Right ventricular arrhythmogenesis in failing human heart: The role of conduction and repolarization remodeling

Qing Lou, Deborah L. Janks, Katherine M. Holzem, Di Lang, Birce Onal, Christina M. Ambrosi, Vadim V. Fedorov, I. Wen Wang, Igor R. Efimov

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Increased dispersion of repolarization has been suggested to underlie increased arrhythmogenesis in human heart failure (HF). However, no detailed repolarization mapping data were available to support the presence of increased dispersion of repolarization in failing human heart. In the present study, we aimed to determine the existence of enhanced repolarization dispersion in the right ventricular (RV) endocardium from failing human heart and examine its association with arrhythmia inducibility. RV free wall preparations were dissected from five failing and five nonfailing human hearts, cannulated and coronary perfused. RV endocardium was optically mapped from an ~6.3 × 6.3 cm2 field of view. Action potential duration (APD), dispersion of APD, and conduction velocity (CV) were quantified for basic cycle lengths (BCL) ranging from 2,000 ms to the functional refractory period. We found that RV APD was significantly prolonged within the failing group compared with the nonfailing group (560 ± 44 vs. 448 ± 39 ms, at BCL = 2,000 ms, P < 0.05). Dispersion of APD was increased in three failing hearts (161 ± 5 vs. 86 ± 19 ms, at BCL = 2,000 ms). APD alternans were induced by rapid pacing in these same three failing hearts. CV was significantly reduced in the failing group compared with the nonfailing group (81 ± 11 vs. 98 ± 8 cm/s, at BCL = 2,000 ms). Arrhythmias could be induced in two failing hearts exhibiting an abnormally steep CV restitution and increased dispersion of repolarization due to APD alternans. Dispersion of repolarization is enhanced across the RV endocardium in the failing human heart. This dispersion, together with APD alternans and abnormal CV restitution, could be responsible for the arrhythmia susceptibility in human HF.

Original languageEnglish (US)
Pages (from-to)H1426-H1434
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume303
Issue number12
DOIs
StatePublished - Dec 15 2012

Keywords

  • Action potential duration
  • Conduction abnormality
  • Dispersion of repolarization
  • Human heart failure
  • Right ventricle

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Lou, Q., Janks, D. L., Holzem, K. M., Lang, D., Onal, B., Ambrosi, C. M., Fedorov, V. V., Wang, I. W., & Efimov, I. R. (2012). Right ventricular arrhythmogenesis in failing human heart: The role of conduction and repolarization remodeling. American Journal of Physiology - Heart and Circulatory Physiology, 303(12), H1426-H1434. https://doi.org/10.1152/ajpheart.00457.2012