Ana Morales

Genetic testing for cardiomyopathy and arrhythmia (CM/ARRH) provides diagnostic information and informs screening for at-risk relatives. Clinical guidelines recommend genetic testing for these conditions; however, data on how genetic test results influence clinical management recommendations are limited. Here, we determined the frequency of cardiologist-recommended management changes for patients following CM/ARRH genetic testing. This was a retrospective cross-sectional study of patients referred for multigene panel testing between April 2016 and April 2024. Genetically-experienced cardiologists at multicenter academic clinical practices were recruited for participation to complete surveys indicating clinical decision making on patients who had genetic testing. Cases for review were randomly selected to have both positive and non-positive results. Among 249 patients (138 positive, 111 non-positive), 136 (54.6%) received clinical management recommendations for their own or their at-risk relatives? care. Of these, 75 (55.1%) received recommendations for the patient?s own care, most frequently additional diagnostic tests/procedures (n=33). Compared to non-positive results, patients with positive results were more likely to receive recommendations for their own management (66/138, 47.8% vs 9/111, 8.1%; P<0.00001). Patients with positive results in arrhythmogenic cardiomyopathy genes had 263% higher odds of recommended management changes compared to those with TTN (OR=3.63, CI:1.40-9.84, P=0.009). The results from CM/ARRH genetic testing on affected patients influenced cardiologists? medical decision making and management recommendations. Additional research is needed to evaluate how genetic testing for CM/ARRH impact health outcomes.

Introduction: Genetic testing is increasingly central to the diagnosis and management of cardiovascular genetic conditions. However, use and follow-through vary across patient populations. Examining clinician perspectives on sociocultural and structural factors influencing testing is important for understanding these differences and informing public health genomics research and implementation efforts. Methods: We conducted semi-structured interviews with 15 cardiologists from health systems across the United States who have integrated cardiogenetics in their practice. Interviews explored experiences diagnosing cardiovascular genetic conditions among patients from underrepresented backgrounds, as well as approaches to incorporating social and contextual information into care. Data were coded thematically and analyzed using a framework analysis guided by the Health Equity Implementation Framework and Social Determinants of Health domains. Results: Clinicians described multi-level factors shaping genetic testing practices, including patient-provider interactions, clinical workflows, health system infrastructure, and broader policy contexts. Key themes included challenges communicating complex genetic information across language and literacy differences; patient trust shaped by prior healthcare experiences; fragmented insurance coverage separating genetic testing from genetic counseling; and challenges interpreting variants of uncertain significance, particularly for populations underrepresented in genomic reference databases. Clinicians also described adaptive strategies—such as interdisciplinary collaboration, telehealth, and patient assistance programs—that supported testing in some settings but were often inconsistent or resource-dependent. Conclusion: Among cardiologists using genetic testing, system-level and sociocultural factors shape the feasibility and downstream use of cardiovascular genetic testing. Findings highlight considerations for public health-informed genomic infrastructure that accounts for social context, supports communication, and reduces reliance on individual clinician workarounds, with implications for clinical decision support and related public health genomics initiatives.

BACKGROUND: Truncating variants (TTNtvs) in the titin ( TTN ) gene have been associated with cardiomyopathies or arrhythmias (C/A) and autosomal recessive neuromuscular diseases (NM). However, the clinical significance of TTNtvs across the entire coding sequence of TTN has not been comprehensively assessed. The purpose of this study was to examine the burden of TTNtvs in C/A and NM cases compared with controls in the genome aggregation database. METHODS: This was a retrospective study of probands who underwent multigene testing (49 740 C/A panel, 24 514 NM panel) that included TTN from November 2017 to October 2021. Burden testing was performed using controls in the genome aggregation database v3.1.2 database, and the analysis was stratified by exon/band location and exon usage in cardiac or skeletal muscle. Frequency and odds ratio of TTNtv alleles in C/A or NM cases and genome aggregation database controls were measured. RESULTS: There were 2446 (4.9%) C/A and 482 (2.0%) NM cases with 2446 and 528 TTNtv alleles, respectively. TTNtvs in all bands were significantly enriched in both C/A and NM cases compared with controls. A significant enrichment of TTNtvs in C/A was observed for exon 358 of the M-band (odds ratio, 2.55 [95% CI, 1.85–3.54]) but not the other M-band exons. CONCLUSIONS: In the largest single-site cohort of C/A and NM cases with TTNtvs, an enrichment of TTNtvs across TTN was observed. These findings expand the clinically relevant regions of TTN .

Cardiogenetic testing was established 20 years ago; more recently, it began to be incorporated in routine clinical care. Key reasons include expanded knowledge of the genetic basis of cardiovascular disease, wider availability of enriched cardiogenetic testing panels, the issuance of clinical recommendations guiding cardiogenetic testing, and enhanced cardiologists’ awareness. Cardiogenetic testing can be valuable at the levels of diagnosis, prognosis, treatment/ management selection, early disease risk detection, and personalized surveillance strategy. Cardiovascular disease-related genes are incorporated in genetic screening panels currently being evaluated for their potential in disease prevention at the general population level. These rapid developments are increasing the number of individuals requiring genetic counseling and personalized cardiovascular care. Advanced expertise is required to determine when genetic testing is needed, which genetic test is more appropriate, and how the patient and their family members should be prepared for the process. To reap the full benefits of cardiogenetic testing and screening, cardiology and genetics providers must collaborate effectively in the cardiology clinics’ setting. This chapter focuses on cardiomyopathies, arrhythmias, familial hypercholesterolemia, and thoracic aortic aneurysm/dissection, as well as the specialized knowledge that cardiovascular genetic counselors need to serve their indispensable, multifaceted role when caring for individuals with these conditions.

With the increasing availability and adoption of genetic testing in cardiovascular disease (CVD), effective post-testing management is becoming crucial for optimizing patient outcomes and providing personalized care. This chapter focuses on key strategies and considerations for interpreting genetic test results in CVD, navigating complex scenarios such as incidental findings (IFs) and variants of unknown significance (VUS), and utilizing advanced tools and databases for evidence-based interpretation. As genetic testing becomes more integrated into routine clinical practice, the ability to communicate results clearly and accurately to patients and their families is paramount. This chapter provides practical guidance on delivering genetic information in a clinically meaningful way while adhering to international recommendations and addressing sensitive issues like non-paternity disclosure and risk assessment for family members through cascade testing. Special attention is given to the unique challenges of testing minors and the ethical frameworks that guide these decisions. Finally, the chapter addresses the psychosocial implications of CVD genetic testing and offers support strategies to help patients and families navigate the impact of their results. As the field of CVD genetics continues to expand, this comprehensive approach is essential for translating genetic data into actionable insights that enhance patient care and family health management.