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Genetic Testing in CVD and Precision Medicine

Reporter: Aviva Lev-Ari, PhD, RN

See

Larry H Bernstein, MD, FCAP, Senior Editor, Author and Curator

and

Aviva Lev-Ari, PhD, RN, Editor and Curator

Genetic Testing in CVD and Precision Medicine

Based on

Cardiovascular Precision Medicine in the Genomics Era

In 2010, we introduced an approach to the evaluation of a personal genome in a clinical context (7). A patient with a family history of coronary artery disease (CAD) and sudden death was evaluated by a cardiac clinical team in conjunction with whole genome sequencing and interpretation. The genomic analysis revealed an increased genetic risk for myocardial infarction and type 2 diabetes. In addition, a pharmacogenomics analysis was performed to assess how the genetics of the patient might influence response to certain drugs, including lipid-lowering therapies and warfarin (7). This clinical assessment, which focused heavily on cardiovascular risk, suggested that whole genome sequencing might provide clinically relevant information for patients.

A 2011 joint statement from the Heart Rhythm Society and the European Heart Rhythm association recommended genetic testing as a class I indication for patients with a number of channelopathies and cardiomyopathies, including long QT syndrome (LQTS), arrhythmogenic right ventricular cardiomyopathy, familial dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM) (8). Similarly, a statement from the American Heart Association and the American College of Cardiology recommended genetic testing for HCM, DCM, and thoracic aortic aneurysms to facilitate familial cascade screening and deduce causative mutations 9, 10.

The diagnostic power of genetic testing is significant across the spectrum of CVDs, ranging from cardiomyopathies to life-threatening arrhythmias 10, 11, 12. In the clinic, genetic testing can:

• 1.

  clarify disease diagnoses: genetic testing can help to clarify the diagnosis of diseases that cause similar clinical presentation (e.g., cardiac hypertrophy could be TTR amyloidosis, Fabry disease, or sarcomeric HCM);

• 2.

  facilitate cascade screening: genetic testing can help to identify relatives at risk for CVD before disease symptoms manifest if a disease-associated variant is found in a proband and then screened for in relatives;

• 3.

  direct more precise therapy: genetic testing can help physicians choose appropriate treatments and plan appropriate timing of those treatments. For example, inherited connective tissue disease due to variants in ACTA2, MYH11, or TGFBR2 might prompt consideration of surgical intervention at a smaller aortic aneurysm diameter (13); and

• 4.

  identify patients for targeted therapies: targeted medical therapies, including antibody-based therapeutics, gene editing, and silencing technologies, are available or under development for several genetic diseases, including LQTS, Duchenne muscular dystrophy (DMD), TTR cardiac amyloidosis (14), and Fabry disease 13, 15.

REFERENCES

SOURCE

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059349/