Stretch-induced sarcoplasmic reticulum calcium leak is causatively associated with atrial fibrillation in pressure-overloaded hearts

2020 ◽  
Author(s):  
Yi Zhang ◽  
Ying Qi ◽  
Jing-Jing Li ◽  
Wen-Jin He ◽  
Xiao-Hang Gao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sarcoplasmic Reticulum ◽  
Left Atrial ◽  
Mechanical Stretch ◽  
Elevated Pressure ◽  
Pathological Process ◽  
Atrial Myocytes ◽  
Haemodynamic Stress ◽  
Galectin 3 ◽  
First Time

Abstract Aims Despite numerous reports documenting an important role of hypertension in the development of atrial fibrillation (AF), the detailed mechanism underlying the pathological process remains incompletely understood. Here, we aim to test the hypothesis that diastolic sarcoplasmic reticulum (SR) Ca2+ leak in atrial myocytes, induced by mechanical stretch due to elevated pressure in the left atrium (LA), plays an essential role in the AF development in pressure-overloaded hearts. Methods and results Isolated mouse atrial myocytes subjected to acute axial stretch displayed an immediate elevation of SR Ca2+ leak. Using a mouse model of transverse aortic constriction (TAC), the relation between stretch, SR Ca2+ leak, and AF susceptibility was further tested. At 36 h post-TAC, SR Ca2+ leak in cardiomyocytes from the LA (with haemodynamic stress), but not right atrium (without haemodynamic stress), significantly increased, which was further elevated at 4 weeks post-TAC. Accordingly, AF susceptibility to atrial burst pacing in the 4-week TAC mice were also significantly increased, which was unaffected by inhibition of atrial fibrosis or inflammation via deletion of galectin-3. Western blotting revealed that type 2 ryanodine receptor (RyR2) in left atrial myocytes of TAC mice was oxidized due to activation and up-regulation of Nox2 and Nox4. Direct rescue of dysfunctional RyR2 with dantrolene or rycal S107 reduced diastolic SR Ca2+ leak in left atrial myocytes and prevented atrial burst pacing stimulated AF. Conclusion Our study demonstrated for the first time the increased SR Ca2+ leak mediated by enhanced oxidative stress in left atrial myocytes that is causatively associated with higher AF susceptibility in pressure-overloaded hearts.

Abstract 15237: Serum Galectin-3 Level Predicts Late Recurrence Following Cryoballoon-based Pulmonary Vein Isolation in Lone Atrial Fibrillation Patients

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Kadri M Gurses ◽  
Muhammed U Yalcin ◽  
Duygu Kocyigit ◽  
Hande Canpinar ◽  
Banu Evranos ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Cardiac Fibrosis ◽  
Cox Regression ◽  
Independent Predictor ◽  
Interstitial Fibrosis ◽  
Early Recurrence ◽  
Cox Regression Analysis ◽  
Galectin 3 ◽  
Af Recurrence

BACKGROUND: Left atrial(LA) interstitial fibrosis is known to be a key contributor to atrial fibrillation(AF) development and maintenance. The role of galectin-3 in the pathogenesis of cardiac fibrosis has been demonstrated in previous studies. We aimed to determine whether serum galectin-3 level is an independent predictor for the late AF recurrence in patients with lone AF who underwent cryoballoon- based pulmonary ven isolation(PVI). METHODS: 100 patients (43.80% male, 56.95± 11.36 years) with lone AF who underwent cryoballoon-based PVI were included in the study. Pre-procedural galectin-3 levels were measured with ELISA. RESULTS: At a follow-up of 12 months, 76 (76%) patients were free of late AF recurrence. Body mass index(BMI) ( 25.04± 1.54 vs. 23.93± 2.08 kg/m2, p=0.002), AF duration [7 (3- 20) vs. 5 (1- 24) months, p=0.024], serum galectine-3 levels [11.10 (4.20- 33.80) vs. 5.70 (2.60- 12.40) ng/mL, p<0.001], left atrial diameter(LAD) (4.30± 0.40 vs.3.79± 0.42 cm, p<0.001) and incidence of early recurrence (60 vs 2%, p<0.001) were found to be significantly higher in patients with late AF recurrence. Serum galectin-3 levels (HR: 1.16, p<0.001), LAD (HR: 3.38, p= 0.042) and early recurrence (HR: 10.92, p<0.001) were found to be independent predictors of late AF recurrence in the multivariate Cox regression analysis. A cut-off level for serum galectin-3 level of 7.9 ng/mL predicted late AF recurrence in lone AF patients with a sensitivity of 93.33% and specificity of 87.76% (AUC: 0.910, p<0.001). CONCLUSION: Pre-procedural serum galectin-3 level is an independent predictor of late AF recurrence following cryoballoon-based PVI in patients with lone AF. Galectin-3 may serve as a novel biomarker to identify patients with high recurrence risk following AF ablation.

