Atrial Fibrillation and Biomarkers of Myocardial Fibrosis

Study Questions:

Are biomarkers of myocardial interstitial fibrosis (collagen type-I crosslinking [CCL+] and deposition [CD+]) associated with prevalent, incident, and recurrent atrial fibrillation (AF)?

Methods:

Serum levels of carboxy-terminal telopeptide of collagen type I (CITP), matrix metalloproteinse-1 (MMP-1), and carboxy-terminal propeptide of procollagen type I (PICP) were measured in two separate cohorts. CCL+ was defined as a CITP:MMP-1 ratio above 1.968. CD+ was defined as PICP >110.8 ng/ml. The first (study 1) consisted of 242 patients with chronic heart failure (HF) and at least one hospitalization for HF, and the outcome examined was incident AF. The second (study 2) included 150 patients who underwent ablation for AF, and the outcome examined was time to AF recurrence. Patients in both studies were classified in three groups: CCL-CD-, CCL-CD+ and CCL+CD- combined, and lastly CCL+CD+. The authors performed survival analyses comparing the time to the specified outcomes in each study between these groups.

Results:

Overall, approximately 30% of patients in both studies were CCL+CD+, 40% were either CCL-CD+ or CCL+CD-, and 30% were CCL-CD-. In study 1, 43 (62%) of the CLL+CD+ patients had AF, compared with 17 (35%) of CCL-CD- patients (reference group), and had threefold higher odds of AF in multivariable analyses. Amongst 112 patients without baseline AF, the CCL+CD+ were 3.6-fold more likely to develop AF compared with the CCL-CD- patients. In study 2, 29% of patients had recurrence of AF at 12 months. CCL+CD+ patients had a 3.8-fold increase in the risk of having AF recurrence post-ablation. Addition of CCL/CD biomarkers to a clinical model improved risk discrimination indices. Last, in a subset of 71 patients with high-density voltage mapping of the left atrium, those classified as CCL+CD+ exhibited lower mean voltage compared with the remaining patients.

Conclusions:

Markers of collagen type-I crosslinking and deposition are associated with prevalent and incident AF.

Perspective:

The study is interesting in that it examines various aspects of the association between circulating biomarkers of myocardial interstitial fibrosis and AF. While it reinforces the concept that myocardial interstitial fibrosis is a driver of AF, the clinical implications are unclear. The sample sizes and number of events were small, decreasing the robustness of the findings, as evidenced by the wide confidence intervals in the analyses. The study is at best hypothesis generating. We are still quite far from considering such markers useful in the management of AF.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: Arrhythmias, Cardiac, Atrial Fibrillation, Biological Markers, Catheter Ablation, Collagen Type I, Fibrosis, Heart Atria, Heart Failure, Matrix Metalloproteinase 1, Recurrence, Risk, Secondary Prevention


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