Right Atrial Conduit Phase Emptying Predicts Risk of Adverse Events in Pediatric Pulmonary Arterial Hypertension

Background: Idiopathic pulmonary arterial hypertension (PAH) is a severe disease associated with a 20% 5-year mortality, often due to right heart failure. Recent studies suggest that compensatory changes in right atrial (RA) function may precede other clinical and echocardiographic evidence of right ventricular dysfunction. No prior prospective study has evaluated the role of RA emptying pattern as a prognostic marker of adverse clinical events in pediatric PAH. Objective: To demonstrate whether RA fractional emptying indices will prospectively predict risk of adverse clinical outcomes in pediatric PAH patients. Methods: Single-center, prospective cohort analysis of 41 patients with idiopathic or heritable PAH and 1:1 age and sex-matched controls with normal echo and electrocardiogram. Right atrial area (RAA) was measured just prior to tricuspid valve opening (RAAmax), at electrical p wave (RAAp), and just after tricuspid valve closing (RAAmin). Right atrial conduit fraction percent (RA cF%) was defined as the percentage of total RAA change happening prior to the electrical p wave = (RAAmax - RAAp)/(RAAmax - RAAmin) * 100. Clinical worsening was analyzed with a predefined composite adverse event outcome. Results: RA measurements were technically feasible in all study participants. The PAH patients (median age 11.9 years) had decreased RA cF% compared with controls (P <.0001), and PAH subjects with lower RA cF% demonstrated higher right ventricular systolic (R = -0.49, P =.019) and end-diastolic (R = -0.52, P =.012) pressure than those with higher RA cF%. Sixteen subjects had a clinical event. Right atrial cF% (hazard ratio = 0.09; P <.001) was highly prognostic for risk of adverse clinical event with area under the curve = 0.90 on receiver operating characteristic curve analysis (median 3.2-year follow-up). Conclusions: Right atrial conduit phase emptying is significantly altered in pediatric PAH. Within the PAH population, decreased RA cF% was prognostic for risk of clinical worsening. The combination of accuracy and ease of measurement could make RA cF% a clinically useful, noninvasive biomarker of early right heart failure and risk of disease progression in pediatric PAH.