B. Leonard Holman

Right ventricular ejection fraction: An indicator of increased mortality in patients with congestive heart failure associated with coronary artery disease

The predictive value of radionuclide ventriculography was studied in 34 patients with depressed left ventricular ejection fraction (less than 40%) and clinically evident congestive heart failure secondary to atherosclerotic coronary artery disease. In addition to left ventricular ejection fraction, right ventricular ejection fraction and extent of left ventricular paradox were obtained in an attempt to identify a subgroup at increased risk of mortality during the ensuing months. The 16 patients who were alive after a 2 year follow-up period had a higher right ventricular ejection fraction and less extensive left ventricular dyskinesia. When a right ventricular ejection fraction of less than 35% was used as a discriminant, mortality was significantly greater among the 21 patients with a depressed right ventricular ejection fraction (71 versus 23%), a finding confirmed by a life table analysis. Depressed right ventricular function was further linked to more severely compromised left ventricular function, as confirmed by a greater reduction in left ventricular ejection fraction and by an increased extent of left ventricular dyskinesia. These patients had a greater prevalence of chronic obstructive pulmonary disease and previous inferior myocardial infarction but the differences between groups were not statistically significant. It appears that the multiple factors contributing to the reduction in right ventricular ejection fraction make it a useful index not only for assessing biventricular function, but also for predicting patient outcome.

Decreased Lymphocyte Beta-Adrenergic-Receptor Density in Patients with Heart Failure and Tolerance to the Beta-Adrenergic Agonist Pirbuterol

We compared the initial and long-term effects of the beta-adrenergic agonist pirbuterol in 12 patients with chronic congestive heart failure. The drugs initial effect was a 35 per cent increase in cardiac index, but there was no significant change in heart rate or mean arterial pressure. After one month of therapy, the mean cardiac index and ejection fraction had returned to base-line values, and no clinical effect was evident in most patients. This apparent tolerance was not accompanied by changes in heart rate, blood pressure, or body weight, and it occurred in the presence of therapeutic drug levels during long-term therapy. The density of beta-adrenergic receptors on lymphocytes from patients treated with pirbuterol was significantly depressed as compared with that of patients with heart failure of comparable severity but not treated with pirbuterol. We conclude that tolerance to the hemodynamic and clinical effects of pirbuterol develops during long-term administration; this tolerance may be related to a decrease in myocardial or vascular beta-adrenergic receptors or both.

Long-term therapy of heart failure with prazosin: A randomized double blind trial☆

Abstract There is evidence that repeated administration of prazosin to patients with severe congestive heart failure results in tolerance to its initial salutary effects as a vasodilator. Therefore, we used a randomized, double blind protocol to evaluate the clinical effectiveness of 2 months of continuous prazosin therapy in 22 patients with severe congestive heart failure. After 2 months, the patients treated with prazosin showed significant improvement in mean New York Heart Association functional class (3.7 ± 0.2 to 2.3 ± 0.2, p

Ejection fraction image: A noninvasive index of regional left ventricular wall motion

Abstract The clinical value of the ejection fraction image, a computerized radionuclide measurement of regional left ventricular wall motion, was assessed in 34 patients. From gated modified left anterior oblique images of the cardiac blood pool, regional ejection fraction images were created. Left ventricular wall motion was classified with ejection fraction imaging as normal, hypokinetic or akinetic in each of three left ventricular regions. Wall motion was similarly characterized with regional analysis (segmental axis shortening, extent of akinetic segments) of contrast angiograms. Results of ejection fraction imaging were assessed in comparison with angiographic analyses. Seventeen patients had asynergy on contrast ventriculography; the other 17 had normal wall motion. There was agreement between the contrast and radionuclide ventriculograms as to presence of asynergy in 33 of 34 patients. In 92 of 102 (90 percent) left ventricular regions evaluated with both contrast and radionuclide methods, the ejection fraction image and contrast angiogram were in agreement regarding presence or absence of wall motion abnormalities. Of 43 abnormal angiographic wall motion descriptions in 35 ventricular regions (8 regions contained both hypokinetic and akinetic segments), 35 (81 percent) were similarly identified with the ejection fraction image. These results suggest that the ejection fraction image is a sensitive indicator of regional left ventricular wall motion.

