title: Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits.
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.
authors.affiliation: Department of Cardiology and Angiology I, Heart Center Freiburg University, Freiburg, Germany. Electronic address: katja.odening@uniklinik-freiburg.de.
authors.forename: Katja E
authors.initials: KE
authors.lastname: Odening
authors.forename: Bernd A
authors.initials: BA
authors.lastname: Jung
authors.forename: Corinna N
authors.initials: CN
authors.lastname: Lang
authors.forename: Rocio
authors.initials: R
authors.lastname: Cabrera Lozoya
authors.forename: David
authors.initials: D
authors.lastname: Ziupa
authors.forename: Marius
authors.initials: M
authors.lastname: Menza
authors.forename: Jatin
authors.initials: J
authors.lastname: Relan
authors.forename: Gerlind
authors.initials: G
authors.lastname: Franke
authors.forename: Stefanie
authors.initials: S
authors.lastname: Perez Feliz
authors.forename: Gideon
authors.initials: G
authors.lastname: Koren
authors.forename: Manfred
authors.initials: M
authors.lastname: Zehender
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Michael
authors.initials: M
authors.lastname: Brunner
authors.forename: Maxime
authors.initials: M
authors.lastname: Sermesant
authors.forename: Daniela
authors.initials: D
authors.lastname: Föll
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D000889:Anti-Arrhythmia Agents; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D003971:Diastole / Q000502:physiology; D005260:Female; D008133:Long QT Syndrome / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D010880:Piperidines; D011725:Pyridines; D011817:Rabbits
chemical_list: D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D011725:Pyridines; C063968:E 4031
keywords: 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