Thomas Behrenbeck

Serial Quantitative Planar Technetium-99m Isonitrile Imaging in Acute Myocardial Infarction: Efficacy for Noninvasive Assessment of Thrombolytic Therapy

Technetium-99m isonitrile is a new myocardial perfusion imaging agent that accumulates according to the distribution of myocardial blood flow. However, unlike thallium-201, it does not redistribute over time. This imaging agent was used with serial quantitative planar imaging to assess the initial risk area of infarction, its change over time and the relation to infarct-related artery patency in 30 patients with a first acute myocardial infarction. Twenty-three of 30 patients were treated with recombinant tissue-type plasminogen activator (rt-PA) within 4 h after the onset of chest pain. Seven patients were treated in the conventional manner without thrombolytic therapy. Technetium-99m isonitrile was injected before or at the initiation of thrombolytic therapy, and imaging was performed several hours later. These initial images demonstrated the area at risk. Repeat imaging was performed 18 to 48 h later and at 6 to 14 days after the onset of myocardial infarction to visualize the ultimate extent of infarction. The initial area at risk varied greatly (range defect integral 2 to 61) both in patients treated with rt-PA and in those who received conventional treatment. For the total group, the initial imaging defect decreased in size in 20 patients and was unchanged or larger in 10 patients. Patients with a patent infarct-related artery had a significantly greater decrease in defect size than did patients with persistent coronary occlusion (-51 +/- 38% versus -1 +/- 26%, p = 0.0001). All patients with a decrease in defect size greater than 30% had a patent infarct-related artery. In 12 patients who also had predischarge quantitative exercise thallium-201 imaging, good agreement existed between the extent and severity of myocardial perfusion defect on the last technetium-99m isonitrile study before discharge and that noted on delayed thallium-201 imaging. It is concluded that serial planar technetium-99m isonitrile myocardial imaging in patients with acute myocardial infarction undergoing thrombolytic therapy offers a new quantitative noninvasive approach for assessment of the initial risk zone as well as the success of reperfusion.

Independent Association Between Obstructive Sleep Apnea and Subclinical Coronary Artery Disease

BACKGROUND Obstructive sleep apnea (OSA) is associated with coronary risk factors, but it is unknown if OSA is associated with development of coronary disease. We evaluated the association between OSA and the presence of subclinical coronary disease assessed by coronary artery calcification (CAC). METHODS Consecutive patients with no history of coronary disease who underwent electron-beam CT within 3 years of polysomnography between March 1991 and December 2003 were included. OSA was defined by an apnea-hypopnea index (AHI) > or = 5 events per hour, and patients were grouped by quartiles of AHI severity. Logistic regression modeled the association between OSA severity and presence of CAC. RESULTS There were 202 patients (70% male; median age, 50 years; mean body mass index, 32 kg/m(2); 8% diabetic; 9% current smokers; 60% hypercholesterolemic; and 47% hypertensive). OSA was present in 76%. CAC was present in 67% of OSA patients and 31% of non-OSA patients (p < 0.001). Median CAC scores (Agatston units) were 9 in OSA patients and 0 in non-OSA patients (p < 0.001). Median CAC score was higher as OSA severity increased (p for trend by AHI quartile < 0.001). With multivariate adjustment, the odds ratio for CAC increased with OSA severity. Using the first AHI quartile as reference, the adjusted odds ratios for the second, third, and fourth quartiles were 2.1 (p = 0.12), 2.4 (p = 0.06), and 3.3 (p = 0.03), respectively. CONCLUSIONS In patients without clinical coronary disease, the presence and severity of OSA is independently associated with the presence and extent of CAC. OSA identifies patients at risk for coronary disease and may represent a highly prevalent modifiable risk factor.

