Rade Babic

Dipyridamole-dobutamine echocardiography: A novel test for the detection of milder forms of coronary artery disease

OBJECTIVES This study was designed to assess the clinical, hemodynamic and diagnostic effects of the addition of dobutamine to dipyridamole echocardiography. BACKGROUND Pharmacologic stress echocardiography with either dipyridamole or dobutamine has gained acceptance because of its safety, feasibility, diagnostic accuracy and prognostic power. The main limitation of the two tests is a less than ideal sensitivity in some patient subsets, such as those with limited coronary artery disease. We hypothesized that two pharmacologic stresses might act synergistically in the induction of ischemia by combining the mechanisms of inappropriate coronary vasodilation (with dipyridamole) and an increase in myocardial oxygen consumption (with dobutamine). METHODS One hundred fifty patients (mean [+/- SD] age 51 +/- 11 years) referred for stress echocardiography were initially studied by dipyridamole-dobutamine echocardiography. The test was stopped during the dipyridamole step in 95 patients for achievement of a predetermined end point (obvious dyssynergy induced by lower or higher dipyridamole dose), and dipyridamole-dobutamine tests were performed in 55 patients (negative dipyridamole echocardiographic test). In the same 150 patients the dobutamine echocardiographic test (up to 40 micrograms/kg body weight per min) was performed on a separate day. RESULTS Significant coronary artery disease (> 50% diameter stenosis of at least one major coronary vessel by quantitative coronary arteriography) was present in 131 patients (one vessel in 115; two vessels in 10, three vessels in 6), with normal coronary arteriography in 19. The feasibility of the dipyridamole-dobutamine test was 96%. Self-limiting side effects occurred in 5% of patients. The peak rate-pressure product was lowest during the dipyridamole test (132 +/- 30) and was comparable during the dobutamine (186 +/- 59) and dipyridamole-dobutamine tests (179 +/- 45, p = NS vs. dobutamine; p < 0.01 vs. dipyridamole). Sensitivity was 71% for dipyridamole, 75% for dobutamine and 92% for dipyridamole-dobutamine echocardiography (dipyridamole vs. dipyridamole-dobutamine, p < 0.01; dobutamine vs. dipyridamole-dobutamine, p < 0.01; dipyridamole vs. dobutamine, p = NS), whereas specificity was 89% for dipyridamole, 79% for dobutamine and 89% for dipyridamole-dobutamine echocardiography (p = NS for all). CONCLUSIONS Routine dobutamine addition to dipyridamole stress testing is clinically useful and well tolerated. It expands the spectrum of the disease detectable by pharmacologic stress echocardiography and allows documentation of milder forms of coronary artery disease that can be missed by conventional dipyridamole or dobutamine stress echocardiography.

Integrated evaluation of relation between coronary lesion features and stress echocardiography results: the importance of coronary lesion morphology

