Browsing by Author "Kafedzic, Srdjan (55246101300)"

[No abstract available]

Aims: We aimed to investigate the rapid induction of therapeutic hypothermia using the ZOLL Proteus Intravascular Temperature Management System in patients with anterior ST-elevation myocardial infarction (STEMI) without cardiac arrest. Methods and results: A total of 50 patients were randomised; 22 patients (88%; 95% confidence interval [CI]: 69-97%) in the hypothermia group and 23 patients (92%; 95% CI: 74-99) in the control group completed cardiac magnetic resonance imaging at four to six days and 30-day follow-up. Intravascular temperature at coronary guidewire crossing after 20.5 minutes of endovascular cooling decreased to 33.6°C (range 31.9-35.5°C). There was a 17-minute (95% CI: 4.6-29.8 min) cooling-related delay to reperfusion. In "per protocol" analysis, median infarct size/left ventricular mass was 16.7% in the hypothermia group versus 23.8% in the control group (absolute reduction 7.1%, relative reduction 30%; p=0.31) and median left ventricular ejection fraction (LVEF) was 42% in the hypothermia group and 40% in the control group (absolute reduction 2.4%, relative reduction 6%; p=0.36). Except for self-terminating paroxysmal atrial fibrillation (32% versus 8%; p=0.074), there was no excess of adverse events in the hypothermia group. Conclusions: We rapidly and safely cooled patients with anterior STEMI to 33.6°C at the time of coronary guidewire crossing. This is ≥1.1°C lower than in previous cooling studies. Except for self-terminating atrial fibrillation, there was no excess of adverse events and no clinically important cooling-related delay to reperfusion. A statistically non-significant numerical 7.1% absolute and 30% relative reduction in infarct size warrants a pivotal trial powered for efficacy. © Europa Digital & Publishing 2017. All rights reserved.

Aim: As a result of a higher prevalence of comorbidities, elderly adults are often underrepresented in clinical trials, and more often experience complications during percutaneous coronary intervention. Our aim was to evaluate clinical outcomes of patients older than 80 years, compared with their younger counterparts, when bioresorbable polymer biolimus A9 drug-eluting stent is used for their treatment. Methods: The prospective, observational e-Nobori registry was created to validate the safety and efficacy of bioresorbable polymer drug-eluting stent in unselected patients. The primary end-point of the study was freedom from target lesion failure defined as a composite of cardiac death, target vessel-related myocardial infarction and clinically-driven target lesion revascularization at 1 year. Results: There were 781 (7.8%) octogenarians, they were less frequently male (62% vs 77%; P < 0.0001) and more often presented as acute coronary syndrome (44% vs 39%; P = 0.0182). The index percutaneous coronary intervention success was lower in the elderly patients (98% vs 99%; P = 0.0398). One-year follow up was completed for 97% of the elderly patients and 99% of the younger patients. The difference in target lesion failure (3.33% vs 2.83%; log–rank P = 0.0114) was mainly driven by increased mortality in octogenarians (3.73% vs 1.47%; P < 0.0001). Elderly patients had more bleeding and vascular complications (2.67% vs 1.05%; P = 0.0001). Conclusions: Despite advanced age, multiple comorbidities and complexity of treated lesions, clinical outcomes are favorable in octogenarians treated by bioresorbable polymer biolimus A9 drug-eluting stent. Geriatr Gerontol Int 2016; 16: 1246–1253. © 2015 Japan Geriatrics Society

