News & Updates

Clinical study results published in the Journal of American College of Cardiology

Recently, 3PrimeDx conducted a clinical study in 135 adults to determine the association of SCN5A cardiac sodium (Na+) channel mRNA splice variants in white blood cells (WBCs) with risk of arrhythmias in heart failure (“Sodium Channel Splicing in Heart Failure Trial;” SOCS-HEFT, ClinicalTrials.gov Identifier NCT01185587). Heart failure is associated with increases of two cardiac SCN5A mRNA splice variants that encode prematurely shortened, nonfunctional Na+ channels. Since WBCs in the blood demonstrate similar SCN5A splicing patterns to the splicing patterns seen in heart tissue, we hypothesized that WBC-derived splice variants might further identify heart failure patients at high risk for arrhythmias relative to conventional risk measures. Heart tissue samples and blood WBCs were compared for SCN5A variants C (VC) and D (VD). The variant levels in the WBCs were compared between heart failure patients divided into three groups: heart failure without an implantable cardioverter-defibrillator (ICD), heart failure with an ICD without appropriate intervention, and heart failure with an ICD with appropriate intervention. Heart tissue-derived SCN5A variant production levels strongly correlated with blood WBC samples for both VC and VD variants (r = 0.78 and 0.75, respectively). After controlling for other factors, heart failure patients who had received an appropriate ICD intervention had higher levels of both WBC-derived SCN5A variants compared to heart failure patients with ICDs who had not (OR= 3.25 (95% CI 1.64-6.45; p=0.001)). A standard statistical approach to analyze diagnostic performance of the test showed that circulating SCN5A variants levels were highly associated with the risk for appropriate ICD intervention (overall test accuracy ³ 97%). In conclusion, levels of SCN5A variants found in blood WBCs were strongly associated with heart tissue variant levels. Furthermore, blood WBC variant levels highly related to arrhythmic risk as measured by ICD events in a heart failure population over one year.

The article  can be found at: http://www.ncbi.nlm.nih.gov/pubmed/24703920.