of normal in all but 1 patient, whose ejection fraction was 41 percent. However, ejection fraction during maximal exercise was lower for the group of patients with mitral prolapse without mitral regurgitation than for normal subjects (average 64 +/- 2 percent, normal 71 +/- 2 percent, p < 0.005). In eight patients with mitral prolapse and mitral regurgitation, the average ejection fraction was normal at rest but was diminished with exercise in comparison with both normal subjects and patients with mitral valve prolapse without mitral regurgitation. Chest pain, arrhythmia and the pattern or extent of mitral valve prolapse on echocardiography were not independently associated with impaired left ventricular functional reserve. We conclude that, although many patients with mitral valve prolapse have normal left ventricular function, there is a subgroup without mitral regurgitation in whom diminished left ventricular functional reserve is suggestive of a cardiomyopathic process.
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To assess left ventricular (LV) diastolic filling at rest in patients with coronary artery disease (CAD), we analyzed high-resolution time-activity curves (10-20 msec/frame) obtained from gated radionuclide angiograms in 231 patients. Peak LV filling rate (PFR), expressed in end-diastolic volumes per second (EDV/sec), was subnormal in CAD patients (1.8 +/- 0.6 [+/- SD] vs normal mean of 3.3 +/- 0.6, p les than 0.001) and time to PFR (TPFR), measured from end-systole to PFR, was prolonged (171 +/- 41 msec vs normal mean of 136 +/- 23 msec, p less than 0.001). These indexes were also abnormal in the 141 patients with normal resting LV ejection fraction (PFR = 2.1 +/- 0.5 EDV/sec; TPFR = 175 +/- 36 msec) and in 123 patients without Q waves on the ECG (PFR = 2.1 +/- 0.5 EDV/sec; TPFR = 168 +/- 38 msec). Abnormal LV filling at rest (PFR less than 2.5 EDV/sec or TPFR greater than 180 msec) was found in 91% of all patients with CAD, 86% of patients with normal resting LV ejection fractions, 85% of patients without Q waves, and 82% of patients with normal resting LV ejection fraction, no resting regional wall motion abnormalities and no Q waves. Thus, LV diastolic filling, evaluated noninvasively by radionuclide angiography, is abnormal in a high percentage of patients with CAD at rest independent of LV systolic function or previous myocardial infarction.