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Assessment of coronary artery disease using coronary computed tomography angiography and biochemical markers

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World Journal of Cardiology 2014年第7期6卷 663-670页

作者： Gitsios Gitsioudis hugo a katus Grigorios Korosoglou Department of Cardiology University of Heidelberg

Chronic inflammatory mechanisms in the arterial wall lead to atherosclerosis,and include endothelial cell damage,inflammation,apoptosis,lipoprotein deposition,calcification and *** computed tomography angiography(CCTA)has been shown to be a promising tool for non-invasive assessment of theses specific compositional and structural changes in coronary *** review focuses on the technical background of CCTA-based quantitative plaque ***,we discuss the available evidence for CCTA-based plaque characterization and the potential role of CCTA for risk stratification of patients with coronary artery disease.

关键词： Atherosclerotic plaque composition Quantification analysis Multi-slice cardiac computed tomography Biomarkers

In vivo cardiac pacemaker function of differentiated human mesenchymal stem cells from adipose tissue transplanted into porcine hearts

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World Journal of Stem Cells 2020年第10期12卷 1133-1151页

作者： Fabrice F Darche Rasmus Rivinius Ann-Kathrin Rahm Eva Köllensperger Uwe Leimer Günter Germann Miriam Reiss Michael Koenen hugo a katus Dierk Thomas Patrick A Schweizer Department of Cardiology Medical University Hospital HeidelbergHeidelberg D-69120Germany DZHK(German Centre for Cardiovascular Research) Partner Site Heidelberg/MannheimUniversity of HeidelbergHeidelberg D-69120Germany HCR(Heidelberg Center for Heart Rhythm Disorders) Department of CardiologyMedical University Hospital HeidelbergHeidelberg D-69120Germany Department of Plastic Surgery ETHIANUM Klinik HeidelbergHeidelberg D-69115Germany Department of Molecular Neurobiology Max-Planck-Institute for Medical ResearchHeidelberg D-69120Germany

BACKGROUND Mesenchymal stem cells(MSC)modified by gene transfer to express cardiac pacemaker channels such as HCN2 or HCN4 were shown to elicit pacemaker function after intracardiac transplantation in experimental animal *** MSC derived from adipose tissue(haMSC)differentiate into cells with pacemaker properties in vitro,but little is known about their behavior after intracardiac *** To investigate whether haMSC elicit biological pacemaker function in vivo after transplantation into pig *** haMSC under native conditions(nhaMSC)or after pre-conditioning by medium differentiation(dhaMSC)(n=6 pigs each,5×106 cells/animal)were injected into the porcine left ventricular free *** receiving PBS injection served as controls(n=6).Four weeks later,total atrioventricular(AV)-block was induced by radiofrequency catheter ablation,and electronic pacemaker devices were implanted for backup stimulation and heart rate *** rate and rhythm of pigs were evaluated during a follow-up of 15 d post ablation by 12-lead-ECG with heart rate assessment,24-h continuous rate monitoring recorded by electronic pacemaker,assessment of escape recovery time,and pharmacological challenge to address catecholaminergic rate ***,hearts were analyzed by histological and immunohistochemical *** In vivo transplantation of dhaMSC into the left ventricular free wall of pigs elicited spontaneous and regular rhythms that were pace-mapped to ventricular injection sites(mean heart rate 72.2±3.6 bpm;n=6)after experimental total AV *** rhythms were stably detected over a 15-d period and were sensitive to catecholaminergic stimulation(mean maximum heart rate 131.0±6.2 bpm;n=6;P<0.001).Pigs,which received nhaMSC or PBS presented significantly lower ventricular rates(mean heart rates 47.2±2.5 bpm and 37.4±3.2 bpm,respectively;n=6 each;P<0.001)and exhibited little sensitivity towards catecholaminergic stimulatio

关键词： Biological cardiac pacemaker Mesenchymal stem cells Differentiation Animal model Cell transplantation Stem cell therapy

Elevated interleukin-6 levels are associated with impaired outcome in cardiac transthyretin amyloidosis

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World Journal of Cardiology 2021年第3期13卷 55-67页

作者： Selina J Hein Maximilian Knoll Fabian Aus dem Siepen Jennifer Furkel Stefan Schoenland Ute Hegenbart hugo a katus Arnt V Kristen Mathias Konstandin Department of Cardiology Pneumology and AngiologyUniversity Hospital HeidelbergHeidelbergBW 69120Germany Department of Radiation Oncology Heidelberg Ion-Beam Therapy CenterGerman Cancer Research CenterUniversity Hospital HeidelbergHeidelbergBW 69120Germany Department of Radiation Oncology Heidelberg University HospitalHeidelbergBW 69120Germany Department of Hematology Oncology and RheumatologyAmyloidosis CenterHeidelberg University HospitalHeidelbergBW 69120Germany Department of Hematology Amyloidosis CenterHeidelberg University HospitalHeidelbergBW 69120Germany Department of Cardiology Medical University Hospital HeidelbergHeidelbergBW 69120Germany Department of Cardiology Amyloidosis CenterUniversity of HeidelbergHeidelbergBW 69120Germany

