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Article ; Online: Interventional Removal of LV Thrombus in a Patient With Cardiogenic Shock and Transitory Ischemic Attack.

Gawaz, Meinrad Paul / Schreieck, Jürgen / Lydia Mueller, Karin Anne / Geisler, Tobias

JACC. Case reports

2023 Volume 15, Page(s) 101860

Abstract: We discuss a 38-year-old bodybuilder who had cardiogenic shock and multiorgan failure. The patient developed significant speech disorders resulting from thromboembolism of a huge, volatile left ventricular thrombus. Because of inoperability and the ... ...

Abstract	We discuss a 38-year-old bodybuilder who had cardiogenic shock and multiorgan failure. The patient developed significant speech disorders resulting from thromboembolism of a huge, volatile left ventricular thrombus. Because of inoperability and the threat of severe ischemic stroke, the thrombus was removed with a snare and application of a cerebral embolic protection device. (
Language	English
Publishing date	2023-04-17
Publishing country	Netherlands
Document type	Case Reports
ISSN	2666-0849
ISSN (online)	2666-0849
DOI	10.1016/j.jaccas.2023.101860
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Article ; Online: Preclinical identification of acute coronary syndrome without high sensitivity troponin assays using machine learning algorithms.

Goldschmied, Andreas / Sigle, Manuel / Faller, Wenke / Heurich, Diana / Gawaz, Meinrad / Müller, Karin Anne Lydia

Scientific reports

2024 Volume 14, Issue 1, Page(s) 9796

Abstract: Preclinical management of patients with acute chest pain and their identification as candidates for urgent coronary revascularization without the use of high sensitivity troponin essays remains a critical challenge in emergency medicine. We enrolled 2760 ...

Abstract	Preclinical management of patients with acute chest pain and their identification as candidates for urgent coronary revascularization without the use of high sensitivity troponin essays remains a critical challenge in emergency medicine. We enrolled 2760 patients (average age 70 years, 58.6% male) with chest pain and suspected ACS, who were admitted to the Emergency Department of the University Hospital Tübingen, Germany, between August 2016 and October 2020. Using 26 features, eight Machine learning models (non-deep learning models) were trained with data from the preclinical rescue protocol and compared to the "TropOut" score (a modified version of the "preHEART" score which consists of history, ECG, age and cardiac risk but without troponin analysis) to predict major adverse cardiac event (MACE) and acute coronary artery occlusion (ACAO). In our study population MACE occurred in 823 (29.8%) patients and ACAO occurred in 480 patients (17.4%). Interestingly, we found that all machine learning models outperformed the "TropOut" score. The VC and the LR models showed the highest area under the receiver operating characteristic (AUROC) for predicting MACE (AUROC = 0.78) and the VC showed the highest AUROC for predicting ACAO (AUROC = 0.81). A SHapley Additive exPlanations (SHAP) analyses based on the XGB model showed that presence of ST-elevations in the electrocardiogram (ECG) were the most important features to predict both endpoints.
MeSH term(s)	Humans ; Male ; Female ; Aged ; Machine Learning ; Acute Coronary Syndrome/diagnosis ; Acute Coronary Syndrome/blood ; Troponin/blood ; Troponin/metabolism ; Middle Aged ; ROC Curve ; Algorithms ; Electrocardiography ; Biomarkers/blood ; Chest Pain/diagnosis ; Aged, 80 and over ; Emergency Service, Hospital
Chemical Substances	Troponin ; Biomarkers
Language	English
Publishing date	2024-04-29
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-60249-6
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Article ; Online: Myocardial Abscess After Myocarditis: Advantages of Multimodal Imaging Detecting the Rare Case of Fungal Abscess.

Senel, Mirac / Schlensak, Christian / Gawaz, Meinrad Paul / Krumm, Patrick / Mueller, Karin Anne Lydia

JACC. Case reports

2022 Volume 6, Page(s) 101694

Abstract: We discuss the rare case of a myocardial abscess of the left ventricle in a 42-year-old man on immunosuppressive therapy after fulminant myocarditis. Multimodal imaging detected the myocardial abscess along with other septic emboli caused by infection ... ...

