Show simple item record

dc.creatorTobón C.
dc.creatorPalacio L.C.
dc.creatorChidipi B.
dc.creatorSlough D.P.
dc.creatorTran T.
dc.creatorTran N.
dc.creatorReiser M.
dc.creatorLin Y.-S.
dc.creatorHerweg B.
dc.creatorSayad D.
dc.creatorSaiz J.
dc.creatorNoujaim S.
dc.descriptionIn clinical practice, reducing the burden of persistent atrial fibrillation by pharmacological means is challenging. We explored if blocking the background and the acetylcholine-activated inward rectifier potassium currents (IK1 and IKACh) could be antiarrhythmic in persistent atrial fibrillation. We thus tested the hypothesis that blocking IK1 and IKACh with chloroquine decreases the burden of persistent atrial fibrillation. We used patch clamp to determine the IC50 of IK1 and IKACh block by chloroquine and molecular modeling to simulate the interaction between chloroquine and Kir2.1 and Kir3.1, the molecular correlates of IK1 and IKACh. We then tested, as a proof of concept, if oral chloroquine administration to a patient with persistent atrial fibrillation can decrease the arrhythmia burden. We also simulated the effects of chloroquine in a 3D model of human atria with persistent atrial fibrillation. In patch clamp the IC50 of IK1 block by chloroquine was similar to that of IKACh. A 14-day regimen of oral chloroquine significantly decreased the burden of persistent atrial fibrillation in a patient. Mathematical simulations of persistent atrial fibrillation in a 3D model of human atria suggested that chloroquine prolonged the action potential duration, leading to failure of reentrant excitation, and the subsequent termination of the arrhythmia. The combined block of IK1 and IKACh can be a targeted therapeutic strategy for persistent atrial fibrillation. Copyright © 2019 Tobón, Palacio, Chidipi, Slough, Tran, Tran, Reiser, Lin, Herweg, Sayad, Saiz and Noujaim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
dc.publisherFrontiers Media S.A.
dc.sourceFrontiers in Pharmacology
dc.subjectPersistent atrial fibrillation
dc.subjectPotassium inward rectifiers
dc.subjectantimalarial agent
dc.subjectinwardly rectifying potassium channel subunit Kir2.1
dc.subjectinwardly rectifying potassium channel subunit Kir3.1
dc.subjectpotassium channel
dc.subjectunclassified drug
dc.subjectaction potential duration
dc.subjectclinical article
dc.subjectdisease burden
dc.subjectdrug effect
dc.subjectdrug mechanism
dc.subjectdrug protein binding
dc.subjectlaboratory test
dc.subjectmathematical model
dc.subjectmolecular docking
dc.subjectmolecular model
dc.subjectpatch clamp technique
dc.subjectpersistent atrial fibrillation
dc.subjectpotassium current
dc.titleThe antimalarial chloroquine reduces the burden of persistent atrial fibrillation
dc.publisher.programFacultad de Ciencias Básicas
dc.publisher.facultyFacultad de Ciencias Básicas
dc.affiliationTobón, C., MATBIOM, Universidad de Medellín, Medellín, Colombia; Palacio, L.C., MATBIOM, Universidad de Medellín, Medellín, Colombia; Chidipi, B., Molecular Pharmacology and Physiology Department, University of South Florida Morsani College of Medicine, Tampa, FL, United States; Slough, D.P., Department of Chemistry, Tufts University, Medford, MA, United States; Tran, T., Cardiology Department, University of South Florida Morsani College of Medicine, Tampa, FL, United States; Tran, N., Cardiology Department, University of South Florida Morsani College of Medicine, Tampa, FL, United States; Reiser, M., Molecular Pharmacology and Physiology Department, University of South Florida Morsani College of Medicine, Tampa, FL, United States; Lin, Y.-S., Department of Chemistry, Tufts University, Medford, MA, United States; Herweg, B., Cardiology Department, University of South Florida Morsani College of Medicine, Tampa, FL, United States; Sayad, D., Cardiology Department, University of South Florida Morsani College of Medicine, Tampa, FL, United States; Saiz, J., Ci2 B, Universitat Politècnica de València, Valencia, Spain; Noujaim, S., Molecular Pharmacology and Physiology Department, University of South Florida Morsani College of Medicine, Tampa, FL, United States
