Mario S. Verani

Severity of Coronary Artery Calcification by Electron Beam Computed Tomography Predicts Silent Myocardial Ischemia

BACKGROUND Detection of subclinical coronary artery disease (CAD) before the development of life-threatening cardiac complications has great potential clinical relevance. Electron beam computed tomography (EBCT) is currently the only noninvasive test that can detect CAD in all stages of its development and thus has the potential to be an excellent screening technique for identifying asymptomatic subjects with underlying myocardial ischemia. METHODS AND RESULTS Over 2.5 years, we prospectively studied 3895 generally asymptomatic subjects with EBCT, 411 of whom had stress myocardial perfusion tomography (SPECT) within a close (median, 17 days) time period. SPECT and exercise treadmill results were compared with the coronary artery calcium score (CACS) as assessed by EBCT. The total CACS identified a population at high risk for having myocardial ischemia by SPECT although only a minority of subjects (22%) with an abnormal EBCT had an abnormal SPECT. No subject with CACS <10 had an abnormal SPECT compared with 2.6% of those with scores from 11 to 100, 11.3% of those with scores from 101 to 399, and 46% of those with scores >/=400 (P<0.0001). CACS predicted an abnormal SPECT regardless of subject age or sex. CONCLUSIONS CACS identifies a high-risk group of asymptomatic subjects who have clinically important silent myocardial ischemia. Our results support the role of EBCT as the initial screening tool for identifying individuals at various stages of CAD development for whom therapeutic decision making may differ considerably.

Guidelines for clinical use of cardiac radionuclide imaging report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on Radionuclide Imaging), developed in collaboration with the American Society of Nuclear Cardiology☆

Abstract It is becoming more apparent each day that despite a strong national commitment to excellence in health care, the resources and personnel are finite. It is therefore appropriate that the medical profession examine the impact of developing technology and new therapeutic modalities on the practice of cardiology. Such analysis, carefully conducted, could potentially affect the cost of medical care without diminishing the effectiveness of that care. To this end, the American College of Cardiology and the American Heart Association in 1980 established a Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures with the following charge: The Task Force of the American College of Cardiology and the American Heart Association shall develop guidelines relative to the role of new therapeutic approaches and of specific noninvasive and invasive procedures in the diagnosis and management of cardiovascular disease. The Task Force shall address, when appropriate, the contribution, uniqueness, sensitivity, specificity, indications, contra-indications and cost-effectiveness of such diagnostic procedures and therapeutic modalities. The Task Force shall emphasize the role and values of the developed guidelines as an educational resource. The Task Force shall include a Chairman and six members, three representatives from the American Heart Association and three representatives from the American College of Cardiology. The Task Force may select ad hoc members as needed upon the approval of the Presidents of both organizations. Recommendations of the Task Force are forwarded to the President of each organization.

Diagnosis of coronary artery disease by controlled coronary vasodilation with adenosine and thallium-201 scintigraphy in patients unable to exercise.

Pharmacological coronary vasodilation induced by dipyridamole is often used in association with thallium-201 myocardial scintigraphy to evaluate the presence and prognostic significance of coronary artery disease. Because dipyridamole acts by blocking the cellular uptake of adenosine, we investigated the usefulness of direct intravenous administration of adenosine, a physiological substance with an exceedingly short (less than 2 seconds) plasma half-life, to induce maximal controlled coronary vasodilation in conjunction with 201Tl scintigraphy. We studied 89 patients (44 men and 45 women; mean age, 64 +/- 10 years [SD]) who were unable to perform an exercise test and were referred for evaluation of suspected coronary artery disease. The intravenous infusion of adenosine began at an initial rate of 50 micrograms/kg/min and was increased by stepwise increments every minute to a maximal rate of 140 micrograms/kg/min. 201Tl was injected intravenously after 1 minute at the highest infusion rate, followed by immediate and delayed (4 hour) tomographic imaging. At the highest infusion rate, adenosine induced a significant (p less than 0.001) decrease in systolic (8.7 +/- 19.3 mm Hg) and diastolic (6.7 +/- 9.4 mm Hg) blood pressures as well as a significant (p = 0.0001) increase in heart rate (14.5 +/- 11.0 beats/min). Side effects occurred in 83% of the patients but resolved spontaneously within 1 or 2 minutes after discontinuing the adenosine infusion. Chest, throat, or jaw pain were the most frequent symptoms and occurred in 57% of the patients. Headache (35%) and flush (29%) were also common. Ischemic electrocardiographic changes occurred in 12% of the patients, and transient first-degree atrioventricular block occurred in 10%.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise echocardiography versus 201Tl single-photon emission computed tomography in evaluation of coronary artery disease. Analysis of 292 patients.

