James R. Corbett

Efficacy of prazosin in the management of chronic congestive heart failure: A 6-month randomized, double-blind, placebo-controlled study

The beneficial effects of acute prazosin therapy in patients with congestive heart failure (CHF) have been well documented; however, its chronic efficacy over several months has not previously been evaluated in a placebo-controlled manner. Therefore, an assessment was made by radionuclide ventriculography of the effect of prazosin, 20 mg/day, on left ventricular ejection fraction and end-systolic and end-diastolic volumes at rest and on peak upright bicycle exercise, as well as its effect on right ventricular ejection fraction at rest, exercise time and work load, and standard clinical variables in 23 patients with stable class III symptoms of CHF. The study consisted of a 6-month randomized, double-blind, controlled evaluation of prazosin versus placebo in patients receiving a stable dose of digitalis and diuretics for at least 1 month. At entry, the prazosin and placebo groups did not differ in any respect. Prazosin caused no demonstrable effect on clinical variables such as status of symptoms, heart rate, mean arterial pressure, and cardiothoracic ratio when compared with placebo. Prazosin also caused no demonstrable effect compared with placebo on absolute or percent changes in radionuclide variables at rest or on peak exercise, or on exercise time or exercise work load. In addition, prazosin had no consistent effect compared with placebo on plasma renin activity or plasma catecholamine levels. However, there was a slight but significant increase in weight (p less than 0.0001) and in plasma renin activity in the upright position (p less than 0.002) with time, as well as a tendency for the diuretic dose to increase with time in both groups. Thus, long-term prazosin therapy generally produces no demonstrable subjective or objective improvement in patients with stable, chronic class III CHF receiving digitalis and diuretic therapy.

Double-blind, randomized, placebo-controlled comparison of propranolol and verapamil in the treatment of patients with stable angina pectoris

This study was performed to compare the relative efficacies of propranolol and verapamil in patients with stable angina pectoris. In 18 patients (16 men, two women, mean age 58 years) with coronary artery disease and angina of effort, the results of low (40 mg every 6 hours) and high-dose (80 mg every 6 hours) propranolol therapy were compared to those of low (80 mg every 6 hours) and high-dose (120 mg every 6 hours) verapamil therapy in a double-blind, randomized, placebo-controlled evaluation which lasted eight weeks: two weeks of placebo therapy, two weeks of propranolol or verapamil (one week low-dose, one week high-dose) therapy, three days of down-titration followed by one week of placebo therapy, two weeks of propranolol or verapamil therapy (whichever was not given earlier in the trial) (one week low-dose, one week hgh-dose) and three days of down-titration. During each period the following were quantitated: (1) chest pains/week; (2) nitroglycerin used/week; (3) transient ischemic S-T segment deviations and highest grade of ventricular ectopic activity on two-channel Holter monitor; (4) S-T segment deviations during supine bicycle exercise; (5) left ventricular volumes and ejection fraction at rest and during exercise (assessed by equilibrium gated blood pool scintigraphy); and (6) pulmonary function studies. Propranolol and high-dose verapamil therapy significantly reduced the frequency of angina, and high-dose verapamil therapy diminished both the need for nitroglycerin and the frequency of transient ischemic S-T segment deviations on Holter monitor. Neither agent exerted a clinically-important deleterious influence on left ventricular volumes or the ejection fraction. Forced vital capacity and forced expiratory volume were worsened by propranolol but not by verapamil. Thus, in the patient with angina of effort, verapamil is a satisfactory therapeutic alternative to propranolol.

Tomographic gated blood pool radionuclide ventriculography: analysis of wall motion and left ventricular volumes in patients with coronary artery disease.

The use of planar radionuclide ventriculography to evaluate global and segmental ventricular function is limited by the superimposition of structures in some projections and the gross segmental resolution of the planar technique. Preliminary reports have suggested the feasibility of tomographic gated radionuclide ventriculography with rotating detector systems. This study tested the hypotheses that 1) tomographic radionuclide ventriculography detects segmental dysfunction at rest not identified with multiview planar studies and single plane contrast ventriculography, and 2) ventricular volumes and ejection fraction calculated from these studies provide data similar to those obtained with angiography and planar radionuclide ventriculography. Gated blood pool tomograms were acquired over 180 degrees at 15 frames per cardiac cycle during the initial 90% of the cardiac cycle. Compared with the multiview planar technique tomographic ventriculography showed an increased sensitivity for detecting left ventricular segments with significant coronary artery stenosis (97 versus 74%, p less than 0.025) without any loss in specificity. Compared with both planar radionuclide and contrast ventriculography, tomographic radionuclide ventriculography also detected more noninfarcted left ventricular segments supplied by stenosed coronary arteries (81 versus 39 and 32%, respectively, p less than 0.01). Tomographic radionuclide ventriculographic measurements of left ventricular volumes and ejection fraction showed close correlations with angiographic and planar radionuclide determinations. Gated blood pool tomography is a sensitive method for the evaluation of segmental wall motion and an accurate method for the measurement of global left ventricular volumes and ejection fraction.

