Intracoronary thallium-201 scintigraphy after thrombolytic therapy for acute myocardial infarction compared with 10 and 100 day intravenous thallium-201 scintigraphy.

Thallium-201 imaging has been utilized to estimate myocardial salvage after thrombolytic therapy for acute myocardial infarction. However, results from recent animal studies have suggested that as a result of reactive hyperemia and delayed necrosis, thallium-201 imaging may overestimate myocardial salvage. To determine whether early overestimation of salvage occurs in humans, intracoronary thallium-201 scans 1 hour after thrombolytic therapy were compared with intravenous thallium-201 scans obtained approximately 10 and 100 days after myocardial infarction in 29 patients. In 10 patients with angiographic evidence of coronary reperfusion, immediate improvement in thallium defects and no interim clinical events, there was no change in imaging in the follow-up studies. Of nine patients with coronary reperfusion but no initial improvement of perfusion defects, none showed worsening of defects in the follow-up images. Six of these patients demonstrated subsequent improvement at either 10 or 100 days after infarction. Seven of 10 patients with neither early evidence of reperfusion nor improvement in perfusion defects had improvement of infarct-related perfusion defects, and none showed worsening. In conclusion, serial scanning at 10 and 100 days after infarction in patients with no subsequent clinical events showed no worsening of the perfusion image compared with images obtained in acute studies. Therefore, there is no evidence that thallium-201 imaging performed early in patients with acute myocardial infarction overestimates improvement.

The pacing stress test: thallium-201 myocardial imaging after atrial pacing. Diagnostic value in detecting coronary artery disease compared with exercise testing.

Many patients suspected of having coronary artery disease are unable to undergo adequate exercise testing. An alternate stress, pacing tachycardia, has been shown to produce electrocardiographic changes that are as sensitive and specific as those observed during exercise testing. To compare thallium-201 imaging after atrial pacing stress with thallium imaging after exercise stress, 22 patients undergoing cardiac catheterization were studied with both standard exercise thallium imaging and pacing thallium imaging. Positive ischemic electrocardiographic changes (greater than 1 mm ST segment depression) were noted in 11 of 16 patients with coronary artery disease during exercise, and in 15 of the 16 patients during atrial pacing. One of six patients with normal or trivial coronary artery disease had a positive electrocardiogram with each test. Exercise thallium imaging was positive in 13 of 16 patients with coronary artery disease compared with 15 of 16 patients during atrial pacing. Three of six patients without coronary artery disease had a positive scan with exercise testing, and two of these same patients developed a positive scan with atrial pacing. Of those patients with coronary artery disease and an abnormal scan, 85% showed redistribution with exercise testing compared with 87% during atrial pacing. Segment by segment comparison of thallium imaging after either atrial pacing or exercise showed that there was a good correlation of the location and severity of the thallium defects (r = 0.83, p = 0.0001, Spearman rank correlation). It is concluded that the location and presence of both fixed and transient thallium defects after atrial pacing are closely correlated with the findings after exercise testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular pressure-volume diagrams and end-systolic pressure-volume relations in human beings.

Assessment of left ventricular pressure-volume relations serially in response to altered loading conditions and heart rate has been difficult to achieve with contrast ventriculography. Accordingly, to study changing pressure-volume relations during altered loading and heart rate, left ventricular pressure and radionuclide absolute volume curves (obtained using a counts-based method with attenuation factor corrections) were recorded in 20 patients. Ventricular pressure and radionuclide volume curves were digitized and synchronized to end-diastole, and pressure-volume plots were subsequently constructed from 32 pressure-volume coordinates throughout the cardiac cycle. In all patients, the correlation between radionuclide absolute volumes and angiographic ventricular volumes was r = 0.92. In 10 patients in whom both radionuclide and angiographic pressure-volume diagrams were constructed, the agreement between the two methods was excellent. With this method, end-systolic pressure-volume relations were examined during altered left ventricular loading conditions, pacing-induced incremental increases in heart rate and pacing-induced ischemia. Using pharmacologically induced changes in left ventricular loading conditions, the slope and volume intercept of the end-systolic pressure-volume line could be calculated as a means of assessing basal contractility. During pacing-induced tachycardia, the slope and volume intercept of the end-systolic pressure-volume line could be calculated to quantify the Treppe effect and assess negative inotropic changes secondary to ischemia. This study supports the validity of using serial recordings of left ventricular pressure and radionuclide volumes to assess left ventricular pressure-volume relations, and indicates that this approach may be useful in the analysis of end-systolic pressure-volume relations in patients.

