Sinisa Stojkovic

Stress echocardiography in the detection of myocardial ischemia. Head-to-head comparison of exercise, dobutamine, and dipyridamole tests.

BackgroundExercise and pharmacological stress echocar-diography have emerged as convenient alternatives to myocardial scintigraphy. The objective of this study was to compare in the same patients the diagnostic values of exercise, dobutamine, and dipyridamole stress echocardiography tests for detection of myocardial ischemia. Methods and ResultsWe performed exercise (maximal treadmill Bruce protocol), dobutamine (up to 40 μg/kg per minute) and dipyridamole (up to 0.84 mg/kg over 10 minutes) stress echocardiography tests, in random sequence and on separate days, in 136 consecutive patients. All patients underwent coronary angiography. Significant coronary artery disease was defined by quantitative coronary angiography as a lesion with a diameter stenosis ≥50%. A stress echocardiogram was considered positive when new or worsening of preexisting wall motion abnormality was observed. Most of the patients (94%) were receiving the same antianginal medication for each stress test; 59 patients were receiving concomitant β-blocker therapy. The prevalence of coronary artery disease was 87.5%, with 108 patients having one-vessel coronary artery disease. Peak heart rate and systolic blood pressure were higher with exercise than with dobutamine or dipyridamole (P<.01). Sensitivity of exercise, dobutamine, and dipyridamole stress echocardiography was 88%, 82%, and 74% (dipyridamole versus exercise, P<.01), respectively. Specificity was 82%, 77%, and 94%, respectively. The overall accuracy was 87%, 82%, and 77% (dipyridamole versus exercise, P<.01), respectively. The accuracy of dipyridamole was higher (P=.02) in the group of patients not receiving β-blockers (84%) than in the patients receiving β-blocker therapy (66%), whereas the accuracy of exercise and dobutamine were only slightly higher in the patients not receiving, β-blockers. Significant side effects occurred in 3%, 11%, and 1% of patients during exercise, dobutamine, and dipyridamole tests, respectively. ConclusionsDespite the different hemodynamic effects, exercise, dobutamine, and dipyridamole echocardiography have high overall diagnostic values. In this group of patients with a predominance of one-vessel coronary artery disease, the overall diagnostic accuracy of stress echocardiography tests was higher for exercise than for dobutamine or dipyridamole. Concomitant β-blocker therapy significantly decreased the accuracy of the dipyridamole stress echocardiography test. Pharmacological stress testing (dipyridamole without β-blockers) can therefore be used as an efficient option for detection of myocardial ischemia in patients who are unable or poorly motivated to exercise adequately.

Differential Effects of Drug-Eluting Stents on Local Endothelium-Dependent Coronary Vasomotion

OBJECTIVES The aim of our study was to compare coronary vasomotion after implantation of a second-generation biolimus A9-eluting stent (BES) and of a sirolimus-eluting stent (SES). BACKGROUND Drug-eluting stents (DES) have been associated with impaired local coronary vasomotion, delayed endothelialization, and increased late thrombotic risk. New DES with different drugs, pharmacokinetics, and polymers have been developed. METHODS Nineteen patients with a BES and 15 patients with a SES were studied 9 months after stent implantation. Endothelium-dependent and -independent coronary vasomotion were tested proximally and distally to the stent as well as at a reference segment during right atrial pacing at increasing heart rates. Quantitative coronary angiographic measurements were performed offline. RESULTS Of the patients with BES, 2 showed vasoconstriction with increased heart rate and 17 showed vasodilatation. Of the patients with a SES, 9 showed vasoconstriction while 6 showed vasodilatation. The SES showed significant vasoconstriction at both the proximal (-2.3 +/- 10% vs. 7.9 +/- 10%) and the distal (-5.4 +/- 9% vs. 6.1 +/- 8%) segments to the stent compared with the BES (p = 0.003 for proximal, p < 0.001 for distal segment). Endothelium-independent vasomotion after intracoronary nitrates did not differ significantly between the 2 groups (p = NS for proximal and distal segment). CONCLUSIONS Unlike the case with the SES, endothelium-dependent vasomotion at adjacent stent segments seems to be preserved after BES implantation. This result may be explained by the different drug release kinetics, DES design, or characteristics of polymer used in the stent system.

