Editorial : "Clinical impact of dyspnea after ticagrelor treatment and the effect of switching to clopidogrel in patients with myocardial infarction".

No Abstract.

Novel 3-dimensional effective regurgitation orifice area quantification serves as a reliable tool to identify severe mitral valve regurgitation.

A precise quantification of mitral regurgitation (MR) severity is essential for treatment and outcome of patients with MR. 3D echocardiography facilitates estimation of MR but selection of patients with necessity of invasive treatment remains challenging. We investigate effective regurgitation orifice area (EROA) quantification by 3D compared to 2D echocardiography in patients with MR and highlight the improved discrimination of MR severity. We consecutively enrolled fifty patients with primary or secondary and at least moderate MR undergoing 2D and 3D colour Doppler echocardiography prior to transcatheter edge-to-edge repair (TEER). Improved accuracy of MR grading using 3D vena contracta area (VCA) as an estimate of EROA was compared to 2D proximal isovelocity surface area (PISA) quantification method and a multiparameter reference standard. Quantification of EROA remarkably varies between 2D and 3D echocardiography and the discrimination between moderate and severe MR was significantly (p = 0.001) different using 2D PISA or 3D VCA, respectively. 3D VCA correlated significantly (r = 0.501, p < 0.001) better with the pre-defined MR severity. We detected crucial differences in the correct identification of severe MR between 2D and 3D techniques, thus 2D PISA significantly (p < 0.0001) underestimates EROA due to clinical and morphological parameters. The assessment of 3D VCA resulted in improved diagnostic accuracy.

Update on antithrombotic therapy and body mass. A Clinical consensus Statement of the ESC Working Group on Cardiovascular Pharmacotherapy and the ESC Working Group on Thrombosis.

Obesity and underweight are a growing health problem worldwide and a challenge for clinicians concerning antithrombotic therapy, due to the associated risks of thrombosis and/or bleeding. This clinical consensus statement updates a previous one published in 2018, by reviewing the most recent evidence on antithrombotic drugs based on body size categories according to the World Health Organization classification. The document focuses mostly on individuals at the extremes of body weight, i.e. underweight and moderate-to-morbid obesity who require antithrombotic drugs, according to current guidelines, for the treatment or prevention of cardiovascular diseases or venous thromboembolism. Managing antithrombotic therapy or thromboprophylaxis in these individuals is challenging, due to profound changes in body composition, metabolism and organ function, altered drug pharmacokinetics and pharmacodynamics, as well as weak or no evidence from clinical trials. The document also includes artificial intelligence simulations derived from in silico pharmacokinetic/pharmacodynamic models, which can mimic the pharmacokinetic changes and help identify optimal regimens of antithrombotic drugs for severely underweight or severely obese individuals. Further, bariatric surgery in morbidly obese subjects is frequently performed worldwide. Bariatric surgery causes specific and additional changes in metabolism and gastrointestinal anatomy, depending on the type of the procedure, which can also impact the pharmacokinetics of antithrombotic drugs and their management. Based on existing literature, the document provides consensus statements on optimising antithrombotic drug management for underweight and all classes of obese patients, while highlighting the current gaps in knowledge in these complex clinical settings, which require personalized medicine and precision pharmacology.

Regulation of Platelet Activation and Coagulation: Current Concepts, Novel Targets, and Therapies.

Antiplatelet and anticoagulant therapies are cornerstones of secondary prevention in high-risk cardiovascular patients. Whereas in former days the focus was set on effective antithrombotic effects, more recent trials and guidelines placed emphasis on a more balanced approach, thus including the bleeding risk for an individualized therapy. Type, strength, combination, and duration are important components to modify the individual bleeding risk. Novel antiplatelet and anticoagulant agents have shown promising results that might offer safer options in the future for high-risk cardiovascular patients. This review aims to give an overview about established drug target and pharmacologic approaches that are currently in the pipeline.

Dynamics of Thrombogenicity and Platelet Function and Correlation with Bleeding Risk in Patients Undergoing M-TEER Using the PASCAL System.

