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There is certain discordance between the functional (hemodynamic) and imaging methods for assessing the characteristics of the atherosclerotic plaques. It would be of practical value to find if there was a correlation between neurotrophins -- brain-derived growth factor (BDNF), neuronal growth factor (NGF) and carotid plaque morphology. Aim: To make a first attempt to combine biochemical and morphological markers to better assess the risk of carotid plaques. Material and Methods: Thirteen consecutive patients (Eastern European -- Caucasian race, 9 males and 4 females; mean age 73.08±7.65 years) with angiographically proven significant carotid atherosclerotic stenoses, referred for carotid stenting were evaluated. Plaque morphology was evaluated with intravascular ultrasound (IVUS) and virtual histology (VH). Serum concentrations of BDNF and NGF were tested and their results compared with a control group of 17 individuals without documented clinically significant atherosclerotic disease, carotid pathology, or cardiovascular risk factors. Results: The patients with significant carotid stenoses had lower mean BDNF values than the reference group (Eastern European, Caucasian race). There was a negative correlation between luminal diameter and BDNF (p=0.049; r=-0.605), and positive correlation between: total Ca2+ area (mm2) and BDNF (r=0.681, p=0.021), proximal Ca2+area and BDNF (p=0.007, r=0.784), fibro-fatty area and total calcium area and NGF (p=0.001). The results of carotid IVUS and VH measurements and serum BDNF and NGF concentrations in patients with carotid stenoses compared to patients without carotid artery disease are discussed. Both groups were free of acute vascular incident in other vascular territories. Conclusion: Preliminary results from a small case series study with intravascular ultrasound and serum levels of BDNF and NGF established a potentially meaningful clinical association between carotid atherosclerosis and neurotrophins, necessitating future expansion of the studies. [ABSTRACT FROM AUTHOR]

Background and Objectives : Patients with atrial fibrillation and coronary artery disease represent a group with a greater risk of mortality. To evaluate patients with atrial fibrillation (AF) and a significant coronary bifurcation lesion and compare the clinical outcomes between the patients on anticoagulant treatment with Vitamin K antagonist (VKA) and those on direct anticoagulant (DOAC). Materials and Methods : This is a prospective study of patients with AF and stable coronary artery disease, who had evidence of a significant coronary bifurcation lesion. A log-rank test was used to assess the difference in mortality between patients taking VKA and those on DOAC. The primary endpoint was the incidence of all-cause and cardiovascular death at mid-term. Results : A total of 226 patients with AF and a significant bifurcation lesion were included. The mean age was 70.9 ± 9.2, and 70% were males. Of the patients, 123 (54.7%) were on VKA treatment, and 103 (45.3%) were taking DOAC. For a median follow-up time of 55 (39-96) months, overall mortality was 40%, whereas CV mortality was 31%. Both all-cause (28.2% versus 50.4%, p = 0.020) and CV death (12.7% versus 24.9%, p = 0.032) were significantly lower in patients taking DOAC versus those on VKA. In patients treated with PCI, CV mortality was significantly lower in patients taking DOAC (21.4% versus 40.5%, p = 0.032). VKA therapy was an independent predictor of cardiovascular death (HR 1.88; 95% CI 1.11-3.18; p = 0.01), together with chronic kidney disease (HR 1.81; 95% CI 1.13-2.92; p = 0.01). Conclusions : Treatment with DOAC in patients with atrial fibrillation and coronary bifurcation lesion was associated with significantly lower mortality independently of the treatment approach. VKA was an independent predictor of CV mortality.

