Abstract 198: Noninvasive Approach Assessing Atrial Mechanics and Serum Biomarkers of Collagen Turnover Provides a Surrogate for Fibrosis and Atrial Fibrillation

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Mahek Mirza ◽  
Farhan Rizvi ◽  
Melissa Albrecht ◽  
Anton Strunets ◽  
Larisa Emelyanova ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Serum Biomarkers ◽  
Imaging Biomarkers ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matrix Remodeling ◽  
Collagen Turnover ◽  
Atrial Fibrosis ◽  
Electrophysiological Properties ◽  
Time To Peak ◽  
New Onset

Introduction: Atrial fibrosis alters myocardial electrophysiological properties, increasing susceptibility to postoperative atrial fibrillation (PoAF); however, its estimation is problematic. We hypothesized that a noninvasive approach using history of AF (HxAF), LA mechanics and serum biomarkers of collagen turnover provides a surrogate for the extent of interstitial atrial fibrosis to identify patients at risk for PoAF. Methods: In patients undergoing cardiac surgery from April-Dec 2013, concentrations of biomarkers reflecting collagen synthesis/degradation and extracellular matrix remodeling were determined in serum from preoperative blood using an enzyme-linked immunosorbent assay, and echocardiographic evaluation was performed using M-mode, 2D, Doppler and 3D speckle tracking. Results: Of 66 patients (68 ±11 y, 67% men), 15 had HxAF and 11 of 51 with no HxAF (22%) developed new onset PoAF. In patients with HxAF, biomarkers for collagen turnover were elevated (Fig A) and correlated with a reduction in LA ejection fraction and global and regional relaxation of the LA wall (p=0.01, Fig B). In patients with no HxAF, procollagen type III (PIIINP) was significantly different in those who developed PoAF (p=0.01) and correlated with reduction in contractility in the posterior LA roof (p=<0.001) with a prolonged time to peak end-diastolic volume (p=0.03). LA size or ventricular structure and function were not different between groups. Conclusion: Surrogate serum and imaging biomarkers correlate with the substrate abnormality that promotes AF. These results need to be validated in larger cohorts to assess the power of these parameters in predicting new onset PoAF.

Atrial Fibrillation and Renin–Angiotensin System Blockade in Hypertension

2009 ◽  
Vol 5 (2) ◽  
pp. 63
Author(s):  
Tonje A Aksnes ◽  
Markus P Schneider ◽  
Sverre E Kjeldsen ◽  
Kristian Wachtell ◽  
Roland E Schmieder ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrial ◽  
Renin Angiotensin System ◽  
Economic Importance ◽  
Atrial Fibrosis ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Onset Atrial Fibrillation ◽  
Left Atrial Dilatation ◽  
New Onset

Atrial fibrillation is prevalent and increases morbidity and mortality. Hypertension is an important risk factor for atrial fibrillation development, and treatment with a blocker of the renin–angiotensin system (RAS) may reduce new-onset atrial fibrillation. Blockade of RAS may prevent left atrial dilatation, atrial fibrosis, dysfunction and conduction velocity slowing, and some studies even indicate direct anti-arrhythmic properties. As the general population is ageing, the prevalence of atrial fibrillation is expected to rise, and methods to prevent or postpone atrial fibrillation development, for example with optimal antihypertensive treatment, may be of clinical, prognostic and economic importance.

scholarly journals Increased serum lysyl oxidase-like 2 levels correlate with the degree of left atrial fibrosis in patients with atrial fibrillation

2017 ◽  
Vol 37 (6) ◽  
Author(s):  
Yingming Zhao ◽  
Kangting Tang ◽  
Xu Tianbao ◽  
Junhong Wang ◽  
Jin Yang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Left Atrium ◽  
Left Atrial ◽  
Cardiac Fibrosis ◽  
Lysyl Oxidase ◽  
Multivariate Regression Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Atrial Fibrosis ◽  
Left Atrial Fibrosis

