Stanley Nattel

Stanley Nattel
Montreal Heart Institute · Department of Medicine

MD

About

920
Publications
91,366
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69,585
Citations
Citations since 2016
175 Research Items
29317 Citations
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Publications

Publications (920)
Article
Full-text available
Background and Objective: Renewal theory is a statistical approach to model the formation and destruction of phase singularities (PS), which occur at the pivots of spiral waves. A common issue arising during observation of renewal processes is an inspection paradox, due to oversampling of longer events. The objective of this study was to characteri...
Article
Inflammation has been implicated in atrial fibrillation (AF), a very common and clinically significant cardiac rhythm disturbance, but its precise role remains poorly understood. Work performed over the past 5 years suggests that atrial cardiomyocytes have inflammatory signalling machinery - in particular, components of the NLRP3 (NACHT-, LRR- and...
Article
Obesity is an important contributing factor to the pathophysiology of atrial fibrillation (AF) and its complications by causing systemic changes, such as altered hemodynamic, increased sympathetic tone and low-grade chronic inflammatory state. In addition, adipose tissue is a metabolically active organ that comprises various types of fat deposits w...
Article
As the most prevalent form of arrhythmia, atrial fibrillation (AF) increases the risk of heart failure, thromboembolism, and stroke, contributing to the raising mortality and morbidity in patients with cardiovascular diseases. Despite the multifaceted nature of AF pathogenesis and complexity of AF pathophysiology, a growing body of evidence indicat...
Article
Electrical storm, characterized by repetitive ventricular tachycardia/fibrillation (VT/VF) over a short period, is becoming commoner with widespread use of implantable cardioverter-defibrillator (ICD) therapy. Electrical storm, sometimes called “arrhythmic storm” or “VT-storm”, is usually a medical emergency requiring hospitalization and expert man...
Article
Cellular senescence, classically defined as stable cell cycle arrest, is implicated in biological processes such as embryogenesis, wound healing and ageing. Senescent cells have a complex senescence-associated secretory phenotype (SASP), involving a range of pro-inflammatory factors with important paracrine and autocrine effects on cell and tissue...
Article
Background Electrical storm (ES) is a life-threatening emergency in patients at high risk of ventricular tachycardia/fibrillation (VT/VF), but the pathophysiology and molecular basis are poorly understood. Objective To explore the electrophysiological substrate for experimental ES. Methods A model was created by inducing chronic complete atrioven...
Article
Recent preclinical and observational cohort studies have implicated imbalances in gut microbiota composition as a contributor to atrial fibrillation (AF). The gut microbiota is a complex and dynamic ecosystem containing trillions of microorganisms, which produces bioactive metabolites influencing host health and disease development. In addition to...
Article
Full-text available
Rationale: Fibrosis promotes the maintenance of atrial fibrillation (AF), making it resistant to therapy. Improved understanding of the molecular mechanisms leading to atrial fibrosis will open new pathways towards effective antifibrotic therapies. Objective: This study aims to decipher the mechanistic interplay between polo-like kinase 2 (PLK2) an...
Article
Full-text available
We have shown that calcium-activated potassium (KCa)-channels regulate fundamental progenitor-cell functions, including proliferation, but their contribution to cell-therapy effectiveness is unknown. Here, we test the participation of KCa-channels in human heart explant-derived cell (EDC) physiology and therapeutic potential. TRAM34-sensitive KCa3....
Article
Dietary intake has been shown to change the composition of gut microbiota and some changes in microbiota (dysbiosis) have been linkedto diabetes, hypertension, and obesity, which are established risk factors for atrial fibrillation (AF). In addition, intestinal dysbiosis generatesmicrobiota-derived bioactive metabolites that might exert proarrhythm...
Article
Full-text available
Background - Atrial fibrillation (AF), the most common sustained arrhythmia, is associated with increased morbidity, mortality, and health-care costs. AF develops over many years and is often related to substantial atrial structural and electrophysiological remodeling. AF may lack symptoms at onset and atrial biopsy samples are generally obtained i...
Article
Full-text available
The pig is commonly used as an experimental model of human heart disease, including for the study of mechanisms of arrhythmia. However, there exist differences between human and porcine cellular electrophysiology: The pig action potential (AP) has a deeper phase-1 notch, a longer duration at 50% repolarization, and higher plateau potentials than hu...
Article
