Exercise response of the systolic pressure to end-systolic volume ratio in patients with coronary artery disease.

The exercise response of the ratio of systolic blood pressure to end-systolic volume was studied in 243 patients with chest pain and coronary artery disease who underwent supine rest and exercise equilibrium radionuclide angiography. There was a wide variation in both rest and exercise variables in this group. The exercise response of the systolic pressure/volume ratio also varied greatly, ranging from a decrease of 59% to an increase of 136%. Twenty-one clinical, catheterization and radionuclide angiographic variables were examined to determine their relation to the exercise response of the systolic pressure/volume ratio; nine variables were individually correlated with this ratio. Multiple regression analysis identified the change in end-diastolic volume index with exercise, rest systolic blood pressure, coronary artery Gensini score and peak work load as significant independent predictors of the exercise response of the systolic pressure/volume ratio; the latter correlated significantly with the change in ejection fraction with exercise (r = 0.73, p less than 0.0001). Its sensitivity for the detection of coronary artery disease in the study group (84%) and its "normalcy rate" in a group of 120 patients with a low likelihood of coronary artery disease (81%) were similar to those of the peak exercise ejection fraction (75 and 82%, respectively). These results demonstrate that the exercise response of the systolic pressure/end-systolic volume ratio is a complex response that is influenced by several pathophysiologic variables in the presence of coronary artery disease. It does not offer any advantage over ejection fraction measurements for the detection of exercise-induced ischemia.

Myocardial stunning in hypertrophic cardiomyopathy: recovery predicted by single photon emission computed tomographic thallium-201 scintigraphy.

A young woman with hypertrophic cardiomyopathy confirmed by echocardiography and cardiac catheterization presented with chest pain and features of a large left ventricular aneurysm. The initial diagnosis was myocardial ischemia with either an evolving or an ancient myocardial infarction. Subsequently, verapamil therapy was associated with complete resolution of the extensive left ventricular wall motion abnormalities, normalization of left ventricular ejection fraction and a minimal myocardial infarction. Normal thallium uptake on single photon emission computed tomographic scintigraphy early in the hospital course predicted myocardial viability in the region of the aneurysm. Thus, orally administered verapamil may reverse spontaneous extensive myocardial ischemia in hypertrophic cardiomyopathy and possibly limit the extent of myocardial infarction in such circumstances.

Estimates of myocardium at risk and collateral flow in acute myocardial infarction using electrocardiographic indexes with comparison to radionuclide and angiographic measures.

OBJECTIVES: This study sought to determine the accuracy of the initial 12-lead electrocardiogram (ECG) in predicting final infarct size after direct coronary angioplasty for myocardial infarction and to examine which physiologic variables known to be determinants of outcome the ST segment changes most closely reflect. BACKGROUND: Myocardium at risk, collateral flow and time to reperfusion have been shown to be independent physiologic predictors of infarct size in animal and clinical models. However, such measurements may be difficult to perform on a routine basis in patients with myocardial infarction. The standard 12-lead ECG is inexpensive and readily available. METHODS: Sixty-seven patients with acute myocardial infarction, ST segment elevation and duration of chest pain < 12 h had an initial injection of technetium-99m sestamibi. Tomographic imaging was performed 1 to 8 h later (after direct coronary angioplasty), and the images were quantified to measure perfusion defect size (myocardium at risk) and severity (a measure of collateral flow). Contrast agent injection and tomographic acquisition were repeated at hospital discharge to measure infarct size. The ST segment elevation score was calculated for each patient according to infarct location and using previously described formulas. RESULTS: ST segment elevation score correlated closest with the radionuclide measure of collateral flow (r = -0.44, p < or = 0.0001), as well as an angiographic measure of collateral flow (r = -0.38, p = 0.05). Although ST segment elevation score correlated weakly with the magnitude of myocardium at risk by technetium-99m sestamibi, it was not as strong as infarct location alone in predicting myocardium at risk ([mean +/- SD] anterior 51 +/- 13% left ventricle vs. inferior 17 +/- 10% left ventricle, p < 0.0001). ST segment elevation score was weakly associated with final infarct size (r = 0.34, p = 0.005). A multivariate ECG model was constructed with infarct location as a surrogate for myocardium at risk, ST segment elevation score as a surrogate for estimated collateral flow, and elapsed time to reperfusion from onset of chest pain. All three variables were independently associated with infarct size. CONCLUSIONS: The initial standard 12-lead ECG can provide insight into myocardium at risk and, to a greater extent, collateral flow and can consequently provide some estimate of subsequent infarct size. However, the confidence limits for such predictors are wide.

