Quantification of Aortic Valve Fibrotic and Calcific Tissue from CTA: Prospective Comparison with Histology.

Background Quantifying the fibrotic and calcific composition of the aortic valve at CT angiography (CTA) can be useful for assessing disease severity and outcomes of patients with aortic stenosis (AS); however, it has not yet been validated against quantitative histologic findings. Purpose To compare quantification of aortic valve fibrotic and calcific tissue composition at CTA versus histologic examination. Materials and Methods This prospective study included patients who underwent CTA before either surgical aortic valve replacement for AS or orthotopic heart transplant (controls) at two centers between January 2022 and April 2023. At CTA, fibrotic and calcific tissue composition were quantified using automated Gaussian mixture modeling applied to the density of aortic valve tissue components, calculated as [(volume/total tissue volume) × 100]. For histologic evaluation, explanted valve cusps were stained with Movat pentachrome as well as hematoxylin and eosin. For each cusp, three 5-µm slices were obtained. Fibrotic and calcific tissue composition were quantified using a validated artificial intelligence tool and averaged across the aortic valve. Correlations were assessed using the Spearman rank correlation coefficient. Intermodality and interobserver variability were measured using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Results Twenty-nine participants (mean age, 63 years ± 10 [SD]; 23 male) were evaluated: 19 with severe AS, five with moderate AS, and five controls. Fibrocalcific tissue composition strongly correlated with histologic findings (r = 0.92; P < .001). The agreement between CTA and histologic findings for fibrocalcific tissue quantification was excellent (ICC, 0.94; P = .001), with underestimation of fibrotic composition at CTA (bias, -4.9%; 95% limits of agreement [LoA]: -18.5%, 8.7%). Finally, there was excellent interobserver repeatability for fibrotic (ICC, 0.99) and calcific (ICC, 0.99) aortic valve tissue volume measurements, with no evidence of a difference in measurements between readers (bias, -0.04 cm3 [95% LoA: -0.27 cm3, 0.19 cm3] and 0.02 cm3 [95% LoA: -0.14 cm3, 0.19 cm3], respectively). Conclusion In a direct comparison, standardized quantitative aortic valve tissue characterization at CTA showed excellent concordance with histologic findings and demonstrated interobserver reproducibility. Clinical trial registration no. NCT06136689 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Almeida in this issue.

Heterogeneous and overlapping mechanisms of ischemia and non-obstructive coronary arteries: in-hospital results of the MOSAIC-COR registry.

INTRODUCTION: Ischemia and non-obstructive coronary arteries (INOCA) remains a significant clinical issue. Recent guidelines underscore the importance of comprehensive coronary physiology assessments to make specific diagnoses and implement tailored treatment strategies. OBJECTIVES: The primary objective was to implement the comprehensive invasive diagnostics. The secondary objective was to determine the pathomechanism of INOCA in consecutive adult patients with symptomatic chronic coronary syndrome, non-invasive evidence of myocardial ischemia, and non-obstructive coronary artery disease included in the prospective MOSAIC-COR registry, and therefore, to define new INOCA subgroups. PATIENTS AND METHODS: All patients underwent comprehensive coronary physiological assessments, including resting full-cycle ratio (RFR), fractional flow reserve (FFR), index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) using a pressure wire and thermodilution method. Coronary artery reactivity was assessed with acetylcholine in a provocative test. RESULTS: A total of 173 patients were enrolled (median age 66 years, 66% female). A high prevalence of typical cardiovascular risk factors was registered. According to physiological assessment, patients were divided into the following subgroups: epicardial vasospastic angina (EVSA) (19%), microvascular vasospastic angina (MVSA) (19%), coronary microcirculatory disease (CMD) (11%), EVSA+CMD (21%), MVSA+CMD (18%), and non-coronary disorder (12%). The diagnosis of MVSA and MVSA+CMD had a higher representation of females (76% and 94%, respectively). CONCLUSIONS: Patients diagnosed with INOCA in the MOSAIC-COR registry exhibit significant symptomatology and a high prevalence of typical cardiovascular risk factors. Myocardial ischemia in this population may be generated by various pathomechanisms which may overlap.

Incidence and predictors of device-related thrombus after left atrial appendage closure with Watchman device.

