Radionuclide analysis of peak filling rate, filling fraction, and time to peak filling rate. Response to supine bicycle exercise in normal subjects and patients with coronary disease

Using gated equilibrium radionuclide angiography, variables of diastolic filling were analyzed at rest and during supine bicycle exercise in normal subjects (Group 1, n = 18), coronary patients with normal resting ejection fractions (Group 2, n = 26), and coronary patients with reduced resting ejection fractions (Group 3, n = 8). Indexes analyzed were peak filling rate and filling fraction during the first third of diastole. At rest, the peak filling rate was significantly lower in coronary patients than in normal subjects (3.18 +/- 0.82 end-diastolic volume [EDV]/s in Group 1 versus 2.41 +/- 0.66 EDV/s in Group 2, p less than 0.005; and 1.34 +/- 0.26 EDV/s in Group 3, p less than 0.001 versus Group 1). These differences persisted at peak exercise. Coronary patients also had significantly lower filling fractions at rest and during exercise than did normal control subjects. The time from end-systole to peak filling rate was longer at rest in patients in Group 2 (203 +/- 52 ms) than in subjects in Group 1 (172 +/- 50 ms, p less than 0.025). This remained true when the time to peak filling was normalized by the R-R interval. Although the exercise time to peak filling was longer in coronary patients in both Groups 2 and 3 than in Group 1, these differences were not apparent when the interval was normalized by the R-R interval. Thus, abnormalities in peak filling rate and filling fraction exist in patients with coronary disease both at rest and during exercise, but large overlaps exist between normal and coronary patients. Caution is advised in comparing the timing of events during diastole because apparent group differences may be related in part to rest or exercise heart rate.     

Effect of nitrates on left ventricular size and function during exercise: Comparison of sublingual nitroglycerin and nitroglycerin paste

To compare the effects of sublingual nitroglycerin and nitroglycerin paste on left ventricular size and performance during supine bicycle exercise, equilibrium radionuclide angiography was performed in 36 persons classified into two groups of normal subjects and two groups of patients with angiographically proved coronary heart disease. Each group underwent a control exercise study, and then one group of normal subjects and one group of patients were restudied after the administration of 0.6 mg of nitroglycerin or 2 inches (5 cm) of nitroglycerin paste (but not both). Data were collected at rest and at peak exercise.In normal subjects exercise resulted in increased ejection fraction, decreased end-systolic volume and little change in end-diastolic volume. After either drug, volumes at rest markedly decreased, and during exercise, ejection fraction increased to levels comparable with pre-drug levels. After nitroglycerin paste the reduction in volume seen at rest persisted during exercise, but after sublingual nitroglycerin end-diastolic volume increased during exercise (88 ± 43 to 113 ± 30 ml [mean ± standard deviation]; p < 0.01). Peak exercise end-diastolic volume after nitroglycerin was still lower than that before nitroglycerin (113 ± 30 versus 120 ± 28 ml, p < 0.05).In patients with coronary disease, ejection fraction did not change during exercise, but both end-diastolic and end-systolic volumes increased. After either drug ejection fraction at rest was unchanged, although ventricular volumes were markedly lower (p < 0.05). Ejection fraction increased with exercise in both groups with coronary disease after either drug. After sublingual nitroglycerin, volumes increased during exercise although the peak exercise end-diastolic volume was still lower than the control value (113 ± 31 versus 145 ± 34 ml; p < 0.01). After paste administration, end-diastolic volume did not change during exercise, and end-systolic volume decreased (41 ± 20 to 36 ± 22 ml; p < 0.05).Thus, sublingual nitroglycerin and nitroglycerin paste improved left ventricular function during exercise. The effect of paste on end-diastolic volume appeared sustained, whereas that of sublingual nitroglycerin was transient, confirming the hypothesis that reduction in end-diastolic volume and, by implication, left ventricular wall tension, is a major mechanism of nitrate action.     