BACKGROUND: Transcatheter mitral valve repair is performed in a patient population at risk for thrombotic and bleeding events. The effects on platelet function and reactivity and their association with bleeding events after mitral transcatheter edge-to-edge therapy (M-TEER) have not been systematically examined. OBJECTIVES: We sought to investigate the association of different parameters of platelet function and thrombogenicity with bleeding events post M-TEER. METHODS: In this single-center study, 100 consecutive patients with mitral regurgitation receiving TEER were analyzed. Blood was taken directly from the guide-catheter in the left atrium before and after placing the device. Blood samples were analyzed using impedance aggregometry (Multiplate) and TEG6s. The results were compared pre- and postprocedural. The primary outcome was any bleeding complication according to the Bleeding Academic Research Consortium classification within 6 months. RESULTS: A total of 41 patients experienced bleeding events. TEG analysis showed a significant decrease in ADP aggregation and increase in ADP inhibition. In ROC-analysis, TEG ADP aggregation and inhibition and Multiplate ADP aggregation showed moderate predictive values for bleeding events. The delta-ADP-Test (Multiplate) showed the strongest prediction of bleeding (area under the curve: 0.69). Adding platelet function and TEG markers to a model of clinical bleeding risk factors improved the prediction for bleeding events. CONCLUSION: This study indicates that thrombogenicity might be affected immediately after M-TEER probably due to changes in flow conditions. In particular, platelet aggregation involving the ADP receptor pathway significantly correlated with postprocedural bleeding events. Whether these results could guide peri-interventional antithrombotic therapy and improve peri- and postprocedural outcome requires further investigation.

MetSCORE: a molecular metric to evaluate the risk of metabolic syndrome based on serum NMR metabolomics.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of medical conditions and risk factors correlating with insulin resistance that increase the risk of developing cardiometabolic health problems. The specific criteria for diagnosing MetS vary among different medical organizations but are typically based on the evaluation of abdominal obesity, high blood pressure, hyperglycemia, and dyslipidemia. A unique, quantitative and independent estimation of the risk of MetS based only on quantitative biomarkers is highly desirable for the comparison between patients and to study the individual progression of the disease in a quantitative manner. METHODS: We used NMR-based metabolomics on a large cohort of donors (n = 21,323; 37.5% female) to investigate the diagnostic value of serum or serum combined with urine to estimate the MetS risk. Specifically, we have determined 41 circulating metabolites and 112 lipoprotein classes and subclasses in serum samples and this information has been integrated with metabolic profiles extracted from urine samples. RESULTS: We have developed MetSCORE, a metabolic model of MetS that combines serum lipoprotein and metabolite information. MetSCORE discriminate patients with MetS (independently identified using the WHO criterium) from general population, with an AUROC of 0.94 (95% CI 0.920-0.952, p < 0.001). MetSCORE is also able to discriminate the intermediate phenotypes, identifying the early risk of MetS in a quantitative way and ranking individuals according to their risk of undergoing MetS (for general population) or according to the severity of the syndrome (for MetS patients). CONCLUSIONS: We believe that MetSCORE may be an insightful tool for early intervention and lifestyle modifications, potentially preventing the aggravation of metabolic syndrome.

GLIDE Score: Scoring System for Prediction of Procedural Success in Tricuspid Valve Transcatheter Edge-to-Edge Repair.

BACKGROUND: Tricuspid valve transcatheter edge-to-edge repair (T-TEER) is the most widely used transcatheter therapy to treat patients with tricuspid regurgitation (TR). OBJECTIVES: The aim of this study was to develop a simple anatomical score to predict procedural outcomes of T-TEER. METHODS: All patients (n = 168) who underwent T-TEER between January 2017 and November 2022 at 2 centers were included in the derivation cohort. Additionally, 126 patients from 2 separate institutions served as a validation cohort. T-TEER was performed using 2 commercially available technologies. Core laboratory assessment of procedural transesophageal echocardiograms was used to determine septolateral and anteroposterior coaptation gap, leaflet morphology, septal leaflet length and retraction, chordal structure density, tethering height, en face TR jet morphology and TR jet location, image quality, and the presence of intracardiac leads. A scoring system was derived using univariable and multivariable logistic regression. Endpoints assessed were immediate postprocedural TR reduction ≥2 grades and TR grade moderate or less. RESULTS: The median age was 82 years (Q1-Q3: 78-84 years); 48% of patients were women; and patients presented with severe (55%), massive (36%), and torrential (8%) TR. Five variables (septolateral coaptation gap, chordal structure density, en face TR jet morphology, TR jet location, and image quality) were identified as best predicting procedural outcome and were incorporated in the GLIDE (Gap, Location, Image quality, density, en-face TR morphology) score (range 0-5). TR reduction ≥2 grades and TR grade moderate or less were observed in >90% of patients with GLIDE scores of 0 and 1 and in only 5.6% and 16.7% of those with GLIDE scores ≥4. The GLIDE score was then externally validated in a separate cohort (area under the curve: 0.77; 95% CI: 0.69-0.86). TR reduction significantly correlated with functional improvement assessed by NYHA functional class and 6-minute walk distance at 3 months. CONCLUSIONS: The GLIDE score is a simple, 5-component score that is readily obtained during patient imaging and can predict successful T-TEER.

