The combination of PICP blood levels and LGE at CMR provides additional prognostic information in idiopathic Dilated Cardiomyopathy

AIMS To determine the prognostic value of multilevel assessment of fibrosis in DCM patients. METHODS AND RESULTS We quantified fibrosis in 209 DCM patients at three levels: i. non-invasive late-gadolinium enhancement (LGE) at cardiovascular magnetic resonance (CMR); ii. blood biomarkers (amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)), iii. Invasive endomyocardial biopsy (EMB, collagen volume fraction (CVF)). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization or life-threatening arrhythmias, after adjusting for known clinical predictors (adjusted hazard ratios (HR): LGE 3.54, 95%CI 1.90-6.60; P < 0.001 and PICP 1.02; 95%CI 1.01-1.03; P = 0.001). The combination of LGE and PICP provides the highest prognostic benefit in prediction (Likelihood Ratio test p = 0.007) and reclassification (NRI: 0.28,p = 0.02; and IDI: 0.139,p = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (Log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated to distinct cardiac transcriptomic profiles. CONCLUSION The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM-patients with LGE and elevated PICP.