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Electro-mechanical (dys-)function in long QT syndrome type 1.

David Ziupa1, Marius Menza2, Susanne Koppermann1

  • 1Department of Cardiology and Angiology I, Heart Center, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany.

International Journal of Cardiology
|July 19, 2018
PubMed
Summary
This summary is machine-generated.

Long QT syndrome (LQTS) type 1 rabbits show normal mechanical function initially. Further repolarization prolongation unmasks distinct systolic and diastolic dysfunction, highlighting the impact of ion channel dysfunction.

Keywords:
Electro-mechanical dysfunctionGenotype differencesI(Kr)-blockadeLong QT syndromeTissue-phase mapping cardiac MRI

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Area of Science:

  • Cardiology
  • Molecular Biology
  • Biophysics

Background:

  • Long QT syndrome (LQTS) is characterized by prolonged cardiac repolarization.
  • Subclinical mechanical dysfunction is associated with LQTS.
  • LQTS type 1 (LQT1) involves loss of IKs function.

Purpose of the Study:

  • To investigate cardiac mechanical function in LQT1 rabbits.
  • To determine how further repolarization prolongation affects mechanical function in LQT1.
  • To elucidate the role of IKr blockade (E-4031) in modifying LQT1 mechanical function.

Main Methods:

  • Tissue phase mapping MRI, ECG, and epicardial action potential recordings in LQT1 and wild-type rabbits.
  • Analysis of ion channel and Ca2+ handling protein expression.
  • In silico single-cell action potential and tension modeling.

Main Results:

  • LQT1 rabbits exhibited longer QT intervals but similar baseline mechanical function compared to wild-type.
  • E-4031 significantly prolonged QT intervals more in LQT1 rabbits.
  • E-4031 unmasked LQT1-specific mechanical alterations, including increased systolic and decreased diastolic peak velocities, correlating with QT prolongation.

Conclusions:

  • Baseline mechanical function in LQT1 is preserved despite QT prolongation.
  • Further repolarization prolongation with an IKr blocker unmasks significant mechanical dysfunction in LQT1.
  • The extent of QT prolongation and the specific ion currents involved are critical for mechanical dysfunction in LQTS.