OBJECTIVES The aim of this study was to analyze, in the same group of patients, the relationship between multiple variables of coronary lesion and results of exercise, dobutamine and dipyridamole stress echocardiography tests. BACKGROUND Integrated evaluation of the relation between stress echocardiography results and angiographic variables should include not only the assessment of stenosis severity but also evaluation of other quantitative and qualitative features of coronary stenosis. METHODS Study population consisted of 168 (138 male, 30 female, mean age 51+/-9 years) patients, on whom exercise (Bruce treadmill protocol), dobutamine (up to 40 mcg/kg/min) and dipyridamole (0.84 mg/kg over 10 min) stress echocardiography tests were performed. Stress echocardiography test was considered positive for myocardial ischemia when a new wall motion abnormality was observed. One-vessel coronary stenosis ranging from mild stenosis to complete obstruction of the vessel was present in 153 patients, and 15 patients had normal coronary arteries. The observed angiographic variables included particular coronary vessel, stenosis location, the presence of collaterals, plaque morphology according to Ambrose classification, percent diameter stenosis and obstruction diameter as assessed by quantitative coronary arteriography. RESULTS Covariates significantly associated with the results of physical and pharmacological stress tests included for all three stress modalities presence of collateral circulation, percent diameter stenosis and obstruction diameter, as well as lesion morphology (p < 0.05 for all, except collaterals for dobutamine stress test, p = 0.06). By stepwise multiple logistic regression analysis, the strongest predictor of the outcome of exercise echocardiography test was only percent diameter stenosis (p = 0.0002). However, both dobutamine and particularly dipyridamole stress echocardiography results were associated not only with stenosis severity - percent diameter stenosis (dobutamine, p = 0.04; dipyridamole, p = 0.003) - but also, and even more strongly, with lesion morphology (dobutamine, p = 0.006; dipyridamole, p = 0.0009). As all of stress echocardiography results were significantly associated with percent diameter stenosis, the best angiographic cutoff in relation to the results of stress echocardiography test was: exercise, 54%; dobutamine, 58% and dipyridamole, 60% (p < 0.05 vs. exercise). CONCLUSIONS Integrated evaluation of angiographic variables have shown that the results of dobutamine and dipyridamole stress echocardiography are not only influenced by stenosis severity but also, and even more importantly, by plaque morphology. The results of exercise stress echocardiography, although separately influenced by plaque morphology, are predominantly influenced by stenosis severity, due to a stronger exercise capacity in provoking myocardial ischemia in milder forms of coronary stenosis.

High Dose Adenosine Stress Echocardiography for Noninvasive Detection of Coronary Artery Disease

OBJECTIVES The aim of this study was to assess the tolerability and incremental diagnostic value of high adenosine doses in stress echocardiography testing in patients with coronary artery disease (CAD). BACKGROUND In comparison with other pharmacologic stress echocardiography tests, standard dose adenosine stress has sub-optimal sensitivity for detecting milder forms of CAD. METHODS Adenosine stress echocardiography was performed in 58 patients using a starting dose of 100 micrograms/kg body weight per min over 3 min followed by 140 micrograms/kg per min over 4 min (standard dose). If no new wall motion abnormality appeared, the dose was increased to 200 micrograms/kg per min over 4 min (high dose). All patients underwent coronary angiography. Significant CAD was defined as > or = 50% diameter stenosis in at least one major coronary artery. Thirty-three patients had one-vessel and seven had multivessel CAD. Coronary angiographic findings were normal in 18 patients. RESULTS The high adenosine dose caused a slight but significant increase over baseline values in rate-pressure product. Limiting side effects occurred in two patients during the standard dose protocol and in one patient receiving the high dose regimen. The test was stopped in 30 patients after the standard adenosine dose regimen because of a provoked new wall motion abnormality. The sensitivity of adenosine echocardiography with the standard dose was 75% (95% confidence interval [CI] 63% to 87%). After completion of the standard dose protocol, 28 patients continued testing with the high dose adenosine protocol. The overall sensitivity of adenosine echocardiography, calculated as cumulative, increased to 92% (95% CI 84% to 100%) with the high dose (p < 0.05). The specificity of adenosine testing was 100% and 88%, respectively, with the standard and high dose regimen (p = 0.617). CONCLUSIONS We believe that use of a higher than usual adenosine dose protocol for stress testing may improve the diagnostic value of adenosine echocardiography, mainly by increasing sensitivity in patients with single-vessel disease without deterioration of the safety profile and with only a mild reduction in specificity.

Efficiency of Ergonovine Echocardiography in Detecting Angiographically Assessed Coronary Vasospasm