Atrial fibrillation (AF) progression is generally accompanied by increased atrial fibrosis and atrial structural remodeling. Lysyl oxidase-like 2 (LOXL2) is known to play an important role in many fibrotic conditions, including cardiac fibrosis. The present study aimed to explore the relationship between serum LOXL2 levels and AF. Fifty-four AF patients and 32 control subjects were enrolled in the study. High-density three-dimensional electroanatomic mapping was performed, and mean bipolar voltage was assessed in AF patients. LOXL2 levels were measured by enzyme-linked immunosorbent assay. All patients underwent echocardiography to assess left atrium size and left ventricle function. Serum LOXL2 levels were significantly elevated in AF patients compared with the control group (526.81 ± 316.82 vs 240.94 ± 92.51 pg/ml, P<0.01). In addition, serum LOXL2 level was significantly correlated with the size of the left atrium (LAD) (r2 = 0.38, P<0.01). Furthermore, the serum LOXL2 levels were significantly higher in AF patients with LAD ≥ 40 mm compared with those with LAD < 40 mm (664.34 ± 346.50 vs 354.90 ± 156.23 pg/ml, P<0.01). And the Spearman’s correlation analysis further revealed that the mean bipolar left atrial voltage was inversely correlated with the LOXL2 (r2 = −0.49, P<0.01) in AF patients. Multivariate regression analysis further demonstrated that serum LOXL2 [odds ratio (OR) 1.013, 95% confidence interval (CI) 1.002–1.024, P<0.05] and LAD (OR 1.704, 95% CI 1.131–2.568, P<0.01) were independent predictors of AF. In conclusion, serum LOXL2 levels were significantly elevated and were correlated with the degree of left atrial fibrosis in AF patients.

scholarly journals Atrial Fibrosis, Ischaemic Stroke and Atrial Fibrillation

2021 ◽  
Vol 10 (4) ◽  
pp. 225-229
Author(s):  
Christian Mahnkopf ◽  
Younghoon Kwon ◽  
Nazem Akoum
Keyword(s):  
Atrial Fibrillation ◽  
Late Gadolinium Enhancement ◽  
Ischaemic Stroke ◽  
Recurrent Stroke ◽  
Future Research ◽  
Prevention Strategies ◽  
Atrial Fibrosis ◽  
Gadolinium Enhancement ◽  
Atrial Remodelling ◽  
New Onset

Atrial fibrosis is an important component of the arrhythmic substrate in AF. Evidence suggests that atrial fibrosis also plays a role in increasing the risk of stroke in patients with the arrhythmia. Patients with embolic stroke of undetermined source (ESUS), who are suspected to have AF but are rarely shown to have it, frequently demonstrate evidence of atrial fibrosis; measured using late-gadolinium enhancement MRI, this manifests as atrial remodelling encompassing structural, functional and electrical properties. In this review, the authors discuss the available evidence linking atrial disease, including fibrosis, with the risk of ischaemic stroke in AF, as well as in the ESUS population, in whom it has been linked to recurrent stroke and new-onset AF. They also discuss the implications of this association on future research that may elucidate the mechanism of stroke and stroke prevention strategies in the AF and ESUS populations.

scholarly journals Sacubitril/valsartan Decreased Atrial Fibrillation Susceptibility by Inhibiting Angiotensin II-induced Atrial Fibrosis through p-Smad2/3, p-JNK, and p-p38 Signaling Pathways

2020 ◽  
Author(s):  
Song-Nan Li ◽  
Jing-Rui Zhang ◽  
Hui Xi ◽  
Chang-Yi Li ◽  
Lei Zhao
Keyword(s):  
Atrial Fibrillation ◽  
Signaling Pathways ◽  
Natriuretic Peptide ◽  
Corn Oil ◽  
Interstitial Fibrosis ◽  
Electrophysiological Study ◽  
Mapk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Atrial Fibrosis ◽  
Cardiac Functions

