Abstract 1837: Effects of the Gap Junction Modifier, GAP-134, on Conduction and Atrial Fibrillation/Flutter Inducibility in Dogs

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Eric I Rossman ◽  
Kun Liu ◽  
Gwen A Morgan ◽  
Robert E Swillo ◽  
John Butera ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Adult Population ◽  
Metabolic Stress ◽  
Right Atrial ◽  
Conduction Time ◽  
Medical Need ◽  
Cardiovascular Morbidity And Mortality ◽  
Right Atrial Appendage ◽  
The Right

Atrial fibrillation (AF) and atrial flutter (AFL), the most common sustained cardiac arrhythmias, are major contributors to cardiovascular morbidity and mortality in the adult population. Current pharmacologic treatment of AF/AFL is only moderately successful and not well tolerated among patients, highlighting an unmet medical need for safer, effective agents. GAP-134 is the first small molecule gap junction modifier developed for the prevention of AF/AFL. In preliminary experiments, this modified antiarrhythmic dipeptide with similar activity to the antiarrhythmic hexapeptide rotigaptide, significantly prevented conduction velocity slowing in rat atrial strips subjected to metabolic stress at 10 nM (5.6±9.4%) and 100 nM (0.4±5.0%) compared to controls (−29.1±5.3%). In the canine sterile pericarditis model, conduction time (CT, n=5) and AF/AFL inducibility (n=9) were measured 2–3 days post-operatively in closed chest studies, using electrodes placed at the right atrial appendage (RAA), the Bachmann’s bundle (BB), and the posterior left atrium (LA). CT, measured between the BB and LA, was significantly faster after GAP-134 infusion (average plasma concentration was 73.1 ng/ml) at RAA pacing rates of 200 bpm (66.2±1.0 ms vs 62.0±1.0 ms; p=2.49E-08), 300 bpm (64.4±0.9 ms vs 61.0±1.3 ms; p=2.67E-03), and 400 bpm (67.2±1.6 ms vs 65.0±1.9 ms; p=0.041). Induction of AF/AFL was attempted using a burst pacing protocol, at all three atrial sites, starting at 500 bpm and increasing at increments of 20 bpm until 800 bpm. The average number of successful AF/AFL inductions per animal was significantly decreased after GAP-134 infusion (2.7±0.6 vs 1.6±0.8; p=0.021), with the total number of inductions being decreased from 24 to 14. Mean AF/AFL duration per induction (603±119 s vs 260±116 s; p=0.021) and mean AF/AFL duration per animal (1364±419 s vs 705±483 s; p=0.049) were also significantly decreased after GAP-134 infusion, with total AF/AFL burden being decreased from 12280 s to 6348 s. In conclusion, GAP-134 shows consistent efficacy on measures of conduction and AF/AFL inducibility in the canine sterile pericarditis model. These findings, along with its oral bioavailability, underscore its potential as a highly effective atrial antiarrhythmic compound.

Abstract 15570: Direct Evidence of Endo-Epicardial Dissociation of the Atrial Wall in Patients With Longstanding Persistent Atrial Fibrillation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Natasja de Groot ◽  
Lisette vd Does ◽  
Ameeta Yaksh ◽  
Paul Knops ◽  
Pieter Woestijne ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Direct Evidence ◽  
Persistent Atrial Fibrillation ◽  
Right Atrial ◽  
Electrode Arrays ◽  
Atrial Wall ◽  
Ablative Therapies ◽  
Epicardial Layer ◽  
Right Atrial Appendage ◽  
The Right

Introduction: Transition of paroxysmal to longstanding persistent atrial fibrillation (LsPAF) is associated with progressive longitudinal dissociation in conduction and a higher incidence of focal fibrillation waves. The aim of this study was to provide direct evidence that the substrate of LsPAF consists of an electrical double-layer of dissociated waves, and that focal fibrillation waves are caused by endo-epicardial breakthrough. Hypothesis: LsPAF in humans is caused by electrical dissociation of the endo- and epicardial layer. Methods: Intra-operative mapping of the endo- and epicardial right atrial wall was performed in 9 patients with induced (N=4), paroxysmal (N=1), persistent (N=2) or longstanding-persistent AF (N=2). A clamp of two rectangular electrode-arrays (128 electrodes; inter-electrode distance 2mm) was introduced through an incision in the right atrial appendage. Series of 10 seconds of AF were analyzed and the incidence of endo-epicardial dissociation (≥15ms) was determined for all 128 endo-epicardial recording sites. Results: In patients with LsPAF the averaged degree of endo-epicardial dissociation was highest (24.9% vs. 5.9%). Using strict criteria for breakthrough (presence of an opposite wave within 4mm and <15ms before the origin of the focal wave), the far majority (77%) of all focal fibrillation waves could be attributed to endo-epicardial excitation. Conclusions: During LsPAF considerable differences in activation of the right endo- and epicardial wall exist. Endo-epicardial fibrillation waves that are out of phase, may conduct transmurally and create breakthrough waves in the opposite layer. This may explain the high persistence of AF and the low succes rate of ablative therapies in patients with LsPAF.

