title: Analysis of lead placement optimization metrics in cardiac resynchronization therapy with computational modelling.
abstract: OBJECTIVE
  The efficacy of cardiac resynchronization therapy (CRT) is known to vary considerably with pacing location, however the most effective set of metrics by which to select the optimal pacing site is not yet well understood. Computational modelling offers a powerful methodology to comprehensively test the effect of pacing location in silico and investigate how to best optimize therapy using clinically available metrics for the individual patient.
  
  
  RESULTS
  Personalized computational models of cardiac electromechanics were used to perform an in silico left ventricle (LV) pacing site optimization study as part of biventricular CRT in three patient cases. Maps of response to therapy according to changes in total activation time (ΔTAT) and acute haemodynamic response (AHR) were generated and compared with preclinical metrics of electrical function, strain, stress, and mechanical work to assess their suitability for selecting the optimal pacing site. In all three patients, response to therapy was highly sensitive to pacing location, with laterobasal locations being optimal. ΔTAT and AHR were found to be correlated (ρ < -0.80), as were AHR and the preclinical activation time at the pacing site (ρ ≥ 0.73), however pacing in the last activated site did not result in the optimal response to therapy in all cases.
  
  
  CONCLUSIONS
  This computational modelling study supports pacing in laterobasal locations, optimizing pacing site by minimizing paced QRS duration and pacing in regions activated late at sinus rhythm. Results demonstrate information content is redundant using multiple preclinical metrics. Of significance, the correlation of AHR with ΔTAT indicates that minimization of QRSd is a promising metric for optimization of lead placement.
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas Hospital, London SE1 7EH, UK.|Institute of Biophysics, Medical University of Graz, Harrachgasse 21/IV, 8010 Graz, Austria.
authors.forename: Andrew
authors.initials: A
authors.lastname: Crozier
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas Hospital, London SE1 7EH, UK.
authors.forename: Bojan
authors.initials: B
authors.lastname: Blazevic
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas Hospital, London SE1 7EH, UK.
authors.forename: Pablo
authors.initials: P
authors.lastname: Lamata
authors.affiliation: Institute of Biophysics, Medical University of Graz, Harrachgasse 21/IV, 8010 Graz, Austria.
authors.forename: Gernot
authors.initials: G
authors.lastname: Plank
authors.affiliation: Department of Cardiology, Guy's and St. Thomas' Hospital, London SE1 7EH, London, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ginks
authors.affiliation: Department of Cardiology, Guy's and St. Thomas' Hospital, London SE1 7EH, London, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Duckett
authors.affiliation: Department of Cardiology, Guy's and St. Thomas' Hospital, London SE1 7EH, London, UK.
authors.forename: Manav
authors.initials: M
authors.lastname: Sohal
authors.affiliation: Department of Cardiology, Guy's and St. Thomas' Hospital, London SE1 7EH, London, UK.
authors.forename: Anoop
authors.initials: A
authors.lastname: Shetty
authors.affiliation: Department of Cardiology, Guy's and St. Thomas' Hospital, London SE1 7EH, London, UK.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Rinaldi
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas Hospital, London SE1 7EH, UK.
authors.forename: Reza
authors.initials: R
authors.lastname: Razavi
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas Hospital, London SE1 7EH, UK.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Niederer
authors.affiliation: Division of Imaging Sciences and Biomedical Engineering, King's College London, St Thomas Hospital, London SE1 7EH, UK np.smith@auckland.ac.nz.|Faculty of Engineering, University of Auckland, 20 Symonds St, Auckland 1010, New Zealand.
authors.forename: Nicolas P
authors.initials: NP
authors.lastname: Smith
mesh_terms: D000200:Action Potentials; D000368:Aged; D000369:Aged, 80 and over; D058406:Cardiac Resynchronization Therapy / Q000379:methods*; D058409:Cardiac Resynchronization Therapy Devices; D022062:Electrophysiologic Techniques, Cardiac; D004867:Equipment Design; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D006339:Heart Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D066230:Patient-Specific Modeling; D011237:Predictive Value of Tests; D012815:Signal Processing, Computer-Assisted; D013318:Stroke Volume; D016896:Treatment Outcome; D016277:Ventricular Function, Left
keywords: Cardiac resynchronization therapy; Computational modelling; Heart failure; Optimization; Patient-specific