Browsing by Author "Ostojic, Miodrag C. (34572650500)"

Background: Lone atrial fibrillation (AF) has been suggested to have a favorable long-term prognosis. Significant interest has been directed at factors predicting arrhythmia progression, and the HATCH score (hypertension, age ≥ 75 years, transient ischemic attack or stroke [2 points], COPD, and heart failure [2 points]) recently has been proposed as a predictive score for AF progression. We investigated long-term outcomes in a large cohort of newly diagnosed lone AF and whether progression from paroxysmal to permanent AF confers an adverse impact on outcomes, including stroke and thromboembolism. Methods: The study was an observational cohort of 346 patients with newly diagnosed lone AF with a mean follow-up of 12.1 ± 7.3 years. Results: Baseline paroxysmal AF was confirmed in 242 patients, and of these, 65 (26.9%) subsequently experienced progression to permanent AF. Older age and development of congestive heart failure during follow-up were the multivariate predictors of AF progression (both P<.01), which was documented in 19.8% of patients with a HATCH score of 0 vs 63.2% with a score of 2 ( P<.001), although the predictive validity of the HATCH score per se was modest (C statistic, 0.6). The annual rate of thromboembolism and heart failure during follow-up were low (0.4% each), and five patients (1.4%) died. AF progression, development of cardiac diseases, and older age were multivariate predictors of adverse outcomes, including thromboembolism (all P<.05). Baseline CHADS2 (congestive heart failure, hypertension, age ≥75, diabetes mellitus, prior stroke or transient ischemic attack) score was not predictive for thromboembolism (C statistic, 0.50; 95% CI, 0.31-0.69). Conclusions: This 12-year follow-up study provides confirmatory evidence of a generally favorable prognosis of lone AF, but adverse outcomes (including stroke and thromboembolism) are significantly infl uenced by age and the (new) development of underlying heart disease. Arrhythmia progression in lone AF is a marker of increased risk for adverse cardiovascular events. © 2012 American College of Chest Physicians.

Since diastolic dysfunction is an early sign of the heart disease, detecting diastolic disturbances is predicted to be the way for early recognizing underlying heart disease in athletes. So-called chamber stiffness index (E/e′)/LVDd was predicted to be useful in distinguishing physiological from pathological left ventricular hypertrophy, because it was shown to be reduced in athletes. It remains unknown whether it is reduced in all athletic population. Standard and tissue Doppler were used to assess cardiac parameters at rest in 16 elite male wrestlers, 21 water polo player, and 20 sedentary subjects of similar age. In addition to (E/e′)/LVDd index, a novel (E/e′)/LVV, (E/e′)/RVe′lat indices were determined. Progressive continuous maximal test on treadmill was used to assess the functional capacity. VO2 max was the highest in water polo players, and higher in wrestlers than in controls. LVDd, LVV, LVM/BH2.7 were higher in athletes. Left ventricular early diastolic filling velocity, deceleration and isovolumetric relaxation time did not differ. End-systolic wall stress was significantly higher in water polo players. RV e′ was lower in water polo athletes. Right atrial pressure (RVE/e′) was the highest in water polo athletes. (E/e′lat)/LVDd was not reduced in athletes comparing to controls (water polo players 0.83 ± 0.39, wrestlers 0.73 ± 0.29, controls 0.70 ± 0.28; P = 0.52), but (E/e′s)/RVe′lat better distinguished examined groups (water polo players 0.48 ± 0.37, wrestlers 0.28 ± 0.15, controls 0.25 ± 0.16, P = 0.015) and it was the only index which predicted VO2 max. In conclusion, intensive training does not necessarily reduce (E/e′lat)/LVDd index. A novel index (E/e′s)/RVe′lat should be investigated furthermore in detecting diastolic adaptive changes. © 2010, Wiley Periodicals, Inc.