Abstract	We discuss the rare case of a myocardial abscess of the left ventricle in a 42-year-old man on immunosuppressive therapy after fulminant myocarditis. Multimodal imaging detected the myocardial abscess along with other septic emboli caused by infection with aspergillus fumigatus, which could be treated effectively with antimycotic strategies. (
Language	English
Publishing date	2022-12-08
Publishing country	Netherlands
Document type	Journal Article
ISSN	2666-0849
ISSN (online)	2666-0849
DOI	10.1016/j.jaccas.2022.101694
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Article ; Online: Machine learning insights into thrombo-ischemic risks and bleeding events through platelet lysophospholipids and acylcarnitine species.

Harm, Tobias / Fu, Xiaoqing / Frey, Moritz / Dittrich, Kristina / Brun, Adrian / Castor, Tatsiana / Borst, Oliver / Müller, Karin Anne Lydia / Geisler, Tobias / Rath, Dominik / Lämmerhofer, Michael / Gawaz, Meinrad Paul

Scientific reports

2024 Volume 14, Issue 1, Page(s) 6089

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Coronary Artery Disease/diagnosis ; Hemorrhage ; Risk Factors ; Machine Learning ; Lysophospholipids ; Lipids ; Carnitine/analogs & derivatives
Chemical Substances	acylcarnitine ; Lysophospholipids ; Lipids ; Carnitine (S7UI8SM58A)
Language	English
Publishing date	2024-03-13
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-56304-x
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Article ; Online: "Mind the Gap": An 85-Year-Old Man with Severe Tricuspid Valve Regurgitation Who Underwent Percutaneous Edge-to-Edge Valve Leaflet Plication Using the New and Advanced MitraClip XTR System.

Mueller, Karin Anne Lydia / Jorbenadze, Rezo / Gawaz, Meinrad / Schreieck, Juergen / Seizer, Peter

The American journal of case reports

2021 Volume 22, Page(s) e928089

Abstract: BACKGROUND Severe tricuspid valve regurgitation (TR) is associated with high cardiovascular mortality. Safe and feasible interventional approaches to treat severe TR are of clinical relevance. The MitraClip is a device that has been approved by the US ... ...

Abstract	BACKGROUND Severe tricuspid valve regurgitation (TR) is associated with high cardiovascular mortality. Safe and feasible interventional approaches to treat severe TR are of clinical relevance. The MitraClip is a device that has been approved by the US Food and Drug Administration (FDA) for the repair of mitral valve lesions. Percutaneous femoral venous access with fluoroscopic and echocardiographic guidance is used to deliver a cobalt-chromium clip to secure the mitral valve leaflets. We report on an 85-year-old man with tricuspid valve regurgitation who underwent percutaneous edge-to-edge tricuspid valve leaflet plication with the new, advanced MitraClip XTR System. CASE REPORT An 85-year-old man with severe TR due to annulus dilation of the right ventricle and short septal leaflet presented repeatedly at our hospital with severe right heart failure symptoms. Transesophageal echocardiography revealed severe TR with a large coaptation gap size of 10.6 mm. Percutaneous edge-to-edge valve repair with the new-generation MitraClip System XTR with wider clip arms could overcome the large coaptation gap. We achieved a strong reduction of TR after deploying 2 MitraClips XTR. The patient recovered quickly and has not been admitted to hospital due to heart failure symptoms since the intervention for more than 6 months. CONCLUSIONS Previous studies have shown the safety and effectiveness of the MitraClip device and supported FDA approval for tricuspid valve repair. This report of a patient with complex tricuspid regurgitation demonstrated the feasible use of the new MitraClip XTR System, which improved edge-to-edge tricuspid valve repair due to its increased span and improved grip.
MeSH term(s)	Aged, 80 and over ; Cardiac Catheterization ; Cardiac Valve Annuloplasty/instrumentation ; Cardiac Valve Annuloplasty/methods ; Humans ; Male ; Tricuspid Valve Insufficiency/diagnostic imaging ; Tricuspid Valve Insufficiency/surgery
Language	English
Publishing date	2021-01-18
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2517183-5
ISSN	1941-5923 ; 1941-5923
ISSN (online)	1941-5923
ISSN	1941-5923
DOI	10.12659/AJCR.928089
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Article ; Online: Thrombus architecture is influenced by the antiplatelet loading treatment in patients with acute myocardial infarction.

