Abstract 1087: Effects of Oral Gap Junction Conduction-Enhancing Antiarrhythmic Peptide GAP-134 on Experimental Atrial Fibrillation in Dogs

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Gabriel Laurent ◽  
Howard Leong-Poi ◽  
Gordon Moe ◽  
Xudong Hu ◽  
Petsy Pui-Sze So ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Electrophysiological Study ◽  
Placebo Treatment ◽  
Refractory Periods ◽  
Percent Change ◽  
Dog Model ◽  
Antiarrhythmic Peptide ◽  
The Mean ◽  
Mechanical Remodeling

Background: Abnormal intercellular communication caused by connexin dysfunction may promote atrial fibrillation (AF). Objective: To assess the effect of the gap junction conduction-enhancing antiarrhythmic peptide GAP-134 on AF inducibility and maintenance in a new dog model of atrial cardiomyopathy. Methods and Results: Twenty four dogs underwent simultaneous atrioventricular pacing (2 weeks at 220 bpm, atrioventricular delay 0 ms), and were randomly assigned to placebo treatment (PACED-PLACEBO; 12 dogs) or oral GAP-134 (PACED-GAP 134; 12 dogs) (starting at day 0). Percent change in left atrial systolic area (Δ% LASA) from baseline to 2 weeks was calculated using trans-esophageal echocardiography. At 2 weeks, animals underwent an open chest electrophysiological study; conduction velocity (CV) when pacing at 150ms cycle length (CL), effective refractory periods (ERP) and AF vulnerability were measured. The mean plasma concentration of GAP-134 was 557 ± 239 nmol/L. GAP-134 increased CV (395.1 ± 63.2 vs 307.8 ± 54.6 mm/s, p<0.01), and shortened ERP at 200ms CL (104.0 ± 8.6 vs 112.8 ± 11.5 ms, P<0.05). GAP-134 significantly reduced AF inducibility [% burst attempts inducing AF] and maintenance [mean AF duration, number of episodes >10min] in dogs with less than 100% ΔLASA (n=5). In dogs with more structural remodeling (ΔLASA ≥100%, n=7), CV increased but AF inducibility was unaffected. Conclusions: Oral GAP-134 prevents CV slowing in a dog model of atrial cardiomyopathy, but attenuates AF inducibility and maintenance only in dogs with less mechanical remodeling.

Metformin therapy confers cardioprotection against the remodeling of gap junction in tachycardia-induced atrial fibrillation dog model

Life Sciences ◽  
2020 ◽  
Vol 254 ◽  
pp. 117759 ◽  
Author(s):  
Jiayi Li ◽  
Biao Li ◽  
Fan Bai ◽  
Yinxu Ma ◽  
Na Liu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Metformin Therapy ◽  
Dog Model

P333Left atrial function by echocardiography is independent of degree of left atrial electrical scar

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
R Gallen ◽  
S Herczeg ◽  
C Mcgorrian ◽  
J Carron ◽  
K Walsh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Left Atrial ◽  
Atrial Function ◽  
Potential Explanation ◽  
Refractory Periods ◽  
Wave Velocities ◽  
Bipolar Voltage ◽  
The Mean ◽  
The Relationship

Abstract Introduction Assessment of left atrial function via transthoracic echocardiography (TTE) is performed most commonly by measuring the transmitral A wave in sinus rhythm. Left atrial (LA) fibrosis plays an important role in the pathogenesis and perpetuation of Atrial Fibrillation (AF). It may be identified by bipolar voltage (BiV) mapping, which can easily be performed at the beginning of a Pulmonary Vein Isolation (PVI) procedure. The relationship between the degree of LA fibrosis, characterised with mapping, and LA function, determined by echocardiography, has not previously been elucidated. Methods Patients were enrolled in a project to evaluate the degree of fibrosis during PVI procedures. Pre-procedure TTEs of those presenting in sinus rhythm were assessed and the transmitral A wave was measured and compared to the degree of scarring seen. The high density electroanatomic maps (HD-EAMs) created during the PVIs were analysed using a novel VHA algorithm after the procedure. All points with voltages &lt; 0.5mV were defined to have electrical scar. Patients were classified into 4 quartiles based on the levels of scar seen (Figure 1). Results 39 patients were included in the evaluation. Average age was 60.6 +/- 13.2 years. 32 (82.0%) of the patients were male. Mean CHADS2VASc score was 1.5. The mean percentage of scar was calculated as 19.6 +/- 15.9%. The average A wave was 0.62 +/- 0.18 ms-1. Pearson’s correlation coefficient showed no relationship between LA scar and either A wave velocities (r = 0.26, p = 0.11) or E:A ratio (r=-0.02, p = 0.91). A significant correlation between A wave velocity and CHADS2VASc was observed (r = 0.49, p = 0.001). Conclusion Our study demonstrates no relationship between degree of LA scarring and reduced LA function on TTE as assessed by the A wave. It has been established that structural remodelling in AF (such as atrial dilatation) may occur independently of the electrical remodelling. A potential explanation for our findings is that the electrical scarring in AF, which results in alterations in refractory periods, precedes the negative remodelling which ultimately results in reduced atrial function. This hypothesis would need to be further evaluated in larger studies. Abstract Figure 1

