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We measured cardiac performance sequentially, using quantitative radionuclide angiocardiography to estimate left ventricular ejection fraction in 55 patients receiving doxorubicin for treatment of cancer. With final doxorubicin dosages greater than 350 mg per square meter, the lowest ejection fraction measured was significantly less than the initial determination. Five patients had severe cardiotoxicity (congestive heart failure). All had an ejection fraction of less than 30 per cent at the time of heart failure, and demonstrated moderate cardiotoxicity (a decline in ejection fraction by at least 15 per cent to a final value of less than 45 per cent) before clinical manifestations. Six patients with moderate toxicity in whom doxorubicin was discontinued did not have heart failure or a further decline in ejection fraction during the follow-up period. Moderate toxicity was continued, but mild toxicity (decline of ejection fraction by greater than 10 per cent, noted in 11 patients) was not well predicted. The assessment of radionuclide left ventricular ejection fraction during doxorubicin therapy may make it possible to avoid congestive heart failure.

The pathophysiologic correlates of right ventricular ejection fraction, as well as its relation to contractile function as assessed by systolic pressure-volume data, were evaluated in 20 patients with chronic obstructive pulmonary disease. Radionuclide and hemodynamic measurements were obtained simultaneously. Baseline determinations were obtained in all patients. In seven patients, studies were repeated after intravenous administration of sodium nitroprusside. This procedure allowed characterization of right ventricular performance at decreased afterload and provided two points necessary for definition of the right ventricular systolic pressure-volume relation. Seventeen of the 20 patients had a depressed right ventricular ejection fraction (less than 45 percent). There was a strong inverse linear correlation between right ventricular ejection fraction and afterload as assessed by peak or mean pulmonary arterial pressure (r = −0.81) and pulmonary vascular resistance index (r = −0.73). Right ventricular ejection fraction also correlated, although less strongly, with preload as assessed by right ventricular end-diastolic volume index (r = −0.56) and mean right atrial pressure (r = −0.51). It did not correlate with cardiac index, the ratio of peak pulmonary arterial pressure to right ventricular end-systolic volume index, arterial oxygen tension or left ventricular ejection fraction. After nitroprusside administration, mean arterial pressure, peak pulmonary arterial systolic pressure and pulmonary vascular resistance index decreased significantly. The slope (E) and the volume intercept (V 0 ) of each pressure-volume line were determined. Administration of dobutamine resulted in a leftward shift from the endsystolic pressure-volume line. There were poor correlations between E and right ventricular ejection fraction, as well as between E and the control ratio between pulmonary arterial systolic pressure and end-systolic volume index. These data demonstrate that, in addition to intrinsic contractile influences, right ventricular ejection fraction is highly dependent on afterload, but less dependent on preload. Right ventricular ejection fraction is a poor indicator of the slope of the systolic pressure-volume relation, raising questions concerning its use as an independent index of chamber contractility.

The acute hemodynamic and functional effects of the relatively selective beta2 adrenoreceptor agonist, terbutaline, was evaluated in a well defined group of eight patients with chronic obstructive pulmonary disease, abnormal right ventricular performance and elevated pulmonary vascular resistance. Radionuclide and hemodynamic data were obtained simultaneously using first pass radionuclide angiocardiography and thermodilution pulmonary arterial catheterization. Terbutaline caused no change in right ventricular end-diastolic volume index but increased right ventricular stroke work index from 13 ±5 to 16 ± 6 g · m/m2 (mean ± standard deviation; p < 0.025). Furthermore, pulmonary vascular resistance index decreased in all patients and for the group decreased from 623 ± 279 to 407 ± 204 dynes · s · cm−5 · m2 (p < 0.05). The extent of this decrease correlated linearly with the level of resting pulmonary vascular resistance (r = 0.76). Right ventricular ejection fraction increased significantly from 35 ± 10 to 46 ± 5 percent; terbutaline resulted in normalization (to greater than 45 percent) of the ejection fraction in five of the eight patients. The changes in right ventricular ejection fraction were greatest in patients with the highest level of pulmonary vascular resistance and the lowest baseline ejection fraction. Left ventricular ejection fraction also increased significantly from 62 ± 10 to 71 ± 10 percent; however, there was no correlation between the change in this variable and either systemic vascular resistance or baseline left ventricular ejection fraction. Systemic oxygen delivery increased from 45 ± 16 to 63 ± 19 ml/min per m2 (p < 0.005) without any change in arterial oxygen tension. This study demonstrates that terbutaline results in substantial augmentation of right ventricular performance. This effect appears to be mediated predominantly through alterations in pulmonary vascular resistance. Terbutaline may provide significant cardiac benefits in addition to its salutory effects on the tracheobronchial tree.