The pacing stress test reexamined: correlation of pacing-induced hemodynamic changes with the amount of myocardium at risk.

To assess the relation between extent of ischemia and the magnitude of hemodynamic changes, 25 patients (5 with normal coronary arteries and 20 with significant coronary obstructive disease) were studied with rapid atrial pacing and thallium scintigraphy at the time of cardiac catheterization. Hemodynamic variables were measured before, during and after maximal pacing. Thallium was injected intravenously during maximal pacing and scans in three standard views were obtained immediately in the catheterization laboratory, with delayed scans obtained 4 hours after the cessation of pacing. The three thallium scans were each subdivided into five segments, and a thallium score was obtained on the basis of the total number of segments that were hypoperfused. Each patient was assigned a total thallium score corresponding to thallium defects at maximal pacing, as well as a redistributed thallium score corresponding to the difference between thallium score at maximal pacing and that 4 hours later. With pacing, patients with normal coronary arteries demonstrated no significant change in baseline hemodynamic variables, whereas patients with coronary artery disease exhibited a decrease in cardiac index, an increase in systemic vascular resistance, a widening of arteriovenous oxygen difference, an increase in pulmonary capillary wedge pressure and mean pulmonary artery pressure during maximal pacing and an increase in left ventricular end-diastolic pressure immediately after pacing. There was a significant correlation (Spearman rank r = 0.64, p less than 0.01) between redistributed thallium score and an increase in left ventricular end-diastolic pressure in the postpacing period. Moreover, there was an even higher correlation (Spearman rank r = 0.90, p less than 0.001) between total thallium score and the postpacing increase in end-diastolic pressure. It is concluded that in patients with coronary artery disease the magnitude of pacing-induced hemodynamic changes reflects both the amount of myocardial tissue at ischemic jeopardy and the total mass of hypoperfused myocardium during maximal pacing stress.

Anomalous left circumflex coronary artery: "normal" variant of uncertain clinical and pathologic significance.

Anomalous origin of the left circumflex artery from the aorta is generally viewed as a benign coronary arterial anomaly. Three such cases are reported in which the anomalous artery was totally occluded. Although coronary atherosclerosis was present in all three cases, the proximal segment of the anomalous circumflex vessel was particularly severely affected in each patient. Two patients had a myocardial infarct in the distribution of the aberrant vessel. Accurate angiographic diagnosis is needed before cardiac surgery is performed, whether for valve replacement or myocardial revascularization, because this variant may be less benign than one believed.

Catenoidal shape of the interventricular septum in idiopathic hypertrophic subaortic stenosis: two dimensional echocardiographic confirmation.

A catenoid is a curved surface with the property of net zero curvature at all points. Morphologic observations have suggested that the interventricular septum in idiopathic hypertrophic subaortic stenosis has a catenoid shape, (that is, concave to the left in the transverse plane and convex to the left in the sagittal plane). To determine if such a septal configuration is present in living patients, six patients with clinically diagnosed idiopathic hypertrophic subaortic stenosis were studied with phased array two dimensional echocardiography, and left ventricular wall segment curvature, thickness and motion were compared with values in six patients with left ventricular hypertrophy secondary to long-standing systemic hypertension, and in six normal subjects. A curvature thickness index was determined from the echocardiographic image for systole and diastole as: curvature thickness index equals segment thickness times the sum of curvatures in the transverse and sagittal planes. In all six patients with idiopathic hypertrophic subaortic stenosis the septum had a catenoidal configuration and showed significantly less (p less than 0.05) septal change in the curvature thickness index during the cardiac cycle than it did in the control groups. In contrast, the left ventricular free wall had significantly greater (p less than 0.05) change of curvature thickness index over the cardiac cycle in patients with idiopathic hypertrophic subaortic stenosis. The hyperkinetic free wall motion seemed to account in part for systolic anterior motion of the anterior mitral leaflet as part of the displacement of the entire mitral apparatus. The catenoid shape of the septum observed in idiopathic hypertrophic subaortic stenosis may account for asymmetric hypertrophy and septal immobility, because a ventricular segment with net zero curvature would develop internal tension but have isometric contraction.

