Vladimir Kanjuh

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.

Diagnostic Value of Pericardial Biopsy

Background—The clinical significance of pericardial biopsy is controversial. The aim of this study was to assess the feasibility and diagnostic value of 3 approaches to pericardial biopsy: fluoroscopic control and standard sampling, pericardioscopy guidance with standard sampling, and pericardioscopy guidance with extensive sampling. Methods and Results—Forty-nine subsequent patients with a large pericardial effusion underwent parietal pericardial biopsy. In group 1 (12 patients, 66.7% males, age 46.7±12.2 years), pericardial biopsy was guided by fluoroscopy (3 to 6 samples per patient). Group 2 included 22 patients (50% males, age 50.8±10.4 years) undergoing 4 to 6 pericardial biopsies per patient guided by pericardioscopy (16F flexible endoscope). In group 3, extensive pericardial sampling was performed, guided by pericardioscopy (15 patients, 53.3% males, age 53.7±12.8 years, 18 to 20 samples per patient). Sampling efficiency was better with pericardioscopy (group 2, 84.9%; group 3, 84.2%) compared with fluoroscopic guidance (group 1, 43.7%;P <0.01). Diagnostic value was defined as a new diagnosis uncovered, etiology revealed, clinical diagnosis confirmed, and the biopsy false-negative. Pericardial biopsy in group 3 had higher diagnostic value than in group 1 in revealing new diagnosis (40% versus 8.3%, P <0.05) and etiology (53.3% versus 8.3%, P <0.05). In group 2, pericardial biopsy had a higher yield in establishing etiology than in group 1 (40.9% versus 8.3%;P <0.05). Pericardial biopsy was false-negative in 58.3% in group 1 in contrast to 6.7% in group 3 (P <0.01). There were no major complications. Conclusions—Pericardioscopic guidance enhanced pericardial sampling efficiency. The diagnostic value of pericardial biopsy was significantly improved by extensive sampling made possible by pericardioscopy.

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.

The incidence of myocarditis in endomyocardial biopsy samples from patients with congestive heart failure

We present the combined experience of three Yugoslavian cardiovascular centers in the application of endomyocardial biopsy for the diagnosis of myocarditis in patients who present clinically with congestive heart failure. The study group comprised 107 patients (mean age, 40.8 years; range, 19 to 61 years). On the basis of patient history and diagnostic tests, the following clinical diagnoses were established: dilated cardiomyopathy (85), myocarditis (16), and alcohol-induced heart disease (6). EMB samples were taken from the left ventricle (95) or both ventricles (12) by use of a Kings College bioptome, with a mean of 3.2 samples per patient. Histologic evidence of myocarditis was noted in 10 of 85 patients (12%) with a clinical diagnosis of dilated cardiomyopathy, in 2 of 6 patients (33%) with alcohol-induced heart disease, and in 12 of 16 patients (75%) with a clinical diagnosis of myocarditis. There was confirmation of the clinically suspected diagnosis in 63% of cases, a change of diagnosis based on histology in 15% of cases, and nonspecific findings in 22%. However, useful information was obtained in 78% of the cases, and there was a 22% incidence of histologically proven myocarditis for the entire group. Our results indicate that endomyocardial biopsy is beneficial in determining the true incidence of myocarditis in patients with a clinical presentation of dilated cardiomyopathy.

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.

Ergonovine-Induced Changes of Coronary Artery Diameter in Patients with Nonsignificant Coronary Artery Stenosis

Background and Purpose:Serum cholesterol is positively associated with the risk of developing coronary heart disease. The aim of this study was to determine the relation between response of coronary arteries to ergonovine provocation and lipid profile in patients with nonsignificant coronary artery disease.Patients and Methods:105 patients (46 male, 59 female, mean age 52 ± 8 years) with chest pain syndrome and nonsignificant coronary artery stenosis (< 50% diameter stenosis) were analyzed. Ergonovine test was performed at the end of diagnostic catheterization. Coronary spasm was defined as total or near total obstruction of the coronary artery. By quantitative coronary arteriography, changes of minimal luminal diameter (MLD) during ergonovine provocation were evaluated. Total cholesterol, LDL and HDL cholesterol, and triglycerides were measured.Results:There was a significant negative correlation between resting MLD and LDL cholesterol (r = –0.215; p = 0.034), and a significant positive correlation between MLD decrease provoked by ergonovine and total cholesterol (r = 0.275; p = 0.006), as well as LDL cholesterol (r = 0.284; p = 0.004), but not for HDL cholesterol and triglycerides (p = NS [not significant]).Conclusion:In patients with nonsignificant coronary artery stenosis evaluated by ergonovine provocation, there was not only a significant negative correlation between MLD and LDL cholesterol, but also a positive correlation between coronary vasoconstriction induced by ergonovine provocation and both total and LDL cholesterol.ZusammenfassungHintergrund und Ziel:Serumcholesterin ist bekanntlich ein wichtiger Risikofaktor für ischämische Herz-Kreislauf-Erkrankungen. Bei Verdacht auf vasospastische Angina pectoris wird mittels intrakoronarer Gabe von Ergonovin in die linke und rechte Herzkranzarterie der Grad der Vasokonstriktion objektiviert. Das Ziel dieser Studie war es, die Korrelation zwischen dem Ergonovineffekt auf Koronararterien und dem Lipidprofil bei Patienten mit einer nichtsignifikanten Koronarkrankheit zu bestimmen.Patienten and Methodik:105 Patienten (46 männlich, 59 weiblich, Alter 52 ± 8 Jahre) mit Herzschmerzen und nichtsignifikanten Koronarstenosen (< 50%ige Verengung des Koronardurchmessers) wurden analysiert. Ein Ergonovintest wurde am Ende der diagnostischen Herzkatheteruntersuchung durchgeführt. Dabei wurde ein Koronarspasmus als total oder subtotal krampfartige Gefäßverengung definiert. Durch die quantitative Auswertung der Koronarangiogramme wurden Änderungen des minimalen Lumendurchmessers (MLD) während der Ergonovinprovokation bewertet. Bei allen Patienten wurden Gesamtcholesterin, LDL- und HDL-Cholesterin sowie Triglyzeride gemessen.Ergebnisse:Es gab eine signifikante negative Korrelation zwischen dem MLD in Ruhe und dem LDL-Cholesterin (r = –0,215; p = 0,034) Eine signifikante positive Korrelation bestand zwischen der MLD-Abnahme – provoziert durch Ergonovin – und dem Gesamtcholesterin (r = 0,275; p = 0,006) sowie dem LDL-Cholesterin (r = 0,284; p = 0.004), aber nicht zum HDL-Cholesterin und zu den Triglyzeriden (p = NS [nicht signifikant]).Schlussfolgerung:Bei Patienten mit einer nichtsignifikanten Koronarstenose fand sich eine signifikante negative Korrelation zwischen dem MLD in Ruhe und dem LDL-Cholesterin. Nach Provokation mit Ergonovin zeigte der Grad des erzeugten Koronarspasmus eine positive Korrelation zum Gesamt- und zum LDL-Cholesterin.

