Quantitative assessment of left atrial fibrosis and its relationship with heart failure with preserved ejection fraction in patients with atrial fibrillation: insights from cardiac MRI

Background Left atrial (LA) myocardial fibrosis is a key structural substrate for the initiation and progression of atrial fibrillation (AF); however, its role in the development of heart failure with preserved ejection fraction (HFpEF) in patients with AF has not been fully explored. Purpose To investigate the association between LA myocardial fibrosis quantified by two methods (the full width at half maximum [FWHM] and the image intensity ratio [IIR] method) and HFpEF in patients with AF. Methods Between April 2024 and July 2024, patients with AF referred for their first pulmonary vein isolation catheter ablation at Fuwai Hospital were prospectively enrolled in this study. All enrolled patients had preserved left ventricular systolic function, defined as left ventricular ejection fraction ≥ 50% on transthoracic echocardiography, and underwent pre-procedural cardiac MRI. All scans were performed using a 3.0-T clinical MRI system. High-resolution 3D late gadolinium enhancement images were acquired. Quantification of LA fibrosis was performed using commercially available ADAS software. LA fibrosis was quantified using FWHM and IIR methods. Patients were categorized as HFpEF or non-HFpEF based on the Heart Failure Association Pre-test assessment, Echocardiography, natriuretic peptides, Functional testing, and Final etiology (HFA-PEFF) score. Results A total of 48 patients with AF were enrolled in this study (mean age 56.8 ± 10.6 years; 70.8% male), of whom 16 (33.3%) were diagnosed with HFpEF. The percentages of total, dense, and interstitial fibrosis assessed by the FWHM method were significantly different from those assessed by the IIR method (all P < 0.01). Compared with AF patients without HFpEF, those with HFpEF exhibited significantly higher percentages of total and interstitial fibrosis as quantified by both methods (all P < 0.01). In univariable logistic regression analysis, the percentages of total and interstitial fibrosis quantified by the FWHM method (total fibrosis: OR 1.34/1%, 95% CI 1.12-1.62, P = 0.002; interstitial fibrosis: OR 1.54/1%, 95% CI 1.18-2.02, P = 0.001), and by the IIR method (total fibrosis: OR 1.20/1%, 95% CI 1.04-1.39, P = 0.013; interstitial fibrosis: OR 1.43/1%, 95% CI 1.12-1.81, P = 0.003), were associated with HFpEF. In multivariable analysis, all associations remained independent after separate adjustment for persistent AF, LA volume index, and E/e'. Receiver operating characteristic analysis revealed that the percentages of interstitial fibrosis, quantified by both methods, exhibited the highest diagnostic performance among the three types of LA fibrosis (area under the curve, 0.863 and 0.818, respectively). Conclusion Despite quantitative differences, LA myocardial fibrosis, as assessed by both FWHM and IIR methods, was associated with HFpEF in patients with AF. These findings suggest that LA fibrosis may serve as a key structural marker associated with HFpEF in this cohort.