Given its complexity, the management of atrial fibrillation (AF) has relied increasingly on expert guideline recommendations; however, discrepancies among these professional societies can lead to confusion among practicing clinicians. This article compares the recommendations in the 2019 American Heart Association (AHA)/American College of Cardiolo...
Article
Full-text available
6,9,10 ✉ Endogenous cardiac pacemaker function regulates the rate and rhythm of cardiac contraction. The mutation p.Lys23Glu in the cohesin protein Shugoshin-1 causes severe heart arrhythmias due to sinoatrial node dysfunction and a debilitating gastrointestinal motility disorder, collectively termed the Chronic Atrial and Intestinal Dysrhythmia Sy...
Article
Full-text available
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...
Article
Atrial fibrillation (AF) is the most common sustained clinical arrhythmia, with a lifetime incidence of up to 37%, and is a major contributor to population morbidity and mortality. Important components of AF management include control of cardiac rhythm, rate and thromboembolic risk. In this narrative review article, we focus on rhythm control thera...
Article
Hormones are potent endo-, para- and autocrine endogenous regulators of the function of multiple organs, including the heart. Endocrine dysfunction promotes a number of cardiovascular diseases, including atrial fibrillation (AF). While the heart is a target for endocrine regulation, it is also an active endocrine organ itself, secreting a number of...
Article
Biomarkers derived from the key components of the pathophysiology of atrial fibrillation (AF) and its complications have the potential to play an important role in earlier characterization of AF phenotype and in risk prediction of adverse clinical events, which may translate into improved management strategies. C-reactive protein, natriuretic pepti...
Article
Inflammation and fibrosis have been implicated in the pathophysiology of atrial fibrillation. Atrial fibrosis causes conduction disturbances and is a central component of atrial remodeling in atrial fibrillation. Cardiac fibroblasts, the cells responsible for fibrosis formation, are activated by inflammatory mediators and growth factors associated...
Article
Obstructive sleep apnea (OSA) creates a complex and dynamic substrate for atrial fibrillation (AF), which is characterized by structural remodeling as a result of long-term OSA as well as transient and acute apnea-associated transient atrial electrophysiological changes. OSA is present in 21% to 74% of patients with AF, and nonrandomized studies su...
Article
Advances in atrial fibrillation (AF) management, perioperative medicine, and surgical techniques have reignited an interest in postoperative AF (POAF). POAF results from the interaction among subclinical atrial substrate, surgery-induced substrate, and transient postoperative factors. Prophylaxis for POAF after cardiac surgery is well established b...
Article
Atrial fibrillation (AF) is an important clinical problem. Chronic pressure/volume overload of the atria promotes AF, particularly via enhanced extracellular matrix (ECM) accumulation manifested as tissue fibrosis. Loading of cardiac cells causes cell-stretch that is generally considered to promote fibrosis by directly activating fibroblasts, the k...
Preprint
Full-text available
Background Atrial fibrillation (AF), the most common sustained arrhythmia, is associated with increased morbidity, mortality, and health-care costs. AF develops over many years and is often related to substantial atrial structural and electrophysiological remodeling. AF may lack symptoms at onset and atrial biopsy samples are generally obtained in...
Article
Full-text available
Rationale A quantitative framework to summarize and explain the quasi-stationary population dynamics of unstable phase singularities (PS) and wavelets in human atrial fibrillation (AF) is at present lacking. Building on recent evidence showing that the formation and destruction of PS and wavelets in AF can be represented as renewal processes, we so...
Article
Rationale: The mechanisms underlying atrial fibrillation (AF), the most common clinical arrhythmia, are poorly understood. Nucleoplasmic Ca ²⁺ regulates gene-expression, but the nature and significance of nuclear Ca ²⁺ -changes in AF are largely unknown. Objective: To elucidate mechanisms by which AF alters atrial cardiomyocyte (CM) nuclear Ca ²⁺ (...
Article
Full-text available
Atrial fibrillation, the most common cardiac arrhythmia, is an important contributor to mortality and morbidity, and particularly to the risk of stroke in humans. Atrial-tissue fibrosis is a central pathophysiological feature of atrial fibrillation that also hampers its treatment; the underlying molecular mechanisms are poorly understood and warran...
Article
Chronic obstructive pulmonary disease (COPD) is highly prevalent among patients with atrial fibrillation (AF), shares common risk factors, and adds to the overall morbidity and mortality in this population. Additionally, it may promote AF and impair treatment efficacy. The prevalence of COPD in AF patients is high and is estimated to be ∼25%. Diagn...
Article
