16 results on '"Rath, Dominik"'
Search Results
2. Cangrelor in cardiogenic shock and after cardiopulmonary resuscitation: A global, multicenter, matched pair analysis with oral P2Y12 inhibition from the IABP-SHOCK II trial
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Droppa, Michal, Vaduganathan, Muthiah, Venkateswaran, Ramkumar V., Singh, Abhayjit, Szumita, Paul M., Roberts, Russel J., Qamar, Arman, Hack, Luis, Rath, Dominik, Gawaz, Meinrad, Fuernau, Georg, de Waha-Thiele, Suzanne, Desch, Steffen, Schneider, Steffen, Ouarrak, Taoufik, Jaffer, Farouc A., Zeymer, Uwe, Thiele, Holger, Bhatt, Deepak L., and Geisler, Tobias
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- 2019
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3. Relative survival potential of platelets is associated with platelet CXCR4/CXCR7 surface exposure and functional recovery following STEMI
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Rath, Dominik, Chatterjee, Madhumita, Meyer, Lennart, Tekath, Nina, Olma, Carolin, Krumm, Patrick, Adams, Constantin, Borst, Oliver, Müller, Karin, Droppa, Michal, Nikolaou, Konstantin, Riethmüller, Joachim, Gawaz, Meinrad, and Geisler, Tobias
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- 2018
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4. Periprocedural platelet inhibition with cangrelor in P2Y12-inhibitor naïve patients with acute coronary syndromes — A matched-control pharmacodynamic comparison in real-world patients
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Droppa, Michal, Spahn, Pascal, Takhgiriev, Khalid, Müller, Karin A.L., Alboji, Ahmed, Straub, Andreas, Rath, Dominik, Jeong, Young-Hoon, Gawaz, Meinrad, and Geisler, Tobias
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- 2016
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5. Thrombus architecture is influenced by the antiplatelet loading treatment in patients with acute myocardial infarction.
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Harm, Tobias, Rath, Dominik, Kreisselmeier, Klaus-Peter, Baas, Livia, Prang, Carolin, Gekeler, Sarah, Schröder, Stephen, Gawaz, Meinrad Paul, Geisler, Tobias, Müller, Iris Irmgard, and Müller, Karin Anne Lydia
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PRASUGREL , *MYOCARDIAL infarction , *ST elevation myocardial infarction , *THROMBOSIS , *GENE expression , *THROMBECTOMY - Abstract
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. 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. 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. 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. 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. Intracoronary thrombus formation is a main cause of acute myocardial infarction. We hypothesized that thrombus architecture is significantly impacted by the antiplatelet treatment strategies before percutaneous coronary intervention. We highlight significant reduction of fibrosis, pro-inflammatory mediators including myeloperoxidase (MPO) and altered thrombo-inflammatory signaling in patients with prasugrel treatment when compared to clopidogrel treatment. Thus, pre-treatment with prasugrel implies a more favorable thrombus composition compared to clopidogrel, thereby lowering the risk of adverse cardiovascular events in prasugrel-treated patients. [Display omitted] • Patients with STEMI show histopathological characteristics in thrombus architecture. • Antiplatelet loading treatment influences thrombus composition. • Thrombo-inflammation within the thrombus was modified by P2Y12 inhibitors. • Myeloperoxidase, platelets, fibrosis, and RNA signaling were affected by prasugrel. • Modified thrombus architecture might be beneficial to lower the cardiovascular risk. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Deceleration capacity is associated with acute respiratory distress syndrome in COVID-19.
