More than size: right atrial cardiomyopathy mechanistic insights in atrial functional tricuspid regurgitation

Background

Tricuspid annular (TA) dilation, as the atrial functional tricuspid regurgitation (AFTR) substrate, is commonly linked to right atrial (RA) enlargement due to atrial fibrillation (AF). Yet only a small number of AF patients develop AFTR, with a higher prevalence in women. Suggesting that atrial size alone does not fully explain interindividual variability or the female predominance. Underlying right atrial cardiomyopathy (ACM), comprised of volumetric, geometric, and structural components, may offer more insights into the annular remodeling mechanism.

Purpose

We sought to define the multicomponent characteristics of right atrial cardiomyopathy and identify its mechanistic and sex-specific determinants of tricuspid annular remodeling.

Methods

We included 210 consecutive patients with pre-AF ablation, high-quality, 3D late gadolinium enhancement. To isolate atrial-driven aetiology, we excluded patients with moderate or greater tricuspid regurgitation, moderate or greater left-sided valvular disease, left ventricular systolic dysfunction, congenital heart disease, pulmonary hypertension, or cardiac implantable electronic devices. The right ACM was characterized across volumetric (indexed volume), geometric (sphericity), and structural (global and regional fibrosis) metrics. TA area and circularity were derived from 3D multiplanar reconstruction. Circularity was calculated as the ratio of the minimum to the maximum diameter. Associations were evaluated with prespecified sex interaction testing, adjusted multivariable linear regression for age, AF type, number of procedures, LVEF, hypertension, and right ventricular size. All reported p-values were corrected for false discovery rate. Beta interaction between sexes was calculated as men – women.

Results

Right atrium indexed volume was the independent predictor of annular dilation (β = 0.56, p < 0.001), whereas fibrosis measures lost independence after adjustment. However, annular circularity was not only independently associated with volume (β = 0.18, p = 0.02) but also RA sphericity (β = 0.14, p = 0.04).

Despite similar RA volumes (β = 0.05, p = 0.74), women exhibited greater annular remodeling than men. Female patients tend to have larger (β = -0.36, p = 0.03), more circular (β = -0.83, p < 0.01) annuli. Moreover, septal peri-annular fibrosis emerged as a sex-specific modifier of annular area (β = -61.1, p = 0.005), showing a positive association in women but not in men.

Conclusions

Tricuspid annular remodeling in AF follows specific pathways, with annular dilation driven by atrial volume and annular circularity reflecting atrial sphericity. Septal peri-annular fibrosis was identified as a determinant of annular remodeling that may predispose women to higher AFTR risk.Sex-Specific Right ACM and TA GeometrySex-Specific Effect of FIbrosis on TA