Conservative management after thrombolysis: the strategy of choice.
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Academic Medical Centers↗
Biomedical subjects
E M Geltman
Publications and source records attributed to E M Geltman.
Increased myocardial perfusion at rest and diminished perfusion reserve in patients with angina and angiographically normal coronary arteries.
Angiographically normal coronary arteries are found in a substantial number of patients evaluated for angina pectoris. One third to one half of such patients demonstrate abnormalities of myocardial perfusion or metabolism when evaluated with invasive techniques. This study was designed to determine whether angina in such patients is attributable to abnormalities of perfusion at rest, maximal perfusion or vasodilator reserve and whether any identified abnormalities were global or regional in nature. Positron emission tomography was performed with oxygen-15-labeled water (H2(15)O) and oxygen-15-labeled carbon monoxide (C15O) before and after intravenous dipyridamole to assess regional myocardial perfusion and perfusion reserve in absolute terms in 16 normal subjects and 17 patients with chest pain and angiographically normal coronary arteries. Eight of the 17 patients had a myocardial perfusion reserve less than 2.5 (the lower limit of normal in studies with positron emission tomography, as well as with other techniques) and 9 of 17 patients had a normal response. In the patients with an impaired perfusion reserve, perfusion at rest was significantly higher than that measured in normal subjects (1.61 +/- 0.38 versus 1.25 +/- 0.28 ml/g per min, p less than 0.02) and maximal flow and perfusion reserve were significantly reduced (2.26 +/- 0.92 versus 4.62 +/- 1.58 ml/g per min and 1.4 +/- 0.5 versus 3.8 +/- 1.1, respectively; p less than 0.001 for both comparisons). Abnormalities of perfusion and perfusion reserve were spatially homogeneous without detectable regional disparities. Thus, nearly half of patients with chest pain and normal coronary arteries have abnormalities of myocardial perfusion that are detectable noninvasively with positron emission tomography and H2(15)O.
Angina Pectoris↗
Nonuniformity in myocardial accumulation of fluorine-18-fluorodeoxyglucose in normal fasted humans.
In initial studies using fluorine-18-fluorodeoxyglucose (FDG) in normal fasted subjects, we observed disparities in the regional myocardial accumulation of this tracer. Accordingly, we systematically evaluated regional myocardial FDG accumulation in comparison with regional myocardial perfusion assessed with oxygen-15-water and oxidative metabolism assessed with carbon-11-acetate in nine normal subjects (four studied after a 5-hr fast and five studied both fasted and following glucose loading). Under fasting conditions, myocardial accumulation of FDG in the septum and anterior wall averaged 80% of that in the lateral and posterior walls (p less than 0.03). In contrast, after glucose loading the regional distribution of myocardial FDG accumulation became more homogeneous. Regional myocardial perfusion, oxidative metabolism, and accumulation of carbon-11-acetate were homogeneous under both conditions. Thus, under fasting conditions there are regional variations in myocardial accumulation of FDG, which are visually apparent, are not associated with concomitant changes in oxidative metabolism or perfusion, and cannot be attributed to partial-volume effects. This significant heterogeneity may limit the specificity of PET with FDG for detecting myocardial ischemia in fasting subjects.
Acetates↗
Three-dimensional functional images of myocardial oxygen consumption from positron tomography.
Images from positron emission tomography (PET) are usually presented as transaxial slices portraying tissue radioactivity. Studies can be difficult to interpret from transaxial images, and the temporal changes in tissue tracer concentrations which permit quantitative determinations of metabolism and perfusion are not displayed. We have developed a method to give quantitatively accurate three-dimensional images of myocardial oxygen consumption from serial images of the myocardial washout of carbon-11-acetate. Following i.v. bolus injection, data are collected for 20-30 min. The time-activity curves for each pixel in the transaxial slices are fit to a monoexponential function to determine the washout rate, which is directly related to the rate of myocardial oxygen utilization. Thus, functional images of myocardial oxygen consumption are produced for all seven slices of PET data. A previously developed method is then used to generate realistic and quantitatively accurate three-dimensional images.
Acetates↗
Mild heart failure: diagnosis and treatment.
