Abstract #1373: High Nt-pro Brain Natriuretic Peptide and Low Carbon Monoxide Lung Diffusion Capacity are Independent Predictors of the Occurrence of Pre-capillary Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis
Authors
Yannick Allanore1, Didier Borderie2, Jérôme Avouac1, Djamila Zerkak1, Christophe Meune3, Julien Wipff1, Eric Hachulla4, Luc Mouthon5, Loic Guillevin5, Olivier Meyer6, Ohvanesse Ekindjian2, André Kahan1.
Purpose
This study examined a prospective cohort of 103 patients with scleroderma followed for 36 months for the development of pulmonary arterial hypertension (PAH) (diagnosed by right heart catheterization (RHC)), progression of overall disease and death.
Methods
Subjects were excluded if they had pre-existing (PAH), heart failure, renal disease, digital ischemia or pregnancy. Their protocol includes performing a RHC if the echocardiogram reveals a RVSP >40, if there was a DLCO <50 without interstitial lung disease or the subject had unexplained dyspnea.
Results
Nineteen subjects had suspected PAH, 13 with elevated RVSP, 6 with unexplained dyspnea or abnormal DLCO. The median follow up on these subjects was 29 months. All 19 subjects underwent RHC and eight patients were diagnosed with PAH. Eight subjects had normal RHC and three had evidence of post-capillary pulmonary hypertension. The average mean PA pressure was 50 ± 14 mmHg. Five of the 8 subjects with PAH were women and the average disease duration at time of diagnosis of PAH was 17 months. 5/8 subjects died during the follow up period at a mean of 11 months from diagnosis of PAH. In univariate analysis, elevated pro-BNP levels and decrease in DLCO/AV (both <70% and <60%) were associated with development of PAH. The mean pro-BNP levels in PAH subjects was 413 vs.127 in remainder of the cohort. In multivariate analysis, both the pro-BNP and the DLCO/VA remained highly predictive of the development of PAH with hazard ratios of 9.97 (1.69-62.42) and 36.66 (3.45-387.6) respectively. When the combination of elevated pro-BNP and DLCO/VA <70% were combined this was very strongly predictive of PAH (HR 47.2, 95%CI 4/9-450.3).
Editorial Comment
Retrospective and cross-sectional studies have shown that patients with scleroderma-associated pulmonary hypertension have a decrease in DLCO and abnormal levels of pro-BNP. One retrospective study showed that the DLCO drops years before the diagnosis of PAH. This is the first study to examine the predictive value of these 2 values in a prospective cohort of patients with scleroderma. As may be expected, abnormalities in pro-BNP and DLCO/VA are strongly predictive of the development of PAH. There were no details in this study about when the abnormal values were found in relation to the diagnosis of PAH. The other question that arises is could this group have actually had pre-existing PAH that was not detected. They did not state that patients had to have a normal echocardiogram to enter. These prospective studies, however, do provide some additional evidence to suggest that there may be an ongoing vascular insult, prior to recognizable clinical events.