Background: Side branch predilatation (SBPD) during coronary bifurcation interventions is a technique that is not recommended by the latest guidelines. However, the data about the clinical outcomes after SBPD are surprisingly few., Aims: The current study aimed to explore the association between SBPD and mortality in long-term follow-up., Methods: All patients with coronary bifurcation stenoses revascularized with percutaneous coronary intervention were included in a prospective registry. Patients with stable angina and a bifurcation lesion with ≥50% diameter stenosis were included in the current analysis. Patients were assigned to two groups - those with SBPD(+) and those without SBPD(-). Propensity score matching was performed to equalize the risk factors and severity of coronary artery disease between the groups. A Kaplan-Meier analysis with a log-rank test for between-group differences was also performed., Results: From January 2013 to June 2021, 813 patients were included in the final study population. The mean age was 67 (10) years. After propensity score matching, 648 patients remained for analysis - 324 in each group. At a median follow-up of 57 months patients in the SBPD(+) group had a higher all-cause mortality (n = 107 (33%) vs. n = 98 [30.2%]; P = 0.045) and cardiovascular mortality (n = 82 [25.3%] vs. n = 70 [21.6%]; P = 0.03) when compared with SBPD(-) patients. SBPD was independently associated with all-cause and cardiovascular mortality., Conclusion: SBPD treatment of coronary bifurcation stenoses is associated with worse patient survival in the follow-up of up to 8 years. SBPD treatment gives better angiographic results, but this did not translate into better clinical outcomes.

Introduction: Carotid stenting may produce significant bradycardia and/or hypotension. This may have negative short- and long-term effects for the elderly high-risk patients. Their cerebral hemodynamics is with exhausted adaptive capacity because of the multiple cardiovascular risk factors, advanced age, and significant stenosis., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Carotid stenting is used with an expanding indications. The neurotrophins are a family of proteins that induce the survival, development, and function of neurons. Carotid stenting alters cerebral blood flow and can affect neurotrophins' levels., Material and Methods: We included 78 people: 39 with significant carotid stenoses (CS) referred for carotid stenting (mean age 67.79 ± 10.53 years) and relatively healthy control group of 39 people without carotid and vertebral artery disease (mean age 57.42 ± 15.77 years). Brain derived reurotrophic factor (BDNF) and neuronal growth factor (NGF) concentrations were evaluated with ELISA method from venous blood - once for the control group; and for the carotid stenting group: before (n33), 24 h after (n22) and at least 1 month after (n18) carotid stenting., Results: There was a difference between the mean neurotrophins' concentration of patients with significant carotid stenoses and the group without: BDNF p  = 0.001, CI (-5.11 to -1.44) (3.10 ± 3.10 ng/ml in CS vs. 6.37 ± 4.67 ng/ml in controls); NGF p  = 0.049, CI (0.64-347.75), 195.67 ± 495.34 pg/ml in CS vs. 21.48 ± 52.81 pg/ml in controls. BDNF levels before carotid stenting (3.10 ± 3.10 ng/ml) were significantly lower than the postprocedural (4.99 ± 2.57 ng/ml) - p  < 0.0001, CI (-2.86 to -0.99). For NGF there was a tendency for lower values after stenting: 195.67 ± 495.34 pg/ml before vs. 94.92 ± 120.06 pg/ml after, but the result did not reach statistical significance. The neurotrophins levels one month after carotid stenting and controls' were not significantly different p  < 0.01 (BDNF 5.03 ± 4.75 ng/ml vs. 6.37 ± 4.67 ng/min; NGF 47.89 ± 54.68 pg/ml vs. 21.48 pg/ml)., Discussion and Conclusion: Periprocedural and mid-term concentrations of neurotrophins after carotid stenting change in non-linear model. This may be due to changes in cerebral perfusion and also might be involved in neuronal recovery and reparation after reperfusion.KEY MESSAGESPeriprocedural and mid-term concentrations of neurotrophins after carotid stenting change in non-linear model.As the majority of them are not specific, their periprocedural change can be used as a clinical correlate to guide changes or even success in carotid stenting.Changes in neutrophins' concentrations may be due to changes in cerebral perfusion and also might be involved in neuronal recovery and reparation after reperfusion.This goes in analogy with cardiac high-sensitive troponin, used as procedural guidance in coronary interventions.

