Rare Cardiac Genetic Variation Is Associated With Postoperative Atrial Fibrillation
Zhanlin Chen, Anirudha S. Chandrabhatla, Anna Pfenniger, Tom Liu, Patrick M. McCarthy, James L. Cox, Stephen F. Chiu, Rod Passman, Philip Greenland, Adam Gordon, S. Chris Malaisrie, Gregory WebsterBACKGROUND:
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%;
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.