C vasospasm plays a major role in provoking myocardial ischemia in patients with variant angina, but also in some patients with acute coronary syndrome including unstable angina, myocardial infarction, and sudden death. Ergonovine provocation has been used for 20 years for detection of coronary artery spasm. Most data on ergonovine testing have been reported in the preselected group of patients with variant angina, establishing ergonovine as a test of high diagnostic confidence. In current clinical practice, when a marked decline in the use of ergonovine testing in the catheterization laboratory is observed, accompanied by promising reports on ergonovine echocardiography, a question remains on the incidence, safety, and usefulness of provocative testing for coronary vasospasm in patients with chest pain syndrome and nonsignificant coronary artery stenosis. Thus, the objectives of our study were to evaluate (1) the incidence of angiographically assessed coronary vasospasm in a consecutive population of patients with nonsignificant coronary artery disease, (2) the efficiency of simultaneously performed ergonovine echocardiography in identifying coronary vasospasm, and (3) the relation between ergonovine echocardiographic and angiographic results. • • • The vasomotor response to ergonovine was studied in 100 consecutive patients (45 men and 55 women, mean age 52 8 years) with chest pain syndrome and hemodynamically nonsignificant coronary stenosis (diameter stenosis, mean 26 10%). No patient had previous myocardial infarction, congestive heart failure, severe congenital or valvular heart disease, or documented cardiomyopathy. Patients with severe hypertension (systolic pressure 180 mm Hg and diastolic pressure 110 mm Hg), recent malignant ventricular arrhythmia, or conduction abnormalities were not considered for the study. All drug medications were stopped 48 hours before testing, except angiotensin-converting enzyme inhibitors and short-acting nitrates. Our institution’s human use committee approved the study, and all patients gave informed consent. According to predominant clinical symptoms, patients were classified into the following categories: chest pain during rest (n 18), chest pain during effort and rest (n 10), nocturnal chest pain (n 9), chest pain in the cold (n 19), and chest pain during stressful situations (n 44). The pretest probability of having coronary artery disease was 60 15%. In 84 patients, submaximal Bruce treadmill, exercise stress electrocardiographic testing was performed before diagnostic angiography; in 16 patients exercise testing was not performed because of poor patient motivation or physical inability to perform adequate exercise tests. No patient developed significant ST-segment changes during and after stress testing, defined as a decrease or increase in ST segment of 0.1 mV 0.08 second after the J point, or rhythm and conduction abnormalities. The ergonovine test was performed in consecutive patients at the end of diagnostic catheterization showing nonsignificant coronary artery stenosis and a normal left ventriculogram. All patients underwent selective coronary angiography using the Judkins technique, and multiple views of each coronary artery were obtained. Angiographic evaluation during ergonovine testing was performed in the view that best showed the coronary lesion. Doses of 0.05, 0.10, and 0.20 mg of ergonovine maleate (total cumulative dose 0.35 mg) were given intravenously in succession at 3-minute intervals, followed by intracoronary injection of nitroglycerin. Angiography was performed before the study, at the end of each stage, and after administration of nitroglycerin. Systemic blood pressure, electrocardiography, and echocardiography for wall motion changes were monitored continuously and recorded at the end of each stage. Electrocardiography was considered positive for myocardial ischemia when 0.1 mV elevation or depression of the ST segment was found 0.08 second after the J point. Coronary arteriographic images were digitized and analyzed (off-line) with the quantitative coronary angiography imaging system (Medis CMS software, version 1.11, Nuenen, The Netherlands) by an observer unaware of patient clinical data and echocardiographic results. After visual inspection of the coronary artery, the frame of optimal clarity in the end-diastolic part of From the University Institute for Cardiovascular Diseases, Department for Diagnostic and Catheterization Laboratories, Clinical Center of Serbia, Belgrade, Yugoslavia. Dr. Ostojic’s address is: University Institute for Cardiovascular Diseases, Department for Diagnostic and Catheterization Laboratories, Clinical Center of Serbia, 8 Koste Todorovica, Belgrade, Yugoslavia. E-mail: miodrag.ostojic@kcs.ac.yu. Manuscript received March 16, 2001; revised manuscript received and accepted July 3, 2001.