BackgroundExercise echocardiography (digital cine-loop technique) and 201TI single-photon emission computed tomography (SPECT) were performed simultaneously in 292 patients being evaluated for coronary artery disease. Methods and ResultsPretreadmill and posttreadmill echocardiographic images of diagnostic quality were obtained in 289 patients, and the left ventricle was divided into anterior, inferior, and lateral regions. Any wall motion or perfusion abnormality observed within each region was classified as totally reversible, fixed, or partially reversible. Exercise echocardiography and SPECT were normal in 137 patients and abnormal in 118 (88% agreement). Equal numbers of regional abnormalities were detected by one test when missed by the other. The two tests had an 82% agreement in detecting the same type of finding within the regions analyzed. SPECT detected more reversible abnormalities than echocardiography, whereas echocardiography detected more fixed abnormalities than SPECT. Regions with a fixed abnormality by echocardiography frequently showed partial reversibility of a perfusion defect by SPECT. Nearly one third of regions with fixed perfusion defects by SPECT demonstrated normal resting function or reversible abnormalities by echocardiography. Sensitivity for coronary artery disease by angiography (≥50% diameter stenosis) in 112 patients was similar for the two tests, ranging from 58% and 61% (echocardiography and SPECT, respectively) for one-vessel disease to 94% for three-vessel disease. The specificities for echocardiography and SPECT were 88% and 81%, respectively. ConclusionsExercise echocardiography had a diagnostic accuracy comparable to that of SPECT for the detection of regional abnormalities produced by significant coronary artery disease. A greater number of abnormal regions were detected with the combined use of both tests.

Quantitative exercise thallium-201 single photon emission computed tomography for the enhanced diagnosis of ischemic heart disease

The clinical utility of exercise thallium-201 single photon emission computed tomography was investigated in 360 consecutive patients who had concomitant coronary arteriography. Tomographic images were assessed visually and from computer-quantified polar maps. Sensitivity for detecting coronary artery disease was comparably high using quantitative and visual analysis, although specificity tended to improve using the former method (87% versus 76%, p = 0.09). Quantitative analysis was superior to the visual method for identifying left anterior descending (81% versus 68%, p less than 0.05) and circumflex coronary artery (77% versus 60%, p less than 0.05) stenoses and detected most patients (92%) with multivessel coronary artery disease. Multivessel involvement was correctly predicted in 65% of the patients with more than one critically stenosed vessel. Exercise variables in patients with significant coronary artery disease were similar whether the tomographic images were normal or abnormal. However, patients with coronary stenoses and normal versus abnormal tomograms had a trend toward more single vessel disease (79% versus 62%, p = 0.07) and moderate coronary stenosis (66% versus 28%, p less than 0.001), but had less proximal left anterior descending artery involvement (8% versus 34%, p = 0.05). Computer-quantified perfusion defect size was directly related to the extent of coronary artery disease. Intra- and interobserver agreement for quantifying defects were excellent (r = 0.98 and 0.97, respectively). In conclusion, quantitative thallium-201 tomography offers improved detection of coronary artery disease, localization of the anatomic site of coronary stenosis, prediction of multivessel involvement and accurate determination of perfusion defect size, while maintaining a high specificity. Quantification of perfusion defects with single photon tomography may become important for assessing the effects of coronary reperfusion and prognostically stratifying patients with coronary artery disease.