Abstract 3492: Increased Late I Na in Left Atrial Myocytes of Left Ventricular Hypertrophy Rabbits and its Role in Genesis of Atrial Early Afterdepolarizations

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Donglin Guo ◽  
Zhen Jiao ◽  
Binu Malhottra ◽  
Chinmay Patel ◽  
Peter R Kowey ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Ventricular Hypertrophy ◽  
Left Atrial ◽  
Ventricular Hypertrophy ◽  
Heart Association ◽  
Elevated Pressure ◽  
Left Ventricular ◽  
Early Afterdepolarizations ◽  
Body Mass Ratio ◽  
Funding Support

Atrial fibrillation is the most common sustained arrhythmia affecting more than 2 million people annually in USA. Previous studies have shown that left ventricular hypertrophy (LVH) results in an increase in the late I Na that plays an important role in genesis of ventricular arrhythmias. We tested the hypothesis that LVH, which is associated with elevated pressure in the left atrium, could enhance the late I Na in left atrial (LA) myocytes, leading to increased trigger activities. Rabbit LVH, which exhibited a significantly greater left ventricle to body mass ratio, was induced using the renovascular hypertension model. Interestingly, early afterdepolarizations (EADs) at action potential phase 2 and 3 occurred in 6 of 10 LA myocytes isolated from 5 LVH rabbits at a pacing cycle length of 2000 ms, whereas EADs were elicited in none of 10 cells isolated from 5 control rabbits ( p <0.01). Spontaneously activities (SA) were observed in 6 of 10 LA myocytes from five LVH rabbits at the pacing rate of 8000 ms. The density of the late I Na was significantly larger in LA myocytes of LVH rabbits than that recorded in control rabbits (0.59±0.02 pA/pF in LVH versus 0.42±0.05 pA/pF in control, n=6, p <0.01). Ranolazine, a late I Na blocker, exerted a concentration-dependent blocking effect on the late I Na in LA myocytes of the rabbits (IC 50 =15.7±0.6 μM) and abolished all of atrial EADs and SA of the LVH rabbits at 30 μM. Our results demonstrate that LVH results in a significant increase in the late I Na in the LA myocytes that may render these cells susceptible to genesis of EADs. The late I Na is a potentially useful ionic target by antiarrhythmic drugs for the treatment of atrial fibrillation in the setting of LVH. This research has received full or partial funding support from the American Heart Association, AHA National Center.

scholarly journals Atrial Fibrillation Is Associated With Increased Spontaneous Calcium Release From the Sarcoplasmic Reticulum in Human Atrial Myocytes

Circulation ◽  
2004 ◽  
Vol 110 (11) ◽  
pp. 1358-1363 ◽  
Author(s):  
Leif Hove-Madsen ◽  
Anna Llach ◽  
Antoni Bayes-Genís ◽  
Santiago Roura ◽  
Enrique Rodriguez Font ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Atrial Myocytes ◽  
Human Atrial Myocytes

Sex differences and arrhythmia recurrence after catheter ablation for atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Tanaka ◽  
S Shizuta ◽  
A Komasa ◽  
T Yoshizawa ◽  
H Kohjitani ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sex Differences ◽  
Catheter Ablation ◽  
Recurrence Rate ◽  
Left Atrial ◽  
Female Gender ◽  
High Recurrence Rate ◽  
Cryoballoon Ablation ◽  
Female Patients ◽  
First Time

