Background/Purpose: Pulmonary arterial hypertension (PAH) is a crucial organ involvement affecting survival of patients with connective tissue disease (CTDs), such as systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD).  Although some powerful PAH-specific drugs improve the survival of patients with idiopathic PAH, the prognosis of patients with PAH associated with SSc remains still poor.  To explore the characteristics relevant to the poor survival of patients with PAH associated with SSc under treatment with PAH-specific drugs, we performed exploratory data analysis using echocardiogram (ECHO) in patients with PAH associated with CTDs. 

Methods: We analyzed 1002 ECHO reports from 54 patients with PAH associated with CTDs, including 22 patients with SSc, and 33 patients with CTDs other than SSc (SLE:12, MCTD:16 and other CTDs: 5), who had been diagnosed as PAH based on right heart catheterization test and treated with PAH-specific drugs between April 2005 and March 2013 in our hospital.  We selected systolic pulmonary arterial pressure (PAP), cardiac output (CO), and right atrial (RA) and left atrial (LA) areas which were traced at end-diastolic time on 4 chamber view as parameters.  Comparison of these parameters between patients with PAH associated with SSc (PAH-SSc(+)) and patients with PAH associated with other CTDs (PAH-SSc(-)) was carried out using mixed effects model in which we set presence or absence of SSc, WHO-functional class (WHO-FC), and age at ECHO performed as fixed effects, and patient as a random effect.  We also compared the serum levels of brain natriuretic peptide (BNP) between patients with PAH-SSc(+) and patients with PAH-SSc(-) with the same strategy.  Representative value estimated by our model was displayed as mean (95% confidence interval) value adjusted for WHO-FC and age.  

Results: PAH-specific drugs used for treatment of the patients, including bosentan, ambrisentan, sildenafil, tadalafil, epoprostenol, and beraprost (an oral prostacyclin analog that is only available in Japan).  Mean of age and WHO-FC, which were substituted into our model to estimate the adjusted values, were 52.2 and 2, respectively.  As shown in Table, systolic PAP was higher and RA area size was smaller in patients with PAH-SSc than in patients with PAH-SSc(-).  By contrast, LA area size was significantly greater in patients with PAH-SSc(+) than in patients with PAH-SSc(-).  Finally, serum level of BNP was higher in patients with PAH-SSc(+) than in patients with PAH-SSc(-) (log[BNP]: 1.906 (1.880 – 1.931), 1.839 (1.817 – 1.861),respectively, p=0.0002, n=2781).  

Conclusion: The results demonstrate that greater LA area size and higher levels of BNP, indicating left ventricular diastolic dysfunction, coexists with PAH associated with SSc.  Thus, the data emphasize the usefulness LA area size as well as RA area size for the appropriate management of patients with PAH-SSc using PAH-specific drugs.