Arrhythmia Mechanisms in the Failing Heart

Background: Heart failure (HF) claims over 200,000 lives annually in the United States alone. Approximately 50% of these deaths are sudden and unexpected, and presumably the consequence of lethal ventricular tachyarrhythmias. Electrical remodeling that occurs at the cellular and tissue network levels predisposes patients with HF to malignant arrhythmias. Our limited understanding of fundamental arrhythmia mechanisms has hampered the development of effective treatment strategies for these patients.

[1]  B. Xiao,et al.  Protein Kinase A Phosphorylation at Serine-2808 of the Cardiac Ca2+-Release Channel (Ryanodine Receptor) Does Not Dissociate 12.6-kDa FK506-Binding Protein (FKBP12.6) , 2004, Circulation research.

[2]  K. Mikoshiba,et al.  Alterations of sarcoplasmic reticulum proteins in failing human dilated cardiomyopathy. , 1995, Circulation.

[3]  W. Lederer,et al.  Modulation of cardiac ryanodine receptors of swine and rabbit by a phosphorylation‐dephosphorylation mechanism. , 1995, The Journal of physiology.

[4]  S. Ertel,et al.  Voltage-gated T-type Ca2+ channels and heart failure. , 1999, Proceedings of the Association of American Physicians.

[5]  J. Ruskin,et al.  Electrical alternans and vulnerability to ventricular arrhythmias. , 1994, The New England journal of medicine.

[6]  W. Stevenson,et al.  Arrhythmias and sudden death in heart failure. , 1997, Japanese circulation journal.

[7]  Sara Negri,et al.  Arrhythmogenesis in catecholaminergic polymorphic ventricular tachycardia: insights from a RyR2 R4496C knock-in mouse model. , 2006, Circulation research.

[8]  F. Leclercq,et al.  Ca2+ currents in compensated hypertrophy and heart failure. , 1998, Cardiovascular research.

[9]  S. Houser,et al.  Functional properties of failing human ventricular myocytes. , 2000, Trends in cardiovascular medicine.

[10]  R. Hajjar,et al.  Targeting Ca2+ cycling proteins and the action potential in heart failure by gene transfer , 2002, Basic Research in Cardiology.

[11]  V. Garsky,et al.  Biochemical and Biophysical Comparison of Native and Chemically Synthesized Phospholamban and a Monomeric Phospholamban Analog (*) , 1996, The Journal of Biological Chemistry.

[12]  W. Schmitz,et al.  Activity of cAMP-dependent protein kinase and Ca2+/calmodulin-dependent protein kinase in failing and nonfailing human hearts. , 1999, Cardiovascular research.

[13]  Donald M Bers,et al.  Calcium, calmodulin, and calcium-calmodulin kinase II: heartbeat to heartbeat and beyond. , 2002, Journal of molecular and cellular cardiology.

[14]  James Coromilas,et al.  Stabilization of cardiac ryanodine receptor prevents intracellular calcium leak and arrhythmias , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[15]  Jiqiu Chen,et al.  PRESERVATION OF MECHANICAL AND ENERGETIC FUNCTION AFTER ADENOVIRAL GENE TRANSFER IN NORMAL RAT HEARTS , 2007, Clinical and experimental pharmacology & physiology.

[16]  F. Verdonck,et al.  Altered Na/Ca exchange activity in cardiac hypertrophy and heart failure: a new target for therapy? , 2002, Cardiovascular research.

[17]  José Jalife,et al.  Arrhythmogenic Mechanisms in a Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia , 2007, Circulation research.

[18]  P. Powers,et al.  Intact &bgr;-Adrenergic Response and Unmodified Progression Toward Heart Failure in Mice With Genetic Ablation of a Major Protein Kinase A Phosphorylation Site in the Cardiac Ryanodine Receptor , 2007, Circulation research.

[19]  D. Burkhoff,et al.  Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure , 2000, Circulation.

[20]  F. Akar.  The perfect storm: defective calcium cycling in insulated fibers with reduced repolarization reserve. , 2007, Circulation research.

[21]  D. Bers,et al.  Ca2+/Calmodulin–Dependent Protein Kinase Modulates Cardiac Ryanodine Receptor Phosphorylation and Sarcoplasmic Reticulum Ca2+ Leak in Heart Failure , 2005, Circulation research.

[22]  E. Marbán,et al.  Gene Therapy to Inhibit the Calcium Channel &bgr; Subunit: Physiological Consequences and Pathophysiological Effects in Models of Cardiac Hypertrophy , 2007, Circulation research.

[23]  David D Spragg,et al.  Mechanisms Underlying Conduction Slowing and Arrhythmogenesis in Nonischemic Dilated Cardiomyopathy , 2004, Circulation research.

[24]  Nicholas S. Peters,et al.  Remodeling of Gap Junctional Channel Function in Epicardial Border Zone of Healing Canine Infarcts , 2003, Circulation research.

