Reproducibility of rest and exercise left ventricular ejection fraction and volumes in chronic aortic regurgitation

To assess the variability of rest and exercise radionuclide ventriculography in patients with aortic regurgitation (AR), 22 patients in stable condition with chronic AR underwent radionuclide ventriculography at rest and during exercise for measurement of left ventricular volumes and ejection fraction (EF) on 2 occasions 3 months apart. For the group, there were no significant differences between the findings of the 2 studies except for a slightly lower exercise end-systolic volume on the second study. The inter-study differences and variabilities (expressed as the standard deviation of differences) for rest and exercise EF and change in EF were 0 +/- 0.04, +0.02 +/- 0.05 and +0.01 +/- 0.05, respectively. Thus, although mean differences were minor, considerable individual variability occurred, the magnitude of which was similar to that reported for other patient populations. In 3 patients who had an initial normal response to exercise (increase in EF greater than or equal to 0.05), the response became abnormal and in 2 who initially had an abnormal response, the response normalized. This variability must be considered in clinical decision-making or in research study design for patients with chronic AR.     

Alterations in left ventricular volumes and ejection fraction at rest and during exercise in patients with aortic regurgitation

This study was performed (1) to determine the changes in left ventricular volumes during exercise in patients with aortic regurgitation, and (2) to evaluate the importance of these alterations in characterizing left ventricular function in these patients. In 15 normal subjects (Group I) and in 17 patients with aortic regurgitation (Group II), left ventricular end-diastolic volume index, end-systolic volume index, ejection fraction and the ratio of peak systolic blood pressure to end-systolic volume index were measured at rest and during supine exercise. The patients with aortic regurgitation were classified into two groups on the basis of symptoms and chest radiographs: Group IIA, minimal or no symptoms, no cardiomegaly or pulmonary venous congestion; Group IIB, definite symptoms, with cardiomegaly and pulmonary venous congestion. Patients with aortic regurgitation had greater left ventricular end-diastolic and end-systolic volume indexes at rest and during exercise (p <0.05) than did normal subjects. During exercise, left ventricular end-diastolic volume index increased in normal subjects (53 ± 13 ml/m² [mean ± standard deviation] at rest, 67 ± 18 ml/m² during exercise, p <0.01), demonstrated a heterogeneous response in patients in Group IIA and increased in patients in Group IIB (180 ± 96 ml/m² at rest, 209 ± 102 ml/m² during exercise, p <0.05). During exercise, left ventricular end-systolic volume index decreased in normal subjects (18 ± 5 ml/m² at rest, $\text{15}\text{\$}\text{?}\text{6}$ ml/m² with exercise, p <0.01), increased in patients in Group IIB (82 ± 60 ml/m² at rest, 118 ± 93 ml/m² during exercise, p <0.05), and showed a variable response in those in Group IIA. At rest, left ventricular ejection fraction was similar in the three groups, but during exercise it increased in Group I (0.71 ± 0.07 at rest, 0.82 ± 0.07 with exercise, p <0.001), was unchanged in Group IIA and decreased in Group IIB (0.59 ± 0.15 at rest, 0.50 ± 0.16 during exercise, p <0.05). During exercise, there was an inverse relation between changes in left ventricular ejection fraction and endsystolic volume, but no relation between changes in end-diastolic volume and ejection fraction. Changes in the systolic pressure-volume ratio provided no more information than changes in end-systolic volume alone. Thus, abnormal alterations in left ventricular volumes occur during exercise in patients with aortic regurgitation and may be helpful in the further characterization of left ventricular performance in these patients.     

Range of normal values for left and right ventricular ejection fraction at rest and during exercise assessed by radionuclide angiocardiography