scholarly journals Effects of Chronic Gap Junction Conduction–Enhancing Antiarrhythmic Peptide GAP-134 Administration on Experimental Atrial Fibrillation in Dogs

2009 ◽  
Vol 2 (2) ◽  
pp. 171-178 ◽  
Author(s):  
Gabriel Laurent ◽  
Howard Leong-Poi ◽  
Iqwal Mangat ◽  
Gordon W. Moe ◽  
Xudong Hu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Antiarrhythmic Peptide

scholarly journals Rate Control in Atrial Fibrillation by Cooling: Effect of Temperature on Dromotropy in Perfused Rabbit Hearts

2011 ◽  
Vol 2011 ◽  
pp. 1-4 ◽  
Author(s):  
Karl Mischke ◽  
Markus Zarse ◽  
Christian Knackstedt ◽  
Patrick Schauerte
Keyword(s):  
Atrial Fibrillation ◽  
Heart Rate ◽  
Rate Control ◽  
Therapeutic Option ◽  
Effect Of Temperature ◽  
Significant Drop ◽  
Refractory Periods ◽  
Sinus Cycle Length ◽  
The Mean ◽  
The Impact

Background. Cooling has emerged as a therapeutic option in critically ill patients (especially after cardiac resuscitation) and might also have a negative dromotropic effect in atrial fibrillation. We sought to determine the impact of cooling on electrophysiologic properties of Langendorff-perfused rabbit hearts.Methods and Results. In 20 isolated Langendorff-perfused rabbit hearts, the temperature of the tissue bath was changed between 17 and 42°C. With decreasing temperature, significant increases of the spontaneous sinus cycle length, decreases of the mean ventricular heart rate during atrial fibrillation, and relevant increases of atrial and ventricular refractory periods were observed (ANOVAP<.01).Conclusions. Cardiac hypothermia leads to a significant drop of mean ventricular heart rate during atrial fibrillation. Negative chronotropy and dromotropy induced by moderate cardiac hypothermia might be a feasible therapeutic approach in patients with hemodynamically relevant tachyarrhythmias in a CCU/ICU setting.

scholarly journals Model-Dependent Effects of the Gap Junction Conduction–Enhancing Antiarrhythmic Peptide Rotigaptide (ZP123) on Experimental Atrial Fibrillation in Dogs

Circulation ◽  
2007 ◽  
Vol 115 (3) ◽  
pp. 310-318 ◽  
Author(s):  
Akiko Shiroshita-Takeshita ◽  
Masao Sakabe ◽  
Ketil Haugan ◽  
James K. Hennan ◽  
Stanley Nattel
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Antiarrhythmic Peptide

The role of angiotensin in electrophysiological gap junction remodeling in human atrial fibrillation

2004 ◽  
Vol 52 (S 1) ◽  
Author(s):  
S Dhein ◽  
A Boldt ◽  
J Garbade ◽  
L Polontchouk ◽  
U Wetzel ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gap Junction ◽  
Human Atrial Fibrillation

scholarly journals P318 Left atrial dysfunction assessed by echocardiography in relation to left atrial fibrosis in patients undergoing ablation for atrial fibrillation

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
E Pilichowska ◽  
J Baran ◽  
P Kulakowski ◽  
B Zaborska
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Systolic Function ◽  
Electrophysiological Study ◽  
Stiffness Index ◽  
P Value ◽  
Group 2 ◽  
Left Atrial Dysfunction ◽  
Left Atrial Fibrosis ◽  
Group 1