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Mizera, Lars, Rath, Dominik, Schoellmann, Anna, Petersen-Uribe, Alvaro, Avdiu, Alban, Zdanyte, Monika, Jaeger, Philippa, Heinzmann, David, Müller, Karin, Gawaz, Meinrad, Eick, Christian, and Duckheim, Martin
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• Deceleration capacity as a marker of the cardiac autonomic function is an objective parameter for quick risk stratification of patients with Covid-19. • DC could in principle be calculated from any device that continuously records the heart rate, even in the outpatient area. • Heart rate variability analysis is a non-invasive procedure assessing the sympathetic and vagal balance of the autonomic nervous system. Acute respiratory distress syndrome (ARDS) is considered the main cause of COVID-19 associated morbidity and mortality. Early and reliable risk stratification is of crucial clinical importance in order to identify persons at risk for developing a severe course of disease. Deceleration capacity (DC) of heart rate as a marker of cardiac autonomic function predicts outcome in persons with myocardial infarction and heart failure. We hypothesized that reduced modulation of heart rate may be helpful in identifying persons with COVID-19 at risk for developing ARDS. We prospectively enrolled 60 consecutive COVID-19 positive persons presenting at the University Hospital of Tuebingen. Arterial blood gas analysis and 24 h-Holter ECG recordings were performed and analyzed at admission. The primary end point was defined as development of ARDS with regards to the Berlin classification. 61.7% (37 of 60 persons) developed an ARDS. In persons with ARDS DC was significantly reduced when compared to persons with milder course of infection (3.2 ms vs. 6.6 ms, p < 0.001). DC achieved a good discrimination performance (AUC = 0.76) for ARDS in COVID-19 persons. In a multivariate analysis, decreased DC was associated with the development of ARDS. Our data suggest a promising role of DC to risk stratification in COVID-19. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Evidence of an interaction between TGF-β1 and the SDF-1/CXCR4/CXCR7 axis in human platelets.
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Rath, Dominik, Chatterjee, Madhumita, Holtkamp, Annabell, Tekath, Nina, Borst, Oliver, Vogel, Sebastian, Müller, Karin, Gawaz, Meinrad, and Geisler, Tobias
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CORONARY heart disease prevention , *TRANSFORMING growth factors-beta , *CHEMOKINES , *BLOOD platelets , *FLOW cytometry - Abstract
Background TGF-β1, SDF-1 and its cognate receptors CXCR4 and CXCR7 are expressed on the surface of human platelets and their expression levels are differently regulated in symptomatic coronary artery disease (CAD). All these proteins and receptors influence outcome in patients with symptomatic CAD. There might be a crosstalk between TGF-β1 and the SDF-1/CXCR4/CXCR7 axis. Interrelations in CAD, especially in the context of platelets, are poorly understood. Therefore, we aimed to provide clinical and experimental evidence of interactions between TGF-β1 and the SDF-1/CXCR4/CXCR7 axis in human platelets. Methods and results Blood samples of the complete cohort (n = 284) were analysed for platelet surface expression levels of TGF-β1, SDF-1, CXCR4 and CXCR7 by flow cytometry. For stimulation assays platelet rich plasma was treated with TGF-β1 or SDF-1 and then analysed by flow cytometry. Multiple regression analyses were run to show independent associations of TGF-β1 with SDF-1, CXCR4, CXCR7 and clinical cofactors. Both, CXCR4 and CXCR7 significantly predicted TGF-β1 (p < 0.001 and p < 0.001, respectively). After stimulation with SDF-1, surface expression of TGF-β1 increased significantly when compared to resting platelets [mean TGF-β1 MFI 19.01 vs. mean TGF-β1 MFI 14.01, p < 0.001]. Upon receptor blocking with either anti-CXCR4 or anti-CXCR7 monoclonal antibodies the enhancing effect of SDF-1 on TGF-β1 surface expression was significantly blunted. Stimulation with TGF-β1 did not alter SDF-1, CXCR4 or CXCR7 expression significantly. Conclusions We provide first clinical and experimental data suggesting a cross-talk between TGF-β and the SDF-1/CXCR4/CXCR7 axis in platelets which does not involve transcriptional modulation as shown previously for other cellular systems. [ABSTRACT FROM AUTHOR]
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- 2016
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8. Platelet expression of transforming growth factor beta 1 is enhanced and associated with cardiovascular prognosis in patients with acute coronary syndrome.
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Rath, Dominik, Chatterjee, Madhumita, Müller, Iris, Müller, Karin, Böckmann, Corinna, Droppa, Michal, Stimpfle, Fabian, Karathanos, Athanasios, Borst, Oliver, Seizer, Peter, Langer, Harald, Schwab, Matthias, Gawaz, Meinrad, and Geisler, Tobias
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TRANSFORMING growth factors-beta , *PLATELET function tests , *GENE expression , *ACUTE coronary syndrome , *FOLLOW-up studies (Medicine) - Abstract
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]
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- 2014
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9. Elevated mitochondrial membrane potential of circulating monocyte-platelet aggregates in patients with coronary heart disease.