Value of Radionuclide Ventriculography in the Immediate Characterization of Patients With Acute Myocardial Infarction

Abstract The ability of admission radionuclide ventriculography to discriminate among various clinical subsets was evaluated in patients with acute myocardial infarction. One hundred patients with acute myocardial infarction were evaluated within 8 ± 3.1 hours (mean ± standard deviation) after the onset of chest pain. Forty-one patients were in Killip functional class I, 52 in class II and 7 in class III. The mean radionuclide left ventricular ejection fraction was significantly lower in patients with higher Killip classification because of significant elevation of mean left ventricular end-systolic volume rather than significantly altered mean end-diastolic volume. Killip classification frequently failed to correlate with ejection fraction in individual cases. Admission chest X-ray findings were categorized according to the presence of findings suggestive of impaired left ventricular function. Mean left ventricular ejection fraction was significantly lower in patients with abnormal than in patients with normal chest X-ray findings because of significant elevations in both mean end-diastolic and end-systolic volumes. The chest X-ray findings frequently failed to correlate with ejection fraction in individual cases. Stepwise linear regression analysis was employed to analyze the ability of historical, physical, electrocardiographic and chest X-ray findings to predict radionuclide left ventricular ejection fraction. The most predictive variables in order of decreasing significance were anterior myocardial infarction, abnormal chest X-ray findings, rales to two thirds of the posterior thorax, previous myocardial infarction, transmural myocardial infarction and heart rate greater than 100 beats/min. However, even these six optimal predictive variables could explain only 42 percent of the observed variability in left ventricular ejection fraction. Thus, early radionuclide ventriculography adds significantly to the discriminant power of clinical and radiographic characterization of ventricular function in patients with acute myocardial infarction.

Prognostic value of resting and submaximal exercise radionuclide ventriculography after acute myocardial infarction in high-risk patients with single and multivessel disease

In patients who survive the acute phase of myocardial infarction, those with multivessel coronary artery disease generally have a worse prognosis than those with single-vessel disease. However, some patients with significant multivessel stenoses have a good prognosis, whereas some with a significant single-vessel stenosis have a poor prognosis. Thus, although definition of coronary anatomy may be helpful, it is a not a fail-safe prognosticator. In this retrospective analysis, the association of abnormalities at rest and during submaximal exercise testing with radionuclide ventriculography after acute myocardial infarction with major cardiac complications (death, recurrent infarction, severe angina or congestive heart failure) in the ensuing 6 months was assessed in patients with single and multivessel disease. Coronary angiography and submaximal exercise testing with radionuclide ventriculography were performed within 3 months of each other in 42 patients. Eleven of the 16 patients with single-vessel coronary stenosis had major cardiac complications. The subsequent course of these 16 patients was correctly predicted by left ventricular ejection fraction (LVEF) less than or equal to 0.40 in 8 patients, by LVEF less than 0.55 in 7 patients, by failure of LVEF to increase by 0.05 units in 13 patients, and by an increase in left ventricular end-systolic volume index (LVESVI) during exercise greater than 5% above baseline in 11 patients. Of the 26 patients with multivessel coronary artery disease, 24 had major cardiac complications. The subsequent course of these 26 patients was correctly predicted in 13 by LVEF less than or equal to 0.40, in 20 by LVEF less than 0.55, in 25 by a failure of LVEF to increase by 0.05 units during exercise, and in 20 by an increase in LVESVI by greater than 5% during exercise. Thus, submaximal exercise testing with radionuclide ventriculography may provide valuable prognostic information concerning the occurrence of major cardiac events after myocardial infarction not only in patients with multivessel disease, but also in those with single-vessel disease. Exercise-induced abnormalities of left ventricular function may have greater prognostic importance than the delineation of coronary arterial anatomy or the assessment of residual left ventricular function at rest.