Sensitivity and specificity of nuclear phase analysis versus ejection fraction in coronary artery disease

Phase standard deviation (SD) and skew characteristics of the first Fourier harmonic of equilibrium radionuclide volume curves were examined and compared during rest and during supine bicycle exercise with ejection fraction (EF) changes and the development of ischemia in 17 control subjects and in 2 groups of patients (n = 57) with coronary artery disease (CAD). Group I comprised 37 patients with CAD; IA was a subgroup of 20 patients with previous myocardial infarction (MI) and IB a subgroup of 17 patients with CAD without MI (all with coronary stenosis greater than 75% diameter narrowing). Group II comprised 20 patients with CAD who had undergone coronary bypass surgery. In the Group I subjects, phase SD was the most sensitive indicator of CAD at rest (Group I, 56%; Group IA, 70%, and Group IB, 29%), and the EF was the most sensitive indicator at submaximal (Group I, 78%; Group IA, 86%, and Group IB, 64%) and maximal exercise (Group I, 70%; Group IA, 93%, and Group IB, 53%). When phase SD and skewness were combined with EF changes, little increase in sensitivity occurred in Group I (rest 61%, submaximal exercise 88% and maximal exercise 76%). The results from Group II subgroups were qualitatively similar to those observed with Group I subgroups. These data reveal a marginally improved sensitivity for detection of CAD during supine bicycle radionuclide ventriculography when phase measurements were added to changes in global EF values.     

Ejection fraction and heart rate correlate with diastolic peak filling rate at rest and during exercise

We investigated the independent variables correlating with the multigated radionuclide peak filling rate (PFR) at rest and during supine bicycle exercise in 20 normal individuals. Independent variables were systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), ejection fraction (LVEF), time to PFR (TPFR), peak ejection rate (PER) and time to PER (TPER). Fifteen subjects completed at least five stages of exercise at 25 watts each. Correlating independent variables were selected by a forward-backward stepwise multiple linear regression (BMDP2R). A partial correlation statistical program was also used to allow control of critical independent variables. The final regression equations were: a) resting state, PFR = -2.5 + 0.03HR + 0.05LVEF + 0.02SBP-0.02DBP, and b) exercise state, PFR = -3.8 + 0.04HR + 0.08LVEF. All independent variables mentioned above correlated with PFR (simple correlations designated as zero partials). However, when LVEF and HR were held constant (second order partials), the correlation of PFR with any of the other independent variables disappeared. In summary, the radionuclide global LV PFR is predominantly correlated to LVEF and HR at rest and during exercise. These correlations should be considered when assessing exercise effects of disease states on PFR.     

Peak systolic blood pressure/end-systolic volume ratio: Assessment at rest and during exercise in normal subjects and patients with coronary heart disease

To assess the utility of a recently proposed index of left ventricular performance, the ratio of peak left ventricular systolic pressure to end-systolic volume, equilibrium radionuclide angiography was used to determine end-systolic volume and the systolic blood pressure obtained by cuff sphygmomanometer to determine peak systolic pressure. Data were analyzed at rest and during supine bicycle exercise in 15 normal subjects (Group 1), 50 patients with coronary artery disease (Group II) and 9 patients with obstructive lung disease and no evidence of coronary artery disease on clinical examination including exercise thallium imaging (Group III). In 15 subjects the correlation between the resting angiographic and radionuclide pressure/volume ratio was excellent (r = 0.929, p <0.005).Forty-seven (94 percent) of the 50 patients in Group II had a depressed pressure/volume ratio at rest or an abnormal change in this ratio during exercise, whereas only 43 (86 percent) of this group had an abnormal ejection fraction at rest or during exercise. Additionally, 3 of 15 subjects in Group I had an abnormal ejection fraction response, defined as less than 0.05 ejection fraction unit increase with exercise (specificity 80 percent), whereas all subjects in Group I had a normal increase in pressure/volume ratio (specificity 100 percent). At rest, neither index identified more patients with coronary artery disease than the other. Of the nine patients in Group III, six had an abnormal ejection fraction response to exercise, whereas only one had an abnormal pressure/volume ratio response.It is concluded that the end-systolic pressure/volume ratio is a useful index of left ventricular performance. In some patients during supine exercise stress it may be more sensitive than the ejection fraction response alone in identifying the presence of coronary artery disease.     

