Montreal Heart Institute
Montreal Heart Institute
Lettre G.,Montreal Heart Institute
Nature Genetics | Year: 2017
A new study reports molecular characterization of the GDF5 locus, which is associated with osteoarthritis risk and adult height in humans. This study provides evidence of positive selection for short stature at GDF5 in modern humans, as well as in archaic Neandertals and Denisovans. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
Dobrev D.,University of Heidelberg |
Carlsson L.,Astrazeneca |
Nattel S.,Montreal Heart Institute
Nature Reviews Drug Discovery | Year: 2012
Atrial fibrillation is the most common type of cardiac arrhythmia, and is responsible for substantial morbidity and mortality in the general population. Current treatments have moderate efficacy and considerable risks, especially of pro-arrhythmia, highlighting the need for new therapeutic strategies. In recent years, substantial efforts have been invested in developing novel treatments that target the underlying molecular determinants of atrial fibrillation, and several new compounds are under development. This Review focuses on the mechanistic rationale for the development of new anti-atrial fibrillation drugs, on the molecular and structural motifs that they target and on the results obtained so far in experimental and clinical studies. © 2012 Macmillan Publishers Limited. All rights reserved.
Nattel S.,Montreal Heart Institute
JACC: Clinical Electrophysiology | Year: 2017
Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. Atrial fibrosis has emerged as an important pathophysiological contributor and has been linked to AF recurrences, resistance to therapy and complications. Here, the author reviews the molecular and cellular mechanisms that control atrial fibrosis. It is important to note that not all tissue fibrosis is identical. For example, reactive (interstitial) fibrosis increases the amount of collagen between cardiac muscle bundles without fundamentally altering muscle bundle architecture. Replacement (reparative) fibrosis replaces dead cardiomyocytes with extracellular matrix tissue and fibroblasts, preserving tissue integrity at the expense of muscle bundle continuity. Replacement fibrosis may be much more disruptive to electric conduction and more difficult to reverse than reactive fibrosis. The author reviews the complex signaling systems that cause fibrosis, including those connected to connective tissue growth factor, angiotensin-II, platelet-derived growth factor, and transforming growth factor-β. The author then considers the molecular constitution of fibrous tissue, including the production and maturation of collagen and the roles of important extracellular matrix proteins such as fibronectin, tenascin-C, and thrombospodin-1. The author then discusses the evolving evidence for an important role of Ca2+ entry in the profibrotic activation of fibroblasts, along with evidence that dysregulation of Ca2+-transporting transient potential receptor channels and inward rectifier K+ channels in AF fibroblasts is profibrotic. Finally, the author reviews the evidence for micro-ribonucleic acid involvement in atrial fibrotic signaling and AF promotion. It is hoped that an improved understanding of the mechanisms controlling atrial fibrosis will open up new opportunities for AF prevention and management. © 2017 American College of Cardiology Foundation
Denault A.Y.,Montreal Heart Institute
Anesthesia and Analgesia | Year: 2017
BACKGROUND:: Portal venous flow pulsatility detected by Doppler ultrasound is a sign of congestive heart failure in noncritically ill patients. The assessment of portal and splenic venous flows has never been reported in patients undergoing cardiac surgery. METHODS:: This is a case series performed in patients undergoing cardiac surgery between February 2014 and February 2015 in which portal and/or splenic venous flows were assessed by the attending anesthesiologist during surgery or by the intensivist after surgery using transthoracic echography in 9 patients or transesophageal echocardiography in 5 patients. Data collection was done retrospectively by reviewing intraoperative and postoperative monitoring documents. The technique of assessment is detailed in this article. RESULTS:: We report the abnormal portal and/or splenic venous flow pulsatility from 14 patients perioperatively. At the time of pulsatility detection, patients had a median cumulative fluid balance of 3.8 L (interquartile range: 0–4.6 L) and a median right atrial pressure of 14.0 mm Hg (interquartile range: 12.0–15.5 mm Hg). In some patients (4/14), signs of right ventricular dysfunction on echocardiography and/or right ventricular pressure monitoring were present. CONCLUSIONS:: Doppler evaluation of portal and splenic venous flow using transthoracic echography and transesophageal echocardiography may represent a promising modality to assess end-organ venous congestion in cardiac surgery patients. © 2017 International Anesthesia Research Society
