An Integrated Imaging and Circulating Biomarker Approach for Secondary Tricuspid Regurgitation

Abstract

Secondary tricuspid regurgitation (sTR) is frequent among patients with heart failure with reduced ejection fraction (HFrEF), however it confers considerable diagnostic challenges. The assessment of neurohumoral activation may constitute a valuable supplement to the current imaging-based diagnostic process. This study sought to investigate the expression of complementary biomarkers in sTR and to evaluate the effectiveness of integrating their assessment into the diagnostic process. We enrolled 576 HFrEF patients recording echocardiographic and biochemical measurements, i.e., N-terminal pro-B-type natriuretic peptide, mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin, C-terminal pro-endothelin-1 (CT-pro-ET1), and copeptin. Plasma levels of the aforementioned neurohormones were significantly elevated with increasing sTR severity (p < 0.001 for all). CT-pro-ET1 and MR-proANP were the closest related to severe sTR (adj. OR 1.46; 95%CI 1.11–1.91, p = 0.006 and adj. OR 1.45, 95%CI 1.13–1.87, p = 0.004, respectively). In patients with moderate-to-severe sTR, adding selected biomarkers (i.e., CT-pro-ET1 and MR-proANP) resulted in a substantial improvement in the discriminatory power regarding long-term mortality (C-statistic: 0.54 vs. 0.65, p < 0.001; continuous NRI 57%, p < 0.001). Circulating biomarkers closely relate to sTR severity and correlate with hemodynamic and morphologic mechanisms of sTR. Specifically, MR-proANP and CT-pro-ET1 are closely linked to the presence of severe sTR, and a combined assessment with the guideline recommended echocardiographic grading significantly improves individual risk stratification.

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints

“…Significant TR produces volume overload of the RV, causing stretch and stress of the myocardium with an accompanying release of cardiac proteins, most notably natriuretic peptides. 98–100 Although circulating natriuretic peptide levels tend to be more influenced by left-sided cardiac disease, ventricular interdependence results in elevations of these markers in the setting of right heart failure. Natriuretic peptide levels have been shown to be predictors of outcomes in primary PH, 101 , 102 and a reduction in septal shift may improve left heart function and reduce pulmonary congestion.…”