Abstract 13939: Cardiac Resynchronization Improves Cardiac Sodium Channel mRNA Splicing Most in Patients With Severe Heart Failure

Introduction: Heart failure (HF) downregulates full-length cardiac sodium channel (SCN5A) mRNA and upregulates the splicing variant D (VD), which encodes a prematurely truncated, nonfunctional channel. Recently, we have shown that the ratio of circulating VD to full-length mRNA can predict the risk of sudden death. Cardiac resynchronization therapy (CRT) improves heart function and decreases arrhythmic events. Nevertheless, the mechanisms are unclear. Hypothesis: We tested whether CRT altered circulating full-length SCN5A mRNA and VD and further investigated its correlation with clinical parameters in HF. Methods: HF patients with new implantable cardioverter-defibrillators (ICDs) for primary prevention were enrolled. Circulating SCN5A and VD levels at baseline and at a follow-up visit were measured and compared using the ratio of VD to total SCN5A transcripts. The change of VD was expressed as the difference between the proportion of VD levels at baseline and at a follow-up visit. Results: A total of 81 ...