Introduction: Left atrial appendage closure (LAAC) with Watchman device prevents thromboembolism in patients with atrial fibrillation (AF). However, thrombus may develop on the atrial surface of the device. Aim: To investigate the incidence and predictors of device-related thrombus (DRT) in patients with AF who were treated with LAAC. Material and methods: Ninety-one consecutive patients with AF underwent LAAC procedure using first-generation Watchman 2.5 device followed by antiplatelet therapy. In our analysis we have included all patients (n = 78) who had clinical follow-up visits with transesophageal echocardiography (TEE) after the procedure. Results: The median (IQR) CHA2DS2-VASc score was 4 (4.0-6.0) and HAS-BLED score was 3 (3.0-4.0). DRTs were observed in 5 (6.4%) patients. When compared with patients without DRT, those with DRT presented more often with lower median ejection fraction (40% (23.5-45.5) versus 55% (48.0-60.0); p = 0.005), lower emptying velocity of LAA (25 cm/s (17.5-27.0) versus 53 cm/s (26.5-78.0); p = 0.009), and with greater depth of implantation (18 mm (14.0-20.5) versus 8 mm (5.0-11.0); p < 0.001). Furthermore, patients with DRT had greater depth of LAA (35 mm (29.5-41.0) versus 29 mm (25.5-31.0); p = 0.003), greater mean (SD) dimension in 900 (22.4 mm (3.2) versus 19 mm (2.7); p = 0.02). Patients with DRT were also younger than those without DRT (67.4 years (7) versus 75 years (8.3), p = 0.045). Conclusions: The DRT after Watchman device implantation remains a rare complication. Its formation was related to several patient and procedural characteristics, which need to be confirmed in larger studies.

Renal Dysfunction Increases Risk of Adverse Cardiovascular Events in 5-Year Follow-Up Study of Intermediate Coronary Artery Lesions.

BACKGROUND Progression of chronic coronary syndrome (CCS) is influenced by chronic kidney disease (CKD). This 5-year follow-up study aimed to assess 100 patients with 118 intermediate coronary artery lesions evaluated by fractional flow reserve (FFR) and intravascular imaging stratified according to renal function. MATERIAL AND METHODS This prospective study enrolled patients with intermediate coronary stenosis identified by coronary angiogram. Patients with severe renal dysfunction (estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m²) were excluded from the study. The remaining were divided into 2 groups according to eGFR: 45-60 ml/min/1.73 m² for mild-to-moderate renal dysfunction and >60 ml/min/1.73 m² for no renal dysfunction. We analyzed intermediate-grade stenoses (40-80% as assessed in coronary angiography) with the use of optical coherence tomography (OCT), FFR, and intravascular ultrasound (IVUS). RESULTS Renal dysfunction patients were older (67.7±8.1 vs 63.6±9.7 years, P=0.044). Lesion characteristics, including plaque type and minimal lumen area in OCT, showed no significant differences between the renal dysfunction and no renal dysfunction groups. Thin-cap fibroatheroma, calcific plaques, lipidic plaques, and fibrous plaques had similar prevalence. FFR values and IVUS parameters did not significantly differ between the groups. Over a 5-year follow-up, individuals with mild-to-moderate renal dysfunction had an elevated risk of all-cause mortality and major adverse cardiovascular events in multivariate analyses adjusted for age and sex. CONCLUSIONS Mild-to-moderate renal dysfunction was not associated with significant differences in OCT- and IVUS-derived plaque morphology nor with functional indices characterizing intermediate-grade coronary stenoses. Renal dysfunction was related to a higher risk of all-cause mortality and major adverse cardiovascular events prevalence in 5-year follow-up.

Extracellular Vesicles to Predict Outcomes After Transcatheter Aortic Valve Implantation - a Prospective, Multicenter Cohort Study.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) is an established treatment for aortic stenosis (AS) in patients at intermediate and high surgical risk. Circulating extracellular vesicles (EVs) are nanoparticles involved in cardiovascular diseases. We aimed to (i) determine the effect of TAVI on plasma concentrations of five EV subtypes and (ii) evaluate the predictive value of EVs for post-TAVI outcomes. METHODS: Blood samples were collected 1 day before TAVI and at hospital discharge. Concentrations of EVs were evaluated using flow cytometry. RESULTS: Concentration of leukocytes EVs decreased after TAVI, compared to the measurement before (p = 0.008). Among 123 patients discharged from the hospital, 19.5% experienced MACCE during the median of 10.3 months. Increased pre-TAVI concentration of phosphatidylserine-exposing EVs was an independent predictor of MACCE in multivariable analysis (OR 5.313, 95% CI 1.164-24.258, p = 0.031). CONCLUSIONS: Patients with increased pre-TAVI concentration of procoagulant, PS-exposing EVs have over fivefold higher odds of adverse outcomes.

