Prognostic relevance of the right ventricular fractional area change to pulmonary artery systolic pressure ratio in pulmonary arterial hypertension: Insights from the FOCUS-PAH registry

Background: In pulmonary arterial hypertension (PAH), echocardiographic ventriculoarterial coupling is traditionally assessed with the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). We aimed to validate the prognostic significance of the fractional area change (FAC)/PASP ratio in PAH. Methods: This study included patients diagnosed with PAH between April 2001 and November 2023 enrolled in the multicentre FOCUS-PAH registry. Only patients with both FAC and PASP data available at PAH diagnosis were considered. The primary outcome of the study was to assess the predictive value of FAC/PASP for 1-year and 5-year all-cause mortality. Results: 347 patients were included. Mean age at PAH diagnosis was 56 ± 17 years; 144 (41.5%) patients were males. The median FAC/PASP ratio at diagnosis was 0.34%/mmHg [IQR 0.25 to 0.52%/mmHg]). 23 (6.6%) patients died during the first year of follow-up and 84 (24.2%) patients died within 5 years. At univariable Cox regression analyses, both low baseline FAC/PASP (i.e., lower than 0.37%/mmHg) and low TAPSE/PASP (i.e., lower than 0.18 mm/mmHg) significantly predicted 1-year all-cause mortality (HR 3.05 [95%CI 1.13–8.22], p-value 0.027, and HR 2.61 [95%CI 1.12–6.10], p-value 0.027, respectively); conversely, low FAC/PASP was associated with significantly higher all-cause mortality at 5 years (HR 1.69 [95%CI 1.08–2.65], p-value 0.023), whereas low TAPSE/PASP ratio was not (HR 1.21 [95%CI 0.77–1.91], p-value 0.405). In a clinical multivariable Cox regression model adjusting for age and World Health Organization functional class, a low FAC/PASP ratio was independently associated with a significantly increased risk of all-cause mortality, both at 1 year (HR 3.00 [95%CI 1.09–8.28], p-value = 0.034) and at 5 years (HR 1.72 [95%CI 1.09–2.72], p-value = 0.021). Conclusions: In this multicentre, observational registry on patients with incident PAH, low baseline FAC/PASP was associated with significantly higher 1-year and 5-year all-cause mortality.