Cardiac Alternans: From Bedside to Bench and Back

Area of Science:

• Cardiology
• Computational Biology
• Physiology

Background:

• Cardiac alternans are dynamical instabilities in the heart's electrical and calcium cycling systems.
• Alternans often precede life-threatening ventricular arrhythmias and sudden cardiac death.
• Understanding alternans is crucial for predicting and preventing cardiac events.

Purpose of the Study:

• To provide a holistic overview of cardiac alternans.
• To integrate clinical, theoretical, and experimental findings on alternans.
• To elucidate the mechanisms, arrhythmic manifestations, and electrocardiographic signatures of alternans.

Main Methods:

• Review of existing clinical observations, theoretical models, and experimental data.
• Summarization of demonstrated cellular and tissue-level alternans mechanisms (3 voltage-driven, 2 calcium-driven).
• Analysis of experimental and simulation results linking alternans to arrhythmogenesis and electrocardiographic characteristics.

Main Results:

• Detailed description of multiple voltage- and calcium-driven alternans mechanisms.
• Demonstration of the relevance of these mechanisms to arrhythmogenesis in various disease states.
• Correlation of alternans mechanisms with specific electrocardiographic patterns observed in patients.

Conclusions:

• Cardiac alternans are both predictors and causal mechanisms of lethal ventricular and atrial arrhythmias.
• Alternans are implicated in a broad spectrum of arrhythmia mechanisms, particularly functional reentry.
• While crucial for functional reentry, alternans play a lesser role in anatomic reentry and focal arrhythmias.