Residual tricuspid regurgitation after tricuspid transcatheter edge-to-edge repair: Insights into the EuroTR registry.

AIMS: Data on the prognostic impact of residual tricuspid regurgitation (TR) after tricuspid transcatheter edge-to-edge repair (T-TEER) are scarce. The aim of this analysis was to evaluate 2-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. METHODS AND RESULTS: Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR registry) we investigated the impact of residual TR on 2-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. The study included a total of 1286 T-TEER patients (mean age 78.0 ± 8.9 years, 53.6% female). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of 2-year all-cause mortality (hazard ratio 2.06, 95% confidence interval 1.30-3.26, p = 0.002). The prevalence of residual TR ≥3+ was four times higher in patients with higher baseline TR (vena contracta >11.1 mm) and more severe tricuspid valve tenting (tenting area >1.92 cm2). Of note, no survival difference was observed in patients with residual TR ≤1+ versus 2+ (76.2% vs. 73.1%, p = 0.461). The rate of NYHA functional class ≥III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p < 0.001). Of note, the degree of TR reduction significantly correlated with the extent of symptomatic improvement (p = 0.012). CONCLUSIONS: T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ versus 2+. Symptomatic improvement correlated with the degree of TR reduction.

Mitral Valve Transcatheter Edge-to-Edge Repair: 1-Year Outcomes From the MiCLASP Study.

BACKGROUND: Mitral transcatheter edge-to-edge repair (M-TEER) is a guideline-recommended treatment option for patients with severe symptomatic mitral regurgitation (MR). Outcomes with the PASCAL system in a post-market setting have not been established. OBJECTIVES: The authors report 30-day and 1-year outcomes from the MiCLASP (Transcatheter Repair of Mitral Regurgitation with Edwards PASCAL Transcatheter Valve Repair System) European post-market clinical follow-up study. METHODS: Patients with symptomatic, clinically significant MR were prospectively enrolled. The primary safety endpoint was clinical events committee-adjudicated 30-day composite major adverse event rate and the primary effectiveness endpoint was echocardiographic core laboratory-assessed MR severity at discharge compared with baseline. Clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year. RESULTS: A total of 544 patients were enrolled (59% functional MR, 30% degenerative MR). The 30-day composite major adverse event rate was 6.8%. MR reduction was significant from baseline to discharge and sustained at 1 year with 98% of patients achieving MR ≤2+ and 82.6% MR ≤1+ (all P < 0.001 vs baseline). One-year Kaplan-Meier estimate for survival was 87.3%, and freedom from heart failure hospitalization was 84.3%. Significant functional and quality-of-life improvements were observed at 1 year, including 71.6% in NYHA functional class I/II, 14.4-point increase in Kansas City Cardiomyopathy Questionnaire score, and 24.2-m improvement in 6-minute walk distance (all P < 0.001 vs baseline). CONCLUSIONS: One-year outcomes of this large cohort from the MiCLASP study demonstrate continued safety and effectiveness of M-TEER with the PASCAL system in a post-market setting. Results demonstrate high survival and freedom from heart failure hospitalization, significant and sustained MR reduction, and improvements in symptoms, functional capacity, and quality of life.

Impact of pulmonary hypertension on outcomes after TEER in patients suffering from mitral regurgitation.

