Personalized medicine to treat arrhythmias

• Most antiarrhythmic drugs were developed when arrhythmia mechanisms were poorly understood.
• Antiarrhythmic drug therapy is not predictably effective and can produce serious side effects.
• Family and population studies identify DNA variants generating the arrhythmia-prone heart.
• Mechanism-based therapy is now being realized in some genomically defined subsets.
• Sequencing may in the future allow presymptomatic intervention in arrhythmia-prone patients.

The efficacy of antiarrhythmic drug therapy is incomplete, with responses ranging from efficacy to no effect to severe adverse effects, including paradoxical drug-induced arrhythmia. Most antiarrhythmic drugs were developed at a time when the mechanisms underlying arrhythmias were not well understood. In the last decade, a range of experimental approaches have advanced our understanding of the molecular and genomic contributors to the generation of an arrhythmia-prone heart, and this information is directly informing targeted therapy with existing drugs or the development of new ones. The development of inexpensive whole genome sequencing holds the promise of identifying patients susceptible to arrhythmias in a presymptomatic phase, and thus implementing preventive therapies.