First-in-Human Experience and Acute Procedural Outcomes Using a Novel Pulsed Field Ablation System: The PULSED AF Pilot Trial

Background: Pulsed field ablation (PFA) is a novel form of ablation using electrical fields to ablate cardiac tissue. There are only limited data assessing the feasibility and safety of this type of ablation in humans. Methods: PULSED AF (Pulsed Field Ablation to Irreversibly Electroporate Tissue and Treat AF; https://www.clinicaltrials.gov ; unique identifier: NCT04198701) is a nonrandomized, prospective, multicenter, global, premarket clinical study. The first-in-human pilot phase evaluated the feasibility and efficacy of pulmonary vein isolation using a novel PFA system delivering bipolar, biphasic electrical fields through a circular multielectrode array catheter (PulseSelect; Medtronic, Inc). Thirty-eight patients with paroxysmal or persistent atrial fibrillation were treated in 6 centers in Australia, Canada, the United States, and the Netherlands. The primary outcomes were ability to achieve acute pulmonary vein isolation intraprocedurally and safety at 30 days. Results: Acute electrical isolation was achieved in 100% of pulmonary veins (n=152) in the 38 patients. Skin-to-skin procedure time was 160±91 minutes, left atrial dwell time was 82±35 minutes, and fluoroscopy time was 28±9 minutes. No serious adverse events related to the PFA system occurred in the 30-day follow-up including phrenic nerve injury, esophageal injury, stroke, or death. Conclusions: In this first-in-human clinical study, 100% pulmonary vein isolation was achieved using only PFA with no PFA system–related serious adverse events.

Why Is Only Type 1 Electrocardiogram Diagnostic of Brugada Syndrome? Mechanistic Insights From Computer Modeling

Background: Three types of characteristic ST-segment elevation are associated with Brugada syndrome but only type 1 is diagnostic. Why only type 1 ECG is diagnostic remains unanswered. Methods: Computer simulations were performed in single cells, 1-dimensional cables, and 2-dimensional tissues to investigate the effects of the peak and late components of the transient outward potassium current (I to ), sodium current, and L-type calcium current (I Ca,L ) as well as other potassium currents on the genesis of ECG morphologies and phase 2 reentry (P2R). Results: Although a sufficiently large peak I to was required to result in the type 1 ECG pattern and P2R, increasing the late component of I to converted type 1 ECG to type 2 ECG and suppressed P2R. Increasing the peak I to promoted spiral wave breakup, potentiating the transition from tachycardia to fibrillation, but increasing the late I to prevented spiral wave breakup by flattening the action potential duration restitution and preventing P2R. A sufficiently large I Ca,L conductance was needed for P2R to occur, but once above the critical conductance, blocking I Ca,L promoted P2R. However, selectively blocking the window and late components of I Ca,L suppressed P2R, countering the effect of the late I to . Blocking either the peak or late components of sodium current promoted P2R, with the late sodium current blockade having the larger effect. As expected, increasing other potassium currents potentiated P2R, with ATP-sensitive potassium current exhibiting a larger effect than rapid and slow component of the delayed rectifier potassium current. Conclusions: The peak I to promotes type 1 ECG and P2R, whereas the late I to converts type 1 ECG to type 2 ECG and suppresses P2R. Blocking the peak I Ca,L and either the peak or the late sodium current promotes P2R, whereas blocking the window and late I Ca,L suppresses P2R. These results provide important insights into the mechanisms of arrhythmogenesis and potential therapeutic targets for treatment of Brugada syndrome.

Phrenic Nerve Injury During Cryoballoon-Based Pulmonary Vein Isolation: Results of the Worldwide YETI Registry