AIM: Data on associations of invasively determined hemodynamic parameters with procedural success and outcomes in patients suffering from mitral regurgitation (MR) undergoing transcatheter edge-to-edge repair of the mitral valve (M-TEER) is limited. METHODS AND RESULTS: We enrolled 239 patients with symptomatic MR of grade 2 + , who received M-TEER. All patients underwent extensive pre-interventional invasive hemodynamic measurements via right heart catheterization (mean pulmonary arterial pressure (mPAP), systolic- (PAPsys) and diastolic pulmonary arterial pressure (PAPdia), pulmonary arterial wedge pressure (PAWP), a-wave, v-wave, pulmonary vascular resistance (PVR), transpulmonary pressure gradient (TPG), cardiac index (CI), stroke volume index (SVI)). mPAP and PAWP at baseline were neither associated with procedural success, immediate reduction of MR, nor residual MR after 6 months of follow-up. The composite outcome (All-cause mortality (ACM) and/or heart failure induced rehospitalization (HFH)) and HFH differed significantly after M-TEER when stratified according to mPAP, PAWP, PAPdia, a-wave and v-wave. ACM was not associated with the afore mentioned parameters. Neither PVR, TPG, CI nor SVI were associated with the composite outcome and HFH, respectively. In multivariable analyses, PAWP was independently associated with the composite outcome and HFH. PVR and SVI were not associated with outcomes. CONCLUSION: PAWP at baseline was significantly and independently associated with HFH and might serve as a valuable parameter for identifying patients at high risk for HFH after M-TEER. ACM and procedural success were not affected by pulmonary arterial pressure before M-TEER. We suggest that the post-capillary component of PH serves as the driving force behind the risk of HFH.

Machine learning insights into thrombo-ischemic risks and bleeding events through platelet lysophospholipids and acylcarnitine species.

Coronary artery disease (CAD) often leads to adverse events resulting in significant disease burdens. Underlying risk factors often remain inapparent prior to disease incidence and the cardiovascular (CV) risk is not exclusively explained by traditional risk factors. Platelets inherently promote atheroprogression and enhanced platelet functions and distinct platelet lipid species are associated with disease severity in patients with CAD. Lipidomics data were acquired using mass spectrometry and processed alongside clinical data applying machine learning to model estimates of an increased CV risk in a consecutive CAD cohort (n = 595). By training machine learning models on CV risk measurements, stratification of CAD patients resulted in a phenotyping of risk groups. We found that distinct platelet lipids are associated with an increased CV or bleeding risk and independently predict adverse events. Notably, the addition of platelet lipids to conventional risk factors resulted in an increased diagnostic accuracy of patients with adverse CV events. Thus, patients with aberrant platelet lipid signatures and platelet functions are at elevated risk to develop adverse CV events. Machine learning combining platelet lipidome data and common clinical parameters demonstrated an increased diagnostic value in patients with CAD and might improve early risk discrimination and classification for CV events.

Apixaban versus Aspirin for Embolic Stroke of Undetermined Source.

BACKGROUND: Rivaroxaban and dabigatran were not superior to aspirin in trials of patients with embolic stroke of undetermined source (ESUS). It is unknown whether apixaban is superior to aspirin in patients with ESUS and known risk factors for cardioembolism. METHODS: We conducted a multicenter, randomized, open-label, blinded-outcome trial of apixaban (5 mg twice daily) compared with aspirin (100 mg once daily) initiated within 28 days after ESUS in patients with at least one predictive factor for atrial fibrillation or a patent foramen ovale. Cardiac monitoring was mandatory, and aspirin treatment was switched to apixaban in case of atrial fibrillation detection. The primary outcome was any new ischemic lesion on brain magnetic resonance imaging (MRI) during 12-month follow-up. Secondary outcomes included major and clinically relevant nonmajor bleeding. RESULTS: A total of 352 patients were randomly assigned to receive apixaban (178 patients) or aspirin (174 patients) at a median of 8 days after ESUS. At 12-month follow-up, MRI follow-up was available in 325 participants (92.3%). New ischemic lesions occurred in 23 of 169 (13.6%) participants in the apixaban group and in 25 of 156 (16.0%) participants in the aspirin group (adjusted odds ratio, 0.79; 95% confidence interval, 0.42 to 1.48; P=0.57). Major and clinically relevant nonmajor bleeding occurred in five and seven participants, respectively (1-year cumulative incidences, 2.9 and 4.2; hazard ratio, 0.68; 95% confidence interval, 0.22 to 2.16). Serious adverse event rates were 43.9 per 100 person-years in those given apixaban and 45.7 per 100 person-years in those given aspirin. The Apixaban for the Treatment of Embolic Stroke of Undetermined Source trial was terminated after a prespecified interim analysis as a result of futility. CONCLUSIONS: Apixaban treatment was not superior to cardiac monitoring-guided aspirin in preventing new ischemic lesions in an enriched ESUS population. (Funded by Bristol-Myers Squibb and Medtronic Europe; ClinicalTrials.gov number, NCT02427126.)

