Left atrial stiffness and sex differences in atrial fibrillation recurrence after catheter ablation

Abstract Background Atrial fibrillation (AF) occurs more frequently in men, but women suffer more AF recurrence; mechanisms are not completely understood. Purpose To explore whether sex related differences in LA stiffness (LAstiffn) in patients with AF ablation could potentially explain differences in AF recurrence. Methods We screened patients with catheter ablation for AF, in sinus rhythm at 3 months post-ablation, with no significant mitral valve disease (< moderate), and with prospectively measured LA volumes [maximum (LAVI) and minimum volume index] by echocardiography. LAStiffn index was estimated as (E/e’)/LA emptying fraction. Outcome endpoint was AF recurrence up to 14 years post ablation. Results A total of 591 patients with AF ablation were studied (mean age 60±10 years; 25% women; Table1). At 3 months post-ablation, LAVI was 36±10 mL/m2 and LAstiffn was 0.31±0.21 1/%. Compared to males, female patients were slightly older, had more frequently hypertension, congestive heart failure, prior stroke/TIA, higher CHA2DS2-VASc score; they less often had persistent AF, coronary artery disease, or dilated cardiomyopathy. Women also had higher LAstiffn (0.37±0.24 vs. 0.29±0.19, P <.0001, Figure 1), despite similar indexed LA volumes (Table1). Rates of AF recurrence at follow-up (median 7.5 years; 347 patients with events) were higher in women vs. men (Figure 2, left; log-rank P<.001) and persisted after adjustment for age, type and duration of AF, body mass index, cardiovascular risk factors and comorbidities, CHA2DS2-VASc score ≥2, LV ejection fraction, and LAVI (adjusted HR 1.58 [1.20-2.08], P=.001). Overall, LA volumes and LAstiffn were higher in patients with older age and more comorbidities (hypertension, congestive heart failure, coronary artery disease, persistent AF, CHA2DS2-VASc score ≥2, etc; P<.01 for all). At multivariable regression analysis, LAVI and LAstiffn correlated with E/e’, LV size and mass, degree of mitral/tricuspid regurgitation, and LV stroke volume index (only LAVI). In addition, LAstiffn was higher in patients with elevated right ventricular systolic pressure (RVSP) >35 mmHg and increase in RVSP more than 10 mmHg from pre-ablation (P<.0001) (correlation R=0.44, P<.0001). At follow-up, after adjusting for age and LAVI, higher LAstiffn remained associated with AF recurrence in women (P=.02, HR 2.82 per unit change, 95% CI, 1.08-6.72; Figure 2, right), but not in men (P=.30). Conclusions LAStiffn is higher in women vs. men and correlates with burden of comorbidities, aging, diastolic dysfunction and pulmonary hypertension, possibly reflecting more extensive LA myopathy, and potentially contributing to sex differences in AF recurrence.Figure 1Table 1