CHF afflicts 15 million persons worldwide despite advances made in its diagnosis and treatment. A thorough physical examination and basic, noninvasive evaluation are essential for establishing the diagnosis of heart failure and for designing an optimal, individualized treatment regimen. Although digitalis and diuretics continue to be used commonly for the treatment of CHF of all severities, the use of vasodilators and ACE inhibitors has increased dramatically, as they are used more widely and earlier in the course of the illness. Because the RAA system contributes significantly to the altered cardiovascular hemodynamics and symptomatology characteristic of heart failure, the ACE inhibitors provide a rational approach to therapy for many patients. Results of controlled clinical trials have shown that selected vasodilators and ACE inhibitors can improve survival in patients with CHF and that patients receiving ACE inhibitors show sustained improvement in clinical class, exercise tolerance, and hemodynamics. Thus the therapeutic spectrum available to the clinician dealing with patients with CHF has broadened substantively over the past decade.
Clinical Laboratory Techniques↗
Enzymatic estimation of the extent of irreversible myocardial injury early after reperfusion.
To determine whether the extent of infarction can be estimated enzymatically soon after reperfusion, the rate of increase of creatine kinase (CK) activity in plasma early after coronary recanalization was compared with infarct size in 18 dogs and 10 patients. In dogs, reperfusion was initiated 2 to 4 hours after coronary occlusion. CK activity was measured in serial plasma samples and infarct size was assessed histochemically at 24 hours. A substantial and consistent fraction of the total CK appearing in plasma over 24 hours (cumulative CK) appeared in plasma soon after reperfusion, i.e., 21 +/- 2% (SE) within 30 minutes and 38 +/- 3% within 1 hour. The rate of increase of plasma CK activity correlated closely with infarct size when CK release was measured during the first 30 minutes (r = 0.92) or 60 minutes (r = 0.92) after reperfusion (n = 18). Similarly, in patients the rate of increase of CK activity measured within 2.5 hours of the time of reperfusion was closely related to infarct size delineated by positron emission tomography 1 to 2 weeks later (r = 0.93). Thus the rate of appearance of CK in plasma early after reperfusion reflects the extent of irreversible injury ultimately sustained and provides a criterion likely to be useful for prospective identification of patients at high risk after coronary recanalization.
Adult↗
Assessment of myocardial oxidative metabolic reserve with positron emission tomography and carbon-11 acetate.
We have previously demonstrated that positron emission tomography (PET) with [11C]acetate allows noninvasive regional quantification of myocardial oxidative metabolism. To assess the metabolic response of normal myocardium to increased work (oxidative metabolic reserve), clearance of myocardial 11C activity after administration of [11C]acetate i.v. was measured with PET in seven normal subjects at rest and during dobutamine infusion. At rest, clearance of 11C was monoexponential and homogeneous. The rate constant of the first phase of 11C clearance, k1, averaged 0.054 +/- 0.014 min-1 at a rate-pressure produce (RPP) of 7329 +/- 1445 mmHg X bpm. During dobutamine infusion, RPP increased by an average of 141% to 17,493 +/- 3582 mm Hg Z bpm. Clearance of 11C became biexponential and remained homogeneous. k1 averaged 0.198 +/- 0.043 min-1 with a mean coefficient of variation of 16%.. k1 and RPP correlated closely (r = 0.91; p less than 0.001), and the slope of the k1/RPP relation remained consistent in all subjects (1.48 +/- 0.42). These findings suggest that PET with [11C]acetate and dobutamine stress may provide a promising approach for evaluation of regional myocardial oxidative metabolic reserve in patients with cardiac diseases of diverse etiologies and for assessment of the efficacy of interventions designed to enhance the recovery of metabolically comprised myocardium.
Acetates↗
Noninvasive estimation of regional myocardial oxygen consumption by positron emission tomography with carbon-11 acetate in patients with myocardial infarction.
