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6. Atrial fibrosis heterogeneity is a risk for atrial fibrillation in pigs with ischaemic heart failure.

Author

Zhang, Zhihao, Vlcek, Julia, Pauly, Valerie, Hesse, Nora, Bauer, Julia, Chataut, Kavi Raj, Maderspacher, Florian, Volz, Lina Sophie, Buchberger, Katharina, Xia, Ruibing, Hildebrand, Bianca, Kääb, Stefan, Schüttler, Dominik, Tomsits, Philipp, and Clauss, Sebastian

Subjects
ATRIAL fibrillation, HEART failure, FIBROSIS, SWINE, LEFT heart atrium, BALLOON occlusion
Abstract

Background: Atrial fibrillation (AF) is the most common arrhythmia and is associated with considerable morbidity and mortality. Ischaemic heart failure (IHF) remains one of the most common causes of AF in clinical practice. However, ischaemia‐mediated mechanisms leading to AF are still incompletely understood, and thus, current treatment approaches are limited. To improve our understanding of the pathophysiology, we studied a porcine IHF model. Methods: In pigs, IHF was induced by balloon occlusion of the left anterior descending artery for 90 min. After 30 days of reperfusion, invasive haemodynamic measurements and electrophysiological studies were performed. Masson trichrome and immunofluorescence staining were conducted to assess interstitial fibrosis and myofibroblast activation in different heart regions. Results: After 30 days of reperfusion, heart failure with significantly reduced ejection fraction (left anterior obique 30°, 34.78 ± 3.29% [IHF] vs. 62.03 ± 2.36% [control], p <.001; anterior–posterior 0°, 29.16 ± 3.61% vs. 59.54 ± 1.09%, p <.01) was observed. These pigs showed a significantly higher susceptibility to AF (33.90% [IHF] vs. 12.98% [control], p <.05). Histological assessment revealed aggravated fibrosis in atrial appendages but not in atrial free walls in IHF pigs (11.13 ± 1.44% vs. 5.99 ±.86%, p <.01 [LAA], 8.28 ±.56% vs. 6.01 ±.35%, p <.01 [RAA]), which was paralleled by enhanced myofibroblast activation (12.09 ±.65% vs. 9.00 ±.94%, p <.05 [LAA], 14.37 ±.60% vs. 10.30 ± 1.41%, p <.05 [RAA]). Correlation analysis indicated that not fibrosis per se but its cross‐regional heterogeneous distribution across the left atrium was associated with AF susceptibility (r =.6344, p <.01). Conclusion: Our results suggest that left atrial cross‐regional fibrosis difference rather than overall fibrosis level is associated with IHF‐related AF susceptibility, presumably by establishing local conduction disturbances and heterogeneity. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Atrial fibrosis heterogeneity is a risk for atrial fibrillation in pigs with ischaemic heart failure

Author

Zhang, Zhihao, primary, Vlcek, Julia, additional, Pauly, Valerie, additional, Hesse, Nora, additional, Bauer, Julia, additional, Chataut, Kavi Raj, additional, Maderspacher, Florian, additional, Volz, Lina Sophie, additional, Buchberger, Katharina, additional, Xia, Ruibing, additional, Hildebrand, Bianca, additional, Kääb, Stefan, additional, Schüttler, Dominik, additional, Tomsits, Philipp, additional, and Clauss, Sebastian, additional

Published
2023
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11. Effects of Sex on the Susceptibility for Atrial Fibrillation in Pigs with Ischemic Heart Failure

Author

Pauly, Valerie, primary, Vlcek, Julia, additional, Zhang, Zhihao, additional, Hesse, Nora, additional, Xia, Ruibing, additional, Bauer, Julia, additional, Loy, Simone, additional, Schneider, Sarah, additional, Renner, Simone, additional, Wolf, Eckhard, additional, Kääb, Stefan, additional, Schüttler, Dominik, additional, Tomsits, Philipp, additional, and Clauss, Sebastian, additional

Published
2023
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15. PO-630-07 INVESTIGATION OF DIABETES-INDUCED ATRIAL REMODELING IN A PRECLINICAL LARGE ANIMAL MODEL

Author

Clauss, Sebastian, primary, Tomsits, Philipp, additional, Vlcek, Julia, additional, Pauly, Valerie, additional, Hesse, Nora, additional, Xia, Ruibing, additional, Loy, Simone, additional, Volz, Lina-Sophie, additional, Villgrater, Hannes Elias, additional, KOTTU, LAKSHME, additional, Renner, Simone, additional, Kaab, Stefan, additional, Wolf, Eckhard, additional, and Schüttler, Dominik, additional

Published
2022
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25. Characterization of a porcine model of atrial arrhythmogenicity in the context of ischaemic heart failure

Author

Clauss, Sebastian, primary, Schüttler, Dominik, additional, Bleyer, Christina, additional, Vlcek, Julia, additional, Shakarami, Mehdi, additional, Tomsits, Philipp, additional, Schneider, Sarah, additional, Maderspacher, Florian, additional, Chataut, Kavi, additional, Trebo, Anna, additional, Wang, Christine, additional, Kleeberger, Jan, additional, Xia, Ruibing, additional, Baloch, Elisabeth, additional, Hildebrand, Bianca, additional, Massberg, Steffen, additional, Wakili, Reza, additional, and Kääb, Stefan, additional

Published
2020
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27. Stability of Circulating Blood-Based MicroRNAs - Pre-Analytic Methodological Considerations