Sudden unexplained death is a common cause of late mortality after aortic valve replacement. To evaluate the occurrence of ventricular arrhythmia in patients with aortic valve replacement, two 24 hour ambulatory electrocardiographic recordings were obtained in 45 such patients (mean age 55 years) who had undergone replacement an average of 3.3 years previously. In 43 patients, ventricular arrhythmia was detected; it was rare (mean premature ventricular complex frequency less than 1 15 min) in 18 patients (40 percent), moderately frequent (mean frequency 1− 10 15 min) in 14 patients (31 percent) and frequent (mean frequency more than 10 15 min) in 11 patients (24 percent). Multiformity was noted in 40 (89 percent), bigeminy in 27 (60 percent), couplets in 27 (60 percent) and ventricular tachycardia in 16 (36 percent) of the 45 patients studied. The occurrence of ventricular arrhythmia was not related to the predominant hemodynamic lesion or to the presence of coronary artery disease as determined at the time of preoperative cardiac catheterization. Radionuclide left ventricular ejection fraction, determined at the time of electrocardiographic monitoring in 39 patients, demonstrated normal left ventricular function (ejection fraction greater than 50 percent) in 27 patients (60 percent), moderately depressed function (ejection fraction 36 to 50 percent) in 8 (21 percent) and severe dysfunction in 4 (10 percent). When patients with abnormal versus normal left ventricular performance were compared, the mean premature ventricular complex frequency was 21 ± 26 15 min versus 5 ± 11 15 min ( p ; couplets occurred in 10 (83 percent) of 12 versus 13 (48 percent) of 27 patients (p

First pass radionuclide angiocardiography under conditions of rest and exercise was utilized to evaluate a group of 16 postoperative patients who had undergone total surgical correction of tetralogy of Fallot. Functional data were related to thallium-201 myocardial imaging at rest, a noninvasive means of detecting right ventricular hypertrophy. All 16 patients were asymptomatic and 15 demonstrated normal right ventricular ejection fraction (equal to or greater than 45 percent) at rest. However, 13 patients manifested abnormal right ventricular ejection fraction responses to exercise (normal response is an absolute increment in an ejection fraction of 5 or greater percent). For the entire group, right ventricular ejection fraction at rest was 55 ± 2 percent, whereas at exercise it was 52 ± 2 percent (p = not significant). In contrast, left ventricular ejection fraction responses were normal in all patients. Thallium-201 imaging revealed substantial right ventricular uptake consistent with residual right ventricular hypertrophy, which was quantifiable in all patients. Thus, abnormalities in right ventricular performance during exercise may be detected readily by this radionuclide approach in these postoperative patients despite their asymptomatic clinical status and generally normal right ventricular performance at rest.

Sequential first pass radionuclide angiocardiography can be performed in rapid succession using gold-195m because of its low radiation dose and short half-life (30.5 seconds). In 25 patients with known or suspected coronary artery disease, first pass studies with gold-195m were obtained using a computerized multicrystal gamma camera at rest (n = 29), at the end of each 3 minute stage of exercise (n = 25) and immediately after exercise (n = 23). In 13 patients, assessment of left ventricular function during exercise with gold-195m was combined with thallium-201 stress scintigraphy. Left ventricular ejection fraction at rest assessed with technetium-99m and gold-195m correlated well (r = 0.93). In addition, repeat left ventricular ejection fractions at rest with gold-195m correlated closely (r = 0.96). Comparing peak exercise left ventricular ejection fraction with ejection fraction at rest, abnormal left ventricular reserve was found in 20 of 25 patients. Various abnormal patterns of left ventricular ejection fraction response were noted, showing the diagnostic potential of serial exercise angiocardiography. Thallium-201 myocardial images, obtained on a single crystal gamma camera after multiple gold-195m injections, were all of good diagnostic quality and were abnormal in 10 of 13 patients. Thus, multiple high count rate first pass studies can be obtained with gold- 195m during and after exercise, allowing serial study Of physiologic changes in left ventricular function during exercise. Thallium-201 myocardial imaging can be performed using the same exercise test, providing direct comparison of myocardial function and perfusion.

