NLP SNP

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.

NCT01185587 Atrial Fibrillation Atrial Flutter Heart Failure

MeSH: Heart Failure Atrial Fibrillation Atrial Flutter

HPO: Atrial fibrillation Atrial flutter Congestive heart failure Left ventricular dysfunction Paroxysmal atrial fibrillation Right ventricular failure

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 ---

Primary Outcomes

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 enrollment

Secondary Outcomes

Description: upstream signals for abnormal SCN5A mRNA splicing

Measure: ACE mRNA

Time: At enrollment

Description: upstream signals for abnormal SCN5A mRNA splicing

Measure: Ang II mRNA

Time: At enrollment

Description: upstream signals for abnormal SCN5A mRNA splicing

Measure: HIF-1α mRNA

Time: At enrollment

2 Sodium Channel Splicing in Obstructive Sleep Apnea (SOCS-OSA)

This study is designed to test whether SCN5A mRNA processing is altered in OSA patients, which may contribute to their increased arrhythmic risk, and whether processing of SCN5A mRNA is modulated by CPAP treatment. Specific aims: 1. Compare sodium channel splicing variants in mild, moderate, or severe OSA patients at baseline to at 1 month after CPAP treatment. In addition, the baseline splicing variants of SCN5A in the OSA patients will be compared to an age-matched control group. 2. Hypoxia-associated upstream regulators of SCN5a mRNA splicing, Hypoxia-inducible factor 1-alpha (HIF-1α), RNA Binding Motif Protein 25 (RBM25) and LUC7-Like 3 Pre-MRNA Splicing Factor (LUC7L3), will be examined in OSA patients before and after 1 month of CPAP treatment.

NCT02725632 Sleep Apnea Syndromes Device: CPAP

MeSH: Apnea Sleep Apnea Syndromes Sleep Apnea, Obstructive

HPO: Apnea Obstructive sleep apnea Sleep apnea

Three truncated SCN5A mRNA splicing variants were identified (denoted variant B (E28B), variant C (E28C), and variant D (E28D)). --- E28C ---

Among them, E28C and E28D abundances were increased 14.2 fold and 3.8 fold respectively in CHF patients compared to controls. --- E28C ---

Primary Outcomes

Measure: The levels of sodium channel splicing variants that are related to the severity of OSA, change from baseline to one month after CPAP treatment.

Time: Four weeks