Cardiac Alternans: From Bedside to Bench and Back

Circ Res. 2023 Jan 6;132(1):127-149. doi: 10.1161/CIRCRESAHA.122.321668. Epub 2023 Jan 5.

Abstract

Cardiac alternans arises from dynamical instabilities in the electrical and calcium cycling systems of the heart, and often precedes ventricular arrhythmias and sudden cardiac death. In this review, we integrate clinical observations with theory and experiment to paint a holistic portrait of cardiac alternans: the underlying mechanisms, arrhythmic manifestations and electrocardiographic signatures. We first summarize the cellular and tissue mechanisms of alternans that have been demonstrated both theoretically and experimentally, including 3 voltage-driven and 2 calcium-driven alternans mechanisms. Based on experimental and simulation results, we describe their relevance to mechanisms of arrhythmogenesis under different disease conditions, and their link to electrocardiographic characteristics of alternans observed in patients. Our major conclusion is that alternans is not only a predictor, but also a causal mechanism of potentially lethal ventricular and atrial arrhythmias across the full spectrum of arrhythmia mechanisms that culminate in functional reentry, although less important for anatomic reentry and focal arrhythmias.

Keywords: Brugada syndrome; atrial fibrillation; cardiovascular diseases; long QT syndrome; myocardial ischemia; torsades de pointes; ventricular fibrillation.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Arrhythmias, Cardiac
  • Calcium*
  • Death, Sudden, Cardiac / etiology
  • Electrocardiography / methods
  • Heart*
  • Humans

Substances

  • Calcium