Gender-related differences in cardiac response to supine exercise assessed by radionuclide angiography.

This study examines the recently reported gender differences in cardiac responses to exercise. The study group consisted of 192 men and 67 women with a low probability of coronary artery disease who underwent supine exercise radionuclide angiography. Men had a lower rest ejection fraction than that of women (0.63 versus 0.66, p = 0.02) and greater increases in ejection fraction with exercise (0.08 versus 0.02, p = 0.0001). The slope relating ejection fraction to metabolic equivalents of exercise (METs) was greater (p = 0.004) for men, even after adjustment for differences in rest ejection fraction and end-diastolic volume index. Compared with men, women had a smaller rest end-diastolic volume index (87 versus 97 ml/m2, p = 0.003) and a greater increase in end-diastolic volume index with exercise (6 versus -2 ml/m2, p = 0.002). The slope relating end-diastolic volume to METs was greater for women, even after adjustment for differences in rest end-diastolic volume index and peak work load. There are clear gender differences in the supine exercise response of ejection fraction and end-diastolic volume that are not explained by differences in exercise capacity.

Noninvasive identification of severe coronary artery disease using exercise radionuclide angiography.

The ability of exercise radionuclide angiography to predict the risk of having significant left main or three vessel coronary artery disease was examined in 681 patients who underwent both radionuclide and coronary angiography. There were significant differences in multiple variables between patients with or without such disease. Logistic regression analysis identified seven variables as independently predictive of the presence of left main or three vessel disease. Using these variables, low, intermediate and high probability groups could be identified. The four most important variables--the magnitude of exercise ST segment depression, peak exercise ejection fraction, peak exercise rate-pressure product and sex of the patient--can provide practical estimates of the risk of having left main or three vessel disease. Exercise radionuclide angiography can provide a clinically useful noninvasive estimate of the risk of having significant left main or three vessel disease.

Identification of severe coronary artery disease using simple clinical parameters.

The purpose of our study was to examine the ability of clinical and resting electrocardiographic variables to provide useful estimates of the probability of three-vessel or left-main coronary artery disease. The study group consisted of 680 patients with symptomatic coronary artery disease who underwent exercise equilibrium radionuclide angiography and coronary angiography within 6 months. Sixteen clinical and electrocardiographic variables were examined by logistic regression analysis. The independently predictive variables were then used to develop convenient graphic estimates of the probability of three-vessel or left-main disease and to classify patients into high-risk (greater than 35%), intermediate-risk (15-35%), or low-risk (less than 15%) groups. Five variables were independently predictive of left-main or three-vessel disease: age, typical angina, diabetes, gender, and both history and electrocardiographic evidence of a prior myocardial infarction. A single graph was constructed that displayed the probability of severe coronary artery disease as a function of a five-point cardiac risk scale, which incorporated these variables. Two hundred sixty-two patients (39% of the study group) were classified as high risk; 127 of these patients (48%) had three-vessel or left-main disease. An additional 96 patients were classified as low risk; nine of these patients (9%) had three-vessel or left-main disease. Five clinical variables that were obtained on an initial patient assessment can provide useful estimates of the likelihood of severe coronary disease.

Association between anterior ST depression and increased myocardial salvage following reperfusion therapy in patients with inferior myocardial infarction.