Author

Glinge, Charlotte, Clauss, Sebastian, Boddum, Kim, Jabbari, Reza, Jabbari, Javad, Risgaard, Bjarke, Tomsits, Philipp, Hildebrand, Bianca, Kääb, Stefan, Wakili, Reza, Jespersen, Thomas, Tfelt-Hansen, Jacob, Glinge, Charlotte, Clauss, Sebastian, Boddum, Kim, Jabbari, Reza, Jabbari, Javad, Risgaard, Bjarke, Tomsits, Philipp, Hildebrand, Bianca, Kääb, Stefan, Wakili, Reza, Jespersen, Thomas, and Tfelt-Hansen, Jacob

Abstract

BACKGROUND AND AIM: The potential of microRNAs (miRNA) as non-invasive diagnostic, prognostic, and predictive biomarkers, as well as therapeutic targets, has recently been recognized. Previous studies have highlighted the importance of consistency in the methodology used, but to our knowledge, no study has described the methodology of sample preparation and storage systematically with respect to miRNAs as blood biomarkers. The aim of this study was to investigate the stability of miRNAs in blood under various relevant clinical and research conditions: different collection tubes, storage at different temperatures, physical disturbance, as well as serial freeze-thaw cycles.METHODS: Blood samples were collected from 12 healthy donors into different collection tubes containing anticoagulants, including EDTA, citrate and lithium-heparin, as well as into serum collection tubes. MiRNA stability was evaluated by measuring expression changes of miR-1, miR-21 and miR-29b at different conditions: varying processing time of whole blood (up to 72 hours (h)), long-term storage (9 months at -80°C), physical disturbance (1 and 8 h), as well as in a series of freeze/thaw cycles (1 and 4 times).RESULTS: Different collection tubes revealed comparable concentrations of miR-1, miR-21 and miR-29b. Tubes with lithium-heparin were found unsuitable for miRNA quantification. MiRNA levels were stable for at least 24 h at room temperature in whole blood, while separated fractions did show alterations within 24 h. There were significant changes in the miR-21 and miR-29b levels after 72 h incubation of whole blood at room temperature (p<0.01 for both). Both miR-1 and miR-21 showed decreased levels after physical disturbance for 8 h in separated plasma and miR-1 in serum whole blood, while after 1 h of disturbance no changes were observed. Storage of samples at -80°C extended the miRNA stability remarkably, however, miRNA levels in long-term stored (9 months) whole blood sampl

Published
2017

28. Stability of Circulating Blood-Based MicroRNAs – Pre-Analytic Methodological Considerations

Author

Glinge, Charlotte, primary, Clauss, Sebastian, additional, Boddum, Kim, additional, Jabbari, Reza, additional, Jabbari, Javad, additional, Risgaard, Bjarke, additional, Tomsits, Philipp, additional, Hildebrand, Bianca, additional, Kääb, Stefan, additional, Wakili, Reza, additional, Jespersen, Thomas, additional, and Tfelt-Hansen, Jacob, additional

Published
2017
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30. Lifetime cumulative activity burden is associated with symptomatic heart failure and arrhythmic risk in patients with arrhythmogenic right ventricular cardiomyopathy: a retrospective cohort study.

Author

Binzenhöfer L, Clauss S, Strauß K, Höpler J, Kraft M, Hoffmann S, Brunner S, Tomsits P, Schüttler D, Massberg S, Kääb S, and Lüsebrink E

Subjects
Humans, Male, Female, Retrospective Studies, Adult, Middle Aged, Risk Assessment, Risk Factors, Exercise, Arrhythmias, Cardiac epidemiology, Arrhythmias, Cardiac physiopathology, Arrhythmias, Cardiac therapy, Arrhythmias, Cardiac diagnosis, Time Factors, Sports statistics & numerical data, Young Adult, Arrhythmogenic Right Ventricular Dysplasia physiopathology, Arrhythmogenic Right Ventricular Dysplasia complications, Arrhythmogenic Right Ventricular Dysplasia diagnosis, Arrhythmogenic Right Ventricular Dysplasia epidemiology, Heart Failure physiopathology, Heart Failure epidemiology
Abstract

Aims: Sports-related physical activity is associated with an increased risk of ventricular dysfunction and arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). However, there are currently no standardized strategies for activity assessment. Thresholds for harmful levels of physical activity suggested by previous studies vary substantially and neither lifetime activity burden nor continuous modelling approaches were considered., Methods and Results: For this single-centre retrospective study, ARVC patients were interviewed to assess sports-related and non-sports-related physical activity between the age of 10 years and the last follow-up. Activity data were aggregated to the median metabolic equivalent of task-hours (METh) per week for each year. The association between cumulative physical activity burden and clinical study endpoints was investigated using Cox regression models. A total of 124 patients (median age: 39.5 years, 48% male) were included in the analysis, of whom 93 had been diagnosed with definite ARVC. Study participants reported a median overall activity of 202.3 METh/week, with 38.7 METh/week attributed to sports-related activity. In the continuous model, cumulative overall activity burden was associated with the occurrence of symptomatic heart failure [hazard ratio (HR) per 100 METh/week: 1.017, 95% CI (1.003, 1.032), P = 0.015], sustained ventricular tachycardia [HR: 1.021, 95% CI (1.006, 1.037), P = 0.007], and implantable cardioverter defibrillator interventions [HR: 1.017, 95%CI (1.000, 1.034), P = 0.048]. This finding was consistent when considering sports-related activity separately as a predictor variable, whereas the resulting hazard ratios did not show a significant association for non-sports-related physical activity., Conclusion: This study demonstrates for the first time that cumulative physical activity as a continuous predictor variable is associated with symptomatic heart failure and arrhythmic risk in ARVC patients. Collaborative research is required in larger cohorts to investigate the influence of potential confounders on event occurrence and to develop threshold recommendations for clinical practice., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Published
2024
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