BACKGROUND Elevated interleukin(IL)-6-levels have been described in familial variant transthyretin amyloidosis(ATTRv)associated polyneuropathy and heart ***,IL-6 in cardiac ATTR amyloidosis(ATTR-CM)and its prognostic value have not been investigated *** We aim to study the correlation between IL-6 levels with clinical presentation(Gillmore-class)and outcome[heart transplantation or death(htx/death)],or the combined endpoint of cardiac decompensation or htx/death in *** IL-6 levels of 106 ATTR-CM patients[54 wild-type ATTRwt,52 ATTRv-CM],15 asymptomatic carriers of ATTR mutations(aATTRv-CM)and 27 healthy donors were quantified using Luminex *** analysis was performed using parametric survival regression *** We found that IL-6 levels from wild-type ATTR patients were significantly elevated compared to healthy controls,while aATTRv-CM carriers and ATTRv-CM patients did not show a significant ***-6 levels showed significantly higher values in increasing Gillmore *** analyses revealed association of low IL-6 levels with cardiac decompensation and htx/death[odds ratio:0.26(0.09-0.72),P=0.01]and htx/death[odds ratio:0.15(0.04-0.58),P=0.006].However,in the multivariate model,no significant improvement of risk prediction was seen for IL-6,while established prognostic factors were significantly associated with *** Raised IL-6 levels correlate with clinical presentation and are associated with worse outcome in ATTR-CM but do not improve stratification in addition to established risk factors.

关键词： Transthyretin amyloidosis Inflammation Heart failure Interleukin-6 Outcome Risk stratification

Quantitative assessment of myocardial blush grade in patients with coronary artery disease and in cardiac transplant recipients

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World Journal of Cardiology 2014年第10期6卷 1108-1112页

作者： Nina Patricia Hofmann Hartmut Dickhaus hugo a katus Grigorios Korosoglou Department of Cardiology University of Heidelberg 69120 Heidel-berg Germany Department of Medical Informatics Univer-sity of Heidelberg 69120 Heidelberg Germany

Quantitative assessment of myocardial perfusion by myocardial blush grade(MBG) is an angiographic computer-assisted method to assess myocardial tissue-level reperfusion in patients with acute coronary syndromes and microvascular integrity in heart transplant recipients with suspected cardiac allograft vasculopathy. This review describes the ability of quantitative MBG as a simple, fast and cost effective modality for the prompt diagnosis of impaired microvascular integrity during routine cardiac catheterization. Herein, we summarize the existing evidence, its usefulness in the clinical routine, and compare this method to other techniques which can be used for the assessment of myocardial perfusion.

关键词： Quantitative myocardial blush grade Prog-nosis Heart transplantation Coronary artery disease

Personalized Computer Simulation of Diastolic Function in Heart Failure

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Genomics, Proteomics & Bioinformatics 2016年第4期14卷 244-252页

作者： Ali Amr Elham Kayvanpour Farbod Sedaghat-Hamedani Tiziano Passerini Viorel Mihalef Alan Lai Dominik Neumann Bogdan Georgescu Sebastian Buss Derliz Mercies Edgar Zitron Andreas E. Posch Maximilian Wurstle Tommaso Mansi hugo A. katus Benjamin Meder Institute for Cardiomyopathies Department of Medicine IIIUniversity of Heidelberg69120 Heidelberg.Germany German Centre for Cardiovascular Research(DZHK) Heidelberg/MannlleimGermany Siemens Healthcare Medical Imaging TechnologiesPrincetonNJ 08540USA Siemens Healthcare Strategy and Innovation91052 ErlangenGermany

The search for a parameter representing left ventricular relaxation from non-invasive and invasive diagnostic tools has been extensive, since heart failure （HF） with preserved ejection fraction （HF-pEF） is a global health problem. We explore here the feasibility using patient-specific cardiac computer modeling to capture diastolic parameters in patients suffering from different degrees of systolic HF. Fifty eight patients with idiopathic dilated cardiomyopathy have undergone thorough clinical evaluation, including cardiac magnetic resonance imaging （MRI）, heart catheterization, echocardiography, and cardiac biomarker assessment. A previously-introduced framework for creating multi-scale patient-specific cardiac models has been applied on all these patients. Novel parameters, such as global stiffness factor and maximum left ventricular active stress, representing cardiac active and passive tissue properties have been computed for all patients. Invasive pressure measurements from heart catheterization were then used to evaluate ventricular relaxation using the time constant of isovolumic relaxation Tau （τ）. Parameters from heart catheterization and the multi-scale model have been evaluated and compared to patient clinical presentation. The model parameter global stiffness factor, representing diastolic passive tissue properties, is correlated significantly across the patient population with τ. This study shows that multi-modal cardiac models can successfully capture diastolic （dys） function, a prerequisite for future clinical trials on HF-pEF.

