Publications by authors named "Constantin von Zur Muehlen"

5 Publications

  • Page 1 of 1

Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in Apoe mice.

Mol Metab 2021 May 12;53:101250. Epub 2021 May 12.

University Heart Center, Department of Cardiology and Angiology I, University of Freiburg and Faculty of Medicine, 55 Hugstetter St, 79106, Freiburg, Germany. Electronic address:

Objective: Interferon regulatory factor (IRF) 5 is a transcription factor known for promoting M1 type macrophage polarization in vitro. Given the central role of inflammatory macrophages in promoting atherosclerotic plaque progression, we hypothesize that myeloid cell-specific deletion of IRF5 is protective against atherosclerosis.

Methods: Female ApoeLysmIrf5 and ApoeIrf5 mice were fed a high-cholesterol diet for three months. Atherosclerotic plaque size and compositions as well as inflammatory gene expression were analyzed. Mechanistically, IRF5-dependent bone marrow-derived macrophage cytokine profiles were tested under M1 and M2 polarizing conditions. Mixed bone marrow chimeras were generated to determine intrinsic IRF5-dependent effects on macrophage accumulation in atherosclerotic plaques.

Results: Myeloid cell-specific Irf5 deficiency blunted LPS/IFNγ-induced inflammatory gene expression in vitro and in the atherosclerotic aorta in vivo. While atherosclerotic lesion size was not reduced in myeloid cell-specific Irf5-deficient Apoe mice, plaque composition was favorably altered, resembling a stable plaque phenotype with reduced macrophage and lipid contents, reduced inflammatory gene expression and increased collagen deposition alongside elevated Mertk and Tgfβ expression. Irf5-deficient macrophages, when directly competing with wild type macrophages in the same mouse, were less prone to accumulate in atherosclerotic lesion, independent of monocyte recruitment. Irf5-deficient monocytes, when exposed to oxidized low density lipoprotein, were less likely to differentiate into macrophage foam cells, and Irf5-deficient macrophages proliferated less in the plaque.

Conclusion: Our study provides genetic evidence that selectively altering macrophage polarization induces a stable plaque phenotype in mice.
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May 2021

Outcome Prediction in Patients with Severe COVID-19 Requiring Extracorporeal Membrane Oxygenation-A Retrospective International Multicenter Study.

Membranes (Basel) 2021 Feb 27;11(3). Epub 2021 Feb 27.

Department of Medicine III (Interdisciplinary Medical Intensive Care), Medical Center, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany.

The role of veno-venous extracorporeal membrane oxygenation therapy (V-V ECMO) in severe COVID-19 acute respiratory distress syndrome (ARDS) is still under debate and conclusive data from large cohorts are scarce. Furthermore, criteria for the selection of patients that benefit most from this highly invasive and resource-demanding therapy are yet to be defined. In this study, we assess survival in an international multicenter cohort of COVID-19 patients treated with V-V ECMO and evaluate the performance of several clinical scores to predict 30-day survival.

Methods: This is an investigator-initiated retrospective non-interventional international multicenter registry study (NCT04405973, first registered 28 May 2020). In 127 patients treated with V-V ECMO at 15 centers in Germany, Switzerland, Italy, Belgium, and the United States, we calculated the Sequential Organ Failure Assessment (SOFA) Score, Simplified Acute Physiology Score II (SAPS II), Acute Physiology And Chronic Health Evaluation II (APACHE II) Score, Respiratory Extracorporeal Membrane Oxygenation Survival Prediction (RESP) Score, Predicting Death for Severe ARDS on V‑V ECMO (PRESERVE) Score, and 30-day survival.

Results: In our study cohort which enrolled 127 patients, overall 30-day survival was 54%. Median SOFA, SAPS II, APACHE II, RESP, and PRESERVE were 9, 36, 17, 1, and 4, respectively. The prognostic accuracy for all these scores (area under the receiver operating characteristic-AUROC) ranged between 0.548 and 0.605.

Conclusions: The use of scores for the prediction of mortality cannot be recommended for treatment decisions in severe COVID-19 ARDS undergoing V-V ECMO; nevertheless, scoring results below or above a specific cut-off value may be considered as an additional tool in the evaluation of prognosis. Survival rates in this cohort of COVID-19 patients treated with V‑V ECMO were slightly lower than those reported in non-COVID-19 ARDS patients treated with V-V ECMO.
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February 2021

Cardiogenic shock: incidence, survival and mechanical circulatory support usage 2007-2017-insights from a national registry.

Clin Res Cardiol 2020 Nov 30. Epub 2020 Nov 30.

Heart Center Freiburg University, Department of Cardiology and Angiology I, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.

