J wave syndromes: molecular and cellular mechanisms

Area of Science:

• Cardiology
• Electrophysiology
• Molecular Biology

Background:

• Early repolarization (ER) was historically considered benign but is now linked to malignant arrhythmias.
• Recent studies identify ER in specific ECG leads as a risk factor for life-threatening arrhythmias, termed early repolarization syndrome (ERS).
• Both Brugada syndrome (BrS) and ERS are characterized by accentuated J waves, classifying them as J wave syndromes.

Purpose of the Study:

• To review the clinical, genetic, cellular, and molecular mechanisms underlying J wave syndromes.
• To explore the shared and distinct features of Brugada syndrome and early repolarization syndrome.
• To discuss potential therapeutic interventions for J wave syndromes.

Main Methods:

• Review of experimental, case-control, and population-based studies.
• Analysis of ECG characteristics, clinical outcomes, and risk factors.
• Exploration of cellular and molecular mechanisms, including action potential notch accentuation and Ito current.

Main Results:

• ERS is associated with increased risk for life-threatening arrhythmias, particularly with ER patterns in inferior or infero-lateral leads.
• J wave syndromes (BrS and ERS) share commonalities in ECG findings, outcomes, risk factors, and arrhythmic mechanisms.
• Differences exist in J wave magnitude and lead location, suggesting a spectrum of phenotypic expression.
• A hypothesis suggests BrS and ERS result from preferential accentuation of the action potential notch in specific ventricular regions, exacerbated by cholinergic agonists.

Conclusions:

• J wave syndromes represent a spectrum of repolarization abnormalities with shared underlying mechanisms.
• Identifying individuals at risk for life-threatening arrhythmias associated with J wave syndromes remains a critical challenge.
• Pharmacological agents like quinidine, cilostazol, and isoproterenol show potential in reversing repolarization abnormalities.