Ticagrelor downregulates the expression of proatherogenic and proinflammatory miR125-b compared to clopidogrel: A randomized, controlled trial.

BACKGROUND: Platelet P2Y12 antagonist ticagrelor reduces cardiovascular mortality after acute myocardial infarction (AMI) compared to clopidogrel, but the underlying mechanism is unknown. Because activated platelets release proatherogenic and proinflammatory microRNAs, including miR-125a, miR-125b and miR-223, we hypothesized that the expression of these miRNAs is lower on ticagrelor, compared to clopidogrel. OBJECTIVES: We compared miR-125a, miR-125b and miR-223 expression in plasma of patients after AMI treated with ticagrelor or clopidogrel. METHODS: After percutaneous coronary intervention on acetylsalicylic acid and clopidogrel, 60 patients with first AMI were randomized to switch to ticagrelor or to continue with clopidogrel. Plasma expression of miR-223, miR-125a-5p, miR-125b was measured using quantitative polymerase chain reaction at baseline and after 72 h and 6 months of treatment with ticagrelor or clopidogrel in patients and one in 30 healthy volunteers. Multiple electrode aggregometry using ADP test was used to determine platelet reactivity in response to P2Y12 inhibitors. RESULTS: Expression of miR-125b was higher in patients with AMI 72 h and 6 months, compared to healthy volunteers (p = 0.001), whereas expression of miR-125a-5p and miR-223 were comparable. In patients randomized to ticagrelor, expression of miR-125b decreased at 72 h (p = 0.007) and increased back to baseline at 6 months (p = 0.005). Expression of miR-125a-5p and miR-223 was not affected by the switch from clopidogrel to ticagrelor. CONCLUSIONS: Ticagrelor treatment leads to lower plasma expression of miR-125b after AMI, compared to clopidogrel. Higher expression of miR-125b might explain recurrent thrombotic events and worse clinical outcomes in patients treated with clopidogrel, compared to ticagrelor.

Chemokine Fractalkine and Non-Obstructive Coronary Artery Disease-Is There a Link?

Non-obstructive coronary artery disease (NO-CAD) constitutes a heterogeneous group of conditions collectively characterized by less than 50% narrowing in at least one major coronary artery with a fractional flow reserve (FFR) of ≤0.80 observed in coronary angiography. The pathogenesis and progression of NO-CAD are still not fully understood, however, inflammatory processes, particularly atherosclerosis and microvascular dysfunction are known to play a major role in it. Chemokine fractalkine (FKN/CX3CL1) is inherently linked to these processes. FKN/CX3CL1 functions predominantly as a chemoattractant for immune cells, facilitating their transmigration through the vessel wall and inhibiting their apoptosis. Its concentrations correlate positively with major cardiovascular risk factors. Moreover, promising preliminary results have shown that FKN/CX3CL1 receptor inhibitor (KAND567) administered in the population of patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), inhibits the adverse reaction of the immune system that causes hyperinflammation. Whereas the link between FKN/CX3CL1 and NO-CAD appears evident, further studies are necessary to unveil this complex relationship. In this review, we critically overview the current data on FKN/CX3CL1 in the context of NO-CAD and present the novel clinical implications of the unique structure and function of FKN/CX3CL1 as a compound which distinctively contributes to the pathomechanism of this condition.

Five-year outcomes in patients with multivessel coronary artery disease undergoing surgery or percutaneous intervention.

The outcomes from real-life clinical studies regarding the optimal revascularization strategy in patients with multivessel coronary artery disease (MVD) are still poorly investigated. In this retrospective study we assessed 5-year outcomes: primary, secondary endpoints and quality of life of 1035 individuals with severe coronary artery disease (CAD) treated either with coronary artery bypass grafting (CABG)-356 patients or percutaneous coronary intervention (PCI)-679 patients according to the recommendation of a local Heart Team (HT). At 5 years no significant difference in overall mortality and rates of myocardial infarctions (MI) were observed between CABG and PCI cohorts (11.0% vs. 13.4% for PCI, P = 0.27 and 9.6% vs. 12.8% for PCI, P = 0.12, respectively). The incidence of major adverse cardiac and cerebrovascular events (MACCE), mainly driven by increased rates of repeat revascularization (RR) were higher in PCI-cohort than in CABG-group (56.1% vs. 40.4%, P < 0.01 and 26.8% vs. 12.6%, P < 0.01, respectively), while CABG-patients experienced stroke more often (7.3% vs. 3.1% for PCI, P < 0.01). In real-life practice with long-term follow-up, none of the two revascularization modalities implemented following HT decisions showed overwhelming superiority: occurrence of death and MI were similar, rates of RR favoured CABG, while incidence of strokes advocated PCI.