Abstract Background: Sacubitril/valsartan (SAC/VAL), combined inhibitors of angiotensin receptor (AT-R) and neprilysin receptor, prevents Angiotensin Ⅱ (AngⅡ) from binding AT1-R and blocks degradation of natriuretic peptides. Despite its efficacy in reducing ventricular fibrosis and preserving cardiac functions, which has been extensively demonstrated in myocardial infarction or pressure overload models, few studies have been conducted to determine whether SAC/VAL could attenuate atrial fibrosis and decrease atrial fibrillation (AF) susceptibility. Methods: Sprague-Dawley rats were divided into three groups after implantation of an osmotic pump preloaded with AngⅡ and received corn oil, VAL, or SAC/VAL treatment for 28 days. Electrophysiological study was performed to determine inducibility and duration of AF. Echocardiography was performed before and 28 days after osmotic mini-pump implantation to evaluate cardiac functions. Enzyme-linked immunosorbent assay was perfomed to detect the serum concentration of atrial natriuretic peptide (ANP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and AngⅡ. Masson staining was performed to determine the extent of interstitial fibrosis. Immunohistochemical, and immunofluorescence staining as well as transwell and MTT assay were also performed. Western blot analysis was perfomed to figure out how SAC/VAL exerts its anti-fibrosis effects in atriums.Results: After 28 days of AngⅡ stimulation, rats in SAC/VAL group exhibited reduced reduced extent of atrial fibrosis, inhibited proliferation, migration, and differentiation of atrial fibroblasts and decreased susceptibility to atrial fibrillation. We further found that SAC/VAL exerted its effect on AngⅡ-induced atrial fibrosis by inhibiting the p-Smad2/3, p-JNK, and p-p38 MAPK signaling pathways in vivo. Conclusions: Our study provided experimental evidence for the inhibition of atrial fibrosis and reduced susceptibility to AF by SAC/VAL. These results emphasize the importance of SAC/VAL in the prevention of AngⅡ-induced atrial fibrosis and may help to enrich the options for atrial fibrillation pharmacotherapy.

Left atrial fibrosis is associated with new-onset heart failure in patients with atrial fibrillation

2017 ◽  
Vol 248 ◽  
pp. 161-165 ◽  
Author(s):  
Peyman N. Azadani ◽  
Jordan B. King ◽  
Mobin Kheirkhahan ◽  
Lowell Chang ◽  
Nassir F. Marrouche ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Left Atrial ◽  
Atrial Fibrosis ◽  
Left Atrial Fibrosis ◽  
New Onset

LOXL2 Inhibitor Attenuates Angiotensin II-Induced Atrial Fibrosis and Vulnerability to Atrial Fibrillation through Inhibition of Transforming Growth Factor Beta-1 Smad2/3 Pathway

2021 ◽  
pp. 1-11
Author(s):  
Yingbiao Wu ◽  
Jin Can ◽  
Shuwen Hao ◽  
Xun Qiang ◽  
Zhongping Ning
Keyword(s):  
Atrial Fibrillation ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Specific Inhibitor ◽  
Matrix Remodeling ◽  
Ang Ii ◽  
Atrial Fibrosis ◽  
Growth Factor Beta

<b><i>Objectives:</i></b> Angiotensin II (Ang II)-induced atrial fibrosis plays a vital role in the development of atrial fibrillation (AF). Lysyl oxidase-like 2 (LOXL2) plays an essential role in matrix remodeling and fibrogenesis, indicating it may involve fibrosis-associated diseases. This study aims to elucidate the role of LOXL2 in AF, and its specific inhibitor can suppress Ang II-induced inflammatory atrial fibrosis and attenuate the enhanced vulnerability to AF. <b><i>Methods:</i></b> Male mice C57BL/6 were subcutaneously infused with either saline or Ang II (2 mg/kg/day) for 4 weeks. DMSO or LOXL2 inhibitor LOXL2-IN-1 hydrochloride (LOXL2-IN-1) at a dose of 100 μg/kg/day were intraperitoneally injected once daily for 4 weeks. Morphological, histological, and biochemical analyses were performed. AF was induced by transesophageal burst pacing in vivo. <b><i>Results:</i></b> Expression of LOXL2 was increased in serum of AF patients and Ang II-treated mice. LOXL2-IN-1 significantly attenuated Ang II-induced AF vulnerability, cardiac hypertrophy, atrial inflammation, and fibrosis. LOXL2-IN-1 suppressed Ang II-induced expression of transforming growth factor beta-1 (TGF-β1) and collagen I and phosphorylation of Smad2/3 in atrial tissue. <b><i>Conclusions:</i></b> LOXL2 is a target of AF, and its inhibitor prevents atrial fibrosis and attenuated enhanced vulnerability to AF potentially through the TGF-β/Smad pathway.

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