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 β1 (TGF‐β1), tissue inhibitor of metalloproteinase 1 (TIMP‐1), and 4q25 single‐nucleotide polymorphisms (SNPs) (rs10033464 and rs220073) were measured. Mean plasma levels of both TGF‐β1 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.

High expression of long noncoding RNA plasmacytoma variant translocation 1 is an independent risk factor for recurrence after radiofrequency ablation in atrial fibrillation patients

“…A previous study suggested that the preoperative and postoperative value of HA in the blood is a useful new index for AF occurrence after coronary artery bypass grafting 29 . TGF‐β1 is associated with AF severity and prognosis after catheter ablation 30,31 . Regression analysis in previous studies consistently revealed that TGF‐β1 was a major risk factor for AF recurrence and may help identify patients likely to have better outcomes after catheter ablation 32,33 …”

“…29 TGF-β1 is associated with AF severity and prognosis after catheter ablation. 30,31 Regression analysis in previous studies consistently revealed that TGF-β1 was a major risk factor for AF recurrence and may help identify patients likely to have better outcomes after catheter ablation. 32,33 In summary, as a prospective study, this study measured the expression of lncRNA PVT1 in the plasma of AF patients for the first time and explored the role of PVT1 level in AF diagnosis and recurrence after RFA using the ROC curve.…”

Genetically Based Atrial Fibrillation: Current Considerations for Diagnosis and Management

“…100,104 This variability may be explained in part by variation in increased levels of circulating biomarkers of myocardial fibrosis in patients with paroxysmal AF. 105 Of note, there is emerging evidence that other SNPs at 4q25 may increase left atrial scar formation and increase nonpulmonary vein triggers for AF recurrence, which may help inform future risk stratification when selecting patients for catheter ablation. 106 However, prospective analyses of these and other SNPs are still needed.…”

Genetically based atrial fibrillation: Current considerations for diagnosis and management

“…There is some conflicting data in another European population the rs10033464 SNP was associated with AF recurrence postablation 92 and in meta‐analysis 103,105 . This variability may be explained in part by variation in increased levels of circulating biomarkers of myocardial fibrosis in patients with paroxysmal AF 106 . Of note, there is emerging evidence that other SNPs at 4q25 may increase LA scar formation and increase nonpulmonary vein triggers for AF recurrence, which may help inform future risk stratification when selecting patients for catheter ablation 107 .…”

“…103,105 This variability may be explained in part by variation in increased levels of circulating biomarkers of myocardial fibrosis in patients with paroxysmal AF. 106 Of note, there is emerging evidence that other SNPs at 4q25 may increase LA scar formation and increase nonpulmonary vein triggers for AF recurrence, which may help inform future risk stratification when selecting patients for catheter ablation. 107 However, prospective analyses of these and other SNPs are still needed.…”