First clinical comparison of Nobori -Biolimus A9 eluting stents with Cypher- Sirolimus eluting stents: Nobori Core nine months angiographic and one year clinical outcomes.

AIM To compare clinical efficacy and safety of stents eluting limus drugs from biodegradable polymer - Nobori, or durable polymer - Cypher. METHODS AND RESULTS From May to August 2006, 107 patients with 142 coronary artery lesions were treated with either Nobori, Biolimus A9 eluting stent (54) or Cypher, Sirolimus eluting stent (53) in five centres. The two groups were well matched for baseline clinical and angiographic characteristics. The in-stent late loss at nine months, the primary endpoint of the study, was 0.10+/-0.26 mm in Nobori, and 0.13+/-0.44 mm in Cypher arm (p=0.660) confirming the hypothesis of the similarity between the two stents. In-stent diameter stenosis of 13+/-10% with Nobori was significantly lower than 20+/-12% with Cypher stent (p=0.002) without significant difference in binary restenosis (1.7% in Nobori and 6.3% in Cypher arm; p=0.32). The rate of major adverse cardiac events at 12 months was 1.9% with Nobori and 4.1% with Cypher stent. CONCLUSIONS The nine months angiographic data from Nobori Core study demonstrate that Biolimus A9 has similar anti-proliferative efficacy to Sirolimus as judged by in-stent late loss and restenosis rate. Low frequency of adverse cardiac events at 12 months indicates that both stents are safe and effective in the studied population.

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.

The Pharmacokinetics of Biolimus A9 after Elution from the Nobori Stent in Patients with Coronary Artery Disease: The NOBORI PK Study

The aim of this study was to assess the pharmacokinetics and tolerability of Biolimus A9 eluted from Nobori coronary stents.

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.

Comparison of exercise, dobutamine-atropine and dipyridamole-atropine stress echocardiography in detecting coronary artery disease

BackgroundDipyridamole and dobutamine stress echocardiography testing are most widely utilized, but their sensitivity remained suboptimal in comparison to routine exercise stress echocardiography. The aim of our study is to compare, head-to-head, exercise, dobutamine and dipyridamole stress echocardiography tests, performed with state-of-the-art protocols in a large scale prospective group of patients.MethodsDipyridamole-atropine (Dipatro: 0.84 mg/kg over 10 min i.v. dipyridamole with addition of up to 1 mg of atropine), dobutamine-atropine (Dobatro: up to 40 mcg/kg/min i.v. dobutamine with addition of up to 1 mg of atropine) and exercise (Ex, Bruce) were performed in 166 pts. Of them, 117 pts without resting wall motion abnormalities were enrolled in study (91 male; mean age 54 ± 10 years; previous non-transmural myocardial infarction in 32 pts, angina pectoris in 69 pts and atypical chest pain in 16 pts). Tests were performed in random sequence, in 3 different days, within 5 day period under identical therapy. All patients underwent coronary angiography.ResultsSignificant coronary artery disease (CAD; ≥50% diameter stenosis) was present in 69 pts (57 pts 1-vessel CAD, 12 multivessel CAD) and absent in 48 pts. Sensitivity (Sn) was 96%, 93% and 90%, whereas specificity (Sp) was 92%, 92% and 87% for Dobatro, Dipatro and Ex, respectively (p = ns). Concomitant beta blocker therapy did not influence peak rate-pressure product and Sn of Dobatro and Dipatro (p = ns).ConclusionWhen state-of-the-art protocols are used, dipyridamole and dobutamine stress echocardiography have comparable and high diagnostic accuracy, similar to maximal post-exercise treadmill stress echocardiography.