dc.relation.referencesAl-Bari, M.A., Chloroquine analogues in drug discovery: New directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases (2015) J. Antimicrob. Chemother., 70, pp. 1608-1621
dc.relation.referencesAnisimov, S.V., Boheler, K.R., Aging-associated changes in cardiac gene expression: Large scale transcriptome analysis (2003) Advances in Gerontology = Uspekhi Gerontologii / Rossiiskaia Akademiia Nauk. Gerontol. Obshchestvo, 11, pp. 67-75
dc.relation.referencesAtienza, F., Jalife, J., Reentry and atrial fibrillation (2007) Heart Rhythm.: Off. J. Heart Rhythm. Soc., 4, pp. S13-S16
dc.relation.referencesBai, J., Gladding, P.A., Stiles, M.K., Fedorov, V.V., Zhao, J., Ionic and cellular mechanisms underlying TBX5/PITX2 insufficiency-induced atrial fibrillation: Insights from mathematical models of human atrial cells (2018) Sci. Rep., 8, p. 15642
dc.relation.referencesBurrell, Z.L., Jr., Martinez, A.C., Chloroquine and hydroxychloroquine in the treatment of cardiac arrhythmias (1958) New Engl. J. Med., 258, pp. 798-800
dc.relation.referencesChung, M.K., Shemanski, L., Sherman, D.G., Greene, H.L., Hogan, D.B., Kellen, J.C., Functional status in rate- Versus rhythm-control strategies for atrial fibrillation: Results of the atrial fibrillation follow-up investigation of rhythm management (AFFIRM) functional status substudy (2005) J. Am. Coll. Cardiol., 46, pp. 1891-1899
dc.relation.referencesColman, M.A., Pinali, C., Trafford, A.W., Zhang, H., Kitmitto, A., A computational model of spatio-temporal cardiac intracellular calcium handling with realistic structure and spatial flux distribution from sarcoplasmic reticulum and t-tubule reconstructions (2017) PloS Comput. Biol., 13
dc.relation.referencesCourtemanche, M., Ramirez, R.J., Nattel, S., Ionic mechanisms underlying human atrial action potential properties: Insights from a mathematical model (1998) Am. J. Physiol., 275, pp. H301-H321
dc.relation.referencesDeGroot, N.M., Schalij, M.J., Fragmented,long-duration,low-amplitude electrograms characterize the origin of focal atrial tachycardia (2006) J. Cardiovasc. Electrophysiol., 17, pp. 1086-1092
dc.relation.referencesDobrev, D., Nattel, S., New insights into the molecular basis of atrial fibrillation: Mechanistic and therapeutic implications (2011) Cardiovasc. Res., 89, pp. 689-691
dc.relation.referencesDuarte, M.R.A., Tobón, C., Cardona, K., Saiz, J., Chloroquine effect on human atrial action potential under normal conditions and during paroxysmal and chronic atrial fibrillation (2013) Columbia:A Simulation Study, PAHCE, pp. 71-75
dc.relation.referencesFilgueiras-Rama, D., Martins, R.P., Mironov, S., Yamazaki, M., Calvo, C.J., Ennis, S.R., Chloroquine terminates stretch-induced atrial fibrillation more effectively than flecainide in the sheep heart (2012) Circ. Arrhythmia Electrophysiol., 5, pp. 561-570
dc.relation.referencesGrandi, E., Pandit, S.V., Voigt, N., Workman, A.J., Dobrev, D., Jalife, J., Human atrial action potential and Ca2+ model: Sinus rhythm and chronic atrial fibrillation (2011) Circ. Res., 109, pp. 1055-1066
