Chromosome 4q25 variants and biomarkers of myocardial fibrosis in patients with atrial fibrillation

Abstract

Introduction Little is known about how genetic predisposition and fibrosis relate in atrial fibrillation (AF). Hence, we sought to determine whether the genetic variants and biomarkers for fibrosis enhance prediction of outcomes after catheter ablation. Methods and Results Consecutive patients who underwent catheter ablation of AF (paroxysmal, 158; nonparoxysmal, 137) or supraventricular tachycardia without AF (n = 70) were studied retrospectively. Plasma levels of transforming growth factor beta 1 (TGF-beta 1), tissue inhibitor of metalloproteinase 1 (TIMP-1), and 4q25 single-nucleotide polymorphisms (SNPs) (rs10033464 and rs220073) were measured. Mean plasma levels of both TGF-beta 1 and TIMP-1 were higher in patients with AF than in the control (all P < .001). Plasma levels of TIMP-1 were higher in patients with recurrence compared with those without recurrence (P = .039). Patients with variant alleles of rs10033464 showed increased recurrence after catheter ablation in patients with paroxysmal AF including after adjustment (P = .027). Patients with TIMP-1 < 107 ng/mL and no variant allele (GG) at rs10033464 had lower recurrence rates compared with other groups in those with paroxysmal AF (logrank; P = .007), whereas there was no significant difference among those patients with persistent forms of AF. Inclusion of biomarkers and genotype improved discrimination of AF recurrence in patients with paroxysmal AF (C-statistic .499 vs .600). Conclusions The combination of plasma TIMP-1 concentrations less than 107 ng/mL and the absence of a variant allele at rs10033464 was associated with lower recurrence rates in patients with paroxysmal AF. This study suggests that 4q25 SNPs and biomarkers for fibrosis may provide additive value in risk stratification for AF recurrence after catheter ablation.