Background: Cryoballoon-based pulmonary vein isolation (PVI) has emerged as an effective treatment for atrial fibrillation. The most frequent complication during cryoballoon-based PVI is phrenic nerve injury (PNI). However, data on PNI are scarce. Methods: The YETI registry is a retrospective, multicenter, and multinational registry evaluating the incidence, characteristics, prognostic factors for PNI recovery and follow-up data of patients with PNI during cryoballoon-based PVI. Experienced electrophysiological centers were invited to participate. All patients with PNI during CB2 or third (CB3) and fourth-generation cryoballoon (CB4)-based PVI were eligible. Results: A total of 17 356 patients underwent cryoballoon-based PVI in 33 centers from 17 countries. A total of 731 (4.2%) patients experienced PNI. The mean time to PNI was 127.7±50.4 seconds, and the mean temperature at the time of PNI was −49±8 °C. At the end of the procedure, PNI recovered in 394/731 patients (53.9%). Recovery of PNI at 12 months of follow-up was found in 97.0% of patients (682/703, with 28 patients lost to follow-up). A total of 16/703 (2.3%) reported symptomatic PNI. Only 0.06% of the overall population showed symptomatic and permanent PNI. Prognostic factors improving PNI recovery are immediate stop at PNI by double-stop technique and utilization of a bonus-freeze protocol. Age, cryoballoon temperature at PNI, and compound motor action potential amplitude loss >30% were identified as factors decreasing PNI recovery. Based on these parameters, a score was calculated. The YETI score has a numerical value that will directly represent the probability of a specific patient of recovering from PNI within 12 months. Conclusions: The incidence of PNI during cryoballoon-based PVI was 4.2%. Overall 97% of PNI recovered within 12 months. Symptomatic and permanent PNI is exceedingly rare in patients after cryoballoon-based PVI. The YETI score estimates the prognosis after iatrogenic cryoballoon-derived PNI. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03645577.

Stimulant Drugs of Abuse and Cardiac Arrhythmias

Nonmedical use of prescription and nonprescription drugs is a worldwide epidemic, rapidly growing in magnitude with deaths because of overdose and chronic use. A vast majority of these drugs are stimulants that have various effects on the cardiovascular system including the cardiac rhythm. Drugs, like cocaine and methamphetamine, have measured effects on the conduction system and through several direct and indirect pathways, utilizing multiple second messenger systems, change the structural and electrical substrate of the heart, thereby promoting cardiac dysrhythmias. Substituted amphetamines and cocaine affect the expression and activation kinetics of multiple ion channels and calcium signaling proteins resulting in EKG changes, and atrial and ventricular brady and tachyarrhythmias. Preexisting conditions cause substrate changes in the heart, which decrease the threshold for such drug-induced cardiac arrhythmias. The treatment of cardiac arrhythmias in patients who take drugs of abuse may be specialized and will require an understanding of the unique underlying mechanisms and necessitates a multidisciplinary approach. The use of primary or secondary prevention defibrillators in drug abusers with chronic systolic heart failure is both sensitive and controversial. This review provides a broad overview of cardiac arrhythmias associated with stimulant substance abuse and their management.

Sex-Related Differences in Atrial Remodeling in Patients With Atrial Fibrillation: Relationship to Ablation Outcomes

Background: Population studies have demonstrated a range of sex differences including a higher prevalence of atrial fibrillation (AF) in men and a higher risk of AF recurrence in women. However, the underlying reasons for this higher recurrence are unknown. This study evaluated whether sex-based electrophysiological substrate differences exist to account for worse AF ablation outcomes in women. Methods: High-density electroanatomic mapping of the left atrium was performed in 116 consecutive patients with AF. Regional analysis was performed across 6 left atrium segments. High-density maps were created using a multipolar catheter (Biosense Webster) during distal coronary sinus pacing at 600 and 300 ms. Mean voltage and conduction velocity was determined. Complex fractionated signals and double potentials were manually annotated. Results: Overall, 42 (36%) were female, mean age was 61±8 years and AF was persistent in 52%. Global mean voltage was significantly lower in females compared with males at 600 ms (1.46±0.17 versus 1.84±0.15 mV, P <0.001) and 300 ms (1.27±0.18 versus 1.57±0.18 mV, P =0.013) pacing. These differences were seen uniformly across the left atrium. Females demonstrated significant conduction velocity slowing (34.9±6.1 versus 44.1±6.9 cm/s, P =0.002) and greater proportion of complex fractionated signals (9.9±1.7% versus 6.0±1.7%, P =0.014). After a median follow-up of 22 months (Q1–Q3: 15–29), females had significantly lower single-procedure (22 [54%] versus 54 [75%], P =0.029) and multiprocedure (24 [59%] versus 60 [83%], P =0.005) arrhythmia-free survival. Female sex and persistent AF were independent predictors of single and multiprocedure arrhythmia recurrence. Conclusions: Female patients demonstrated more advanced atrial remodeling on high-density electroanatomic mapping and greater post-AF ablation arrhythmia recurrence compared with males. These changes may contribute to sex-based differences in the clinical course of females with AF and in part explain the higher risk of recurrence.