John B. Bingham

Heart failure in outpatients: a randomized trial of digoxin versus placebo.

The view that digitalis clinically benefits patients with heart failure and sinus rhythm lacks support from a well-controlled study. Using a randomized, double-blind, crossover protocol, we compared the effects of oral digoxin and placebo on the clinical courses of 25 outpatients without atrial fibrillation. According to a clinicoradiographic scoring system, the severity of heart failure was reduced by digoxin in 14 patients; in nine of these 14, improvement was confirmed by repeated trials (five patients) or right-heart catheterization (four patients). The other 11 patients had no detectable improvement from digoxin. Patients who responded to digoxin had more chronic and more severe heart failure, greater left ventricular dilation and ejection-fraction depression, and a third heart sound. Multivariate analysis showed that the third heart sound was the strongest correlate of the response to digoxin (P less than 0.0001). These data suggest that long-term digoxin therapy is clinically beneficial in patients with heart failure unaccompanied by atrial fibrillation whose failure persists despite diuretic treatment and who have a third heart sound.

Early changes in left ventricular size and function after correction of left ventricular volume overload

The ability to predict early postoperative left ventricular size and function in patients with isolated aortic or mitral regurgitation was determined utilizing multigated blood pool imaging before and 2 to 4 weeks after valve replacement (aortic valve, 20 patients; mitral valve, 20 patients). Early postoperatively, ejection fraction decreased significantly (p <0.001) in both patient groups (from 0.55 ± 12 to 0.40 ± 0.14 [mean ± 1 standard deviation] in patients with aortic regurgitation and from 0.66 ± 0.09 to 0.48 ± 0.11 in patients with mitral regurgitation). The decrease in ejection fraction was associated with a large decrease in stroke volume with minimal or no change in end-systolic volume; it was unrelated to the preoperative ejection fraction. Early postoperative ejection fraction correlated best with preoperative end-systolic volume and was normal in 14 (67 percent) of 21 patients with a preoperative ejection fraction above 0.60; 4 (27 percent) of 15 patients with a preoperative ejection fraction of 0.50 to 0.60; and in 0 of 4 patients with a preoperative ejection fraction below 0.50 (p <0.05). In addition, a repeated scan in 16 patients late (1 to 2 years) after operation showed a further reduction in endsystolic volume in patients with aortic regurgitation with an increase in ejection fraction toward preoperative values. There was no significant change in patients with mitral regurgitation. End-diastolic volume decreased significantly (p <0.001) early postoperatively (from 162 ± 60 to 102 ± 41 ml/m2 in patients with aortic regurgitation and from 131 ± 40 to 78 ± 30 ml/m2 in patients with mitral regurgitation). This decrease was closely related to a decrease in stroke volume and was unrelated to preoperative ejection fraction. Early postoperative end-diastolic volume correlated best with the preoperative end-systolic volume. The major part of the reduction in end-diastolic volume occurred within 2 weeks of valve replacement. Removal of chronic left ventricular volume overload due to aortic or mitral regurgitation produces a decrease in ejection fraction and end-diastolic volume. The early reduction is in part a result of altered loading conditions and may not necessarily imply alterations in myocardial contractile function. The reduction in ejection fraction appears to persist in patients with mitral regurgitation.

Influence of coronary artery disease on pulmonary uptake of thallium-201

An increased pulmonary thallium-201 concentration has been observed in exercise stress thallium perfusion imaging in patients with coronary artery disease. To understand the cause of this lung uptake, studies were performed in experimental animals and in patients undergoing stress thallium perfusion imaging. The extraction fraction of thallium-201 by the lungs was measured in a group of eight dogs using a dual isotope technique. Basal thallium-201 extraction fraction at rest was 0.09 +/- 0.009. After administration of isoproterenol, it decreased to 0.06 +/- 0.02 (difference not significant). After balloon obstruction of the left atrium (which increased mean left atrial pressure and pulmonary transit time) and after administration of acetylcholine as a bolus injection (which prolonged pulmonary transit time only) it increased to 0.19 +/- 0.02 (p < 0.01). Lung thallium-201 activity was measured in 86 patients who had undergone cardiac catheterization and stress-redistribution myocardial perfusion imaging. The initial/final lung activity ratio was 1.41 +/- 0.03 in patients with no significant coronary artery disease, 1.52 +/- 0.03 (difference not significant) in patients with single vessel coronary disease, 1.60 +/- 0.05 (p < 0.05) in those with two vessel disease and 1.59 +/- 0.05 (p < 0.05) in those with triple vessel disease. Quantitation of lung activity in 30 of these patients indicated that the increased ratio in patients with multivessel coronary artery disease was due to a transient absolute increase in the thallium-201 concentration immediately after maximal exercise. The data imply that increased pulmonary concentration of thallium-201 during exercise is a consequence of left ventricular failure.

Spectrum of global left ventricular responses to supine exercise. Limitation in the use of ejection fraction in identifying patients with coronary artery disease.