PURPOSE: To determine electrocardiographic features associated with myocardial salvage following reperfusion therapy in patients with inferior myocardial infarction. PATIENTS AND METHODS: Ninety-two consecutive patients with acute inferior myocardial infarction were treated with reperfusion therapy in a tertiary care center. Several features were measured on the presenting electrocardiogram, including the presence or absence of ST depression in the chest leads and the total magnitudes of ST elevation or depression, and were then evaluated for their association with myocardial salvage. Myocardial salvage (% of left ventricle) was the difference between myocardium at risk and final infarct size. Tomographic myocardial perfusion imaging with technetium-99m sestamibi was performed acutely to measure myocardium at risk and repeated prior to hospital discharge to measure final infarct size. RESULTS: The amount of myocardium at risk of infarction in the 92 patients was 19.1%+/-11.3% (range 1% to 68%), and the final infarct size was 10.6%+/-10.0% (range 0% to 45%). Thus, myocardial salvage in the 92 patients was 8.5%+/-8.4% (range -11% to 35%) of the left ventricle, or 0.51+/-0.38 (range 0.0 to 1.0) when expressed as a fraction of the myocardium at risk (salvage index). The presence or absence of anterior ST depression was the only one of seven electrocardiographic variables that was associated with myocardial salvage. Myocardial salvage was significantly greater in patients with anterior ST depression compared with those without it (10.6%+/-9.0% versus 5.9%+/-6.7%, P=0.025). Myocardium at risk was significantly greater in patients with anterior ST depression compared with those without the depression (22.8%+/-12.2% versus 14.6%+/-8.3%, P=0.0006), and infarct size tended to be larger (12.1%+/-10.4% versus 8.7%+/-9.4%, P=0.10). Myocardial salvage as a fraction of the myocardium at risk (salvage index) was similar between the two patient groups (0.52+/-0.37 versus 0.50+/-0.39, P=NS). CONCLUSION: The presence of anterior ST depression during inferior myocardial infarction identifies a group of patients with the potential for greater myocardial salvage with reperfusion therapy. Such patients derive greater absolute benefit from reperfusion therapy because they have a larger amount of myocardium at risk, although their response to therapy (salvage index) is not intrinsically different.

Influence of age and sex on left ventricular filling at rest in subjects without clinical cardiac disease.

Left ventricular (LV) filling at rest was studied by radionuclide ventriculography using alternate R-wave gating in 42 patients (29 men, 13 women) who had a low likelihood of cardiac disease. LV filling measurements differed little between men and women. Age was correlated positively with atrial filling duration (r = 0.55), atrial filling duration fraction (r = 0.52) and atrial filling fraction (r = 0.56) and negatively with rapid filling fraction (r = -0.58). Age was not correlated with peak filling rate, time to peak filling rate and first-half filling fraction. The heart rate at rest was significantly negatively correlated with rapid (r = -0.62), slow (r = -0.81) and atrial (r = -0.72) filling durations, but not with isovolumic duration. The heart rate at rest was weakly positively correlated with peak filling rate in end-diastolic volume per second (r = 0.36) and negatively correlated with first-half filling fraction (r = -0.35). Systolic pressure at rest influenced atrial filling duration. LV ejection fraction and end-diastolic volume index were not correlated significantly with LV filling in relatively normal subjects.

Influence of left ventricular diastolic filling on symptoms and survival in patients with decreased left ventricular systolic function.

The relation between left ventricular (LV) filling variables measured by gated blood pool radionuclide ventriculography and clinical symptoms and survival was examined in 93 patients who had decreased LV systolic function. The diastolic data were not significantly associated with clinical symptoms. Time to peak filling rate, peak filling rate and ejection fraction were associated independently with survival free of cardiac death (chi-square = 7.74, 5.91 and 3.92, respectively, by stepwise Cox regression analysis). A short time to peak filling rate or increased peak filling rate was associated with decreased survival, whereas the opposite indicated a good prognosis. One-year Kaplan-Meier survival was 73 and 98% when time to peak filling rate was below or above the median value of 167 ms, respectively, 82 and 90% when peak filling rate was above or below the median value of 1.67 end-diastolic volumes per second, respectively, and 76 and 95% when LV ejection fraction was below or above the median value of 0.35, respectively. Thus, filling variables (time to peak filling rate and peak filling rate) measured by radionuclide ventriculography may be valuable in predicting survival in patients with decreased LV systolic function.

Significance of anterior ST depression in inferior wall acute myocardial infarction.

