Colchicine added to standard therapy further reduces fibrosis in pigs with myocardial infarction.


Journal

Journal of cardiovascular medicine (Hagerstown, Md.)
ISSN: 1558-2035
Titre abrégé: J Cardiovasc Med (Hagerstown)
Pays: United States
ID NLM: 101259752

Informations de publication

Date de publication:
01 11 2023
Historique:
medline: 2 10 2023
pubmed: 29 9 2023
entrez: 29 9 2023
Statut: ppublish

Résumé

The anti-inflammatory drug colchicine improves the outcome of patients with myocardial infarction (MI). As an intense inflammatory and fibrotic response after MI may lead to scar expansion and left ventricular (LV) remodeling, the clinical benefit of colchicine could be related to a positive effect on the infarct scar and LV remodeling. Pigs underwent left anterior descending artery occlusion through an angioplasty balloon for 90 min and were then randomized into two groups: standard therapy [ACE inhibitor, beta blocker, mineralocorticoid receptor antagonist (MRA), aspirin] plus colchicine (n = 14) or standard therapy alone (n = 13). The pigs were treated for 30 days and underwent two cardiac magnetic resonance (CMR) scans at 72 h and 30 days. The pigs were then sacrificed the day after the second CMR. The primary efficacy end point was the extent of fibrosis in the infarct zone (calculated on eight samples from this zone and averaged). In the hearts explanted after 31 days, pigs in the colchicine group had less fibrosis in the infarct zone than the other animals [41.6% (20.4-51.0) vs. 57.4% (42.9-66.5); P = 0.022]. There was a trend toward a higher myocardial salvage index (MSI; an index of the efficacy of revascularization) in pigs on colchicine (P = 0.054). Conversely, changes in LV volumes, ejection fraction and mass did not differ between groups. Colchicine therapy for 1 month after reperfused MI further reduces myocardial fibrosis when added to standard therapy, while it does not have additional effects on LV remodeling.

Sections du résumé

BACKGROUND
The anti-inflammatory drug colchicine improves the outcome of patients with myocardial infarction (MI). As an intense inflammatory and fibrotic response after MI may lead to scar expansion and left ventricular (LV) remodeling, the clinical benefit of colchicine could be related to a positive effect on the infarct scar and LV remodeling.
METHODS
Pigs underwent left anterior descending artery occlusion through an angioplasty balloon for 90 min and were then randomized into two groups: standard therapy [ACE inhibitor, beta blocker, mineralocorticoid receptor antagonist (MRA), aspirin] plus colchicine (n = 14) or standard therapy alone (n = 13). The pigs were treated for 30 days and underwent two cardiac magnetic resonance (CMR) scans at 72 h and 30 days. The pigs were then sacrificed the day after the second CMR. The primary efficacy end point was the extent of fibrosis in the infarct zone (calculated on eight samples from this zone and averaged).
RESULTS
In the hearts explanted after 31 days, pigs in the colchicine group had less fibrosis in the infarct zone than the other animals [41.6% (20.4-51.0) vs. 57.4% (42.9-66.5); P = 0.022]. There was a trend toward a higher myocardial salvage index (MSI; an index of the efficacy of revascularization) in pigs on colchicine (P = 0.054). Conversely, changes in LV volumes, ejection fraction and mass did not differ between groups.
CONCLUSION
Colchicine therapy for 1 month after reperfused MI further reduces myocardial fibrosis when added to standard therapy, while it does not have additional effects on LV remodeling.

Identifiants

pubmed: 37773884
doi: 10.2459/JCM.0000000000001554
pii: 01244665-202311000-00011
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

840-846

Informations de copyright

Copyright © 2023 Italian Federation of Cardiology - I.F.C. All rights reserved.

