Genetics of atrial fibrillation—practical applications for clinical management: if not now, when and how?

Abstract

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, favoring the restoration and maintenance of sinus rhythm safely. Current therapies for rhythm control of AF include anti-arrhythmic drugs (AAD) 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, signaling molecules and myocardial structural proteins associated with familial (early-onset) AF. Conversely, genome-wide association studies (GWAS) 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.

In-silico drug trials for precision medicine in atrial fibrillation: From ionic mechanisms to electrocardiogram-based predictions in structurally-healthy human atria

“…Methodologically, our study demonstrates the power of insilico drug trials conducted in human whole-atria models constructed based on hundreds of ionic current profiles, with perfect control over the parameters studied and high spatiotemporal resolution. Frontiers in Physiology frontiersin.org 13 4.1 Precision medicine for atrial fibrillation management: In-silico drug trials Currently, rhythm control therapy for AF follows a "onesize fits all" approach (Kany et al, 2021). However, the response of individual patients to rhythm control therapy is highly variable, and predicting its success is still a challenge (Kany et al, 2021).…”

“…Frontiers in Physiology frontiersin.org 13 4.1 Precision medicine for atrial fibrillation management: In-silico drug trials Currently, rhythm control therapy for AF follows a "onesize fits all" approach (Kany et al, 2021). However, the response of individual patients to rhythm control therapy is highly variable, and predicting its success is still a challenge (Kany et al, 2021). Previous studies have demonstrated that analyzing AF complexity through the ECG might help predicting flecainide cardioversion efficacy (Zeemering et al, 2018).…”

Cardiogenetics: the role of genetic testing for inherited arrhythmia syndromes and sudden death

“…It therefore appears possible that PRSs may play a diagnostic role in the future. Furthermore, the future approach of genetic evaluation in common arrhythmias such as AF is likely to be driven via PRSs with an initial focus on predicting the response to anti-arrhythmic drugs and catheter ablation 46…”

Impact of Genomics on the Future of Healthcare

“…Such programs are still seen as a commercial endeavor, but perhaps in the future, genetic testing programs could become government-led health checks for everyone. With the guidance and support of the government, genetic testing data can be collected to detect and avoid increased risk factors in susceptible populations, and to detect and control familial epidemics, such as atrial fibrillation (Kany et al, 2021). (Kany et al, 2021) This will also help health authorities formulate policies, coordinate medical resources, provide medical security, reduce the incidence of high-risk groups and prevent diseases.…”