Apelin increases atrial conduction velocity, refractoriness, and prevents inducibility of atrial fibrillation

Kim, Young M; Lakin, Robert; Zhang, Hao; Liu, Jack; Sachedina, Ayaaz K; Singh, Maneesh H.; Wilson, Emily; Perez, Marco; Verma, Subodh; Quertermous, Thomas; Olgin, Jeffrey E.; Backx, Peter H.; Ashley, Euan A.

doi:10.1172/jci.insight.126525

Cited by 16 publications

(11 citation statements)

References 53 publications

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“…In the context of our present findings, we hypothesize that these previously reported correlations were not causal and that apelin more likely reflects electrical remodeling rather than structural remodeling. This theory also corresponds with experimental findings showing that apelin increases atrial conduction velocity, refractoriness, shortens action potential, affects multiple ionic currents and prevents the inducibility of atrial fibrillation (51,52).…”

Section: Discussionsupporting

confidence: 88%

Association Between Apelin and Atrial Fibrillation in Patients With High Risk of Ischemic Stroke

Böhm

Snopek

Tóthová

et al. 2021

Front. Cardiovasc. Med.

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Background: Atrial fibrillation (AF) is associated with high risk of stroke preventable by timely initiation of anticoagulation. Currently available screening tools based on ECG are not optimal due to inconvenience and high costs. Aim of this study was to study the diagnostic value of apelin for AF in patients with high risk of stroke.Methods: We designed a multicenter, matched-cohort study. The population consisted of three study groups: a healthy control group (34 patients) and two matched groups of 60 patients with high risk of stroke (AF and non-AF group). Apelin levels were examined from peripheral blood.Results: Apelin was significantly lower in AF group compared to non-AF group (0.694 ± 0.148 vs. 0.975 ± 0.458 ng/ml, p = 0.001) and control group (0.982 ± 0.060 ng/ml, p < 0.001), respectively. Receiver operating characteristic (ROC) analysis of apelin as a predictor of AF scored area under the curve (AUC) of 0.658. Apelin's concentration of 0.969 [ng/ml] had sensitivity = 0.966 and specificity = 0.467. Logistic regression based on manual feature selection showed that only apelin and NT-proBNP were independent predictors of AF. Logistic regression based on selection from bivariate analysis showed that only apelin was an independent predictor of AF. A logistic regression model using repeated stratified K-Fold cross-validation strategy scored an AUC of 0.725 ± 0.131.Conclusions: Our results suggest that apelin might be used to rule out AF in patients with high risk of stroke.

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Section: Discussionsupporting

confidence: 88%

Association Between Apelin and Atrial Fibrillation in Patients With High Risk of Ischemic Stroke

Böhm

Snopek

Tóthová

et al. 2021

Front. Cardiovasc. Med.

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“…Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) have been reported to contribute to extracellular matrix remodeling of atria in AF (13). Kim et al found that increasing ELA bioavailability in mice is beneficial for treating and preventing AF (14). Further, in search of new biomarkers for determining the prognosis of arrhythmia and AF, we tested serum biomarker levels through ELISA, including MMP-9, TIMP-1, and ELA.…”

Section: Ela Protects Patients With Arrhythmias Against Af and Heart Failurementioning