News Article | February 28, 2017
Exelerence Holdings Inc., an investment company focused on the rapidly growing internet infrastructure industry is pleased to announce the appointment of Mr. Pierre Blouin to its Board of Directors. Exelerence owns and operates METRO OPTIC, a provider of high-speed fiber optic networks and I.C.E DATACENTERS, a carrier-neutral provider of network-centric datacenters in Canada. Mr. Blouin spent 30 years in the North American telecom and technology industry and recently retired as Chief Executive Officer of Manitoba Telecom Services Inc. and MTS Allstream. Previously, he occupied various senior executive positions within the BCE group of companies including President and Chief Executive Officer of Bell Mobility Inc., Chief Executive Officer of BCE Emergis Inc. and Group President, Consumer Markets for Bell Canada. Mr. Blouin is also an active corporate director and currently sits on the Board of Fortis Inc., the National Bank of Canada and the Montreal Heart Institute Foundation. “We are delighted and honoured that Mr. Blouin has accepted to join our Board of Directors,” said Michael Bucheit, CEO of Exelerence Holdings Inc. “His extensive leadership experience in the rapidly evolving telecommunications industry will provide us with valuable strategic guidance and assist us in accelerating our client-driven growth in high-speed networks and network-centric datacenters.” “I am pleased to join the board of such a dynamic company that owns solid and unique network assets and strong datacenter expertise. Its skilled and dedicated workforce is well positioned to meet customer demands in the fast-growing cloud market. I am looking forward to work with management and board members to support the company in rapid growth,” commented Pierre Blouin. About Metro Optic (http://www.metrooptic.com): METRO OPTIC is an independent provider of datacenter-neutral high-speed fiber network solutions. Since its inception, Metro Optic offers specialized telecommunications services and solutions to medium and large sized businesses, telecom carriers, cloud operators, wholesalers and datacenter operators. Its carrier-neutral datacenter at 875 Saint-Antoine is the fiber-densest interconnection center in Montreal. About I.C.E Datacenters (http://www.icedatacenters.com): I.C.E DATACENTERS (Interconnection and Colocation for the Enterprise) operates multiple datacenter sites and interconnection hubs in Canada. These include leading interconnection sites in downtown Montreal and in Markham (Toronto). I.C.E Datacenters combines deep datacenter expertise serving global enterprises and cloud operators in the U.S. and Canada with extensive know-how in operating high-speed fiber networks.
Nattel S.,Montreal Heart Institute |
Harada M.,Montreal Heart Institute |
Harada M.,Hamamatsu Medical Center
Journal of the American College of Cardiology | Year: 2014
Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. AF and its complications are responsible for important population morbidity and mortality. Presently available therapeutic approaches have limited efficacy and nontrivial potential to cause adverse effects. Thus, new mechanistic knowledge is essential for therapeutic innovation. Atrial arrhythmogenic remodeling, defined as any change in atrial structure or function that promotes atrial arrhythmias, is central to AF. Remodeling can be due to underlying cardiac conditions, systemic processes and conditions such as aging, or AF itself. Recent work has underlined the importance of remodeling in AF, provided new insights into basic mechanisms, and identified new biomarker/imaging approaches to follow remodeling processes. The importance of intracellular Ca2+ handling abnormalities has been highlighted, both for the induction of triggered ectopic activity and for the activation of Ca2+-related cell signaling that mediates profibrillatory remodeling. The importance of microRNAs, which are a new class of small noncoding sequences that regulate gene expression, has emerged in both electrical and structural remodeling. Remodeling related to aging, cardiac disease, and AF itself is believed to underlie the progressive nature of the arrhythmia, which contributes to the complexities of long-term management. New tools that are being developed to quantify remodeling processes and monitor their progression include novel biomarkers, imaging modalities to quantify/localize fibrosis, and noninvasive monitoring/mapping to better characterize the burden of AF and identify arrhythmic sources. This report reviews recent advances in the understanding of the basic pathophysiology of atrial remodeling and potential therapeutic implications. © 2014 by the American College of Cardiology Foundation Published by Elsevier Inc.