Micro- and macrovascular consequences of atherosclerosis, arterial hypertension, dyslipidemia, and smoking can affect neurotransmission and markers for neuronal activity. The potential direction and specifics are under study. It is also known that optimal control of hypertension, diabetes, and dyslipidemia in midlife may positively affect cognitive functioning later in life. However, the role of hemodynamically significant carotid stenoses in neuronal activity markers and cognitive functioning is still being debated. With the increased use of interventional treatment for extracranial carotid disease, the question of whether it might affect neuronal activity indicators and whether we can stop or even reverse the path of cognitive deterioration in patients with hemodynamically severe carotid stenoses naturally emerges. The existing state of knowledge provides us with ambiguous answers. We sought the literature for possible markers of neuronal activity that can explain any potential difference in cognitive outcomes and guide us in the assessment of patients throughout carotid stenting. The combination of biochemical markers for neuronal activity with neuropsychological assessment and neuroimaging may be important from practical point of view and may provide the answer to the question for the consequences of carotid stenting for long-term cognitive prognosis., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To determine the rate of functionally significant (fractional flow reserve, FFR ≤ 0.80) coronary bifurcation stenoses that are considered anatomically significant based on angiographic estimation and to define predictors of functional significance of stenoses in main vessel and side branch., Background: To date, the rate of functionally significant stenoses in angiographic significant coronary bifurcation stenoses has not been specifically determined., Methods: Patients with significant angiographic bifurcation lesions defined as diameter stenosis >50% in main vessel and/or side branch were included. FFR was performed in main vessel (MV) and side branch (SB) before and after percutaneous coronary intervention (PCI). The protocol was approved by the local ethics committee., Results: Overall, 171 patients with bifurcation lesions were included. Mean FFR in MV was 0.80 ± 0.01 and 0.84 ± 0.09 in SB. 46% (n = 78) of bifurcation lesions were functionally significant when assessed with FFR. Diameter stenosis in main vessel, lesion length, side branch territory and SYNTAX score (SS) were found as predictors for lesion functional severity (main vessel FFR ≤ 0.80). At the time of follow-up, there were no differences between the treated and deferred group regarding rates of all-cause death, cardio-vascular death, MACEs and POCE., Conclusion: Less than half of all angiographic significant bifurcation lesions were functionally significant when assessed with FFR. There was no difference in clinical outcomes at mean time of three years follow-up in treated and deferred lesion., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Carlos Collet reports receiving research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc. and Abbott Vascular; and consultancy fees from Heart Flow Inc, Opsens, Abbott Vascular and Philips Volcano. The other co-authors have no conflict of interest related to this manuscript., (© 2021 The Authors.)

Considerable progress has been made in the treatment of coronary bifurcation stenosis. Anatomical characteristics of the vessel and lesion, however, fail to give information about the functional significance of the bifurcation stenosis. To the best of our knowledge, there is no study that systematically establishes the baseline functional significance of coronary stenosis and its effect on procedural and clinical outcomes. Patients with significant angiographic bifurcation lesions defined as diameter stenosis > 50% in main vessel and/or side branch were included. FFR was performed in main vessel (MV) and side branch (SB) before and after percutaneous coronary intervention (PCI). 169 patients from Fiesta study (derivation cohort) and 555 patients from prospective bifurcation registry (clinical effect cohort) were analyzed to validate angiographic prediction score (BFSS) used to determine the potentially functional significance of coronary bifurcation stenosis. Bifurcation functional significance score (including the following parameters-SYNTAX ≥ 11, SB/MB BARI score, MV %DS ≥ 55%, main branch (MB) %DS ≥ 65%, lesion length ≥ 25 mm) with a maximum value of 11 was developed. A cut-off value of 6.0 was shown to give the best discriminatory ability-with accuracy 87% (sensitivity 77%, specificity 96%, p < 0.001). There was also a significant difference in all-cause mortality between patients with BFSS ≥ 6.0 vs. BFSS < 6.0-25.5% vs. 18.4%, log-rank p = 0.001 as well as cardiac mortality: BFSS ≥ 6.0 vs. BFSS < 6.0-17.7% vs. 14.5%, log-rank (p = 0.016). The cardiac mortality was significantly lower in patients with smaller absolute SB territory, p = 0.023. An angiographic score (BFSS) with good discriminatory ability to determine the functional significance of coronary bifurcation stenosis was developed. The value for BFSS ≥ 6.0 can be used as a discriminator to define groups with higher risk for all-cause and cardiac mortality. Also, we found that the smaller side branches pose greater mortality risk., (© 2021. The Author(s).)