Abstract Background Several previous studies reported female sex is associated with high recurrence rate of atrial tachyarrhythmia (ATA) after catheter ablation (CA) for atrial fibrillation (AF). Purpose We investigated the relationship between sex differences and recurrence rate of ATA after CA for AF in a large single-center database. Methods We enrolled consecutive 2033 patients undergoing first time CA for AF in our institution between Feb.2004 and Dec. 2017. We compared the long-term outcomes between female (N=603) and male (N=1430). Results Female patients were older (70.8 vs. 66.3, p&lt;0.0001), and had lower prevalence of persistent AF (23.1% vs. 33.5%, p&lt;0.0001). Also, left atrial dimension was smaller (40.0 vs. 41.1, p=0.0005). and prior antiarrhythmic drug use was more prevalent (38.2% vs. 28.7%, p&lt;0.0001) in female patients. Ablation method for pulmonary vein isolation (PVI) was radiofrequency catheter ablation in 1634 patients (80.4%) and cryoballoon ablation in 399 (20.6%). Median follow-up duration was 1342±115 days. The 3-year ATA recurrence rate after first CA was 35.8% overall: 39.9% in female and 34.2% in male (Log-rank P=0.01). A multivariate analysis revealed that the factors associated with higher ATA recurrence rate were female (p=0.01), persistent AF (p=0.006), and larger left atrial dimension (p=0.007). Conclusions Female gender is an independent predictor of arrhythmia recurrence after CA for AF. Funding Acknowledgement Type of funding source: None

scholarly journals Galectin-3 in Heart Failure with Preserved Ejection Fraction and Persistent Atrial Fibrillation Versus Sinus Rhythm. Correlation with Left Atrial Volume and N-Terminal Pro B-Type Natriuretic Peptide

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Bertoni M ◽  
◽  
Traini AM ◽  
Celli A ◽  
Bini C ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Left Atrial ◽  
Independent Predictor ◽  
Left Atrial Volume ◽  
Atrial Remodeling ◽  
Preserved Ejection Fraction ◽  
Atrial Volume ◽  
Left Atrial Remodeling ◽  
Galectin 3

Background: Galectin-3 (Gal-3) is considered both a profibrotic biomarker in Heart Failure with preserved Ejection Fraction (HFpEF) and a biomarker of atrial remodeling in Atrial Fibrillation (AF). The Left Atrial Volume Index (LAVI) is an echocardiographic parameter considered an index of left atrial remodeling. Aim of this study was to analyse the relation of Gal-3 levels with both LAVI and N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) in patients with HFpEF and Persistent AF (HFpEF-PAF). Methods: Serum Gal-3 and NT-proBNP, along with LAVI were measured. A comparison of such parameters between 49 patients with HFpEF-PAF and 53 patients with HFpEF and sinus rhythm (HEpEF-SR) was made. Results: Galectin-3, NT-proBNP and LAVI were significantly higher in patients with HFpEF-PAF compared to HFpEF-SR (23±7 ng/mL vs 19.5±8.5 ng/mL, p=0.027; 3,406.8±2,321.9 pg/mL vs 1,459.6±1,372 pg/mL, p<0.001; 40.1±11mL/m² vs 28.4±7.7 mL/m², p<0.001, respectively). In HFpEF-PAF, Gal- 3 showed a significant correlation with both NT-proBNP (r=0.40, p=0.0038) and LAVI (r=0.28, p=0.044). We found a significant association between patients with higher levels of Gal-3 >17.8 ng/mL and HFpEF-PAF (p=0.002). Finally, a multivariate logistic regression analysis adjusted for age, sex and traditional clinical AF risk factors showed that Gal-3 >17,8 ng/mL (OR 3.862, 95% CI 1.416 to 10.532, p=0.008) was an independent predictor of PAF. Conclusions: In patients with HFpEF-PAF Gal-3 was higher and related with both NT-proBNP and LAVI. The latter correlation may be relevant because LAVI is considered an index of left atrial remodeling. Moreover, higher levels of Gal-3>17,8 ng/mL were an independent predictor of PAF.

scholarly journals Analysis of the Correlation of Galectin-3 Concentration with the Measurements of Echocardiographic Parameters Assessing Left Atrial Remodeling and Function in Patients with Persistent Atrial Fibrillation