We previously demonstrated in experimental studies that myocardial oxygen consumption (MVO2) can be estimated noninvasively with positron emission tomography (PET) from analysis of the myocardial turnover rate constant (k) after administration of carbon-11 (11C) acetate. To determine regional k in healthy human subjects and to estimate alterations in MVO2 accompanying myocardial ischemia, we administered [11C]acetate to five healthy human volunteers and to six patients with myocardial infarction. Extraction of [11C]acetate by the myocardium was avid and clearance from the blood-pool rapid yielding myocardial images of excellent quality. Regional k was homogeneous in myocardium of healthy volunteers (coefficient variation = 11%). In patients, k in regions remote from the area of infarction was not different from values in myocardium of healthy human volunteers (0.061 +/- 0.025 compared with 0.057 +/- 0.008 min-1). In contrast, MVO2 in the center of the infarct region was only 6% of that in remote regions (p less than 0.01). In four patients studied within 48 hr of infarction and again more than seven days after the acute event, regional k and MVO2 did not change. The approach developed should facilitate evaluation of the efficacy of interventions designed to enhance recovery of jeopardized myocardium and permit estimation of regional MVO2 and metabolic reserve underlying cardiac disease of diverse etiologies.
Acetates↗
Relationship of QRS scoring system to enzymatic and pathologic infarct size: the role of infarct location.
A method for estimating infarct size from 12-lead ECGs has been developed but not extensively validated. To assess its accuracy, ECG scores from 62 patients admitted to the coronary care unit at Barnes Hospital were compared to infarct size calculated from plasma MB creatine kinase (MB-CK) activity. A second cohort of 29 patients enrolled in the Multicenter Investigation of the Limitation of Infarct Size (MILIS) was evaluated as a test set and to provide pathologic correlates. Patients with conduction system disease, ventricular hypertrophy, or multiple infarctions were excluded, as were those in the Barnes group who had undergone thrombolytic therapy. ECGs obtained early (days 3 to 7 in the Barnes group and day 3 in the MILIS group) or late (days 8 to 14 in the Barnes group) were scored manually and by computer. QRS scores from early ECGs of patients with anterior infarctions correlated closely with MB-CK estimates of infarct size (r = 0.71 [Barnes] and 0.85 [MILIS] and with anatomic data (r = 0.78). Enzymatic and pathologic infarct size also correlated well (r = 0.85). Correcting for body surface area by means of total CK-derived infarct size or use of QRS scores from late ECGs did not alter the correlation coefficients. Among patients with inferior infarctions QRS scores corresponded poorly with MB-CK infarct size (r = 0.28 [Barnes] and r = -0.42 [MILIS]) and pathologic infarct size (r = -0.20), despite a significant relationship between pathologic and MB-CK estimates (r = 0.62).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Delineation of impaired regional myocardial perfusion by positron emission tomography with H2(15)O.
Positron emission tomography with 15O-labeled water (H2(15)O) can be used to delineate abnormal regional myocardial blood flow in experimental animals. To determine the feasibility of this method in humans, we studied 33 subjects (9 normal volunteers and 24 patients with angiographically documented coronary artery disease) at rest and after myocardial hyperemia induced with intravenous infusion of dipyridamole. At rest, the myocardial region demonstrating the lowest relative H2(15)O activity exhibited 71 +/- 8% of activity in the region with peak activity in control subjects and 62 +/- 17% in patients (p = NS). After the dipyridamole infusion, differences between the two groups were accentuated. In control subjects, activity in the region with lowest relative radioactivity averaged 77 +/- 5% of that in the region with peak activity. In patients, it averaged 55 +/- 22% of activity in the region with peak activity (p less than 0.01). Results in patients with ischemia with or without a history of remote myocardial infarction were not significantly different. In 22 of the 24 patients, the region with lowest relative perfusion corresponded anatomically to the region of myocardium distal to a stenosis. Thus, delineation of regional myocardial perfusion in patients with coronary artery disease is possible with positron emission tomography and H2(15)O. Further studies will be necessary to prospectively determine sensitivity and specificity.
Adult↗
Differentiation of ischemic from nonischemic cardiomyopathy with positron emission tomography.