Early tomographic myocardial perfusion imaging with technetium-99m sestamibi was performed during inferior wall acute myocardial infarction to determine the relation between the amount and location of myocardium at risk and the presence or absence or anterior ST depression. The total size of the acute perfusion defect and its lateral and septal borders were measured in 29 consecutive patients who were admitted with > 30 minutes of chest pain and acute inferior ST elevation on their initial electrocardiogram. The 22 patients with anterior ST depression had significantly more left ventricular myocardium at risk than the 19 patients who did not have anterior ST depression (23 +/- 2% of the left ventricle vs 15 +/- 1%, p = 0.008). All 8 patients with > 25% of the left ventricle at risk had anterior ST depression. Patients with anterior ST depression had a significantly greater lateral extent of the acute perfusion defect (49 degrees +/- 8 degrees from the midinferior wall vs 23 degrees +/- 7 degrees, p = 0.002). There was no difference in the septal border of the perfusion defect between patients with and without anterior ST depression (-44 degrees +/- 4 degrees vs -46 degrees +/- 7 degrees, p = NS). No patient had a measurable anterior perfusion defect. Although there is considerable overlap between groups with and without anterior ST depression, anterior ST depression is a simple and readily available indicator of myocardium at risk in inferior wall acute myocardial infarction.

Guidelines for the interpretation of the exercise radionuclide ventriculogram for diagnosing coronary artery disease.

In 622 patients with known coronary artery anatomy, heart rate (HR).blood pressure (BP) product and left ventricular (LV) ejection fraction (EF) at maximal supine exercise measured by radionuclide ventriculography were used to estimate, by logistic regression analysis, the probabilities of absence of significant coronary artery disease (CAD), presence of significant CAD, presence of multivessel CAD and presence of 3-vessel CAD. Thus, for example, estimated probabilities of each of the aforementioned 4 categories of CAD are 0.39, 0.61, 0.32 and 0.12, respectively, for HR.BP product of 26,000 beats.mm Hg/min and LVEF of 0.6 at maximal exercise and 0.08, 0.92, 0.77 and 0.48, respectively, for HR.BP of 15,000 and LVEF of 0.4. The graphic presentations of these estimated probabilities form useful guidelines for interpreting the results of exercise radionuclide ventriculography. In addition, specific cutoff values at maximal exercise defined 2 groups: (HR.BP product greater than or equal to 21,000 beats.mm Hg/min and LVEF greater than or equal to 0.55) with a high (70%) likelihood of absence of significant CAD or 1-vessel CAD and a low (7%) likelihood of 3-vessel CAD, and (HR.BP product less than 21,000 and LVEF less than 0.55) with a high (72%) likelihood of multivessel CAD and a low (8%) likelihood of absence of CAD.

Prevention of late ventricular dilatation after acute myocardial infarction by successful thrombolytic reperfusion.

To examine the sequential changes in left ventricular volume after thrombolytic therapy for acute myocardial infarction, gated radionuclide ventriculography was performed within 12 hours of thrombolysis and at 1 and 6 weeks in 34 consecutive patients who received intravenous thrombolytic therapy in the Thrombolysis in Myocardial Infarction Trial. Angiographic confirmation of immediate reperfusion (mean 5.6 hours after onset of symptoms) that persisted at 24 hours was noted in 24 patients; 10 patients were not reperfused. A small (9.5%), but significant (p = 0.05), increase in end-diastolic volume index was noted in the reperfused group between 1 and 6 weeks; however, a marked degree of dilatation (35%) was noted in the non-reperfused group (p = 0.01). The change in left ventricular volume between 1 and 6 weeks differed in the 2 groups for both end-diastolic volume index and end-systolic volume index (p = 0.01 and p = 0.02, respectively). By 6 weeks, both end-diastolic volume index and end-systolic volume index were greater in the nonreperfused group (p less than 0.05). Between the acute and 6-week studies, definite increases in end-diastolic volume index (p less than 0.05) and end-systolic volume index (p less than 0.01) occurred commonly in the nonreperfused group but rarely in the reperfused group. Compared to the nonreperfused group, the reperfused group also had significantly higher ejection fractions at both 1 and 6 weeks (p less than 0.05). The change in end-diastolic volume index between 1 and 6 weeks correlated significantly and inversely with the ejection fraction at 1 week (r = -0.60, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular systolic response to exercise in patients with systemic hypertension without left ventricular hypertrophy.

