Clinical Implications of Atrial Fibrillation Provoked by Acetylcholine

Background The coronary spasm provocation test using acetylcholine (ACh) is useful for diagnosing vasospastic angina (VSA). Paroxysmal atrial fibrillation (PAF) during ACh testing is frequent and usually transient. However, the clinical implications of PAF provoked by ACh is unknown. Deterioration of the left atrial (LA) reservoir strain is associated with new-onset of atrial fibrillation (AF) and fibrosis of the left atrium; additionally, ACh shortens the action potential duration and facilitates AF in the fibrotic atria in the human AF model. Hence, this study aimed to investigate the relationship between LA function and occurrence of AF during the ACh test. Methods We studied a consecutive cohort of 100 patients (60.1±14.5 years, 39 women) without history of AF who underwent the ACh test in our centers from 2015 to 2022. Echocardiographic data were available for all the patients. PAF was defined as lasting >30 s during the ACh test. Based on the occurrence of AF during the ACh test, the patients were divided into two groups: provoked PAF group (n=29) vs. non AF group (n=71). LA function was assessed via two-dimensional speckle-tracking echocardiography. Occurrences of spontaneous AF were recorded as clinical events during long-term follow-up. Results The observation period was 675 (114.5-1789.5) days, and 65 patients (65%) were tested positive in the ACh test and diagnosed with VSA. LA volume index was similar between provoked PAF and non AF groups (26.9±7.4 mL/m 2 vs. 27.1±8.5 mL/m 2 , p =0.89). In contrast, LA reservoir (27.6±5.2% vs. 34.8±6.8%, p <0.001) and conduit (13.4±5.1% vs. 18.4±6.2%, p <0.001) strain were significantly lower in provoked PAF group than in non AF group. The provoked PAF group had a lower LA booster strain (14.1±5.6% vs. 16.4±6.3%, p =0.093) than non AF group. A multiple regression analysis showed that LA reservoir strain was independently associated with the provoked PAF during ACh test (OR 0.81, 95% CI: 0.72-0.91, p <0.001). In the provoked PAF group, spontaneous AF occurred in three patients (10.3%), one of whom was treated with pulmonary vein isolation, whereas there were no events of PAF in the non AF group. Conclusion The occurrence of PAF during the ACh test suggests dysfunction of left atria and may predict future PAF.