This study was undertaken to determine whether positron emission tomography (PET) performed after the intravenous injection of 11C-palmitate permits differentiation of patients with ischemic from those with nonischemic dilated cardiomyopathy. PET was performed after intravenous injection of 11C-palmitate in 10 patients with ischemic and in 10 with nonischemic dilated cardiomyopathy. Regions of homogeneously severely depressed accumulation of 11C-palmitate, representing 15% or more of the expected myocardial cross-sectional area, were observed in 8 of 10 patients with ischemic but in none of 10 patients with nonischemic cardiomyopathy. Patients with nonischemic cardiomyopathy had marked spatial heterogeneity of the accumulation of palmitate throughout the left ventricular myocardium, whereas most tomographic sections from patients with ischemic cardiomyopathy accumulated 11C-palmitate more homogeneously in regions exclusive of discrete defects indicative of remote infarction. Thus, a larger number of discrete noncontiguous regions (17 +/- 5 compared with 12 +/- 4, p less than 0.001) and greater reduction of average 11C-palmitate content (59 +/- 6 compared with 64 +/- 10% maximal myocardial radioactivity, p less than 0.05) were seen in the tomographic reconstructions from patients with nonischemic than in those from patients with ischemic cardiomyopathy. These findings support the hypothesis that multiple myocardial infarctions underlie the process seen as dilated cardiomyopathy in patients with coronary artery disease. Our findings indicate that PET permits differentiation of patients with ischemic from those with nonischemic cardiomyopathy.
Cardiomyopathy, Dilated↗
Lack of myocardial necrosis despite clinical and electrocardiographic criteria of acute transmural infarction.
The development of "pathologic" Q waves with ST segment elevation is considered diagnostic of transmural myocardial infarction. Previous reports have suggested that myocardial ischemia without infarction can result in electrocardiographic abnormalities simulating those of acute infarction. However, lack of infarction has been poorly documented in these reports. If real, this phenomenon could have an impact on the management of patients with apparent acute infarction. This study describes a patient with documented severe myocardial ischemia and electrocardiographic evidence of acute transmural myocardial infarction, in whom significant myocardial necrosis has been excluded definitively.
Aged↗
Enhancement of metabolism of jeopardized myocardium by nifedipine.
To define effects of nifedipine on regional metabolism in jeopardized myocardium we quantified accumulation of carbon-11 labeled palmitate ([11C]palmitate) in patients with acute myocardial infarction by positron emission tomography in a randomized, double-blind, placebo controlled study. Tomographic studies were performed prior to treatment as soon as possible after hospital admission. Subsequent studies were performed seven days later. Twenty-two patients with acute myocardial infarction were randomized to treatment with nifedipine (n = 13) or placebo (n = 9). The dosage of active medication was guided by a "third party observer" to avoid iatrogenic hypotension. Treatment was initiated within 9.6 +/- 1 hours after the onset of symptoms of infarction. The extent of the zone of abnormal accumulation of [11C]palmitate was similar in pre-treatment positron emission tomograms from patients subsequently given nifedipine compared with those given placebo. In subsequent positron emission tomography studies, patients treated with nifedipine exhibited improved metabolism of [11C]palmitate (by 16 +/- 10%, SE, P less than 0.05) compared with no change in patients given placebo. Neither enzymatic estimates of infarct size nor scintigraphic estimates of left ventricular ejection fraction differed in the two groups. Patients given nifedipine and manifesting substantial improvement in accumulation of [11C]palmitate had a high incidence of chest pain and recurrent infarction compared with those given placebo in whom no improvement was evident. These observations suggest that some regions of myocardium were benefited transiently by nifedipine but that they remained at high risk for recurrent injury. Thus, patients benefited transiently by drugs early after the onset of infarction may require aggressive intervention such as angioplasty or early coronary bypass surgery. Accordingly, they should be evaluated angiographically early for identification of lesions with unusually high risk.
Blood Pressure↗
Assessment of coronary thrombolysis.
The efficacy of coronary thrombolysis may be assessed by several invasive and noninvasive means, including coronary angiography, contrast and radionuclide angiography, thallium 201 or 99mTc-pyrophosphate scintigraphy, positron emission tomography, cardiac ultrasonography, electrocardiography, and analysis of plasma creatine kinase activity. Each technique has its own strengths and limitations, but when used in concert these methods may provide insight into the physiology of coronary reperfusion and the efficacy of reperfusion in individual patients and populations.
Angiocardiography↗
Coronary thrombolysis with intravenous streptokinase.
