Precision Medicine in the Management of Dilated Cardiomyopathy: JACC State-of-the-Art Review

Diane Fatkin; Inken G Huttner; Jason C Kovacic; J G Seidman; Christine E Seidman

doi:10.1016/j.jacc.2019.10.011

Precision Medicine in the Management of Dilated Cardiomyopathy: JACC State-of-the-Art Review

J Am Coll Cardiol. 2019 Dec 10;74(23):2921-2938. doi: 10.1016/j.jacc.2019.10.011.

Authors

Diane Fatkin¹, Inken G Huttner², Jason C Kovacic³, J G Seidman⁴, Christine E Seidman⁵

Affiliations

¹ Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Kensington, New South Wales, Australia; Cardiology Department, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia. Electronic address: d.fatkin@victorchang.edu.au.
² Molecular Cardiology and Biophysics Division, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia; St. Vincent's Clinical School, Faculty of Medicine, UNSW Sydney, Kensington, New South Wales, Australia.
³ The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
⁴ Howard Hughes Medical Institute, Boston, Massachusetts; Department of Genetics, Harvard Medical School, Boston, Massachusetts.
⁵ Department of Genetics, Harvard Medical School, Boston, Massachusetts; Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts.

PMID: 31806137
DOI: 10.1016/j.jacc.2019.10.011

Abstract

Precision medicine promises to dramatically improve patient outcomes and reduce health care costs through a shift in focus from disease treatment to prevention and individualized therapies. For families with inherited cardiomyopathies, efforts to date have been directed toward discovery and functional characterization of single disease-causing variants. With advances in sequencing, the cataloging of personal genetic variation has been expedited, providing improved insights into the key importance of the genes in which variants occur. These advances have propelled seminal opportunities for successful variant-targeted disease-reversing therapy. New challenges have also emerged-particularly interpretation of the rapidly rising numbers of "variants of unknown significance." For treatments based on patient genotype to be feasible on a wider scale, these obstacles need to be overcome. Here the authors focus on genetics of dilated cardiomyopathy and provide a roadmap for implementing genomic information into future patient management.

Keywords: dilated cardiomyopathy; functional genomics; genetics; precision medicine.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Cardiomyopathy, Dilated / diagnosis
Cardiomyopathy, Dilated / genetics*
Genetic Predisposition to Disease*
Genetic Testing / methods*
Genomics / methods*
Genotype
Humans
Phenotype
Precision Medicine / methods*