In order to reach a world-wide consensus on the normal rangeof left (LV) and right ventricular (RV) ejection fraction (EF)at rest and during exercise, pooled data of 1200 normal subjectsfrom 28 leading centres in the field of nuclear cardiology (68%of those contacted) was analysed. Weighted mean normal valuesfor LVEF at rest were 62.3±6.1% (1SD) with a lower limitof normal of 50% and for RVEF 52.3±6.2% (N=365) witha lower limit of normal of 40%. During exercise, LVEF increasedin 475 subjects by +8.0 EF% (range 3–15%), a normal increasebeing accepted to be 5% over a normal resting value for bothLVEF and RVEF. Subgroup analysis of results at rest revealedno significant differences regarding selection of normal subjects(based on normal catheterization findings vs. normal volunteerswith low probability of disease), age or sex. During exercise,however, significantly larger increases in LVEF measurementswere noted for men versus women (P<0.01), for normal volunteersversus subjects selected as ‘normals’ based on anormal coronary angiogram (P<0.001) and for younger versusolder subjects (P<0.001). Data on reproducibility and variabilityshowed that radionuclide angiocardiography can be consideredto be a reliable method today. No consensus was found for measurementsof regional LV function or wall motion mainly because of differencesin methodology used. These normal values may serve as generalguidelines for future applications of these techniques but factorswhich may influence the normal range as defined and discussedin this study should be recognized.     

Right and left ventricular ejection fraction and left ventricular volume changes at rest and during exercise in normal subjects

The effect of exercise upon right and left ventricular ejectionfractions (RVEF and LVEF) as well as the changes upon left ventricularend-diastolic and end-systolic volume indices (LVEDVI and LVESVI)were investigated. Twenty-two normal subjects were studied atrest and during upright submaximal exercise. RVEF was determinedusing a first-pass method. LVEF was measured using multiplegated blood pool imaging. During the exercise test ECGs remained normal. HR and BP increasedsignificantly (P<0.01). RVEF increased from 44%±4(mean±SD) to 60%±6 (P<0.001). LVEF increasedfrom 62%±6 to 76±5 (P<0.001). A wider scatterwas observed in RVEF than in LVEF. There was a 14% increasein LVEDV-index and a 14% decrease in LVESV-index (P<0.001).A multiple regression analysis with RVEF as the dependent variableand HR, systolic BP, LVEF, LVEDV-index and LVESV-index as independentvariables showed a significant correlation between RVEF andLVEF and systolic BP (P<0.05). Our data provide insight intothe mechanisms by which the pump performance is increased innormal subjects. The central mechanisms observed are the Starlingeffect and an increase in contractility of the myocardium. Thisis connected in the general circulation to an increase in afterload,indicating a redistribution of blood from the vascular bedsto the muscles and to the heart.     

Noninvasive assessment of myocardial contractility in asymptomatic patients with severe aortic regurgitation and normal left ventricular ejection fraction at rest

In 14 asymptomatic patients with isolated aortic insufficiency the slope k of the end-systolic pressure-volume relation was determined noninvasively with equilibrium radionuclide angiography. The results were compared with changes in left ventricular ejection fraction during maximal physical stress. Nine normal volunteers served as a control group. Patients with aortic insufficiency did not differ significantly from the control group with respect to left ventricular ejection fraction at rest (aortic insufficiency 62 + 8 percent, control 65 ± 6; probability [p] = not significant [NS]), physical work capacity (aortic insufficiency 113 ± 31 watts, control 117 ± 25; p = NS) or age (aortic insufficiency 40 ± 10 years, control 47 ± 7; p = NS).The slope (k) of the end-systolic pressure-volume relation was found to be significantly lower in the group with aortic insufficiency (3.1 ± 1.1) than in the control group (4.1 ± 0.5; p < 0.05). Patients with aortic insufficiency could be classified into two subgroups with respect to the slope k. In subgroup A (n = 7) the slope fell within the normal range (4.0 ± 0.6) as defined by the control group, and the left ventricular exercise reserve was normal (6 percent ± 1). In subgroup B (n = 7) the slope was significantly lower (2.2 ± 0.6, p < 0.01), indicating depressed myocardial contractility, and all patients experienced left ventricular dysfunction during exercise (left ventricular exercise reserve ?5 ± 5 percent). Thus, noninvasive determination of the end-systolic pressure-volume relation identified two subsets of asymptomatic patients with aortic insufficiency, one with impaired myocardial contractility and normal left ventricular exercise reserve and a second group with depressed myocardial contractility and left ventricular dysfunction during exercise.Therefore, an abnormal baseline contractile state in asymptomatic patients with aortic insufficiency may be uncovered by noninvasive determination of the end-systolic pressure-volume relation or by assessing the left ventricular exercise reserve. Serial studies in a larger group of patients undergoing surgical correction of the valve lesion are indicated to determine whether this information will be helpful in evaluating when to operate on asymptomatic patients with aortic insufficiency.     

