Author
Niels Voigt
Other affiliations: University of Duisburg-Essen, Dresden University of Technology, Montreal Heart Institute ...read more
Bio: Niels Voigt is an academic researcher from University of Göttingen. The author has contributed to research in topics: Atrial fibrillation & Ryanodine receptor. The author has an hindex of 37, co-authored 117 publications receiving 6219 citations. Previous affiliations of Niels Voigt include University of Duisburg-Essen & Dresden University of Technology.
Papers published on a yearly basis
Papers
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TL;DR: Enhanced SR Ca2+ leak through CaMKII-hyperphosphorylated RyR2, in combination with larger INCX for a given SR Ca 2+ release and increased diastolic [Ca2+]i-voltage coupling gain, causes AF-promoting atrial delayed afterdepolarizations/triggered activity in cAF patients.
Abstract: Background—Delayed afterdepolarizations (DADs) carried by Na+-Ca2+-exchange current (INCX) in response to sarcoplasmic reticulum (SR) Ca2+ leak can promote atrial fibrillation (AF). The mechanisms leading to delayed afterdepolarizations in AF patients have not been defined. Methods and Results—Protein levels (Western blot), membrane currents and action potentials (patch clamp), and [Ca2+]i (Fluo-3) were measured in right atrial samples from 76 sinus rhythm (control) and 72 chronic AF (cAF) patients. Diastolic [Ca2+]i and SR Ca2+ content (integrated INCX during caffeine-induced Ca2+ transient) were unchanged, whereas diastolic SR Ca2+ leak, estimated by blocking ryanodine receptors (RyR2) with tetracaine, was ≈50% higher in cAF versus control. Single-channel recordings from atrial RyR2 reconstituted into lipid bilayers revealed enhanced open probability in cAF samples, providing a molecular basis for increased SR Ca2+ leak. Calmodulin expression (60%), Ca2+/calmodulin-dependent protein kinase-II (CaMKII) a...
525 citations
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TL;DR: The ways in which cardiac disease states, extracardiac factors, and abnormal genetic control lead to the arrhythmia are discussed, including the potential therapeutic implications that might arise from an improved mechanistic understanding.
Abstract: Atrial fibrillation (AF) is an extremely common cardiac rhythm disorder that causes substantial morbidity and contributes to mortality. The mechanisms underlying AF are complex, involving both increased spontaneous ectopic firing of atrial cells and impulse reentry through atrial tissue. Over the past ten years, there has been enormous progress in understanding the underlying molecular pathobiology. This article reviews the basic mechanisms and molecular processes causing AF. We discuss the ways in which cardiac disease states, extracardiac factors, and abnormal genetic control lead to the arrhythmia. We conclude with a discussion of the potential therapeutic implications that might arise from an improved mechanistic understanding.
488 citations
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TL;DR: A comprehensive understanding of AF pathophysiology is expected to foster the development of improved pharmacological and nonpharmacological therapeutic approaches and to greatly improve clinical management.
Abstract: Atrial fibrillation (AF) is the most common clinically relevant arrhythmia and is associated with increased morbidity and mortality. The incidence of AF is expected to continue to rise with the aging of the population. AF is generally considered to be a progressive condition, occurring first in a paroxysmal form, then in persistent, and then long-standing persistent (chronic or permanent) forms. However, not all patients go through every phase, and the time spent in each can vary widely. Research over the past decades has identified a multitude of pathophysiological processes contributing to the initiation, maintenance, and progression of AF. However, many aspects of AF pathophysiology remain incompletely understood. In this review, we discuss the cellular and molecular electrophysiology of AF initiation, maintenance, and progression, predominantly based on recent data obtained in human tissue and animal models. The central role of Ca(2+)-handling abnormalities in both focal ectopic activity and AF substrate progression is discussed, along with the underlying molecular basis. We also deal with the ionic determinants that govern AF initiation and maintenance, as well as the structural remodeling that stabilizes AF-maintaining re-entrant mechanisms and finally makes the arrhythmia refractory to therapy. In addition, we highlight important gaps in our current understanding, particularly with respect to the translation of these concepts to the clinical setting. Ultimately, a comprehensive understanding of AF pathophysiology is expected to foster the development of improved pharmacological and nonpharmacological therapeutic approaches and to greatly improve clinical management.
463 citations
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TL;DR: It is demonstrated that larger basal inward rectifier K+ current in cAF consists of increased IK1 activity and constitutively active IK,ACh, which may represent a new therapeutic target in AF.