Mismatch of left ventricular function and infarct size demonstrated by technetium-99m isonitrile imaging after reperfusion therapy for acute myocardial infarction : identification of myocardial stunning and hyperkinesia

Quantitation of perfusion defect size using tomographic imaging with technetium-99m-hexakis-2-methoxy isobutyl isonitrile was performed at the time of hospital discharge in 32 patients with a first myocardial infarction who underwent successful coronary reperfusion within 8 h of the onset of chest pain. Reperfusion was accomplished with thrombolysis or primary coronary angioplasty. Radionuclide angiography was performed at discharge and 6 weeks later. There was a close correlation between perfusion defect size and values for ejection fraction and regional wall motion both at discharge (r = -0.80 and -0.75, respectively) and 6 weeks later (r = -0.81 and -0.81, respectively). There was no overall group difference in ejection fraction between the value at discharge and at 6 weeks; however, five patients had a significant increase (greater than or equal to 0.08) and six had a significant decrease (greater than or equal to 0.08) in ejection fraction. In patients with a significant increase at 6 weeks, ejection fraction was significantly lower at discharge than the value predicted from perfusion defect size (0.37 +/- 0.09 measured versus 0.47 +/- 0.13 predicted, p less than 0.05) and it improved at 6 weeks to near predicted values (0.51 +/- 0.07). In patients with a significant decrease at 6 weeks, ejection fraction was significantly higher at discharge than the value predicted from perfusion defect size (0.60 +/- 0.10 measured versus 0.50 +/- 0.10 predicted, p less than 0.05) and it decreased at 6 weeks to near predicted levels (0.51 +/- 0.09). Left ventricular ejection fraction at the time of hospital discharge is a potentially misleading index of the efficacy of reperfusion therapy for myocardial infarction. In a significant minority (34%) of patients this index does not accurately reflect perfusion defect size, apparently because of the effects of myocardial stunning and compensatory hyperkinesia.

Coronary calcification by electron beam computed tomography and obstructive coronary artery disease: a model for costs and effectiveness of diagnosis as compared with conventional cardiac testing methods☆

OBJECTIVES The purpose of this study was to determine if electron beam computed tomography (EBCT) has potential as a cost-effective approach to diagnosis of obstructive coronary disease. BACKGROUND Coronary calcification quantified by EBCT is closely related to the extent of atherosclerosis. METHODS A model based upon published sensitivities (Se)/specificities (Sp) for diagnosis in an ambulatory patient of obstructive coronary disease (> or =50% stenosis) and population prevalence was tested for angiography alone, or treadmill exercise, stress echocardiography, stress thallium or predetermined EBCT calcium score outpoints, followed by angiography if indicated. RESULTS Total direct testing costs increased in proportion to disease prevalence whereas cost-effectiveness, direct costs/patient diagnosed correctly with disease, decreased as a function of prevalence. Using an EBCT calcium score of 168 (Se/Sp = 71%/90%) provided for the least costly and most cost-effective noninvasive pathway. Calcium scores of 80 (Se/Sp = 84%/84%) and 37 (Se/Sp = 90%/77%) were also cost-effective when prevalence of disease was < or =70%; but results for a >0 calcium score (Se/Sp = 95%/46%) cutpoint were not superior to conventional methods. Calcium score cutpoints of 37, 80 or 168 provided similar or superior overall negative and positive predictive values to conventional noninvasive testing pathways across all prevalence subgroups. CONCLUSIONS In ambulatory patients evaluated for obstructive coronary disease, a testing pathway utilizing quantification of coronary calcium by EBCT as an initial noninvasive testing approach minimized direct costs, and maximized cost-effectiveness in population groups with low/ moderate disease prevalence (< or =70%); as expected, direct angiography as the first and only test proved most cost-effective in patients with a high prevalence (>70%) of disease.

Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women

While the risk for symptomatic atherosclerotic disease increases after menopause, currently recognized risk factors do not identify ongoing disease processes in low-risk women. This study tested the hypothesis that circulating cell-derived microparticles may reflect disease processes in women defined as low risk by the Framingham risk score. The concentration and phenotype of circulating microparticles were evaluated in a cross-sectional study of apparently healthy menopausal women, screened for enrollment into the Kronos Early Estrogen Prevention Study. Microparticles were evaluated by flow cytometry, and coronary artery calcification (CAC) was scored using 64-slice computed tomography scanners. The procoagulant activity of isolated microparticles was determined with a sensitive fluorescent thrombin generation assay. Chronological age, body mass index, serum lipids, systolic blood pressure (Framingham risk score < 10%, range 1-3%), and high-sensitivity C-reactive protein did not differ significantly among women with low (0 < 35; range, 0.3-32 Agatston units) or high (>50; range, 93-315 Agatston units) CAC compared with women without calcification. The total concentration and percentage of microparticles derived from platelets and endothelial cells were greatest in women with high CAC scores. The thrombin-generating capacity of the isolated microparticles correlated with phosphatidylserine expression, which also was greatest in women with high CAC scores. The percentages of microparticles expressing granulocyte and monocyte markers were not significantly different among groups. Therefore, the characterization of platelet and endothelial microparticles may identify early menopausal women with premature CAC who would not otherwise be identified by the usual risk factor analysis.