Aim: As a result of a higher prevalence of comorbidities, elderly adults are often underrepresented in clinical trials, and more often experience complications during percutaneous coronary intervention. Our aim was to evaluate clinical outcomes of patients older than 80 years, compared with their younger counterparts, when bioresorbable polymer biolimus A9 drug-eluting stent is used for their treatment. Methods: The prospective, observational e-Nobori registry was created to validate the safety and efficacy of bioresorbable polymer drug-eluting stent in unselected patients. The primary end-point of the study was freedom from target lesion failure defined as a composite of cardiac death, target vessel-related myocardial infarction and clinically-driven target lesion revascularization at 1 year. Results: There were 781 (7.8%) octogenarians, they were less frequently male (62% vs 77%; P < 0.0001) and more often presented as acute coronary syndrome (44% vs 39%; P = 0.0182). The index percutaneous coronary intervention success was lower in the elderly patients (98% vs 99%; P = 0.0398). One-year follow up was completed for 97% of the elderly patients and 99% of the younger patients. The difference in target lesion failure (3.33% vs 2.83%; log–rank P = 0.0114) was mainly driven by increased mortality in octogenarians (3.73% vs 1.47%; P < 0.0001). Elderly patients had more bleeding and vascular complications (2.67% vs 1.05%; P = 0.0001). Conclusions: Despite advanced age, multiple comorbidities and complexity of treated lesions, clinical outcomes are favorable in octogenarians treated by bioresorbable polymer biolimus A9 drug-eluting stent. Geriatr Gerontol Int 2016; 16: 1246–1253. © 2015 Japan Geriatrics Society

Background: Newly or already diagnosed cancer might significantly influence the clinical presentation, outcome, and therapy of acute pulmonary embolism (PE). Methods: Out of 1745 patients with acute PE, 66 patients were diagnosed with cancer during an initial hospitalization due to acute PE (where PE was the first clinical manifestation of cancer), 165 patients had known cancer treated in the last 6 months, and 1514 patients had acute PE without known or suspected cancer. The primary end-point of the present study was all-cause hospital death. The secondary end-points were the proportion of patients treated with thrombolysis and who had severe disease, and the ocurrence of major or clinically relevant nonmajor bleeding. Results: Patients with PE as the first presentation of cancer had the highest hospital mortality rate compared to the other two groups (HR for the mortality rate in patients without cancer as a reference, adjusted to four-stratum mortality risk, and Charlson's comorbidity index was 3.440; 95% confidence interval (CI), 1.795–6.591; p < 0.001). Patients with known cancer before PE had a significantly lower chance of being treated with thrombolysis than patients without cancer (OR, 0.523; 95% CI, 0.339–0.807; p = 0.003); additionally, this difference was attenuated but remained when the OR was adjusted to age (OR, 0.542; 95% CI, 0.351–0.838; p = 0.006). Patients with known cancer had a higher frequency of high-risk PE compared with patients without cancer (18.2% vs. 12.8%; p < 0.001). Patients with PE as the first manifestation of cancer had a higher frequency of intermediate-high-risk PE than those without (36.4% vs. 30.9%; p < 0.001). There was no significant difference in bleeding during hospitalization between groups. Conclusion: Patients with cancer had a more severe presentation of acute PE than patients without. Furthermore, patients with PE as the first manifestation of cancer had the highest hospital mortality rate, and patients with known cancer were least likely to be treated with thrombolysis. © 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

Background: Newly or already diagnosed cancer might significantly influence the clinical presentation, outcome, and therapy of acute pulmonary embolism (PE). Methods: Out of 1745 patients with acute PE, 66 patients were diagnosed with cancer during an initial hospitalization due to acute PE (where PE was the first clinical manifestation of cancer), 165 patients had known cancer treated in the last 6 months, and 1514 patients had acute PE without known or suspected cancer. The primary end-point of the present study was all-cause hospital death. The secondary end-points were the proportion of patients treated with thrombolysis and who had severe disease, and the ocurrence of major or clinically relevant nonmajor bleeding. Results: Patients with PE as the first presentation of cancer had the highest hospital mortality rate compared to the other two groups (HR for the mortality rate in patients without cancer as a reference, adjusted to four-stratum mortality risk, and Charlson's comorbidity index was 3.440; 95% confidence interval (CI), 1.795–6.591; p < 0.001). Patients with known cancer before PE had a significantly lower chance of being treated with thrombolysis than patients without cancer (OR, 0.523; 95% CI, 0.339–0.807; p = 0.003); additionally, this difference was attenuated but remained when the OR was adjusted to age (OR, 0.542; 95% CI, 0.351–0.838; p = 0.006). Patients with known cancer had a higher frequency of high-risk PE compared with patients without cancer (18.2% vs. 12.8%; p < 0.001). Patients with PE as the first manifestation of cancer had a higher frequency of intermediate-high-risk PE than those without (36.4% vs. 30.9%; p < 0.001). There was no significant difference in bleeding during hospitalization between groups. Conclusion: Patients with cancer had a more severe presentation of acute PE than patients without. Furthermore, patients with PE as the first manifestation of cancer had the highest hospital mortality rate, and patients with known cancer were least likely to be treated with thrombolysis. © 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.

