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Abstract: Aims: Only limited data exist about the role of point of care CYP2C19 testing in the acute setting in the early phase of acute coronary syndromes (ACS). Therefore, the present study was designed to investigate the impact of CYP2C19 loss-of–function point-of-care (POC) genotyping in patients presenting with acute coronary syndromes (ACS) and treated with dual antiplatelet therapy in the emergency setting. Methods and Results: 137 subjects with ACS scheduled for percutaneous coronary intervention were consecutively enrolled. Pre- and on-treatment platelet aggregation was assessed by multiple electrode aggregometry (MEA) after stimulation with adenosine diphosphate (ADP). Patients were loaded according to current guideline adherent indications and contraindications for use of P2Y12 inhibitors in ACS. POC genotyping for CYP2C19*2 was performed in the emergency room after obtaining a buccal swab using the Spartan RX CYP2C19 system and obtaining patient’s informed consent. Prasugrel and ticagrelor treated patients had significantly lower PR compared to clopidogrel-treated patients. The benefits of prasugrel and ticagrelor compared to clopidogrel treated patients in terms of platelet inhibition were more pronounced in CYP2C19*2 carriers. Non-carriers showed similar inhibition regardless of particular P2Y12 inhibitor treatment. Statistical analyses adjusting for factors associated with response (e.g. smoking) revealed that CYP2C19*2 allele carrier status and loading with different type of P2Y12 receptor blockers were significant predictors of on-treatment platelet reactivity in the early phase of ACS. Conclusion: The results of this pilot study of treatment of patients in the early phase of ACS indicate that CYP2C19*2 POC genotyping might help to identify patients at risk with poor response to clopidogrel treatment, thereby benefiting from reloading and switching to alternative P2Y12 receptor inhibition. [Copyright &y& Elsevier]

Objective : Monocyte infiltration is a critical step in the pathophysiology of plaque instability in coronary artery disease (CAD). Macrophage migration inhibitory factor (MIF) is involved in atherosclerotic plaque progression and instability leading to intracoronary thrombosis. Gremlin-1 (Grem1) has been recently identified as endogenous inhibitor of MIF. To date there are no data on the clinical impact of this interaction in cardiovascular patients. Methods and results : Plasma levels of MIF and Grem1 were determined by enzyme-linked immunoassay in patients with acute coronary syndromes (ACS, n = 120; stable CAD, n = 166 and healthy control subjects, n = 25). MIF levels were significantly increased in ACS compared to stable CAD and healthy control (ACS: median 2.85; IQR 3.52 ng/ml; versus SAP: median 1.22; IQR 2.99 ng/ml; versus healthy control: median 0.10; IQR 0.09 ng/ml, p < 0.001). Grem1 levels were significantly higher in ACS and stable CAD patients compared to healthy control (ACS: median 211.00; IQR 130.47 ng/ml; SAP: median 220.20; IQR 120.93 ng/ml, versus healthy control: median 90.57; IQR 97.68 ng/ml, p < 0.001). Grem1/MIF ratio was independently associated with ACS, whereas the single parameters were not associated with the presence of ACS. Furthermore, Grem1/MIF ratio was associated with angiographic signs of intracoronary thrombi and severity of thrombus burden. Conclusion : These novel findings suggest a potential role of Grem1/MIF ratio to indicate acuity of CAD and the grade of plaque stability. Prospective angiographic cohort studies involving plaque imaging techniques are warranted to further characterize the prognostic role of this novel risk marker in CAD patients. [ABSTRACT FROM AUTHOR]