dc.relation.referencesGreenwood, J.R., Calkins, D., Sullivan, A.P., Shelley, J.C., Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution (2010) J. Computer-Aided Mol. Design, 24, pp. 591-604
dc.relation.referencesHagens, V.E., Van Veldhuisen, D.J., Kamp, O., Rienstra, M., Bosker, H.A., Veeger, N.J., Effect of rate and rhythm control on left ventricular function and cardiac dimensions in patients with persistent atrial fibrillation: Results from the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study (2005) Heart Rhythm.: Off. J. Heart Rhythm. Soc., 2, pp. 19-24
dc.relation.referencesHarris, L., Downar, E., Shaikh, N.A., Chen, T., Antiarrhythmic potential of chloroquine: New use for an old drug (1988) Can. J. Cardiol., 4, pp. 295-300
dc.relation.referencesHeidenreich, E.A., Ferrero, J.M., Doblare, M., Rodriguez, J.F., Adaptive macro finite elements for the numerical solution of monodomain equations in cardiac electrophysiology (2010) Ann. Biomed. Eng., 38, pp. 2331-2345
dc.relation.referencesHumphrey, W., Dalke, A., Schulten, K., VMD: Visual molecular dynamics (1996) J. Mol. Graphics, 14 (33-8). , 27-8
dc.relation.referencesIijima, H., Dunbar, J.B., Jr., Marshall, G.R., Calibration of effective van der Waals atomic contact radii for proteins and peptides (1987) Proteins, 2, pp. 330-339
dc.relation.referencesKalifa, J., Tanaka, K., Zaitsev, A.V., Warren, M., Vaidyanathan, R., Auerbach, D., Mechanisms of wave fractionation at boundaries of high-frequency excitation in the posterior left atrium of the isolated sheep heart during atrial fibrillation (2006) Circulation, 113, pp. 626-633
dc.relation.referencesKarunajeewa, H.A., Salman, S., Mueller, I., Baiwog, F., Gomorrai, S., Law, I., Pharmacokinetics of chloroquine and monodesethylchloroquine in pregnancy (2010) Antimicrob. Agents Chemother., 54, pp. 1186-1192
dc.relation.referencesKneller, J., Zou, R., Vigmond, E.J., Wang, Z., Leon, L.J., Nattel, S., Cholinergic atrial fibrillation in a computer model of a two-dimensional sheet of canine atrial cells with realistic ionic properties (2002) Circ. Res., 90, pp. E73-E87
dc.relation.referencesKoura, T., Hara, M., Takeuchi, S., Ota, K., Okada, Y., Miyoshi, S., Anisotropic conduction properties in canine atria analyzed by high-resolution optical mapping: Preferential direction of conduction block changes from longitudinal to transverse with increasing age (2002) Circulation, 105, pp. 2092-2098
dc.relation.referencesKumar, S., Teh, A.W., Medi, C., Kistler, P.M., Morton, J.B., Kalman, J.M., Atrial remodeling in varying clinical substrates within beating human hearts: Relevance to atrial fibrillation (2012) Prog. In Biophys. Mol. Biol., 110, pp. 278-294
dc.relation.referencesLiao, J.N., Chao, T.F., Liu, C.J., Wang, K.L., Chen, S.J., Tuan, T.C., Risk and prediction of dementia in patients with atrial fibrillation a nationwide population-based cohort study (2015) Int. J. Cardiol., 199, pp. 25-30
dc.relation.referencesMahler, J., Persson, I., A study of the hydration of the alkali metal ions in aqueous solution (2012) Inorg. Chem., 51, pp. 425-438
dc.relation.referencesMorris, G.M., Huey, R., Lindstrom, W., Sanner, M.F., Belew, R.K., Goodsell, D.S., Autodock4 and AutoDockTools4: Automated docking with selective receptor flexibility (2009) J. Comput. Chem., 30, pp. 2785-2791
dc.relation.referencesMoslehi, J., DePinho, R.A., Sahin, E., Telomeres and mitochondria in the aging heart (2012) Circ. Res., 110, pp. 1226-1237
dc.relation.referencesNarayan, S.M., Krummen, D.E., Targeting stable rotors to treat atrial fibrillation (2012) Arrhythm Electrophysiol. Rev., 1, pp. 34-38