Prognostic Implications of Immature Platelet Fraction at 5-Year Follow-up Among ACS Patients Treated With Dual Antiplatelet Therapy.

Objective: Platelets are strongly associated with cardiovascular events due to their role in thrombotic processes. Reticulated platelets have higher prothrombotic potential. The aim of the study was to evaluate the effectiveness of immature platelet fraction (IPF) in predicting long-term clinical outcomes in patients with acute coronary syndrome (ACS). Methods: This prospective, observational study enrolled patients with ACS treated with dual antiplatelet therapy comprising acetylsalicylic acid and clopidogrel or ticagrelor. The primary outcome was a composite endpoint defined as major adverse cardiovascular events (MACE): all-cause death, myocardial infarction (MI), ischemic stroke, or unplanned revascularization. IPF was determined using flow cytometry in the first 24 h of hospitalization. MACE were evaluated by 2 physicians based on electronic databases and source documentation including discharge letters received from patients upon telephone contact. Results: Overall, there were 140 ACS patients (mean age 65.1 ± 11.7, 37 females [26.4%]) included in this study. Of them, 22.9% had diabetes mellitus, 69.3% hyperlipidemia, 25% had a history of MI. The median IPF values were 2.85 [1.8-4.2] %. Clinical follow-up (median time: 57 months [interquartile range 55-59 months]) was available for 130 patients (92.9%). MACE occurred in 27 patients (20.8%). There were higher rates of MACE at higher IPF tertiles (3rd vs 1st tertile: HR = 5.341 95% CI: 1.546-18.454, P = .008). Cox regression analyses showed that IPF level was independently associated with MACE. Time-dependent receiver-operating characteristic curve analysis revealed area under the curve of 0.656 for 5-year outcome with an IPF cutoff point of 3.45% being 63.0% sensitive and 65.0% specific for MACE. Conclusions: The study showed IPF may be an independent predictor of long-term mortality and MACE (ClinicalTrials.gov number, NCT06177587).

Long COVID and its cardiovascular consequences: What is known?

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high morbidity and mortality and has been a source of substantial challenges for healthcare systems globally. Despite a full recovery, a significant proportion of patients demonstrate a broad spectrum of cardiovascular, pulmonary and neurological symptoms that are believed to be caused by long-term tissue damage and pathological inflammation, which play a vital role in disease development. Microvascular dysfunction also causes significant health problems. This review aimed to critically appraise the current data on the long-term cardiovascular sequelae of coronavirus disease 2019 (COVID-19), with a primary focus on cardiovascular symptoms such as chest pain, fatigue, palpitations, and breathlessness, and more significant disease entities including myocarditis, pericarditis and postural tachycardia syndrome. Potential risk factors identified in recent studies that contribute towards the development of long COVID are also included alongside a summary of recent advances in diagnostics and putative treatment options.

Immature platelet fraction and immature platelet count as novel biomarkers of elevated platelet reactivity in NSTE-ACS patients receiving dual antiplatelet therapy.

BACKGROUND: Antiplatelet therapy is the cornerstone of treatment for patients presenting with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI). Some patients may not respond to such therapy adequately, which is associated with a greater risk of ischemic events. Reticulated platelets are the youngest, largest, and most active platelet subtype. They have been initially shown to be associated with an increased risk of cardiovascular (CV) events and increased platelet activity. OBJECTIVES: The aim of the presented study was to evaluate whether the immature platelet fraction (IPF) reflects the response to antiplatelet treatment in invasively managed ACS patients. MATERIAL AND METHODS: This prospective study enrolled ACS patients treated with PCI and dual antiplatelet therapy (DAPT) comprising acetylsalicylic acid (ASA) and clopidogrel or ticagrelor. In all patients, venous blood was collected within 24 h after the procedure. Platelet parameters were measured, including IPF using the Sysmex hematological analyzer and adenosine diphosphate (ADP)-induced platelet reactivity using the Multiplate® Analyzer. RESULTS: A total of 108 patients were enrolled, including 62 with ST-segment elevation ACS (STE-ACS) and 46 with non-ST-segment elevation ACS (NSTE-ACS). Of them, 20.4% had diabetes mellitus, 26.9% had a history of MI and 59.2% of smoking. Spearman's correlation analysis demonstrated that higher IPF and immature platelet count (IPC) values are associated with increased ADP-induced platelet reactivity (respectively: rho = 0.387, 95% confidence interval (95% CI): 0.101-0.615, p = 0.008; and rho = 0.458, 95% CI: 0.185-0.666, p = 0.001) in NSTE-ACS but not in STE-ACS patients. CONCLUSION: Immature platelet count and IPF may be valuable markers of platelet activity in patients with NSTE-ACS treated invasively and receiving DAPT (ClinicalTrials.gov No. NCT06177587).