Radionuclide left ventricular volume curves in angiographically proved normal subjects and patients with three-vessel coronary disease

To determine the diagnostic value of measurements obtained from radionuclide left ventricular volume curves, we compared 12 patients with normal coronary arteries (NL) to 12 patients with three-vessel coronary artery disease (3V CAD). Maximum and mean rates of ejection and filling, times of maximum ejection and filling, durations of systole and diastole, and percentages of ejection and filling during each third were measured at rest and during exercise. The only group differences at rest were a 39 msec (p = 0.002) delay in the time of maximal filling and a 6% (p = 0.04) decrease in first third filling fraction in the 3V CAD patients. The overlap in values for these two parameters, however, did not allow good separation of the patients into NL and 3V CAD groups. During exercise, maximal and mean rates of ejection and filling were significantly lower in the 3V CAD group, but these measurements did not improve on the discriminative value of heart rate and ejection fraction alone. Thus, in both the resting and exercise states, measurements of instantaneous changes in left ventricular volume added little diagnostic information.     

Radionuclide ventriculographic responses to graded supine and upright exercise: Critical role of the Frank-starling mechanism at submaximal exercise

To assess the influence of work load and posture on the response to exercise, 25 patients with coronary artery disease (CAD) and 17 normal subjects underwent graded supine and upright exercise radionuclide ventriculography. In both groups, end-diastolic counts increased with supine exercise (p < 0.001). The ejection fraction and peak systolic pressure-end-systolic volume relation increased in normal subjects (p < 0.02), but not in patients with CAD. At upright rest, end-diastolic counts decreased in both groups (p < 0.001) and then increased with exercise (p < 0.001). The increase in end-diastolic counts was most pronounced on the transition from upright rest to the 150-kpm work load and resulted in a significant increase in stroke counts (p < 0.05) for both patients with CAD and normal subjects, without a measurable change in the ejection fraction or the peak systolic pressure-end-systolic volume relation. Later in exercise, end-diastolic counts plateaued, and the ejection fraction and the peak systolic pressure, end-systolic volume relation increased only among normal subjects. Thus, lowlevel upright exercise is highly dependent on the Starling mechanism in both normal subjects and patients with CAD, with enhanced contractility apparent only during more vigorous exercise in normal subjects.     

Assessment of early ventricular systole by first pass radionuclide angiography: useful method for detection of left ventricular dysfunction at rest in patients with coronary artery disease.

To identify abnormal left ventricular function without exercise stress in patients with coronary artery disease first-pass radionuclide angiograms were analyzed in 32 normal subjects (Group I); 31 patients with coronary disease and normal contrast ventriculograms (Group II); and 17 patients with coronary disease and depressed left ventricular function (Group III). Total ejection fraction (EF) was computed with standard angiographic methods and from each time-activity curve. During the first third of systole, ejection fraction was determined manually by averaging three to five beats and the value compared with that obtained with contrast ventriculography: (Formula: see text). Both total radionuclide ejection fraction (r = 0.95) and first-third ejection fraction (r = 0.91) correlated well with angiography. Intraobserver and interobserver variation was small, averaging 0.02 +/- 0.02 (range 0 to 0.05). The radionuclide first-third ejection fraction was 0.25 or greater in normal subjects and less than 0.25 in 29 of 31 patients (94 percent) in Group II and in all patients in Group III. It is concluded that the first-third ejection fraction obtained with first pass angiography identifies subtle abnormalities of left ventricular function at rest in more than 90 percent of patients with coronary disease that may not be recognized by total ejection fraction alone.     

Rate of change of left ventricular ejection fraction during exercise is superior to the peak ejection fraction for predicting functionally significant coronary artery disease.

