Aims Longitudinal change in left atrial (LA) structure and function could be helpful in predicting risk for incident atrial fibrillation (AF). We used cardiac magnetic resonance (CMR) imaging to explore the relationship between change in LA structure and function and incident AF in a multi-ethnic population free of clinical cardiovascular disease at baseline. Methods and results In the Multi-Ethnic Study of Atherosclerosis (MESA), 2338 participants, free at baseline of clinically recognized AF and cardiovascular disease, had LA volume and function assessed with CMR imaging, at baseline (2000–02), and at Exam 4 (2005–07) or 5 (2010–12). Free of AF, 124 participants developed AF over 3.8 ± 0.9 years (2015) following the second imaging. In adjusted Cox regression models, an average annualized change in all LA parameters were significantly associated with an increased risk of AF. An annual decrease of 1-SD unit in total LA emptying fractions (LAEF) was most strongly associated with risk of AF after adjusting for clinical risk factors for AF, baseline LA parameters, and left ventricular mass-to-volume ratio (hazard ratio per SD = 1.91, 95% confidence interval = 1.53–2.38, P < 0.001). The addition of change in total LAEF to an AF risk score improved model discrimination and reclassification (net reclassification improvement = 0.107, P = 0.017; integrative discrimination index = 0.049, P < 0.001). Conclusion In this multi-ethnic study population free of clinical cardiovascular disease at baseline, a greater increase in LA volumes and decrease in LA function were associated with incident AF. The addition of change in total LAEF to risk prediction models for AF improved model discrimination and reclassification of AF risk.

Introduction Relations between heart failure and clinically manifested stroke are well known, but the associations between heart and brain early abnormalities are not totally clear. Aims We explore relations of subclinical brain abnormalities with early cardiac dysfunction in a large healthy middle-aged biracial cohort. Methods The CARDIA study enrolled 5,115 young adults aged 18–30 years at baseline (1985–1986). We assessed 719 Caucasian and African-American participants of the CARDIA study, with echocardiograms and brain MRI at follow-up year-25 (2010–2011). Echocardiography assessed aortic root diameter; LVEF; circumferential, longitudinal, and radial deformation. Cerebral MRI DTI, and, on a subset, ASL perfusion sequences were used to assess white matter fractional anisotropy and grey matter cerebral blood flow (CBF). Linear regression explored relations between cardiac parameters and cerebral measures, adjusting for anthropometrics, risk factors, and brain constitutional variation. Results Mean age 50±4 years, SBP 118±15mmHg; 60% white, and 48% men. Mean CBF was 46±9mL/100g/min and white matter fractional anisotropy was 0.31±0.02. Worse circumferential deformation and larger aortic root related to worse white matter fractional anisotropy. Worse radial systolic deformation was related to worse CBF in multivariable models. LVEF did not relate to early brain abnormalities. Conclusions In spite of no apparent effect of LV ejection fraction, early subclinical cardiac dysfunction and brain abnormalities are present and associated in middle-aged generally healthy individuals.

Background Longitudinal change in left atrial (LA) structure and function could be helpful in predicting risk for incident AF. We used cardiac magnetic resonance (CMR) imaging to explore the relationship between change in LA structure and function and incident AF in a multi-ethnic population free of clinical cardiovascular disease at baseline. Methods and results In the Multi-Ethnic Study of Atherosclerosis (MESA), 2338 participants, free at baseline of clinically recognized AF and cardiovascular disease, had LA volume and function assessed with CMR imaging, at baseline (2000–02), and at Exam 4 (2005–07) or 5 (2010–12). Free of AF, 124 participants developed AF over 3.8±0.9 years (to 2015) following the second imaging. In adjusted Cox regression models, an average annualized change in all LA parameters were significantly associated with an increased risk of AF. An annual decrease of 1–SD unit in total LA emptying fractions (LAEF) was most strongly associated with risk of AF after adjusting for AF clinical risk factors, baseline LA parameters and left ventricular mass-to-volume ratio (hazard ratio per SD=1.91,95% confidence interval=1.53–2.38, P<0.001). The addition of change in total LAEF to an AF risk score improved model discrimination and reclassification (net reclassification improvement=0.107, P=0.017; integrative discrimination index=0.049, P<0.001). Model discrimination, NRI and IDI Model: CHARGE-AF risk factors# + Baseline LA variable + ΔLA variable CHARGE-AF ΔLAVImin (mL/m2/y) ΔTotal LAEF (%/y) ΔPeak LA Strain (%/y) C-statistic (95% CI) 0.757 (0.721–0.794) 0.787 (0.749–0.824) 0.779 (0.737–0.820) 0.770 (0.732–0.808) NRI† (p-value) – 0.000 (0.991) 0.107 (0.017) 0.017 (0.634) IDI (p-value) – 0.049 (<0.001) 0.049 (<0.001) 0.018 (<0.001) Calibration chi2* (p-value) 19.3 (0.02) 11.68 (0.232) 5.751 (0.765) 3.673 (0.932) AF: atrial fibrillation; LA: left atrium; EF: emptying fractions; Δ: annual change; VImin: minimum indexed volume; CI: confidence interval; NRI: net reclassification improvement; IDI: integrative discrimination index #CHARGE-AF risk factors: age, race, height, weight, systolic and diastolic blood pressure, use of antihypertensive medication, smoking status, diabetes, MI and CHF by the second imaging. † Categories for NRI: <2.5%, 2.5%-5% and >5%. *Model calibration: Grønnesby and Borgan's modified Hosmer-Lemeshow chi-square statistic for survival analysis. Kaplan-Meier curves of ΔTotal LAEF Conclusion In this multi-ethnic study population free of clinical cardiovascular disease at baseline, a greater increase in LA volumes and decrease in LA function were associated with incident AF. The addition of change in total LAEF to risk prediction models for AF improved model discrimination and reclassification of AF risk. Acknowledgement/Funding This research was supported by contracts HHSN2682015ehz745.01623I,N01-HC-95159-69 from the NHLBI and UL1-TR-ehz745.016240,UL1-TR-001079,R01-HL-127659 from NIH