scholarly journals A jobb pitvari fülcse echokardiográfiás vizsgálata és annak klinikai jelentősége

2019 ◽  
Vol 160 (12) ◽  
pp. 443-447
Author(s):  
Attila Nemes ◽  
Kálmán Havasi ◽  
László Sághy ◽  
Mária Kohári ◽  
Tamás Forster
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Data ◽  
Thrombus Formation ◽  
Atrial Appendage ◽  
Present Review ◽  
Right Atrial ◽  
Right Heart ◽  
Right Atrial Appendage ◽  
The Right

Abstract: In case of atrial fibrillation, there is a higher risk of thrombus formation, which could affect the right heart as well. Visualization of the right atrial appendage is difficult; the aim of the present review was to demonstrate the role of routine echocardiographic techniques and to show related clinical data. Orv Hetil. 2019; 160(12): 443–447.

scholarly journals Atrial anti-tachycardia pacing resulting in termination of atrial flutter: intracardiac electrograms providing insight into the mechanism of arrhythmia termination

2019 ◽  
Vol 47 (7) ◽  
pp. 3389-3393
Author(s):  
Shingo Maeda ◽  
Masahiko Goya ◽  
Atsuhiko Yagishita ◽  
Yoshihide Takahashi ◽  
Mihoko Kawabata ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Atrial Flutter ◽  
Randomized Study ◽  
Right Atrial ◽  
Dual Chamber Pacemaker ◽  
Af Ablation ◽  
Right Atrial Appendage ◽  
Ablation Study ◽  
The Right ◽  
Insight Into

The “MINimizE Right Ventricular pacing to prevent Atrial fibrillation and heart failure” (MINERVA) multicenter randomized study demonstrated that atrial anti-tachycardia pacing (A-ATP) can effectively decrease the burden of atrial fibrillation (AF) in patients with bradycardia and atrial tachyarrhythmias. We herein describe the unique electrophysiological results of AF ablation in a patient for whom atrial flutter (AFL) was terminated by A-ATP from a Medtronic dual-chamber pacemaker. In this case, the atrial activation sequence indicated that the tachycardia was a right atrial typical flutter and that A-ATP from the right atrial appendage would thus be more likely to terminate the tachycardia. This is a novel case involving documented intracardiac electrograms captured during an AF ablation study in a patient in whom AFL was successfully terminated by A-ATP. These findings provide insight into the mechanisms by which A-ATP can terminate atrial arrhythmias.

scholarly journals Atrial Fibrillation Drivers: Redefining the Electrophysiological Substrate

2020 ◽  
Author(s):  
Markus Rottmann ◽  
Anna Pfenniger ◽  
Shin Yoo ◽  
David Johnson ◽  
Gail Elizabeth Geist ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Veins ◽  
Persistent Atrial Fibrillation ◽  
Right Atrial ◽  
Atrial Pacing ◽  
New Paradigm ◽  
Density Mapping ◽  
Right Atrial Appendage ◽  
The Right ◽  
Activation Delay

