Prospective multicentric validation of a novel prediction model for paroxysmal atrial fibrillation

Schmidt, Constanze; Benda, Sebastian; Kraft, Patricia; Wiedmann, Felix; Pleger, Sven T.; Büscher, Antonius; Thomas, Dierk; Wachter, Rolf; Schmid, Christian David; Eils, Roland; Katus, Hugo A.; Kallenberger, Stefan M.

doi:10.1007/s00392-020-01773-z

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…Previously, the end‐systolic diameter and end‐diastolic diameter of the left ventricle as well as left atrial diameter were identified as strong predictors of AF. 50 In the future, analyzing transcriptional modules associated with these miRNAs could reveal pathways associated with the molecular pathology of AF. Known associations of miRNAs with AF could be confirmed (miR‐21, miR‐29b, and miR‐34a) and new associations with AF were identified (miR‐9, miR‐23a, miR‐485).…”

Section: Discussionmentioning

confidence: 99%

MicroRNAs Regulate TASK‐1 and Are Linked to Myocardial Dilatation in Atrial Fibrillation

Wiedmann

Kraft

Kallenberger

et al. 2022

JAHA

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Background Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. However, underlying molecular mechanisms are insufficiently understood. Previous studies suggested that microRNA (miRNA) dependent gene regulation plays an important role in the initiation and maintenance of AF. The 2‐pore‐domain potassium channel TASK‐1 (tandem of P domains in a weak inward rectifying K + channel–related acid sensitive K + channel 1) is an atrial‐specific ion channel that is upregulated in AF. Inhibition of TASK‐1 current prolongs the atrial action potential duration to similar levels as in patients with sinus rhythm. Here, we hypothesize that miRNAs might be responsible for the regulation of KCNK3 that encodes for TASK‐1. Methods and Results We selected miRNAs potentially regulating KCNK3 and studied their expression in atrial tissue samples obtained from patients with sinus rhythm, paroxysmal AF, or permanent/chronic AF. MiRNAs differentially expressed in AF were further investigated for their ability to regulate KCNK3 mRNA and TASK‐1 protein expression in human induced pluripotent stem cells, transfected with miRNA mimics or inhibitors. Thereby, we observed that miR‐34a increases TASK‐1 expression and current and further decreases the resting membrane potential of Xenopus laevis oocytes, heterologously expressing hTASK‐1. Finally, we investigated associations between miRNA expression in atrial tissues and clinical parameters of our patient cohort. A cluster containing AF stage, left ventricular end‐diastolic diameter, left ventricular end‐systolic diameter, left atrial diameter, atrial COL1A2 (collagen alpha‐2(I) chain), and TASK‐1 protein level was associated with increased expression of miR‐25, miR‐21, miR‐34a, miR‐23a, miR‐124, miR‐1, and miR‐29b as well as decreased expression of miR‐9 and miR‐485. Conclusions These results suggest an important pathophysiological involvement of miRNAs in the regulation of atrial expression of the TASK‐1 potassium channel in patients with atrial cardiomyopathy.

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Section: Discussionmentioning

confidence: 99%

MicroRNAs Regulate TASK‐1 and Are Linked to Myocardial Dilatation in Atrial Fibrillation

Wiedmann

Kraft

Kallenberger

et al. 2022

JAHA

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“…While validated in Hispanic patients at large, disaggregation is not reported, making it difficult to know if this tool is appropriate to use in all Hispanic subgroups. More novel risk tools, such as the ECHO-AF score [ 65 ], do not report the ethnic breakdown of their study cohorts, preventing validated use in Hispanic populations. Among the well-established risk factors for AF incorporated into these risk algorithms are age, HTN, DM, obesity, myocardial infarction, coronary artery disease, and HF.…”