Exercise testing in asymptomatic or minimally symptomatic aortic regurgitation: relationship of left ventricular ejection fraction to left ventricular filling pressure during exercise

Exercise radionuclide angiography is being used to evaluate left ventricular function in patients with aortic regurgitation. Ejection fraction is the most common variable analyzed. To better understand the rest and exercise ejection fraction in this setting, 20 patients with asymptomatic or minimally symptomatic severe aortic regurgitation were studied. All underwent simultaneous supine exercise radionuclide angiography and pulmonary gas exchange measurement and underwent rest and exercise measurement of pulmonary artery wedge pressure (PAWP) during cardiac catheterization. Eight patients had a peak exercise PAWP less than 15 mm Hg (group 1) and 12 had a peak exercise PAWP greater than or equal to 15 mm Hg (group 2). Group 1 patients were younger and more were in New York Heart Association class I. Group 1 patients also had a higher mean rest ejection fraction (0.64 +/- 0.08 vs 0.49 +/- 0.13, p less than 0.01, higher exercise ejection fraction (0.63 +/- 0.10 vs 0.40 +/- 0.18, p less than 0.01), lower end-systolic volume (38 +/- 13 vs 79 +/- 36 ml/m2, p less than 0.01) and higher peak oxygen uptake (24.9 +/- 5.1 vs 16.6 +/- 4.9 ml/kg/min, p less than 0.01) than group 2 patients. However, the two groups had similar cardiothoracic ratios, changes in ejection fractions with exercise, and rest and exercise regurgitant indexes. Using multiple regression analysis, the best correlate of the exercise PAWP was peak oxygen uptake (r = -0.78, p less than 0.01). No other measurement added significantly to the regression. When peak oxygen uptake was excluded, rest and exercise ejection fraction also correlated significantly (r = -0.62 and r = -0.60, respectively, p less than 0.01). Patients with asymptomatic or minimally symptomatic severe aortic regurgitation have a wide spectrum of cardiac performance in terms of the PAWP during exercise. The absolute rest and exercise ejection fraction and the level of exercise achieved are noninvasive variables that correlate with exercise PAWP in aortic regurgitation, but the change in ejection fraction with exercise by itself is not.     

Exercise testing in aortic regurgitation: comparison of radionuclide left ventricular ejection fraction with exercise performance at the anaerobic threshold and peak exercise

Serial radionuclide left ventricular ejection fractions (EF) were measured during graded supine exercise in 16 control patients and 35 asymptomatic or minimally symptomatic patients with severe aortic regurgitation (AR). Simultaneous pulmonary gas exchange analysis permitted determination of the anaerobic threshold, which is the point during exercise at which lactic acid begins to accumulate in the blood. The EF and oxygen uptake were measured at rest, anaerobic threshold and peak exercise. The mean EF (±1 standard deviation) in control patients increased from 0.65 ± 0.06 at rest to 0.73 ± 0.05 at anaerobic threshold (p < 0.01). No further change in EF occurred between anaerobic threshold and peak exercise (0.73 ± 0.09). Peak oxygen uptake in control patients was 20 ± 4 ml/ kg/min. Patients with AR were classified into 2 groups based on a peak oxygen uptake >16 ml/ kg/min (Group I, n = 26) and < 16 ml/kg/min (Group II, n = 9). In Group I the mean oxygen uptake at the anaerobic threshold and peak exercise was similar to or greater than that in control patients, whereas in Group II patients it was less than in control pa- tients. In Group I, the mean rest EF (0.62 ± 0.07) was similar to that in control patients; there was no change at the anaerobic threshold (0.61 ± 0.10), and then it decreased at peak exercise (0.57 ± 0.12, p < 0.05). In Group II, the mean rest EF (0.44 ± 0.12) was below that in control patients (p < 0.01); there was a decrease at the anaerobic threshold (0.35 ± 0.10, p < 0.01), and then it decreased further at peak exercise (0.30 ±0 0.09, p < 0.05). The anaerobic threshold and peak oxygen uptake reflect rest and exercise left ventricular EF in AR and may provide an additional approach of assessing cardiac performance in these patients. Exercise-induced changes in left ventricular EF should be based on the changes occurring before the anaerobic threshold, because changes between anaerobic threshold and peak exercise are of uncertain diagnostic value.     