Nonparallel changes in global left ventricular chamber volume and muscle mass during the first year after transmural myocardial infarction in humans

OBJECTIVES This study was designed to serially assess time-dependent changes in both chamber volume and myocardial muscle mass after infarction in humans. BACKGROUND Dilation of the left ventricular chamber has been previously described after transmural myocardial infarction. METHODS Global left ventricular chamber volumes and muscle mass were quantified by using cine computed tomographic scanning in 18 patients at hospital discharge and 6 weeks, 6 months and 1 year after an initial transmural myocardial infarction (12 anterior and 6 inferior). No patient had heart failure during the initial hospital stay or on any subsequent follow-up visit. RESULTS The patients with anterior myocardial infarction (estimated infarct extent 27 +/- 2% of left ventricle) demonstrated a progressive increase in left ventricular end-diastolic volume from 148 +/- 9 ml (mean +/- SEM) at hospital discharge to 180 +/- 9 ml at 1 year after infarction (p < 0.001). However, global left ventricular muscle mass decreased significantly during the 1st 6 weeks after infarction but returned by 1 year to nearly the value determined at hospital discharge (177 +/- 13 vs. 165 +/- 10 g, p = NS). The changes in global muscle mass did not parallel the steady and progressive increases in chamber end-diastolic volume. The end-diastolic chamber volume to muscle mass ratio, an index of global left ventricular wall tension, increased steadily after hospital discharge but remained level by 1 year after infarction. The time course of changes in global end-systolic chamber volume was roughly proportional to the concomitant changes in end-diastolic volume. During this same time period, left ventricular stroke volume remained constant or improved from that determined at baseline. Global left ventricular end-diastolic and end-systolic volumes remained relatively static during the 1st year in the patient subgroup with inferior wall myocardial infarction (estimated infarct extent 10 +/- 1% of left ventricle), but global muscle (myocardial) mass initially decreased and then increased in a pattern similar, although of smaller magnitude, to that observed in patients with anterior wall myocardial infarction. CONCLUSIONS Overall, left ventricular end-diastolic and end-systolic chamber volumes increase progressively from hospital discharge to 1 year after an initial transmural myocardial infarction in patients with a moderately large anterior wall infarction but remain stable in patients with a small inferior wall infarction. Concurrently, total left ventricular muscle mass decreases significantly during the initial 6 weeks after infarction (presumed largely secondary to changes in the necrotic segments) but then returns to the hospital discharge baseline values by 1 year. These data are consistent with the late development of, at most, limited ventricular hypertrophy in the noninfarcted myocardium that occurs well after the early and progressive left ventricular chamber dilation observed in patients with a moderate to large myocardial infarction. These data, in particular as applied to patients with anterior infarction, suggest that ventricular wall tension is significantly elevated at least during the 1st year after an initial transmural myocardial infarction. These observations may explain the potential utility of agents aimed at reducing afterload or ventricular wall tension during the early convalescent phase after myocardial infarction.

Relation of left ventricular volume and function over one year after acute myocardial infarction to infarct size determined by technetium-99m sestamibi.