Références

Tsao CW, Aday AW, Almarzooq ZI, et al. Heart Disease and stroke statistics-2022 update: a report from the American Heart Association. Circulation 2022; 145:e153–e639.
Del Buono MG, Garmendia CM, Seropian IM, et al. Heart failure after ST-elevation myocardial infarction: beyond left ventricular adverse remodeling. Curr Probl Cardiol 2022; 48:101215.
Jessup M, Brozena S. Heart failure. N Engl J Med 2003; 348:2007–2018.
Bhatt AS, Ambrosy AP, Velazquez EJ. Adverse remodeling and reverse remodeling after myocardial infarction. Curr Cardiol Rep 2017; 19:71.
Frantz S, Hundertmark MJ, Schulz-Menger J, Bengel FM, Bauersachs J. Left ventricular remodelling postmyocardial infarction: pathophysiology, imaging, and novel therapies. Eur Heart J 2022; 43:2549–2561.
Imazio M, Nidorf M. Colchicine and the heart. Eur Heart J 2021; 42:2745–2760.
Tong DC, Quinn S, Nasis A, et al. Colchicine in patients with acute coronary syndrome: the australian cops randomized clinical trial. Circulation 2020; 142:1890–1900.
Tardif JC, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med 2019; 381:2497–2505.
Mewton N, Roubille F, Bresson D, et al. Effect of colchicine on myocardial injury in acute myocardial infarction. Circulation 2021; 144:859–869.
NIH. Guide for the care and use of laboratory animals, 8th ed. Washington, DC: National Academies Press. 2011.
Pastormerlo LE, Burchielli S, Ciardetti M, et al. Myocardial salvage is increased after sympathetic renal denervation in a pig model of acute infarction. Clin Res Cardiol 2021; 110:711–724.
van Kats JP, Duncker DJ, Haitsma DB, et al. Angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade prevent cardiac remodeling in pigs after myocardial infarction: role of tissue angiotensin II. Circulation 2000; 102:1556–1563.
Duncker DJ, Boontje NM, Merkus D, et al. Prevention of myofilament dysfunction by beta-blocker therapy in postinfarct remodeling. Circ Heart Fail 2009; 2:233–242.
Bacchetta MD, Salemi A, Milla F, et al. Low-dose spironolactone: effects on artery-to-artery vein grafts and percutaneous coronary intervention sites. Am J Ther 2009; 16:204–214.
Sheibani M, Zamani N, Gerami AH, Akhondi H, Hassanian-Moghaddam H. Clinical, laboratory, and electrocardiographic findings in colchicine toxicity: 10 years of experience. Front Med 2022; 9:872528.
Dariolli R, Naghetini MV, Marques EF, et al. Allogeneic pASC transplantation in humanized pigs attenuates cardiac remodeling postmyocardial infarction. PLoS One 2017; 12:e0176412.
Gallet R, Dawkins J, Valle J, et al. Exosomes secreted by cardiosphere-derived cells reduce scarring, attenuate adverse remodelling, and improve function in acute and chronic porcine myocardial infarction. Eur Heart J 2017; 38:201–211.
Bøtker HE, Kaltoft AK, Pedersen SF, Kim WY. Measuring myocardial salvage. Cardiovasc Res 2012; 94:266–275.
Faragli A, Tanacli R, Kolp C, et al. Cardiovascular magnetic resonance feature tracking in pigs: a reproducibility and sample size calculation study. Int J Cardiovasc Imag 2020; 36:703–712.
Tang VW. Collagen, stiffness, and adhesion: the evolutionary basis of vertebrate mechanobiology. Mol Biol Cell 2020; 31:1823–1834.
Frangogiannis NG. The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol 2014; 11:255–265.
Saxena A, Russo I, Frangogiannis NG. Inflammation as a therapeutic target in myocardial infarction: learning from past failures to meet future challenges. Transl Res 2016; 167:152–166.
Deftereos S, Giannopoulos G, Angelidis C, et al. Anti-inflammatory treatment with colchicine in acute myocardial infarction: a pilot study. Circulation 2015; 132:1395–1403.
Ong SB, Hernández-Reséndiz S, Crespo-Avilan GE, et al. Inflammation following acute myocardial infarction: multiple players, dynamic roles, and novel therapeutic opportunities. Pharmacol Ther 2018; 186:73–87.
Toso A, Leoncini M, Magnaghi G, et al. Rationale and design of COLchicine On-admission to Reduce inflammation in Acute Coronary Syndrome (COLOR-ACS) study. J Cardiovasc Med 2023; 24:52–58.
Andreis A, Imazio M, De Ferrari GM. Colchicine for the treatment of cardiovascular diseases: old drug, new targets. J Cardiovasc Med 2021; 22:1–8.
Andreis A, Imazio M, Casula M, Avondo S, De Ferrari GM. Colchicine efficacy and safety for the treatment of cardiovascular diseases. Intern Emerg Med 2021; 16:1691–1700.
Andreis A, Imazio M, Avondo S, et al. Adverse events of colchicine for cardiovascular diseases: a comprehensive meta-analysis of 14 188 patients from 21 randomized controlled trials. J Cardiovasc Med 2021; 22:637–644.

Auteurs

Alberto Aimo (A)

Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna.
Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

Daina Martinez-Falguera (D)

Institut del Cor, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.

Andrea Barison (A)

Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna.
Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

Veronica Musetti (V)

Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna.
Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

Silvia Masotti (S)

Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna.
Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

Paolo Morfino (P)

Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna.

Claudio Passino (C)

Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna.
Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

Giulia Martinelli (G)

Institut del Cor, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.

Angela Pucci (A)

Histopathology Department, University Hospital of Pisa, Italy.

Veronica Crisostomo (V)

Jesús Usón Minimally Invasive Surgery Centre, Cáceres.
CIBERCV, Instituto de Salud Carlos III, Madrid.

Francisco Sanchez-Margallo (F)

Jesús Usón Minimally Invasive Surgery Centre, Cáceres.
CIBERCV, Instituto de Salud Carlos III, Madrid.

Virginia Blanco-Blazquez (V)

Jesús Usón Minimally Invasive Surgery Centre, Cáceres.
CIBERCV, Instituto de Salud Carlos III, Madrid.

Carolina Galvez-Monton (C)

Institut del Cor, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.

Michele Emdin (M)

Interdisciplinary Center for Health Sciences, Scuola Superiore Sant'Anna.
Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.

Antoni Bayes-Genis (A)

Institut del Cor, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.
Department of Medicine, Universitat Autònoma de Barcelona, Barcelona.
CIBERCV, Carlos III Institute of Health, Madrid, Spain.

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