Quantification of myocardial infarction during coronary occlusion and myocardial salvage after reperfusion using cardiac imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile

Myocardial imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile was investigated as a means to assess myocardial infarct size during coronary occlusion and to quantify the extent of salvaged myocardium after coronary occlusion followed by reperfusion. Open chest dogs underwent either a permanent coronary artery occlusion (Group 1, n = 16) or a 2 h occlusion followed by reperfusion (Group 2, n = 15). Animals in both groups were killed 48 h after occlusion. During coronary occlusion, 23 of the 25 dogs that survived the coronary occlusions had abnormal myocardial scintigrams. The scintigraphic perfusion defect size correlated well with the pathologic infarct size (r = 0.85 and 0.95 by planar and tomographic imaging, respectively). The planar scintigraphic defect size, but not the tomographic defect size, overestimated the pathologic size. The planar scintigraphic defect size observed during coronary occlusion was markedly reduced 48 h after reperfusion (24.8 +/- 12.8% to 10.6 +/- 9.7% of the left ventricle, p less than 0.003). The uptake of technetium-99m hexakis 2-methoxyisobutyl isonitrile in the ischemic myocardium increased significantly 48 h after reperfusion (p less than 0.003) and correlated with the increase in regional myocardial blood flow, as assessed by radioactive microspheres (r = 0.83, p less than 0.01). Thus, myocardial imaging with technetium-99m hexakis 2-methoxyisobutyl isonitrile allows reliable demonstration of the presence of acute infarction, estimation of infarct size and quantification of the extent of salvaged myocardium after coronary reperfusion.

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.

Dobutamine Echocardiography and Quantitative Rest-Redistribution 201Tl Tomography in Myocardial Hibernation Relation of Contractile Reserve to 201Tl Uptake and Comparative Prediction of Recovery of Function

BACKGROUND The purposes of this study were to evaluate the comparative accuracy of dobutamine echocardiography and quantitative rest-redistribution 201Tl tomography in the prediction of recovery of function after revascularization and to assess the relation of contractile reserve to thallium uptake. METHODS AND RESULTS Thirty-four patients with stable coronary disease and regional dysfunction underwent dobutamine echocardiography (2.5 up to 40 micrograms.kg-1.min-1) and rest-redistribution 201Tl tomography 1 day before revascularization. Resting echocardiography and scintigraphy were repeated at > or = 6 weeks. Before revascularization, resting 201Tl uptake was similar in segments demonstrating biphasic or sustained improvement and was higher than in those exhibiting no change or worsening function during dobutamine. After revascularization, 201Tl uptake increased only in segments that showed a biphasic response (from 66 +/- 12% to 78 +/- 13%; P < .05). Biphasic response had a sensitivity of 74% and specificity of 89% for prediction of recovery. The use of biphasic or sustained improvement responses increased the sensitivity to 86% with a decrease in specificity to 68%. Qualitative thallium assessment provided a high sensitivity (98%) but poor specificity (27%). Quantification of thallium uptake, however, improved its accuracy: a maximal uptake (at rest or redistribution) of > or = 60% yielded a 90% sensitivity and a 56% specificity. CONCLUSIONS In patients with myocardial hibernation, biphasic response during dobutamine is less sensitive but more specific for recovery of function, whereas indexes of 201Tl scintigraphy are in general more sensitive and less specific, the least accurate being a qualitative assessment of thallium uptake. The sensitivity and specificity of both methods, however, can be altered depending on the quantitative criteria of thallium uptake or combination of responses of the myocardium to dobutamine.