Left ventricular ejection fraction response during exercise in asymptomatic systemic hypertension

To study the effect of mild-to-moderate elevations in diastolic blood pressure (BP) on systolic left ventricular (LV) function, 28 hypertensive patients and 20 normal subjects underwent upright exercise first-pass radionuclide angiography. All were asymptomatic, had normal rest and exercise electrocardiographic findings and no evidence of LV hypertrophy or coronary artery disease. LV function at rest was similar in the 2 groups, but with exercise hypertensive patients had a greater end-systolic volume (69 +/- 19 vs 51 +/- 19 ml, p less than 0.002) and lower ejection fraction (EF) (0.59 +/- 0.09 vs 0.72 +/- 0.07, p less than 0.0001), stroke volume (101 +/- 28 vs 130 +/- 36 ml, p less than 0.005) and peak oxygen uptake (23 +/- 7 vs 33 +/- 9 ml/kl/min, p less than 0.05). Hypertensive patients were separated into 3 groups: group 1-12 patients with an increase in EF with exercise greater than or equal to 0.05; group 2-7 patients with a change in EF with exercise less than 0.05; and group 3-9 patients with a decrease in EF with exercise greater than or equal to 0.05. Group 3 hypertensive patients were older, had a higher heart rate at rest and lower peak oxygen uptake. Rest LV function was similar in the 3 hypertensive subgroups, but exercise end-systolic volumes were higher in groups 2 and 3. Exercise thallium-201 images was normal in all but 1 of 14 hypertensive group 2 or 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mechanisms for an abnormal radionuclide left ventricular ejection fraction response to exercise in patients with chronic, severe aortic regurgitation.

To clarify the mechanisms for an abnormal radionuclide left ventricular (LV) ejection fraction response to exercise in patients with chronic, severe aortic regurgitation (AR), we studied seven control patients and 21 patients with AR. We used exercise radionuclide angiography and catheterization of the right and left sides of the heart to obtain a calculation of LV chamber elastance. The control and AR groups had similar heart rates, systolic blood pressure responses to exercise, and exercise durations. In both patient groups, LV end-diastolic volume did not change with exercise. In contrast to the decrease in LV end-systolic volume (p less than 0.05) and increase in LV ejection fraction (p less than 0.01) in the control group, LV end-systolic volume in the patients with AR increased, resulting in little change in their LV ejection fraction. By stepwise multiple regression analysis, the radionuclide LV ejection fraction at peak exercise in patients with AR was determined by the LV chamber elastance, LV end-systolic volume, and stroke volume at peak exercise (cumulative r = 0.79, p less than 0.02); the change in radionuclide LV ejection fraction from rest to peak exercise was determined by the corresponding change in systemic vascular resistance, regurgitant index, and LV end-diastolic and end-systolic volumes (cumulative r = 0.88, p less than 0.02). These data demonstrate that in patients with AR, the radionuclide LV ejection fraction at peak exercise is principally determined by the cumulative effects of chronic, severe AR on LV systolic chamber performance, and the change in radionuclide LV ejection fraction from rest to peak exercise is principally established by peripheral vascular responses.     

Course of ejection fraction, regurgitation fraction and ventricular volumes during exertion in chronic aortic insufficiency. Study using technetium 99m gamma-cineangiography

