Niklas Beyhoff1, Sarah Brix1, Iris R Betz1, Robert Klopfleisch2, Anna Foryst-Ludwig1, Alexander Krannich3, Philipp Stawowy4, Fabian Knebel5, Jana Grune1, Ulrich Kintscher6. 1. Institute of Pharmacology, Center for Cardiovascular Research, Charité - Universitaetsmedizin Berlin, Berlin, Germany; Deutsches Zentrum für Herz-Kreislauf-Forschung (German Centre for Cardiovascular Research), Partner site Berlin, Berlin, Germany. 2. Department of Veterinary Pathology, College of Veterinary Medicine, Freie Universitaet Berlin, Berlin, Germany. 3. Berlin Institute of Health, Clinical Research Unit - Biostatistics Unit, Berlin, Germany. 4. Department of Medicine/Cardiology, Deutsches Herzzentrum Berlin, Berlin, Germany. 5. Department of Cardiology and Angiology, Campus Mitte, Charité - Universitaetsmedizin Berlin, Berlin, Germany; Deutsches Zentrum für Herz-Kreislauf-Forschung (German Centre for Cardiovascular Research), Partner site Berlin, Berlin, Germany. 6. Institute of Pharmacology, Center for Cardiovascular Research, Charité - Universitaetsmedizin Berlin, Berlin, Germany; Deutsches Zentrum für Herz-Kreislauf-Forschung (German Centre for Cardiovascular Research), Partner site Berlin, Berlin, Germany. Electronic address: ulrich.kintscher@charite.de.
Abstract
BACKGROUND: The subendocardium is highly vulnerable to damage and is thus affected even in subclinical disease stages. Therefore, methods reflecting subendocardial status are of great clinical relevance for the early detection of cardiac damage and the prevention of functional impairment. The aim of this study was to investigate the potential ability of myocardial strain parameters to evaluate changes within the subendocardium. METHODS: Male 129/Sv mice were injected with isoproterenol (ISO; n = 32) to induce isolated subendocardial fibrotic lesions or saline as appropriate control (n = 15). Transthoracic echocardiography was performed using a 30-MHz linear-frequency transducer coupled to a high-resolution imaging system, and acquired images were analyzed for conventional and strain parameters. The degree of collagen content within the different cardiac layers was quantified by histologic analysis and serum levels of tissue inhibitor of metalloproteinase-1, a biomarker for fibrosis, were assessed. RESULTS: ISO treatment induced a marked increase in subendocardial collagen content in response to cell loss (control vs ISO, 0.6 ± 0.3% vs 5.8 ± 0.9%; P < .001) and resulted in a moderate increase in left ventricular wall thickness with preserved systolic function. Global longitudinal peak strain (LS) and longitudinal strain rate were significantly decreased in ISO-treated animals (LS, -15.49% vs -11.49% [P = .001]; longitudinal strain rate, -4.81 vs -3.88 sec-1 [P < .05]), whereas radial and circumferential strain values remained unchanged. Global LS was associated with subendocardial collagen content (r = 0.46, P = .01) and tissue inhibitor of metalloproteinase-1 serum level (r = 0.52, P < .05). Further statistical analyses identified global LS as a superior predictor for the presence of subendocardial fibrosis (sensitivity, 84%; specificity, 80%; cutoff value, -14.4%). CONCLUSION: Assessment of LS may provide a noninvasive method for the detection of subendocardial damage and may consequently improve early diagnosis of cardiac diseases.
BACKGROUND: The subendocardium is highly vulnerable to damage and is thus affected even in subclinical disease stages. Therefore, methods reflecting subendocardial status are of great clinical relevance for the early detection of cardiac damage and the prevention of functional impairment. The aim of this study was to investigate the potential ability of myocardial strain parameters to evaluate changes within the subendocardium. METHODS: Male 129/Svmice were injected with isoproterenol (ISO; n = 32) to induce isolated subendocardial fibrotic lesions or saline as appropriate control (n = 15). Transthoracic echocardiography was performed using a 30-MHz linear-frequency transducer coupled to a high-resolution imaging system, and acquired images were analyzed for conventional and strain parameters. The degree of collagen content within the different cardiac layers was quantified by histologic analysis and serum levels of tissue inhibitor of metalloproteinase-1, a biomarker for fibrosis, were assessed. RESULTS:ISO treatment induced a marked increase in subendocardial collagen content in response to cell loss (control vs ISO, 0.6 ± 0.3% vs 5.8 ± 0.9%; P < .001) and resulted in a moderate increase in left ventricular wall thickness with preserved systolic function. Global longitudinal peak strain (LS) and longitudinal strain rate were significantly decreased in ISO-treated animals (LS, -15.49% vs -11.49% [P = .001]; longitudinal strain rate, -4.81 vs -3.88 sec-1 [P < .05]), whereas radial and circumferential strain values remained unchanged. Global LS was associated with subendocardial collagen content (r = 0.46, P = .01) and tissue inhibitor of metalloproteinase-1 serum level (r = 0.52, P < .05). Further statistical analyses identified global LS as a superior predictor for the presence of subendocardial fibrosis (sensitivity, 84%; specificity, 80%; cutoff value, -14.4%). CONCLUSION: Assessment of LS may provide a noninvasive method for the detection of subendocardial damage and may consequently improve early diagnosis of cardiac diseases.
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Authors: Kathleen Pappritz; Jana Grune; Oliver Klein; Niklas Hegemann; Fengquan Dong; Muhammad El-Shafeey; Jie Lin; Wolfgang M Kuebler; Ulrich Kintscher; Carsten Tschöpe; Sophie Van Linthout Journal: Sci Rep Date: 2020-02-27 Impact factor: 4.379
Authors: Tomas Lapinskas; Sebastian Kelle; Jana Grune; Anna Foryst-Ludwig; Heike Meyborg; Sarah Jeuthe; Ernst Wellnhofer; Ahmed Elsanhoury; Burkert Pieske; Rolf Gebker; Ulrich Kintscher; Philipp Stawowy Journal: J Am Heart Assoc Date: 2020-01-31 Impact factor: 5.501
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