244. Cardiovascular Genomics: Intro to Cardiovascular Genetics in Electrophysiology with Dr. James Daubert

The field of Cardiovascular Genomics has advanced tremendously over the past two decades, having a significant clinical impact and changing the perception of the role and scope of genetic testing in several cardiovascular domains.  To kickstart the Cardiovascular Genomics series, CardioNerds Dr. Sara Coles (FIT at Duke University), Dr. Colin Blumenthal (CardioNerds Academy faculty and FIT at UPenn), and Dr. Karla Asturias (CardioNerds Academy fellow and medicine resident at Pennsylvania Hospital) have a great discussion with Dr. James Daubert, a clinical electrophysiologist at Duke University, with a particular interest in inherited arrhythmia syndromes and sports cardiology. In this episode, we review basic concepts of cardiovascular genomics and genetics in electrophysiology while discussing when to (and when not to!) test our patients and their families and how to approach those results. Audio editing by CardioNerds academy intern, Pace Wetstein. This episode was developed in collaboration with the American Society of Preventive Cardiology and is supported with unrestricted educational funds from Illumina, Inc. All CardioNerds content is planned, produced, and reviewed solely by CardioNerds. This CardioNerds Cardiovascular Genomics series is a multi-institutional collaboration made possible by contributions of stellar fellow leads and expert faculty from several programs. Pearls • Notes • References CardioNerds Cardiovascular Genomics PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes - Genetics in Electrophysiology The first step is identifying the right phenotype! Getting the right phenotype is crucial, as genetic testing done in a patient without a clear phenotype (or an incorrect one) would lead to significant anxiety, unnecessary tests and interventions, and potentially misleading and dangerous conclusions for patients and their families. Genetic testing typically should be reserved for patients with a confirmed or suspected diagnosis of an inherited disease or for individuals with a previously diagnosed pathogenic variant in a first-degree relative.1 Discuss with your patient! Genetic counseling is essential and recommended for all patients before and after genetic testing. It should include a thorough discussion of risks, benefits, and possible outcomes, including variants of uncertain significance.2 Cardiovascular genetics is a dynamic and rapidly evolving field. New information can cause a variant of uncertain significance to be reclassified as a pathogenic or likely pathogenic variant or to be downgraded to benign or likely benign as variant databases expand. Another possibility is that new research might identify novel genes for a particular disease, which could warrant retesting, particularly for phenotype-positive and genotype-negative patients.1 Brugada syndrome is an inherited arrhythmogenic disorder characterized by ST-segment elevation in the right precordial leads and malignant ventricular arrhythmias, with occasional conduction disease and atrial arrhythmias. It is diagnosed in patients with ST-segment elevation ≥ 2 mm in ≥ 1 lead among the right precordial leads, with a type I morphology (J-point elevation with slowly descending or concave ST segment elevation merging into a negative T wave), shown in the image below. This pattern can be observed spontaneously or after provocative drug testing (e.g., procainamide). Pathogenic genetic variants in SCN5A that result in loss of function of the cardiac sodium channel are identified in approximately 20% of cases.3,4 Image adapted from Batchvarov VN. The Brugada Syndrome – Diagnosis, Clinical Implications and Risk Stratification. Eur Cardiol Rev. 2014;9(2):82. doi:10.15420/ECR.2014.9.2.82 Measure the QT interval yourself!