(Circulation. 1998;98:2404-2414.)
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports |
Mechanisms Underlying Spontaneous and Induced Ventricular Arrhythmias in Patients With Idiopathic Dilated Cardiomyopathy
From the Cardiovascular Division, Washington University School of Medicine St. Louis, Mo.
Correspondence to Steven M. Pogwizd, MD, Section of Cardiology, University of Illinois at Chicago, 840 S Wood St M/C 787, Chicago, IL 60612.
Background—To define the electrophysiological mechanism(s) of inducible and spontaneously occurring ventricular arrhythmias associated with nonischemic cardiomyopathy, 3-dimensional intraoperative mapping from 156 intramural sites was performed in 6 patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation.
Methods and Results—Electrode density was sufficient to determine the mechanism for 52 of 74 beats of nonsustained ventricular tachycardia (VT) induced by programmed stimulation and 9 of 11 beats of spontaneous ventricular arrhythmias. The first, second, and third extrastimuli (S2 through S4) conducted with progressively greater degrees of conduction delay (total activation times [TAs] of 144±5, 166±5, and 194±5 ms, respectively) owing to slow conduction and on occasion intramural block. The first beats of induced VT arose from subendocardial or subepicardial sites distant from areas of marked conduction delay by a focal mechanism on the basis of the absence of intervening electrical activity between the termination of the last extrastimulus and the initiation of VT (123±31 ms). Subsequent beats arose by a focal mechanism and conducted with a TA of 127±6 ms (P=NS versus initiating beats of VT [118±9 ms]). Spontaneous ventricular arrhythmias initiated in the subendocardium by a focal mechanism and conducted with a TA of 138±5 ms. Tissue analysis demonstrated a variable degree of interstitial fibrosis at sites of focal activation. Sites of conduction delay or block typically exhibited marked interstitial and/or replacement fibrosis but were spatially distant from sites initiating VT.
Conclusions—Spontaneous and induced ventricular arrhythmias in patients with end-stage idiopathic cardiomyopathy can arise in the subendocardium or subepicardium by a focal mechanism.
Key Words: tachycardia • heart failure • mapping
This article has been cited by other articles:
 |
|
 |
|
  W. Chen, J. A. Wasserstrom, and Y. Shiferaw Role of coupled gating between cardiac ryanodine receptors in the genesis of triggered arrhythmias Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H171 - H180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Stewart, O. V. Aslanidi, D. Noble, P. J. Noble, M. R. Boyett, and H. Zhang Mathematical models of the electrical action potential of Purkinje fibre cells Phil Trans R Soc A, June 13, 2009; 367(1896): 2225 - 2255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Miura, Y. Wakayama, H. Endoh, M. Nakano, Y. Sugai, M. Hirose, H. E.D.J. ter Keurs, and H. Shimokawa Spatial non-uniformity of excitation-contraction coupling can enhance arrhythmogenic-delayed afterdepolarizations in rat cardiac muscle Cardiovasc Res, October 1, 2008; 80(1): 55 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Rudy, M. J. Ackerman, D. M. Bers, C. E. Clancy, S. R. Houser, B. London, A. D. McCulloch, D. A. Przywara, R. L. Rasmusson, R. J. Solaro, et al. Systems Approach to Understanding Electromechanical Activity in the Human Heart: A National Heart, Lung, and Blood Institute Workshop Summary Circulation, September 9, 2008; 118(11): 1202 - 1211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. C. Wu, R. G. Weiss, D. R. Thiemann, K. Kitagawa, A. Schmidt, D. Dalal, S. Lai, D. A. Bluemke, G. Gerstenblith, E. Marban, et al. Late gadolinium enhancement by cardiovascular magnetic resonance heralds an adverse prognosis in nonischemic cardiomyopathy. J. Am. Coll. Cardiol., June 24, 2008; 51(25): 2414 - 2421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. DeSantiago, X. Ai, M. Islam, G. Acuna, M. T. Ziolo, D. M. Bers, and S. M. Pogwizd Arrhythmogenic Effects of {beta}2-Adrenergic Stimulation in the Failing Heart Are Attributable to Enhanced Sarcoplasmic Reticulum Ca Load Circ. Res., June 6, 2008; 102(11): 1389 - 1397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Den Ruijter, G. Berecki, A. O. Verkerk, D. Bakker, A. Baartscheer, C. A. Schumacher, C. N.W. Belterman, N. de Jonge, J. W.T. Fiolet, I. A. Brouwer, et al. Acute Administration of Fish Oil Inhibits Triggered Activity in Isolated Myocytes From Rabbits and Patients With Heart Failure Circulation, January 29, 2008; 117(4): 536 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Masse, E. Downar, V. Chauhan, E. Sevaptsidis, and K. Nanthakumar Ventricular fibrillation in myopathic human hearts: mechanistic insights from in vivo global endocardial and epicardial mapping Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2589 - H2597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Katra, T. Oya, G. S. Hoeker, and K. R. Laurita Ryanodine receptor dysfunction and triggered activity in the heart Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2144 - H2151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Anderson