＜Editors' Choice＞ Differential effects of combination therapy on the components of the risk stratification table in patients with idiopathic or heritable pulmonary arterial hypertension in a Japanese population

Abstract

Risk stratification by ESC/ERS guideline is recommended to estimate the vital prognosis and select the treatment strategy in patients with idiopathic or heritable pulmonary arterial hypertension (IPAH/HPAH). However, we are not confident whether we can achieve low-risk status in the risk table at the follow-up shortly after combination therapy. Therefore, we aimed to verify the effects of combination therapy in IPAH/HPAH on each category of the risk table at diagnosis and at the first follow-up. We retrospectively analyzed 10 consecutive patients with IPAH/HPAH with no previous treatment history diagnosed at Nagoya University Hospital between October 2014 and January 2019. Four categories including symptoms, exercise tolerance, BNP levels and hemodynamics were validated both at baseline and at the first follow-up of right heart catheterization. Score of 1, 2 and 3 were assigned to the low risk, intermediate risk and high risk, respectively. In each category the highest score was adopted. The scores at diagnosis were compared with those at the first follow-up. The result shows that all patients were female, median age was 32 years old, and were treated with initial combination therapy. The median total risk score also was improved from 2.6 to 1.4 (p<0.01). However, the score in exercise tolerance was not improved (3 to 2.5 p=0.16). In conclusion, at the first follow up shortly after the initial combination therapy of IPAH/HPAH, the mean total risk score was significantly improved, however, even patients in the low-risk status may not achieve improvement in exercise tolerance.

Keywords: exercise tolerance; pulmonary arterial hypertension; risk score.

Fig. 1

Abridged risk assessment in pulmonary arterial hypertension The prognostic/predictive factors were classified into the following four categories based on the risk assessment table for pulmonary arterial hypertension (PAH) patients proposed in the 2015 European Society of Cardiology/Society European Respiratory (6,7). The prognostic/predictive factors were classified into the following four categories: (i) subjective symptoms such as signs of right heart failure, progression of symptoms, and functional classification by WHO; referred to as symptoms; (ii) exercise capacity indicated by either 6-min walk distance (6MWD) and/or cardiopulmonary exercise (CPX); referred to as exercise tolerance; (iii) B-type natriuretic peptide (BNP); referred to as a biomarker; and (iv) echocardiography and right heart catheterization referred to as hemodynamics. Low, moderate, and high risk of prognostic factors were scored as 1, 2, and 3, respectively. WHO: World Health Organization 6WMD: six-minute walk distance VO₂: oxygen uptake VE/VCO₂: ventilation/carbon dioxide output BNP: brain natriuretic peptide NT-proBNP: N-terminal pro-brain natriuretic peptide CMR: cardiovascular magnetic resonance RAP: right atrial pressure CI: cardiac index

Fig. 2

Changes in mean PAP, PVR and CI, between baseline and first follow-up PAP: pulmonary arterial pressure PVR: pulmonary vascular resistance CI: cardiac index

Fig. 3

Changes in total risk score average, between baseline and first follow-up

Fig. 4

Changes in risk score average of Symptoms (i), Exercise tolerance (ii), Biomarker (iii) and Hemodynamics (iv), between baseline and first follow-up

Fig. 5

Changes in risk score average of PeakVO₂, PeakVO₂ predict, VE/VCO₂ slope and 6WMD, between baseline and first follow-up VO₂: oxygen uptake VE/VCO₂: ventilation/carbon dioxide output 6WMD: six-minute walk distance