dc.relation.referencesNarayan, S.M., Krummen, D.E., Enyeart, M.W., Rappel, W.J., Computational mapping identifies localized mechanisms for ablation of atrial fibrillation (2012) PloS One, 7
dc.relation.referencesNarayan, S.M., Krummen, D.E., Rappel, W.J., Clinical mapping approach to diagnose electrical rotors and focal impulse sources for human atrial fibrillation (2012) J. Cardiovasc. Electrophysiol., 23, pp. 447-454
dc.relation.referencesNarayan, S.M., Krummen, D.E., Shivkumar, K., Clopton, P., Rappel, W.J., Miller, J.M., Treatment of atrial fibrillation by the ablation of localized sources: CONFIRM (Conventional Ablation for Atrial Fibrillation with or without Focal Impulse and Rotor Modulation) trial (2012) J. Am. Coll. Cardiol., 60, pp. 628-636
dc.relation.referencesNarayan, S.M., Patel, J., Mulpuru, S., Krummen, D.E., Focal impulse and rotor modulation ablation of sustaining rotors abruptly terminates persistent atrial fibrillation to sinus rhythm with elimination on follow-up: A video case study (2012) Heart Rhythm.: Off. J. Heart Rhythm. Soc., 9, pp. 1436-1439
dc.relation.referencesNoujaim, S.F., Pandit, S.V., Berenfeld, O., Vikstrom, K., Cerrone, M., Mironov, S., Up-regulation of the inward rectifier K+ current (I K1) in the mouse heart accelerates and stabilizes rotors (2007) J. Physiol., 578, pp. 315-326
dc.relation.referencesNoujaim, S.F., Stuckey, J.A., Ponce-Balbuena, D., Ferrer-Villada, T., Lopez-Izquierdo, A., Pandit, S., Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets (2010) FASEB J.: Off. Publ. Fed. Am. Soc. Exp. Biol., 24, pp. 4302-4312
dc.relation.referencesNoujaim, S.F., Stuckey, J.A., Ponce-Balbuena, D., Ferrer-Villada, T., Lopez-Izquierdo, A., Pandit, S.V., Structural bases for the different anti-fibrillatory effects of chloroquine and quinidine (2011) Cardiovasc. Res., 89, pp. 862-869
dc.relation.referencesOlshansky, B., Combining ablation of atrial fibrillation with ablation of atrial flutter: Are we there yet? (2004) J. Am. Coll. Cardiol., 43, pp. 2063-2065
dc.relation.referencesPegan, S., Arrabit, C., Zhou, W., Kwiatkowski, W., Collins, A., Slesinger, P.A., Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification (2005) Nat. Neurosci., 8, pp. 279-287
dc.relation.referencesPodd, S.J., Freemantle, N., Furniss, S.S., Sulke, N., First clinical trial of specific IKACh blocker shows no reduction in atrial fibrillation burden in patients with paroxysmal atrial fibrillation: Pacemaker assessment of BMS 914392 in patients with paroxysmal atrial fibrillation (2016) Eur.: Eur. Pacing Arrhythmias Cardiac Electrophysiol.: J. Working Groups Cardiac Pacing Arrhythmias Cardiac Cell. Electrophysiol. Eur. Soc. Cardiol., 18, pp. 340-346
dc.relation.referencesPond, A.L., Scheve, B.K., Benedict, A.T., Petrecca, K., Van Wagoner, D.R., Shrier, A., Expression of distinct ERG proteins in rat, mouse, and human heart (2000) Relat. Funct. I(Kr) Channels J. Biol. Chem., 275, pp. 5997-6006
dc.relation.referencesRienstra, M., Van Veldhuisen, D.J., Hagens, V.E., Ranchor, A.V., Veeger, N.J., Crijns, H.J., Gender-related differences in rhythm control treatment in persistent atrial fibrillation: Data of the Rate Control Versus Electrical Cardioversion (RACE) study (2005) J. Am. Coll. Cardiol., 46, pp. 1298-1306
dc.relation.referencesRietbrock, S., Heeley, E., Plumb, J., Van Staa, T., Chronic atrial fibrillation: Incidence, prevalence, and prediction of stroke using the Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack (CHADS2) risk stratification scheme (2008) Am. Heart J., 156, pp. 57-64
dc.relation.referencesRiou, B., Barriot, P., Rimailho, A., Baud, F.J., Treatment of severe chloroquine poisoning (1988) New Engl. J. Med., 318, pp. 1-6