Abstract PURPOSE Left atrial (LA) fibrosis is the hallmark of LA remodeling in atrial fibrillation (AF), alters LA function and may predict poor catheter ablation (CA) outcome. LA fibrosis may be assessed invasively using electroanatomical mapping (EAM) during electrophysiological study. The aim was to assess LA function parameters in relation to degree of LA fibrosis derived from EAM in patients with AF. METHODS Patients (pts) n = 39 (79% males, mean age 56+/-10) with non-valvular AF were studied with TTE and TEE before first CA during sinus rhythm. LA strain (LAS) and strain rate (LASR) were analyzed in reservoir (r), conduit (cd) and contractile (ct) phases. The velocities of mitral A, E" and A" were measured with Doppler. E/E" and LA stiffness index - the ratio of E/E" to LASr were assessed. LA appendage flow velocity (LAAv) was measured in TEE. LA volume using biplane area-length method was calculated. The EAM of LA was build using Carto System before CA. Low amplitude potentials area (LAPA) was quantitatively analyzed and expressed as a percentage of LA surface using the cut-off &lt;0.5 mV to detect sites of fibrosis. LA parameters were compared between mild (LAPA &lt;10%) moderate (LAPA 10-40%) and extensive degree of LA fibrosis (LAPA &gt;40%) (table). RESULTS The mean LA volume was 35 ± 11 mL/m². The LAPA ranged from 2 to 78 % of LA surface. Reduced LA function was observed in the LAPA &gt;40% group. Extensive LAPA altered mainly LA compliance parameters. Traditional LA systolic function parameters did not differ in relation to degree of LAPA. CONCLUSION LA compliance is mostly affected by LA fibrosis, thus LA diastolic parameters may be useful in the noninvasive assessment of LA fibrosis. Whether these parameters should be a part of the proper selection of candidates for CA requires further studies. LA function parameters LA parameters Group 1 LAPA &lt;10% n = 13 Group 2 LAPA &gt;10% &lt;40% n = 13 Group 3 LAPA &gt;40% n = 13 P-value Group 1 + 2 vs 3 Mitral A 0.55 ± 0.10 0.55 ± 0.24 0.73 ± 0.32 0.077 A" 9.19 ± 1.74 7.85 ± 1.43 7.92 ± 2.40 0.376 LASr 31.48 ± 4.52 26.48 ± 8.79 19.63 ± 6.76 &lt;0.001 LAScd 17.30 ± 3.05 15.44 ± 6.93 10.91 ± 4.04 0.003 LASct 14.18 ± 5.36 11.05 ± 3.67 8.72 ± 4.78 0.024 LASRr 1.22 ± 0.19 1.24 ± 0.21 0.92 ± 0.20 &lt;0.001 LASRct -1.71 ± 0.46 -1.37 ± 0.34 -1.04 ± 0.33 &lt;0.001 LA stiffness 0.20 ± 0.07 0.34 ± 0.17 0.63 ± 0.29 &lt;0.001 LAAv 0.83 ± 0.18 0.55 ± 0.17 0.60 ± 0.16 0.178

scholarly journals Plasma natriuretic peptide level is an independent determinant of major clinical outcomes in atrial fibrillation patients without heart failure: the Fushimi AF Registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y Hamatani ◽  
M Iguchi ◽  
Y Aono ◽  
K Ishigami ◽  
S Ikeda ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Clinical Outcomes ◽  
Prognostic Marker ◽  
Oral Anticoagulants ◽  
Systemic Embolism ◽  
The Mean

