Leveraging a Genetic Proxy to Investigate the Effects of Lifelong Cardiac Sodium Channel Blockade
The <i>SCN5A</i> T220I variant, consistent with a previously described weak loss-of-function effect, acted like a genetic proxy for cardiac sodium channel blockade. This enabled us to gain new potentially clinically relevant insights for pharmacological sodium channel blockade, such as after myocardial infarction, which would be too risky to investigate with clinical trials. Our findings may also inspire redesign of cardiac sodium channel blockers.
Authors
- Dominic S. Zimmerman (ORCID: https://orcid.org/0000-0002-3544-3229)
- Julian Wanner (ORCID: https://orcid.org/0000-0002-1487-7909)
- Henrike Heyne (ORCID: https://orcid.org/0000-0001-9893-3850)
- Joel Rämö (ORCID: https://orcid.org/0000-0002-6429-5149)
- Girish N. Nadkarni (ORCID: https://orcid.org/0000-0001-6319-4314)
- Patrick T. Ellinor (ORCID: https://orcid.org/0000-0002-2067-0533)
- Teemu Niiranen (ORCID: https://orcid.org/0000-0002-7394-7487)
- Sean J. Jurgens (ORCID: https://orcid.org/0000-0002-1605-9782)
- Marie Pierre Krafft (ORCID: https://orcid.org/0000-0002-3379-2783)
Institutions
- Broad Institute (US)
- Mount Sinai Health System (US)
- Harvard University (US)
- Hasso Plattner Institute (DE)
- Turku University Hospital (FI)
- Finnish Institute for Health and Welfare (FI)
- Massachusetts General Hospital (US)
- Institute for Molecular Medicine Finland (FI)
- Mass General Brigham (US)
- Amsterdam University of Applied Sciences (NL)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Circulation
- Published
- 2025-11-24
- DOI
- https://doi.org/10.1161/circulationaha.125.075057
- Primary Topic
- Cardiac electrophysiology and arrhythmias
- Type
- article
- Field-Weighted Citation Impact
- 0.00