Left ventricular function was evaluated with rest and supine bicycle exercise-multigated blood pool scans in 53 patients who had previously undergone coronary angiography for evaluation of a chest pain syndrome. There were 21 normal patients (less than 25% stenosis in any coronary artery, left ventricular end-diastolic pressure less than or equal to 12 mm Hg, and normal left ventriculography) and 32 patients with coronary artery disease (CAD) (greater than 50% narrowing in 1 or more major coronary arteries). Thirty-two (60%) were receiving propranolol at the time of the study. The normal patient group had a significant increase in mean ejection fraction (EF) during exercise (+0.08 +/- 0.09), while the CAD group had no increase (0 +/- 0.11; p less than 0.05). Mean end-systolic volume decreased significantly in the normal group (-5 +/- 8 ml/m2) but demonstrated no significant change in the CAD group (1 +/- 12 ml/m2; p less than 0.05 compared with normal patients). There was no significant change in mean end-diastolic volume in either group. Mean ejection rate, mean peak systolic pressure/end-systolic volume ratio, and mean pulmonary blood volume ratio also differed in the normal versus CAD patients. Despite mean differences, there was considerable overlap in both groups of individual EF responses: 8 of 21 (38%) of the normal group did not have an increase in EF of 0.05 with exercise, while 15 of 32 (47%) of the CAD group did have an increase in EF of 0.05 with exercise. However, the addition of peak systolic pressure/end-systolic volume ratio and pulmonary blood volume (exercise/rest) ratio improved the sensitivity for detecting CAD from 53 to 84% without adversely affecting specificity. Thus, there is a wide spectrum of left ventricular EF responses to supine exercise. In our patient population, EF alone was an insensitive and nonspecific marker of CAD. The addition of other parameters of global left ventricular function, which may be generated using radionuclide angiography, helps distinguish patients with CAD from normal subjects.

Of linens and laces—The eighth anniversary of the gated blood pool scan

Evaluation of ventricular performance is essential in the diagnosis and long-term management of patients with heart disease. This can be most easily performed clinically using simple tools. When more definitive objective assessment of cardiac function is indicated, the equilibrium gated blood pool study provides reliable angiographic evaluation of the heart. It will continue as a mainstay in the armamentarium of cardiology.

Cardiac nuclear imaging: Principles, instrumentation and pitfalls☆

The requirements for cardiac imaging with nuclear techniques are: (1) a radiolabeled tracer that is distributed in proportion to the function under investigation; (2) a collimator to allow photons arising only from specific areas of the heart to interact with the imaging device; (3) an imaging device to convert the gamma photon energy into an electrical signal that can be processed and displayed; and (4) a computer to record the information and permit quantification and optimal display of the data. One characteristic of nuclear imaging techniques is the requirement of averaging of a number of cardiac cycles to provide data for interpretation, whereas th information recorded with nuclear probes can be analyzed on a beat by beat basis. The data can be reviewed both visually and quantitatively. Semiautomatic methods of measuring ejection fraction, which correlate well with data from cardiac catheterization, have been in clinical use for several years. However, these techniques are not capable of correctly analyzing the data from all patients. Particular errors occur with gating, tracking the edge of the ventricle or in the selection of a background area, which may result in the calculation of an erroneous election fraction. In the future, short-lived radiopharmaceutical agents will result in a lower radiation burden to patients and higher quality studies in a shorter period of time, and tomographic techniques should provide new insights into the structure and function of the heart.

Scintigraphic evaluation of left ventricular aneurysm

Gated cardiac blood pool scintigraphy is a noninvasive method to assess regional and global left ventricular function in the patient with suspected true or false left ventricular aneurysm after a myocardial infarction. The procedure is easy to perform and provides reproducible, high resolution images that can accurately distinguish from diffuse contractile abnormalities often present after myocardial infarction. An overall accuracy rate of 96 percent for detection of left ventricular aneurysm can be obtained with gated cardiac blood pool scintigraphy as compared with contrast left ventriculography. The procedure also permits assessment of functional reserve of the noninvolved myocardium and thus can provide valuable information on whether enough viable myocardium will remain after aneurysmectomy. The addition of thallium-201 myocardial perfusion scintigraphy may aid in the separation of viable from scarred myocardium at the edge of the aneurysm. Both radionuclide techniques are well suited for screening the patient after infarction with persistent congestive heart failure, malignant arrhythmia or systemic emboli in whom a left ventricular aneurysm may have developed.

Comparison of three semiautomatic methods for determination of left ventricular ejection fraction from gated cardiac blood pool images.

A number of computer programs exist for the determination of ejection fraction from gated blood pool images. Three commercially available algorithms were compared on the same radionuclide data from 50 catheterized patients. The methods used were: (1) simple thresholding, (2) second derivative edge determination, and (3) a combination of these two. There was good correlation with catheterization ejection fraction for all three methods using smoothed data [r=0.781, 0.77, 0.84 respectively (P<0.01)]. However, interobserver variance was significantly decreased (P<0.01) by use of the second derivative method when compared with the other two methods and catheterization. Thus, if accuracy and low interobserver variance are required, then a combination of a second derivative and thresholding method is preferable.