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Vogel, Sebastian, Rath, Dominik, Jing Lu, Chatterjee, Madhumita, Geisler, Tobias, and Gawaz, Meinrad
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CORONARY disease , *MITOCHONDRIAL membranes , *MONOCYTES , *BLOOD platelet aggregation , *APOPTOSIS , *CARDIOLOGY , *PATIENTS - Published
- 2015
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10. Continuous low-dose thrombolysis in patients with intermediate-high risk pulmonary embolism: A retrospective analysis.
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Droppa, Michal, Zdanyte, Monika, Henes, Jessica Kristin, Gawaz, Meinrad, Borst, Oliver, and Rath, Dominik
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PULMONARY embolism , *THROMBOLYTIC therapy , *RETROSPECTIVE studies - Published
- 2023
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11. Cangrelor in cardiogenic shock and after cardiopulmonary resuscitation: A global, multicenter, matched pair analysis with oral P2Y12 inhibition from the IABP-SHOCK II trial.
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Droppa, Michal, Vaduganathan, Muthiah, Venkateswaran, Ramkumar V., Singh, Abhayjit, Szumita, Paul M., Roberts, Russel J., Qamar, Arman, Hack, Luis, Rath, Dominik, Gawaz, Meinrad, Fuernau, Georg, de Waha-Thiele, Suzanne, Desch, Steffen, Schneider, Steffen, Ouarrak, Taoufik, Jaffer, Farouc A., Zeymer, Uwe, Thiele, Holger, Bhatt, Deepak L., and Geisler, Tobias
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CARDIOGENIC shock , *CARDIOPULMONARY resuscitation , *PERCUTANEOUS coronary intervention , *SURGICAL stents , *MYOCARDIAL infarction , *CARDIAC arrest - Abstract
Aims: Cangrelor has a potentially favorable pharmacodynamic profile in cardiogenic shock (CS). We aimed to evaluate the clinical course of CS patients undergoing percutaneous coronary intervention (PCI) treated with cangrelor.Methods and Results: We retrospectively identified 136 CS patients treated with cangrelor. Patients were 1:1 matched to CS patients from the IABP-SHOCK II trial not receiving cangrelor by age, sex, cardiac arrest, type of myocardial infarction, culprit lesion, glycoprotein IIb/IIIa inhibitor, and oral P2Y12-receptor inhibitor and followed-up for 12 months. The study cohort consisted of 88 matched pairs. Thirty-day and 12-month mortality was 29.5% and 34.1% in cangrelor-treated patients and 36.4% and 47.1% in control group (P = 0.34 and P = 0.08, respectively). The rate of definite acute stent thrombosis was 2.3% in both groups. Moderate and severe bleeding events occurred in 21.6% in the cangrelor and 19.3% in the control group (P = 0.71). Patients treated with cangrelor more frequently experienced ≥1 TIMI flow grade improvement during PCI (92.9% vs. 81.2%, P = 0.02).Conclusion: Cangrelor treatment was associated with similar bleeding risk and significantly better TIMI flow improvement compared with oral P2Y12 inhibitors in CS patients undergoing PCI. The use of cangrelor in CS offers a potentially safe and effective antiplatelet option and should be evaluated in randomized trials. [ABSTRACT FROM AUTHOR]- Published
- 2019
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12. Cardiac MRI left ventricular global function index and quantitative late gadolinium enhancement in unrecognized myocardial infarction.