Multicenter registry of Impella-assisted high-risk percutaneous coronary interventions and cardiogenic shock in Poland (IMPELLA-PL).

BACKGROUND: Impella is a percutaneous mechanical circulatory support device for treatment of cardiogenic shock (CS) and high-risk percutaneous coronary interventions (HR-PCIs). IMPELLA-PL is a national retrospective registry of Impella-treated CS and HR-PCI patients in 20 Polish interventional cardiological centers, conducted from January 2014 until December 2021. AIMS: We aimed to determine the efficacy and safety of Impella using real-world data from IMPELLA-PL and compare these with other registries. METHODS: IMPELLA-PL data were analyzed to determine primary endpoints: in-hospital mortality and rates of mortality and major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months post-discharge. RESULTS: Of 308 patients, 18% had CS and 82% underwent HR-PCI. In-hospital mortality rates were 76.4% and 8.3% in the CS and HR-PCI groups, respectively. The 12-month mortality rates were 80.0% and 18.2%, and post-discharge MACCE rates were 9.1% and 22.5%, respectively. Any access site bleeding occurred in 30.9% of CS patients and 14.6% of HR-PCI patients, limb ischemia in 12.7% and 2.4%, and hemolysis in 10.9% and 1.6%, respectively. CONCLUSIONS: Impella is safe and effective during HR-PCIs, in accordance with previous registry analyses. The risk profile and mortality in CS patients were higher than in other registries, and the potential benefits of Impella in CS require investigation.

Long-term mortality after transcatheter aortic valve implantation for aortic stenosis in immunosuppression-treated patients: a propensity-matched multicentre retrospective registry-based analysis.

Introduction: Data regarding patients with a previous medical record of immunosuppression treatment who have undergone transcatheter aortic valve implantation (TAVI) are limited and extremely inconclusive. Available studies are mostly short term observations; thus there is a lack of evidence on efficacy and safety of TAVI in this specific group of patients. Aim: To compare the in-hospital and long-term outcomes between patients with or without a medical history of immunosuppressive treatment undergoing TAVI for aortic valve stenosis (AS). Material and methods: We conducted a retrospective registry-based analysis including patients undergoing TAVI for AS at 5 centres between January 2009 and August 2017. The primary endpoint was long-term all-cause mortality. Secondary endpoints comprised major vascular complications, life-threatening or disabling bleeding, stroke and new pacemaker implantation. Results: Of 1451 consecutive patients who underwent TAVI, two propensity-matched groups including 25 patients with a history of immunosuppression and 75 patients without it were analysed. No differences between groups in all-cause mortality were found in a median follow-up time of 2.7 years following TAVI (p = 0.465; HR = 0.73; 95% CI: 0.30-1.77). The rate of major vascular complications (4.0% vs. 5.3%) was similar in the two groups (p = 1.000). There were no statistically significant differences in the composite endpoint combining life-threatening or disabling bleeding, major vascular complications, stroke and new pacemaker implantation (40.0% vs. 20.0%, p = 0.218). Conclusions: Patients who had undergone TAVI for AS had similar long-term mortality regardless of whether they had a previous medical record of immunosuppression. Procedural complication rates were comparable between the groups.

Impact of previous coronary artery revascularization on outcomes in patients undergoing transcatheter aortic valve implantation.

