Claire Bouleti1, Thomas Mathivet2, Jean-Michel Serfaty3, Nicolas Vignolles4, Elodie Berland2, Catherine Monnot1, Philippe Cluzel5, Philippe Gabriel Steg6, Gilles Montalescot4, Stéphane Germain7. 1. Collège de France, Centre for Interdisciplinary Research in Biology (CIRB), 11, place Marcelin Berthelot, Paris F-75005, France; CNRS UMR 7241, Paris F-75005, France; INSERM U 1050, Paris F-75005, France; Service de Cardiologie, Hôpital Bichat, AP-HP, F-75018, France; DHU FIRE, Université Paris Diderot, France. 2. Collège de France, Centre for Interdisciplinary Research in Biology (CIRB), 11, place Marcelin Berthelot, Paris F-75005, France; CNRS UMR 7241, Paris F-75005, France; INSERM U 1050, Paris F-75005, France. 3. Plateforme d'Imagerie du petit animal, Service de Radiologie, Hôpital Bichat, AP-HP, F-75018, France. 4. Institut de cardiologie (AP-HP), ACTION study group, France; INSERM U937, Pitié-Salpêtrière University Hospital, Université Paris 6, France. 5. Service de radiologie, Hôpital La Pitié-salpêtrière, AP-HP, Paris, France. 6. Service de Cardiologie, Hôpital Bichat, AP-HP, F-75018, France; DHU FIRE, Université Paris Diderot, France. 7. Collège de France, Centre for Interdisciplinary Research in Biology (CIRB), 11, place Marcelin Berthelot, Paris F-75005, France; CNRS UMR 7241, Paris F-75005, France; INSERM U 1050, Paris F-75005, France; Equipe labellisée Ligue contre le Cancer, France; Service de Pathologie, Hôpital Saint-Louis, AP-HP, F-75010 Paris, France. Electronic address: stephane.germain@college-de-france.fr.
Abstract
BACKGROUND: No-reflow in ST-segment elevation acute myocardial infarction (STEMI) is associated with a poor clinical prognosis. Its pathophysiological mechanisms are not fully elucidated yet but enhanced vascular permeability plays a key role in this phenomenon. Angiopoietin-like 4 (ANGPTL4) has been implicated in vascular permeability in experimental models of acute myocardial infarction (AMI). We therefore sought to investigate whether baseline ANGPTL4 serum levels are associated with no-reflow after primary percutaneous coronary intervention (PPCI). METHODS: We studied a group of 41 patients presenting with a first STEMI within 12h of onset of symptoms and who underwent successful PPCI. Blood samples were obtained from all patients on admission before the start of the procedure, for ANGPTL4 level measurement. No-reflow was assessed by cardiac magnetic resonance imaging (MRI), the reference method. RESULTS: MRI-detected no-reflow was observed in 20 patients (48.8%). Variables independently associated with no-reflow on multivariate logistic regression analysis were: lower ANGPTL4 serum levels (odds ratio 0.82, 95% CI 0.70-0.98, P=0.02), higher troponin T peak (odds ratio 1.03, 95% CI 1.00-1.05, P=0.03), higher incidence of left anterior descending coronary artery (LAD) as culprit artery (odds ratio 14.61, 95% CI 1.24-172.49, P=0.03), and higher C-reactive protein levels (odds ratio 1.18, 95% CI 1.00-1.39, P=0.05). CONCLUSION: ANGPTL4 serum levels predict MRI-detected no-reflow after successful PPCI in STEMI patients. Given the recently demonstrated therapeutic role of ANGPTL4 in diminishing no-reflow and limiting infarct size in pre-clinical animal models, these findings in humans may open up new possibilities in the field of research.
BACKGROUND: No-reflow in ST-segment elevation acute myocardial infarction (STEMI) is associated with a poor clinical prognosis. Its pathophysiological mechanisms are not fully elucidated yet but enhanced vascular permeability plays a key role in this phenomenon. Angiopoietin-like 4 (ANGPTL4) has been implicated in vascular permeability in experimental models of acute myocardial infarction (AMI). We therefore sought to investigate whether baseline ANGPTL4 serum levels are associated with no-reflow after primary percutaneous coronary intervention (PPCI). METHODS: We studied a group of 41 patients presenting with a first STEMI within 12h of onset of symptoms and who underwent successful PPCI. Blood samples were obtained from all patients on admission before the start of the procedure, for ANGPTL4 level measurement. No-reflow was assessed by cardiac magnetic resonance imaging (MRI), the reference method. RESULTS: MRI-detected no-reflow was observed in 20 patients (48.8%). Variables independently associated with no-reflow on multivariate logistic regression analysis were: lower ANGPTL4 serum levels (odds ratio 0.82, 95% CI 0.70-0.98, P=0.02), higher troponin T peak (odds ratio 1.03, 95% CI 1.00-1.05, P=0.03), higher incidence of left anterior descending coronary artery (LAD) as culprit artery (odds ratio 14.61, 95% CI 1.24-172.49, P=0.03), and higher C-reactive protein levels (odds ratio 1.18, 95% CI 1.00-1.39, P=0.05). CONCLUSION:ANGPTL4 serum levels predict MRI-detected no-reflow after successful PPCI in STEMI patients. Given the recently demonstrated therapeutic role of ANGPTL4 in diminishing no-reflow and limiting infarct size in pre-clinical animal models, these findings in humans may open up new possibilities in the field of research.