Background: Transcatheter tricuspid edge-to-edge repair (TEER) is a novel therapy for patients with significant tricuspid regurgitation (TR). Although the intervention has been suggested to improve outcomes, TR patients are at substantial residual risk after TEER and the identification of targeted adjunctive therapies is required. We recently demonstrated that a hypercirculatory TR phenotype exists, which is characterized by volume expansion, venous congestion and adverse prognosis after TEER. Total blood volume is divided between the unstressed volume, which fills the vascular space, and stressed blood volume (SBV), which generates intravascular pressure. SBV has recently been identified as important mediator of hemodynamic derangements in heart failure and might pose an attractive treatment target. We sought to investigate the role of SBV in severe TR and its implications for TEER.

Methods and Results: A total of 279 patients underwent right heart catheterization (RHC) prior to TEER. SBV was estimated (eSBV) from hemodynamic variables fit to a comprehensive cardiovascular model and normalized to 70 kg body weight. eSBV was associated with obesity, volume retention, renal and hepatic dysfunction, cardiac chamber remodeling, right ventricular (RV)/pulmonary artery (PA) coupling, elevated cardiac and PA pressures, lower systemic vascular resistance and lower venous distensibility (p<0.05 for all). After TEER, patients with eSBV above the median demonstrated lower procedural success rates, less reduction in RA-pressures and less reduction in clinical signs of volume overload as compared to lower eSBV patients (p<0.05 for all). Higher eSBV was a powerful and independent predictor of the occurrence of the composite of death and heart failure hospitalization during a median follow-up of 618 days (p<0.05 for all). eSBV modulated the prognostic value of RV/PA coupling as well as hypercirculation.

Conclusion: In severe TR patients eSBV is associated with obesity, impaired renal and liver function, cardiac remodelling, unfavourable hemodynamics, attenuated reduction of venous congestion in response to TEER as well as adverse clinical outcomes. Estimation of SBV provides a means of identification of TR patients in need of adjunctive targeted therapies and should be incorporated in future trials in the field.