Precision Medicine in Cardiac Electrophysiology: Where we are and Where we Need to Go

Introduction The treatment of arrhythmias is complex and there are many options including drug therapy, ablation techniques, and implantable devices. Selection of the right treatment strategy is complicated by the fact that patients with apparently the same clinical picture may respond differently to a given therapy, indicating some underlying molecular and cellular differences. We now know this is mediated in a large part by the genetics, and patients with similar phenotypes may have differing genotypes. Understanding this genotype–phenotype relationship is key in modern medicine. Areas covered We have conducted an exhaustive review of the literature surrounding the genetic basis of arrhythmias and have presented a comprehensive summary of the available information. We have demonstrated how understanding the underlying genetic and molecular derangements in arrhythmias has resulted in effective targeted treatments. We have further highlighted novel therapies in arrhythmia management based on emerging genomic research. Expert opinion The future of cardiac electrophysiology, and indeed all cardiovascular medicine, lies in the development of targeted therapies that can effectively treat the individual patient, based on their specific genetic attributes and variations. Future genetic research which drives the development of innovative therapies holds the promise of delivering such personalized therapies in cardiac electrophysiology. Article highlights When anti-arrhythmic drugs were first being developed, the underlying cellular and molecular basis of arrhythmias were largely unknown, and thus there were no clear therapeutic targets for these drugs. Drug effects vary greatly from patient to patient, and this may relate to differences in the underlying molecular derangements of relatively similar phenotypes. These differences, in turn, are determined by the genotypes of the diseases. We are now nearing the limits of what this “one-size-fits-all” approach to arrhythmia management can offer. We are now charged with the task of exploring the genetic basis of arrhythmias (and cardiomyopathies), in order to develop more personalized therapies. We have already discovered several causative genetic variants for various arrhythmias and arrhythmia syndromes. This has helped us understand the normal electrophysiologic function of the cardiac myocyte and has helped us develop many genotype-specific treatments. However, the genetic basis of arrhythmias in a substantial number of cases is still unknown. There is room for plenty of research and discovery still. As we go beyond merely discovering the genetic and molecular derangements that cause diseases, and as we delve into gene therapy, we are likely to develop highly personalized treatments for arrhythmias. Gene delivery systems such as human gene transfer using non-immunogenic vectors and clustered regularly interspaced short palindromic repeats (CRISPR)-gene editing technologies are being developed to treat a wide array of diseases, and they may be used in arrhythmia management in the future