The value of fractional and coronary flow reserve in predicting myocardial recovery in patients with previous myocardial infarction

AIMS The aim of the study was to evaluate the relation between fractional flow reserve (FFR) and simultaneously evaluated coronary flow reserve by thermodilution (CFRthermo), with the improvement of left ventricular (LV) function in patients with previous myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS Study population consisted of 46 patients (mean age 53 +/- 7 years; 36 male) with previous MI and significant coronary stenosis undergoing PCI of infarct-related coronary artery. In all patients, we evaluated FFR and CFRthermo by single pressure/thermo wire during maximal hyperaemia before and immediately after PCI. We performed echocardiographic assessment of LV ejection fraction before and 6 months after PCI. Dobutamine stress echocardiography test was also performed before PCI. LV functional improvement was observed in 33/46 (72%) of patients. In patients with LV functional recovery in comparison with patients with no recovery, there was a significant difference in FFR before PCI (0.56 +/- 0.14 vs. 0.70 +/- 0.07, P < 0.001), improvement of FFR (0.35 +/- 0.14 vs. 0.21 +/- 0.07, P < 0.001), improvement of CFRthermo (1.3 +/- 0.6 vs. 0.5 +/- 0.3, P < 0.001), and CFRthermo after PCI (2.6 +/- 0.7 vs. 2.0 +/- 0.4, P < 0.001). When only parameters evaluated before PCI were taken into account, FFR before angioplasty (P = 0.001) and dobutamine-assessed viability (P = 0.006) were the most significant multivariate predictors of myocardial recovery. When all significant univariate parameters were evaluated, the most significant independent predictors for improvement in myocardial function were the improvement of CFRthermo during angioplasty (P < 0.001) and FFR before angioplasty (P = 0.002). CONCLUSION Simultaneous evaluation of FFR and CFRthermo provide significant complementary data on the improvement in myocardial function in patients with previous MI. However, the evaluation of FFR before angioplasty identifies viable myocardium that may recover following revascularization and may be used as an alternative to non-invasive testing.

Efficiency, safety, and long-term follow-up of retrograde approach for CTO recanalization: initial (Belgrade) experience with international proctorship.

BACKGROUND  Retrograde approach increases the success rate for percutaneous recanalization of complex chronic total occlusion (CTO) of coronary arteries. OBJECTIVES  The purpose of this study was to describe our initial experience of retrograde percutaneous coronary intervention for CTO program, focusing on its safety and feasibility, and long-term clinical follow-up. METHODS  The study was a single center retrospective registry which included a total of 40 patients, of 590 CTO treated patients (6.7%), between January 2008 and October 2011, who underwent retrograde approach for CTO recanalization. RESULTS  Mean occlusion duration was 37.8 ± 40.3 months. Overall success recanalization rate was 87.5% (35/40). Septal collaterals were used to access the occlusion in all cases (100%). Retrograde guidewire crossing of collateral channels was successful in 36/40 (90.0%) patients with success rate of CTO recanalization in these patients of 97.2%. Retrograde approach as the primary strategy was applied in 23/40 (57.5%) patients, retrograde approach immediately after antegrade failure attempt was performed in 8/40 (20.0%) patients, and retrograde approach as elective procedure, after previously failed antegrade attempt, was performed in 9/40 (22.5%) patients. The success rate of these strategies was: 87.0% (20/23 patients) for primary, 87.5% (7/8 patients) for retrograde immediately after antegrade failure, and 88.9% (8/9 patients) for retrograde after previous failed antegrade attempt, respectively. Total in-hospital major adverse cardiac events (MACE) rate was 5.0% (2 non-Q-wave myocardial infarctions). The MACE free survival at median follow-up of 20 months was 89% (95% CI: 78-100%). CONCLUSIONS  This study has demonstrated that adequate training and international proctorship for this complex and demanding technique is a necessity and prerequisite to achieve high overall success rates, with acceptable complication rates and excellent long-term survival rate.