Optimal Antithrombotic Strategies in Cardiogenic Shock.

Cardiogenic shock (CS) represents a critical condition with a high mortality rate. The most common cause of CS is coronary artery disease, and patients typically present with myocardial infarction, necessitating immediate treatment through percutaneous coronary intervention (PCI) and often requiring mechanical circulatory support. CS is associated with a prothrombotic situation, while on the other hand, there is often a significant risk of bleeding. This dual challenge complicates the selection of an optimal antithrombotic strategy. The choice of antithrombotic agents must be personalized, taking into consideration all relevant conditions. Repeated risk assessment, therapeutic monitoring, and adjusting antithrombotic therapy are mandatory in these patients. This review article aims to provide an overview of the current evidence and practical guidance on antithrombotic strategies in the context of CS.

Outcomes of patients undergoing edge-to-edge mitral valve repair with the Edwards PASCAL transcatheter valve repair system under conscious sedation.

BACKGROUND: The development of the PASCAL transcatheter valve repair system for treating mitral regurgitation (MR) greatly extends therapeutic options. AIMS: To assess the safety, efficacy, and time efficiency of the PASCAL system in transcatheter edge-to-edge repair (TEER) under conscious sedation (CS). METHODS: This is a retrospective, two-center, German registry study consisting of 211 patients who underwent TEER using the PASCAL system under CS. The endpoints were to assess (1) technical, device, and procedural success as per Mitral Valve Academic Research Consortium (MVARC), (2) conversion rate to general anesthesia (GA), (3) hospital length of stay (LoS), (4) New York Heart Association (NYHA) class, and (5) MR compared to baseline at 30-day. RESULTS: A total of 211 patients with a mean age of 78.4 ± 8.9 years, with 51.4% being female and 86.7% belonging to NYHA functional class III/IV and EuroSCORE II 6.3 ± 4.9%, were enrolled. Procedural success attained was 96.9%, and six patients (2.8%) required conversion from CS to GA. At 30 days follow-up, a significant improvement in MR was found in 96 patients (54.2%) patients with 0/1 grade MR and 45 patients (29.5%) were in NYHA functional class III + IV. Moreover, TEER under CS has a short hospital LoS (6.71 ± 5.29 days) and intensive care unit LoS (1.34 ± 3.49 days) with a 2.8% mortality rate. CONCLUSIONS: Performing TEER with the PASCAL system under CS resulted in appreciable (96.9%) procedural success with low mortality and is a safe and promising alternative to GA with positive clinical outcomes.

Prevention of cerebral thromboembolism by oral anticoagulation with dabigatran after pulmonary vein isolation for atrial fibrillation: the ODIn-AF trial.