The pacing stress test: a reexamination of the relation between coronary artery disease and pacing-induced electrocardiographic changes.

Electrocardiographic (ECG) changes during graded pacing-induced tachycardia have been considered unreliable as a test for the presence of coronary artery disease (CAD) because of poor sensitivity and specificity. As a result, atrial pacing has not been widely used as an alternative to exercise testing. However, the limited value of the pacing stress test may be related to technical aspects, such as the duration of pacing and ECG monitoring. To study this problem, 22 patients undergoing coronary cineangiography underwent standard exercise stress testing and graded tachycardia induced by atrial pacing. A 12-lead ECG recorder was used for both tests. Pacing tachycardia was terminated when 85% of maximal predicted heart rate had been achieved or when significant ischemic chest pain accompanied by diagnostic ECG changes occurred. The ECG was considered positive if at least 1 mm of horizontal or downsloping ST-segment depression was present. Six patients with normal or minimally diseased coronary arteries were compared to 16 patients with significant CAD. Of the patients without significant CAD, 5 (83%) had a negative electrocardiogram during both exercise and pacing. Of 16 patients with CAD, the electrocardiogram was positive for ischemia in 10 patients (63%) during exercise, in 15 (94%) during atrial pacing and in 12 (80%) after pacing. When the presence or absence of ECG changes was compared between the exercise and the pacing tests, there was a concordance of 90% (Fisher p less than 0.0015). Two patients without significant CAD (33%) had chest pain during both exercise and pacing. Among patients with CAD, 7 (44%) had chest pain during exercise and 8 (50%) had chest pain during atrial pacing.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of intraventricular pressures at catheterization with postmortem ventricular curvature-thickness indexes in human hearts with aortic valve dysfunction.

It has been proposed that the pressure-producing activity of the ventricular wall segments, left and right free walls, and interventricular septum can be characterized by a curvature-thickness index (CTI) derived from the Laplace relation. Thirty patients with isolated aortic valve disease were examined clinically by cardiac catheterization and at autopsy after coronary arteriography and fixation of the heart in distention. The CTI for each segment was determined from wall thickness on postmortem radiographs, which is considered to represent tension in the Laplace relation, and from curvatures. The left ventricular shape was determined as the ratio of maximal diameter to chamber length. Segment CTIs were compared with peak systolic pressure in the respective chamber or with right and left ventricular pressure differences for the septum. A significant correlation was found between peak pressure and the CTI for ventricular free walls (r = 0.933, P less than 0.001), which was not improved by including ventricular distention as a predictor in a multivariate linear regression analysis. The left ventricular diameter-to-length ratio varied from 0.63 to 0.83 (average 0.74) and showed no significant differences related to type of aortic valve dysfunction. The results suggest that the CTI could serve as a useful index for evaluation of interventricular pressure and might be applicable to noninvasive diagnostic methods as well as postmortem studies.

Neovascularization and coronary atherosclerotic plaque: cinematographic localization and quantitative histologic analysis.

A new technique was developed for analyzing the neovascularization associated with coronary artery atherosclerosis: cinematography during silicone polymer injection of the coronary arteries of fixed and cleared human hearts, followed by histologic analysis in routine and 1-micron-thick, Epon-embedded sections. Twenty-two hearts obtained at autopsy were studied. On the basis of cinematographic findings, individual regions of the coronary arteries were classified as negative, positive, or abundantly positive for neovascularization. Positive and abundantly positive areas, which invariably occurred in segments exhibiting changes of atherosclerosis, contained numerous small vessels in the adventitia and outer media (4.7 +/- 1.5 and 9.8 +/- 1.3 [SE] vessel profiles/artery cross-section in positive and abundantly positive areas, versus 1.0 +/- 0.6 in negative regions). Abundantly positive areas, which occurred in coronary artery segments demonstrating the most extensive atherosclerotic change, contained numerous small vessels in the inner media or in the plaque itself. Some of these microvessels were in close proximity to mast cells, which represent potentially rich sources of mediators affecting vascular tone and permeability. Vessels were not observed in the inner media or in atherosclerotic plaque in areas designated either positive or negative by cinematography. These findings show how our approach can be used both to define the three-dimensional, in situ configuration of coronary artery neovascularization and to characterize the histology of this process in detail. They also confirm previous work indicating that areas of coronary arteries involved by atherosclerosis frequently exhibit extensive neovascularization.