OBJECTIVE--To detect and characterise rapid temporal changes in the left ventricular response to exercise in patients with ischaemic heart disease and to relate these changes to the functional severity of coronary artery disease. BACKGROUND--The gamma camera does not allow the detection of rapid changes in cardiac function during exercise radionuclide ventriculography, the monitoring of which may improve the assessment of patients with ischaemic heart disease. METHODS--A miniature nuclear probe (Cardioscint) was used to monitor continuously left ventricular function during exercise in 31 patients who had coronary angiography for suspected coronary artery disease. A coronary angiographic jeopardy score was calculated for each patient. RESULTS--The coronary jeopardy score ranged from 0 to 12 (median 4). Ejection fraction fell significantly during exercise from 46% to 34%. Patients were divided into two groups based on the response of their ejection fraction to exercise. In 14 patients (group I), the peak change in ejection fraction coincided with the end of exercise, whereas in the other 17 patients (group II) the peak change in ejection fraction occurred before the end of exercise, resulting in a brief plateau. The peak change in ejection fraction and the time to its occurrence were independent predictors of coronary jeopardy (r = -0.59, p < 0.001 for peak change and r = -0.69, p < 0.001 for time to that change). The rate of change in ejection fraction was the strongest predictor of coronary jeopardy (r = -0.81, p < 0.001). In group I the peak change in ejection fraction was a poor predictor severity of coronary disease (r = -0.28, NS), whereas the time to peak and the rate of change in ejection fraction were good predictors (r = -0.65 and r = -0.73, p < 0.01). In group II the peak, the time to the peak, and the rate of change in ejection fraction were good predictors of coronary jeopardy (r = -0.75, r = -0.61, and r = -0.83, p < 0.01). CONCLUSION--The rate of change of ejection fraction during exercise can be assessed by continuous monitoring of left ventricular function with the nuclear probe, and is the best predictor of functionally significant coronary artery disease.     

The influence of age and gender on left ventricular response to supine exercise in asymptomatic normal subjects

The performance of normal subjects during radionuclide ventriculography has been related to age, but the combined effects of age and sex on exercise ventricular function are not well described. We studied 55 normal volunteers, 27 men (age = 30 ± 10 years) and 28 women (age = 33 ± 14 years), free of chest pain syndromes, during supine rest/exercise radionuclide ventriculography performed to fatigue. Resting left ventricular ejection fraction did not differ between male and female subjects (64 ± 5.4 vs 64 ± 6.1; p = NS). Both the peak left ventricular ejection fraction (78 ± 4.4 vs 72 ± 9.2; p < 0.001) and the change in ejection fraction with exercise (14 ± 4.0 vs 7.9 ± 7.0; p < 0.001) were significantly greater in men compared to respective values in women. Regression analysis showed that sex (r = 0.51; p < 0.001) but not age (r = −0.18; p = 0.19) was a significant predictor of change in ejection fraction with exercise. Data on left ventricular volume response to exercise, available in 43 subjects, revealed that men had a greater percentage of decline in end-systolic volume with exercise than women (−47 ± 15 vs −24 ± 26; p < 0.001). It is concluded that sex exerts a significant influence on normal left ventricular response to fatigue-limited supine exercise and that the gender difference is mediated, in part, by left ventricular end-systolic volume response to exercise.     

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.     

Elucidation of physiologic lengthening of left ventricular ejection time during early upright exercise

To elucidate the relationship between heart rate (HR) and left ventricular ejection time (LVET) during early exercise, 30 patients with chest pain were studied at 1 (1′) and 4 minutes (4′). Mean results for control → 1′ exercise: HR 79 to 105 beats per minute, LVET 247 to 260 msec. Thus instead of shortening as predicted by the HR change at 1′ of exercise, LVET rose significantly (p < 0.001). Subsequently LVET fell as HR continued rising, and by 4′ had fallen toward control level. This phenomenon is comparable to the paradoxical decline in LVET as HR decreases early post-exercise and is comparably explained by transiently disproportionate change in determinants of LVET, stroke volume, and ejection rate. Absence of difference in response of exercise-positive (ST depression ≥ 1 mm) and exercise-negative patients, also supports this initial paradoxical lengthening in LVET as a physiologic response.     

Reproducibility of equilibrium radionuclide ventriculography in patients with coronary artery disease: Response of left ventricular ejection fraction and regional wall motion to supine bicycle exercise