BACKGROUND AND OBJECTIVES: Long-term oral anticoagulation (OAC) following successful catheter ablation of atrial fibrillation (AF) remains controversial. Prospective data are missing. The ODIn-AF study aimed to evaluate the effect of OAC on the incidence of silent cerebral embolic events and clinically relevant cardioembolic events in patients at intermediate to high risk for embolic events, free from AF after pulmonary vein isolation (PVI). METHODS: This prospective, randomized, multicenter, open-label, blinded endpoint interventional trial enrolled patients who were scheduled for PVI to treat paroxysmal or persistent AF. Six months after PVI, AF-free patients were randomized to receive either continued OAC with dabigatran or no OAC. The primary endpoint was the incidence of new silent micro- and macro-embolic lesions detected on brain MRI at 12 months of follow-up compared to baseline. Safety analysis included bleedings, clinically evident cardioembolic, and serious adverse events (SAE). RESULTS: Between 2015 and 2021, 200 patients were randomized into 2 study arms (on OAC: n = 99, off OAC: n = 101). There was no significant difference in the occurrence of new cerebral microlesions between the on OAC and off OAC arm [2 (2%) versus 0 (0%); P = 0.1517] after 12 months. MRI showed no new macro-embolic lesion, no clinical apparent strokes were present in both groups. SAE were more frequent in the OAC arm [on OAC n = 34 (31.8%), off OAC n = 18 (19.4%); P = 0.0460]; bleedings did not differ. CONCLUSION: Discontinuation of OAC after successful PVI was not found to be associated with an elevated risk of cerebral embolic events compared with continued OAC after a follow-up of 12 months.

Stratification of hypertension and SARS-CoV-2 infection by quantitative NMR spectroscopy of human blood serum.

BACKGROUND: Diagnostic approaches like the nuclear magnetic resonance spectroscopy (NMR) based quantification of metabolites, lipoproteins, and inflammation markers has helped to identify typical alterations in the blood serum of COVID-19 patients. However, confounders such as sex, and comorbidities, which strongly influence the metabolome, were often not considered. Therefore, the aim of this NMR study was to consider sex, as well as arterial hypertension (AHT), when investigating COVID-19-positive serum samples in a large age-and sex matched cohort. METHODS: NMR serum data from 329 COVID-19 patients were compared with 305 healthy controls. 134 COVID-19 patients were affected by AHT. These were analyzed together with NMR data from 58 hypertensives without COVID-19. In addition to metabolite, lipoprotein, and glycoprotein data from NMR, common laboratory parameters were considered. Sex was considered in detail for all comparisons. RESULTS: Here, we show that several differences emerge from previous NMR COVID-19 studies when AHT is considered. Especially, the previously described triglyceride-rich lipoprotein profile is no longer observed in COVID-19 patients, nor an increase in ketone bodies. Further alterations are a decrease in glutamine, leucine, isoleucine, and lysine, citric acid, HDL-4 particles, and total cholesterol. Additionally, hypertensive COVID-19 patients show higher inflammatory NMR parameters than normotensive patients. CONCLUSIONS: We present a more precise picture of COVID-19 blood serum parameters. Accordingly, considering sex and comorbidities should be included in future metabolomics studies for improved and refined patient stratification. Due to metabolic similarities with other viral infections, these results can be applied to other respiratory diseases in the future.

The functionality of our human body is driven by a large number of small molecules, called metabolites. These metabolites can be associated with health but also disease conditions. In this study, we used a technology called nuclear magnetic resonance spectroscopy (NMR) to determine metabolite and protein concentrations in the blood of acutely-infected COVID-19 patients and compared these results with disease severity and clinical laboratory data. We particularly focus on patients with the very common cardiovascular condition, arterial hypertension (AHT), and important factors such as sex, age and medication. Our findings provide a more detailed insight into COVID-19 and which individuals are at higher risk for more severe disease.

Thrombus architecture is influenced by the antiplatelet loading treatment in patients with acute myocardial infarction.

