Modifying Ventricular Fibrillation by Targeted Rotor Substrate Ablation: Proof‐of‐Concept from Experimental Studies to Clinical VF

Abstract

Introduction 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. Methods and 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.

Spatiotemporal Progression of Early Human Ventricular Fibrillation

“…The ASI map of this patient reveals regions of elevated ASI that are consistent with the rotational activity in the isochronal maps. This patient was described in an earlier report (8) and had, prior to ablation, repetitive ICD shocks due to VF refractory to antiarrhythmic drugs. Targeted ablation was carried out at the site identified in the right panels of Fig.…”

“…Third, the mapping system only registers the endocardium and is not able to record intramural events or epicardial activation. The system, however, is able to determine endocardial spatio-temporal activity that has mechanistic relevance (8,23). Combining endocardial mapping with an epicardial registration modality would be an interesting future direction.…”

“…Nonetheless, early VF is an important link in the chain of events leading to sustained VF, and is also the time period in which symptoms such as syncope first present. Thus, an improved understanding of early VF is critical to improve current and emerging VF therapies including antiarrhythmic drugs, defibrillation, and ablation (8). Furthermore, our findings are complementary to seminal work performed in longer duration VF (29) in which alternative mechanisms may predominate.…”

“…Recent work in our laboratory mapped human VF and demonstrated that spiral waves, identified visually from computed phase maps, were present in the majority of patients (7). Furthermore, this study found that sustained episodes requiring defibrillation to terminate were characterized by greater spiral wave stability (7), and that ablation of VF sources increased the VF threshold in an animal model and patient with clinical VF (8). …”

Impact of number of co-existing rotors and inter-electrode distance on accuracy of rotor localization

“…Rotor mapping and targeting using focal impulse and rotor modulation (FIRM) is one of the most well-studied approaches to catheter ablation of persistent AF [9] and VF [10]. Several mechanisms have been proposed as to how focal ablation of the rotor region results in AF termination [11].…”