FUTURE DIRECTIONS IN GENETIC AF
As medical care continues to move towards a personalized, precision-based approach, genetic testing and recognition of genetically mediated disease processes will rise to the forefront in medical diagnosis, treatment, and prognosis. This too includes the recognition that a sizable proportion of the AF population manifests a genetically mediated form of AF, and this paradigm is even more true for patients with early onset or lone AF in the absence of structural heart disease. While this paradigm shift is in its relative infancy, research is emerging that will support enhanced recognition and care of these patients.
At this time, there remains heterogeneity across medical centers as it relates to which patients are referred for genetic testing.109 The future of this field will rely on the development of risk stratification models for AF based on genetic profile, family history, and patient phenotype information; effective treatment plans based on a patient’s genetic profile (including rate control strategy, medical rhythm control and ablation therapy)110; and evaluation for long-term progression of disease based on, likely, a combination of genetic and environmental factors.111 It may bear to reason, as well, that there are subsets of the AF population that may be at differential risk for thromboembolic events and stroke when compared to the AF population at large. While there is emerging data to suggest that AF PRS112, 113 may predict cardioembolic stroke risk, future prospective studies in this space are needed. Creating a genetic profile using both common and rare variation is becoming increasingly affordable with even whole genome sequence data nearly within reach for many patients. As these costs continue to come down, the medical community must be prepared to utilize these data. While new research programs seek to sequence more diverse cohorts, these data are often completely deidentified with little to no phenotype data. Additional cohorts with phenotype information are needed to provide fine-tuned associations across detailed phenotypes. Medical biobanks that incorporate a subject’s complete medical record and genomic profile, provide a fertile space for medical research and require further investment.
Among patients with AF as part of a greater cardiomyopathic process, such as those with TTN and Lamin A/C mutations, recognition of an underlying genetic etiology should heighten awareness and screening for ventricular tachyarrhythmias and ventricular dysfunction.114 These patients are at increased risk of not only AF but also non-sustained ventricular tachycardia and atrioventricular block and would likely benefit from more frequent arrhythmia monitoring.115 If a genetic cardiomyopathy is suspected, patients should be referred to genetic counseling and, if appropriate, a cardiologist with experience caring for patients with genetically mediated cardiomyopathies. Early recognition is important for future screening in the index patient, as well as for relevant family screening for arrhythmia and LV dysfunction. The growth of our understanding of genetic cardiomyopathies and their interaction with AF presents an exciting new challenge in the care of these patients. As the field continues to learn more about this subset of patients, we anticipate the development of diagnostic and therapeutic plans based in part on a patient’s genetic profile.