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Published on: February 26, 2013
Calcium Handling Abnormalities as a Target for Atrial Fibrillation Therapeutics: How Close to Clinical
Jordi Heijman1, Niels Voigt, Shokoufeh Ghezelbash
1Institute of Pharmacology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany.
Insights
Atrial fibrillation (AF) treatments face challenges with current drugs. Targeting calcium (Ca) handling abnormalities offers a promising new therapeutic strategy for effective AF rhythm control with fewer side effects.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Atrial fibrillation (AF) is a prevalent cardiac arrhythmia causing significant morbidity and mortality.
- Current antiarrhythmic drugs for AF rhythm control have limited efficacy and notable adverse effects, including proarrhythmia.
- Emerging research highlights the critical role of calcium (Ca) handling abnormalities in AF pathophysiology.
Purpose of the Study:
- To review AF-related Ca handling abnormalities.
- To discuss existing drugs targeting atrial Ca handling.
- To explore novel therapeutic targets and experimental drugs for AF.
Main Methods:
- Literature review of experimental studies on Ca handling in AF.
- Analysis of current antiarrhythmic agents and their mechanisms.
- Evaluation of novel therapeutic targets and investigational drugs.
Main Results:
- Ca handling abnormalities are central to AF, influencing ectopic activity, reentry, and remodeling.
- Existing drugs targeting Ca handling have limitations.
- Several novel targets and experimental compounds show therapeutic potential.
Conclusions:
- Targeting Ca handling abnormalities presents a promising avenue for developing new AF therapeutics.
- Further research is needed to assess the clinical translation of these novel approaches.
- Developing safer and more effective AF treatments relies on understanding Ca dysregulation.
Abstract:
Atrial fibrillation (AF) is the most common cardiac arrhythmia with a substantial impact on morbidity and mortality. Antiarrhythmic drugs play a major role in rhythm-control therapy of AF. However, currently available agents exhibit limited efficacy and pronounced adverse effects, notably drug-induced proarrhythmia. Recent experimental studies have identified that Ca handling abnormalities are critical elements in AF pathophysiology with central roles in atrial ectopic activity, reentry, and atrial remodeling suggesting that Ca handling abnormalities could be promising targets for novel AF therapeutics. Here, we summarize key aspects of AF-related Ca-handling abnormalities, describe currently available compounds targeting atrial Ca handling, and highlight potential novel targets and experimental drugs currently under investigation. Finally, we assess how close AF therapeutics based on Ca-handling abnormalities are to clinical implementation.
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