Identification of Hibernating Myocardium: Comparative Accuracy of Myocardial Contrast Echocardiography, Rest-Redistribution Thallium-201 Tomography and Dobutamine Echocardiography

OBJECTIVES We sought to evaluate the comparative accuracy of myocardial contrast echocardiography (MCE), quantitative rest-redistribution thallium-201 (Tl-201) tomography and low and high dose (up to 40 microg/kg body weight per min) dobutamine echocardiography (DE) in identifying myocardial hibernation. BACKGROUND Myocardial contrast echocardiography can assess myocardial perfusion and may therefore be useful in predicting myocardial hibernation. However, its accuracy in comparison to myocardial perfusion scintigraphy and to that of high dose DE remains to be investigated. METHODS Eighteen patients (aged [+/- SD] 57 +/- 10 years) with stable coronary artery disease and ventricular dysfunction underwent the above three modalities before coronary revascularization. Myocardial contrast echocardiography was achieved with intracoronary Albunex. Rest echocardiographic and Tl-201 studies were repeated > or = 6 weeks after revascularization. RESULTS Of 109 revascularized segments with severe dysfunction, 46 (42%) improved. Left ventricular ejection fraction increased from 38 +/- 14% to 45 +/- 13% at follow-up (p = 0.003). Rest Tl-201 uptake and the ratio of peak contrast intensity of dysfunctional to normal segments with MCE were higher (p < 0.01) in segments that recovered function compared with those that did not. Myocardial contrast echocardiography, thallium scintigraphy and any contractile reserve during DE had a similar sensitivity (89% to 91%) with a lower specificity (43% to 66%) for recovery of function. A biphasic response during DE was the most specific (83%) and the least sensitive (68%) (p < 0.01). The best concordance with MCE was Tl-201 (80%, kappa 0.57). Changes in ejection fraction after revascularization related significantly to the number of viable dysfunctional segments by all modalities (r = 0.54 to 0.65). CONCLUSIONS In myocardial hibernation, methods evaluating rest perfusion (MCE, Tl-201) or any contractile reserve have a similar high sensitivity but a low specificity for predicting recovery of function. A limited contractile reserve (biphasic response) increases the specificity of DE. Importantly, the three techniques identified all patients who had significant improvement in global ventricular function.

Provocation of coronary artery spasm by the cold pressor test. Hemodynamic, arteriographic and quantitative angiographic observations.

In this study we attempted to determine if the cold pressor test, a known sympathetic reflexogenic stimulus, could precipitate coronary artery spasm. Thirty-five patients undergoing coronary arteriography for evaluation of chest pain syndromes were given the cold pressor test. During 1 minute of cold pressor stimulation, aortic systolic pressure increased 18.1 ± 9.7 mm Hg (mean ± SD) and heart rate did not change significantly. Focal coronary artery spasm was provoked in seven patients, each of whom had an atheromatous plaque at the site of spasm. Four of six patients with a precatheterization clinical diagnosis of variant angina (group 1) had coronary artery spasm, and two of the four had associated ischemic manifestations. Of 14 patients in whom classic angina (group 2) was diagnosed before cardiac catheterization, two manifested focal coronary spasm. One of 15 patients thought to have atypical chest pain (group 3) manifested spasm. There were no significant differences in baseline variables (aortic systolic or diastolic pressure, heart rate, double product and left ventricular end-diastolic pressure) or hemodynamic response (aortic systolic pressure, heart rate or double product) to cold pressor stimulation between patients in each group and between those who manifested spasm and those who did not. Ventricular ectopy and ventricular tachycardia developed in one patient but were readily reversed with intravenous nitroglycerin. Quantitative angiography showed that the luminal diameter of normal coronary segments significantly decreased in each group of patients in response to cold pressor stimulation, but this response was most pronounced in the variant angina group (-12.7 ± 11.5% from control in group 1, −5.1 ± 10.2% in group 2, and −7.9 ± 9.6% in group 3; p < 0.001 for each group). Patients who are prone to coronary spasm may represent one extreme of a spectrum of reactivity to a coronary vasoconstrictive stimulus. The cold pressor test can provoke focal coronary artery spasm in certain patients and may be a useful nonpharmacologic provocative screening test to aid in the diagnosis of this phenomenon.