Miodrag Ostojic

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.

Outcome Comparison of 600- and 300-mg Loading Doses of Clopidogrel in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction Results From the ARMYDA-6 MI (Antiplatelet therapy for Reduction of MYocardial Damage during Angioplasty-Myocardial Infarction) Randomized Study

OBJECTIVES The purpose of this study was to compare 600- and 300-mg clopidogrel loading doses in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND Given the high thrombotic risk of patients with STEMI, greater platelet inhibition may improve outcome in those patients receiving percutaneous coronary intervention (PCI). Although observational data suggest that pretreatment with a 600-mg clopidogrel loading dose may be more effective than the 300-mg regimen in primary PCI, this hypothesis has never been tested in a randomized study. METHODS A total of 201 patients undergoing primary PCI for STEMI randomly received a 600-mg (n = 103) or 300-mg (n = 98) clopidogrel loading dose before the procedure. The primary endpoint was the evaluation of the infarct size, defined as the area under the curve of cardiac markers. RESULTS Infarct size was significantly lower in the high-dose regimen: median creatine kinase-myocardial band 2,070 ng/ml (interquartile range [IQR]: 815 to 2,847 ng/ml) versus 3,049 ng/ml (IQR: 1,050 to 7,031 ng/ml) in the 300-mg group, p = 0.0001; troponin-I 255 ng/ml (IQR: 130 to 461 ng/ml) versus 380 ng/ml (IQR: 134 to 1,406 ng/ml), p < 0.0001. In the 600-mg arm, Thrombolysis In Myocardial Infarction flow grade <3 after PCI was less frequent (5.8% vs. 16.3%, p = 0.031), left ventricular ejection fraction at discharge was improved (52.1 ± 9.5% vs. 48.8 ± 11.3%, p = 0.026), 30-day major adverse cardiovascular events were fewer (5.8% vs. 15%, p = 0.049), and bleeding/entry site complications were not increased (secondary endpoints). CONCLUSIONS In STEMI patients, pre-treatment with a 600-mg clopidogrel loading dose before primary PCI was associated with a reduction of the infarct size compared with a 300-mg loading dose, as well as with improvement of angiographic results, residual cardiac function, and 30-day major adverse cardiovascular events; further studies are warranted to evaluate impact of such strategy on survival.

Somatic DNA damage in interventional cardiologists: a case-control study

Interventional cardiologists who work in cardiac catheterization laboratories are exposed to low doses of ionizing radiation that could pose a health hazard. DNA damage is considered to be the main initiating event by which radiation damage to cells results in development of cancer and hereditary disease. The aim of the present study was to assess the effects of chronic low‐dose X‐ray radiation exposure on somatic DNA damage of interventional cardiologists working in highvolume cardiac catheterization laboratories. For this analysis, we used peripheral lymphocytes and the assay for micronuclei (MNs), which is considered to be a reliable biological dosimeter for radiation exposure. We obtained peripheral blood from 62 physicians (mean age±se = 40.6±1.5 years): 31 interventional cardiologists (group I, exposed) and 31 age‐ and sex‐matched clinical cardiologists (group II, nonexposed). Interventional cardiologists showed higher MN values (group I=20.5±1.6 vs. group II=12.8±1.3, P=0.001), although some overlap was apparent in the individual subject analysis. A correlation between years of professional activity and MN frequency value was detectable for interventional cardiologists (r=0.428, P=0.02) but not for clinical cardiologists (r=0.253, P=0.17). The results indicated that, overall, interventional cardiologists working in a high‐volume catheterization laboratory have higher levels of somatic DNA damage when compared with clinical cardiologists working outside the catheterization laboratory. The amount of this damage varies and is only weakly related to the duration of professional exposure, which suggests that a dominant modulation of the underlying genetic substrate by environmental factors has a role in determining the harm in individual physicians.

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.