We investigated circulating levels of inflammatory biomarkers pentraxin-3 (PTX3), cyclophilin A (CypA), and heparin-binding epidermal growth factor-like growth factor (HB-EGF); oxidative stress; and antioxidant status markers in the patients with ST-segment elevation acute myocardial infarction (STEMI) to better understand a relationship between inflammation and oxidative stress. We examined the impact of oxidative stress on high values of inflammatory parameters. The study included 87 patients with STEMI and 193 controls. We observed a positive correlation between PTX3 and HB-EGF (ρ = 0.24, P =.027), CyPA, and sulfhydryl (SH) groups (ρ = 0.25, P =.026), and a negative correlation between PTX3 and SH groups (ρ = −0.35, P =.001) in patients with STEMI. To better understand the effect of the examined parameters on the occurrence of high concentrations of inflammatory parameters, we grouped them using principal component analysis. This analysis identified the 4 most contributing factors. Optimal cutoff values for discrimination of patients with STEMI from controls were calculated for PTX3 and HB-EGF. An independent predictor for PTX3 above the cutoff value was a “metabolic-oxidative stress factor” comprised of glucose and oxidative stress marker prooxidant-antioxidant balance (odds ratio = 4.449, P =.030). The results show that higher PTX3 values will occur in patients having STEMI with greater metabolic and oxidative stress status values. © The Author(s) 2020.

Aims: To examine the relationship between admission glucose (AG) level and short-term in-hospital mortality and to investigate the association between hyperglycemia and major bleeding in PE patients with and without DMT2. Methods: We evaluated 1165 patients with diagnosed acute PE with multi-detector computed tomography pulmonary angiography (MDCT-PA) enrolled in the Regional multicenter PE registry (REPER). The study population was classified to patients with diabetes mellitus type 2 (DMT2) and those without diabetes. According to quartiles of AG patients, both groups separately were categorized into four subgroups (DMT2 I: < 7.5 mmol/L; II: 7.5–10.0 mmol/L; III: 10.0–15.7 mmol/L; IV: > 15.7 mmol/L and (non-DMT2 I: < 5.5 mmol/L; II: 5.5–6.3 mmol/L; III: 6.3–7.9 mmol/L; IV: > 7.9 mmol/L). Results: All-cause mortality was higher in the DMT2 group (9.5% vs. 18.2%, p < 0.001), and PE-cause mortality was 6% for the patients without DMT2 and 12.4% for DMT2 patients (p = 0.02). The patients in the fourth AG quartiles in both groups, without DMT2 and with DMT2, had significantly higher all-cause and PE-cause in-hospital mortality compared with the first quartile. Rates of major bleeding were similar between the groups. On the multivariable analysis, after adjusting for age, gender and mortality risk, the adherence in the fourth AG quartile had an independent predictive value for all-cause death (HR 2.476, 95% CI 1.017–6.027) only in DM patients. Conclusion: In our cohort of patients with acute PE, diabetes was associated with increased rates for all-cause and PE-cause mortality. © 2021, Springer-Verlag Italia S.r.l., part of Springer Nature.

