Pharmacogenomics, personalized medicine, and heart failure.

Abstract Heart failure, a major clinical problem affecting millions of people, may be modified by the genetic diversity of the affected individuals. A novel medical approach, personalized medicine, seeks to use genetic information to "personalize" and improve diagnosis, prevention, and therapy. The personalized management of heart failure involves a large spectrum of potential applications, from diagnostics of monogenic disorders, to prevention and management strategies based on modifier genes, to pharmacogenomics. In rare monogenic disorders causing heart failure, recent guidelines now assist the clinician in molecular diagnostics, genetic counseling, and therapeutic choices. Several lines of evidence suggest that common polymorphic variants of modifier genes can influence the susceptibility to heart failure, and it is expected that more advanced high throughput technologies will allow the discovery of a number of novel modifier genes that could be used for prognostic profiling and development of novel therapeutics. Finally, using pharmacogenomic approaches to affect heart failure management appears very promising. Common genetic variants of beta-adrenergic receptors, alpha-adrenergic receptors, and endothelin receptors among others significantly alter the response to heart failure therapy. This knowledge could be used to personalize and optimize heart failure therapy based on the patient's genetic profile. While the advances in technologies will continue to transition personalized medicine from the research to the clinical setting, physicians and in particular cardiologists need to reshape clinical diagnostics paradigms, learn how to use new genomic information to change management decisions, and provide the patients with appropriate education and management recommendations.