Genotype influence in responses to therapy for atrial fibrillation

ABSTRACT

Introduction: Over the last decade, tremendous progress has been made in defining the genetic architecture of atrial fibrillation (AF). This has in part been driven by poor understanding of the pathophysiology of AF, limitations of current therapies and failure to target therapies to the underlying mechanisms.

Areas covered: Genetic approaches to AF have identified mutations encoding cardiac ion channels, and signaling proteins linked with AF and genome-wide association studies have uncovered common genetic variants modulating AF risk. These studies have provided important insights into the underlying mechanisms of AF and defined responses to therapies. Common AF-risk alleles at the chromosome 4q25 locus modulate response to antiarrhythmic drugs, electrical cardioversion and catheter ablation. While the translation of these discoveries to the bedside care of individual patients has been limited, emerging evidence supports the hypothesis that genotype-directed approaches that target the underlying mechanisms of AF may not only improve therapeutic efficacy but also minimize adverse effects.

Expert commentary: There is an urgent need for randomized controlled trials that are genotype-based for the treatment of AF. Nonetheless, emerging data suggest that selecting therapies for AF that are genotype-directed may soon be upon us.

KEYWORDS:

• Atrial fibrillation
• genetics
• pharmacogenomics
• ablation
• genotype

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This work was in part supported by National Institutes of Health grants R01 HL092217 and R01 HL124935.