Nav Channel Complex Heterogeneity: New Targets for the Treatment of Arrhythmia?
Despite major breakthroughs in cardiovascular diagnostics and therapies over the past century, diseases of the heart remain the number one cause of death in the United States, nearing 600,000 deaths per year.1 Most of these deaths (200,000-400,000/year2) are due to cardiac arrhythmia where syncope and sudden death are often the first manifestations of heart disease. Foundational work of Keating and colleagues in the mid-1990's cemented the critical role of ion channel dysfunction in human arrhythmia.3 Today, we now know that ~35% of sudden unexplained death and ~20% of sudden infant death syndrome cases may be explained by mutations in cardiac ion channels ("cardiac channelopathies").4, 5 Further, defects in ion channel function have widely been observed in common forms of heart failure.6 This year marks the 25th anniversary of publication of the preliminary Cardiac Arrhythmia Suppression Trial (CAST) findings in New England Journal of Medicine.7 Here, we discuss new findings from Abriel and colleagues on Nav channel macromolecular complexes reported in this issue of Circulation8, and reflect on lessons learned in the ensuing years after CAST that may help propel advances in treatment of cardiovascular disease over the next quarter century.
- Received May 26, 2014.
- Accepted May 30, 2014.