CA125 Predicts Right Heart Hemodynamic and Function and Identifies Distinct Congestion Phenotypes: Guidance for Therapy

Abstract

<h3>Purpose</h3> Elevated carbohydrate antigen 125 (CA125) correlates with serosal effusions and has previously been thought to be associated with the clinical severity of heart failure (HF) and fluid congestion. We assessed CA125 as a predictor of hemodynamics and investigated the additive prognostic benefit of B-type natriuretic peptide (BNP). <h3>Methods</h3> Between 2015-2019, 235 patients hospitalized for HF were prospectively assessed for CA125 and BNP serum levels simultaneously with echocardiography and right heart study. <h3>Results</h3> CA125 correlated positively with intracardiac pressures and inversely with cardiac index (CI). The strongest correlation was for right atrial pressure (RAP) (ρ = 0.82, p<0.001). CA125 >42 U/mL had a sensitivity of 95.8% and specificity of 95.3% for the prediction of RAP ≥11 mmHg. The predictive accuracy of CA125 vs BNP was superior for RAP (AUC 0.99 vs 0.84, p<0.001) and right ventricular (RV) pressure (AUC 0.99 vs 0.82, p<0.001), but BNP was better for the prediction of pulmonary capillary wedge pressure (AUC 0.95 vs 0.82, p<0.001) and CI (AUC 0.92 vs 0.84, p=0.03). Elevated CA125 was independently associated with increased right heart pressures, while BNP with left-sided filling pressures and lower CI (p<0.05). Combining CA125 and BNP values delineated 4 distinct HF congestion phenotypes (Figure): high CA125-high BNP - reduced ejection fraction (HFrEF) with RV dysfunction; low CA125-high BNP - HFrEF with preserved RV function; and high CA125-low BNP and low CA125-low BNP - preserved EF, with and without RV dysfunction, respectively. <h3>Conclusion</h3> CA125 predicts and quantifies right heart function and hemodynamic. CA125-BNP congestion phenotypes can be used as a guidance for diagnosis (improved diagnosis of HFpEF and delineation of congestion status) and therapy (LVAD candidate selection and individualized drug therapies and titration).