Left Ventricular Fibrosis on T1 Mapping is Associated with Increased Risk of Incident Atrial Fibrillation: Results from the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: T1 mapping and extracellular volume fraction (ECV) are validated markers of diffuse myocardial fibrosis on cardiac magnetic resonance (CMR). Factors promoting left ventricular (LV) fibrosis are also linked to incident atrial fibrillation (AF), but whether ECV expansion is associated with increased AF risk remains unknown. OBJECTIVES: We evaluated whether baseline LV-ECV independently predicts incident AF. METHODS: We studied 1,261 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) free of AF at baseline who underwent myocardial T1-mapping between 2010-2012. Participants were followed prospectively for incident AF. Associations between ECV and incident AF were assessed using multivariable Cox models adjusted for CHARGE-AF risk factors, with additional analyses adjusting for myocardial scar, left atrial (LA) structure and function, and LV ejection fraction (LVEF). RESULTS: During a median follow-up of 7.82 years, 156 participants developed AF. ECV was independently associated with incident AF after adjustment for CHARGE-AF risk factors (HR 1.105 per 1% increase; 95% CI 1.045-1.168; p<0.001). Participants in the highest ECV quartile (>28.6%) had approximately a two-fold higher risk of AF compared with the lowest quartile (HR 1.914; 95% CI 1.198-3.058; p=0.007). Associations remained significant after adjusting for myocardial scar, LA parameters and LVEF. Higher ECV was associated with adverse LA remodeling, including increased LA volume and impaired atrial emptying (p<0.05), and remained associated with AF after LA adjustment. CONCLUSION: Diffuse LV interstitial fibrosis quantified by ECV independently predicts incident AF and is associated with adverse atrial remodeling, supporting ventricular fibrosis as an early substrate for AF development.