Introduction: Coexistence of coronary artery disease (CAD) in patients with severe aortic stenosis (AS) referred for transcatheter aortic valve implantation (TAVI) raises questions regarding the safety and efficacy of TAVI in this subset of patients. Aim: To evaluate the impact of previous coronary revascularization in terms of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) on clinical outcomes after TAVI. Material and methods: A total of 507 consecutive patients who underwent TAVI were divided into: non-revascularization (NR), post-PCI and post-CABG groups. The endpoints were established according to VARC-2 definitions. Results: Patients with previous coronary revascularization (36.7% of the population) were younger, more often male and their EuroSCORE II risk evaluation was significantly higher (NR 7.9% vs. post-PCI 8.0% vs. post-CABG 20.5%, p < 0.0001). Patients after PCI or CABG prior to TAVI had similar 30-day all-cause mortality rates as those without coronary revascularization at baseline (NR vs. post-PCI vs. post-CABG: 8.1% vs. 5.5% vs. 6.8%, respectively; p = 0.6). There were no differences in 12-month all-cause mortality rates between groups (NR vs. post-PCI vs. post-CABG: 15.3% vs. 14.2% vs. 16.9%, respectively; log-rank p = 0.67). In the Cox proportional-hazards regression model, acute kidney injury stage 2-3 (HR = 3.7, 95% CI: 2.14-6.33; p < 0.001) and post-TAVI stroke (HR = 3.5, 95% CI: 1.57-7.8; p = 0.002) were independently correlated with 1-year mortality. Conclusions: TAVI seems to be a safe and effective procedure for the treatment of severe AS in patients with previous coronary revascularization.

Safety and efficacy of percutaneous atrial appendage closure followed by antiplatelet therapy in a high-risk population: single-center experience with a WATCHMAN device.

Introduction: In our everyday practice we encounter many patients with non-valvular atrial fibrillation with either a contraindication to oral anticoagulation or with its inefficiency. Aim: To investigate whether left atrial appendage closure (LAAC) followed by post-procedure antiplatelet therapy is safe and efficient in a high-risk population. Material and methods: Ninety-one (48 males) consecutive patients with non-valvular atrial fibrillation (NVAF) underwent an LAAC procedure using a first-generation WATCHMAN 2.5 device followed by antiplatelet therapy. Clinical and transesophageal echocardiography data were collected at baseline and at the follow-up visit. Results: The median (IQR) CHA2DS2-VASc score was 5 (4.0-6.0) and the HAS-BLED score was 3 (3.0-4.0); the mean (SD) age was 74.4 (8.4). A bleeding history was observed in 89% of patients and 24.2% of patients had a history of stroke or transient ischemic attack (TIA). The procedure was successful in 98.9%. Post-procedure therapy was dual antiplatelet therapy in 85 patients; 3 patients received single antiplatelet therapy and the therapy was maintained until the follow-up visit. Peri-procedural complications were tamponade (3.3%), pericardial effusion (2.2%) and two deaths (2.2%) with no bleeding or vascular complications. The median follow-up was 67 (52.75-84.75) days. Primary safety endpoint (bleeding BARC type 3 or more, tamponade, pericardial effusion, and device embolization) and primary efficacy endpoint (stroke or TIA, hemorrhagic stroke, peripheral embolism, cardiovascular (CV) and non-CV death) were observed in 2 and 4 patients, respectively. Conclusions: The LAAC procedure followed by antiplatelet therapy seems to be safe and efficient in the high-risk population. Further studies in this field are required.

The cytokine trio - visfatin, placental growth factor and fractalkine - and their role in myocardial infarction with non-obstructive coronary arteries (MINOCA).

Myocardial infarction with nonobstructive coronary arteries (MINOCA) remains a puzzling clinical entity. It is characterized by clinical evidence of myocardial infarction (MI) with normal or near-normal coronary arteries in angiography. Given the complex etiology including multiple possible scenarios with varied pathogenetic mechanisms, profound investigation of the plausible biomarkers of MINOCA may bring further pathophysiological insights and novel diagnostic opportunities. Cytokines have a great diagnostic potential and are used as biomarkers for many diseases. An unusual trio of visfatin, placental growth factor (PlGF) and fractalkine (CX3CL1) can directly promote vascular dysfunction, inflammation and angiogenesis through the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. They are redundant in physiological processes and become overexpressed in the pathomechanisms underlying MINOCA. The knowledge about their concentration might serve as a valuable diagnostic and/or therapeutic tool for assessing vascular endothelial function. Here we analyze the current knowledge on visfatin, PlGF and CX3CL1 in the context of MINOCA and present the novel clinical implications of their combined expression as predictors or indicators of this condition.