Background: We performed high-density mapping of persistent atrial fibrillation (AF) in animals and patients (1) to test that AF is due to greater than or equal 1 reentry, and (2) to characterize activation delay and reentries pre/ post pulmonary vein isolation (PVI). We determined electrophysiological characteristics that may predispose to the induction, maintenance, and reduction of AF. Methods and Results: This study includes 48 dogs and nine patients. 43 AF- and five sinus/ paced rhythm dogs (3-14 weeks rapid atrial pacing) were studied at open chest surgery with 117 epicardial electrograms (EGMs) (2.5mm dist.) in 6 bi-atrial regions. Rotational activity automatically detected with a new algorithm tracking the earliest and latest activation in all regions (5+/-2 per region) were stable over 424+/-505ms [120-4940ms]. Reentry stability was highest in the right atrial appendage (RAA) (405+/-219ms) and the posterior left atrium (PLA) (267+/-115ms) and anchored between >=3 zones of activation delay (15+/-5ms, median 13ms) defined as >10ms per 2.5mm. Cycle length (CL) and degree of focal fibrosis were highest in the PLA and left atrial free wall (LAFW) with 94+/-7ms, 96+/-5ms, and 49+/-14%, 47+/-19%. Fiber crossing density correlated with the stability of rotational activity (R=0.6, P<0.05). Activation delay was 2x higher in AF compared to sinus rhythm/paced rhythm (interval 200-500ms). Activation delay zones > 10ms were at the same locations, but increased 4x during AF vs. SR and were located at fiber crossings, fibrosis/ fat zones. Stability of rotational activity correlated with Organization Index (OI), Fraction Index (FI), Shannon's Entropy (ShEn), and CL (R>0.5, p< 0.0001). PVI in five hearts increased CL [2-14%] and reduced stability of rotational activity in nearly all regions remote to the pulmonary veins (PVs). Also in the clinical evaluation in nine patients using the HD-catheter (16 electrodes, 3mm dist.) activation delay at the reentrant trajectory was 2x higher at edges with maximal delay (20.5+/-8.1ms, median 19.6ms) vs (9.3+/-8.8ms, median 9.2ms) and 1.4 x higher during AF (13.0+/-18.7ms, median 7.2ms) compared to SR/ CS-pacing (18.0+/-11.6ms, median 17.7ms). Conclusion: Rotational activities in all bi-atrial regions anchored between small frequency-dependent activation delay zones in AF. PVI led to beneficial remodeling in bi-atrial regions remote to the PVs. These data may identify a new paradigm for persistent AF.

scholarly journals Prominent Eustachian Valve Mimicking Thrombus in Right Atrium Diagnosed with Computed Tomography in a Patient with Atrial Fibrillation

2020 ◽  
pp. 1-2
Author(s):  
Ibrahim SARI ◽  
Gülsüm Bingöl ◽  
Ibrahim SARI ◽  
Muharrem Nasıfov ◽  
Özge Özden Tok ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Right Atrium ◽  
Left Atrial Appendage ◽  
Thrombus Formation ◽  
Correct Diagnosis ◽  
Atrial Appendage ◽  
Right Atrial ◽  
Eustachian Valve ◽  
Right Atrial Appendage ◽  
The Right

A 51-year-old man presented with paroxsysmal atrial fibrillation (AF). Transthoracic echocardiography revealed mass of 2.3x0.6 cm adjacent to the superior part of the right atrium (RA) compatible with thrombus. Although thrombus formation in the setting of AF is more common in left atrial appendage and left atrium it can also be seen in right atrial appendage and RA. We performed cardiac computerized tomography (CCT) in order to clarify the nature of mass in RA and exclude coronary stenosis. CCT showed prominent eustachian valve measuring 3.2 cm which was not clear on echocardiography. This case underscores the importance of complementary cardiovascular imaging to facilitate the correct diagnosis.

scholarly journals Paroxysmal Atrial Fibrillation With Both Triggers and Rotational Drivers Within the Right Atrial Appendage

2019 ◽  
Vol 1 (4) ◽  
pp. 607-611
Author(s):  
Marshall B. Marcus ◽  
Jamie A. Shein ◽  
Aditi S. Vaishnav ◽  
Stavros E. Mountantonakis
Keyword(s):  
Atrial Fibrillation ◽  
Paroxysmal Atrial Fibrillation ◽  
Atrial Appendage ◽  
Right Atrial ◽  
Right Atrial Appendage ◽  
The Right

scholarly journals Atrial dilation as a substrate for atrial fibrillation in the canine complete chronic atrioventricular block model

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Smoczynska ◽  
H.D.M Beekman ◽  
R.W Chui ◽  
S Rajamani ◽  
M.A Vos
Keyword(s):  
Atrial Fibrillation ◽  
Atrioventricular Block ◽  
Volume Overload ◽  
Right Atrial ◽  
Funding Source ◽  
Private Company ◽  
Structural Remodeling ◽  
2D Echocardiography ◽  
Atrial Enlargement ◽  
The Right

