Clonal hematopoiesis is associated with long-term adverse outcomes following cardiac surgery Journal Article
| Authors: | Ninni, S.; Vicario, R.; Coisne, A.; Woitrain, E.; Tazibet, A.; Stewart, C. M.; Diaz, L. A. Jr; White, J. R.; Koussa, M.; Dubrulle, H.; Juthier, F.; Jungling, M.; Vincentelli, A.; Edme, J. L.; Nattel, S.; de Winther, M.; Geissmann, F.; Dombrowicz, D.; Staels, B.; Montaigne, D. |
| Article Title: | Clonal hematopoiesis is associated with long-term adverse outcomes following cardiac surgery |
| Abstract: | BACKGROUND: Cardiac surgery triggers sterile innate immune responses leading to postoperative complications. Clonal hematopoiesis (CH) is associated with short-term inflammation-mediated outcomes after cardiac surgery. The impact of CH on long-term postoperative outcomes remains unknown. METHODS AND RESULTS: In this cohort study, patients undergoing elective cardiac surgery were included from January 2017 to September 2019. Patients were screened for CH using a predefined gene panel of 19 genes. Recorded clinical events were all-cause death, major adverse cardiac and cerebral events including cardiovascular death, myocardial infarction or nonscheduled coronary revascularization, stroke, and hospitalization for acute heart failure. The primary study outcome was time to a composite criterion including all-cause mortality and major adverse cardiac and cerebral events. Among 314 genotyped patients (median age: 67 years; interquartile range 59–74 years), 139 (44%) presented with CH, based on a variant allelic frequency ≥1%. Carriers of CH had a higher proportion of patients with a history of atrial fibrillation (26% for CH versus 17% for non-CH carriers, P=0.022). The most frequently mutated genes were DNMT3A, TET2, and ASXL1. After a median follow-up of 1203 [813–1435] days, the primary outcome occurred in 50 patients. After multivariable adjustment, CH was independently associated with a higher risk for the primary outcome (hazard ratio, 1.88 [95% CI, 1.05–3.41], P=0.035). Most adverse events occurred in patients carrying TET2 variants. CONCLUSIONS: In patients undergoing cardiac surgery, CH is frequent and associated with a 2-fold increased long-term risk for major adverse clinical outcomes. CH is a novel risk factor for long-term postcardiac surgery complications and might be useful to personalize management decisions. © 2024 The Author(s). |
| Keywords: | survival; adult; aged; middle aged; unclassified drug; dna binding protein; tet2 protein, human; gene mutation; major clinical study; single nucleotide polymorphism; genetics; mutation; dna-binding proteins; proto-oncogene proteins; heart left ventricle failure; inflammation; cohort analysis; gene frequency; genetic variation; risk factors; transcription factor; creatinine; risk factor; time factors; risk assessment; postoperative complication; postoperative complications; coronary artery bypass graft; hospitalization; body mass; adverse outcome; heart failure; heart infarction; epidemiology; echocardiography; heart left ventricle ejection fraction; repressor protein; repressor proteins; atrial fibrillation; dna (cytosine 5) methyltransferase; heart surgery; cerebrovascular accident; dna methyltransferase 3a; adverse event; time factor; procedures; acute heart failure; clonal hematopoiesis; cardiovascular mortality; estimated glomerular filtration rate; dioxygenase; asxl1 protein, human; sanger sequencing; humans; human; male; female; article; heart muscle revascularization; cardiac surgical procedures; all cause mortality; major adverse cardiac event; cardiac surgery; tet methylcytosine dioxygenase 2; dna (cytosine-5-)-methyltransferases; proto oncogene protein; dioxygenases; asxl transcriptional regulator 1; dnmt3a protein, human |
| Journal Title: | Journal of the American Heart Association |
| Volume: | 13 |
| Issue: | 17 |
| ISSN: | 2047-9980 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2024-09-03 |
| Start Page: | e034255 |
| Language: | English |
| DOI: | 10.1161/jaha.123.034255 |
| PUBMED: | 39206728 |
| PROVIDER: | scopus |
| PMCID: | PMC11646528 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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