The intrinsic variability and accuracy of left ventricular ejection fraction determined by multiple gated cardiac blood pool imaging was evaluated in 83 patients. Ejection fraction by gated studies correlated well with data from first pass radionuclide angiocardiography (r = 0.94) and from contrast angiography (r = 0.84). Intra- and interobserver variabilities of absolute ejection fraction were minimal (mean +/- standard deviation 1.4 +/- 1.2 and 1.6 +/- 1.5 percent, respectively) and were not different for normal (ejection fraction 55 percent or greater) and abnormal patients. Ejection fraction was determined twice in 70 patients: on the same day at intervals separated by 1 to 2 hours (41 patients) and on 2 different days (29 patients). Ejection fraction ranged from 18 to 91 percent and was normal in 37 patients. There was no difference in mean serial variabilities of absolute ejection fraction for all repeat studies performed on the same and separate days (3.3 +/- 3.1 versus 4.3 +/- 3.1 percent (not significantly different). The mean variability of absolute ejection fraction for repeat studies in normal patients was significantly greater than in abnormal patients (5.4 +/- 4.4 versus 2.1 +/- 2.0 percent, P less than 0.01). The incidence rate of absolute interstudy changes of 5 percent or more was significantly higher in normal than in abnormal patients (P less than 0.01). This differential variability should be considered in interpreting sequential changes in left ventricular ejection fraction. To be attributed to nonrandom physiologic alterations, the absolute change in ejection fraction should be 10 percent or more in normal patients and 5 percent or more in abnormal patients.

The feasibility of performing rapid sequential first pass radionuclide angiocardiography using a new short-lived radiotracer, gold-195m (195mAu) half-life 30.5 seconds) was evaluated. This radionuclide emits a 262 keV gamma ray and is the daughter of mercury-195 (195mHg) (half-life 41.6 hours). The prototype tabletop 195mHg/195mAu generator produced 20 to 25 mCi of 195mAu in 2 ml of eluate (yield of 40 percent). The breakthrough of 195mHg in the eluate was 0.02 percent of the amount of 195mHg in the generator. The eluate contained 20 microCi of 195mHg per study, resulting in an estimated human radiation dose of 0.007 rad/study to the whole body and 0.34 rad/study to the kidney. Four dogs each had 15 to 20 sequential first pass studies performed with 195mHg at 3 to 10 minute intervals using a computerized multicrystal gamma camera. During the left ventricular phase, 160,000 to 190,000 counts/s were acquired. The end-diastolic left ventricular region of interest contained 3,000 to 6,000 counts (background- and decay-corrected). Multiple reproducible values for left ventricular ejection fraction were obtained during stable conditions. The mean (+/- standard deviation) interstudy variability was 4 +/- 2 percent. During infusion of isoproterenol, rapid increase of left ventricular ejection fraction was demonstrated. Excellent agreement was observed between studies performed with technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA) and 195mAu. The mean interstudy difference was 4 +/- 3 percent. Thus, sufficiently high yield and dose are obtained from the 195mHg/195mAu generator for reliable high count rate first pass determination of left ventricular ejection fraction. This new short-lived radiotracer makes possible rapid sequential assessments of ventricular function at greatly reduced patient exposure to radiation.

First-pass radionuclide angiocardiography allows noninvasive determination of right and left ventricular performance from a single study. Analysis is made from the high frequency components of the regional radionuclide time-activity curves. Both regional and global ventricular performance can be assessed at rest and during exercise. Sequential studies can be performed to evaluate therapeutic interventions. This technique has been applied in a broad spectrum of patients with cardiac and pulmonary disease and has been shown to have major clinical impact.

Fourteen patients with chronic obstructive pulmonary disease, mild to moderate pulmonary hypertension, and diminished right ventricular (RV) ejection fraction were studied acutely with use of a combined radionuclide-hemodynamic approach to assess and contrast the effects of 3 vasodilators on RV performance and central hemodynamic function. Nitroglycerin significantly decreased mean right atrial pressure, RV end-diastolic volume index, mean pulmonary artery pressure, cardiac index, and arterial oxygen tension, but did not affect pulmonary vascular resistance index and increased RV ejection fraction. Nitroprusside had similar effects on mean right atrial pressure, RV end-diastolic volume index, mean pulmonary artery pressure, cardiac index, and arterial oxygen tension, but also mildly decreased pulmonary vascular resistance index and did not alter RV ejection fraction. In contrast, hydralazine decreased pulmonary vascular resistance index and increased cardiac index and RV ejection fraction. The increase in ejection fraction correlated well with the decrease in pulmonary vascular resistance. These data suggest that in patients with mild to moderate secondary pulmonary hypertension, acute administration of hydralazine results in a substantial improvement in RV performance by virtue of decreasing pulmonary vascular resistance. In contrast, nitroglycerin and nitroprusside demonstrate predominant effects that reduce preload, cardiac index, and arterial oxygen tension. Based on these data, afterload reduction with vasodilators such as hydralazine may be potentially useful in selected patients with pulmonary disease and secondary pulmonary hypertension and appear preferable to agents that primarily reduce preload. Further long-term studies are necessary to establish therapeutic efficacy.