Combined low dose dipyridamole-dobutamine stress echocardiography to identify myocardial viability

OBJECTIVES We sought to evaluate the effects of combined administration of infra-low dose dipyridamole and low dose dobutamine on assessment of myocardial viability. BACKGROUND Low dose pharmacologic stress echocardiography with either dobutamine or dipyridamole infusion has been proposed for the recognition of myocardial viability. METHODS Thirty-four patients with rest wall motion dyssynergy by two-dimensional echocardiography and with angiographically proved coronary artery disease underwent in combination with two-dimensional echocardiographic monitoring: 1) low dose (5 to 10 microgram/kg per min over 3 min) dobutamine infusion; 2) infra-low dose (0.28 mg/kg over 4 min) dipyridamole infusion; 3) combination of infra-low dose dipyridamole infusion immediately followed by low dose dobutamine infusion (combined dipyridamole-dobutamine). RESULTS Follow-up rest echocardiography was available in 30 patients. After revascularization, 82 segments showed a contractile improvement of > or = 1 grade, whereas 63 segments remained unchanged. The sensitivity of dobutamine, dipyridamole and combined dipyridamole-dobutamine for predicting recovery was 72% (95% confidence interval [CI] 60.9% to 81.3%), 67% (CI 55.8% to 77%) and 94% (CI 86.3% to 97.9%), respectively. The specificity of dipyridamole, dobutamine and combined dipyridamole-dobutamine was 95% (CI 86.7% to 99%), 92% (CI 82.4% to 97.3%) and 89% (CI 78.4% to 95.4%), respectively. The accuracy of the dobutamine, dipyridamole and combined dipyridamole-dobutamine test was 80%, 79% and 92%, respectively (combined dipyridamole-dobutamine vs. dobutamine, p < 0.05; combined dipyridamole-dobutamine vs. dipyridamole, p < 0.01). CONCLUSIONS Infra-low dose dipyridamole added to low dose dobutamine recruits an inotropic reserve in asynergic segments that were nonresponders after either dobutamine or dipyridamole alone and destined to recover after revascularization.

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.

Prognostic significance of new atrial fibrillation and its relation to heart failure following acute myocardial infarction

New‐onset atrial fibrillation (AF) after acute myocardial infarction (AMI) frequently occurs in association with postinfarction complications, particularly with heart failure (HF).

Gender-related differences in presentation, treatment and long-term outcome in patients with first-diagnosed atrial fibrillation and structurally normal heart: the Belgrade atrial fibrillation study.

BACKGROUND Several studies have investigated gender-related differences in atrial fibrillation (AF), but limited data are available in relation to gender-related differences in presentation, treatment and long-term outcomes of patients with first-diagnosed AF and structurally normal heart. OBJECTIVE To compare gender-related clinical characteristics, presentation, treatment and long-term outcomes in a cohort of patients with first-diagnosed non-valvular AF and a structurally normal heart, following a 10-year follow-up. METHODS Observational cohort study of patients with AF between 1992 and 2007. RESULTS Of 862 patients (mean age 52.2±12.1 years), 315 (36.5%) were female. Paroxysmal AF and hypertension were significantly more prevalent in females, while persistent AF was more common amongst males (all p<0.001). Female patients were more symptomatic (p=0.002). After a mean follow-up of 10.1±6.1 years, more male patients developed tachycardiomyopathy (6.0% vs. 1.9%, p=0.02). In multivariate analysis, male gender remained significantly associated with tachycardiomyopathy (HR 3.1, 95% CI: 1.3-7.4, p=0.012). The rate of transition to permanent AF, thromboembolism, hemorrhage, all-cause mortality, cardiovascular and sudden death did not significantly differ between male and female patients. CONCLUSIONS Gender differences are evident in AF. Male patients were less asymptomatic or more frequently developed persistent AF. Male patients were also at higher risk of tachycardiomyopathy, suggesting that these patients require more attention to rate control during follow-up.