关键词： Dilated cardiomyopathy Tau Myocardial stiffness Computer-based 3D modelPersonalized medicine Diastolic function

Interventional treatment of the left subclavian in 2 patients with coronary steal syndrome

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World Journal of Cardiology 2017年第1期9卷 65-70页

作者： Julia Heid Britta Vogel Arnt Kristen Wanda Kloos Benedikt Kohler hugo a katus Grigorios Korosoglou Department of Internal MedicineⅢ University Hospital Heidelberg69120 HeidelbergGermany

In patients with history of coronary artery disease angina pectoris is usually attributed to the progression of atherosclerotic lesions. However,in patients with previous coronary artery bypass graft operation(CABG) using internal mammary artery grafts,great vessel disease should also be considered. Herein we present two patients with history of CABG whose symptoms were suspicious for coronary ischemia. During cardiac catheterization reverse blood flow was observed from the left artery disease to the left internal mammary artery(LIMA) graft in both cases. After angioplasty and stent implantation of the left subclavian artery antegrade flow was restored in the LIMA grafts and both patients had complete resolution of symptoms.

关键词： Coronary steal syndrome Coronary artery bypass graft Left subclavian artery Reverse blood flow Cardiac catheterization

Feasibility of real-time magnetic resonance imaging-guided endomyocardial biopsies:An in-vitro study

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World Journal of Cardiology 2015年第7期7卷 415-422页

作者： Dirk Lossnitzer Sebastian A Seitz Birgit Krautz Bernhard Schnackenburg Florian André Grigorios Korosoglou hugo a katus Henning Steen Department of Cardiology University Hospital Heidelberg Philips Medical Systems

AIM: To investigate if magnetic resonance(MR)-guided biopsy can improve the performance and safety of such procedures. METHODS: A novel MR-compatible bioptome was evaluated in a series of in-vitro experiments in a 1.5T magnetic resonance imaging(MRI) system. The bioptome was inserted into explanted porcine and bovine hearts under real-time MR-guidance employing a steady state free precession sequence. The artifact produced by the metal element at the tip and the signal voids caused by the bioptome were visually tracked for navigation and allowed its constant and precise localization. RESULTS: Cardiac structural elements and the target regions for the biopsy were clearly visible. Our method allowed a significantly better spatial visualization of the bioptoms tip compared to conventional X-ray guidance. The specific device design of the bioptome avoided inducible currents and therefore subsequent heating. The novel MR-compatible bioptome provided a superior cardiovascular magnetic resonance(imaging) soft-tissue visualization for MR-guided myocardial biopsies. Not at least the use of MRI guidance for endomyocardial biopsies completely avoided radiation exposure for both patients and ***: MRI-guided endomyocardial biopsies provide a better than conventional X-ray guided navigation and could therefore improve the specificity and reproducibility of cardiac biopsies in future studies.

关键词： Endomyocardial biopsy Cardiovascular magnetic resonance(imaging) Magnetic resonance imaging-guided interventions Real-time imaging

SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy

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Genomics, Proteomics & Bioinformatics 2022年第1期20卷 129-146页

作者： Jes-Niels Boeckel Maximilian Mobius-Winkler Marion Muller Sabine Rebs Nicole Eger Laura Schoppe Rewati Tappu Karoline E.Kokot Jasmin M.Kneuer Susanne Gaul Diana M.Bordalo Alan Lai Jan Haas Mahsa Ghanbari Philipp Drewe-Boss Martin Liss hugo A.katus Uwe Ohler Michael Gotthardt Ulrich Laufs Katrin Streckfuss-Bomeke Benjamin Meder Department of Cardiology Angiology and PneumologyUniversity Hospital HeidelbergD-69120 HeidelbergGermany Klinik und Poliklinik fur Kardiologie Universitatskrankenhaus LeipzigD-04103 LeipzigGermany German Center for Cardiovascular Research(DZHK) Partner site HeidelbergD-69120 HeidelbergGermany Clinic for General and Interventional Cardiology/Angiology Herz-und Diabeteszentrum NRWRuhr-Universitat BochumD-32545 Bad OeynhausenGermany Department of Cardiology and Pneumology University HospitalGeorg-August University GoettingenD-37075 GoettingenGermany German Center for Cardiovascular Research(DZHK) Partner site GoettingenD-37075 GoettingenGermany Berlin Institute for Medical Systems Biology Max Delbruck Center for Molecular Medicine in the Helmholtz AssociationD-10115 BerlinGermany Institute of Biology Humboldt Universitat zu BerlinD-10099 BerlinGermany Neuromuscular and Cardiovascular Cell Biology Max Delbruck Center for Molecular Medicine in the Helmholtz AssociationD-13092 BerlinGermany German Center for Cardiovascular Research(DZHK) Partner site BerlinD-10117 BerlinGermany Stanford Genome Technology Center Department of GeneticsStanford Medical SchoolPalo AltoCA 94304USA

