Stanley NattelMontreal Heart Institute · Department of Medicine
Stanley Nattel
MD
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Publications (962)
Background
Cardiac surgery triggers sterile innate immune responses leading to postoperative complications. Clonal hematopoiesis (CH) is associated with short‐term inflammation‐mediated outcomes after cardiac surgery. The impact of CH on long‐term postoperative outcomes remains unknown.
Methods and Results
In this cohort study, patients undergoing...
Atrial fibrillation (AF) is the most common arrhythmia in the world. Human genetics can provide strong AF therapeutic candidates, but the identification of the causal genes and their functions remains challenging. Here, we applied an AF fine-mapping strategy that leverages results from a previously published cross-ancestry genome-wide association s...
Aims
The concept of “atrial cardiomyopathy” (AtCM) had been percolating through the literature since its first mention in 1972. Since then, publications using the term were sporadic until the decision was made to convene an expert working group with representation from four multinational arrhythmia organizations to prepare a consensus document on a...
BACKGROUND
Atrial fibrillation (AF) and ventricular fibrillation (VF) episodes exhibit varying durations, with some spontaneously ending quickly while others persist. A quantitative framework to explain episode durations remains elusive. We hypothesized that observable self-terminating AF and VF episode lengths, whereby durations are known, would c...
Aims
Cellular senescence is a stress-related or aging response believed to contribute to many cardiac conditions; however, its role in atrial fibrillation (AF) is unknown. Age is the single most important determinant of the risk of AF. The present study was designed to (i) evaluate AF susceptibility and senescence marker expression in rat models of...
Aims
Recent studies suggest that bioactive mediators called resolvins promote an active resolution of inflammation. Inflammatory signalling is involved in the development of the substrate for atrial fibrillation (AF). The aim of this study is to evaluate the effects of resolvin-D1 on atrial arrhythmogenic remodelling resulting from left ventricular...
Atrial cardiomyopathy is a condition that causes electrical and contractile dysfunction of the atria, often along with structural and functional changes. Atrial cardiomyopathy most commonly occurs in conjunction with ventricular dysfunction, in which case it is difficult to discern the atrial features that are secondary to ventricular dysfunction f...
Introduction: Sinoatrial node (SAN) dysfunction commonly occurs in atrial cardiomyopathy (ACM: “tachy-brady syndrome”), often requiring pacemaker implantation, but mechanisms are unknown. Atrial-selective myosin light chain-4 (MYL-4) mutations cause familial ACM with a high rate of early SAN dysfunction and pacemaker requirement. We studied rats en...
Introduction: Cellular senescence, a stress and age-related response, is often characterized by p16 expression in p16 positive (p16 ⁺ ) senescent cells. Senescent cells secrete profibrotic and proinflammatory factors as parts of a “senescence associated secretory phenotype”. The role of cellular senescence in myocardial infarction (MI) is unclear....
Almost half of patients recovering from open chest surgery experience atrial fibrillation (AF) that results principally from inflammation in the pericardial space surrounding the heart. Given that post-operative AF is associated with increased mortality, effective measures to prevent AF after open-chest surgery are highly desirable. In this study,...
Background: Despite being central to atrial fibrillation (AF) and ventricular fibrillation (VF) mechanisms and therapy, the factors governing AF and VF termination are poorly understood. It has been noted that ratio of system size ( L ) and the two-point spatial correlation length (ξ 2 ) are associated with time until termination in transient spati...
Background:
Small-conductance Ca2+-activated K+ (SK)-channel inhibitors have antiarrhythmic effects in animal models of atrial fibrillation (AF), presenting a potential novel antiarrhythmic option. However, the regulation of SK-channels in human atrial cardiomyocytes and its modification in patients with AF are poorly understood and were the objec...
Objectives
To determine the role of MYL4 regulation of lysosomal function and its disturbance in fibrotic atrial cardiomyopathy.
Background
We have previously demonstrated that the atrial-specific essential light chain protein MYL4 is required for atrial contractile, electrical, and structural integrity. MYL4 mutation/dysfunction leads to atrial f...
Long QT syndrome (LQTS) is an inherited cardiac rhythm disorder associated with increased incidence of cardiac arrhythmias and sudden death. LQTS type 5 (LQT5) is caused by dominant mutant variants of KCNE1, a regulatory subunit of the voltage-gated ion channels generating the cardiac potassium current IKs. While mutant LQT5 KCNE1 variants are know...
Introduction: Atrial fibrillation (AF) causes atrial remodeling, leading to progressive resistance to therapy. Changes in cell metabolism likely contribute to remodeling; here, we studied the nature and time course of mitochondrial (MITO) changes during AF . Methods: Atrial cardiomyocytes were isolated from control dogs and dogs kept in AF for 24 h...
Background: Age is a major risk factor for heart failure with preserved ejection fraction (HFpEF); however, the underlying mechanisms are poorly understood. Cellular senescence is an aging and stress related response; senescent cells (SCs) secrete bioactive substances that produce a variety of pathological changes. The role of senescence in HFpEF i...
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...
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...
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...
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...
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...
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...
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...
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...
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...
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....
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...
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...
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...
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...
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...
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 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...
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...
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...
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...
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...
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...
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...
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...
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...
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⁺ (...
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...
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...
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...
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...
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;...
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...
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...
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...