Harm, Tobias / Rath, Dominik / Kreisselmeier, Klaus-Peter / Baas, Livia / Prang, Carolin / Gekeler, Sarah / Schröder, Stephen / Gawaz, Meinrad Paul / Geisler, Tobias / Müller, Iris Irmgard / Müller, Karin Anne Lydia

Thrombosis research

2023 Volume 230, Page(s) 45–54

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Humans ; Prasugrel Hydrochloride/pharmacology ; Prasugrel Hydrochloride/therapeutic use ; Clopidogrel/therapeutic use ; ST Elevation Myocardial Infarction/drug therapy ; ST Elevation Myocardial Infarction/etiology ; Percutaneous Coronary Intervention/adverse effects ; Treatment Outcome ; Myocardial Infarction/drug therapy ; Myocardial Infarction/etiology ; Platelet Aggregation Inhibitors/adverse effects ; Thrombosis/etiology ; RNA
Chemical Substances	Prasugrel Hydrochloride (G89JQ59I13) ; Clopidogrel (A74586SNO7) ; Platelet Aggregation Inhibitors ; RNA (63231-63-0)
Language	English
Publishing date	2023-08-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	121852-9
ISSN	1879-2472 ; 0049-3848
ISSN (online)	1879-2472
ISSN	0049-3848
DOI	10.1016/j.thromres.2023.08.004
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Article ; Online: The Subtilisin-Like Protease Furin Regulates Hemin-Dependent Ectodomain Shedding of Glycoprotein VI.

Fink, Annalena / Rohlfing, Anne-Katrin / Dicenta, Valerie / Schaale, David / Kremser, Marcel / Laspa, Zoi / Sigle, Manuel / Fu, Xiaoqing / Pelzer, Andreas / Fischer, Melina / Münzer, Patrick / Castor, Tatsiana / Müller, Karin Anne Lydia / Borst, Oliver / Lämmerhofer, Michael / Gawaz, Meinrad Paul

Thrombosis and haemostasis

2023 Volume 123, Issue 7, Page(s) 679–691

Abstract: Introduction: Hemolysis results in release of free hemoglobin and hemin liberation from erythrocytes. Hemin has been described to induce platelet activation and to trigger thrombosis.: Methods: We evaluated the effect of hemin on platelet function ... ...

Abstract	Introduction: Hemolysis results in release of free hemoglobin and hemin liberation from erythrocytes. Hemin has been described to induce platelet activation and to trigger thrombosis. Methods: We evaluated the effect of hemin on platelet function and surface expression of the platelet collagen receptor glycoprotein VI (GPVI). Isolated platelets were stimulated with increasing concentrations of hemin. Results: We found that hemin strongly enhanced platelet activation, aggregation, and aggregate formation on immobilized collagen under flow. In contrast, we found that surface expression of GPVI was significantly reduced upon hemin stimulation with high hemin concentrations indicating that hemin-induced loss of surface GPVI does not hinder platelet aggregation. Loss of hemin-induced surface expression of GPVI was caused by shedding of the ectodomain of GPVI as verified by immunoblotting and is independent of the GPVI or CLEC-2 mediated ITAM (immunoreceptor-tyrosine-based-activation-motif) signaling pathway as inhibitor studies revealed. Hemin-induced GPVI shedding was independent of metalloproteinases such as ADAM10 or ADAM17, which were previously described to regulate GPVI degradation. Similarly, concentration-dependent shedding of CD62P was also induced by hemin. Unexpectedly, we found that the subtilisin-like proprotein convertase furin controls hemin-dependent GPVI shedding as shown by inhibitor studies using the specific furin inhibitors SSM3 and Hexa-D-arginine. In the presence of SSM3 and Hexa-D-arginine, hemin-associated GPVI degradation was substantially reduced. Further, SSM3 inhibited hemin-induced but not CRP-XL-induced platelet aggregation and thrombus formation, indicating that furin controls specifically hemin-associated platelet functions. Conclusion: In summary, we describe a novel mechanism of hemin-dependent GPVI shedding and platelet function mediated by furin.
MeSH term(s)	Humans ; Hemin/pharmacology ; Hemin/metabolism ; Furin/metabolism ; Furin/pharmacology ; Platelet Membrane Glycoproteins/metabolism ; Blood Platelets/metabolism ; Platelet Aggregation ; Platelet Activation
Chemical Substances	Hemin (743LRP9S7N) ; Furin (EC 3.4.21.75) ; Platelet Membrane Glycoproteins
Language	English
Publishing date	2023-04-10
Publishing country	Germany
Document type	Journal Article
ZDB-ID	518294-3
ISSN	2567-689X ; 0340-6245
ISSN (online)	2567-689X
ISSN	0340-6245
DOI	10.1055/s-0043-1768057
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Article ; Online: Immune signature of patients with cardiovascular disease – in-depth immunophenotyping predicts increased risk for a severe course of COVID-19

