Enhanced Risk Profiling of Implanted Defibrillator Shocks With Circulating SCN5A mRNA Splicing Variants: A Pilot Trial

Study Questions:

Is there an association of SCN5A cardiac sodium (Na+) channel mRNA splice variants in white blood cells (WBCs) with risk of arrhythmias in heart failure (HF) patients?


Simultaneously obtained myocardial core samples and WBCs were compared for SCN5A variants C (VC) and D (VD). Circulating variant levels were compared between HF patients divided into three groups: HF without an implantable cardioverter-defibrillator (ICD), HF with an ICD without appropriate intervention, and HF with an ICD with appropriate intervention.


Myocardial tissue-derived SCN5A variant expression levels strongly correlated with circulating WBC samples for both VC and VD variants (r = 0.78 and 0.75, respectively). After controlling for covariates, HF patients who had received an appropriate ICD intervention had higher expression levels of both WBC-derived SCN5A variants compared to HF patients with ICDs who had not (odds ratio, 3.25; 95% confidence interval, 1.64-6.45; p = 0.001). Receiver operating characteristics analysis revealed that circulating SCN5A variants levels were highly associated with the risk for appropriate ICD intervention (area under the curve ≥0.97).


Circulating expression levels of SCN5A variants were strongly associated with myocardial tissue levels and with arrhythmic risk, as measured by ICD events in a HF population within 1 year.


Current primary prevention ICD guidelines fail to identify the majority of HF patients who succumb to sudden cardiac death, and the majority of patients who do meet low EF criteria do not suffer from a malignant arrhythmia. The current pilot study is encouraging. WBC SCN5A variant levels should be tested prospectively, before ICD implantation, to assess their prognostic value.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Acute Heart Failure

Keywords: Sodium, Heart Failure, Myocardium, Death, Sudden, Cardiac, Defibrillators, Implantable, Leukocytes, Primary Prevention

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