To evaluate the reproducibility of ejection fraction (EF) and regional wall motion (RWM) analyses by rest and exercise equilibrium radionuclide ventriculography (RNV) in the presence of coronary artery disease (CAD), 18 patients underwent two maximum, multistage supine bicycle exercise studies separated by an interval of 2 weeks. There were no significant differences in EF between the two studies, both at rest (56.0 ± 13.8% vs 58.2 ± 11.7%, p = NS) and with exercise (51.1 ± 17.6% vs 54.3 ± 17.6%, p = NS) and a highly significant correlation was shown between the two groups of values (rest r = 0.90, exercise r = 0.93, p < 0.001). There was no significant difference in the change from rest to exercise (?4.9 ± 12.0% vs ?3.8 ± 11.5%, p = NS) between the two studies and the correlation was highly significant (r = 0.69, p < 0.01). The interstudy variabilities were 2.2 ± 6.1% and 1.2 ± 7.3% for rest and exercise, respectively, and 2.0 ± 9.2% for the change from rest to exercise. Ninety-four percent of both rest and exercise regions had similar RWM. Eighty-one percent of the abnormally contracting regions were common to both exercise studies. Utilizing conventional criteria for the diagnosis of CAD, 11 patients had abnormal EF response and nine had abnormal RWM response to exercise on both studies. Combining EF and RWM criteria resulted in the diagnosis of CAD in 15 patients in both studies. We conclude that: (1) there were no significant differences in rest and exercise radionuclide EF and RWM between two supine bicycle exercise studies performed 2 weeks apart in patients with stable CAD and there were significant correlations between the two studies; (2) despite these correlations, the interstudy variabilities emphasize the need for the inclusion of reproducibility studies in all evaluations of interventions by exercise radionuclide ventriculography; and (3) the variations in EF and RWM response to exercise result in a lack of uniformity between the two studies regarding the diagnosis of CAD based on conventional RNV criteria.     

Hemodynamic effects of inhaled terbutaline in congestive heart failure patients without lung disease: Beneficial cardiotonic and vasodilator beta-agonist properties evaluated by ventricular catheterization and radionuclide angiography

To evaluate the hemodynamic effects of the beta-adrenergic receptor agonist, terbutaline sulfate, when given by inhalation in ventricular dysfunction, 0.5 mg of the agent was given by nebulizer to 13 patients with congestive heart failure (nine coronary heart disease and four with idiopathic cardiomyopathy). Data were obtained before and 10 and 30 minutes post inhalation, by right heart catheterization and by gated equilibrium radionuclide ventriculography. All patients responded with increased cardiac output (3.5 to 4.3 L/min, p < 0.01) and stroke volume (40 to 49 ml, p < 0.01) without change in heart rate. Decreases occurred in peripheral vascular resistance (1924 to 1443 dsc^?5, p < 0.01), left ventricular filling pressure (21 to 15 mm Hg, p < 0.01), and systemic arterial oxygen tension (81 to 72 mm Hg, p < 0.05). Both left and right ventricular ejection fractions rose (0.24 to 0.38 and 0.36 to 0.51, both p < 0.01) with concomitant declines in blventricular end-diastolic volumes. All variables indicated changed rapidly at 10 minutes post inhalation and returned to control levels by 30 minutes after the agent. Thus moderate inhaled doses of terbutaline produce prompt, potent, and transient salutary hemodynamic effects due to its peripheral vasodilator and cardiotonic properties, without untoward arrhythmogenic or anginal provoking influences in the present study.     

Comparative effects of diltiazem,propranolol, and placebo on exercise performance using radionuclide ventriculography in patients with symptomatic coronary artery disease: Results of a double-blind,randomized, crossover study

The effects of oral diltiazem (120 mg), propranolol (100 mg), and placebo on exercise performance and left ventricular function were compared before and during symptom-limited supine bicycle exercise by means of multigated radionuclide ventriculography in 12 patients with documented, symptomatic coronary artery disease; a double-blind, randomized crossover protocol was used. Diltiazem increased ejection fraction (EF) at submaximal exercise (+7.0 absolute percentage points, p < 0.02) and maximal exercise (+8.1 percentage points, p < 0.01). Exercise EF was increased by 13.6 percentage points (p < 0.02) in patients with decreased ventricular function (resting EF <50%). Propranolol had no effect on exercise EF at any stage, even when patients with EF <50% were excluded. The increase in total exercise time was significant after diltiazem (+27%, p < 0.01) but not after propranolol (+16%, p = NS). As expected, propranolol decreased both resting (?9 bpm, p < 0.01) and exercise heart rates (?27 bpm, p < 0.001), whereas diltiazem had no significant effect. Propranolol decreased resting diastolic blood pressure (?8 mm Hg, p < 0.02), exercise systolic (?27 mm Hg, p < 0.001) and diastolic (?9 mm Hg, p < 0.01) blood pressures, and rest (p < 0.01) and exercise (p < 0.001) double product. Diltiazem decreased resting systolic blood pressure (?9 mm Hg, p < 0.01) and both resting (?8 mm Hg, p < 0.001) and exercise (?9 mm Hg, p < 0.01) diastolic blood pressures. Diltiazem decreased double product at submaximal (p < 0.005) but not maximal exercise. Angina limited exercise in four patients after diltiazem compared to eight and seven patients after placebo and propranolol respectively (p < 0.05). Thus, diltiazem improved exercise performance with the use of radionuclide ventriculography during symptom-limited supine bicycle ergometry to a greater extent than did propranolol or placebo, and this effect was most apparent in those with decreased left ventricular function.     