[No abstract available]

Background: It has been shown that coronary flow velocity reserve (CFVR) measurement by transthoracic Doppler echocardiography (TTDE) during dobutamine (DOB) provocation provides a more accurate functional evaluation of myocardial bridging (MB) compared to adenosine. However; the cut-off value of CFVR during DOB for identification of MB associated with myocardial ischemia has not been fully clarified. Purpose: This prospective study aimed to determine the cut-off value of TTDE-CFVR during DOB in patients with isolated-MB, as compared with stress-induced wall motion abnormalities (VMA) during exercise stress-echocardiography (SE) as reference. Methods: Eighty-one symptomatic patients (55 males [68%], mean age 56 ± 10 years; range: 27–74 years) with the existence of isolated-MB on the left anterior descending artery (LAD) and systolic MB-compression ≥50% diameter stenosis (DS) were eligible to participate in the study. Each patient underwent treadmill exercise-SE, invasive coronary angiography, and TTDE-CFVR measurements in the distal segment of LAD during DOB infusion (DOB: 10–40 µg/kg/min). Using quantitative coronary angiography, both minimal luminal diameter (MLD) and percent DS at MB-site at end-systole and end-diastole were determined. Results: Stress-induced myocardial ischemia with the occurrence of WMA was found in 23 patients (28%). CFVR during peak DOB was significantly lower in the SE-positive group compared with the SE-negative group (1.94 ± 0.16 vs. 2.78 ± 0.53; p < 0.001). ROC analyses identified the optimal CFVR cut-off value ≤ 2.1 obtained during high-dose dobutamine (>20 µg/kg/min) for the identification of MB associated with stress-induced WMA, with a sensitivity, specificity, positive and negative predictive value of 96%, 95%, 88%, and 98%, respectively (AUC 0.986; 95% CI: 0.967–1.000; p < 0.001). Multivariate logistic regression analysis revealed that MLD and percent DS, both at end-diastole, were the only independent predictors of ischemic CFVR values ≤2.1 (OR: 0.023; 95% CI: 0.001–0.534; p = 0.019; OR: 1.147; 95% CI: 1.042–1.263; p = 0.005; respectively). Conclusions: Non-invasive CFVR during dobutamine provocation appears to be an additional and important noninvasive tool to determine the functional severity of isolated-MB. A transthoracic CFVR cut-off ≤2.1 measured at a high-dobutamine dose may be adequate for detecting myocardial ischemia in patients with isolated-MB. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Diabetes mellitus is an independent risk factor for stroke and atrial fibrillation. Therefore, the risk/benefit profile of the oral factor Xa inhibitor edoxaban stratified by diabetes is of clinical interest. Methods: 21,105 patients enrolled in ENGAGE AF-TIMI 48 were stratified into 2 pre-specified groups: without (N = 13,481) and with diabetes (N = 7,624). Results: On average, patients with diabetes were younger, and had a higher body mass index, CHA2DS2-VASc score and baseline endogenous Factor Xa activity. After multivariate adjustments, patients with diabetes had a similar rate of stroke and systemic embolism compared to those without diabetes (adjusted hazard ratio (HRadj) 1.08; 95% confidence interval (CI) 0.94–1.24; p = 0.28). However, the risk of major bleeding was significantly higher in patients with diabetes (HRadj 1.28; 95% CI 1.14–1.44; p < 0.001). The treatment effect of edoxaban (vs warfarin) was not modified by diabetes (all p-interactions > 0.05), a finding supported by the preserved edoxaban concentrations and inhibition of Factor Xa regardless of diabetes. The HRs of stroke and systemic embolism in patients receiving the higher-dose edoxaban regimen vs warfarin were 0.93 and 0.84 (p-interaction = 0.54) in those with and without diabetes respectively. The higher-dose edoxaban regimen reduced major bleeding (by 19–21%) and cardiovascular death (by 7–17%) regardless of diabetes (p-interactions = 0.81 and 0.33 respectively). Conclusion: Patients with diabetes in ENGAGE AF-TIMI 48 had higher bleeding risk, but after adjustment similar stroke risk, compared to those without diabetes. The higher-dose edoxaban regimen had similar efficacy compared to warfarin, while reducing bleeding and cardiovascular mortality, irrespective of diabetes. © 2020 Elsevier B.V.

