Paced P-wave duration as a significant predictor for atrial high-rate episodes in patients with cardiac implantable electronic devices

Introduction: Atrial pacing can unmask or aggravate a preexisting interatrial block (IAB). Our study aimed to determine whether atrial pacing is associated with the development of atrial high-rate episodes (AHRE) during follow-up. Methods and Results: Patients with dual-chamber cardiac implantable electronic devices (CIED), no previous documented atrial fibrillation, and with a 6-month minimum follow-up were included. In all patients, sinus and paced P-wave duration was measured. AHRE was defined as an episode of atrial rate ≥ 225 bpm with a minimum duration of 5 min, excluding those documented during the first three months after implantation. Two hundred twenty patients were included (75 ± 10 years, 61% male). After a mean follow-up of 59±25 months, 46% of patients presented AHRE. Mean paced P-wave duration was significantly longer than the sinus P-wave duration (154±27 vs 115±18 ms; p < 0.001). Sinus and paced P-waves were significantly longer in those who developed AHRE (sinus: 119±20 vs 112±16; p = 0.006; paced: 161±29 vs 148±23; p < 0.001). A paced P-wave ≥160 ms was the best predictor of AHRE, especially those lasting >24 h (OR 4.2 (95% CI) [1.6-11.4]; p = 0.004). Conclusion: Atrial pacing significantly prolongs P-wave duration and is associated with further development of AHRE. A paced P-wave ≥160 ms is a strong predictor of AHRE and should be taken into consideration as a new definition of IAB in the presence of atrial pacing.

Optimizing Transesophageal Atrial Pacing in Mice to Detect Atrial Fibrillation

Mice are routinely used to investigate molecular mechanisms underlying the atrial fibrillation (AF) substrate. We sought to optimize transesophageal rapid atrial pacing (RAP) protocols for the detection of AF susceptibility in mouse models. Hypertensive and control C57Bl/6J mice were subjected to burst RAP at a fixed stimulus amplitude. The role of parasympathetic involvement in pacing-related atrioventricular (AV) block and AF was examined using an intraperitoneal injection of atropine. In a crossover study, burst and decremental RAP at twice diastolic threshold were compared for induction of AV block during pacing. The efficacy of burst and decremental RAP to elicit an AF phenotype was subsequently investigated in mice deficient in the lymphocyte adaptor protein (Lnk-/-) resulting in systemic inflammation, or the paired-like homeodomain 2 transcription factor (Pitx2+/-) as a positive control. When pacing at a fixed stimulus intensity, pacing-induced AV block with AF induction occurred frequently, so that there was no difference in AF burden between hypertensive and control mice. These effects were prevented by atropine administration, implicating parasympathetic activation due to ganglionic stimulation as the etiology. When mice with AV block during pacing were eliminated from analysis, male Lnk-/- mice displayed an AF phenotype only during burst RAP compared to controls whereas male Pitx2+/- mice showed AF susceptibility during burst and decremental RAP. Notably, Lnk-/- and Pitx2+/- females exhibited no AF phenotype. Our data support the conclusion that multiple parameters should be used to ascertain AF inducibility and facilitate reproducibility across models and studies.