confidence: 99%

ELABELA acts as a protective biomarker in patients with atrial fibrillation

Cui¹,

Zhou²,

Xu³

2021

J Thorac Dis

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Background: Atrial fibrillation (AF) is the most common type of clinical arrhythmia. An early diagnosis can be beneficial in the prevention of complications, such as heart failure (HF) and stroke. In this study, we revealed that ELABELA (ELA) acts as a protective factor in patients with arrhythmia and could serve as a prognostic marker for AF and its associated complication of HF. Methods: We tested the expression level of potential biomarkers including matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and ELA with enzyme-linked immunosorbent assay (ELISA) in serum derived from 131 patients (patients with AF =103; patients with paroxysmal supraventricular tachycardia =28). The impact of clinical risk factors and biomarkers on AF occurrence was evaluated using binary logistic analysis. Results: The ELA expression level was lower in AF patients than in the negative controls (P<0.0001).Expression of ELA was negatively correlated with brain natriuretic peptide (BNP) expression in all the samples.In the binary logistic analysis, high levels of BNP and lower levels of ELA were significantly associated with an increased risk of AF (P<0.0001) and could be used as prognostic markers for patients with AF.Conclusions: Expression of ELA showed a protective role in AF patients. The ELA level was negatively correlated with BNP levels, which has been shown to predict a high risk of HF independently and consistently. Additionally, lower levels of ELA were associated with a high risk of AF and HF in patients with arrhythmia.

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“…The pathophysiological basis for this strong relationship between apelin and AF is the fact that apelin directly or indirectly affects many processes and pathways associated with AF. Among other effects, it increases atrial conduction velocity and refractoriness, prevents the inducibility of AF, modulates cardiac sodium current, shortens action potential duration in atrial myocytes via its effects on multiple ionic channels, affects the renin-angiotensin-aldosterone signalling pathway and acts as a second catalytic substrate for ACE2 (22)(23)(24)(25). Whether the change in plasmatic levels of apelin is caused by atrial stretch (32) or is rather a refl ection of electrical remodelling of atria as suggested by our previous study ( 21) merits further research.…”

Section: Discussionmentioning

confidence: 99%

“…Apelin is an endogenous peptide with a wide range of effects on cardiovascular system, including several processes directly or indirectly linked with AF. Among other effects, it increases atrial conduction velocity, refractoriness, prevents the inducibility of AF, modulates cardiac sodium current, shortens action potential duration in atrial myocytes via its effects on multiple ionic channels, affects the renin-angiotensin-aldosterone signalling pathway and acts as a second catalytic substrate for angiotensin-converting enzyme 2 (ACE2) (22)(23)(24)(25)(26).…”

Section: U N C O R R E C T E Dmentioning

confidence: 99%

Plasmatic apelin shows a promising potential as a screening biomarker for atrial fibrillation

BEZAK¹,

SNOPEK²,

TOTHOVA³

et al. 2023

BLL

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OBJECTIVES: Purpose of this study was to evaluate properties of apelin, a peptide detectable in peripheral blood, for atrial fi brillation (AF) detection in a diverse population of patients covering a broad spectrum from healthy to polymorbid patients. BACKGROUND: AF is the most common cardiac arrhythmia with constantly increasing incidence and prevalence. Currently available diagnostic tools do not provide suffi cient detection rate. Large proportion of patients with AF remains undiagnosed and the possibility of screening at-risk groups would be signifi cantly benefi cial. METHODS: We designed this study as a multi-centre retrospective study. Study population included 183 patients. 64 in non-AF and 119 in AF group. RESULTS: Apelin plasma concentration was signifi cantly lower in AF group compared to non-AF group (p < 0.001). Receiver operating characteristic analysis of apelin as a predictor of AF scored area under the curve of 0.79, sensitivity = 0.941 and specifi city = 0.578. Multivariate analysis using logistic regression adjusted for age, BMI, apelin, dilated LV, dilated LA, arterial hypertension, and gender showed only apelin and age to be statistically signifi cant contributors for AF. CONCLUSION: Apelin might be a promising biomarker for detecting AF in our study population. These results suggest promising potential of apelin as a screening biomarker for AF (Tab. 2, Fig. 1, Ref. 46).

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Apelin increases atrial conduction velocity, refractoriness, and prevents inducibility of atrial fibrillation

Cited by 16 publications

References 53 publications

Association Between Apelin and Atrial Fibrillation in Patients With High Risk of Ischemic Stroke

Association Between Apelin and Atrial Fibrillation in Patients With High Risk of Ischemic Stroke

ELABELA acts as a protective biomarker in patients with atrial fibrillation

Plasmatic apelin shows a promising potential as a screening biomarker for atrial fibrillation

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