Electromechanical reciprocity and arrhythmogenesis in long-QT syndrome and beyond

Katja E Odening*, Henk J van der Linde, Michael J Ackerman, Paul G A Volders, Rachel M A Ter Bekke*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

Abstract

An abundance of literature describes physiological and pathological determinants of cardiac performance, building on the principles of excitation-contraction coupling. However, the mutual influencing of excitation-contraction and mechano-electrical feedback in the beating heart, here designated 'electromechanical reciprocity', remains poorly recognized clinically, despite the awareness that external and cardiac-internal mechanical stimuli can trigger electrical responses and arrhythmia. This review focuses on electromechanical reciprocity in the long-QT syndrome (LQTS), historically considered a purely electrical disease, but now appreciated as paradigmatic for the understanding of mechano-electrical contributions to arrhythmogenesis in this and other cardiac conditions. Electromechanical dispersion in LQTS is characterized by heterogeneously prolonged ventricular repolarization, besides altered contraction duration and relaxation. Mechanical alterations may deviate from what would be expected from global and regional repolarization abnormalities. Pathological repolarization prolongation outlasts mechanical systole in patients with LQTS, yielding a negative electromechanical window (EMW), which is most pronounced in symptomatic patients. The electromechanical window is a superior and independent arrhythmia-risk predictor compared with the heart rate-corrected QT. A negative EMW implies that the ventricle is deformed-by volume loading during the rapid filling phase-when repolarization is still ongoing. This creates a 'sensitized' electromechanical substrate, in which inadvertent electrical or mechanical stimuli such as local after-depolarizations, after-contractions, or dyssynchrony can trigger abnormal impulses. Increased sympathetic-nerve activity and pause-dependent potentiation further exaggerate electromechanical heterogeneities, promoting arrhythmogenesis. Unraveling electromechanical reciprocity advances the understanding of arrhythmia formation in various conditions. Real-time image integration of cardiac electrophysiology and mechanics offers new opportunities to address challenges in arrhythmia management.

Original languageEnglish
Pages (from-to)3018-3028
Number of pages14
JournalEuropean Heart Journal
Volume43
Issue number32
Early online date21 Apr 2022
DOIs
Publication statusPublished - 21 Aug 2022

Keywords

  • Arrhythmogenesis
  • CANINE MODEL
  • CONTRACTION-EXCITATION FEEDBACK
  • Electromechanical reciprocity
  • Electromechanical window
  • Long-QT syndrome
  • MECHANOELECTRIC FEEDBACK
  • MONOPHASIC ACTION-POTENTIALS
  • Mechanical dispersion
  • Mechanical function
  • RABBIT MODELS
  • RISK STRATIFICATION
  • TO-BEAT VARIABILITY
  • TORSADE-DE-POINTES
  • VENTRICULAR-ARRHYTHMIAS
  • WALL-MOTION ABNORMALITY

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