[25]  S. Perry,et al.  Sites on the cytoplasmic region of phospholamban involved in interaction with the calcium-activated ATPase of the sarcoplasmic reticulum. , 1999, European journal of biochemistry.

[26]  A. Feldman,et al.  Phospholamban gene ablation improves calcium transients but not cardiac function in a heart failure model. , 2004, Cardiovascular research.

[27]  N. Alpert,et al.  Alterations in sarcoplasmic reticulum gene expression in human heart failure. A possible mechanism for alterations in systolic and diastolic properties of the failing myocardium. , 1993, Circulation research.

[28]  R. Winslow,et al.  Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, II: model studies. , 1999, Circulation research.

[29]  J Jalife,et al.  A mechanism of transition from ventricular fibrillation to tachycardia : effect of calcium channel blockade on the dynamics of rotating waves. , 2000, Circulation research.

[30]  D. Kass,et al.  Dynamic changes in conduction velocity and gap junction properties during development of pacing-induced heart failure. , 2007, American journal of physiology. Heart and circulatory physiology.

[31]  Gary M Brittenham,et al.  Optical mapping reveals conduction slowing and impulse block in iron-overload cardiomyopathy. , 2003, The Journal of laboratory and clinical medicine.

[32]  Donald M. Bers,et al.  β-Adrenergic Enhancement of Sarcoplasmic Reticulum Calcium Leak in Cardiac Myocytes Is Mediated by Calcium/Calmodulin-Dependent Protein Kinase , 2007 .

[33]  David C. Warltier,et al.  Characterization of a Novel PKA Phosphorylation Site, Serine-2030, Reveals No PKA Hyperphosphorylation of the Cardiac Ryanodine Receptor in Canine Heart Failure , 2005, Circulation research.

[34]  Jeffrey S. Smith,et al.  Dissociation of Phospholamban Regulation of Cardiac Sarcoplasmic Reticulum Ca2+ATPase by Quercetin* , 1996, The Journal of Biological Chemistry.

[35]  G. Morley,et al.  Early Onset Heart Failure in Transgenic Mice with Dilated Cardiomyopathy , 2000, Pediatric Research.

[36]  S. Houser,et al.  Contribution of reverse-mode sodium-calcium exchange to contractions in failing human left ventricular myocytes. , 1998, Cardiovascular research.

[37]  C. Antzelevitch,et al.  Cellular Mechanisms Underlying the Development of Catecholaminergic Ventricular Tachycardia , 2005, Circulation.

[38]  N S Peters,et al.  Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. , 1997, Circulation.

[39]  Donald M Bers,et al.  Beta-adrenergic enhancement of sarcoplasmic reticulum calcium leak in cardiac myocytes is mediated by calcium/calmodulin-dependent protein kinase. , 2007, Circulation research.

[40]  R. Hullin,et al.  Increased availability and open probability of single L-type calcium channels from failing compared with nonfailing human ventricle. , 1998, Circulation.

[41]  Donald M. Bers,et al.  Upregulated Na/Ca exchange is involved in both contractile dysfunction and arrhythmogenesis in heart failure , 2002, Basic Research in Cardiology.

[42]  A. Kleber,et al.  Slow conduction in cardiac tissue: insights from optical mapping at the cellular level. , 2001, Journal of electrocardiology.

[43]  R. Hajjar,et al.  Overwhelming evidence of the beneficial effects of SERCA gene transfer in heart failure. , 2001, Circulation research.

[44]  Y Rudy,et al.  Electrophysiologic effects of acute myocardial ischemia. A mechanistic investigation of action potential conduction and conduction failure. , 1997, Circulation research.

[45]  D. Rosenbaum,et al.  T-wave alternans: marker, mechanism, and methodology for predicting sudden cardiac death. , 2003, Journal of electrocardiology.

[46]  Kenneth R. Laurita,et al.  Transmural Heterogeneity of Calcium Handling in Canine , 2003, Circulation research.

[47]  Steven Poelzing,et al.  Altered connexin43 expression produces arrhythmia substrate in heart failure. , 2004, American journal of physiology. Heart and circulatory physiology.

[48]  Charles Antzelevitch,et al.  Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes. , 2007, American journal of physiology. Heart and circulatory physiology.

[49]  Michael Kohlhaas,et al.  Increased Sarcoplasmic Reticulum Calcium Leak but Unaltered Contractility by Acute CaMKII Overexpression in Isolated Rabbit Cardiac Myocytes , 2006, Circulation research.

[50]  D. Bers,et al.  Ca2+/Calmodulin-Dependent Protein Kinase II Phosphorylation of Ryanodine Receptor Does Affect Calcium Sparks in Mouse Ventricular Myocytes , 2006, Circulation research.