Effect of Sublingually Administered Nitroglycerin on Regional Myocardial Blood Flow in Patients With Coronary Artery Disease

The effect of sublingually administered nitroglycerin on regional myocardial specific blood flow (in ml/min per 100 g tissue) was evaluated with a xenon-133 washout technique in 31 patients in a resting nonstressed state. Eight patients had normal coronary arteriograms (Group 1), 12 had coronary artery disease without collateral vessels (Group 2) and 11 had coronary artery disease with collateral vessels (Group 3). Although nitroglycerin caused a similar decrease in mean arterial blood pressure and blood pressure-heart rate product in all three groups, the decrease in regional myocardial blood flow was significantly less in Group 3 (-8+/-6% [mean+/-standard error of the mean]) than in Group 1 (-31+/-5%), P less than 0.05); an intermediary decrease occurred in Group 2 (-23+/-5%). Within Group 3, there was a mean increase in regional myocardial blood flow after nitroglycerin in the five patients whose collateral vessels were of a higher angiographic grade and arose from non-stenosed coronary arteries, whereas a reduction was observed in the six patients with none or only one of these findings (+10+/-7% versus -23+/-3%, P less than 0.001). This study suggests that even in the resting state, in some patients with coronary artery disease enhancement of regional myocardial blood flow can occur after sublingual administration of nitroglycerin and is probably mediated through well functioning collateral vessels. It is possible that the drugs effects on both the coronary and systemic circulation may relieve angina in some patients with coronary artery disease.

Detection and sizing of acute myocardial infarcts with 99mTc (Sn) tetracycline.

Abstract Myocardial scintigraphy was performed in 28 patients with the technetium chelate, 99mTc (Sn) tetracycline. Acutely infarcted myocardium was visualized as an area of increased radioactivity. All 14 patients with definite clinical evidence of acute myocardial infarction and two of five patients in whom the evidence of infarction was equivocal had abnormal scintigrams. Scintigraphy gave normal results in nine patients in whom an acute lesion failed to evolve. Peak activity occurred one to three days after the clinical onset of chest pain. Old infarcts did not concentrate 99mTc (Sn) tetracycline. (N Engl J Med 291:159–163, 1974)

Oral amrinone in refractory congestive heart failure

The acute effects of an oral preparation of amrinone, a recently synthesized cardiotonic agent, were assessed noninvasively in nine patients who had advanced heart failure that persisted despite treatment with digitalis, diuretic drugs and afterload-reducing agents. All patients demonstrated an improvement in left ventricular ejection fraction determined by radionuclide ventriculography (20.3 +/- 2.8 to 30.8 +/- 4.8 percent [mean +/- standard error of the mean], p less than 0.005) after a single dose of amrinone. Initial effects were seen within 1 hour, with the peak effect occurring at 1 to 3 hours; persistent effects were demonstrable at 4 to 6 hours. No change in blood pressure, heart rate or rhythm was observed, and there was no clinical evidence of myocardial ischemia. Continued benefit was demonstrated by radionuclide ventriculography in two patients treated for 1 and 6 weeks, respectively, although two other patients experienced major side effects with the chronic administration of amrinone. Although orally administered amrinone shows promise as a potentially useful agent in the treatment of advanced heart failure, the safety of this drug remains to be established.

Measurement of infarct size using single photon emission computed tomography and technetium-99m pyrophosphate: A description of the method and comparison with patient prognosis

The application of dual tracer transaxial emission computed tomography of the heart was studied with use of technetium-99m pyrophosphate and technetium-99m-labeled red blood cells for measuring infarct size in 20 patients with acute myocardial infarction and 10 without infarction. Imaging was performed with a standard gamma camera and with a multidetector transaxial emission computed tomographic body scanner 3 hours after injection of technetium-99m pyrophosphate. Immediately after the scanning procedure, technetium-99m pertechnetate was injected to label red blood cells, and the scanning protocol was repeated. Technetium-99m pyrophosphate was detected in the anterior wall with involvement of the interventricular septum or lateral wall in patients with electrocardiographic criteria for anterior infarction, whereas uptake was detected in the diaphragmatic left ventricular wall with involvement of the posterior, posteroseptal or posterolateral left ventricle or of the right ventricle in patients with electrocardiographic criteria for inferior or posterior infarction. Infarct size measured from transaxial images ranged from 14.0 to 117.0 g in weight. There was a direct relation between infarct size and patient prognosis in that, of the 13 patients with infarct greater than 40 g, 11 (85 percent) had complications, whereas only 2 (29 percent) of 7 patients with an infarct less than 40 g had complications during a follow-up period averaging 17.8 months (p less than 0.05).