Abstract Background Atrial fibrillation (AF) increases the risk of death, stroke/systemic embolism and heart failure (HF). Plasma natriuretic peptide (NP) level is an important prognostic marker in HF patients. However, little is known regarding the prognostic significance of plasma NP level in AF patients without HF. Purpose The aim of this study is to investigate the relationship between plasma NP level and clinical outcomes such as all-cause death, stroke/systemic embolism and HF hospitalization during follow-up period in AF patients without HF. Methods The Fushimi AF Registry is a community-based prospective survey of AF patients in our city. The inclusion criterion of the registry is the documentation of AF at 12-lead electrocardiogram or Holter monitoring at any time, and there are no exclusion criteria. We started to enroll patients from March 2011, and follow-up data were available for 4,466 patients by the end of November 2019. From the registry, we excluded 1,220 patients without a pre-existing HF (defined as having one of the following; prior hospitalization for HF, New York Heart Association class ≥2, or left ventricular ejection fraction &lt;40%). Among 3,246 AF patients without HF, we investigated 1,189 patients with the data of plasma BNP (n=401) or N-terminal pro-BNP (n=788) level at the enrollment. We divided the patients according to the quartile of each plasma BNP or NT-pro BNP level and compared the backgrounds and outcomes between these 4 groups stratified by plasma NP level. Results Of 1,189 patients, the mean age was 72.1±10.2 years, 454 (38%) were female and 684 (58%) were paroxysmal AF. The mean CHADS2 and CHA2DS2-VASc score were 1.6±1.1 and 2.9±1.5, respectively. Oral anticoagulants were prescribed in 671 (56%) at baseline. The median (interquartile range) BNP and N-terminal pro-BNP level were 84 (38, 176) and 500 (155, 984) pg/ml, respectively. Patients with high plasma NP level were older, and demonstrated lower prevalence of paroxysmal AF, higher CHADS2 and CHA2DS2-VASc scores and higher prevalence of chronic kidney disease and oral anticoagulants prescription (all P&lt;0.01). A total of 165 all-cause death, 114 stroke/systemic embolism and 103 HF hospitalization occurred during the median follow-up period of 5.0 years. Kaplan-Meier curves demonstrated that higher plasma NP level was significantly associated with the incidences of all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF (Figure 1A). Multivariable Cox regression analysis revealed that plasma NP level could stratify the risk of clinical outcomes even after adjustment by type of AF, CHA2DS2-VASc score, chronic kidney disease and oral anticoagulant prescription (Figure 1B). Conclusion Plasma NP level is a significant prognostic marker for all-cause death, stroke/systemic embolism and HF hospitalization in AF patients without HF, suggesting the importance of measuring plasma NP level in AF patients even without HF. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals Comparison of Left Atrial Appendage Occlusion versus Non-Vitamin-K Antagonist Oral Anticoagulation in High-Risk Atrial Fibrillation: An Update

2021 ◽  
Vol 8 (6) ◽  
pp. 69
Author(s):  
Shaojie Chen ◽  
K. R. Julian Chun ◽  
Zhiyu Ling ◽  
Shaowen Liu ◽  
Lin Zhu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
High Risk ◽  
Vitamin K ◽  
Major Bleeding ◽  
Left Atrial ◽  
Left Atrial Appendage ◽  
Vitamin K Antagonists ◽  
Left Atrial Appendage Occlusion ◽  
The Mean

Transcatheter left atrial appendage occlusion (LAAO) is non-inferior to vitamin K antagonists (VKAs) in preventing thromboembolic events in atrial fibrillation (AF). Non-vitamin K antagonists (NOACs) have an improved safety profile over VKAs; however, evidence regarding their effect on cardiovascular and neurological outcomes relative to LAAO is limited. Up-to-date randomized trials or propensity-score-matched data comparing LAAO vs. NOACs in high-risk patients with AF were pooled in our study. A total of 2849 AF patients (LAAO: 1368, NOACs: 1481, mean age: 75 ± 7.5 yrs, 63.5% male) were enrolled. The mean CHA2DS2-VASc score was 4.3 ± 1.7, and the mean HAS-BLED score was 3.4 ± 1.2. The baseline characteristics were comparable between the two groups. In the LAAO group, the success rate of device implantation was 98.8%. During a mean follow-up of 2 years, as compared with NOACs, LAAO was associated with a significant reduction of ISTH major bleeding (p = 0.0002). There were no significant differences in terms of ischemic stroke (p = 0.61), ischemic stroke/thromboembolism (p = 0.63), ISTH major and clinically relevant minor bleeding (p = 0.73), cardiovascular death (p = 0.63), and all-cause mortality (p = 0.71). There was a trend toward reduction of combined major cardiovascular and neurological endpoints in the LAAO group (OR: 0.84, 95% CI: 0.64–1.11, p = 0.12). In conclusion, for high-risk AF patients, LAAO is associated with a significant reduction of ISTH major bleeding without increased ischemic events, as compared to “contemporary NOACs”. The present data show the superior role of LAAO over NOACs among high-risk AF patients in terms of reduction of major bleeding; however, more randomized controlled trials are warranted.

Sign in / Sign up

Export Citation Format

Share Document