BACKGROUND: Intracoronary thrombus formation is a main cause of acute myocardial infarction triggered by platelet activation. However, there are no data on the impact of different treatment strategies with antiplatelet agents before percutaneous coronary intervention (PCI) on histological characteristics of thrombus formation. OBJECTIVE: In this study, we investigate the impact of preinterventional administration of the P2Y12-inhibitors clopidogrel and prasugrel on thrombus composition, highlighting significant changes associated with the antiplatelet pre-treatment. METHODS: We prospectively enrolled 104 consecutive patients with ST-segment elevation myocardial infarction (STEMI) undergoing immediate PCI and thrombus aspiration by immunohistochemical staining along with RNA-sequencing employing Nanostring analysis. Fifty-two patients were treated with either prasugrel loading (60 mg) or clopidogrel loading (600 mg) prior to PCI, respectively. RESULTS: In Patients with STEMI, intracoronary thrombus architecture was significantly altered between patients pre-treated with prasugrel when compared to clopidogrel. Fibrin content of thrombi was significantly decreased (41.8 % versus 66.7 %, p = 0.009) after pre-treatment with prasugrel compared to clopidogrel. Furthermore, levels of MPO positive cells in intracoronary thrombi were significantly decreased in patients with prasugrel pre-treatment (90.5 versus 201.1, p = 0.014) indicating an association of antiplatelet pre-treatment and the inflammatory responses during thrombus formation. Most strikingly, we observed significant differences among both pre-treatment groups regarding altered RNA expression and signaling pathways of thrombo-inflammatory processes within the thrombotic material, which were independently associated with antiplatelet strategies. CONCLUSIONS: Our study elucidates the impact of antiplatelet pre-treatment on thrombus remodeling and architecture, thereby lowering the risk of recurrent adverse cardiovascular events in prasugrel-treated patients.

De-escalation or abbreviation of dual antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention: a Consensus Statement from an international expert panel on coronary thrombosis.

Conventional dual antiplatelet therapy (DAPT) for patients with acute coronary syndromes undergoing percutaneous coronary intervention comprises aspirin with a potent P2Y purinoceptor 12 (P2Y12) inhibitor (prasugrel or ticagrelor) for 12 months. Although this approach reduces ischaemic risk, patients are exposed to a substantial risk of bleeding. Strategies to reduce bleeding include de-escalation of DAPT intensity (downgrading from potent P2Y12 inhibitor at conventional doses to either clopidogrel or reduced-dose prasugrel) or abbreviation of DAPT duration. Either strategy requires assessment of the ischaemic and bleeding risks of each individual. De-escalation of DAPT intensity can reduce bleeding without increasing ischaemic events and can be guided by platelet function testing or genotyping. Abbreviation of DAPT duration after 1-6 months, followed by monotherapy with aspirin or a P2Y12 inhibitor, reduces bleeding without an increase in ischaemic events in patients at high bleeding risk, particularly those without high ischaemic risk. However, these two strategies have not yet been compared in a head-to-head clinical trial. In this Consensus Statement, we summarize the evidence base for these treatment approaches, provide guidance on the assessment of ischaemic and bleeding risks, and provide consensus statements from an international panel of experts to help clinicians to optimize these DAPT approaches for individual patients to improve outcomes.

Large-scale lipidomics profiling reveals characteristic lipid signatures associated with an increased cardiovascular risk.

BACKGROUND AND AIMS: Patients with cardiovascular disease (CVD) are at high risk to develop adverse events. The distinct risk of developing adverse cardiovascular (CV) events is not solely explained by traditional risk factors. Platelets are essentially involved in progression of CVD including coronary artery disease (CAD) and platelet hyperreactivity leads to development of adverse CV events. Alterations in the platelet lipidome lead to platelet hyperresponsiveness and thus might alter the individual risk profile. In this study, we investigate the platelet lipidome of CAD patients by untargeted lipidomics and elucidate alterations in the lipid composition of patients with adverse CV events. METHODS: We characterized the platelet lipidome in a large consecutive CAD cohort (n = 1057) by an untargeted lipidomics approach using liquid chromatography coupled to mass spectrometry. RESULTS: The platelet lipidome in this study identified 767 lipids and characteristic changes occurred in patients with adverse CV events. The most prominent upregulated lipids in patients with cardiovascular events primarily belong to the class of phospholipids and fatty acyls. Further, upregulated platelet lipids are associated with an increased cardiovascular or bleeding risk and independently associated with adverse events. In addition, alterations of the platelet lipidome are associated with modulation of in vitro platelet functions. CONCLUSIONS: Our results reveal that the composition of the platelet lipidome is altered in CVD patients with an increased cardiovascular risk and distinct platelet lipids may indicate adverse events. Results of this study may contribute to improved risk discrimination and classification for cardiovascular events in patients with CVD. Main findings of this study and hypothetical impact of altered platelet lipid signatures in patients with adverse cardiovascular events on platelet function and clinical outcome. LPE lysophosphatidylethanolamines, CAR acylcarnitines, FA fatty acids.