Left atrial appendage closure with Watchman device in prevention of thromboembolic complications in patients with atrial fibrillation: First experience in Serbia

Introduction. Atrial fibrillation (AF) is the major cause of stroke, particularly in older patients over 75 years of age. European Society of Cardiology guidelines recommend chronic anticoagulation therapy in patients with atrial fibrillation if CHA2DS2-VASc score is ≥ 1 [CHA2DS2-VASc score for estimating the risk of stroke in patients with nonrheumatic AF consisting of the first letters of patients condition: C - congestive heart failure; H - hypertension; A2 - age ≥ 75 years; D - diabetes mellitus; S2 - prior stroke, transitory ischaemic attack (TIA) or thrombolism; V - vascular disease; A - age 65-74 years; Sc - sex category]. However, a significant number of patients have a high bleeding risk, or are contraindicated for chronic oral anticoagulation, and present a group of patients in whom alternative treatment options for thromboembolic prevention are required. Transcatheter percutaneous left atrial appendage closure (LAAC) devices have been recommended in patients with contraindications for chronic anticoagulant therapy. Case report. We present our first three patients with nonvalvular AF and contraindications for chronic anticoagulant therapy who were successfully treated with implantation of LAAC Watchman device in Catheterization Laboratory of the Clinic for Cardiology, Clinical Center of Serbia in Belgrade Conclusion. Our initial results with Watchman LAAC device are promising and encouraging, providing real alternative in patients with non-valvular AF and contraindication for chronic anticoagulant therapy and high bleeding risk.

Stenting and Surgery for Coronary VasospasmStenting und Chirurgie bei Koronarspasmus. Mit der falschen Wahl misslingt die Lösung des Problems

A 55-year-old man, with a history of medically uncontrolled coronary vasospasm, presented for evaluation of chest pain 6 months after implantation of left internal mammary artery. Due to recurrent episodes of vasospastic angina and serious complications of coronary spasm (ventricular fibrillation, myocardial infarction), a stent had previously been implanted in the proximal part of left anterior descending artery at the site of angiographically and ergonovine-proven coronary spasm, with subsequent in-stent restenosis.ZusammenfassungEin 55-jähriger Patient mit therapeutisch unkontrollierbaren koronaren Vasospasmen wurde 6 Monate nach Implantation der linken A. mammaria interna zur Abklärung von Brustschmerzen vorstellig. We - gen der wiederholten vasospastischen Anfälle und Komplikationen mit Kammerflimmern und Myokardinfarkt war zuvor ein Stent in die proximale LAD implantiert worden mit nachfolgender In-Stent- Restenose, nachdem angiographisch und mittels Ergonovintest schwere Koronarspasmen festgestellt worden waren.

Stenting and Surgery for Coronary Vasospasm

A 55-year-old man, with a history of medically uncontrolled coronary vasospasm, presented for evaluation of chest pain 6 months after implantation of left internal mammary artery. Due to recurrent episodes of vasospastic angina and serious complications of coronary spasm (ventricular fibrillation, myocardial infarction), a stent had previously been implanted in the proximal part of left anterior descending artery at the site of angiographically and ergonovine-proven coronary spasm, with subsequent in-stent restenosis.ZusammenfassungEin 55-jähriger Patient mit therapeutisch unkontrollierbaren koronaren Vasospasmen wurde 6 Monate nach Implantation der linken A. mammaria interna zur Abklärung von Brustschmerzen vorstellig. We - gen der wiederholten vasospastischen Anfälle und Komplikationen mit Kammerflimmern und Myokardinfarkt war zuvor ein Stent in die proximale LAD implantiert worden mit nachfolgender In-Stent- Restenose, nachdem angiographisch und mittels Ergonovintest schwere Koronarspasmen festgestellt worden waren.