Supine exercise radionuclide angiography was performed in 367 men to assess left ventricular (LV) systolic response to exercise; 58 had systemic hypertension without LV hypertrophy on a resting electrocardiogram and 309 were normotensive. All patients met the following criteria defining a low pretest likelihood of coronary artery disease: age less than 50 years; normal electrocardiographic response to exercise; absence of typical or atypical chest pain; and exercise heart rate greater than 120 beats/min. Patients taking beta-receptor blockers were excluded. There were no significant differences between hypertensive and normotensive groups in peak exercise heart rate, workload or exercise duration. However, hypertensive patients had significantly higher peak exercise systolic blood pressures and peak exercise rate-pressure products. There were no differences between patients with and without hypertension in resting ejection fraction, peak exercise ejection fraction (hypertensive patients 0.71 +/- 0.01, normotensive patients 0.70 +/- 0.05) or change in ejection fraction at peak exercise (hypertensive patients 0.07 +/- 0.01, normotensive patients 0.07 +/- 0.04). Diastolic and systolic ventricular volumes tended to be smaller in the hypertensive patients, but the difference was not statistically significant. The change in systolic volume with exercise was similar in the 2 groups (hypertensive -10 +/- 3 ml/m2, normotensive -10 +/- 1 ml/m2). In the absence of electrocardiographic evidence of LV hypertrophy, systemic hypertension does not influence LV systolic response to exercise.

Anatomic and functional significance of a hypotensive response during supine exercise radionuclide ventriculography.

The significance of a decline in systolic blood pressure (BP) during supine exercise was examined in 820 patients who underwent both supine exercise gated equilibrium radionuclide ventriculography and coronary angiography. Twenty-seven patients, 3% of the study population, had a decrease in systolic BP at peak exercise of more than 10 mm Hg from the systolic BP at rest. Other indicators of ischemia--angina, ST-segment depression, a decrease in ejection fraction and wall motion abnormality during exercise--were present frequently but not uniformly in these patients. Although most patients had a decline in ejection fraction and a new wall motion abnormality with exercise, 4 patients had an increase in ejection fraction with exercise without any regional wall motion abnormalities. Coronary angiography in the 27 patients with systolic hypotension demonstrated severe coronary artery disease (CAD). Twenty-two patients (81%) had 3-vessel or left main CAD. Twenty of these 22 patients with 3-vessel CAD had at least 2 arteries with 90% or more diameter stenoses. Systolic hypotension during supine exercise radionuclide angiography is infrequent, usually associated with evidence of global and regional left ventricular dysfunction, and a marker of very severe CAD.

An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty (the FESTIVAL study).

Maximal benefits of coronary reperfusion after acute myocardial infarction (AMI) with ST-segment elevation may be attenuated by neutrophil-mediated reperfusion injury. Inflammatory mediators released from potentially viable myocytes cause activation of neutrophils, which traverse the endothelium and enter the myocardium. This process involves interaction between the neutrophil-expressed CD11/CD18 and endothelial-expressed intercellular adhesion molecule-1 (ICAM-1). Preclinical studies have shown that monoclonal antibodies (MAb) to CD18 can limit infarct size and preserve left ventricular function. We sought to determine the initial clinical safety and tolerability of Hu23F2G (LeukArrest), a humanized MAb to CD11/CD18, in patients with AMI who underwent percutaneous transluminal coronary angioplasty (PTCA). Sixty patients with AMI were randomized to low- (0.3 mg/kg) or high-dose (1.0 mg/kg) Hu23F2G or to placebo immediately before PTCA. We found no clinically significant differences in vital signs, physical examination, laboratory evaluation, or need for subsequent cardiac interventions. In Hu23F2G treatment groups, serum concentration of Hu23F2G increased rapidly to 3,234 +/- 1,298 microg/L (low-dose group) and 15,558 +/- 4409 microg/L (high-dose group) between 5 and 60 minutes, then declined over 72 hours to near-baseline values. Myocardial single-photon emission computed tomographic imaging 120 to 260 hours after PTCA showed no statistically significant differences in final left ventricular defect size. Hu23F2G was well tolerated, with no increase in adverse events, including infections. Thus, Hu23F2G appears safe and well tolerated in patients undergoing PTCA for AMI.

Use of the internal mammary artery for myocardial revascularization in a patient with radiation-induced coronary artery disease.

