Abstract
Background
Patients with systemic sclerosis (SSc) are at risk of developing pulmonary arterial hypertension (PAH), which is often diagnosed late when the benefits of vasoactive therapies are limited. The concept of exercise pulmonary hypertension as a possible transitional phase anticipating resting PAH has been assessed in several pathologies, but has not been endorsed by the latest European Guidelines, because not supported by sufficient data.
Purpose
To evaluate whether PASP values at rest and at peak exercise, estimated at echocardiography, could be predictors of further development of PAH.
Methods
Four hundred and twenty-nine SSc patients without a previous diagnosis of PAH, enrolled at 4 referral Centres, underwent standard exercise Doppler echocardiography with PASP estimation at rest and at peak stress. Patients were then followed-up to assess the development of PAH, as diagnosed by a complete diagnostic work-up including right heart catheterization. PAH was defined by pre-capillary pulmonary hypertension (mean pulmonary artery pressure ≥25 mmHg with pulmonary arterial wedge pressure ≤15 mmHg), without significant interstitial lung disease and/or left heart disease.
Results
During the median follow-up of 75 months (IQR 29–114), 16 patients developed PAH. A combined cut-off of ≥24 mmHg as resting PASP and ≥40 as peak PASP was identified as the best predictor of further development of PAH (see Figure). Both resting PASP and peak PASP were predictors of PAH at univariate analysis (resting PASP OR 1.13, 95% C.I. 1.07–1.19, p<0.0001; peak PASP OR 1.13, 95% C.I. 1.07–1.18, p<0.0001). At multivariate analysis, only peak PASP was independently associated to PAH development (OR 1.13, 95% C.I. 1.04–1.18, p<0.001). Only one patient among those with resting PASP <24 mmHg and peak PASP <40 mmHg (34.7% of the total population) developed PAH during the follow-up (after 10 years from normal exercise Doppler echocardiography).
Kaplan-Meier curves
Conclusions
Exercise increase in PASP is an independent predictor of later development of PAH in SSc. An increase in exercise PASP is frequent and is not necessarily associated with a later development of PAH, whereas the very high negative predictive value of a normal PASP both at rest and at peak exercise can be used in the clinical practice to confidently rule out about one third of patients.
Acknowledgement/Funding
Italian Ministry of Health (Ricerca Finalizzata 2011-2012)
Improvements in French Risk Stratification Score were Correlated with Reductions in Mean Pulmonary Artery Pressure in Pulmonary Arterial Hypertension: A Subanalysis of the Japan Pulmonary Hypertension Registry (JAPHR)