Background: The COMET-CTO trial was a randomized prospective study that assessed long-term follow-up in patients with chronic total occlusion (CTO) in coronary arteries treated with percutaneous coronary intervention (PCI) or with optimal medical therapy (OMT). During the 9-month follow-up, the incidence of major adverse cardiac events (MACE) did not differ between the two groups; no death or myocardial infarction (MI) was observed. There was a significant difference in quality of life (QoL), assessed by the Seattle Angina Questionnaire (SAQ), in favor of the PCI group. Here we report long-term follow-up results (56 ± 12 months). Methods: Between October 2015 and May 2017, a total of 100 patients with CTO were randomized into two groups of 50 patients: PCI CTO or OMT group. The primary endpoint of the current study was the incidence of MACE defined as cardiac death, MI, and revascularization [PCI or coronary artery bypass graft (CABG)]. As the secondary exploratory outcome, we analyzed all the cause-mortality rate. Results: Out of 100 randomized patients, 92 were available for long-term follow-up (44 in the PCI group and 48 in the OMT group). The incidence of MACE did not differ significantly between the two groups (p = 0.363). Individual components of MACE were distributed, respectively: cardiac death (OMT vs. PCI group, 6 vs. 3, p = 0.489), MI (OMT vs. PCI group, 1 vs. 0, p = 1), and revascularization (PCI: OMT vs. PCI group, 2 vs. 2, p = 1; CABG: OMT vs. PCI group, 1 vs. 1, p = 1). There was no significant difference between the two groups regarding the individual component of MACE. Six patients died from non-cardiac causes [five deaths were reported in the OMT group and one death in the PCI group (p = 0.206)]. Kaplan-Meier survival curves for MACE did not differ significantly between the study groups (log-rank 0.804, p = 0.370). Regarding the secondary exploratory outcome, a total of 15 patients died at 56 ± 12 months (11 in the OMT and 4 in the PCI group) (p = 0.093). The Kaplan-Meier survival curves for all-cause mortality rates did not differ significantly between the two groups (log rank 3.404, p = 0.065). There were no statistically significant differences between OMT and PCI groups in all five SAQ domains. There was a significant improvement in three SAQ domains in the PCI group: PL (p < 0.001), AF (p = 0.007), and QoL (p = 0.001). Conclusion: After 56 ± 12 months of follow-up, the incidence of MACE, as well as QoL measured by SAQ, did not differ significantly between the PCI and OMT groups. Copyright © 2023 Juricic, Stojkovic, Galassi, Stankovic, Orlic, Vukcevic, Milasinovic, Aleksandric, Tomasevic, Dobric, Nedeljkovic, Beleslin, Dikic, Banovic, Ostojic and Tesic.

At the moment of signing the Stent for Life (SFL) Initiative on August 31st, 2009, it was shown that, in Serbia during 2008, 48% of patients with ST-elevation myocardial infarction (STEMI) did not receive any reperfusion and only 19% and 33% received primary percutaneous coronary intervention (p-PCI) or hospital thrombolysis, respectively. However, during 2009, there was a trend towards a substantial increase in p-PCI procedures. This was the result of the commitment of cardiologists, the contract signed by the Health Insurance Fund (HIF) for remuneration of catheterisation laboratory (cathlab) staff for each p-PCI procedure (2005), and the provision of new cathlabs by the Ministry of Health (MOH). The number of PCI centres and trained cardiologists has been rising simultaneously. Direct mobile telephone contact with interventional cardiologists has facilitated the transport of patients directly to cathlabs (from 7.5% before 2009 to 34.2% in 2010 and 2011). Although the number of patients treated with p-PCI is increasing (2006 - 647 p-PCIs; 2007 - 1,248 p-PCIs; 2008 -1,794 p-PCIs; 2009 - 2,468 p-PCIs; 2010 - 3,216 and 2011 - 3,498 p-PCIs), the percentage of patients who are treated within 120 minutes of establishing a diagnosis (first medical contact) is still not satisfactory (38%). © 2012 Europa Edition. All rights reserved.