Tachycardia and hypertension enhance tracer efflux from the spinal cord

Background Disruption of cerebrospinal fluid (CSF)/interstitial fluid (ISF) exchange in the spinal cord is likely to contribute to central nervous system (CNS) diseases that involve abnormal fluid accumulation, including spinal cord oedema and syringomyelia. However, the physiological factors that govern fluid transport in the spinal cord are poorly understood. The aims of this study were to determine the effects of cardiac pulsations and respiration on tracer signal increase, indicative of molecular movement following infusion into the spinal cord grey or white matter. Methods In Sprague Dawley rats, physiological parameters were manipulated such that the effects of spontaneous breathing (generating alternating positive and negative intrathoracic pressures), mechanical ventilation (positive intrathoracic pressure only), tachycardia (heart atrial pacing), as well as hypertension (pharmacologically induced) were separately studied. Since fluid outflow from the spinal cord cannot be directly measured, we assessed the molecular movement of fluorescent ovalbumin (AFO-647), visualised by an increase in tracer signal, following injection into the cervicothoracic spinal grey or white matter. Results Tachycardia and hypertension increased AFO-647 tracer efflux, while the concomitant negative and positive intrathoracic pressures generated during spontaneous breathing did not when compared to the positive-pressure ventilated controls. Following AFO-647 tracer injection into the spinal grey matter, increasing blood pressure and heart rate resulted in increased tracer movement away from the injection site compared to the hypotensive, bradycardic animals (hypertension: p = 0.05, tachycardia: p < 0.0001). Similarly, hypertension and tachycardia produced greater movement of AFO-647 tracer longitudinally along the spinal cord following injection into the spinal white matter (p < 0.0001 and p = 0.002, respectively). Tracer efflux was strongly associated with all blood vessel types. Conclusions Arterial pulsations have profound effects on spinal cord interstitial fluid homeostasis, generating greater tracer efflux than intrathoracic pressure changes that occur over the respiratory cycle, demonstrated by increased craniocaudal CSF tracer movement in the spinal cord parenchyma.

Blockade of Exosome Release Suppresses Atrial Fibrillation by Alleviating Atrial Fibrosis in Canines With Prolonged Atrial Pacing

Background: Clinical studies have shown that exosomes are associated with atrial fibrillation (AF). However, the roles and underlying mechanisms remain unclear. Hence, this study aimed to investigate the function of exosomes in AF development.Methods: Twenty beagles were randomly divided into the sham group (n = 6), the pacing group (n = 7), and the pacing + GW4869 group (n = 7). The pacing and GW4869 groups underwent rapid atrial pacing (450 beats/min) for 7 days. The GW4869 group received intravenous GW4869 injection (an inhibitor of exosome biogenesis/release, 0.3 mg/kg, once a day) during pacing. Electrophysiological measurements, transmission electron microscopy, nanoparticle tracking analysis, western blotting, RT-PCR, Masson's staining, and immunohistochemistry were performed in this study.Results: Rapid atrial pacing increased the release of plasma and atrial exosomes. GW4869 treatment markedly suppressed AF inducibility and reduced the release of exosomes. After 7 days of pacing, the expression of transforming growth factor-β1 (TGF-β1), collagen I/III, and matrix metalloproteinases was enhanced in the atrium, and the levels of microRNA-21-5p (miR-21-5p) were upregulated in both plasma exosomes and the atrium, while the tissue inhibitor of metalloproteinase 3 (TIMP3), a target of miR-21-5p, showed a lower expression in the atrium. The administration of GW4869 abolished these effects.Conclusions: The blockade of exosome release with GW4869 suppressed AF by alleviating atrial fibrosis in a canine model, which was probably related to profibrotic miR-21-5p enriched in exosomes and its downstream TIMP3/TGF-β1 pathway.

Atrial High-Rate Event Incidence and Predictors in Patients With Permanent Pacemaker Implantation

Objective: The present study aims to investigate the incidence and predictors of atrial high-rate events (AHREs) in patients with permanent pacemaker implants.Methods: A total of 289 patients who were implanted with a dual-chamber pacemaker due to complete atrioventricular block or symptomatic sick sinus syndrome (SSS) and had no previous history of atrial fibrillation were included in the present study. AHREs are defined as events with an atrial frequency of ≥175 bpm and a duration of ≥5 min. The patients were divided into two groups according to whether or not AHREs were detected during the follow-up: group A (AHRE+, n = 91) and group N (AHRE–, n = 198).Results: During the 12-month follow-up period, AHREs were detected in 91 patients (31.5%). The multivariate Cox regression analysis revealed that patient age [odds ratio [OR] = 1.041; 95% confidence interval [CI], 1.018–1.064; and P &lt; 0.001], pacemaker implantation due to symptomatic SSS (OR = 2.225; 95% CI, 1.227–4.036; and P = 0.008), and the percentage of atrial pacing after pacemaker implantation (OR = 1.010; 95% CI, 1.002–1.017; and P = 0.016) were independent AHRE predictors.Conclusion: The AHRE detection rate in patients with pacemaker implants was 31.5%. Patient age, pacemaker implantation due to symptomatic SSS, and the percentage of atrial pacing after pacemaker implantation were independent AHRE predictors.

