Objective We mapped human ventricular fibrillation (VF) to define mechanistic differences between episodes requiring defibrillation versus those that spontaneously terminate. Background VF is a leading cause of mortality, yet episodes may also self-terminate. We hypothesized that the initial maintenance of human VF is dependent upon the formation and stability of VF rotors. Methods We enrolled 26 consecutive patients (age 64±10 years, n=13 with LV dysfunction) during ablation procedures for ventricular arrhythmias, using 64-electrode basket catheters in both ventricles to map VF prior to prompt defibrillation per IRB-approved protocol. Fifty-two inductions were attempted and 36 VF episodes were observed. Phase analysis was applied to identify bi-ventricular rotors in the first 10 seconds or until VF terminated, whichever came first (11.4±2.9 seconds to defibrillator charging). Results Rotors were present in 16 of 19 patients with VF, and in all patients with sustained VF. Sustained, but not self-limiting VF, was characterized by greater rotor stability: (1) rotors were present in 68±17% of cycles in sustained versus 11±18% of cycles in self-limiting VF (p<0.001); with (2) maximum continuous rotations greater in sustained (17±11, range 7–48) versus self-limiting VF (1.1±1.4, range 0–4, p<0.001). Additionally, biventricular rotor locations in sustained VF were conserved across multiple inductions (7/7 patients, p=0.025). Conclusions In patients with and without structural heart disease, the formation of stable rotors identifies individuals whose VF requires defibrillation from those in whom VF spontaneously self-terminates. Future work should define the mechanisms that stabilize rotors and evaluate whether rotor modulation may reduce subsequent VF risk.

Background Mechanisms of atrial fibrillation (AF) initiation are incompletely understood. We hypothesized that rate-dependent changes (restitution) in action potential duration (APD) and activation latency are central targets for clinical interventions that induce AF. We tested this hypothesis using clinical experiments and computer models. Methods and Results In 50 patients (20 persistent, 23 paroxysmal AF, 7 controls), we used monophasic action potential catheters to define left atrial APD restitution, activation latency and AF incidence from premature extrastimuli. Isoproterenol (n=14), adenosine (n=10), or rapid pacing (n=36) were then initiated to determine impact on these parameters. Compared with baseline in AF patients, isoproterenol and rapid pacing decreased activation latency (64±14vs 31±13 vs 24±14 ms, p<0.05), steepened maximum APD restitution slope (0.8±0.7 vs 1.7±0.5 vs 1.1±0.5, p<0.05), and increased AF incidence (12% vs 64% vs 84%, p<0.05). Conversely, adenosine shortened APD (p<0.05), yet increased activation latency (86±27 ms, p=0.002) so that maximum APD restitution slope did not steepen (1.0±0.5, p=NS) and AF incidence was unchanged (10%, p=NS). In controls, no intervention steepened APD restitution or initiated AF. Computational modeling revealed that isoproterenol steepened APD restitution by increased ICaL and decreased activation latency via enhanced IKr inactivation, while rapid pacing steepened APD restitution via increased IK1. Conclusions Steep APD restitution is a common pathway for AF initiation by isoproterenol and tachycardia, via reduced activation latency that enables engagement of steep APD restitution at rapid rates. Modeling suggests AF initiation from each intervention uses distinct ionic mechanisms. This insight may help design interventions to prevent AF.

Objective: Precurved cochlear implant (CI) electrode arrays have demonstrated superior audiometric outcomes compared with straight electrodes in a handful of studies. However, previous comparisons have often failed to account for preoperative hearing and age. This study compares hearing outcomes for precurved and straight electrodes by a single manufacturer while controlling for these and other factors in a large cohort. Study Design: Retrospective cohort study. Setting: Tertiary academic medical center. Patients: Two hundred thirty-one adult CI recipients between 2015 and 2021 with cochlear (Sydney, Australia) 522/622 (straight) or 532/632 (precurved) electrode arrays. Interventions: Postactivation speech recognition and audiometric testing. Main Outcome Measures: Speech recognition testing (consonantnucleus-consonant word [CNCw] and AzBio) was collected at 6 and 12 months postactivation. Hearing preservation was characterized by a low-frequency pure-tone average shift, or the change between preoperative and postoperative low-frequency pure-tone average. Results: Two hundred thirty-one patients (253 ears) with 6-month and/or 12-month CNCw or AzBio testing were included. One hundred forty-nine (59%) and 104 (41%) ears were implanted with straight and precurved electrode arrays, respectively. Average age at implantation was 70 years (interquartile range [IQR], 58-77 y). There was no significant difference in mean age between groups. CNCw scores were significantly different ( p = 0.001) between straight (51%; IQR, 36-67%) and precurved arrays (64%; IQR, 48-72%). AzBio scores were not significantly different ( p = 0.081) between straight (72%; IQR, 51-87%) and precurved arrays (81%; IQR, 57-90%). Controlling for age, race, sex, preoperative hearing, and follow-up time, precurved electrode arrays performed significantly better on CNCw (b = 10.0; 95% confidence interval, 4.2-16.0; p < 0.001) and AzBio (b = 8.9; 95% confidence interval, 1.8-16.0;, p = 0.014) testing. Hearing preservation was not different between electrodes on adjusted models. Conclusion: During the study period, patients undergoing placement of precurved electrode arrays had significantly higher CNC and AzBio scores than patients receiving straight electrodes, even after controlling for age, preoperative hearing, and follow-up time. Professional Practice Gap and Educational Need: Understanding the difference in audiometric outcomes between precurved and straight electrode arrays will help to guide electrode selection. Learning Objective: To understand differences in speech recognition scores postoperatively by electrode array type (precurved versus straight).