Background Body-mass index (BMI) and diabetes have increased worldwide, whereas global average blood pressure and cholesterol have decreased or remained unchanged in the past three decades. We quantified how much of the effects of BMI on coronary heart disease and stroke are mediated through blood pressure, cholesterol, and glucose, and how much is independent of these factors. Methods We pooled data from 97 prospective cohort studies that collectively enrolled 1·8 million participants between 1948 and 2005, and that included 57 161 coronary heart disease and 31 093 stroke events. For each cohort we excluded participants who were younger than 18 years, had a BMI of lower than 20 kg/m2, or who had a history of coronary heart disease or stroke. We estimated the hazard ratio (HR) of BMI on coronary heart disease and stroke with and without adjustment for all possible combinations of blood pressure, cholesterol, and glucose. We pooled HRs with a random-effects model and calculated the attenuation of excess risk after adjustment for mediators. Findings The HR for each 5 kg/m2 higher BMI was 1·27 (95% CI 1·23-1·31) for coronary heart disease and 1·18 (1·14-1·22) for stroke after adjustment for confounders. Additional adjustment for the three metabolic risk factors reduced the HRs to 1·15 (1·12-1·18) for coronary heart disease and 1·04 (1·01-1·08) for stroke, suggesting that 46% (95% CI 42-50) of the excess risk of BMI for coronary heart disease and 76% (65-91) for stroke is mediated by these factors. Blood pressure was the most important mediator, accounting for 31% (28-35) of the excess risk for coronary heart disease and 65% (56-75) for stroke. The percentage excess risks mediated by these three mediators did not differ significantly between Asian and western cohorts (North America, western Europe, Australia, and New Zealand). Both overweight (BMI ≥25 to <30 kg/m2) and obesity (BMI ≥30 kg/m2) were associated with a significantly increased risk of coronary heart disease and stroke, compared with normal weight (BMI ≥20 to <25 kg/m2), with 50% (44-58) of the excess risk of overweight and 44% (41-48) of the excess risk of obesity for coronary heart disease mediated by the selected three mediators. The percentages for stroke were 98% (69-155) for overweight and 69% (64-77) for obesity. Interpretation Interventions that reduce high blood pressure, cholesterol, and glucose might address about half of excess risk of coronary heart disease and three-quarters of excess risk of stroke associated with high BMI. Maintenance of optimum bodyweight is needed for the full benefits.

Background: Mitral annular calcification (MAC) has been suggested as a reliable, time-averaged marker of atherosclerosis and is associated with coronary artery disease, heart failure, ischemic stroke, and increased mortality. Data on the relationship between MAC and cardiovascular morbidity and mortality in atrial fibrillation (AF) are sparse, with the exception of the relationship between MAC and stroke. We investigated the association of MAC with cardiovascular morbidity, stroke, cardiovascular mortality, and all-cause death in a cohort of middle-aged patients with AF with a mean 10-year follow-up. Methods: This was an observational study of patients with nonvalvular AF between 1992 and 2007. Results: Of 1,056 patients, 33 (3.1%) had MAC; they were more likely to be older and female and to have a dilated left atrium, reduced left ventricular ejection fraction, permanent AF, hypertension, and/or diabetes mellitus (all P < .05). Total follow-up was 10,418.5 years (mean, 9.9 ± 5.9 years), and the mean age was 52.7 ± 12.2 years. In univariate analysis, MAC was associated with all-cause death, cardiovascular death, stroke, new cardiac morbidity (all P < .05), and the composite end point of ischemic stroke, myocardial infarction (MI), and all-cause death (P < .001). In multivariate analyses, MAC was related to all-cause death (hazard ratio [HR], 4.3; 95% CI, 1.8-10.0; P < .001), cardiovascular death (HR, 3.5; 95% CI, 1.2-10.4; P = .025), the composite end point (HR, 2.1; 95% CI, 1.0-4.3; P = .048), and new cardiac morbidity (HR, 2.4; 95% CI, 1.3-4.5; P = .005). There was no significant relationship between MAC and stroke or MI in the multivariate analyses. Conclusions: MAC is associated with increased cardiovascular morbidity, cardiovascular mortality, and all-cause mortality of patients with AF. MAC should be acknowledged as a marker of increased cardiovascular risk in middle-aged patients with AF. © 2011 American College of Chest Physicians.

