Na+ Channel mRNA Regulation in Heart Failure

NCT03313882 | Completed

• 1 other identifier: Study00001184
• Study Type: observational
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

Human heart failure (HF) has been associated with reduced cardiac sodium channel current and other electrical remodeling. Recently, the investigators have shown that downregulation of cardiac Na+ channels (SCN5A) can contribute to arrhythmic risk and that upregulation can mitigate that risk. Furthermore, the investigators have shown that the reduction in cardiac SCN5A mRNA abundance is reflected in circulating white blood cells (WBCs), which also express SCN5A, and that a reduction in SCN5A is highly predictive of appropriate implanted cardiac defibrillator (ICD) therapy. These data suggest that SCN5A regulation contributes to arrhythmic risk in HF. Other electrical remodeling events thought to contribute to arrhythmic risk include reductions in K+ currents, including Ito, IK1 and IKs are responsible. These current reductions have been linked to reduced transcription, translation and expression of the corresponding channel subunits, such as Kv4.3, Kir2.1, KvLQT1, and accessory proteins including minK and K+ channel interacting protein 2. That all these ion channels are downregulated may suggest a common mechanism to reduce ion channel expression. In this application, the investigators intend to explore an entirely novel mechanism by which SCN5A and other ion channel mRNA abundances are reduced in HF.

Conditions

Heart Failure

Keywords

RNA Stability; HuR protein; SCN5A

Outcome Measures

Primary Outcomes (1)

• ion channel expression

  mRNA and protein levels of cardiac ion channels, cardiac ion currents

  Baseline

Secondary Outcomes (1)

• HuR change

  Baseline

Study Arms (3)

donor

donor: normal heart samples from donor

Other: no intervention is involved

ICM

ICM: heart samples with ischemic cardiomyopathy

Other: no intervention is involved

NICM

NICM: heart samples with non-ischemic cardiomyopathy

Other: no intervention is involved

Interventions

no intervention is involved OTHER

ICM; NICM; donor

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

heart samples from healthy donor or from patients with ischemic or non-ischemic cardiomyopathy

You may qualify if:

• ischemic or non-ischemic cardiomyopathy Healthy Donor heart

You may not qualify if:

• Not diagnosed with ischemic or non-ischemic cardiomyopathy

Sponsors & Collaborators

• University of Minnesota: lead

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2017
• First Posted: October 18, 2017
• Study Start: August 1, 2011
• Primary Completion: April 1, 2016
• Study Completion: August 1, 2021
• Last Updated: March 2, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share