Alternative mRNA splicing is a fundamental process to increase the versatility of the *** humans,cardiac mRNA splicing is involved in the pathophysiology of heart *** in the splicing factor RNA binding motif protein 20(RBM20) cause severe forms of *** identify novel cardiomyopathy-associated splicing factors,RNA-seq and tissue-enrichment analyses were performed,which identified up-regulated expression of Sam68-Like mammalian protein 2(SLM2) in the left ventricle of dilated cardiomyopathy(DCM) *** the human heart,SLM2 binds to important transcripts of sarcomere constituents,such as those encoding myosin light chain2(MYL2),troponin 13(TNNI3),troponin T2(TNNT2),tropomyosin 1/2(TPM1/2),and titin(TTN).Mechanistically,SLM2 mediates intron retention,prevents exon exclusion,and thereby mediates alternative splicing of the mRNA regions encoding the variable proline-,glutamate-,valine-,and lysine-rich(PEVK) domain and another part of the I-band region of *** summary,SLM2 is a novel cardiac splicing regulator with essential functions for maintaining cardiomyocyte integrity by binding to and processing the mRNAs of essential cardiac constituents such as titin.

关键词： Splicing Titin Dilated cardiomyopathy KHDRBS3 SLM2

Long noncoding RNA MALAT1-derived mascRNA is involved in cardiovascular innate immunity

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Journal of Molecular Cell Biology 2016年第2期8卷 178-181页

作者： Martina Gast Blanche Schroen Antje Voigt Jan Haas Uwe Kuehl Dirk Lassner Carsten Skurk Felicitas Escher Xiaomin Wang Adelheid Kratzer Katharina Michalik Anna Papageorgiou Tim Peters Madlen Loebel Sabrina Wilk Nadine Althof Kannanganattu VPrasanth hugo katus Benjamin Meder Shinichi Nakagawa Carmen Scheibenbogen Heinz-Peter Schultheiss Ulf Landmesser Stefanie Dimmeler Stephane Heymans Wolfgang Poller Department of Cardiology and Pneumology Campus Benjamin FranklinCharite–Universitatsmedizin BerlinBerlinGermany Center for Heart Failure Research Cardiovascular Research Institute Maastricht(CARIM)Maastricht UniversityMaastrichtNetherlands Institute of Biochemistry Campus Charite MitteCharite–Universitatsmedizin BerlinBerlinGermany Otto-Meyerhof-Centrum University of HeidelbergHeidelbergGermany Medizinische Klinik University of HeidelbergHeidelbergGermany Institute for Cardiac Diagnostics and Therapy(IKDT) BerlinGermany Institute for Cardiovascular Regeneration Goethe University FrankfurtFrankfurtGermany Institute for Medical Immunology Campus Virchow KlinikumCharite–Universitatsmedizin BerlinBerlinGermany Berlin Center forRegenerative Therapies(BCRT) Charite–Universitatsmedizin BerlinBerlinGermany Department of CellandDevelopmental Biology University of Illinois at Urbana-ChampaignUrbanaIL 61801USA RNA Biology Laboratory RIKEN Advanced Research InstituteWakoSaitama 351-0198Japan German Center for Cardiovascular Research(DZHK) Site BerlinGermany DZHK Site Rhein-MainGermany

Dear Editor,Next-generation sequencing revealed that the majority of the human genome is transcribed but has no coding *** is estimated that.30000 long noncoding RNAs(lncRNAs)are expressed in humans,but their functions are largely unknown(Suckau et al.,2009;Rinn and Chang,2012;Poller et al.,2013).Consideration of noncoding genomic elements in pathogenetic studies is warranted and enabled by technological advances allowing comprehensive transcriptome mapping of protein-coding genes as well as small and long ncRNAs.

关键词： MALAT1 immunity