Twenty patients with a first acute myocardial infarction (AMI) (15 anterior, 5 inferior) who received successful reperfusion therapy underwent tomographic imaging with technetium-99m (Tc-99m) sestamibi and radionuclide ventriculography at discharge, 6 weeks, and 1 year after AMI. Patency of the infarct-related artery after reperfusion (thrombolysis, 8 patients; coronary angioplasty, 12 patients) was confirmed by angiogrpahy in all patients. Tc-99m sestamibi perfusion defect at discharge (a measure of infarct size) was quantitated using previous methods and expressed as a percentage of the left ventricle (28 +/- 19%, range 0 to 59%). This perfusion defect size correlated closely with ejection fraction at discharge (r = -0.87), 6 weeks (r = -0.81) and at 1 year (r = -0.78, all p less than 0.0001). Perfusion defect size at discharge also correlated closely with end-systolic volume index at discharge (r = 0.71, p less than 0.0005), 6 weeks (r = 0.63, p less than 0.005) and at 1 year (r = 0.76, p less than 0.0001). Perfusion defect size at discharge did not correlate significantly with end-diastolic volume index at discharge or at 6 weeks, but did correlate at 1 year (r = 0.66, p less than 0.005). There was no significant group change in end-systolic or end-diastolic volume indexes from discharge to 1 year later, although 7 patients had definite individual changes in end-diastolic volume index (3 increased and 4 decreased). There was no relation between defect size and late changes in end-systolic volume index, but there was a weak correlation between defect size and late changes in end-diastolic volume index (r = 0.42, p = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of Ventricular Ejection Fraction: A Comparison of Available Imaging Methods

Knowledge of left ventricular ejection fraction has been shown to provide diagnostic and prognostic information in patients with known or suspected heart disease. In clinical practice, the ejection fraction can be determined by using one of the five currently available imaging techniques: contrast angiography, echocardiography, radionuclide techniques of blood pool and first pass imaging, electron beam computed tomography, and magnetic resonance imaging. In this review, we discuss the clinical application as well as the advantages and disadvantages of each of these methods as it relates to determination of ventricular ejection fraction.

Primary Angioplasty in Myocardial Infarction: Assessment of Improved Myocardial Perfusion With Technetium-99m Isonitrile

Technetium-99m-hexakis-2-methoxy-2-isobutyl-isonitrile (technetium-99m isonitrile) is a new radiopharmaceutical compound that reflects myocardial perfusion. Its kinetics, especially its lack of redistribution after intravenous administration, permits the assessment of changes in myocardial perfusion without delay of therapy. Tomographic images at rest were obtained immediately and 6 to 10 days later in 17 consecutive patients undergoing successful primary angioplasty during their first transmural myocardial infarction. Thirteen patients had anterior infarction. The initial (acute) defect size before angioplasty of 48 +/- 17% of the left ventricle decreased significantly (p less than 0.0001) to 29 +/- 19% on the late scans. There was no correlation between the time to therapy and the reduction in defect size. Twelve of the 17 patients, including 7 of the 11 patients treated after 4 h, demonstrated a definite reduction in the initial defect size. Eight patients with angiographically proved persistent coronary occlusion underwent a similar imaging sequence. The initial defect size in this group remained unchanged on the late scans (24 +/- 16% versus 26 +/- 18%, p = NS). Primary angioplasty is an effective approach toward salvaging myocardium; comparison with thrombolytic drug therapy must await the results of controlled clinical trials.

Evaluation of the coronary venous system using electron beam computed tomography.

New therapeutic strategies in interventional cardiology and electrophysiology involve the coronary veins. This study examines the potential usefulness of electron beam computed tomography to obtain detailed noninvasive definition of the coronary venous anatomy and of arteriovenous relationships. Electron beam computed tomography allows acquisition and three-dimensional reconstruction of tomographic images of the beating heart with high spatial and temporal resolution. Contrast-enhanced, thin-section electron beam computed tomographic coronary arteriographic images of 34 patients (21 men and 13 women, age 60 ± 10 years) were analyzed. The visibility of the coronary veins and their spatial relationship to the coronary arteries were assessed qualitatively on two- and three-dimensional displays. The coronary sinus was visible in 91%, the great cardiac vein in 100%, the middle cardiac vein in 88%, at least one vein overlying the lateral surface of the left ventricle in 97%, the anterior interventricular vein in 97%, and the small cardiac vein in 68%. A left marginal and a left posterior vein were seen in 44%, one of the two in 38%, and neither in 3%. The course of the anterior interventricular vein was parallel to the left anterior coronary artery in 79% and a crossover between the two vessels at an obtuse angle occurred in 12%. Contrast-enhanced electron beam computed tomography imaging of the heart noninvasively provides information on the coronary venous system and arteriovenous relationships that may help guide new interventional procedures.