Abstract Background Atrial fibrillation (AF) is the most common cardiac arrhythmia treated in clinical practice. Structural remodeling is characterized by atrial enlargement and contributes to the therapeutic resistance in patients with long-standing AF. Purpose To study the atrial arrhythmogenic and echocardiographic consequences induced by volume overload in the complete chronic atrioventricular block (CAVB) dog. Methods Echocardiographic and electrophysiological data was obtained in 14 anaesthetized Mongrel dogs, in acute AV-block (AAVB), after 6 weeks of CAVB (CAVB6) and CAVB10. Left atrial (LA) volume was determined with 2D echocardiography by using the biplane method. An electrocardiogram and monophasic action potentials (MAP) at the right atrial (RA) free wall were recorded. Atrial effective refractory period (AERP) was determined by continuous programmed electrical stimulation (PES) of 20 beats with a cycle length of 400 ms and an extrastimulus with decremental design until refractoriness was reached. A continuous PES protocol of 20 beats with an extrastimulus 5 ms longer than the AERP was applied for 150 seconds to trigger AF. After 5 min without arrhythmias, autonomic neuromodulation was performed by intravenous infusion (IV) of acetylcholine (1,5μg/kg/min to 6,0μg/kg/min) for 20 min followed by prompt IV infusion of isoprenaline (3μg/min) until the atrial heart rate increased by 20 bpm. PES with an extrastimulus was repeated for 150 seconds to induce AF. Results LA volume increased from 13.7±3.2 ml at AAVB to 20.5±5.9 ml* at CAVB6, and 22.7±6.0 ml* at CAVB10 (Fig. 1A). AERP was similar at AAVB, CAVB6, and CAVB10 (115.8±11.9, 117.3±11.7, and 106.8±12.1 ms respectively). Repetitive AF paroxysms of &gt;10 seconds were induced in 1/14 (7%) dogs at AAVB, 1/11 (9%) at CAVB6, and 5/10 (50%)* at CAVB10 (*p&lt;0.05) upon PES (Fig. 1B). Combined neuromodulation and PES did not increase the AF inducibility rate, but prolonged the longest episode of AF in the inducible dogs from 55±49 seconds to 236±202 seconds* at CAVB10 (Fig. 1C). LA volume was higher in inducible dogs 25.0±4.9 ml compared to 18.4±4.2 ml in non-inducible dogs at CAVB10. Conclusion Sustained atrial dilation forms a substrate for repetitive paroxysms of AF. Neuro-modulation prolongs AF episode duration in susceptible dogs. This animal model can be used to study structural remodeling of the atria and possible therapeutic advances in the management of AF. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Research

Right Atrial Thrombosis and Pulmonary Embolism: A Narrative Review

2020 ◽  
Vol 46 (08) ◽  
pp. 895-907
Author(s):  
Nina D. Anfinogenova ◽  
Oksana Y. Vasiltseva ◽  
Alexander V. Vrublevsky ◽  
Irina N. Vorozhtsova ◽  
Sergey V. Popov ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Pulmonary Embolism ◽  
High Risk ◽  
Transesophageal Echocardiography ◽  
Three Dimensional ◽  
Right Atrial ◽  
Treatment Protocols ◽  
High Risk Patients ◽  
Risk Patients ◽  
The Right

AbstractPrompt diagnosis of pulmonary embolism (PE) remains challenging, which often results in a delayed or inappropriate treatment of this life-threatening condition. Mobile thrombus in the right cardiac chambers is a neglected cause of PE. It poses an immediate risk to life and is associated with an unfavorable outcome and high mortality. Thrombus residing in the right atrial appendage (RAA) is an underestimated cause of PE, especially in patients with atrial fibrillation. This article reviews achievements and challenges of detection and management of the right atrial thrombus with emphasis on RAA thrombus. The capabilities of transthoracic and transesophageal echocardiography and advantages of three-dimensional and two-dimensional echocardiography are reviewed. Strengths of cardiac magnetic resonance imaging (CMR), computed tomography, and cardiac ventriculography are summarized. We suggest that a targeted search for RAA thrombus is necessary in high-risk patients with PE and atrial fibrillation using transesophageal echocardiography and/or CMR when available independently on the duration of the disease. High-risk patients may also benefit from transthoracic echocardiography with right parasternal approach. The examination of high-risk patients should involve compression ultrasonography of lower extremity veins along with the above-mentioned technologies. Algorithms for RAA thrombus risk assessment and protocols aimed at identification of patients with RAA thrombosis, who will potentially benefit from treatment, are warranted. The development of treatment protocols specific for the diverse populations of patients with right cardiac thrombosis is important.

Sign in / Sign up

Export Citation Format

Share Document