Dominant frequency increase rate predicts transition from paroxysmal to long-term persistent atrial fibrillation.

BACKGROUND: Little is known about the mechanisms underlying the transition from paroxysmal to persistent atrial fibrillation (AF). In an ovine model of long-standing persistent AF we tested the hypothesis that the rate of electric and structural remodeling, assessed by dominant frequency (DF) changes, determines the time at which AF becomes persistent. METHODS AND RESULTS: Self-sustained AF was induced by atrial tachypacing. Seven sheep were euthanized 11.5±2.3 days after the transition to persistent AF and without reversal to sinus rhythm; 7 sheep were euthanized after 341.3±16.7 days of long-standing persistent AF. Seven sham-operated animals were in sinus rhythm for 1 year. DF was monitored continuously in each group. Real-time polymerase chain reaction, Western blotting, patch clamping, and histological analyses were used to determine the changes in functional ion channel expression and structural remodeling. Atrial dilatation, mitral valve regurgitation, myocyte hypertrophy, and atrial fibrosis occurred progressively and became statistically significant after the transition to persistent AF, with no evidence for left ventricular dysfunction. DF increased progressively during the paroxysmal-to-persistent AF transition and stabilized when AF became persistent. Importantly, the rate of DF increase correlated strongly with the time to persistent AF. Significant action potential duration abbreviation, secondary to functional ion channel protein expression changes (CaV1.2, NaV1.5, and KV4.2 decrease; Kir2.3 increase), was already present at the transition and persisted for 1 year of follow up. CONCLUSIONS: In the sheep model of long-standing persistent AF, the rate of DF increase predicts the time at which AF stabilizes and becomes persistent, reflecting changes in action potential duration and densities of sodium, L-type calcium, and inward rectifier currents.

Impact of COVID-19 on the incidence of cardiac arrhythmias in implantable cardioverter defibrillator recipients followed by remote monitoring.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has been a fast-growing worldwide pandemic. AIMS: We aimed to investigate the incidence of cardiac arrhythmias among a large French cohort of implantable cardioverter defibrillator recipients over the first 5 months of 2020. METHODS: Five thousand nine hundred and fifty-four implantable cardioverter defibrillator recipients were followed by remote monitoring during the COVID-19 period (from 01 January to 31 May 2020). Data were obtained from automated remote follow-up of implantable cardioverter defibrillators utilizing the Implicity® platform. For all patients, the type of arrhythmia (atrial fibrillation, ventricular tachycardia or ventricular fibrillation), the number of ventricular arrhythmia episodes and the type of implantable cardioverter defibrillator-delivered therapy were recorded. RESULTS: A total of 472 (7.9%) patients presented 4917 ventricular arrhythmia events. An increase in ventricular arrhythmia incidence was observed after the first COVID-19 case in France, and especially during weeks #10 and #11, at the time of major governmental measures, with an increase in the incidence of antitachycardia pacing delivered therapy. During the 11 weeks before the lockdown order, the curve of the percentage of live-stream television coverage of COVID-19 information matched the ventricular arrhythmia incidence. During the lockdown, the incidence of ventricular arrhythmia decreased significantly compared with baseline (0.05±0.7 vs. 0.09±1.2 episodes per patient per week, respectively; P<0.001). Importantly, no correlation was observed between ventricular arrhythmia incidence and the curve of COVID-19 incidence. No changes were observed regarding atrial fibrillation/atrial tachycardia episodes over time. CONCLUSIONS: An increase in ventricular arrhythmia incidence was observed in the 2 weeks before the lockdown order, at the time of major governmental measures. Ventricular arrhythmia incidence decreased dramatically during the lockdown.

Long-term frequency gradients during persistent atrial fibrillation in sheep are associated with stable sources in the left atrium.

BACKGROUND: Dominant frequencies (DFs) of activation are higher in the atria of patients with persistent than paroxysmal atrial fibrillation (AF), and left atrial (LA)-to-right atrial (RA) DF gradients have been identified in both. However, whether such gradients are maintained as long-term persistent AF is established remains unexplored. We aimed at determining in vivo the time course in atrial DF values from paroxysmal to persistent AF in sheep and testing the hypothesis that an LA-to-RA DF difference is associated with LA drivers in persistent AF. METHODS AND RESULTS: AF was induced using RA tachypacing (n=8). Electrograms were obtained weekly from an RA lead and an implantable loop recorder implanted near the LA. DFs were determined for 5-second-long electrograms (QRST subtracted) during AF in vivo and in ex vivo optical mapping. Underlying structural changes were compared with weight-matched controls (n=4). After the first AF episode, DF increased gradually during a 2-week period (7±0.21 to 9.92±0.31 Hz; n=6; P<0.05). During 9 to 24 weeks of AF, the DF values on the implantable loop recorder were higher than the RA (10.6±0.08 versus 9.3±0.1 Hz, respectively; n=7; P<0.0001). Subsequent optical mapping confirmed a DF gradient from posterior LA-to-RA (9.1±1.0 to 6.9±0.9 Hz; P<0.05) and demonstrated patterns of activation compatible with drifting rotors in the posterior LA. Persistent AF sheep showed significant enlargement of the posterior LA compared with controls. CONCLUSIONS: In the sheep, transition from paroxysmal to persistent AF shows continuous LA-to-RA DF gradients in vivo together with enlargement of the posterior LA, which harbors the highest frequency domains and patterns of activation compatible with drifting rotors.

Time- and frequency-domain analyses of atrial fibrillation activation rate: the optical mapping reference.

BACKGROUND: Time- and frequency-domain estimates of activation rate have been proposed to guide atrial fibrillation (AF) ablation in patients, but their electrophysiological correlates are unclear. OBJECTIVE: This study sought to examine the relative correlation of average electrical cycle length (CL) and dominant frequency (DF) during AF with reference optical mapping measures. METHODS: Eight sheep hearts were Langendorff-perfused and superfused with oxygenated Tyrode solution inside a tank representing the human thorax. Optical mapping (DI-4-ANEPPS) of 4 × 4 cm2 in the left atrium was performed at 0.5 mm/pixel and 600 fps. A 20-pole catheter was placed in the optical field of view to acquire 1.2-kHz unipolar recordings by the EnSite NavX System (ENS; St. Jude Medical, St. Paul, MN) optimized for CL and DF calculation. During AF, 5-second-long simultaneous optical and electrical signals were analyzed for CL and DF. RESULTS: During pacing, DF measurements had fewer false results than CL (6.6% to 2.5% vs. 21.5% to 4.4% depending on filtering, P <.001). During AF in regions showing periodic waves on both sides of the catheter optical 1,000/CL versus DF correlation showed 95% confidence identity and was better than unipolar measurements in the ENS (adjusted R(2): 0.58879 vs. 0.12902; P < 10(-6)). DFs of unipolar signals correlated better than CLs with DFs of optical signals. Similarly, bipolar DF correlation with optical DF was not different from identity (P >.157), but the bipolar CL showed smaller identity with the optical CL (P <.0004). CONCLUSION: DF values of unipolar and bipolar signals correlate with those of optical signals better than CL values for the respective signals.