Background Pulmonary vein (PV) stenosis is a complication of atrial fibrillation (AF) ablation. The incidence of PV stenosis after routine post-ablation imaging remains unclear and is limited to single-centre studies. Our objective was to determine the incidence and predictors of PV stenosis following circumferential radiofrequency ablation in the...
Article
Full-text available
The Canadian Cardiovascular Society (CCS) atrial fibrillation (AF) guidelines program was developed to aid clinicians in the management of these complex patients, as well as to provide direction to policy makers and health care systems regarding related issues. The most recent comprehensive CCS AF guidelines update was published in 2010. Since then...
Article
Aims: Inflammation plays a role in atrial fibrillation (AF), but classical anti-inflammatory molecules are ineffective. Recent evidence suggests that failure of inflammation-resolution causes persistent inflammatory signaling and a novel drug-family called resolvins promotes inflammation-resolution. Right heart disease (RHD) is associated with AF;...
Article
Full-text available
Rationale: Post-operative atrial fibrillation (POAF) is a common and troublesome complication of cardiac surgery. POAF is generally believed to occur when post-operative triggers act on a pre-existing vulnerable substrate, but the underlying cellular and molecular mechanisms are largely unknown. Objective: To identify cellular POAF-mechanisms in ri...
Article
Full-text available
Importance Contemporary guidelines recommend that atrial fibrillation (AF) be classified based on episode duration, with these categories forming the basis of therapeutic recommendations. While pragmatic, these classifications are not based on pathophysiologic processes and may not reflect clinical outcomes. Objective To evaluate the association o...
Article
Background Atrial flutter (AFL) and atrial fibrillation (AF) are associated with AF-promoting atrial remodeling, but no experimental studies have addressed remodeling with sustained AFL. Objectives This study aimed to define the atrial remodeling caused by sustained atrial flutter (AFL) and/or atrial fibrillation (AF). Methods Intercaval radiofre...
Article
Full-text available
Atrial fibrillation (AF) is a highly prevalent arrhythmia, with substantial associated morbidity and mortality. There have been significant management advances over the past 2 decades, but the burden of the disease continues to increase and there is certainly plenty of room for improvement in treatment options. A potential key to therapeutic innova...
Article
Full-text available
Atrial fibrillation (AF) alters atrial-cardiomyocyte (ACM) Ca2+-handling, promoting ectopic-beat formation. Here, we examined the effects of AF-associated remodeling on Ca2+-related action-potential (AP) dynamics and consequences for AF-susceptibility. AF was maintained electrically (x1 week) in dogs by right-atrial (RA) tachypacing. ACMs isolated...
Article
Full-text available
AMP-activated protein kinase (AMPK) is the cellular stress-sensing molecule. Apart from maintaining cellular energy balance, AMPK also controls expression and regulation of ion channels and ion transporters, including cytosolic Ca2+ handling proteins. Emerging evidence suggests that metabolic impairment plays a crucial role in the pathogenesis of a...
Article
Full-text available
Aims No studies have assessed the specific contributions of atrial fibrillation (AF)-related atrial vs. associated ventricular arrhythmia to remodelling. This study assessed the roles of atrial arrhythmia vs. high ventricular rate in AF-associated remodelling. Methods and results Four primary dog-groups (12/group) were subjected to 3-week pacing:...
Article
Background: The use of an intraprocedural observation and pharmacologic challenges have been proposed as a means to differentiate permanent pulmonary vein (PV)-left atrial conduction block from inadequate ablation lesions. Objective: We sought to determine the prevalence and clinical impact of spontaneous and adenosine-provoked reconnection usin...
Article
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Article
Full-text available
Background: Despite a century of research, no clear quantitative framework exists to model the fundamental processes responsible for the continuous formation and destruction of phase singularities (PS) in cardiac fibrillation. We hypothesized PS formation/destruction in fibrillation could be modeled as self-regenerating Poisson renewal processes,...
Article
Background: Conditions affecting the right heart, including diseases of the lungs and pulmonary circulation, promote atrial fibrillation (AF), but the mechanisms are poorly understood. Objectives: This study sought to determine whether right heart disease promotes atrial arrhythmogenesis in a rat model of pulmonary hypertension (PH) and, if so,...
Article
Heart diseases are a major cause of morbidity and mortality world-wide. Lysyl oxidase (LOX) and related LOX-like (LOXL) isoforms play a vital role in remodelling the extracellular matrix (ECM). The LOX family controls ECM formation by cross-linking collagen and elastin chains. LOX/LOXL proteins are copper-dependent amine oxidases that catalyse the...