Assessment of right ventricular function at rest and during exercise in patients with coronary heart disease: A new approach using equilibrium radionuclide angiography

To evaluate a new method of calculating right ventricular ejection fraction by equilibrium radionuclide angiography and to assess its response during supine bicycle exercise, 20 normal persons and 50 patients with angiographically documented coronary artery disease were studied. Each subject underwent a resting equilibrium and first pass right ventricular study as well as symptom-limited graded bicycle exercise while supine. The correlation between the two methods in all 70 cases was good (r = 0.81). Inter- and intraobserver variability was small (3.9 ejection fraction units or less) and serial reproducibility (two studies performed 2 weeks apart) was also good (4 ejection fraction units or less). There was no difference in the right ventricular ejection fraction at rest when normal subjects and patients with coronary disease were compared (0.49 ± 0.10 versus 0.46 ± 0.08). Ejection fraction increased with exercise in normal subjects (0.49 ± 0.10 to 0.64 ± 0.12, p < 0.005). As a group, patients with right coronary stenosis (alone or in combination with other lesions) showed no change in ejection fraction with exercise (0.46 ± 0.13 to 0.45 ± 0.12); and ejection fraction increased with exercise in patients with coronary disease without right coronary stenosis (0.46 ± 0.08 to 0.53 ± 0.11, p < 0.05). Among patients with both significant right and left coronary artery disease more severe right ventricular dysfunction during exercise was seen in the presence of more severe left ventricular dysfunction. It is concluded that during exercise the right ventricle shows dysfunction caused in part by local ischemia as well as by altered loading conditions due to left ventricular dysfunction. Equilibrium angiography is a useful and reliable method for evaluating right ventricular function in man.     

Right and left ventricular dysfunction in patients with chronic obstructive lung disease: Assessment by first-pass radionuclide angiography

To evaluate the relationship between right and left ventricular function in patients with obstructive lung disease, we studied 10 normal subjects (group 1) and 37 patients with chronic obstructive pulmonary disease by first pass radionuclide angiography. These 37 patients were divided into three groups: nine with mild chronic obstructive pulmonary disease (group 2), 20 with severe chronic obstructive pulmonary disease (group 3) and eight with severe chronic obstructive pulmonary disease and primary left ventricular disease (group 4). In each subject right ventricular ejection fraction (RVEF), left ventricular ejection fraction (LVEF) and ejection fraction during first third of systole (first third LVEF) were calculated. LVEF RVEF First-Third LVEF Group 1 0.60 ± 0.05 0.52 ± 0.03 0.29 ± 0.04 Group 2 0.61 ± 0.08 0.52 ± 0.03 0.29 ± 0.02 Group 3 0.58 ± 0.09 0.46 ± 0.091 0.24 ± 0.061 Group 4 0.51 ± 0.061 0.44 ± 0.091 0.20 ± 0.031 1 p < 0.05 versus 1. All subjects in group 2 had normal left ventricular and right ventricular function. In group 3,11 of 10 (55 per cent) had a low RVEF and three of 20 (15 per cent) a low LVEF. However eight of 20 in this group (40 per cent) had a depressed first-third LVEF. The correlation between decline in RVEF and first-third LVEF was good r = 0.73. We conclude that (1) certain indices of early systolic left ventricular ejection are abnormal in many patients with chronic obstructive pulmonary disease and correlate with the decline in right ventricular function; (2) this is not seen in patients with mild chronic obstructive pulmonary disease and is worse in patients with underlying left-sided heart disease.     