Technepine: A high-affinity 99mtechnetium probe to label the dopamine transporter in brain by SPECT imaging

Increasing evidence suggests that the dopamine transporter, localized on dopamine neurons, is a marker for a number of physiological and pathological states (KaufmanandMadras, 1991,1993; Madras et al., 1990a, Schoemaker et al., 1985; Singer et al., 1991). With the development of sensitive probes, brainimaging and mea- surement of the transporter have become feasible in re- cent years (Brownell et al., in press; Innis et al., 1991; Frost et al., 1993; Madras et al., 1991; Morns et al., sub- mitted; Seibyl et al., 1995; van Dyke et a1.,1995; Wonget al., 1993,1995). Drugs of many chemical classes, includ- ing cocaine, bind to the dopamine transporter (Seeman, 1993). Nevertheless, effective imaging agents have been developed almost exclusively from the phenyltropane analogue of cocaine WIN 35,428 or CFT, a potent dopa- mine transport inhibitor (Clarke et al., 1973; Heikkila et al., 1979). The impetus for developing [llC]WIN 35,428 as a PET ligand (Hantraye et al., 1992; Madras, 1994; Madras et al., 1991, 1994; Wong et al., 1993; Meltzer et al., 1993) and y-emitting analogues for SPECT imaging (e.g., RTI-55, the 4-iodophenyl analogue of WIN 35,428, Canfield et al., 1990; Boja et al., 1991; Innis et al., 1991) arose directly from our observations of the binding of WIN 35,428 to the dopamine transporter. Unlike previ- ous dopamine transport inhibitors (noncocaine conge- ners) proposed for brain imaging(Kuhar et a1.,1990), the radiolabeled form of WIN 35,428 binds to the dopamine transporter in brain striatum with very low levels of non- specific binding (Madras et al., 1989a,b) and distributes principally to dopamine-rich regions of brain, as we re- ported in 1989 (Canfield et al., 1989) and subsequently (Canfield et al., 1990; Kaufman et al., 1991; Kaufman and Madras, 1992). SPECT imaging techniques are more practical than PET for routine clinical studies because of the lesser

“Luxury perfusion” with99mTc-HMPAO and123I-IMP SPECT imaging during the subacute phase of stroke

To compare the merits of123I-isopropyl-iodoam-phetamine (123I-IMP) and99mTc-HMPAO in showing abnormal brain uptake distribution during cerebral ischemia, we studied ten patients during the subacute phase of their stroke, a period where metabolism and blood flow are frequently uncoupled. SPECT imaging was performed using both radiopharmaceuticals in the 10 patients from 48 h to 4 weeks after onset of symptoms. Two patients out of the 10 had similar defects with123I-IMP and99mTc-HMPAO SPECT, the location of the defects corresponding to the area of infarction observed on CT. Six patients had normal99mTc-HMPAO SPECT and abnormal123I-IMP SPECT with defects in the area of infarction shown by CT. The remaining 2 patients had hyperactive abnormalities on99mTc-HMPAO in areas corresponding to defects on the123I-IMP images. Two of the patients with SPECT mismatches were studied again more than 1 month after onset. On reexamination,99mTc-HMPAO SPECT which was previously normal or hyperactive became hypoactive with a focal area of decreased activity corresponding to the defect on123I-IMP. Crossed cerebellar diaschisis was found in 7 patients with99mTc-HMPAO and was absent for both123I-IMP and99mTc-HMPAO in 3. We suggest that SPECT with99mTc-HMPAO could show transient hyperemia not demonstrated by123I-IMP whereas in some cases cerebral infarction would be more difficult to demonstrate with99mTc-HMPAO than with123I-IMP. SPECT with both tracers is recommended to follow the evolution of strokes in terms of regional cerebral blood flow and tissue metabolism.