Natural Course of Nonsevere Secondary Tricuspid Regurgitation

Background: Secondary tricuspid regurgitation (sTR) is frequent in patients with heart failure with reduced ejection fraction and is associated with adverse outcomes despite guideline-directed therapy. However, little is known about the natural course of nonsevere sTR and its relation to cardiac remodeling and outcomes. The aims of this study were therefore to investigate the natural course of sTR progression using quantitative measurements, to assess the prognostic impact on long-term mortality, and to identify risk factors associated with progressive sTR.

Methods: A total of 216 patients with heart failure with reduced ejection fraction receiving guideline-directed therapy were included in this long-term observational study. Progression of sTR was quantitatively defined as an increase of 0.2 cm² in effective regurgitant orifice area or 15 mL in regurgitant volume, with transition to at least moderate sTR. Kaplan-Meier and Cox regression analyses were applied to assess survival during a 5-year follow-up period.

Results: Among patients with nonsevere sTR at baseline, 62 (29%) experienced sTR progression. Progressive sTR was accompanied by larger left and right atrial volumes (P = .02 and P < .02, respectively) and a higher prevalence of atrial fibrillation (P < .04). During a median follow-up period of 60 months (interquartile range, 37-60 months), 82 patients died. Progression of sTR conveyed a higher risk for long-term mortality (hazard ratio, 1.77; 95% CI, 1.1-2.83; P < .02), even after multivariate adjustment for bootstrap-selected (adjusted hazard ratio, 1.70; 95% CI, 1.06-2.74; P < .03) and clinical confounder (adjusted hazard ratio, 1.80; 95% CI, 1.07-3.05; P < .03) models.

Conclusions: The incidence of progressive sTR despite guideline-directed therapy is associated with adverse cardiac and valvular remodeling as well as a significantly higher long-term mortality. Biatrial enlargement as well as atrial fibrillation are associated with the development of subsequent progressive sTR and may help identify patients at risk for sTR progression, potentially creating a window of opportunity for closer follow-up and newly arising minimally invasive transcatheter repair therapies.