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Next-generation sequencing increases the diagnostic yield in aborted sudden cardiac death
caused by hereditary heart disease
Brøndberg AK1, Christiansen MK1, Thorsen K2 Pedersen LN2, Jensen HK1
1 Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark
2 Department
of Molecular Medicine (MOMA), Aarhus University Hospital, Denmark
Methods
Purpose
Sudden cardiac death (SCD) in young adults is often caused by inherited heart
disease. Until now the genetic diagnostic tools in patients with SCD or survivors after
cardiac arrest have targeted the presumed phenotype which often can be difficult to
define. We aimed to overcome these limitations by applying next-generation
sequencing (NGS) to a cohort of non-ischemic aborted SCD victims.
Patient selection
We identified all patients ≤50 years of age with an Implantable cardioverter
defibrillator (ICD) received at Aarhus University Hospital from 1999 to 2013 (n=433).
Data was extracted from the Danish Pacemaker and ICD registry. All patients with
unexplained ventricular tachycardia (VT), ventricular fibrillation (VF) or recurrent
malignant syncope were study candidates. Eighty (78%) of eligible patients
participated in the study.
Figure 1, Flow diagram showing patient selection.
Results
Figure 2, Diagram showing genetic analysis work flow.
Median age (IQR) at the time of ICD implantation was 38
(30:43). The most frequent symptom at disease onset was VF,
followed by VT and recurrent malignant syncope of which 7
were inducible to ventricular arrhythmia with an electrophysiological study (EPS) (table 1).
Seventeen (21%) participants were found to have a possible
rare pathogenic gene variant. In 63 (79%) participants we did
not find any significant genetic variants.
Conclusion
NGS considerably increases the number of molecular-genetic
diagnoses in patients with aborted SCD. However, a great
number of VUS complicates the clinical interpretation.
Correspondence: Anders Krogh Brøndberg, MD, [email protected]