1 - Centro Hospitalar Universitário de Lisboa Central, EPE / Hospital de D. Estefânia; 2 - Instituto de Ciências Biomédicas Abel Salazar; 3 - Centro Hospitalar Universitário de Lisboa Central, EPE / Hospital de Santa Marta
- Poster no Congresso Português de Cardiologia, 2024
Resumo: Background: Inherited cardiomyopathies and arrhythmias (ICAs) are a clinically heterogeneous and prevalent group of disorders characterised by high genetic and allelic heterogeneity, incomplete penetrance/ age-related penetrance and variable expressivity, and are associated with increased risk of sudden cardiac death and heart failure. Family screening isrecommended by cardiovascular societies with clinical evaluation and genetic testing to identify at-risk relatives, and thus improving their surveillance and management.
Aim: To report the outcome of family screening after identification of a (likely) pathogenic variant in a symptomatic patient with ICAs.
Methods: Retrospective review of genotype, phenotypic and clinical outcome data of 190 relatives of 65 probands with a clinical and molecular diagnosis of ICAs (hypertrophic cardiomyopathy [29], dilated cardiomyopathy [21], arrhythmogenic right ventricular cardiomyopathy [4], Non-compaction cardiomyopathy [3], long QT syndrome [5] and Brugarda syndrome [2]) referred to our Genetics Department (2016-2022) in a Portuguese tertiary hospital. Results: After genetic counselling 190 at-risk relatives underwent a genetic testing and overall, 111/190 (58%) were genotypepositive (G+) and 79/190 were genotype-negative (G-) leading to discharge from clinical follow-up. 168/190 (88%) relatives were phenotype-negative (P-) at the first appointment and 22/190 (12%) were phenotype-positive (P+). After clinical evaluation, 18/168 (11%) of the previous P- received a clinical diagnosis consistent with G+ status, and 3/168 (2%) had other traits associated with ICAs. 89/168 (53%) of P- were G+ and 22/22 (100%) P+ were also G+. During follow-up, 7/111 (6%) received an implantable cardioverter defibrillator in primary prevention and 4/111 (4%) in secondary prevention, 1/111 (1%) required cardiac resynchronization therapy, 1/111 underwent septal reduction therapy, 1/111 (1%) cardiac transplantation. 19/111 (17%) started medical therapy, and 58/111 (52%) remained asymptomatic and maintained routine follow-up. Lastly, 2/111 of the G+P+ relatives died due to complications associated with their ICAs diagnosis.
Conclusion: Family screening allows an early identification of at-risk relatives and discharge of family members G-P-. Timely management of G+ relatives in an earlier disease stage might led to better clinical outcomes. Longer-term follow-up is necessary to better understand clinical outcomes, particularly of the G+P- patients.
Palavras Chave: Inherited cardiomyopathies; Genetic Counseling