Supplementary Material for: Prevalence, Pathophysiologic Mechanisms, and Clinical Outcomes of Tricuspid Regurgitation in the Elderly: Results from the TREY Registry

Background:
The prevalence of secondary tricuspid regurgitation (TR) increases with aging. To date, the exact mechanisms and phenotypes of secondary TR in the elderly have not been completely defined. This knowledge would inform patient selection for the evolving transcatheter options.
Methods:
Consecutive older subjects (≥60-year-old) were enrolled in the prospective Tricuspid Regurgitation in the ElderlY (TREY) Registry (ClinicalTrials.gov ID: NCT05784883). TR severity was determined according to a multiparametric approach, and a detailed analysis of right-heart chambers and tricuspid valve (TV) was systematically conducted. The TH/AD ratio was calculated as TV tenting height divided by diastolic tricuspid annulus diameter.
Results:
Out of 435 patients (age, 66±6 years; 46% female), 42% had mild and 16% had moderate/severe TR. Even mild TR (as compared with none/trace TR) was associated with TV and right-heart chamber remodeling (including higher tricuspid annulus [TA] diameter, p=0.002; TV leaflet length, p<0.001; right ventricular basal diameter, p=0.001; and right atrial area, p=0.003). On ROC curve analysis, the following criteria of TV remodeling were associated with moderate/severe TR: TA diastolic diameter, TV tenting area, and TV lateral leaflet length (AUC, 0.79[95% CI: 0.73-0.86]; 0.75[95% CI: 0.67-0.82]; and 0.72[95% CI: 0.64-0.79]; respectively). Among those with none (n=181), one (n=138), two (n=43), and all-three criteria (n=29); the frequency of moderate/severe TR was: 5.5%, 18.1%, 25.6%, and 72.4%; respectively. TH/AD ratio could differentiate ventricular (vs. atriogenic) functional TR at a cut-off value of 0.185 (specificity, 100%; sensitivity, 81%; AUC, 0.94[95% CI: 0.88-0.98]); with higher values suggesting a predominant ventricular TR and lower values suggesting an atriogenic mechanism. At a median follow up of 281 days (IQR: 216-614 days), patients with moderate/severe TR had a higher all-cause mortality (41.5%, log rank p=0.035), while the mortality in mild and none/trace TR was not significantly different (21.1% and 17.4%).
Conclusion:
Significant secondary TR is prevalent among older subjects and is associated with progressive remodeling of right-heart chambers and TV geometry that starts with mild TR, while mortality is increased when TR is ≥moderate. TA dilatation, increased tenting, and leaflet elongation are three major determinants of the development of secondary TR. A novel parameter that integrates leaflet tethering and annular dilatation could differentiate ventricular vs. atriogenic functional TR.