Aims: The aim of this study was to determine the accuracy of the intracoronary electrocardiogram (icECG) to detect ischaemia during bifurcation lesion percutaneous coronary intervention (PCI) with fractional flow reserve (FFR) as a reference., Methods and Results: Patients with significant bifurcation lesions defined as FFR ≤0.80 were included. FFR and icECG were performed in the main vessel (MV) and side branch (SB) before and after provisional stenting. icECG was recorded with an uninsulated proximal wire end connected to a unipolar lead. The diagnostic accuracy of the icECG for the detection of ischaemia in the SB after MV stenting was determined with FFR as a reference. Overall, 37 patients were included. Seventeen bifurcations had an SB FFR ≤0.80 after MV stenting and 20 patients had an ST-segment elevation on the icECG. There was significant correlation between SB FFR and ST-segment elevation on the icECG (r=-0.533, p<0.001). The diagnostic accuracy of icECG ST-elevation to detect functionally significant SB stenosis revealed an AUC of 0.71 (95% CI: 0.64-0.80) with a sensitivity of 88% and specificity of 75% with a positive predictive value of 75% and negative predictive value of 88%. Neither SB FFR nor icECG correlated with SB percent diameter stenosis after MV stenting., Conclusions: Intracoronary ECG has a good ability to predict functionally significant stenosis at the SB after MV stenting during bifurcation PCI. This method provides a novel strategy to assess the significance of an SB lesion without the need of a pressure wire.

Background: The influence of periprocedural ischaemia on coronary artery bifurcation stenting (percutaneous coronary intervention [PCI]) remains uncertain., Aim: To determine the differences in rates of end procedural ischaemia after bifurcation lesion PCI detected with intracoronary electrocardiography (icECG)., Methods: Unipolar icECGs were recorded before, during, and after stent placement and at the end of procedure in side branch (SB) and main branch (MB). Coronary wire was placed in all distal vessels with diameter > 1.5 mm to "map" the distal zones of ischaemia. The patient population consisted of patients with stable/unstable angina with troponin I evaluated before and after PCI., Results: We studied 147 patients (68% males) with mean age of 64 ± 9 years. One hundred and forty-two patients had icECG recordings at the end of PCI from all locations of the treated region; 36% of patients had MB ST segment elevation (STE) and 31% had icECG STE in the SB region (p = 0.378). The icECG had sensitivity of 82% and specificity of 81% to detect troponin I elevation, with positive predictive value of 81% and negative predictive value of 83%. The independent predictors of troponin increase (> 5 × N) were: sex (for female gender, OR = 0.130, CI 0.017-0.995, p = 0.049), previous myocardial infarction (OR = 33.23, CI 2.802-394.1, p = 0.005), and icECG STE in MB or SB or occlusion of secondary SB (OR = 7.877, CI 2.474-25.07, p < 0.001) and for any troponin elevation were double product - SBPxHR (OR = 0.999, CI 0.999-1.00, p = 0.022) and icECG STE in MB or SB or occlusion of secondary SB (OR = 9.762, CI 3.273-29.12, p < 0.001)., Conclusions: Intracoronary electrocardiography is a highly sensitive and specific method for determination of ischaemic regions and prediction of elevated troponin I.

This article describes the development of the p-PCI network in Bulgaria. Even though interventional treatment of STEMI in the country was introduced around 1990, it was not performed on a regular basis which made it largely inefficient. The paper tracks the network evolution with all the problems encountered and the solutions undertaken until the present moment. Historically, all the important factors concerning the implementation, such as spreading of PCI centres, networks and infrastructure, training and certification, emergency medical service, public awareness campaigns, 24/7 work, reimbursement, etc., are reviewed. Finally, the current increase of the percentage of STEMI patients treated by p-PCI and the decrease of overall STEMI mortality rates are shown, clearly demonstrating the huge value of the SFL know-how and contribution.