Previous studies have shown that variations of the ejection fraction (EF) during exercise were representative of the contractile state of the left ventricle: an increased EF on effort is considered to be physiological, whilst a decrease would indicate latent LV dysfunction unmasked during exercise. This hypothesis was tested by performing Technetium 99 gamma cineangiography at equilibrium under basal conditions and at maximal effort in 8 healthy subjects and 44 patients with pure, severe aortic regurgitation to measure the ejection and regurgitant fractions and the variations in end systolic and end diastolic LV volume. In the control group the EF increased and end systolic volume decreased significantly on effort whilst the regurgitant fraction and end diastolic volume were unchanged. In the 44 patients with aortic regurgitation no significant variations in EF, end systolic and end diastolic volumes were observed because the individual values were very dispersed. Variations of the EF and end systolic volume were inversely correlated. The regurgitant fraction decreased significantly on effort. Based on the variations of the EF and end systolic volume three different types of response to effort could be identified: in 7 patients, the EF increased on effort and end systolic volume decreased without any significant variation in the end diastolic volume, as in the group of normal control subjects; in 22 patients, a reduction in EF was observed on effort, associated with an increased end systolic volume. These changes indicated latent IV dysfunction inapparent at rest and unmasked by exercise; in a third group of 15 patients, the EF decreased on effort despite a physiological decrease in end systolic volume due to a greater decrease in end diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation of right ventricular ejection fraction to exercise capacity in chronic left ventricular failure

Although the left ventricle is traditionally viewed as the heart's main pumping chamber, no correlation has been shown between left ventricular (LV) ejection fraction (EF) at rest and exercise capacity in patients with chronic LV failure. Because vasodilators with venodilating activity increase exercise capacity more than predominant arterial dilators in patients with LV failure, right ventricular (RV) function may relate to exercise capacity in these patients. In 25 patients with chronic LV failure, caused by coronary artery disease in 12 patients and idiopathic dilated cardiomyopathy in 13 patients, RVEF and LVEF at rest were measured by radionuclide angiography. Maximal upright bicycle exercise testing was also performed to determine maximal oxygen consumption, which averaged only 13 ± 4 ml/min/kg. The LVEF at rest was 26 ± 10% and did not correlate with maximal oxygen consumption (r = 0.08). However, the RVEF was 41 ± 12% and correlated with maximal oxygen consumption (r = 0.70, p < 0.001) in the same patients. The correlation was stronger (r = 0.88) in patients with coronary artery disease than in those with idiopathic dilated cardiomyopathy (r = 0.60). Thus, RVEF at rest is more predictive of exercise capacity than LVEF in the same patients with chronic LV failure. These results are consistent with the clinical observation that only venodilating agents increase exercise capacity of patients with chronic LV failure.     

Comparison of effects of isometric and supine bicycle exercise on left ventricular performance in patients with aortic regurgitation and normal ejection fraction at rest

The effects of handgrip and supine bicycle exercise on hemodynamics and left ventricular (LV) performance were compared in 25 patients with moderate to severe aortic regurgitation (AR) and normal LV ejection fraction at rest (greater than or equal to 50%) and in 10 control subjects. In both groups, heart rate, systolic blood pressure, rate-pressure product, and LV output were higher during supine bicycle exercise. Compared with the controls, in patients with AR, stroke volume was unchanged during supine bicycle exercise. LV end-diastolic volume increased during handgrip exercise but was unchanged during supine bicycle exercise. LV end-systolic volume increased and ejection fraction decreased during both forms of exercise. Of 25 patients with AR, 15 (60%) during handgrip exercise and 19 (76%) during supine bicycle exercise had an abnormal ejection fraction response (p less than 0.05). In patients with moderate to severe AR and normal LV ejection fraction at rest, both handgrip and supine bicycle exercise induced LV dysfunction. An abnormal LV ejection fraction response occurred more often with supine bicycle exercise. Handgrip exercise may be a useful alternative method for detecting LV dysfunction in patients with AR in whom adequate bicycle exercise cannot be accomplished.     

Criteria for the accurate interpretation of changes in left ventricular ejection fraction and cardiac volumes as assessed by rest and exercise gated radionuclide angiography