Section: Risk Assessment In Hispanic Individuals In the Usamentioning

confidence: 99%

Unique Cardiovascular Disease Risk Factors in Hispanic Individuals

Gomez

Blumer

Rodríguez

2022

Curr Cardiovasc Risk Rep

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Purpose of Review This review summarizes contemporary data on unique cardiovascular disease (CVD) risk factors in Hispanic individuals in the USA, and how addressing these factors is important in addressing health equity. Recent Findings Recent studies have shown high rates of traditional CVD risk factors in Hispanic individuals such as obesity, hypertension, diabetes, hyperlipidemia, and emerging CVD risk factors like hypertensive disorders of pregnancy, psychological stress, and occupational exposures. However, most studies fail to consider the significant heterogeneity in risk factor burden and outcomes in atherosclerotic CVD by Hispanic subgroup. Heart failure and rhythm disorders are less well studied in Hispanic adults, making risk assessment for these conditions difficult. High levels of CVD risk factors in Hispanic youth given an aging Hispanic population overall highlight the importance of risk mitigation among these individuals. Summary In brief, these data highlight the significant, unique burden of CVD risk among Hispanic individuals in the USA and predict a rising burden of disease among this growing and aging population. Future CVD research should focus on including robust, diverse Hispanic cohorts as well as specifically delineating results for disaggregated Hispanic groups across CVDs. This will allow for better risk assessment, prevention, and treatment decisions to promote health equity for Hispanic patients.

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“…in the prediction of stroke and bleeding risks 143 , 144 and are typically derived from large-scale registries and trials that investigated the relevant clinical outcomes. Statistical models have also been applied to several of the current challenges in AF management, including early AF detection, 90 , 91 rhythm-control management, 100 and AF recurrence prediction. 101 Several statistical models have combined conventional risk scores based on clinical characteristics with biomarkers to increase their predictive performance.…”

Section: Data-driven Models For Af Managementmentioning

confidence: 99%

Computational models of atrial fibrillation: achievements, challenges, and perspectives for improving clinical care

Heijman

Sutanto

Crijns

et al. 2021

Cardiovascular Research

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Despite significant advances in its detection, understanding and management, atrial fibrillation (AF) remains a highly prevalent cardiac arrhythmia with major impact on morbidity and mortality of millions of patients. AF results from complex, dynamic interactions between risk factors and comorbidities that induce diverse atrial remodeling processes. Atrial remodeling increases AF vulnerability and persistence, while promoting disease progression. The variability in presentation and wide range of mechanisms involved in initiation, maintenance and progression of AF, as well as its associated adverse outcomes, make the early identification of causal factors modifiable with therapeutic interventions challenging, likely contributing to suboptimal efficacy of current AF management. Computational modeling facilitates the multilevel integration of multiple datasets and offers new opportunities for mechanistic understanding, risk prediction and personalized therapy. Mathematical simulations of cardiac electrophysiology have been around for 60 years and are being increasingly used to improve our understanding of AF mechanisms and guide AF therapy. This narrative review focuses on the emerging and future applications of computational modeling in AF management. We summarize clinical challenges that may benefit from computational modeling, provide an overview of the different in silico approaches that are available together with their notable achievements, and discuss the major limitations that hinder the routine clinical application of these approaches. Finally, future perspectives are addressed. With the rapid progress in electronic technologies including computing, clinical applications of computational modeling are advancing rapidly. We expect that their application will progressively increase in prominence, especially if their added value can be demonstrated in clinical trials.

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Prospective multicentric validation of a novel prediction model for paroxysmal atrial fibrillation

Cited by 5 publications

References 29 publications

MicroRNAs Regulate TASK‐1 and Are Linked to Myocardial Dilatation in Atrial Fibrillation

MicroRNAs Regulate TASK‐1 and Are Linked to Myocardial Dilatation in Atrial Fibrillation

Unique Cardiovascular Disease Risk Factors in Hispanic Individuals

Computational models of atrial fibrillation: achievements, challenges, and perspectives for improving clinical care

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