Intracoronary thallium-201 assessment of thrombolysis in acute myocardial infarction. Validation of the method of imaging before and after therapy.

In order to study acute changes in perfusion with intracoronary thrombolytic therapy, we have used ten times the pretherapy intracoronary thallium-201 dose for the posttherapy study. Because of the larger posttherapy dose, the posttherapy images had ten times as many counts as the pretherapy images. Since the change in image quality between the pretherapy and posttherapy studies might affect interpretation, we studied the effect of image statistics on interpretation of perfusion scintigraphy. The pretherapy and posttherapy images were scored on a four-point scale in five segments on each of three views. In 31 patients, Poisson-distributed pseudorandom noise was added to the posttherapy study in order to match the statistical accuracy of the pretherapy study. A blinded interpretation of the pretherapy and posttherapy noise-added images was performed in the same way as the initial unblinded interpretation. The mean difference between the unblinded pretherapy and posttherapy scores (the improvement in thallium distribution with therapy) was 2.5+/-0.8 (standard error) compared with the difference between the blinded pretherapy and posttherapy noise-added scores which was 2.6+/-1.0. The correlation between readings of similar pairs of data was higher than the correlation between pretherapy and posttherapy studies. Thus, the difference in statistic quality of the pretherapy and posttherapy studies did not affect the interpretation of these studies. Therefore, our evaluation of pretherapy and posttherapy studies using a ten-fold increase in thallium-201 dosage is valid.

Pathology of the stone heart syndrome. Massive myocardial contraction band necrosis and widely patent coronary arteries.

Among 201 patients dying at some time after cardiac surgery employing cardiopulmonary bypass and studied at autopsy following postmortem coronary arteriography and fixation of the heart in a distended state there were 4 (2%) with the stone heart syndrome. All 4 fo these patients had undergone aortic valve surgery for aortic stenosis employing hypothermic anoxic arrest. At the conclusion of an uncomplicated operation the heart was firm, contracted, prone to fibrillate, and could not sustain the circulation. Pathological study showed widely patent coronary arteries and severe contraction band necrosis of the inner portions of both ventricular walls. The observations here, as in previous studies, suggest that contraction band necrosis may be elicited by a brisk reflow phase following a potentiating phase of anoxic arrest of the myocardium. The stone heart syndrome appears to be simply the manifestations produced by massive contraction band necrosis in a severely hypertrophied heart.

Cardiac sarcoid: a clinicopathologic study of 84 unselected patients with systemic sarcoidosis.

Although sarcoid may involve the myocardium, there is little information on its incidence or significance. We studied 84 consecutive autopsied patients with sarcoidosis. The patients ranged in age from 18--80 years (average 46 years) and 61% were women; 23 (27%) of them had myocardial granulomas. In eight (35%) these were clinically silent, and in 15 (65%) there was a history of heart failure and/or arrhythmias and conduction defects. Of the 23 patients, only four (17%) had grossly evident, widespread myocardial lesions: three of these four (75%) had documented arrhythmias. All four had sudden, unexpected death at an average age of 36 years; in only two had sarcoid been suspected during life. The other 19 patients (83%) had microscopically evident granulomatous involvement. Of these, eight (42%) had a thythm or conduction disturbance and three (16%) sudden death, although none of those who suffered sudden death had a recognized rhythm or conduction disturbance. Nine (15%) of those without cardiac sarcoidosis had a rhythm or conduction disturbance and eight (13%) suffered a sudden death. The results show that although myocardial involvement occurs in at least 25% of patients with sarcoid, it most often involves a small portion of myocardium and is clinically silent. Since some of the 61 patients in whom myocardial lesions were not identified may still have had small microscopic granulomas, the true incidence of myocardial sarcoid may be even greater than suggested here. Rhythm and conduction disturbances are more common in the cardiac sarcoid group, but the findings suggest that only the small subset of patients with severe, grossly evident myocardial sarcoid are at increased risk for sudden death.

