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Journal of the American College of Cardiology

Clinical Articles, News & Views

Atrial fibrillation therapy modulated by single nucleotide polymorphism

A common single nucleotide polymorphism (SNP) associated with atrial fibrillation (AF) could modulate response to antiarrhythmic drug (AAD) therapy, supporting the stratification of therapeutic approaches by genotype, according to a study published recently in the Journal of the American College of Cardiology.1

Recent genome-wide association studies have identified three loci, on chromosomes 4q25 (near PITX2), 16q22 (in ZFHX3), and 1q21 (in KCNN3), that associate with either typical or lone AF, the authors say. They suggest that variable mechanisms contribute to AF susceptibility, and that response to therapy may be genotype dependent

Researchers from Vanderbilt University Medical Center (Nashville, Tennessee) studied 478 and 198 Caucasian patients in the discovery cohort and validation cohort, respectively, who were prospectively enrolled in the Vanderbilt AF registry. Response was defined prospectively as successful rhythm control if the patient remained on the same AAD therapy for a minimum of six months with ≥75% reduction in symptomatic AF burden. They also evaluated AF recurrence by 12-lead electrocardiogram (ECG) at three, six, and 12 months. Symptomatic patients were given a 24- to 48-h Holter monitor or 30-day event recorder when AF recurrence was not captured by 12-lead ECG.

In the discovery cohort, 399 (83%) patients were successfully rhythm controlled. Multiple clinical variables (including age, hypertension, lone AF) failed to significantly predict response to AADs; however, single nucleotide polymorphism (SNP) rs10033464 at 4q25 was an independent predictor of successful rhythm control in patients with typical AF, carrying the ancestral allele versus carriers of variant.

In the validation cohort, 143 (72%) patients met the criteria for successful rhythm control, and rs10033464 was again an independent predictor of successful rhythm control. This SNP (rs10033464) was an independent predictor of AF recurrence in the discovery (39% AF recurrence) and validation (38% AF recurrence) cohorts respectively.

In an accompanying editorial2 authors from Duke University Medical Center, Durham, North Carolina, said: “Although this innovative study associating the SNP rs10033464 with AAD response breaks new ground, it should be considered hypothesis generating until confirmed by a randomized, double-blinded trial. We share the authors’ optimism that the genomic revolution will yield opportunities to inform and tailor treatment, but this study raises several questions”.

“Parvez et al. are to be commended for extending the epidemiological associations between several SNPs and AF to an exploration of potential therapeutic ramifications. Lacking patient-specific predictors for efficacy, current AF drug selection considers only comorbidities in an effort to merely minimize proarrhythmia. Pharmacogenetic insights could theoretically help predict efficacy and toxicity. Although we are closer to the beginning than to everyday use in the clinic, Parvez et al. have started us on an exciting journey.”


1. Parvez B, Vaglio J, Rowan S, et al. Symptomatic Response to Antiarrhythmic Drug Therapy Is Modulated by a Common Single Nucleotide Polymorphism in Atrial Fibrillation. JACC 2012.

2. Daubert JP, Pitt GS. Can Polymorphisms Predict Response to Antiarrhythmic Drugs in Atrial Fibrillation? JACC 2012.

Published on: July 24, 2012

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  • ArrhythmiaAlliance
  • Stars
  • Anticoagulation Europe
  • Atrial Fibrillation Association

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