Analysis of ventricular emptying and filling indexes during acute increases in arterial pressure

Using equilibrium radionuclide angiography, an evaluation was made of the response of left ventricular ejection and filling rates at rest and during acute increases in afterload in 8 normal volunteer subjects and 10 patients with previous transmural myocardial infarctions. Using the postatropine point for comparison, normal patients increased ejection time and decreased peak ejection rate (-3.90 +/- 0.49 vol/s to -3.41 +/- 0.95 vol/s) and peak filling rate (3.94 +/- 0.88 vol/s to 3.51 +/- 0.38 vol/s). Infarct patients had similar responses, although all indexes were lower than the corresponding values in the normal subjects. At rest, the ratio of peak filling to emptying rate was similar in the normal subjects and the infarct patients (1.01 +/- 0.24 versus 0.99 +/- 0.25, respectively) and maintained that relationship after atropine (0.91 +/- 0.11 versus 0.81 +/- 0.21) and at the peak increase in arterial pressure (1.07 +/- 0.21 versus 1.02 +/- 0.32). The ratio of time to peak filling/time to peak emptying behaved in similar fashion regardless of the differences in the absolute values. In this study, left ventricular filling and emptying behaved in a similar fashion in response to the alteration in arterial pressure in normal subjects and in patients with previous myocardial infarctions.     

Endothelin-1 and peak oxygen consumption in patients with heart failure with preserved ejection fraction

BackgroundMechanisms of exercise intolerance in patients with heart failure with preserved ejection fraction (HFpEF) are not well understood. Pulmonary hypertension, a common accompaniment in patients with HFpEF, is associated with poor outcomes. While Endothelin -1 (ET-1) plays a mechanistic role in pulmonary hypertension, its role in exercise intolerance in HFpEF is not well established.ObjectiveTo explore the association between plasma ET-1 levels and maximal oxygen consumption (pVO2), and their changes over 24 weeks in HFpEF.MethodsThis is a post-hoc analysis of the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial. We performed linear regressions to assess the relationship between plasma ET-1 and pVO2. We also used linear regressions to determine whether ET-1 was associated with change in peak VO2 (ΔpVO₂).ResultsA total of 210 patients were included. Baseline plasma ET-1 levels were associated with older age, higher NT-proBNP levels, higher serum creatinine levels, and higher prevalence of atrial fibrillation. Patients with higher ET1 levels also had higher plasma galectin-3 and CITP levels. After multiple adjustments, baseline ET1 levels were associated with lower pVO₂ (β -0.927, SE 0.196, p < 0.001). Over 24 weeks, the change in ET1 levels was associated with the change in pVO2 (multivariable adjusted β -0.415, SE 0.115, p = 0.018). Baseline ET1 levels did not modify the effect of sildenafil on change in peak VO₂.ConclusionsPlasma ET1 levels are significantly associated with lower exercise oxygen consumption both at baseline and longitudinally over 24 weeks. Future studies should explore Endothelin-1 antagonism to improve exercise tolerance in HFpEF.     

Radionuclide analysis of pulmonary blood volume: The response to spontaneous angina pectoris and sublingual nitroglycerin in patients with coronary artery disease

By manually assigning pulmonary regions of interest and deriving pulmonary time-activity (volume) curves, we were able to make count estimates of pulmonary blood volume (PBV) from gated cardiac blood pool scans. Five patients with coronary heart disease developed angina spontaneously while under a gamma camera. This produced an increase in cardiac volumes (p < 0.05), a reduction in left ventricular ejection fraction (p < 0.01), along with a marked increase in PBV (0.010 ± 0.002 to 0.015 ± 0.003 untils, p < 0.05). Nitroglycerin was then administered and reduced PBV in association with a return to normal in cardiac systolic function and size. In patients with stable chronic ischemic heart disease, sublingual nitroglycerin also reduced PBV (p < 0.05), although not as much as when administered during an anginal episode. We conclude that gated imaging of the chest can be utilized to follow changes in PBV serially. These changes can be utilized to evaluate clinically important changes in hemodynamic status and the response to pharmacologic interventions.