Why the study?
Arrhythmogenic cardiomyopathy features gradual fibro-fatty myocardial replacement, but visualizing diffuse and patchy fibrosis patterns remains challenging with standard cardiac imaging modalities.
Are circulating biomarkers of fibrosis (PICP and ICTP) elevated in diagnosed arrhythmogenic cardiomyopathy patients compared to preclinical variant carriers, and do they correlate with ventricular function?
Observational (n=45)
Are circulating biomarkers of fibrosis (PICP and ICTP) elevated in diagnosed arrhythmogenic cardiomyopathy patients compared to preclinical variant carriers, and do they correlate with ventricular function?
Circulating biomarkers of collagen synthesis (PICP) and the PICP/ICTP ratio are elevated in diagnosed arrhythmogenic cardiomyopathy and correlate with ventricular dysfunction, suggesting potential utility as biomarkers for pro-fibrotic remodeling.
Supports PICP/ICTP as fibrosis markers in diagnosed ACM; hypothesis-generating for monitoring, pending prospective validation.
Arrhythmogenic cardiomyopathy (ACM) is a progressive inheritable disease which is characterized by a gradual fibro-(fatty) replacement of the myocardium. Visualization of diffuse and patchy fibrosis patterns is challenging using clinically applied cardiac imaging modalities (e.g., late gadolinium enhancement, LGE). During collagen synthesis and breakdown, carboxy–peptides are released into the bloodstream, specifically procollagen type-I carboxy-terminal propeptides (PICP) and collagen type-I carboxy-terminal telopeptides (ICTP). We collected the serum and EDTA blood samples and clinical data of 45 ACM patients (age 50.11 ± 15.53 years, 44% female), divided into 35 diagnosed ACM patients with a 2010 ARVC Task Force Criteria score (TFC) ≥ 4, and 10 preclinical variant carriers with a TFC < 4. PICP levels were measured using an enzyme-linked immune sorbent assay and ICTP levels with a radio immunoassay. Increased PICP/ICTP ratios suggest a higher collagen deposition. We found significantly higher PICP and PICP/ICTP levels in diagnosed patients compared to preclinical variant carriers (p < 0.036 and p < 0.027). A moderate negative correlation existed between right ventricular ejection fractions (RVEF) and the PICP/ICTP ratio (r = −0.46, p = 0.06). In addition, significant correlations with left ventricular function (LVEF r = −0.53, p = 0.03 and end-systolic volume r = 0.63, p = 0.02) were found. These findings indicate impaired contractile performance due to pro-fibrotic remodeling. Follow-up studies including a larger number of patients should be performed to substantiate our findings and the validity of those levels as potential promising biomarkers in ACM.
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Voorn et al. (2023) conducted an observational in Arrhythmogenic cardiomyopathy (n=45). PICP and ICTP biomarker assessment vs. Preclinical variant carriers was evaluated on PICP and PICP/ICTP levels (p=<0.036 and <0.027).
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