The aim of this randomized prospective study was to evaluate the quality of life (QoL) using the “Seattle Angina Questionnaire” (SAQ) in patients with chronic total occlusion (CTO) in coronary arteries treated with either percutaneous coronary intervention (PCI) or optimal medical therapy (OMT), or only with OMT. The potential benefits of recanalization of CTO by PCI have been controversial because of the scarcity of randomized controlled trials. A total of 100 patients with CTO were randomized (1:1) prospectively into the PCI CTO or the OMT group (50 patients in each group). There were no baseline differences in the SAQ scores between the groups, except for physical limitation scores (P = 0.03). During the mean follow-up (FUP) of 275 ± 88 days, patients in the PCI group reported less physical activity limitations (72.7 ± 21.3 versus 60.5 ± 27, P = 0.014), less frequent angina episodes (89.8 ± 17.6 versus 76.8 ± 27.1, P = 0.006), better QoL (79.9 ± 22.7 versus 62.5 ± 25.5, P = 0.001), greater treatment satisfaction (91.2 ± 13.6 versus 81.4 ± 18.4, P = 0.003), and borderline differences in angina stability (61.2 ± 26.5 versus 51.0 ± 23.7, P = 0.046) compared to patients in the OMT group. There were no significant differences in SAQ scores in the OMT group at baseline and during the FUP. There was a statistically significant increase in all five domains in the PCI group. Symptoms and QoL measured by the SAQ were significantly improved after CTO PCI compared to OMT alone. © 2021, International Heart Journal Association. All rights reserved.

Objectives: The aim of this study was to assess the pharmacokinetics and tolerability of Biolimus A9 eluted from Nobori coronary stents. Background: The release kinetics and pharmacokinetics of drugs delivered via coronary stents have been shown to play an essential role in the efficacy and safety of drug eluting stents. Methods: Twenty patients with coronary artery disease were treated with single 14-mm (10 patients) or 28-mm long stent (10 patients). Blood samples were drawn at 16 time points to determine the pharmacokinetics of Biolimus A9. At seven time points, complete laboratory and toxicology panels were assessed to screen for potential Biolimus A9 toxicity. The primary endpoint of the study was the systemic blood concentrations of Biolimus A9 after 28 days and 6 months as measured using highly specific and sensitive liquid chromatography- tandem mass spectrometry assay. Results: At 28 days, 6 patients (30%) had quantifiable Biolimus A9 concentrations in blood. The highest Biolimus A9 blood concentration measured in any sample was 32.2 pg/mL. The median time to maximum concentration was 2 hr, ranging from 0.05 hr to 3 months. Six months after stent implantation, only 1 of 20 patients had measurable Biolimus A9 concentrations at the lowest level of quantification, while at 9 months no sample had quantifiable Biolimus A9 concentrations. Laboratory and toxicology assessments did not indicate any impact of Biolimus A9 on the evaluated parameters. Conclusion: Results of this study suggest that systemic exposure to Biolimus A9 was very low and that Biolimus A9 was well tolerated. © 2008 Wiley-Liss, Inc.