Günter, Manina / Mueller, Karin Anne Lydia / Salazar, Mathew / Gekeler, Sarah / Prang, Carolin / Harm, Tobias / Gawaz, Meinrad Paul / Autenrieth, Stella E.

medRxiv

Abstract: Objective: SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD ... ...

Abstract	Objective: SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at hospital admission are still missing. Here, we investigated whether the severity of SARS-CoV-2 infection can be predicted by analyzing the immunophenotype in the blood of CVD patients. Approach and Results: We prospectively analyzed the peripheral blood of 94 participants, including CVD patients with acute SARS-CoV-2 infection, uninfected CVD patients, and healthy donors using a 36-color spectral flow cytometry panel. Clinical assessment included blood sampling, echocardiography, and electrocardiography. Patients were classified by their ISARIC WHO 4C-Mortality-Score on the day of admission into three subgroups of an expected mild, moderate, or severe course of COVID-19. Unsupervised data analysis revealed 40 clusters corresponding to major circulating immune cell populations. This revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4<sup>+</sup> T cells, and plasmablasts than uninfected CVD patients. In contrast, fewer dendritic cells, CD16<sup>+</sup> monocytes, innate lymphoid cells, and CD8<sup>+</sup> T cell subsets were detected in SARS-CoV-2-infected CVD patients. We identified an immune signature characterized by low frequencies of MAIT and intermediate effector CD8<sup>+</sup> T cells in combination with a high frequency of NKT cells that is predictive for CVD patients with a severe course of SARS-CoV-2 infection on hospital admission. Conclusion: Acute SARS-CoV-2 infected CVD patients revealed marked changes in abundance and phenotype of several immune cell populations associated with COVID-19 severity. Our data indicate that intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.
Keywords	covid19
Language	English
Publishing date	2023-04-26
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.04.24.23288921
Database	COVID19

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Article ; Online: Immune signature of patients with cardiovascular disease - in-depth immunophenotyping predicts increased risk for a severe course of COVID-19

Guenter, Manina / Mueller, Karin Anne Lydia / Salazar, Mathew James / Gekeler, Sarah / Prang, Carolin / Harm, Tobias / Gawaz, Meinrad / Autenrieth, Stella E.