Background: A central element in the management of cardiogenic shock (CS) comprises mechanical circulatory support (MCS) systems to maintain cardiac output (CO). This study aims to quantify incidence, outcome and influence of MCS in CS over the last decade.

Methods: All patients hospitalized with CS in a tertiary university hospital in Germany between 2007 and 2017 were identified utilizing the international coding system ICD-10 with code R57.0. Application of MCS was identified via German procedure classification codes (OPS).

Results: 383,983 cases of cardiogenic shock were reported from 2007 to 2017. Patients had a mean age of 71 years and 38.5% were female. The incidence of CS rose by 65.6% from 26,828 cases in 2007 (33.1 per 100,000 person-years, hospital survival 39.2%) to 44,425 cases in 2017 (53.7 per 100,000 person-years, survival 41.2%). In 2007, 16.0% of patients with CS received MCS (4.6 per 100,000 person-years, survival 46.6%), dropping to 13.9% in 2017 (6.6 per 100,000 person-years, survival 38.6%). Type of MCS changed over the years, with decreasing use of the intra-aortic balloon pump (IABP), an increase in extracorporeal membrane oxygenation (VA-ECMO) and percutaneous ventricular assist device (pVAD) usage. Significant differences regarding in-hospital survival were observed between the devices (survival: overall: 40.2%; medical treatment = 39.5%; IABP = 49.5%; pVAD = 36.2%; VA-ECMO = 30.5%; p < 0.001).

Conclusions: The incidence of CS is increasing, but hospital survival remains low. MCS was used in a minority of patients, and the percentage of MCS usage in CS has decreased. The use rates of the competing devices change over time.
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November 2020

Predictors of survival in patients with acute coronary syndrome undergoing percutaneous coronary intervention of unprotected left main coronary artery stenosis.

Catheter Cardiovasc Interv 2020 07 11;96(1):E27-E33. Epub 2019 Sep 11.

Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Objective: Aim of this study was to investigate predictors of survival in unstable patients with high SYNTAX-1-score.

Background: In significant unprotected left main coronary artery (ULMCA) stenosis, treatment options include percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG). While CABG is recommended for stable patients with ULMCA stenosis and a SYNTAX-1-score > 32, PCI may be preferable in unstable or high operative risk patients.

Methods: Retrospective single-center all-comers registry study.

Results: A total of 142 patients underwent ULMCA-PCI (~72.9 years, 23.2% females, 54.2% survival in 2-year follow-up), 84 of whom had a SYNTAX-1 > 32 (37.4 ± 12.8). Patients in the high-SYNTAX-1-group (score > 32) were more often in an acute condition compared to low-SYNTAX-2-group (score ≤ 32) including acute myocardial infarction (76.2% vs. 57.4%, p = .024), cardiogenic shock (48.2% vs. 14.8%, p = .001), or need for mechanical support (36.1% vs. 11.1%, p = .001). Survival was predicted by the acute condition including cardiogenic shock (OR 0.06 and 0.05) and myocardial infarction (OR 0.03 and 0.34) in both groups. Performance of the SYNTAX-1-score was limited in our patient collective in both groups (c-index 0.65 vs. 0.63) while SYNTAX-2-PCI-score performed better (c-index 0.67 vs. 0.67). EuroScore II had the best discriminative ability (c-index 0.87 vs. 0.78).

Conclusions: The majority of patients undergoing ULMCA-PCI presented in acute conditions with high SYNTAX-1-score, and is therefore underrepresented in clinical trials. Prognosis was best predicted by the acute condition and the EuroScore II. These data suggest that therapy in unstable patients should be guided by clinical condition over the anatomical SYNTAX-1-score.
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July 2020

Imaging assessment of bioresorbable vascular scaffolds.

Cardiovasc Interv Ther 2018 Jan 1;33(1):11-22. Epub 2017 Aug 1.

ThoraxCenter, Erasmus Medical Center, Rotterdam, The Netherlands.

Vascular reparative therapy has become a reality with bioresorbable scaffolds (BRSs). To assess acute and long-term performance of the device, multimodality imaging would be essential. Radiopacity of metal hinders the imaging assessment, whereas radiolucent polymeric scaffolds allow for a precise imaging assessment with either invasive or non-invasive modality at baseline and at follow-up, which is one of the advantages of polymeric BRSs. Recent large trials evaluating clinical results of the first-generation BRS technology raised concerns about the safety and efficacy of these devices, namely, scaffold thrombosis. Intensive research with multimodality imaging in the field is being conducted to have in-depth understanding of the issues, which will facilitate the improvement of implantation techniques and the development of the next-generation BRSs. The current review focuses on the clinical application of the imaging modalities to assess the short- and long-term performance of the Absorb BVS.
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January 2018