Key result
Rare cardiac gene variants are linked to ~80% higher odds of postoperative atrial fibrillation.
Why the study?
The contribution of rare genetic variants to new-onset postoperative atrial fibrillation (POAF) is poorly characterized.
Does the presence of rare pathogenic or likely pathogenic variants in cardiac genes increase the risk of postoperative atrial fibrillation in adults undergoing surgery?
Cohort (n=49,913)
Does the presence of rare pathogenic or likely pathogenic variants in cardiac genes increase the risk of postoperative atrial fibrillation in adults undergoing surgery?
Rare pathogenic or likely pathogenic variants in cardiomyopathy genes are significantly associated with an increased risk of postoperative atrial fibrillation and reduced long-term AF-free survival.
Rare cardiac gene variants may flag elevated POAF risk after surgery; leaves open whether genetic screening improves perioperative outcomes.
BACKGROUND: New-onset postoperative atrial fibrillation (POAF) is a common surgical complication, yet the contribution of rare genetic variants to POAF is poorly characterized. METHODS: We conducted a cohort study including 49 913 adults who underwent surgery without a preoperative diagnosis of atrial fibrillation (AF). All participants had whole-genome sequencing linked to electronic health record data. Pathogenic or likely pathogenic (LP) variants were identified in 141 cardiac genes associated with early-onset AF. The primary outcome was POAF, defined as a new diagnosis of AF within 30 days of surgery; the secondary outcome was freedom from AF over 5 years. Multivariable regression and propensity-score matching were used to evaluate the associations between pathogenic/LP variants and POAF. RESULTS: Among 49 913 participants, 2298 underwent cardiac surgery and 47 615 underwent noncardiac surgery. The prevalence of pathogenic/LP variants was 6.0% in the cardiac surgery group (138/2298) and 4.1% in the noncardiac surgery group (1947/47 615). Overall, carriers of ≥1 pathogenic/LP variant had higher odds of POAF than noncarriers (6.6% versus 4.0%; odds ratio [OR], 1.8 [95% CI, 1.4–2.1]). In cardiac surgery, 36.0% of pathogenic/LP carriers (78/216) developed POAF versus 23.4% of noncarriers (492/2082; OR, 2.3 [95% CI, 1.4–3.2]), and in noncardiac surgery, POAF occurred in 3.8% of carriers (74/1947) versus 2.5% of noncarriers (1465/45 668; OR, 1.5 [95% CI, 1.2–1.9]). Pathogenic/LP variants in cardiomyopathy-only genes (n=589; OR, 1.8 [95% CI, 1.3–2.6]) or in genes associated with both cardiomyopathy and arrhythmia (n=1059; OR, 1.8 [95% CI, 1.4–2.3]) were significantly associated with POAF, whereas variants in arrhythmia-only genes (n=454; OR, 1.3 [95% CI, 0.8–2.1]) were not. Five-year freedom from AF was lower among pathogenic/LP variant carriers in both cardiac surgery (53% versus 64%; P =0.010) and noncardiac surgery (92% versus 94%; P =0.002). CONCLUSIONS: Rare pathogenic/LP variants in cardiomyopathy genes were associated with risk of POAF and reduced AF-free survival over long-term follow-up across cardiac and noncardiac surgery.
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Chen et al. (2026) conducted a cohort in Postoperative atrial fibrillation (n=49,913). Pathogenic or likely pathogenic (LP) variants in cardiac genes vs. Noncarriers was evaluated on Postoperative atrial fibrillation (POAF), defined as a new diagnosis of AF within 30 days of surgery (OR 1.8, 95% CI 1.4-2.1). Carriers of ≥1 rare pathogenic or likely pathogenic variant in cardiac genes had higher odds of postoperative atrial fibrillation than noncarriers (6.6% vs 4.0%; OR 1.8, 95% CI 1.4-2.1).
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