title: Beneficial Effect on Cardiac Resynchronization From Left Ventricular Endocardial Pacing Is Mediated by Early Access to High Conduction Velocity Tissue: Electrophysiological Simulation Study.
abstract: BACKGROUND
  Cardiac resynchronization therapy (CRT) delivered via left ventricular (LV) endocardial pacing (ENDO-CRT) is associated with improved acute hemodynamic response compared with LV epicardial pacing (EPI-CRT). The role of cardiac anatomy and physiology in this improved response remains controversial. We used computational electrophysiological models to quantify the role of cardiac geometry, tissue anisotropy, and the presence of fast endocardial conduction on myocardial activation during ENDO-CRT and EPI-CRT.
  
  
  RESULTS
  Cardiac activation was simulated using the monodomain tissue excitation model in 2-dimensional (2D) canine and human and 3D canine biventricular models. The latest activation times (LATs) for LV endocardial and biventricular epicardial tissue were calculated (LVLAT and TLAT), as well the percentage decrease in LATs for endocardial (en) versus epicardial (ep) LV pacing (defined as %dLV=100×(LVLATep-LVLATen)/LVLATep and %dT=100×(TLATep-TLATen)/TLATep, respectively). Normal canine cardiac anatomy is responsible for %dLV and %dT values of 7.4% and 5.5%, respectively. Concentric and eccentric remodeled anatomies resulted in %dT values of 15.6% and 1.3%, respectively. The 3D biventricular-paced canine model resulted in %dLV and %dT values of -7.1% and 1.5%, in contrast to the experimental observations of 16% and 11%, respectively. Adding fast endocardial conduction to this model altered %dLV and %dT to 13.1% and 10.1%, respectively.
  
  
  CONCLUSIONS
  Our results provide a physiological explanation for improved response to ENDO-CRT. We predict that patients with viable fast-conducting endocardial tissue or distal Purkinje network or both, as well as concentric remodeling, are more likely to benefit from reduced ATs and increased synchrony arising from endocardial pacing.
authors.affiliation: From the Department of Biomedical Engineering, King's College London, London, United Kingdom (E.R.H., J.M.B., S.C., T.J., A.W.C.L., M.S., R.R., C.A.R., S.A.N.); Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (J.M.B., S.C., T.J., M.S., C.A.R.); Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway (E.W.R.); and Institut für Biophysik, Medizinische Universität, Graz, Austria (G.P.).
authors.forename: Eoin R
authors.initials: ER
authors.lastname: Hyde
authors.affiliation: From the Department of Biomedical Engineering, King's College London, London, United Kingdom (E.R.H., J.M.B., S.C., T.J., A.W.C.L., M.S., R.R., C.A.R., S.A.N.); Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (J.M.B., S.C., T.J., M.S., C.A.R.); Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway (E.W.R.); and Institut für Biophysik, Medizinische Universität, Graz, Austria (G.P.).
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Behar
authors.affiliation: From the Department of Biomedical Engineering, King's College London, London, United Kingdom (E.R.H., J.M.B., S.C., T.J., A.W.C.L., M.S., R.R., C.A.R., S.A.N.); Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (J.M.B., S.C., T.J., M.S., C.A.R.); Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway (E.W.R.); and Institut für Biophysik, Medizinische Universität, Graz, Austria (G.P.).
authors.forename: Simon
authors.initials: S
authors.lastname: Claridge
authors.affiliation: From the Department of Biomedical Engineering, King's College London, London, United Kingdom (E.R.H., J.M.B., S.C., T.J., A.W.C.L., M.S., R.R., C.A.R., S.A.N.); Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (J.M.B., S.C., T.J., M.S., C.A.R.); Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway (E.W.R.); and Institut für Biophysik, Medizinische Universität, Graz, Austria (G.P.).
authors.forename: Tom
authors.initials: T
authors.lastname: Jackson
authors.affiliation: From the Department of Biomedical Engineering, King's College London, London, United Kingdom (E.R.H., J.M.B., S.C., T.J., A.W.C.L., M.S., R.R., C.A.R., S.A.N.); Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (J.M.B., S.C., T.J., M.S., C.A.R.); Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway (E.W.R.); and Institut für Biophysik, Medizinische Universität, Graz, Austria (G.P.).
authors.forename: Angela W C
authors.initials: AW
authors.lastname: Lee
authors.affiliation: From the Department of Biomedical Engineering, King's College London, London, United Kingdom (E.R.H., J.M.B., S.C., T.J., A.W.C.L., M.S., R.R., C.A.R., S.A.N.); Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (J.M.B., S.C., T.J., M.S., C.A.R.); Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway (E.W.R.); and Institut für Biophysik, Medizinische Universität, Graz, Austria (G.P.).
authors.forename: Espen W
authors.initials: EW
authors.lastname: Remme
authors.affiliation: From the Department of Biomedical Engineering, King's College London, London, United Kingdom (E.R.H., J.M.B., S.C., T.J., A.W.C.L., M.S., R.R., C.A.R., S.A.N.); Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (J.M.B., S.C., T.J., M.S., C.A.R.); Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway (E.W.R.); and Institut für Biophysik, Medizinische Universität, Graz, Austria (G.P.).
authors.forename: Manav
authors.initials: M
authors.lastname: Sohal
authors.affiliation: From the Department of Biomedical Engineering, King's College London, London, United Kingdom (E.R.H., J.M.B., S.C., T.J., A.W.C.L., M.S., R.R., C.A.R., S.A.N.); Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (J.M.B., S.C., T.J., M.S., C.A.R.); Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway (E.W.R.); and Institut für Biophysik, Medizinische Universität, Graz, Austria (G.P.).
authors.forename: Gernot
authors.initials: G
authors.lastname: Plank
authors.affiliation: From the Department of Biomedical Engineering, King's College London, London, United Kingdom (E.R.H., J.M.B., S.C., T.J., A.W.C.L., M.S., R.R., C.A.R., S.A.N.); Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (J.M.B., S.C., T.J., M.S., C.A.R.); Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway (E.W.R.); and Institut für Biophysik, Medizinische Universität, Graz, Austria (G.P.).
authors.forename: Reza
authors.initials: R
authors.lastname: Razavi
authors.affiliation: From the Department of Biomedical Engineering, King's College London, London, United Kingdom (E.R.H., J.M.B., S.C., T.J., A.W.C.L., M.S., R.R., C.A.R., S.A.N.); Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (J.M.B., S.C., T.J., M.S., C.A.R.); Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway (E.W.R.); and Institut für Biophysik, Medizinische Universität, Graz, Austria (G.P.).
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Rinaldi
authors.affiliation: From the Department of Biomedical Engineering, King's College London, London, United Kingdom (E.R.H., J.M.B., S.C., T.J., A.W.C.L., M.S., R.R., C.A.R., S.A.N.); Department of Cardiology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom (J.M.B., S.C., T.J., M.S., C.A.R.); Institute for Surgical Research, Oslo University Hospital, Rikshospitalet and KG Jebsen Cardiac Research Centre, University of Oslo, Oslo, Norway (E.W.R.); and Institut für Biophysik, Medizinische Universität, Graz, Austria (G.P.). steven.niederer@kcl.ac.uk.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Niederer
mesh_terms: D000818:Animals; D016880:Anisotropy; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D004285:Dogs; D022062:Electrophysiologic Techniques, Cardiac; D004699:Endocardium / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006352:Heart Ventricles / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans
keywords: cardiac resynchronization therapy; electric stimulation; electrophysiology; heart failure; heart ventricles