Molecular genetic screening after non-ischaemic sudden cardiac arrest and no overt cardiomyopathy in real life: A major tool for the aetiological diagnostic work-up - 14/06/24
, Estelle Gandjbakhch c, d, e, Isabelle Magnin-Poull a, Julie Proukhnitzky c, d, e, Céline Bordet e, Aurélien Palmyre b, Adrien Bloch f, Véronique Fressart f, Philippe Charron b, c, d, e, ⁎ Graphical abstract |
Highlights |
• | Sixty-six patients with non-ischaemic sudden cardiac arrest without LV structural disease. |
• | A genetic variant of interest was found in 1/3 of tested patients. |
• | Most patients had no phenotypic clues, but genetic testing was still profitable. |
• | Many had channelopathies and arrhythmogenic RV cardiomyopathy-associated genes. |
• | 1/3 of variants were (likely) pathogenic, so useful for family screening. |
Abstract |
Background |
With the development of advanced sequencing techniques, genetic testing has emerged as a valuable tool for the work-up of non-ischaemic sudden cardiac arrest (SCA).
Aims |
To evaluate the effectiveness of genetic testing in patients with unexplained SCA, according to clinical phenotype.
Methods |
All patients who underwent molecular genetic testing for non-ischaemic SCA with no left ventricular cardiomyopathy between 2012 and 2021 in two French university hospitals were included.
Results |
Of 66 patients (mean age 36.7±11.9years, 54.5% men), 21 (31.8%; 95% confidence interval 22.4–45.3%) carried a genetic variant: eight (12.1%) had a pathogenic or likely pathogenic (P/LP) variant and 13 (19.7%) had a variant of uncertain significance (VUS). Among 37 patients (56.1%) with no phenotypic clues, genetic testing identified a P/LP variant in five (13.5%), mainly in RYR2 (n=3) and SCN5A (n=2), and a VUS in nine (24.3%). None of the nine patients with phenotypic evidence of channelopathies had P/LP variants, but two had VUS in RYR2 and NKX2.5. Among the 20 patients with suspected arrhythmogenic cardiomyopathy, three P/LP variants (15.0%) and two VUS (10.0%) were found in DSC2, PKP2, SCN5A and DSG2, TRPM4, respectively. Genetic testing was performed sooner after cardiac arrest (P<0.001) and results were obtained more rapidly (P=0.02) after versus before 2016.
Conclusion |
This study highlights the utility of molecular genetic testing with a genetic variant of interest identified in one-third of patients with unexplained SCA. Genetic testing was beneficial even in patients without phenotypic clues, with one-fourth of patients carrying a P/LP variant that could have direct implications.
Le texte complet de cet article est disponible en PDF.Keywords : Genetics, Sudden cardiac arrest, Out-of-hospital cardiac arrest, Idiopathic ventricular fibrillation, Non-structural heart disease
Plan
Vol 117 - N° 6-7
P. 382-391 - juin 2024 Retour au numéro
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