Atrial Fibrillation Clinical Trial
Official title:
ST-segment Elevation With Procainamide as an ECG Endophenotype of AF
The purpose of this study is to look for a similarity in people's genes that may help understand which people could benefit from certain drugs for the treatment of atrial fibrillation (AF).
Current drug therapies to suppress AF are incompletely and unpredictably effective and carry
significant (albeit generally small) risks of serious adverse effects, including drug-induced
long QT syndrome (diLQTS), other forms of proarrhythmia, increased mortality through
uncertain mechanisms, and extracardiac toxicity. Identification of clinical and genetic
subtypes of AF will permit stratification of therapeutic approaches and thereby facilitate
the practice of personalized medicine. Furthermore, limited success of drug therapy and
increase in drug toxicity in AF is probably because the arrhythmia represents a final common
pathway of multiple initiating mechanisms, including some that are genetically-defined.
Identifying specific intermediate phenotypes ("endophenotypes") associated with defined
clinical courses in AF represents a potential method to systematically subtype patients by
underlying mechanism and represents a much-needed clinical advance. Clinical endophenotypes
that have been studied include atrial fibrillatory rate, prolonged signal-averaged P-wave
duration, and biomarker profiles. The endophenotype we will study here is right precordial ST
segment elevation, seen not only in Brugada syndrome (BrS) (where it is unmasked by sodium
channel blocking drugs) but also commonly in early-onset ('lone') AF and in patients with
AF-associated rare variants in genes encoding the cardiac sodium channel α- or β-subunits.
Taken together these data suggest the hypothesis to be tested in this study, that variants in
multiple genes can culminate in a similar AF-prone substrate by reducing sodium current that
can be identified by screening for baseline or manifest right precordial ST segment elevation
endophenotype after sodium channel block with intravenous procainamide.
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