Aims: To examine the relationship between admission glucose (AG) level and short-term in-hospital mortality and to investigate the association between hyperglycemia and major bleeding in PE patients with and without DMT2. Methods: We evaluated 1165 patients with diagnosed acute PE with multi-detector computed tomography pulmonary angiography (MDCT-PA) enrolled in the Regional multicenter PE registry (REPER). The study population was classified to patients with diabetes mellitus type 2 (DMT2) and those without diabetes. According to quartiles of AG patients, both groups separately were categorized into four subgroups (DMT2 I: < 7.5 mmol/L; II: 7.5–10.0 mmol/L; III: 10.0–15.7 mmol/L; IV: > 15.7 mmol/L and (non-DMT2 I: < 5.5 mmol/L; II: 5.5–6.3 mmol/L; III: 6.3–7.9 mmol/L; IV: > 7.9 mmol/L). Results: All-cause mortality was higher in the DMT2 group (9.5% vs. 18.2%, p < 0.001), and PE-cause mortality was 6% for the patients without DMT2 and 12.4% for DMT2 patients (p = 0.02). The patients in the fourth AG quartiles in both groups, without DMT2 and with DMT2, had significantly higher all-cause and PE-cause in-hospital mortality compared with the first quartile. Rates of major bleeding were similar between the groups. On the multivariable analysis, after adjusting for age, gender and mortality risk, the adherence in the fourth AG quartile had an independent predictive value for all-cause death (HR 2.476, 95% CI 1.017–6.027) only in DM patients. Conclusion: In our cohort of patients with acute PE, diabetes was associated with increased rates for all-cause and PE-cause mortality. © 2021, Springer-Verlag Italia S.r.l., part of Springer Nature.

This prospective, first-in-man, open-label multicenter study sought to assess the pharmacokinetics of sirolimus after Ultimaster drug-eluting stent implantation (coated with sirolimus and bioabsorbable co-polymer) in patients with de novo coronary artery disease (the TCD-10023 PK study). The primary endpoint was sirolimus concentration in peripheral whole blood at 28 days after stent implantation. In addition, safety, tolerability, therapeutic outcome and vasomotor response after stent implantation were studied. Twenty patients were enrolled in the study. Blood samples for the measurements of sirolimus concentration were collected at eight time points during first 48 h, at 7 days and 28 days after stent implantation. Patients underwent 6-month angiographic and up to 12 months clinical follow-up. At 28 days, only two of 20 patients had sirolimus concentrations above lower limit of quantification (20.0 pg/mL). The highest sirolimus blood concentration was 105 pg/mL. The median maximum concentration was 36.8 pg/mL (range 22.9-41.5 pg/mL) for stent 3.0 × 15 mm and 87.2 pg/mL (range 60.0-105.0 pg/mL) for 3 × 28 mm stent. The median systemic exposure, as measured by the area under the time-concentration curve, was 8.3 ng h/mL (range 6.47-28.0 ng h/mL). At 6 months, endothelial function was well preserved, and up to 12 months, there were no signs of sirolimus toxicity nor any other safety concerns. Our results demonstrate that implantation of Ultimaster stent resulted in almost nondetectable sirolimus in blood after 28 days. These findings were translated into exceptional safety profile, without any sign of systemic toxicity. © 2014 Société Française de Pharmacologie et de Thérapeutique.

This prospective, first-in-man, open-label multicenter study sought to assess the pharmacokinetics of sirolimus after Ultimaster drug-eluting stent implantation (coated with sirolimus and bioabsorbable co-polymer) in patients with de novo coronary artery disease (the TCD-10023 PK study). The primary endpoint was sirolimus concentration in peripheral whole blood at 28 days after stent implantation. In addition, safety, tolerability, therapeutic outcome and vasomotor response after stent implantation were studied. Twenty patients were enrolled in the study. Blood samples for the measurements of sirolimus concentration were collected at eight time points during first 48 h, at 7 days and 28 days after stent implantation. Patients underwent 6-month angiographic and up to 12 months clinical follow-up. At 28 days, only two of 20 patients had sirolimus concentrations above lower limit of quantification (20.0 pg/mL). The highest sirolimus blood concentration was 105 pg/mL. The median maximum concentration was 36.8 pg/mL (range 22.9-41.5 pg/mL) for stent 3.0 × 15 mm and 87.2 pg/mL (range 60.0-105.0 pg/mL) for 3 × 28 mm stent. The median systemic exposure, as measured by the area under the time-concentration curve, was 8.3 ng h/mL (range 6.47-28.0 ng h/mL). At 6 months, endothelial function was well preserved, and up to 12 months, there were no signs of sirolimus toxicity nor any other safety concerns. Our results demonstrate that implantation of Ultimaster stent resulted in almost nondetectable sirolimus in blood after 28 days. These findings were translated into exceptional safety profile, without any sign of systemic toxicity. © 2014 Société Française de Pharmacologie et de Thérapeutique.

