The combination of PICP blood levels and LGE at CMR provides additional prognostic information in idiopathic Dilated Cardiomyopathy
Anne G Raafs, Job A J Verdonschot, Michiel T H M Henkens, Bouke P Adriaans, Ping Wang, Kasper Derks, Myrurgia A Abdul Hamid, Christian Knackstedt, Vanessa P M van Empel, Javier Díez, Hans-Peter Brunner-La Rocca, Han G Brunner, Arantxa González, Sebastiaan C A M Bekkers, Stephane R B Heymans, Mark R Hazebroek
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.
CITATION Eur J Heart Fail. 2021 Apr 30. doi: 10.1002/ejhf.2201. Online ahead of print.