Nattel S.,Montreal Heart Institute
Canadian Journal of Cardiology | Year: 2011
The 2011 Canadian Cardiovascular Society Atrial Fibrillation (AF) Guidelines provide detailed recommendations for AF management, as well as extensive background information. The Guidelines documents highlight many important unresolved questions and areas of clinical need that could benefit from basic research investigations. This article discusses basic research priorities emanating from the Guidelines reflections. Topics addressed include forms of AF and their interrelations, limitations of the presently available experimental models of AF, genetic factors, determinants of drug efficacy for pharmacologic cardioversion, mechanisms of AF-related thromboembolism, ventricular rate control, drugs for rhythm control, upstream therapy, mechanisms by which catheter ablation controls AF, mechanisms of postoperative AF, and the possibility of novel patient-based surgical procedures. A guidelines-to-bench approach to research may allow for the development of important, clinically relevant new knowledge with impacts on patient management and future AF guidelines. © 2011 Canadian Cardiovascular Society.
Calderone A.,Montreal Heart Institute
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2012
Scar formation following an ischemic insult to the heart is referred to as reparative fibrosis and represents an essential physiological response to heal the damaged myocardium. The biological events of reparative fibrosis include inflammation, the deposition of collagen by my fibroblasts, sympathetic innervations, and angiogenesis. Several studies have further reported that scar formation was associated with the recruitment of neural crest-derived cardiac resident nestin + cells that display characteristics consistent with a neural progenitor/stem cell phenotype. During the reparative fibro tic response, these Nestin + cells participate in neural remodeling and represent a novel cellular substrate of angiogenesis. In addition, a subpopulation of Nestin + cells identified in the normal heart expressed cardiac progenitor transcriptional factors and may directly contribute to myocardial regeneration following ischemic damage. Nestin protein was also detected in endothelial cells of newly formed blood vessels in the scar and may represent a marker of revascularization. Lastly, Nestin was induced in a subpopulation of smooth muscle a-act in + scar-derived my fibroblasts, and the expression of the intermediate filament protein may provide a proliferative advantage. Collectively, these data demonstrate that diverse populations of Nestin + cells participate in cardiac wound healing. © 2012 the American Physiological Society.
Dobrev D.,TU Dresden |
Nattel S.,Montreal Heart Institute
The Lancet | Year: 2010
Inadequacies in current therapies for atrial fibrillation have made new drug development crucial. Conventional antiarrhythmic drugs increase the risk of ventricular proarrhythmia. In drug development, the focus has been on favourable multichannel-blocking profiles, atrial-specific ion-channels, and novel non-channel targets (upstream therapy). Molecular modification of the highly effective multichannel blocker, amiodarone, to improve safety and tolerability has produced promising analogues such as dronedarone, although this drug seems less effective than does amiodarone. Vernakalant, an atrial-selective drug with reduced proarrhythmic risk, might be useful for cardioversion in atrial fibrillation. Ranolazine, another atrial-selective agent initially developed as an antianginal, has efficacy for atrial fibrillation and is being tested in prospective clinical trials. So-called upstream therapy with angiotensin-converting enzyme and angiotensin-receptor inhibitors, statins, or omega-3 fatty acids and fish oil that target atrial remodelling could be effective, but need further clinical validation. We focus on the basic and clinical pharmacology of newly emerging antiarrhythmic drugs and non-traditional approaches such as upstream therapy for atrial fibrillation. © 2010 Elsevier Ltd. All rights reserved.
Asgar A.W.,Montreal Heart Institute |
Mack M.J.,Heart Hospital Baylor Plano |
Stone G.W.,Columbia University
Journal of the American College of Cardiology | Year: 2015
The development of secondary mitral regurgitation (MR) due to left ventricular dysfunction, also known as functional MR, is strongly associated with a poor prognosis in patients with heart failure. The mechanisms underlying secondary MR are multifactorial; accurate imaging assessment of secondary MR may be challenging and nuanced; and the appropriate roles of medical, surgical, and interventional therapies for management of secondary MR are controversial and evolving. In this review, the pathophysiology, evaluation, and prognosis of secondary MR in patients with heart failure are discussed, and we evaluate in detail the evidence for the various therapeutic approaches for secondary MR, including guideline-directed medication for left ventricular dysfunction, cardiac resynchronization therapy and revascularization when appropriate, and mitral valve surgery and transcatheter interventions. The role of a multidisciplinary heart team in determining the optimal management strategy for secondary MR is also discussed. © 2015 American College of Cardiology Foundation.