Abstract: Background— The molecular mechanism of increased background inward rectifier current (IK1) in atrial fibrillation (AF) is not fully understood. We tested whether constitutively active acetylcholine (ACh)-activated IK,ACh contributes to enhanced basal conductance in chronic AF (cAF). Methods and Results— Whole-cell and single-channel currents were measured with standard voltage-clamp techniques in atrial myocytes from patients with sinus rhythm (SR) and cAF. The selective IK,ACh blocker tertiapin was used for inhibition of IK,ACh. Whole-cell basal current was larger in cAF than in SR, whereas carbachol (CCh)-activated IK,ACh was lower in cAF than in SR. Tertiapin (0.1 to 100 nmol/L) reduced IK,ACh in a concentration-dependent manner with greater potency in cAF than in SR (−logIC50: 9.1 versus 8.2; P<0.05). Basal current contained a tertiapin-sensitive component that was larger in cAF than in SR (tertiapin [10 nmol/L]-sensitive current at −100 mV: cAF, −6.7±1.2 pA/pF, n=16/5 [myocytes/patients] versus SR, −...
434 citations
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TL;DR: Biochemical, functional, and modeling studies point to a combination of increased sarcoplasmic reticulum Ca2+ load related to phospholamban hyperphosphorylation and ryanodine receptor dysregulation and enhanced SERCA2a activity as underlying mechanisms for cellular arrhythmogenesis in pAF patients.
Abstract: Background—Electrical, structural, and Ca2+-handling remodeling contribute to the perpetuation/progression of atrial fibrillation (AF). Recent evidence has suggested a role for spontaneous sarcoplasmic reticulum Ca2+-release events in long-standing persistent AF, but the occurrence and mechanisms of sarcoplasmic reticulum Ca2+-release events in paroxysmal AF (pAF) are unknown. Method and Results—Right-atrial appendages from control sinus rhythm patients or patients with pAF (last episode a median of 10–20 days preoperatively) were analyzed with simultaneous measurements of [Ca2+]i (fluo-3-acetoxymethyl ester) and membrane currents/action potentials (patch-clamp) in isolated atrial cardiomyocytes, and Western blot. Action potential duration, L-type Ca2+ current, and Na+/Ca2+-exchange current were unaltered in pAF, indicating the absence of AF-induced electrical remodeling. In contrast, there were increases in SR Ca2+ leak and incidence of delayed after-depolarizations in pAF. Ca2+-transient amplitude and s...
373 citations
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28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。
18,940 citations
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TL;DR: This document summarizes current research, plans, and recommendations for future research, as well as providing a history of the field and some of the techniques used, currently in use, at the National Institutes of Health.
Abstract: Jeffrey L. Anderson, MD, FACC, FAHA, Chair
Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect
Nancy M. Albert, PhD, RN, FAHA
Biykem Bozkurt, MD, PhD, FACC, FAHA
Ralph G. Brindis, MD, MPH, MACC
Mark A. Creager, MD, FACC, FAHA[#][1]
Lesley H. Curtis, PhD, FAHA
David DeMets, PhD[#][1]
Robert A
6,967 citations
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TL;DR: The Task Force for the management of atrial fibrillation of the European Society of Cardiology has been endorsed by the European Stroke Organisation (ESO).
Abstract: The Task Force for the management of atrial fibrillation of the European Society of Cardiology (ESC)
Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC
Endorsed by the European Stroke Organisation (ESO)
5,255 citations
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4,960 citations
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Leipzig University1, University of Belgrade2, Leiden University3, Uppsala University4, University of Modena and Reggio Emilia5, University of Barcelona6, Carol Davila University of Medicine and Pharmacy7, National and Kapodistrian University of Athens8, François Rabelais University9, University of Melbourne10, Royal Melbourne Hospital11, University of Lisbon12, University of Birmingham13, University of Groningen14, University Medical Center Groningen15, University of Central Lancashire16
TL;DR: The content of these European Society of Cardiology (ESC) Guidelines has been published for personal and educational use only and no commercial use is authorized.
Abstract: Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight <60 kg, concomitant use of dronedarone, erythromycin, ciclosporine or ketokonazole"instead of "Edoxaban 60 mg reduced to 30 mg once daily, and edoxaban 30 mg reduced to 15mg once daily, if any of the following: creatinine clearance of 30-50 mL/min, body weight <60 kg, concomitant us of verapamil or quinidine or dronedarone."
4,285 citations