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1108
Author(s):  
Paweł Wałek ◽  
Urszula Grabowska ◽  
Elżbieta Cieśla ◽  
Janusz Sielski ◽  
Joanna Roskal-Wałek ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Systolic Function ◽  
Persistent Atrial Fibrillation ◽  
Atrial Remodeling ◽  
Left Atrial Wall ◽  
Galectin 3 ◽  
Echocardiographic Parameters ◽  
Fibrosis Marker ◽  
And Function

Galectin-3 (gal-3) is a fibrosis marker and may play a role in fibrosis of the left atrium (LA). Left atrial wall fibrosis may influence the transition from paroxysmal to non-paroxysmal atrial fibrillation (AF). In this study, we assessed the correlation of gal-3 concentration with the main echocardio-graphic parameters evaluating dimensions, volume, compliance, and left atrial contractility during AF and after successful electrical cardioversion (DCCV). The study included 63 patients with left atrial enlargement who qualified for DCCV due to persistent AF. The procedure recovered sinus rhythm in 43 (68.3%) patients. The concentration of gal-3 was negatively correlated with the echocardiographic parameters of LA including dimensions (LA length pre, rho = −0.38; p = 0.003), volume (LAV pre, rho = −0.39; p = 0.003), compliance (LASr mean post, rho = −0.33) and contractility (pLASRct mean post, rho = −0.33; p = 0.038). Negative correlations of gal-3 concentration were also observed in relation to the volume and contractility of the left ventricle. The concentration of gal-3 significantly negatively correlates with the size, systolic function, and compliance of the LA wall in patients with persistent AF. Determining gal-3 concentration in patients with persistent AF may help in the assessment of remodeling of the LA wall.

scholarly journals miR−21 and NT-proBNP Correlate with Echocardiographic Parameters of Atrial Dysfunction and Predict Atrial Fibrillation

2020 ◽  
Vol 9 (4) ◽  
pp. 1118
Author(s):  
Jan-Thorben Sieweke ◽  
Tobias Jonathan Pfeffer ◽  
Saskia Biber ◽  
Shambhabi Chatterjee ◽  
Karin Weissenborn ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Confidence Interval ◽  
Left Atrial ◽  
Area Under The Curve ◽  
Serum Biomarkers ◽  
Atrial Remodeling ◽  
Circulating Biomarkers ◽  
Atrial Remodelling ◽  
Galectin 3 ◽  
Echocardiographic Parameters

This study aimed to investigate the association of circulating biomarkers with echocardiographic parameters of atrial remodelling and their potential for predicting atrial fibrillation (AF). In patients with and without AF (n = 21 and n = 60) the following serum biomarkers were determined: soluble ST2 (sST2), Galectin−3 (Gal-3), N-terminal pro-brain natriuretic peptide (NT-proBNP), microRNA (miR)−21, −29a, −133a, −146b and −328. Comprehensive transthoracic echocardiography was performed in all participants. Biomarkers were significantly altered in patients with AF. The echocardiographic parameter septal PA-TDI, indicating left atrial (LA) remodelling, correlated with concentrations of sST2 (r = 0.249, p = 0.048), miR−21 (r = −0.277, p = 0.012), miR−29a (r = −0.269, p = 0.015), miR−146b (r = −0.319, p = 0.004) and miR−328 (r = −0.296, p = 0.008). In particular, NT-proBNP showed a strong correlation with echocardiographic markers of LA remodelling and dysfunction (septal PA-TDI: r = 0.444, p < 0.001, LAVI/a’: r = 0.457, p = 0.001, SRa: r = 0.581, p < 0.001). Multivariate Cox regressions analysis highlighted miR−21 and NT-proBNP as predictive markers for AF (miR−21: hazard ratio (HR) 0.16; 95% confidence interval (CI) 0.04–0.7, p = 0.009; NT-proBNP: HR 1.002 95%CI 1.001–1.004, p = 0.006). Combination of NT-proBNP and miR−21 had the best accuracy to discriminate patients with AF from those without AF (area under the curve (AUC)= 0.843). Our findings indicate that miR−21 and NT-proBNP correlate with echocardiographic parameters of atrial remodeling and predict AF, in particular if combined.

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