Genetics of atrial fibrillation-practical applications for clinical management: if not now, when and how?
Shinwan KanyBruno ReissmannAndreas MetznerPaulus F KirchhofDawood DarbarRenate B SchnabelPublished in: Cardiovascular research (2022)
The prevalence and economic burden of atrial fibrillation (AF) are predicted to more than double over the next few decades. In addition to anticoagulation and treatment of concomitant cardiovascular conditions, early and standardized rhythm control therapy reduces cardiovascular outcomes as compared with a rate control approach, favouring the restoration, and maintenance of sinus rhythm safely. Current therapies for rhythm control of AF include antiarrhythmic drugs (AADs) and catheter ablation (CA). However, response in an individual patient is highly variable with some remaining free of AF for long periods on antiarrhythmic therapy, while others require repeat AF ablation within weeks. The limited success of rhythm control therapy for AF is in part related to incomplete understanding of the pathophysiological mechanisms and our inability to predict responses in individual patients. Thus, a major knowledge gap is predicting which patients with AF are likely to respond to rhythm control approach. Over the last decade, tremendous progress has been made in defining the genetic architecture of AF with the identification of rare mutations in cardiac ion channels, signalling molecules, and myocardial structural proteins associated with familial (early-onset) AF. Conversely, genome-wide association studies have identified common variants at over 100 genetic loci and the development of polygenic risk scores has identified high-risk individuals. Although retrospective studies suggest that response to AADs and CA is modulated in part by common genetic variation, the development of a comprehensive clinical and genetic risk score may enable the translation of genetic data to the bedside care of AF patients. Given the economic impact of the AF epidemic, even small changes in therapeutic efficacy may lead to substantial improvements for patients and health care systems.
Keyphrases
- atrial fibrillation
- catheter ablation
- left atrial
- oral anticoagulants
- left atrial appendage
- direct oral anticoagulants
- early onset
- end stage renal disease
- healthcare
- heart failure
- ejection fraction
- newly diagnosed
- chronic kidney disease
- genome wide
- percutaneous coronary intervention
- blood pressure
- copy number
- prognostic factors
- stem cells
- late onset
- patient reported outcomes
- genome wide association
- heart rate
- case report
- peritoneal dialysis
- left ventricular
- chronic pain
- coronary artery disease
- cross sectional
- risk factors
- cell therapy
- quality improvement
- radiofrequency ablation
- protein kinase
- mesenchymal stem cells
- preterm birth
- deep learning
- acute coronary syndrome
- bone marrow