Some patients with unstable angina and critical stenosis of the left anterior descending coronary artery (LAD) present with Wellens syndrome (WS), i.e., inverted or biphasic T-waves in the anterior precordial leads. We assessed clinical, angiographic, electro- and echocardiographic characteristic of patients with WS. In this retrospective study, clinical, angiographic, electro- and echocardiographic characteristic of 35 patients with WS were compared to 57 patients with critical LAD stenosis and normal resting electrocardiogram (ECG), and 45 subjects with normal coronary angiogram. QTc dispersion was measured from the 12-lead ECG as the difference between longest and shortest QTc intervals. Mechanical dispersion was defined as the time difference between the longest and shortest contraction durations which were measured as the time from the first deflection of the QRS complex to maximum myocardial shortening of each 18 segmental longitudinal strain curves derived by speckle tracking echocardiography. There were no significant differences in the complexity and location of the LAD lesion, anterograde and collateral flow in LAD and coronary artery dominance between patients with WS and normal ECG (P > 0.05, for all). Patients with WS had lower global longitudinal strain (GLS) and more pronounced both QTc and myocardial mechanical dispersion than patients with critical LAD stenosis and normal ECG, and control subjects (P < 0.05). T-wave changes in patients with WS are associated with more profound regional myocardial dysfunction and increased QTc and myocardial mechanical dispersion. Similar angiographic characteristics of the LAD lesion were seen in patients with WS and normal ECG. © 2017, Springer Science+Business Media Dordrecht.

Objective: The pre-test probability (PTP) model for obstructive coronary artery disease (CAD) was updated in 2019 by the European Society of Cardiology (ESC). To our knowledge, this model was never externally validated in a population with a high incidence of CAD. The aim of this study is to validate the new PTP ESC model in our population, which has a high CAD incidence, and to compare it with the previous PTP ESC model from 2013. Methods: We retrospectively analysed 1294 symptomatic patients with suspected CAD referred to our centre between 2015 and 2019. In all patients, the PTP score was calculated based on age, gender, and symptoms according to the ESC model from 2013 (2013-ESC-PTP) and 2019 (2019-ESC-PTP). All patients underwent invasive coronary angiography (ICA). Results: Of the 1294 patients, obstructive CAD was diagnosed in 533 patients (41.2%). The 2019-ESC-PTP model categorised significantly more patients into the low probability group (PTP < 15%) than the 2013-ESC-PTP model (39.8% vs. 5.6%, p < 0.001). Obstructive CAD prevalence was underestimated using 2019-ESC-PTP at all PTP levels (calibration intercept 1.15, calibration slope 0.96). The 2013-ESC-PTP overestimated obstructive CAD prevalence (calibration intercept −0.24, calibration slope 0.73). The discrimination measured with an area under the curve was similar for both models, indicating moderate accuracy of the models. Conclusion: In high-risk Serbian population, both the 2013 and 2019 ESC-PTP models had moderate accuracy in diagnosing CAD, with the 2019-ESC-PTP underestimating the prevalence of CAD and the 2013-ESC-PTP overestimating it. Further studies are warranted to establish PTP models for high-risk countries. © 2024 Hellenic Society of Cardiology