title: Modifying Ventricular Fibrillation by Targeted Rotor Substrate Ablation: Proof-of-Concept from Experimental Studies to Clinical VF.
abstract: BACKGROUND
  Recent work has suggested a role for organized sources in sustaining ventricular fibrillation (VF). We assessed whether ablation of rotor substrate could modulate VF inducibility in canines, and used this proof-of-concept as a foundation to suppress antiarrhythmic drug-refractory clinical VF in a patient with structural heart disease.
  
  
  RESULTS
  In 9 dogs, we introduced 64-electrode basket catheters into one or both ventricles, used rapid pacing at a recorded induction threshold to initiate VF, and then defibrillated after 18±8 seconds. Endocardial rotor sites were identified from basket recordings using phase mapping, and ablation was performed at nonrotor (sham) locations (7 ± 2 minutes) and then at rotor sites (8 ± 2 minutes, P = 0.10 vs. sham); the induction threshold was remeasured after each. Sham ablation did not alter canine VF induction threshold (preablation 150 ± 16 milliseconds, postablation 144 ± 16 milliseconds, P = 0.54). However, rotor site ablation rendered VF noninducible in 6/9 animals (P = 0.041), and increased VF induction threshold in the remaining 3. Clinical proof-of-concept was performed in a patient with repetitive ICD shocks due to VF refractory to antiarrhythmic drugs. Following biventricular basket insertion, VF was induced and then defibrillated. Mapping identified 4 rotors localized at borderzone tissue, and rotor site ablation (6.3 ± 1.5 minutes/site) rendered VF noninducible. The VF burden fell from 7 ICD shocks in 8 months preablation to zero ICD therapies at 1 year, without antiarrhythmic medications.
  
  
  CONCLUSIONS
  Targeted rotor substrate ablation suppressed VF in an experimental model and a patient with refractory VF. Further studies are warranted on the efficacy of VF source modulation.
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.|Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Krummen
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.|Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Hayase
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.|Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Vampola
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.|Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
authors.forename: Gordon
authors.initials: G
authors.lastname: Ho
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.|Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
authors.forename: Amir A
authors.initials: AA
authors.lastname: Schricker
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.|Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
authors.forename: Gautam G
authors.initials: GG
authors.lastname: Lalani
authors.affiliation: Department of Medicine, University of California, San Diego, California, USA.|Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Baykaner
authors.affiliation: Department of Bioengineering, University of California, San Diego, California, USA.
authors.forename: Taylor M
authors.initials: TM
authors.lastname: Coe
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, California, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Clopton
authors.affiliation: Department of Physics, University of California, San Diego, California, USA.
authors.forename: Wouter-Jan
authors.initials: WJ
authors.lastname: Rappel
authors.affiliation: Department of Bioengineering, University of California, San Diego, California, USA.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Omens
authors.affiliation: Stanford University, Palo Alto, California, USA.
authors.forename: Sanjiv M
authors.initials: SM
authors.lastname: Narayan
mesh_terms: D000818:Animals; D018780:Body Surface Potential Mapping / Q000379:methods*; D004285:Dogs; D005240:Feasibility Studies; D006329:Heart Conduction System / Q000601:surgery*; D010865:Pilot Projects; D025321:Surgery, Computer-Assisted / Q000379:methods*; D016896:Treatment Outcome; D014693:Ventricular Fibrillation / Q000175:diagnosis* / Q000601:surgery*
keywords: catheter ablation; implantable cardioverter defibrillator; phase mapping; rotors; ventricular fibrillation