title: Interplay of electrical wavefronts as determinant of the response to cardiac resynchronization therapy in dyssynchronous canine hearts.
abstract: BACKGROUND
  The relative contribution of electromechanical synchronization and ventricular filling to the optimal hemodynamic effect in cardiac resynchronization therapy (CRT) during adjustment of stimulation-timings is incompletely understood. We investigated whether optimal hemodynamic effect in CRT requires collision of pacing-induced and intrinsic activation waves and optimal filling of the left ventricle (LV).
  
  
  RESULTS
  CRT was performed in dogs with chronic left bundle-branch block (n=8) or atrioventricular (AV) block (n=6) through atrial (A), right ventricular (RV) apex, and LV-basolateral pacing. A 100 randomized combinations of A-LV/A-RV intervals were tested. Total activation time (TAT) was calculated from >100 contact mapping electrodes. Mechanical interventricular dyssynchrony was determined as the time delay between upslopes of LV and RV pressure curves. Settings providing an increase in LVdP/dtmax (maximal rate of rise of left ventricular pressure) of ≥90% of the maximum LVdP/dtmax value were defined as optimal (CRTopt). Filling was assessed by changes in LV end-diastolic volume (EDV; conductance catheter technique). In all hearts, CRTopt was observed during multiple settings, providing an average LVdP/dtmax increase of ≈15%. In AV-block hearts, CRTopt exclusively depended on interventricular-interval and not on AV-interval. In left bundle-branch block hearts, CRTopt occurred at A-LV intervals that allowed fusion of LV-pacing-derived activation with right bundle-derived activation. In all animals, CRTopt occurred at settings resulting in the largest decrease in TAT and mechanical interventricular dyssynchrony, whereas LV EDV hardly changed.
  
  
  CONCLUSIONS
  In left bundle-branch block and AV-block hearts, optimal hemodynamic effect of CRT depends on optimal interplay between pacing-induced and intrinsic activation waves and the corresponding mechanical resynchronization rather than filling.
authors.affiliation: Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Strik
authors.forename: Lars B
authors.initials: LB
authors.lastname: van Middendorp
authors.forename: Patrick
authors.initials: P
authors.lastname: Houthuizen
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ploux
authors.forename: Arne
authors.initials: A
authors.lastname: van Hunnik
authors.forename: Marion
authors.initials: M
authors.lastname: Kuiper
authors.forename: Angelo
authors.initials: A
authors.lastname: Auricchio
authors.forename: Frits W
authors.initials: FW
authors.lastname: Prinzen
mesh_terms: D000818:Animals; D054537:Atrioventricular Block / Q000503:physiopathology / Q000628:therapy*; D002037:Bundle-Branch Block / Q000503:physiopathology / Q000628:therapy*; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D004867:Equipment Design; D006439:Hemodynamics; D011897:Random Allocation
keywords: bundle–branch block; cardiac resynchronization therapy; electrophysiology