medRxiv

Abstract	Objective: SARS-CoV-2 infection can lead to life-threatening clinical manifestations. Patients with cardiovascular disease (CVD) are at higher risk for severe courses of COVID-19. However, strategies to predict the course of SARS-CoV-2 infection in CVD patients at hospital admission are still missing. Here, we investigated whether the severity of SARS-CoV-2 infection can be predicted by analyzing the immunophenotype in the blood of CVD patients. Approach and Results: We prospectively analyzed the peripheral blood of 94 participants, including CVD patients with acute SARS-CoV-2 infection, uninfected CVD patients, and healthy donors using a 36-color spectral flow cytometry panel. Clinical assessment included blood sampling, echocardiography, and electrocardiography. Patients were classified by their ISARIC WHO 4C-Mortality-Score on the day of admission into three subgroups of an expected mild, moderate, or severe course of COVID-19. Unsupervised data analysis revealed 40 clusters corresponding to major circulating immune cell populations. This revealed little differences between healthy donors and CVD patients, whereas the distribution of the cell populations changed dramatically in SARS-CoV-2-infected CVD patients. The latter had more mature NK cells, activated monocyte subsets, central memory CD4<sup>+</sup> T cells, and plasmablasts than uninfected CVD patients. In contrast, fewer dendritic cells, CD16<sup>+</sup> monocytes, innate lymphoid cells, and CD8<sup>+</sup> T cell subsets were detected in SARS-CoV-2-infected CVD patients. We identified an immune signature characterized by low frequencies of MAIT and intermediate effector CD8<sup>+</sup> T cells in combination with a high frequency of NKT cells that is predictive for CVD patients with a severe course of SARS-CoV-2 infection on hospital admission. Conclusion: Acute SARS-CoV-2 infected CVD patients revealed marked changes in abundance and phenotype of several immune cell populations associated with COVID-19 severity. Our data indicate that intensified immunophenotype analyses can help identify patients at risk of severe COVID-19 at hospital admission, improving clinical outcomes through specific treatment.
Keywords	covid19
Language	English
Publishing date	2023-04-26
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.04.24.23288921
Database	COVID19

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Article ; Online: Recovery of systemic hyperinflammation in patients with severe SARS-CoV-2 infection.

Langnau, Carolin / Janing, Henrik / Kocaman, Hüseyin / Gekeler, Sarah / Günter, Manina / Petersen-Uribe, Álvaro / Jaeger, Philippa / Koch, Barbara / Kreisselmeier, Klaus-Peter / Castor, Tatsiana / Rath, Dominik / Gawaz, Meinrad Paul / Autenrieth, Stella E / Mueller, Karin Anne Lydia

Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals

2022 Volume 28, Issue 1, Page(s) 97–110

Abstract: Introduction: Patients with cardiovascular disease (CVD) and acute SARS-CoV-2 infection might show an altered immune response during COVID-19.: Material and methods: Twenty-three patients with CVD and SARS-CoV-2 infection were prospectively enrolled ... ...

Abstract	Introduction: Patients with cardiovascular disease (CVD) and acute SARS-CoV-2 infection might show an altered immune response during COVID-19. Material and methods: Twenty-three patients with CVD and SARS-CoV-2 infection were prospectively enrolled and received a cardiological assessment at study entry and during follow-up visit. Inclusion criteria of our study were age older than 18 years, presence of CVD, and acute SARS-CoV-2 infection. The median age of the patient cohort was 69 (IQR 55-79) years. 12 (52.2%) patients were men. Peripheral monocytes and chemokine/cytokine profiles were analysed. Results: Numbers of classical and non-classical monocytes were significantly decreased during acute SARS-CoV-2 infection compared to 3-month recovery. While classical monocytes reached the expected level in peripheral blood after 3 months, the number of non-classical monocytes remained significantly reduced. Discussion: All three monocyte subsets exhibited changes of established adhesion and activation markers. Interestingly, they also expressed higher levels of pro-inflammatory cytokines like macrophage migration inhibitory factor (MIF) at the time of recovery, although MIF was only slightly increased during the acute phase. Conclusion: Changes of monocyte phenotypes and increased MIF expression after 3-month recovery from acute SARS-CoV-2 infection may indicate persistent, possibly long-lasting, pro-inflammatory monocyte function in CVD patients.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Monocytes ; Cytokines ; Chemokines
Chemical Substances	Cytokines ; Chemokines
Language	English
Publishing date	2022-11-23
Publishing country	England
Document type	Journal Article
ZDB-ID	1324372-x
ISSN	1366-5804 ; 1354-750X
ISSN (online)	1366-5804
ISSN	1354-750X
DOI	10.1080/1354750X.2022.2148745
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