The ratio of right ventricular fractional area change over pulmonary artery systolic pressure predicts prognosis in pulmonary arterial hypertension

Abstract 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). However, TAPSE may not accurately reflect global right ventricular (RV) function in initial stages of the disease and may lack sensitivity in advanced PAH. Conversely, echocardiographically-derived RV fractional area change (FAC) may better reflect global RV systolic function. Purpose We aimed to investigate FAC/PASP ratio as a novel prognostic marker in PAH. Methods All consecutive patients with incident PAH enrolled in the multicenter FOCUS-PAH registry between April 2001 and November 2023 were included. Only patients with both FAC and PASP data available at PAH diagnosis were considered. The study primary outcome was to assess FAC/PASP as a predictor of 1-year all-cause mortality 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. Median FAC/PASP at PAH diagnosis was 0.34%/mmHg IQR 0.25-0.52%/mmHg). 23 (6.6%) patients died during the first year of follow-up and 84 (24.2%) patients died within 5 years. As compared to 1-year survivors, patients who died at one year were significantly older (68±17 years vs 56±17 years, p-value 0.017) and more frequently male (65.2% vs 39.8%, p-value 0.017), and had higher prevalence of chronic kidney disease (34.8% vs 5.4%, p-value 0.016). At ROC curve analysis, the FAC/PASP value with the highest accuracy in predicting 1-year all-cause death was 0.37%/mmHg (sensitivity 48.1%, specificity 78.3%, AUC 0.650). Baseline FAC/PASP was low ( 0.37%/mmHg) in 18 (78.3%) of the 23 patients who died at one year and in 55 (65.5%) of the 84 patients who died at 5 years. At univariable Cox regression analyses, both low baseline FAC/PASP and low TAPSE/PASP ( 0.18 mm/mmHg) significantly predicted 1-year all-cause mortality (HR 3.050 95 CI 1.132-8.215, p-value 0.027, and HR 2.608 95%CI 1.115-6.101, p-value 0.027, respectively); conversely, low FAC/PASP was associated with significantly higher all-cause mortality at 5 years (HR 1.687 95%CI 1.076-2.645, p-value 0.027), whereas low TAPSE/PASP ratio was not (HR 1.213 95%CI 0.770-1.909, p-value 0.405). At the multivariable Cox regression models adjusted for age and WHO functional class, low FAC/PASP ratio predicted significantly higher 1-year and 5-year all-cause mortality (HR 3.000 95%CI 1.088-8.276, p-value 0.034, and HR 1.718 95%CI 1.085-2.722, p-value 0.021, respectively), whereas low TAPSE/PASP predicted significantly higher 1-year all-cause mortality (p-value 0.021) but not 5-year all-cause death (p-value 0.227). Conclusions In this multicenter, observational, prospective study on patients with incident PAH, low baseline FAC/PASP was associated with significantly higher mid-term and long-term all-cause mortality.Figure 1 Figure 2