Rare Cardiac Genetic Variation Is Associated With Postoperative Atrial Fibrillation

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.