Use of Genetics in the Clinical Evaluation and Management of Heart Failure

Abstract

Inherited forms of cardiomyopathy are common causes of heart failure. Applications of genetics in the evaluation and management of heart failure include the determination of inheritance patterns within families with cardiomyopathy, the evaluation of affected patients for syndromic features, the determination of people within families who are at risk of heart failure, and the identification of responsible gene mutations. Family planning may also be assisted by determination of a clear mutation that predisposes to heart failure. Genetic counseling is critical, and it should accompany the use of genetic testing in cardiovascular diseases. With the rapid pace of growth in technology that is used to determine DNA sequence, costs have declined and clinical application of genetic testing has expanded. This is particularly relevant for heart failure, because each of the familial forms of cardiomyopathy may be caused by a mutation in many different genes. Most families share a unique gene mutation, and appropriate interpretation of novel DNA variants is essential for proper use. The evaluation of risk of arrhythmia in familial forms of heart failure may benefit from genetic testing, as mutations in the genes encoding lamin A/C, desmin, and cardiac troponin T are associated with increased risk of sudden cardiac death. Because of its complexity and the rapid rate of change in available genetic testing options, the genetic evaluation of heart failure is best suited to tertiary referral centers with specific expertise in this area.

Targeted next-generation sequencing detects novel gene–phenotype associations and expands the mutational spectrum in cardiomyopathies

“…In fact, a phenotype-specific targeted gene testing [ 30 ] might miss to identify several variants in cardiomyopathic patients. Conversely, a comprehensive gene testing could enhance the diagnostic and prognostic implications of genetic screening by not only allowing an early diagnosis of inherited cardiomyopathic forms but also by contributing to a more accurate prognostic stratification and patient management [ 31 ].…”

A Clinical Approach to a Family History of Sudden Death

“…26 Additional criteria include delayed contrast enhancement on cardiac magnetic resonance imaging, LV aneurysm, LV outflow tract gradient, and occasionally a specific gene mutation from which arrhythmia risk can be inferred. [27][28][29][30] For instance, mutations in TNNT2 encoding cardiac troponin T are known to carry increased risk of arrhythmia despite a relative paucity of left ventricular hypertrophy. 31 A few syndromic disorders can present with HCM, and family history may help to recognize some of them.…”

SVAD: A genetic database curates non-ischemic sudden cardiac death-associated variants

“…It is rapidly applied to clinical practice and allows scientists to investigate the genetic variants contributing to specific phenotypes when combined with large-scale annotated genetic databases [31]. At present, clinical research aims to exploit the potential of genetic variation as risk predictors or biomarkers to prevent SCD based on the clinical stages of patients and their relatives [32][33][34][35][36]. Therefore, genetic testing is considered practicable in early diagnosis, prognostic stratification, and therapeutic interventions [36,37].…”