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.