Risk prediction with the Global Registry of Acute Coronary Events (GRACE) risk model is guideline-recommended in acute coronary syndrome (ACS) patients. However, the performance of more contemporary scores derived from ACTION (Acute Coronary Treatment and Intervention Outcomes Network) and National Cardiovascular Data (NCDR) registries remains incompletely understood. We aimed to compare these models in German ACS patients. A total of 1567 patients with (Non-)ST-segment elevation myocardial infarction (NSTEMI: 1002 patients, STEMI: 565 patients) undergoing invasive management at University Hospital Düsseldorf (Germany) from 2014 to 2018 were included. Overall in-hospital mortality was 7.5% (NSTEMI 3.7%, STEMI 14.5%). Parameters for calculation of GRACE 1.0, GRACE 2.0, ACTION and NCDR risk models and in-hospital mortality were assessed and risk model performance was compared. The GRACE 1.0 risk model for prediction of in-hospital mortality discriminated risk superior (c-index 0.84) to its successor GRACE 2.0 (c-index 0.79, p GRACE1.0vsGRACE2.0 = 0.0008). The NCDR model performed best in discrimination of risk in ACS overall (c-index 0.89; p ACTIONvsNCDR < 0.0001; p GRACEvsNCDR < 0.0001) and showed superior performance compared to GRACE in NSTEMI and STEMI subgroups (p GRACEvsNCDR both < 0.02). ACTION and GRACE risk models performed comparable to each other (both c-index 0.84, p GRACEvsACTION = 0.68), with advantages for ACTION in NSTEMI patients (c-index 0.87 vs. 0.84 (GRACE); p GRACEvsACTION = 0.02). ACTION and GRACE 2.0 showed the most accurate calibration of all models. In a contemporary German patient population with ACS, modern NCDR and ACTION risk models showed superior performance in prediction of in-hospital mortality compared to the gold-standard GRACE model. • External validation study of updated NCDR, GRACE and ACTION risk models for mortality risk prediction in German ACS patients. • NCDR and -to a lesser extent- ACTION risk models discriminated risk for in-hospital mortality better than GRACE models. • ACTION and GRACE 2.0 showed the most accurate calibration of all risk models. [ABSTRACT FROM AUTHOR]

Background . Functional recovery and prognosis after acute coronary syndromes (ACS) are mainly driven by the extent of reperfusion injury and myocardial repair mechanisms. Transforming growth factor-beta 1 (TGF-β1) is critically involved in cardiac injury, repair and remodeling. In this study, we investigated the prognostic role of platelet TGF-β1 surface expression and circulating TGF-β1 levels in patients with coronary artery disease (CAD). Methods and results . Expression of TGF-β1 in platelets and circulating TGF-β1 levels were investigated by flow cytometry and ELISA, respectively, among patients with ACS and stable CAD undergoing percutaneous coronary intervention (PCI). In a cohort study, platelet and circulating TGF-β1 was measured in 299 patients with symptomatic CAD (stable CAD = 145, ACS = 154) at the time of PCI. The primary combined endpoint was defined as death and/or STEMI during 12-month follow-up. Platelets expressed TGF-β1 and circulating TGF-β1 showed a weak, but significant negative correlation. TGF-β1 surface expression was significantly elevated on platelets in ACS patients compared to patients with stable CAD (median MFI 13.4 vs. median MFI 11.7, p = 0.003). During follow-up, lower platelet expression of TGF-β1 was associated with all-cause mortality (median MFI 11.0 vs. median MFI 13.9, p = 0.011) as well as for the combined endpoint of death and/or STEMI, (median MFI 10.8 vs. median MFI 13.9, p = 0.006). In multivariate analysis platelet TGF-β1 expression was independently associated with the combined primary endpoint in the overall cohort (Hazard Ratio 0.31, 95% Confidence Interval 0.11–0.89, p = 0.029) and was strongly associated with prognosis in ACS patients. There was no significant association of circulating TGF-β1 levels neither with the presence of ACS nor the occurrence of the primary endpoint. Conclusion . These findings highlight a potential role of platelet expressed TGF-β1 in ACS and indicate a prognostic value of TGF-β1 on clinical outcomes in patients with acute coronary syndromes. Large scale studies are warranted to further evaluate the regulatory mechanisms of platelet TGF-β1 expression- and its prognostic impact in CAD. [ABSTRACT FROM AUTHOR]