Although serial left ventricular ejection fraction and volumetric measurements using gated radionuclide angiography are commonly used to evaluate clinical changes and therapeutic outcomes in individual patients, criteria are not available for accurately interpreting whether a change in any of these hemodynamic measurements is clinically meaningful. Accordingly, the magnitude of inherent variability among sequential measurements of hemodynamic variables assessed by gated radionuclide angiography was investigated in a double-blind placebo-controlled fashion in 39 patients during two placebo periods separated by 6 weeks. All patients analyzed had remained clinically stable during the study period. Although the mean values for all hemodynamic variables between the two placebo periods were minimally changed, the differences in individual patients were striking. Criteria were developed to allow meaningful interpretation of changes in hemodynamic variables by estimating the likelihood that an observed change is due to variability alone. On the basis of this analysis of placebo radionuclide angiographic data, variation due to chance alone is unlikely to account for all variability if a change observed between the two rest gated studies in a patient is greater than or equal to 7% units for left ventricular ejection fraction, greater than or equal to 45 ml/m2 for end-diastolic volume index, greater than or equal to 35 ml/m2 for end-systolic volume index, greater than or equal to 20 ml/m2 for stroke volume index and greater than or equal to 1.25 liters/min per m2 for cardiac index. An observed 4% unit change in left ventricular ejection fraction (increase or decrease) after a medical intervention in an individual patient occurs by random variation greater than 25% of the time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prognosis of chronic non-dystrophic and surgically treated aortic insufficiency

Between January 1972 and March 1983, 123 patients with isolated non dystrophic aortic insufficiency underwent aortic valve replacement. During a mean follow-up period of 4.3 years per patient, 25.6 p. 100 of the patients died, including a 4.1 p. 100 hospital death rate. The actuarial survival rate was 74 p. 100 at 5 years and 62 p. 100 at 10 years. The main causes of mortality were heart failure, dysrhythmias and sudden death. A study of prognostic factors based on the preoperative data showed that clinical, radiological, electrocardiographic and haemodynamic signs were informative. In agreement with other authors, we found that preoperative cardiac dilatation and left ventricular dysfunction were predictive of a poor prognosis.     

Effect of rate on left ventricular volumes and ejection fraction during chronic ventricular pacing

Resting left ventricular (LV) function was evaluated in 22 patients with permanent ventricular pacemakers. LV ejection fraction and volume indexes were determined by gated blood pool scintigraphy at ventricular pacing rates of 50-100 beats/min. In patients with a normal heart size, increases in pacing rates resulted in significant linear decreases in stroke volume index and ejection fraction. However, end-systolic volume index and cardiac index did not change. Patients with cardiomegaly appeared to respond differently. End-diastolic volume index decreased significantly as the pacing rate was increased from 50 to 100 beats/min. Ejection fraction was significantly reduced only at pacing rates of 90 and 100 beats/min. Mean cardiac index was highest at ventricular pacing rates of 70-90 beats/min. Increases in cardiac index, achieved by increasing the pacing rate, were maintained over a 4.3-month follow-up. Patients with underlying sinus rhythm had a 27% increase in cardiac output in association with an increase in ejection fraction from 55% to 62% when sinus rhythm was compared to ventricular pacing at a rate of 60 beats/min. These data suggest that patients with cardiomegaly have a narrow range of optimal pacing rates at rest.     

Association between the exercise ejection fraction response and systolic wall stress in patients with chronic aortic insufficiency

We studied the exercise ejection fraction response in 56 patients with chronic aortic insufficiency. All had left ventricular dilatation but preserved resting ejection fraction and minimal or no symptoms. The exercise ejection fraction increased by 0.05 units or greater in 18 (32%) patients (group I), remained within 0.05 units of the resting value in 18 (32%) patients (group II), and fell by 0.05 units or greater in 20 (36%) patients (group III). There were no significant differences among the groups in left ventricular end-diastolic dimension, end-systolic dimension, or fractional shortening by echocardiography or in resting left ventricular volumes and ejection fraction by radionuclide angiography. Left ventricular end-systolic wall stress was significantly higher in group III than in either group I or group II (89 +/- 20 vs 70 +/- 18 and 69 +/- 17 X 10(3) dyne/cm2; p less than .005). At peak exercise there were no differences among groups in systolic blood pressure. However, end-systolic volume increased from 65 +/- 28 to 77 +/- 36 ml/m2 in group III and fell from 50 +/- 21 to 28 +/- 18 ml/m2 in group I during exercise. Thus, at peak exercise end-systolic volume was nearly three times greater in group III than in group I. Although stress could not be determined directly during exercise, the directional changes in its determinants suggest that it also would have been higher in group III patients. A highly significant inverse correlation was present between the ejection fraction response and the change in end-systolic volume (r = -.87, p less than .0001).(ABSTRACT TRUNCATED AT 250 WORDS)