Coronary thrombolysis can be achieved with several lytic agents administered via the intravenous or intracoronary routes. Streptokinase, when administered intravenously, produces coronary thrombolysis in from 34 to 75 per cent of patients. Intravenous administration has the advantage of rapid administration without the risks or delays inherent in the performance of cardiac catheterization, although lysis rates are lower than those achieved with intracoronary administration. Administration early after infarction (in the first 4 hours) is associated with improved ventricular function and reduced mortality.
Clinical Trials as Topic↗
Importance of continued activation of thrombin reflected by fibrinopeptide A to the efficacy of thrombolysis.
Factors responsible for initial success or failure of coronary thrombolysis and persistent recanalization or early reocclusion have not been thoroughly elucidated. Both adequate initial clot lysis and preclusion of rethrombosis are required. Failure may reflect clot lysis followed immediately or somewhat later by rethrombosis. To determine whether differences in the intensity and persistence of the activation of thrombin are determinants of success or failure of recanalization, plasma fibrinopeptide A, a fibrinogen product liberated by thrombin, was serially assayed in 19 patients treated with intravenous streptokinase. In patients exhibiting recanalization (n = 9), plasma fibrinopeptide A decreased after administration of streptokinase but before administration of heparin. In patients without initially apparent recanalization, fibrinopeptide A increased, suggesting ongoing thrombosis, and subsequently decreased promptly after heparin. In patients with initial recanalization followed by overt reocclusion the pattern was different. Despite recanalization, fibrinopeptide A continued to rise markedly. Elevations persisted despite administration of heparin. Thus, inhibition of activation of thrombin is associated with successful recanalization. Conversely, persistent activation of thrombin may be a predisposing factor to both apparent initial failure of recanalization and overt early reocclusion.
Coronary Disease↗
Oblique magnetic resonance imaging of the cardiovascular system.
This exhibit demonstrates that cardiac anatomy can be imaged by MRI in oblique planes that are equivalent to views obtained radiographically or at angiocardiography. These MR images may be obtained either by simple patient positioning or by electronic rotation of the imaging axis. The advantages of this technique include its simplicity and its ability to show detailed anatomy noninvasively. Major cardiac structures including chambers, walls, vessels and bronchi are optimally demonstrated in long axis or cross section. This permits estimation of chamber volume, wall thickness, vessel position and variations from normal. Smaller structures are also well visualized. These include the pericardium, papillary muscles, azygos vein and some cross sectional anatomy of the coronary arteries and veins. The valvular structures can be shown during diastole or systole. The ability of MRI to show these cardiac structures due to the intrinsic contrast differences in signal intensity between muscle, fat, flowing blood and lung suggest an important future for MR cardiac imaging in a broad group of congenital and acquired diseases of the heart, pericardium and great vessels.
Heart↗
Exercise training reduces coronary risk and effectively rehabilitates hemodialysis patients.
This study examines the effects of 12 months of endurance exercise training (cycling, walking and jogging) on lipid profiles, glucose metabolism, blood pressure, anemia and psychological function in 14 hemodialysis patients. Maximal aerobic capacity (VO2max) increased 18% in the exercisers (p less than 0.01), but did not change in 11 controls. This was associated with a reduction in depression, a decrease in dosages of antihypertensive medications, a significant increase in hematocrit and hemoglobin levels (red cell mass rose, plasma volume did not change), a decrease in plasma triglyceride by 23% (p less than 0.05) and an increase in high-density lipoprotein cholesterol (HDL-C) levels by 21% (p less than 0.01) (both HDL-C and triglyceride levels worsened in the sedentary controls), and an 18% increase in glucose disappearance rates (p less than 0.05) in spite of a 52% decrease in fasting insulin levels (p less than 0.01), suggesting that insulin sensitivity improved. These results demonstrate that some of the complications present in hemodialysis patients may be caused by their sedentary life-style, rather than endstage renal disease itself. This suggests that rehabilitation through exercise is possible for these patients. By reducing coronary risk factors in hemodialysis patients, exercise training may also decrease their heightened morbidity and mortality from atherosclerotic complications. These possibilities need to be examined in a longitudinal study.
Adult↗