Background: Pulmonary arterial hypertension (PAH) is an interdisciplinary challenge. Although right ventricular (RV) dysfunction is a major determinant of outcome in PAH, echocardiographic measures of RV function are poorly represented by current risk models, proposed by the 2015 ESC/ERS guideline on pulmonary hypertension. 

Objective: The objective of this study was to identify echocardiographic variables of right heart dysfunction, which are associated with adverse outcome and to develop a non-invasive, echocardiography-based risk score for PAH patients. 

Methods: We analyzed clinical and echocardiographic data and related them to organ failure (death or lung transplantation) in 243 patients with PAH. Measurements included vital parameters and NT-proBNP concentrations. Echocardiographic variables comprised RV chamber diameters, right atrial area, fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), 2D RV strain, measured by speckle tracking, and pericardial effusion. We used univariable and multivariable Cox regression analysis to predict complete lung failure (all-cause mortality or lung transplantation) based on clinical and echocardiographic parameters. Each predictor of the final model was assigned to a point score indicating the strength of association with the primary outcome. This score allows to estimate the individual risk of all-cause mortality or lung transplantation within 5 years.

Results: Median age was 65 years, 66.7% were males and median NT-proBNP concentration was 1,545 pg/ml. During a median follow-up time of 4.2 years 75 patients died (n=64) or underwent lung transplantation (n=11). In univariable analysis NT-proBNP (Hazard ratio [HR] 1.00 [95% Confidence Interval [CI] 1.00-1.00], p-value 0.0047), systolic blood pressure (HR 0.98 [CI 0.97-0.99], p-value 0.0037), FAC (HR 0.97 [CI 0.95-1.00], p-value 0.048), RV medial diameter (HR 1.03 [CI 1.00-1.06], p-value 0.043) and TAPSE (HR 0.89 [CI 0.84-0.94], p-value <0.001) were associated with the primary outcome. In the multivariable Cox regression model, TAPSE (HR 0.90 [CI 0.84-0.96], p-value 0.002) remained a significant predictor. The final model resulted in a C-index of 0.672. The assigned point score allowed to estimate the risk of the primary outcome within 5 years (Figure 1).

Conclusion: A clinical easily applicable point based score integrating non-invasive parameters of right heart function and morphology improves prediction of organ failure in patients with pulmonary hypertension.

Figure 1: Risk prediction chart