The purpose of this research is to see if investigators can detect truncated mRNA splice variants of the cardiac voltage-gated sodium (Na+) channel gene, SCN5A, in patients with a weak heart (Heart Failure) with or without an implantable cardioverter-defibrillator (ICD) and compare them to patients with a normal heart. Hypothesis: 1. Patients with reduced left ventricular ejection fraction have increased abundances truncated mRNA splice variants of the SCN5A gene, which portends to sodium channel dysfunction and an increased risk for sudden cardiac death. 2. Patients with implantable cardioverter-defibrillator devices (ICDs) who have experienced shock therapy have increased abundances of truncated mRNA splice variants of the SCN5A gene compared to similar congestive heart failure patients who have not experienced shock therapy.
Description: We will correlate the amount of white cell Na+ channel splice variants with ejection fraction in patients with an without heart failure and with the number of shocks in the patients with ICDs.
Measure: Amount of sodium channel splice variants Time: At enrollmentDescription: upstream signals for abnormal SCN5A mRNA splicing
Measure: ACE mRNA Time: At enrollmentDescription: upstream signals for abnormal SCN5A mRNA splicing
Measure: Ang II mRNA Time: At enrollmentDescription: upstream signals for abnormal SCN5A mRNA splicing
Measure: HIF-1α mRNA Time: At enrollmentCohort
There are 4 SNPs
A different SCN5A gene abnormality, the E161K mutation, has been shown to lead to decreased sodium current density and a an 11.9 mV positive shift in the cell membrane half-maximal activation potential.11 --- E161K ---
Relative levels of the full length mRNA isoform, E28A, were decreased by 24.7% in patients with CHF compared to control. --- E28A ---
Previously, we showed that the least sensitive measure was a reduction in E28A abundance by 24%. --- E28A ---
These three splicing variants for the nonfunctional sodium channel gene product were denoted E28B, E28C, and E28D. --- E28C ---
At the same time, the E28C and E28D mRNA abundances were increased 14.2 fold and 3.8 fold respectively in CHF patients compared to controls. --- E28C ---
These three splicing variants for the nonfunctional sodium channel gene product were denoted E28B, E28C, and E28D. --- E28C --- --- E28D ---
At the same time, the E28C and E28D mRNA abundances were increased 14.2 fold and 3.8 fold respectively in CHF patients compared to controls. --- E28C --- --- E28D ---