Fibroblast activities are associated with prolonged QTc and pulmonary arterial hypertension in patients with systemic sclerosis.

Objective: In systemic sclerosis patients (SSc), we aimed at exploring the potential of serum biomarkers of fibrosis and immune-cell activity to detect subclinical heart involvement determined by electrocardiographic (ECG) alterations.

Methods: A panel of extracellular matrix (ECM) turnover biomarkers quantifying type III and VI collagen formation (PRO-C3 and PRO-C6), type IV collagen turnover (PRO-C4), MMP-degraded type III, IV, VI and VII collagen (C3M, C4M, C6M and C7M), human neutrophil elastase degraded elastin and calprotectin (ELA-HNE and CPa9-HNE), MMP-degraded C-reactive protein (CRPM), MMP-degraded and citrullinated vimentin (VICM) were measured by competitive ELISAs in serum from 102 well-characterised systemic sclerosis patients. Correlations to ECG-changes as well as clinical and paraclinical manifestations were explored.

Results: PRO-C3 and PRO-C6, biomarkers of fibroblast activation, were significantly increased in patients with prolonged QTc (>450ms) (p=0.043 and p=0.027, respectively), while no difference was detected for PRO-C4, C3M, C4M, C6M, and C7M. The ELA-HNE biomarker was significantly reduced in patients with prolonged QTc (>450ms). No difference was found for the CPa9-HNE, CRPM, VICM, and C4G. The PRO-C3 and PRO-C6 biomarkers were also significantly increased in the patients with pulmonal arterial hypertension (PAH) (p=0.041 and p=0.019, respectively), and increased with NYHA class (p=0.024 and p=0.045, respectively). In addition, C6M were significantly increased with NYHA class (p=0.021).

Conclusions: Patients with SSc and prolonged QTc, presence of PAH and high NYHA class presented an altered tissue turnover, particularly associated with increased fibroblast activation. Our study indicates that serum-based biomarkers could serve as convenient biomarkers of subtle cardiac disease in SSc but further studies are needed to confirm this.