Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits

Katja E. Odening, Bernd A. Jung, Corinna N. Lang, Rocio Cabrera Lozoya, David Ziupa, Marius Menza, Jatin Relan, Gerlind Franke, Stefanie Perez Feliz, Gideon Koren, Manfred Zehender, Christoph Bode, Michael Brunner, Maxime Sermesant, Daniela Föll

Research output: Contribution to journalArticlepeer-review

Abstract

Background Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias. Objective To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS. Methods Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities. In the same rabbits' hearts, monophasic APDs were assessed in corresponding segments. Results In LQT2 and E4031-treated rabbits, APD was longer in all left ventricular segments (P <.01) and APD dispersion was greater than that in LMC rabbits (P <.01). In diastole, peak radial velocities (Vr) were reduced in LQT2 and E4031-treated compared to LMC rabbits in LV base and mid (LQT2: -3.36 ± 0.4 cm/s, P <.01; E4031-treated: -3.24 ± 0.6 cm/s, P <.0001; LMC: -4.42 ± 0.5 cm/s), indicating an impaired diastolic function. Regionally heterogeneous diastolic Vr correlated with APD (LQT2: correlation coefficient [CC] 0.38, P =.01; E4031-treated: CC 0.42, P <.05). Time-to-diastolic peak Vr were prolonged in LQT2 rabbits (LQT2: 196.8 ± 2.9 ms, P <.001; E4031-treated: 199.5 ± 2.2 ms, P <.0001, LMC 183.1 ± 1.5), indicating a prolonged contraction duration. Moreover, in transgenic LQT2 rabbits, diastolic time-to-diastolic peak Vr correlated with APD (CC 0.47, P =.001). In systole, peak Vr were reduced in LQT2 and E4031-treated rabbits (P <.01) but longitudinal velocities or ejection fraction did not differ. Finally, random forest machine learning algorithms enabled a differentiation between LQT2, E4031-treated, and LMC rabbits solely based on "mechanical" magnetic resonance imaging data. Conclusions The prolongation of APD led to impaired diastolic and systolic function in transgenic and drug-induced LQT2 rabbits. APD correlated with regional diastolic dysfunction, indicating that LQTS is not purely an electrical but an electromechanical disorder.

Original languageEnglish
Pages (from-to)1533-1541
Number of pages9
JournalHeart Rhythm
Volume10
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

Keywords

  • CardiacMRI
  • Cardiacelectrophysiology
  • Diastolic function
  • Long QTsyndrome
  • Rabbits
  • Repolarization

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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