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Krumm, Patrick, Zitzelsberger, Tanja, Weinmann, Melanie, Mangold, Stefanie, Rath, Dominik, Nikolaou, Konstantin, Gawaz, Meinrad, Kramer, Ulrich, and Klumpp, Bernhard Daniel
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MYOCARDIAL infarction complications , *GADOLINIUM , *MAGNETIC resonance imaging , *DIAGNOSTIC imaging ,MYOCARDIAL infarction diagnosis - Abstract
Purpose: To compare left ventricular global function index (LVGFI) and quantitative late gadolinium enhancement (LGE) in patients with unrecognized myocardial infarction (UMI), recognized myocardial infarction (RMI) and without myocardial infarction (MI).Material and Methods: Under waiver of the Institutional Review Board 235 patients (age 63.5±10.5years, 57 female) were retrospectively evaluated. All patients had undergone cardiac MRI at 1.5T for symptoms of CAD. 67 patients (29%) had suffered a known RMI before. Functional imaging and full-intensity late gadolinium enhancement (LGE) imaging were evaluated for LVGFI and quantitative LGE mass.Results: Of 168 patients without history of RMI, 48 patients (29%) had UMI, 120 patients had no MI. LVGFI was lower in RMI patients (34±8% [range 16;52]), and UMI patients (35±8% [range 10;51]), compared to patients with no MI (38±7% [range 16;55]) respectively and similar between RMI and UMI patients. RMI patients had full-intensity LGE in 11±6% of left ventricular myocardial mass (LVMM). UMI patients had LGE in 9±5% of LVMM. RMI patients had significantly more LGE than UMI patients (p=0.0096).Conclusion: LGE quantification is effective to assess infarction scar size in RMI and UMI patients. LVGFI provides information on cardiac function and morphology but does not allow for a reliable differentiation between patients with and without history of MI, due small differences and wide overlap of LVGFI values for all three patient groups. This may be a reason why LVGFI is not applied in clinical routine. [ABSTRACT FROM AUTHOR]- Published
- 2017
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13. Impact of counterbalance between macrophage migration inhibitory factor and its inhibitor Gremlin-1 in patients with coronary artery disease.
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Müller, Iris I., Müller, Karin A.L., Karathanos, Athanasios, Schönleber, Heiko, Rath, Dominik, Vogel, Sebastian, Chatterjee, Madhumita, Schmid, Martina, Haas, Maximilian, Seizer, Peter, Langer, Harald, Schaeffeler, Elke, Schwab, Matthias, Gawaz, Meinrad, and Geisler, Tobias
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MACROPHAGE migration inhibitory factor , *CORONARY disease , *ANGIOGRAPHY , *ENZYME-linked immunosorbent assay , *THROMBOSIS - Abstract
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]
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- 2014
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14. Impact of point-of-care testing for CYP2C19 on platelet inhibition in patients with acute coronary syndrome and early dual antiplatelet therapy in the emergency setting.
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Stimpfle, Fabian, Karathanos, Athanasios, Droppa, Michal, Metzger, Janina, Rath, Dominik, Müller, Karin, Tavlaki, Elli, Schäffeler, Elke, Winter, Stefan, Schwab, Matthias, Gawaz, Meinrad, and Geisler, Tobias
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POINT-of-care testing , *PLATELET aggregation inhibitors , *ACUTE coronary syndrome , *EMERGENCY medicine , *ANGIOPLASTY , *ADENOSINE diphosphate - Abstract
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]
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- 2014
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15. INHIBITORY MECHANISMS OF VERY LOW DOSE RIVAROXABAN IN NON-ST-ELEVATION MYOCARDIAL INFARCTION.
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Geisler, Tobias, Muenzer, Patrick, Alnaggar, Nada, Geue, Sascha, Tegtmeyer, Roland, Rath, Dominik, Droppa, Michal, Seizer, Peter, Heitmeier, Stefan, Heemskerk, Johan W.M., Jennings, Lisa, Storey, Robert, Angiolillo, Dominick, Rocca, Bianca, Spronk, Henri, Cate, Hugo Ten, Gawaz, Meinrad, and Borst, Oliver
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- 2018
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16. TCT-239 Comparison of safety and periprocedural complications of transfemoral aortic valve replacement in local anesthesia in reduced versus complete heart team.
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Droppa, Michal, Katzenberger, Thomas, Krause, Roland, Borst, Oliver, Rath, Dominik, Müller, Karin, Meinrad, Gawaz, and Geisler, Tobias
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AORTIC valve diseases ,AORTIC valve surgery - Published
- 2017
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