dc.relation.referencesRodriguez-Menchaca, A.A., Navarro-Polanco, R.A., Ferrer-Villada, T., Rupp, J., Sachse, F.B., Tristani-Firouzi, M., The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel (2008) Proc. Natl. Acad. Sci. U. States America, 105, pp. 1364-1368
dc.relation.referencesRyu, K., Sahadevan, J., Khrestian, C.M., Stambler, B.S., Waldo, A.L., Use of fast fourier transform analysis of atrial electrograms for rapid characterization of atrial activation-implications for delineating possible mechanisms of atrial tachyarrhythmias (2006) J. Cardiovasc. Electrophysiol., 17, pp. 198-206
dc.relation.referencesSanchez-Chapula, J.A., Salinas-Stefanon, E., Torres-Jacome, J., Benavides-Haro, D.E., Navarro-Polanco, R.A., Blockade of currents by the antimalarial drug chloroquine in feline ventricular myocytes (2001) J. Pharmacol. Exp. Ther., 297, pp. 437-445
dc.relation.referencesSanchez-Chapula, J.A., Navarro-Polanco, R.A., Culberson, C., Chen, J., Sanguinetti, M.C., Molecular determinants of voltage-dependent human ether-a-go-go related gene (HERG) K+ channel block (2002) J. Biol. Chem., 277, pp. 23587-23595
dc.relation.referencesSastry, G.M., Adzhigirey, M., Day, T., Annabhimoju, R., Sherman, W., Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments (2013) J. Computer-Aided Mol. Design, 27, pp. 221-234
dc.relation.referencesSchotten, U., Greiser, M., Benke, D., Buerkel, K., Ehrenteidt, B., Stellbrink, C., Atrial fibrillation-induced atrial contractile dysfunction: A tachycardiomyopathy of a different sort (2002) Cardiovasc. Res., 53, pp. 192-201
dc.relation.referencesShelley, J.C., Cholleti, A., Frye, L.L., Greenwood, J.R., Timlin, M.R., Uchimaya, M., EPIK: A software program for pK(a) prediction and protonation state generation for drug-like molecules (2007) J. Computer-Aided Mol. Design, 21, pp. 681-691
dc.relation.referencesShivakumar, D., Williams, J., Wu, Y., Damm, W., Shelley, J., Sherman, W., Prediction of Absolute Solvation Free Energies using Molecular Dynamics Free Energy Perturbation and the OPLS Force Field (2010) J. Chem. Theory Comput., 6, pp. 1509-1519
dc.relation.referencesShukla, A., Curtis, A.B., Avoiding permanent atrial fibrillation: Treatment approaches to prevent disease progression (2014) Vasc. Health Risk Manage., 10, pp. 1-12
dc.relation.referencesSingh-Manoux, A., Fayosse, A., Sabia, S., Canonico, M., Bobak, M., Elbaz, A., Atrial fibrillation as a risk factor for cognitive decline and dementia (2017) Eur. Heart J., 38, pp. 2612-2618
dc.relation.referencesSkibsbye, L., Jespersen, T., Christ, T., Maleckar, M.M., Van Den Brink, J., Tavi, P., Refractoriness in human atria: Time and voltage dependence of sodium channel availability (2016) J. Mol. Cell. Cardiol., 101, pp. 26-34
dc.relation.referencesStas, P., Faes, D., Noyens, P., Conduction disorder and QT prolongation secondary to long-term treatment with chloroquine (2008) Int. J. Cardiol., 127, pp. e80-e82
dc.relation.referencesTakemoto, Y., Slough, D.P., Meinke, G., Katnik, C., Graziano, Z.A., Chidipi, B., Structural basis for the antiarrhythmic blockade of a potassium channel with a small molecule (2018) FASEB J.: Off. Publ. Fed. Am. Soc. Exp. Biol., 32, pp. 1778-1793
dc.relation.referencesTeixeira, R.A., Borba, E.F., Pedrosa, A., Nishioka, S., Viana, V.S., Ramires, J.A., Evidence for cardiac safety and antiarrhythmic potential of chloroquine in systemic lupus erythematosus (2014) Eur.: Eur. Pacing Arrhythmias Cardiac Electrophysiol.: J. Working Groups Cardiac Pacing Arrhythmias Cardiac Cell. Electrophysiol. Eur. Soc. Cardiol., 16, pp. 887-892
