Natural history of bivalvular functional regurgitation

Aims Bivalvular functional regurgitation (BVFR) defined as concomitant mitral and tricuspid insufficiency has not been described or systematically assessed before. Therefore, this study sought to define incidence, impact and natural history of BVFR in heart failure with reduced ejection fraction (HFrEF) to provide the foundation for risk assessment and directions for potential treatment strategies. Methods and results We enrolled 1021 consecutive patients with HFrEF under guideline-directed medical therapy and performed comprehensive echocardiographic and neurohumoral profiling. All-cause mortality during a 5 years of follow-up served as the primary endpoint. Thirty percent of patients suffered from moderate or severe BVFR. Long-term mortality increased with the presence and severity of functional regurgitation (FR) with severe BVFR representing the highest risk-subset (P<0.001). Severe BVFR patients were more symptomatic and displayed an adverse remodelling and neurohumoral activation pattern (all P<0.05). Severe BVFR was associated with excess mortality independently of clinical [adjusted hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.39-1.84; P<0.001] and echocardiographic (adjusted HR 1.31, 95% CI 1.11-1.54; P=0.001) confounders, guideline-directed medical therapy (adjusted HR 1.55, 95% CI 1.35-1.79; P<0.001) and neurohumoral activation (adjusted HR 1.31, 95% CI 1.07-1.59; P=0.009). Moderate BVFR (n=99) comprised equal baseline characteristics and similar risk as isolated severe FR (HR 0.95, 95% CI 0.69-1.30; P=0.73). Conclusion This long-term outcome study shows the multi-faceted nature of FR and defines BVFR as an important clinical entity associated with impaired functional class, adverse cardiac remodelling, and excess risk of mortality. Moderate BVFR conveys similar risk as isolated severe FR reflecting the deleterious impact of the global regurgitant load on the failing heart and the need of an integrated understanding for risk-assessment.