Original InvestigationHematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation
Central Illustration
Section snippets
Cohort and preoperative clinical assessment
The clinical cohort is part of the POMI-AF (Post-Operative Myocardial Incident & Atrial Fibrillation; NCT03376165) study, approved by the institutional ethics committee (Comité de Protection des Personnes Ile de France V). Written informed consent was obtained from all patients before inclusion.
Patients (≥18 years of age) were referred to the cardiovascular surgery department at Lille University Hospital for AVR (with or without coronary artery bypass grafting) because of severe aortic valve
HSM is highly prevalent in patients undergoing cardiac surgery
HSM was assessed using deep targeted DNA sequencing of leukocytes from 104 patients (52 with POAF and 52 in sinus rhythm) elected for AVR using a large panel of 576 genes (HemePACT panel) (Supplemental Table 2). The median age of the 104 patients was 70 years (IQR: 66-75 years), 36% were women, and 29% had type 2 diabetes mellitus. As a result of the patient selection process, patients with POAF and those in sinus rhythm had comparable distributions regarding age, BMI, diabetic status, and sex (
Discussion
Our results show that patients undergoing cardiac surgery display a high prevalence of HSM (as high as 60% with the most inclusive definition), which increases with age. HSM most frequently occurs in 2 genes (DNMT3A and TET2) encoding epigenetic regulators. Moreover, we found that the presence of HSM is associated with: 1) increased circulating monocyte counts, specifically inflammatory CD64+ monocytes; 2) circulating classical inflammatory monocyte gene profiles indicative of activation and
Conclusions
HSM is frequent in patients undergoing cardiac surgery. Its prevalence critically depends on the gene number included in the definition, with the broadest definition identifying patients at very high risk for POAF following surgery. This increased risk for POAF could be related to an increased postoperative inflammatory response driven by primed monocytes and increased atrial vulnerability driven by an immune shift in the atrial myocardium (Central Illustration). Assessment of HSM and/or its
Funding Support and Author Disclosures
This study was supported by grants from Fédération Française de Cardiologie, Fondation Leducq convention 16CVD01 (“Defining and Targeting Epigenetic Pathways in Monocytes and Macrophages That Contribute to Cardiovascular Disease”), the European Genomic Institute for Diabetes (ANR-10-LABX-0046), Fondation Pour la Recherche Médicale (REFERENCE PROJET EQU202203014650), and Agence Nationale de la Recherche (TOMIS leukocytes: ANR-CE14-0003-01). Dr Staels is a recipient of an Advanced European
Acknowledgments
The authors thank Bertrand Accart and the Biological Resources Center of Centre Hospitalier de Lille (BB 0033-00030) for handling and providing biological samples from the POMI-AF study.
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The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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Drs Ninni, and Dombrowicz are co-first authors.
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Drs Kuznetsova and Vicario are co-second authors.
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Drs Staels and Montaigne are co–senior authors.