dc.relation.referencesTobon, C., Ruiz-Villa, C.A., Heidenreich, E., Romero, L., Hornero, F., Saiz, J., A three-dimensional human atrial model with fiber orientation. Electrograms arrhythmic activation patterns relat (2013) PloS One, 8
dc.relation.referencesTraebert, M., Dumotier, B., Meister, L., Hoffmann, P., Dominguez-Estevez, M., Suter, W., Inhibition of hERG K+ currents by antimalarial drugs in stably transfected HEK293 cells (2004) Eur. J. Pharmacol., 484, pp. 41-48
dc.relation.referencesVan Wagoner, D.R., Electrophysiological remodeling in human atrial fibrillation (2003) Pacing Clin. Electrophysiol.: PACE, 26, pp. 1572-1575
dc.relation.referencesVest, J.A., Wehrens, X.H., Reiken, S.R., Lehnart, S.E., Dobrev, D., Chandra, P., Defective cardiac ryanodine receptor regulation during atrial fibrillation (2005) Circulation, 111, pp. 2025-2032
dc.relation.referencesVoigt, N., Friedrich, A., Bock, M., Wettwer, E., Christ, T., Knaut, M., Differential phosphorylation-dependent regulation of constitutively active and muscarinic receptor-activated IK,ACh channels in patients with chronic atrial fibrillation (2007) Cardiovasc. Res., 74, pp. 426-437
dc.relation.referencesVoigt, N., Trausch, A., Knaut, M., Matschke, K., Varro, A., Van Wagoner, D.R., Left-to-right atrial inward rectifier potassium current gradients in patients with paroxysmal versus chronic atrial fibrillation (2010) Circ. Arrhythmia Electrophysiol., 3, pp. 472-480
dc.relation.referencesVolkova, M., Garg, R., Dick, S., Boheler, K.R., Aging-associated changes in cardiac gene expression (2005) Cardiovasc. Res., 66, pp. 194-204
dc.relation.referencesWalfridsson, H., Anfinsen, O.G., Berggren, A., Frison, L., Jensen, S., Linhardt, G., Is the acetylcholine-regulated inwardly rectifying potassium current a viable antiarrhythmic target? Translational discrepancies of AZD2927 and A7071 in dogs and humans (2015) Eur.: Eur. Pacing Arrhythmias Cardiac Electrophysiol.: J. Working Groups Cardiac Pacing Arrhythmias Cardiac Cell. Electrophysiol. Eur. Soc. Cardiol., 17, pp. 473-482
dc.relation.referencesWhite, N.J., Cardiotoxicity of antimalarial drugs (2007) Lancet Infect. Dis., 7, pp. 549-558
dc.relation.referencesWishart, D.S., Knox, C., Guo, A.C., Cheng, D., Shrivastava, S., Tzur, D., Drugbank: A knowledgebase for drugs, drug actions and drug targets (2008) Nucleic Acids Res, 36, pp. D901-D906
dc.relation.referencesWolf, P.A., Abbott, R.D., Kannel, W.B., Atrial fibrillation as an independent risk factor for stroke: The Framingham Study (1991) Stroke
dc.relation.referencesJ. Cereb. Circ., 22, pp. 983-988
dc.relation.referencesWorkman, A.J., Kane, K.A., Rankin, A.C., The contribution of ionic currents to changes in refractoriness of human atrial myocytes associated with chronic atrial fibrillation (2001) Cardiovasc. Res., 52, pp. 226-235
dc.relation.referencesWozniacka, A., Cygankiewicz, I., Chudzik, M., Sysa-Jedrzejowska, A., Wranicz, J.K., The cardiac safety of chloroquine phosphate treatment in patients with systemic lupus erythematosus: The influence on arrhythmia, heart rate variability and repolarization parameters (2006) Lupus, 15, pp. 521-525
dc.relation.referencesZimetbaum, P., Antiarrhythmic drug therapy for atrial fibrillation (2012) Circulation, 125, pp. 381-389
dc.relation.referencesZlochiver, S., Yamazaki, M., Kalifa, J., Berenfeld, O., Rotor meandering contributes to irregularity in electrograms during atrial fibrillation (2008) Heart Rhythm.: Off. J. Heart Rhythm. Soc., 5, pp. 846-854

Files in this item


There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record