[51]  S. Houser,et al.  T-type Ca2+ current is expressed in hypertrophied adult feline left ventricular myocytes. , 1993, Circulation research.

[52]  Y. Ohizumi,et al.  Stimulation of sarcoplasmic reticulum Ca(2+)-ATPase by gingerol analogues. , 1996, Biological & pharmaceutical bulletin.

[53]  Woo Jin Park,et al.  Restoration of mechanical and energetic function in failing aortic-banded rat hearts by gene transfer of calcium cycling proteins. , 2007, Journal of molecular and cellular cardiology.

[54]  A Mugelli,et al.  Ionic basis of action potential prolongation of hypertrophied cardiac myocytes isolated from hypertensive rats of different ages. , 1994, Cardiovascular research.

[55]  B. Albat,et al.  Calcium Currents in Diseased Human Cardiac Cells , 1995, Journal of cardiovascular pharmacology.

[56]  H. T. ter Keurs,et al.  Ser-2030, but not Ser-2808, is the major phosphorylation site in cardiac ryanodine receptors responding to protein kinase A activation upon beta-adrenergic stimulation in normal and failing hearts. , 2006, The Biochemical journal.

[57]  Joseph A. Hill,et al.  Electrical remodeling in cardiac hypertrophy. , 2003, Trends in cardiovascular medicine.

[58]  H Calkins,et al.  Beat‐to‐Beat Repolarization Lability Identifies Patients at Risk for Sudden Cardiac Death , 1998, Journal of cardiovascular electrophysiology.

[59]  W. Catterall.  Structure and regulation of voltage-gated Ca2+ channels. , 2000, Annual review of cell and developmental biology.

[60]  A J Levi,et al.  The electrophysiological characteristics of hypertrophied ventricular myocytes from the spontaneously hypertensive rat , 1993, Journal of hypertension.

[61]  G. Tomaselli,et al.  What Causes Sudden Death in Heart Failure? , 2004, Circulation research.

[62]  D. Kass,et al.  Ionic mechanism of action potential prolongation in ventricular myocytes from dogs with pacing-induced heart failure. , 1996, Circulation research.

[63]  D. Rosenbaum,et al.  Transmural Electrophysiological Heterogeneities Underlying Arrhythmogenesis in Heart Failure , 2003, Circulation research.

[64]  D. Kass,et al.  Mechanisms of altered excitation-contraction coupling in canine tachycardia-induced heart failure, I: experimental studies. , 1999, Circulation research.

[65]  Edward J Ciaccio,et al.  Heterogeneous gap junction remodeling in reentrant circuits in the epicardial border zone of the healing canine infarct. , 2006, Cardiovascular research.

[66]  D. Burkhoff,et al.  PKA Phosphorylation Dissociates FKBP12.6 from the Calcium Release Channel (Ryanodine Receptor) Defective Regulation in Failing Hearts , 2000, Cell.

[67]  B. O’Rourke,et al.  Partial Inhibition of Sodium/Calcium Exchange Restores Cellular Calcium Handling in Canine Heart Failure , 2004, Circulation research.

[68]  I. Cohen,et al.  Calcium channel heterogeneity in canine left ventricular myocytes , 2003, The Journal of physiology.

[69]  T Liu,et al.  Ventricular hypertrophy amplifies transmural repolarization dispersion and induces early afterdepolarization. , 2001, American journal of physiology. Heart and circulatory physiology.

[70]  J. Pu,et al.  Alterations of Na+ currents in myocytes from epicardial border zone of the infarcted heart. A possible ionic mechanism for reduced excitability and postrepolarization refractoriness. , 1997, Circulation research.

[71]  A. Marks.  Novel therapy for heart failure and exercise-induced ventricular tachycardia based on 'fixing' the leak in ryanodine receptors. , 2006, Novartis Foundation symposium.

[72]  G. Hasenfuss,et al.  Calcium handling proteins in the failing human heart , 2004, Basic Research in Cardiology.

[73]  S. Bryant,et al.  Membrane current changes in left ventricular myocytes isolated from guinea pigs after abdominal aortic coarctation. , 1993, Cardiovascular research.

[74]  Mark E Anderson,et al.  Multiple downstream proarrhythmic targets for calmodulin kinase II: moving beyond an ion channel-centric focus. , 2007, Cardiovascular research.

[75]  K. R. SIPIDO,et al.  A Critical Role for L‐type Ca2+ Current in the Regulation of Ca2+ Release from the Sarcoplasmic Reticulum in Human Ventricular Myocytes from Dilated Cardiomyopathy , 1998, Annals of the New York Academy of Sciences.

[76]  H. Calkins,et al.  Beat-to-beat QT interval variability: novel evidence for repolarization lability in ischemic and nonischemic dilated cardiomyopathy. , 1997, Circulation.

[77]  D. H. Will,et al.  Hemodynamics in Normal Cattle , 1962, Circulation research.