Supine versus upright anterior images: comparison in T1-201 myocardial scintigraphy.

In patients undergoing exercise thallium-201 myocardial scintigraphy, activity in the inferior wall on anterior images may appear diminished when the standard supine view is used, but normal when the view is acquired with the patient upright. To determine the clinical significance of this observation, the distribution of thallium-201 activity was semiquantitatively assessed in supine and upright anterior images obtained immediately after exercise in 93 patients (65 men, 28 women). The presence of inferior wall and coronary artery disease was established with coronary angiography or from documentation of previous myocardial infarction. Supine and upright images were compared with use of receiver operating characteristic curves. In male patients diagnostic accuracy for identification of both inferior wall and coronary artery disease was improved through the use of the upright anterior image. In women, there was no significant difference in reader performance with upright and supine images. Upright anterior images should be routinely obtained in men in order to reduce the frequency of false-positive identification of inferior wall defects.

Comparison of early thallium-201 scintigraphy and gated blood pool imaging for predicting mortality in patients with acute myocardial infarction.

The extent of abnormality in early thallium-201 and gated cardiac blood pool scintigrams has been reported to be useful for predicting mortality in patients with acute myocardial infarction (AMI). To compare the two techniques, 91 patients admitted consecutively with evident or strongly suspected AMI underwent both imaging studies within 15 hours of the onset of symptoms. Patients with pulmonary edema or shock were excluded. AMI developed in 84% of patients, and 6-month mortality for the entire group was 16%. A thallium defect score of 7.0 or greater (corresponding to at least a moderate reduction of activity involving 40% of the left ventricular circumference) identified a subgroup of 14 patients with 64% 6-month mortality rate. Similarly, a left ventricular ejection fraction of 35% or less identified a high-risk subgroup of 10 patients with a 6-month mortality of 60%. Mortality in the remaining patients was 8% for thallium score less than 7 and 11% for ejection fraction greater than 35%. The mortality rate was highest among patients who had concordant high-risk scintigrams (five of six, 83%), lowest in those with concordant low-risk studies (five of 64, 8%) and intermediate in those with discordant results (four of 11, 36%). Of a number of clinical variables, only the appearance of Q waves, peak creatine kinase greater than 1000 IU/I, and history of infarction were significantly associated with mortality. High-risk thallium or blood pool scintigraphic results were significantly more predictive and a thallium score of 7 or greater was more sensitive for detecting nonsurvivors than ejection fraction 35% or less at a similar level of specificity. Stepwise multiple logistic analysis showed that the thallium score was the best predictor of mortality, but that appearance of Q waves and ejection fraction were additive. Using these three variables, 11 patients were calculated to have a 50% or greater chance of dying and eight (73%) actually died, compared with six of 70 (9%) with a calculated chance of death of less than 50%. These results in a prospectively identified and consecutive group of patients support the value of early thallium and blood pool scintigraphy for separating high- and low-risk subgroups of hemodynamically stable infarct patients.

The effect of caffeine on exercise tolerance and left ventricular function in patients with coronary artery disease.

STUDY OBJECTIVE: To determine whether acute oral caffeine ingestion by patients with coronary artery disease results in decreased treadmill exercise performance or deterioration of echocardiographic measures of systolic or diastolic left ventricular function. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Referral-based cardiovascular exercise laboratory at an urban teaching hospital. PATIENTS: Thirteen volunteers with clinically stable coronary artery disease who had exercise tests after a 2-week caffeine-free washout period. Patients continued treatment with standard antianginal medications during the study period. INTERVENTIONS: Maximal exercise treadmill testing and exercise echocardiography were done at baseline, after acute ingestion of a placebo beverage (97% caffeine-free coffee), or after drinking an identical beverage containing 250 mg of caffeine sodium benzoate. MEASUREMENTS AND MAIN RESULTS: Acute ingestion of caffeine produced a serum level of 4.50 +/- 0.16 micrograms/mL, but had no effect on resting supine heart rate, blood pressure, left ventricular fractional shortening, posterior left ventricular wall thinning or peak rates of increase in left ventricular diastolic dimension. Despite a small increase in peak systolic blood pressure during exercise (baseline, 153 +/- 8; placebo, 154 +/- 8; caffeine, 161 +/- 7 mm Hg; P less than 0.05), exercise duration, time to onset of angina, and time to 0.1 mV ST depression did not differ after ingestion of placebo or caffeine. Rate-pressure product at onset of angina and onset of 0.1 mV of ST depression were also unchanged. In response to exercise, echocardiographic measures of left ventricular systolic and diastolic function were unchanged after caffeine compared with placebo ingestion. CONCLUSIONS: These data suggest that patients with exercise-induced ischemia who are receiving appropriate antianginal therapy tolerate the caffeine-equivalent of three cups of coffee without detrimental effect on intensity of ischemia, myocardial function, or exercise duration.

