Background/Purpose:   Pulmonary hypertension (PH) is the most  frequent cause of death in Systemic Sclerosis (SSc).   It is critical to identify patients  early  to begin treatment before onset of irreversible heart failure.    The PHAROS registry is a prospective observational longitudinal cohort study to better understand the natural history of this problem. This analysis looks at outcomes of patients at high risk for developing PH, the Pre PAH group.  

Methods:  Pre-PAH is defined by one of the following entry criteria: echocardiogram systolic pulmonary arterial pressure (sPAP) of ≥40mmHg, or DLCO<55% predicted or  FVC%/DLCO% ratio >1.6.  PFTs, 6 minute walk test (6MW), and sPAP were performed yearly.  If PH was clinically suspected, a right heart catheterization was performed. A mean pulmonary artery pressure (MPAP) ≥25 mmHg on right-heart catheterization (RHC) was required for the diagnosis of PH.  Descriptive statistics, changes in baseline studies, such as PFTs and 6MWT, at the time of diagnosis of PH, Kaplan-Meier estimate of the time to PH diagnosis and survival of the Pre PAH group were studied.     

Results:  253 patients were enrolled in the Pre-PAH group: 35 developed PH at follow-up (New PH),  21 PAH (Group 1), 11 pulmonary venous hypertension (WHO Group 2) and 3 PH secondary to interstitial fibrosis (WHO Group 3).  By 4 years, PH developed   in 24% of these high risk patients .  There was no difference in the age, sex, disease duration or SSc subgroup in patients with New PH and those with no PH. All patients had long disease duration (mean 11.7 years of Raynaud’s) and 64% had limited  SSc.  The baseline DLCO was low in both groups (46.66 in New PH group vs 51.3 in the no-PH group) but there was not a further significant decrease in those who had a repeat DLCO at the time of diagnosis of PH.    there was no difference in 6MW distance at baseline, but patients with New PH had a significant decrease in the mean 6MW distance of 60.27 meters at the time of the diagnosis of PH, compared to the no PH group  (-13m) (p<0.01)   Those that  progressed to PH also exhibited significant oxygen desaturation during 6MW ( saturation < 92%) both at baseline and at time of diagnosis of PH which was not experienced by the no PAH group (p<0.01).  There were 22 deaths in the pre PAH group:  3 year survival was 92%. Three of the 35 New PH patients died of PH, 6 pre-PAH died of interstitial lung disease , 6 had multisystem SSc deaths, and 7 others were either non SSc or unknown.  Patients who died had   lower DLCO at baseline than those who were still living, 35% vs 51% (p<0.01)  

Conclusion:    We show that 24% of the prePAH  SSc patients developed PH by 4 years.  In addition to the known high risk features of long standing limited scleroderma and a low DLCO, patients   had a decreasing 6MW distance and significant 02 desaturation prior to the diagnosis of PH by RHC.   Overall, 3 year survival of these patients at 92% was fair, but  deaths in these high risk patients  were  associated with a very low DLCO.   Our study shows the usefulness of the serial 6MW distance and exercise induced hypoxia to determine patients that may progress to PH.     We hope that early identification and treatment of SSc -PH will significantly alter the long-term outcome of these patients.  

thanks to Peilin Cui for statistical analysis