Dipyridamole-Atropine-Induced Myocardial Infarction in a Patient with Patent Epicardial Coronary Arteries

Background: The diagnostic accuracy of the physical and pharmacological stress echocardiography tests is higher than routine exercise electrocardiography. They have an acceptable safety profile and have been rarely associated with severe adverse effects. Case Report: We present a case of acute anterior myocardial reinfarction immediately after exercise and pharmacological (dipyridamole-atropine) stress echocardiography testing 1 month after successful stent implantation in LAD. Our patient was a 43-year-old man with a history of heavy smoking and hypertension. Remarkably, the stress echocardiogram was non-diagnostic few hours before the infarction occurred. Angiography performed 4 months after the reinfarction revealed neither a culprit lesion nor stent thrombosis. Conclusion: Aggressive “last generation” pharmacological stress testing may provide optimal diagnostic accuracy, but as in our case, complications may occur, even after negative stress testing. To our knowledge, this is the first reported case of an acute myocardial infarction as a severe complication of stress testing, which developed in a patient after stent implantation.Hintergrund: Die diagnostische Wertigkeit der Belastungs- und pharmakologischen Stressechokardiographie ist besser als ein Routine-Belastungs-EKG. Die Stressechokardiographie hat eine niedrige Komplikationsrate und selten Nebenwirkungen. Kasuistik: Wir berichten über einen Patienten mit akutem Vorderwandreinfarkt am selben Tag nach einer für eine Ischämie negativen Stressechokardiographie (kombinierte Belastungs- und Dipyridamol-Atropin-Stressechokardiographie), 1 Monat nach der erfolgreichen Stentimplantation im RIVA. Der Patient war 43 Jahre alt, starker Raucher und eingestellter Hypertoniker. Bei der Herzkatheteruntersuchung 4 Monate nach der Reinfarzierung konnte ein offenes Koronargefäß ohne relevante Stenose oder Stentthrombose nachgewiesen werden. Schlussfolgerung: Der aggressive, kombinierte, pharmakologische Stresstest hat eine optimale diagnostische Wertigkeit für die Diagnose der koronaren Herzkrankheit. Er kann aber auch nach unauffälligem Testergebnis Komplikationen verursachen, wie in diesem Fall gezeigt werden konnte. Unseres Wissens ist das der erste beschriebene Fall eines Myokardinfarkts nach Stressechokardiographie bei Zustand nach erfolgreicher Stentimplantation.

Paclitaxel-eluting stents

Percutaneous coronary intervention and stent implantation is rapidly becoming the most commonly used form of revascularization. The long term results of this procedure are limited by restenosis which is a phenomenon predominantly caused by proliferation of smooth muscle cells. Many devices and pharmaceutical agents have been unsuccessful in preventing this problem. Paclitaxel is an antiproliferative drug that has been extensively studied for the prevention of restenosis. This article will review the trial results of the currently available stent platforms and discuss some of the ongoing studies and future directions for the development of new paclitaxel-eluting stents.

1053-2 Cath-Lab Assistant: Integrated Image Analysis and Relational Database Program

Cardiac catheterization techniques deal with large amount of image data from which quantitative parameters are extracted. Our program provides relational database organization and management functions for both images and measurement data. In addition, it integrates database with our previously developed image analysis programs for intravascular ultrasound (IVUS) and coronary angiography. The program runs in Microsoft Windows environment and does not require specialized imaging hardware. Program consists of three functional modules: image database system, IVUS contour extraction/analysis module and coronary angiography contour extraction/analysis module, Image database system provides image retrieval, storage and display together with extracted quantitative data. Each database record includes data on patient administration, medical history and noninvasive test results. User is provided with browse and search controls for database navigation, as well as with query by example and lists and reports generation. Analysis programs are incorporated into the database through OLE (Object Linking and Embedding) technique, which enables user to launch appropriate image analysis program simply by clicking the mouse over the chosen image. Extracted analysis data are automatically stored in the appropriate database record. Furthermore, any other image processing/analysis Windows program that supports OLE and can act as OLE server may be linked with the database by simple Clipboard cut and paste operations. All images and data can be exported to other Windows applications (text processors, spreadsheets, statistical and data presentation software). In practical testing the program proved to be user friendly, interactive and flexible. It was particularly useful for integration of both images and quantitative data obtained by coronary angiography and by IVUS, being helpful in the validation of the latter technique, and providing better insight into the extent and severity of coronary arteriosclerotic disease.