Assessment of long-term therapy with milrinone and the effects of milrinone withdrawal.

To assess the long-term efficacy of milrinone in patients with severe congestive heart failure, we obtained hemodynamic measurements (systemic arterial and right heart catheterization) in 13 patients at baseline and after intravenous administration of milrinone. After continuous oral milrinone therapy of 8 +/- 4 months duration, repeat hemodynamic study was performed in patients on oral milrinone therapy, after withdrawal of milrinone, and after readministration of milrinone intravenously. Comparison of initial baseline and withdrawal hemodynamic measurements for the group as a whole showed no interval progression of heart failure, as reflected by the pulmonary capillary wedge pressure (27 +/- 8 to 24 +/- 12 mm Hg, NS) or the cardiac index (2.0 +/- 0.4 to 2.1 +/- 0.8 liters/min/m2, NS). Individual comparisons of milrinone-free hemodynamics revealed that five patients had improved hemodynamically, three patients were unchanged, and five patients had deteriorated, four of whom manifested dependence on milrinone with a progressive hemodynamic decline after milrinone withdrawal which required readministration of milrinone on an emergency basis. Continued efficacy of milrinone was observed on readmission after withdrawal: pulmonary capillary wedge pressure fell from 27 +/- 8 to 16 +/- 10 mm Hg (p = .001) initially and from 24 +/- 12 to 13 +/- 11 mm Hg (p = .001) at readministration, while cardiac index rose from 2.0 +/- 0.4 to 2.8 +/- 0.5 liters/min/m2 (p = .001) initially and from 2.1 +/- 0.8 to 2.7 +/- 0.5 liters/min/m2 (p = .005) upon readministration.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemodynamic determinants of thallium-201 lung uptake in patients during atrial pacing stress.

The present investigation was undertaken to define the hemodynamic determinants of lung uptake of thallium-201 (TI-201) in man during stress. Graded tachycardia was induced by atrial pacing with continuous hemodynamic monitoring in 21 patients (6 normal, 15 with coronary artery disease). At peak pacing, 80 MEq (2.2 mCi) of TI-201 was injected intravenously and imaging commenced within 5 minutes. Lung activity was expressed as a percentage of peak myocardial activity on the anterior image (Lung TI-201 Index). The influence of rest, peak and post pacing hemodynamic parameters including cardiac index, pulmonary capillary wedge pressure, left ventricular end-diastolic pressure, pulmonary artery pressure, and heart rate on Lung TI-201 Index was examined using step-wise multiple regression. Change in cardiac index from rest to peak pacing was negatively correlated, while pulmonary capillary wedge pressure at peak pacing was positively correlated to Lung TI-201 Index (combined r value of 0.75). No other parameter had a significant correlation. In summary, lung uptake of TI-201 activity during atrial pacing stress appears to depend on: changes in cardiac output which may determine tissue contact time and thus influence extraction efficiency, and hydrostatic pressure in the pulmonary capillary bed.

Angiogenic activity of adipose tissue.

Adipose tissue has been used to promote wound healing and to revascularize ischemic myocardium. We explored whether fat from various sources was angiogenic in the cornea. Rabbit subcutaneous and omental fat induced grossly visible neovascularization of all rabbit corneas studied, and at a similar rate and intensity. Neovascularization was not observed in any cornea following control implantation of liver or muscle. Neovascularization was blocked in all rabbits in which indomethacin was administered orally 3 days before implantation of fat and continued following implantation, suggesting that prostaglandins are associated with fat induced angiogenesis.