Feasibility and efficacy using the KODEX-EPD imaging system in right atrial flutter ablation: a single center experience

Background Isthmus-dependent right atrial flutter is the most frequently encountered atrial flutter in clinical practice (80–90% of atrial flutters). Purpose The aim of our study was to assess as first experience the feasibility and safety of radiofrequency catheter ablation (RFCA) of cavo-tricuspid isthmus (CTI) guided by KODEX-EPD imaging system in patients presenting with typical atrial flutter (AFL). Methods 16 consecutive patients (mean age 68,46±7,8 years, 80% males) with diagnosis of AFL underwent RFCA guided by KODEX-EPD imaging system. In 15 patients the analysis performed during tachycardia showed a counter-clockwise activation. In 1 patient no tachycardia could be induced and the ablation was performed in sinus rhythm with fixed pacing from the coronary sinus. The KODEX-EPD imaging system was also used to guide ablation and to confirm persistent bidirectional block after ablation. Results Mean procedural time was 37,6±8,2 min, mean radiofrequency ablation time was 7,8±3,4 min, and mean fluoroscopy time was 2,1±1,2 min. All procedures were acutely successful with interruption of AFL during RFCA along the inferior CTI in 15 patients and achievement of the bidirectional conduction block in 16 patients proven by atrial pacing medial and lateral to the ablation line. There were no major procedural and 30-day complications. Over a mean follow-up of 18 months, we observed no recurrence of arrhythmia and no complications. Conclusions Our study shows that RFCA for AFL using the KODEX-EPD imaging system is feasible, safe, and effective. FUNDunding Acknowledgement Type of funding sources: None.

The impact of abnormal conduction zone on outcomes after catheter ablation for atrial fibrillation

Background The abnormal conduction zone (ACZ) in the left atrium (LA) has attracted attention as an arrhythmia substrate in atrial fibrillation (AF). Purpose We investigated whether the ACZ affects outcomes after catheter ablation (CA) for AF. Methods We studied 78 patients (42 Non-paroxysmal AF, 49 males, and 68±10 years) who received CA for AF. High-density LA mapping during high right atrial pacing was constructed gaining than 2000 points (average 4377±846 points). Isochronal activation maps created at 5-ms interval setting. ACZ was identified by locating a site with isochronal crowding of ≥3 isochrones, and ≥8 isochrones were defined as the conduction block zone (CBZ) in a 4-mm diameter tag (conduction velocity were calculated as ≤27 cm/s and≤10 cm/s, respectively). Result Recurrent AF was detected in 25/78 patients (32%) during the follow-up period (9.2±3.0 month). ACZ and CBZ were distributed linearly, and ACZ was observed in 73 of 78 patients and 8 of these 73 patients had the CBZ. Univariate analysis revealed that elevated body mass index (26.2±3.8 vs. 24.3±3.3 kg/m2, P=0.0303), the higher prevalence of non-paroxysmal AF (72% vs. 45%, P=0.0272), larger LA diameter (47.6±6.6 vs. 42.1±6.9 mm, P=0.0014), and longer length of ACZ (79.7±45.1 vs. 52.9±35.7 mm, P=0.0058) were associated with recurrent AF after CA. On multivariate analysis, longer ACZ was independently associated with recurrent AF. Moreover, patients with longer ACZ (cutoff value: 84 mm) had a higher risk of recurrent AF than shorter ACZ (12/22; 55% vs 13/56; 23%, log-rank P=0.0024). Conclusion The length of ACZ was associated with recurrent AF after CA. FUNDunding Acknowledgement Type of funding sources: None.