Combination of Circulating Type I Collagen-Related Biomarkers Is Associated With Atrial Fibrillation

A combination of circulating biomarkers associated with excessive myocardial collagen type-I cross-linking or CCL+ (i.e., decreased carboxy-terminal telopeptide of collagen type-I to matrix metalloproteinase-1 ratio) and with excessive myocardial collagen type-I deposition or CD+ (i.e., increased carboxy-terminal propeptide of procollagen type-I) has been described in heart failure (HF) patients and associates with poor outcomes.

The purpose of this study was to investigate whether the CCL+CD+ combination of biomarkers associates with atrial fibrillation (AF).

Biomarkers were analyzed in serum samples from 242 HF patients (study 1) and 150 patients referred for AF ablation (study 2). Patients were classified into 3 groups (CCL-CD-, CCL+CD- or CCL-CD+, and CCL+CD+) in accordance to biomarker threshold values. Left atrial electroanatomic high-density mapping was performed in 71 patients from study 2.

In study 1, 53.7% patients had AF at baseline and 19.6% developed AF (median follow-up 5.5 years). Adjusted odds and hazard ratios associated with baseline and new-onset AF, respectively, were both ≥3.3 (p ≤ 0.050) in CCL+CD+ patients compared with CCL-CD- patients, with nonsignificant changes in the other group. In study 2, 29.3% patients had AF recurrence during 1-year post-ablation. The adjusted hazard ratio for AF recurrence was 3.4 (p = 0.008) in CCL+CD+ patients compared with CCL-CD- patients, with nonsignificant changes in the other group. The CCL+CD+ combination added incremental predictive value over relevant covariables. CCL+CD+ patients exhibited lower left atrial voltage than the remaining patients (p = 0.005).

A combination of circulating biomarkers reflecting excessive myocardial collagen type-I cross-linking and deposition is associated with higher AF prevalence, incidence, and recurrence after ablation.