A 9-year-old boy with clinical stage IIA Hodgkin's disease underwent radiotherapy to the neck and mediastinum. Twenty-two years later, he sought medical attention because of angina pectoris. Cardiac catheterization revealed proximally located high-grade stenoses of the left main, left anterior descending, circumflex, and right coronary arteries. He underwent coronary artery bypass grafting with use of the left internal mammary artery to the left anterior descending coronary artery and reversed saphenous vein grafts to the circumflex and right coronary arteries. The postoperative course was uncomplicated. Previous radiotherapy to the mediastinum should be considered a risk factor for the development of premature coronary artery disease. Surgical revascularization is the preferred method of management. A combination of an internal mammary artery graft and a saphenous vein graft should be used in young patients.

Radionuclide measurement of left ventricular volume.

Count rates observed at end-diastole and end-systole in the region of the left ventricle on gated radionuclide angiograms were correlated with corresponding estimates by biplane contrast angiography of left ventricular volumes in 37 patients. When count rates were normalized for number of cardiac cycles processed, time per frame, isotope decay, and count rate observed in venous blood after equilibrium, there was a strong correlation between normalized left ventricular count rate and contrast angiographic volume, whether the venous sample was counted in a well counter or with the use of the same gamma camera. The latter technique was judged easier and more accurate. The derived regression equations yielded a good estimate of ventricular volume from left ventricular count rates when prospectively compared with contrast angiographic volumes in a further 17 patients. Interobserver variability of both the radionuclide and the contrast angiographic estimate of the left ventricular volume was similar. Changes in left ventricular stroke volume induced by sublingual administration of nitroglycerin as measured by the radionuclide method correlated reasonably with corresponding changes in stroke volume measured by the dye-dilution method. It is concluded that left ventricular volumes obtained noninvasively by the radionuclide technique were accurate and were subject to the same interobserver variability as the contrast angiographic technique.

Failure of interventions to maintain mitochondrial function in ischemic myocardium.

The purpose of this study was to investigate whether pyruvate (2.5 mmol/kg), the combination of glucose (3.9 mmol/kg) and insulin (0.13 unit/kg) with potassium (9.27 meq/kg), or sodium dichloroacetate (120 mg/kg) infused for 15 minutes before and 20 minutes after ligation of the left anterior descending coronary arterv in anesthetized dogs restricted the depression in mitochondrial respiratory function induced by ischemia. Myocardial blood flow after ligation in the three groups was o.2 ml/min per gram or less in ischemic subendocardium and was similar to that in saline-infused controls that had also undergone coronary artery ligation. The depressions induced in mitochondrial respiratory control index and state 3 respiration by ischemia in the subendocardium and subepicardium of the three treatment groups, when compared with corresponding nonischemic tissue, were not significantly improved from the control values. It was concluded that these three interventions fail to preserve mitochondrial respiration in ischemic myocardium.

Cardiac involvement in Lyme disease: manifestations and management.

Cardiac involvement in Lyme disease may manifest as atrioventricular block, myopericarditis, and left ventricular dysfunction. Diagnosis depends on recognition of the systemic nature of Lyme disease, including cardiac involvement, and its natural history. Serologic tests that are both sensitive and specific may aid in diagnosis. Although current recommendations for the treatment of Lyme disease with carditis include antibiotics and salicylates or corticosteroids, these types of therapy have not been unequivocally demonstrated to alter the natural history of cardiac involvement. Supportive therapy may necessitate temporary transvenous cardiac pacing in symptomatic patients.

Cardiac asystole masquerading as temporal lobe epilepsy.

Episodic behavior associated with impairment of consciousness is a protean clinical manifestation that may suggest a wide range of medical or neurologic disorders. We describe a patient whose symptoms of an epigastric "aura" followed by loss of consciousness suggested temporal lobe epilepsy. The episodic behavior was refractory to antiepileptic drug therapy. Prolonged video-electroencephalographic monitoring confirmed that the clinical events were cardiogenic related to asystole. Antiepileptic drug therapy was discontinued, and a cardiac pacemaker was inserted. The clinical patterns that distinguish syncope from seizures and the importance of prolonged video-electroencephalographic monitoring are discussed.