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Heart Rhythm. 2013 Oct;10(10):1533-41. doi: 10.1016/j.hrthm.2013.07.038. Epub 2013 Jul 26.

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

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Department of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany. Electronic address:



Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias.


To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS.


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.


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.


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.


APD; APD(75); CC; Cardiac MRI; Cardiac electrophysiology; Diastolic function; ECG; EPS; I(Ca,L); I(Kr); IV; L-type Ca2+ current; LMC; LQT2; LQTS; LV; Long QT syndrome; MAP; MRI; QTc; Rabbits; Repolarization; SD; TTP; Vr; Vr_dia; Vz; Vz_dia; [Ca(2+)](i); action potential duration; action potential duration at 75% of repolarization; correlation coefficient; cytoplasmic Ca(2+) concentration; diastolic peak long-axis velocities; diastolic peak radial velocities; electrocardiogram; electrophysiological study; heart-rate corrected QT; intravenously; left ventricle/ventricular; long QT syndrome; long QT syndrome type 2; long-axis velocities; magnetic resonance imaging; monophasic action potential; pVT; polymorphic ventricular tachycardia; radial velocities; rapid delayed rectifier potassium current; standard deviation; time-to-peak velocities; wild-type littermate control

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