How Will Genetics Inform the Clinical Care of Atrial Fibrillation?

Abstract

Susceptibility to atrial fibrillation (AF) is determined by well-recognized risk factors such as diabetes mellitus or hypertension, emerging risk factors such as sleep apnea or inflammation, and increasingly well-defined genetic variants. As discussed in detail in a companion article in this series, studies in families and in large populations have identified multiple genetic loci, specific genes, and specific variants increasing susceptibility to AF. Since it is becoming increasingly inexpensive to obtain genotype data and indeed whole genome sequence data, the question then becomes to define whether using emerging new genetics knowledge can improve care for patients both before and after development of AF. Examples of improvements in care could include identifying patients at increased risk for AF (and thus deploying increased surveillance or even low-risk preventive therapies should these be available), identifying patient subsets in whom specific therapies are likely to be effective or ineffective or in whom the driving biology could motivate the development of new mechanism-based therapies or identifying an underlying susceptibility to comorbid cardiovascular disease. While current guidelines for the care of patients with AF do not recommend routine genetic testing, this rapidly increasing knowledge base suggests that testing may now or soon have a place in the management of select patients. The opportunity is to generate, validate, and deploy clinical predictors (including family history) of AF risk, to assess the utility of incorporating genomic variants into those predictors, and to identify and validate interventions such as wearable or implantable device-based monitoring ultimately to intervene in patients with AF before they present with catastrophic complications like heart failure or stroke.

Early-Onset Atrial Fibrillation and the Prevalence of Rare Variants in Cardiomyopathy and Arrhythmia Genes

“…We previously proposed that it should be patients diagnosed before 45 years of age. However, our results demonstrate that the likelihood of a disease-associated variant is approximately the same (10%) in the 40- to 49- and 50- to 59-year age groups, with a decrease after 60 years of age. These data suggest that genetic testing for early-onset AF could be considered in patients diagnosed with AF up to 60 years of age, with a stronger recommendation for patients diagnosed before 30 years of age.…”

Clinical Care of Hyperthyroidism Using Wearable Medical Devices in a Medical IoT Scenario

“…Relatively inexpensive domestic infusion monitoring devices have been marketed, but they can only be monitored individually and cannot be networked for systematic management [ 1 ]. Clinical infusion work still suffers from untimely fluid replacement, inaccurate infusion speed, and failure to detect infusion failure in time.…”

A Higher Polygenic Risk Score Is Associated with a Higher Recurrence Rate of Atrial Fibrillation in Direct Current Cardioversion-Treated Patients

“…Similar to this study, multiple studies have observed the trend of significant association of AF recurrence only with a higher PRS and generally not with the SNVs themselves. One likely reason for this is that the SNVs associated with AF are frequently located outside of coding regions and thus not directly involved in the pathogenesis of AF [41,42]. Indeed, all eight SNVs investigated here are located in non-coding regions.…”

“…As such, recent studies have utilized whole-genome sequencing in conjunction with GWAS to permit the calculation of PRS using a far greater number of SNVs [37][38][39][40][44][45][46][47][48]. This has been made possible by the increasing availability of whole-genome sequencing [37,41,42,49].…”