Early detection of left ventricular dysfunction in chronic aortic regurgitation as assessed by contrast angiography, echocardiography, and rest and exercise scintigraphy

Abstract The best method for detecting early left ventricular (LV) dysfunction in patients with chronic aortic regurgitation is uncertain. Variables used previously to identify LV dysfunction have included (1) angiographic measurements to identify an LV end-systolic volume index (LVESVI) ≥60 ml/m 2 , (2) echocardiographic measurements to identify LV end-systolic dimension (LVESD) ≥5.5 cm or LV fractional shortening ≤25%, and (3) depressed LV ejection fraction (EF) at rest and/or an LVEF or LVESVI that deteriorates with exercise as detected by myocardial scintigraphic measurements. The hypothesis was tested that radionuclide ventriculography with exercise allows earlier detection of important LV dysfunction in patients with aortic regurgitation than the other variables. In 15 consecutive asymptomatic or only minimally symptomatic patients (8 men and 7 women, mean age 44 years) with isolated 2 to 4+ aortic regurgitation (1) rest and exercise-gated radionuclide ventriculography, (2) M-mode echocardiography, and (3) LV angiography were performed. No other cause of LV dysfunction was apparent in 13 patients; 1 patient had moderate systemic arterial hypertension and 1 had 50% luminal diameter narrowing of the proximal left anterior descending coronary artery. Ten patients did not have an increase in LVEF >0.05 EF units at peak exercise (0.58 ± 0.11 to 0.50 ± 0.12, mean ± standard deviation [SD]) (Group 2), whereas 5 had a normal LVEF response to exercise (0.63 ± 0.08 to 0.69 ± 0.07) (Group 1). Eight of the 10 patients with abnormal LVEF responses to exercise had a decrease in LVEF >10% during exercise. The same 8 patients also had an increase in LVESVI with exercise, whereas the 5 patients with normal LVEF responses to exercise had normal or blunted LVESVI responses to exercise. Only 4 of the 10 patients with exercise-induced LV dysfunction had an angiographic LVESVI ≥60 ml/m 2 , and only 1 had an echocardiographically determined LVESD ≥5.5 cm. Serial follow-up rest and exercise scintigraphic and echocardiographic measurements were made in 8 of the patients a mean of 9.4 months after the initial measurements; 3 patients were in Group 1 and 5 in Group 2. The 5 patients in Group 2 again demonstated abnormal LV function during exercise stress, and 2 of the 3 patients in Group 1 then demonstrated an abnormal LV functional response during exercise. Therefore, it is concluded that (1) exercise radionuclide ventriculography identifies LV dysfunction earlier than traditionally used assessments, (2) LV dysfunction appears to persist in patients that demonstrate it and develop in others that did not have it originally, and (3) echocardiographic dilatation of the LVESD to 5.5 cm appears to be a late and relatively unusual occurrence.

Effect of chronic oral digoxin therapy on ventricular function at rest and peak exercise in patients with ischemic heart disease

The effect of chronic digoxin therapy on left ventricular ejection fraction, left ventricular volumes and cardiac output was assessed using multigated blood pool imaging both at rest and during supine exercise in 14 patients with known ischemic heart disease. Digoxin had no significant effect on ejection fraction at rest or at peak exercise. Neither exercise nor digoxin therapy had a significant influence on stroke volume index. Cardiac index was also not significantly influenced by digoxin either at rest (3.1 ± 1.15 without digoxin versus 2.9 ± 1.03 liters/min per m2 during digoxin therapy) or at peak exercise (5.1 ± 2.08 versus 5.1 ± 2.04 liters/min per m2, respectively), although the increase in heart rate resulted in a significant increase in cardiac index with exercise in each state (p <0.01). End-diastolic and end-systolic volume indexes both tended to be smaller at rest after digoxin therapy than before, but this difference was not significant. In the eight patients with an ejection fraction at rest of less than 0.50 (range 0.15 to 0.47), both end-diastolic and end-systolic volume indexes increased significantly with exercise (p <0.05) irrespective of therapy with digoxin. Conversely, in the six patients with a well preserved (greater than 0.50) ejection fraction at rest, digoxin prevented the exerciseinduced increase in end-diastolic and end-systolic volume indexes, and at peak exercise end-systolic volume index was significantly smaller during digoxin therapy than before it (p <0.05). It is concluded that chronic digoxin therapy in patients with stable ischemic heart disease (1) does not have a significant deleterious functional effect on the nonfailing heart, and (2) does not result in a significant change in left ventricular function at rest, but that it (3) does provide improved ventricular function at peak exercise in patients with well preserved left ventricular function at rest.

Measurement of myocardial infarct size by technetium pyrophosphate single-photon tomography

The primary determinant of prognosis after acute myocardial infarction (AMI) is the size of the acute infarct. The present study evaluates 46 patients with different infarct distributions and sizes to test the hypothesis that single photon emission computed tomography with technetium-99m pyrophosphate (Tc-99m-PPi) and blood pool overlay allows measurements of AMI size that provide insight into prognosis irrespective of infarct location. Identical Tc-99m-PPi and ungated blood pool projections were acquired over 180 degrees with a rotating gamma camera. Reconstructed sections were color-coded and superimposed for purposes of infarct localization. Areas of increased pyrophosphate uptake within myocardial infarcts were thresholded at 65% of peak activity. The blood pool was thresholded at 50% and subtracted so as to determine an endocardial border for the left ventricle. Using this method, myocardial infarcts weighed 2.5 to 81.2 g. The correlation of infarct mass with prognosis showed that patients without previous AMI and with acute infarcts that weighed more than 40 g had an increased frequency of death and congestive heart failure (p less than 0.001). The correlation of measured infarct mass with peak serum creatine kinase level was significant (r = 0.83, p less than 0.001; y = 0.015x + 13.20). The correlation coefficients for anterior, inferior and nontransmural AMI were not significantly different from those for the entire group. In conclusion, tomographically determined infarct mass data correlate with subsequent clinical prognosis, and Tc-99m-PPi tomography with blood pool overlay is a safe and effective means of sizing infarcts in patients with AMI.

Early positive technetium-99m stannous pyrophosphate images as a marker of reperfusion after thrombolytic therapy for acute myocardial infarction

Fourteen patients with transmural acute myocardial infarction (AMI) were treated with intravenous streptokinase a mean of 4 +/- 1 hours after chest pain and underwent technetium-99m stannous pyrophosphate (Tc-99m-PPi) imaging 7 +/- 2 hours after the onset of chest pain. The early Tc-99m-PPi images were obtained to test the hypothesis that an early, strongly abnormal Tc-99m-PPi image suggests reperfusion. Eleven of 14 patients had early peaking (within 16 hours) serum creatine kinase isoenzyme levels (CK-B) at a mean of 11 +/- 3 hours. Ten of 14 patients had 3+ or 4+ acute Tc-99m-PPi images. Eight of 11 patients had patent infarct-related vessels at cardiac catheterization 15 days after AMI. One patient who had both an early positive Tc-99m-PPi image and CK-B peak level had an occluded infarct-related artery at catheterization. Acute left ventricular (LV) ejection fraction (EF) by radionuclide ventriculography was compared with LVEF on day 15, and improved from 0.37 +/- 0.13 to 0.50 +/- 0.16 (p = 0.004) in the 10 patients with strongly positive acute Tc-99m-PPi images. LVEF also improved from 0.37 +/- 0.12 to 0.49 +/- 0.15 (p = 0.003) in the 11 patients with early peaking serum CK-B values. Three patients without evidence of reperfusion failed to improve the LVEF from the initial value to the one obtained at hospital discharge. Six control patients had acute Tc-99m-PPi images 10 +/- 2 hours after chest pain; none had strongly positive acute Tc-99m-PPi images, and the mean time to peak CK-B was 19 +/- 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of left ventricular mass by single-photon emission computed tomography with thallium-201.

To test the hypothesis that single-photon emission computed tomography (SPECT) might permit accurate, noninvasive measurement of LV mass, SPECT measurements of LV mass to LV weight were compared in 20 mongrel dogs. Projection images of the left ventricle were acquired after intravenous injection of thallium-201 (TI-201). Transverse sections were reconstructed using filtered backprojection. Coronal sections were extracted from the reconstructed volume. The boundary of LV uptake of TI-201 in each coronal section was defined automatically using a threshold detector. Scintigraphic LV mass [total number of volume elements (voxels) showing TI-201 uptake X voxel volume X specific gravity of myocardium] was compared to actual LV weight. There was good correlation between scintigraphic LV mass and LV weight. Mean LV weight was 68 +/- 20 g (+/- standard deviation) (range 27 to 94). Mean SPECT LV mass was 66 +/- 19 g (range 28 to 100). Linear regression analysis yielded the following relation: SPECT LV mass = 0.87 X LV weight + 6.79 (r = 0.91, root-mean-square deviation from regression = 7.5). SPECT measurements were reproducible, with a coefficient of variation of 0.24%. Thus, SPECT of LV TI-201 distribution can be used to measure LV mass in canine myocardium.