Multiple downstream proarrhythmic targets for calmodulin kinase II: Moving beyond an ion channel-centric focus Cardiovasc Res, March 1, 2007; 73(4): 657 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Bers Altered Cardiac Myocyte Ca Regulation In Heart Failure. Physiology, December 1, 2006; 21(6): 380 - 387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Stempien-Otero, A. Plawman, J. Meznarich, T. Dyamenahalli, G. Otsuka, and D. A. Dichek Mechanisms of Cardiac Fibrosis Induced by Urokinase Plasminogen Activator J. Biol. Chem., June 2, 2006; 281(22): 15345 - 15351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pott and J. I. Goldhaber Is the Ryanodine Receptor a Target for Antiarrhythmic Therapy? Circ. Res., May 26, 2006; 98(10): 1232 - 1233. [Full Text] [PDF]
|
|
|
|
|
|
J. P. Daubert, W. Zareba, W. J. Hall, C. Schuger, A. Corsello, A. R. Leon, M. L. Andrews, S. McNitt, D. T. Huang, A. J. Moss, et al. Predictive Value of Ventricular Arrhythmia Inducibility for Subsequent Ventricular Tachycardia or Ventricular Fibrillation in Multicenter Automatic Defibrillator Implantation Trial (MADIT) II Patients J. Am. Coll. Cardiol., January 3, 2006; 47(1): 98 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhang, I. Ramachandra, Z. Liu, B. Muneer, S. M. Pogwizd, and B. He Noninvasive three-dimensional electrocardiographic imaging of ventricular activation sequence Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2724 - H2732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Xiong, Y. Tian, D. DiSilvestre, and G. F. Tomaselli Transmural Heterogeneity of Na+-Ca2+ Exchange: Evidence for Differential Expression in Normal and Failing Hearts Circ. Res., August 5, 2005; 97(3): 207 - 209. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Abraham, C. A. Henrikson, L. Tung, M. G. Chang, M. Aon, T. Xue, R. A. Li, B. O' Rourke, and E. Marban Antiarrhythmic Engineering of Skeletal Myoblasts for Cardiac Transplantation Circ. Res., July 22, 2005; 97(2): 159 - 167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Katra and K. R. Laurita Cellular Mechanism of Calcium-Mediated Triggered Activity in the Heart Circ. Res., March 18, 2005; 96(5): 535 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M T Kearney, K A A Fox, A J Lee, W P Brooksby, A M Shah, A Flapan, R J Prescott, R Andrews, P D Batin, D L Eckberg, et al. Predicting sudden death in patients with mild to moderate chronic heart failure Heart, October 1, 2004; 90(10): 1137 - 1143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Moriwaki, A. Stempien-Otero, M. Kremen, A. E. Cozen, and D. A. Dichek Overexpression of Urokinase by Macrophages or Deficiency of Plasminogen Activator Inhibitor Type 1 Causes Cardiac Fibrosis in Mice Circ. Res., September 17, 2004; 95(6): 637 - 644. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J Janse Electrophysiological changes in heart failure and their relationship to arrhythmogenesis Cardiovasc Res, February 1, 2004; 61(2): 208 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Hsia, D. J. Callans, and F. E. Marchlinski Characterization of Endocardial Electrophysiological Substrate in Patients With Nonischemic Cardiomyopathy and Monomorphic Ventricular Tachycardia Circulation, August 12, 2003; 108(6): 704 - 710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Saumarez, L. Chojnowska, R. Derksen, M. Pytkowski, M. Sterlinski, C. L.-H. Huang, N. Sadoul, R. N.W. Hauer, W. Ruzyllo, and A. A. Grace Sudden Death in Noncoronary Heart Disease Is Associated With Delayed Paced Ventricular Activation Circulation, May 27, 2003; 107(20): 2595 - 2600. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M Scoote, P A Poole-Wilson, and A J Williams The therapeutic potential of new insights into myocardial excitation-contraction coupling Heart, April 1, 2003; 89(4): 371 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Ciaccio Premature excitation and onset of reentrant ventricular tachycardia Am J Physiol Heart Circ Physiol, October 1, 2002; 283(4): H1703 - H1712. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wu, J. Temple, R. Zhang, I. Dzhura, W. Zhang, R. Trimble, D. M. Roden, R. Passier, E. N. Olson, R. J. Colbran, et al. Calmodulin Kinase II and Arrhythmias in a Mouse Model of Cardiac Hypertrophy Circulation, September 3, 2002; 106(10): 1288 - 1293. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kadish Primary prevention ofsudden death using ICD therapy: incremental steps J. Am. Coll. Cardiol., March 6, 2002; 39(5): 788 - 789. [Full Text] [PDF]
|
|
|
|
|
|
D. M. Bers Calcium and Cardiac Rhythms: Physiological and Pathophysiological Circ. Res., January 11, 2002; 90(1): 14 - 17. [Full Text] [PDF]
|
|
|
|
 |
|
 X.H.T. WEHRENS and A.R. MARKS Myocardial Disease in Failing Hearts: Defective Excitation-Contraction Coupling Cold Spring Harb Symp Quant Biol, January 1, 2002; 67(0): 533 - 542. [Abstract] [PDF]
|
|
|
|
|
|
A. O. Verkerk, M. W. Veldkamp, A. Baartscheer, C. A. Schumacher, C. Klopping, A. C.G. van Ginneken, and J. H. Ravesloot Ionic Mechanism of Delayed Afterdepolarizations in Ventricular Cells Isolated From Human End-Stage Failing Hearts Circulation, November 27, 2001; 104(22): 2728 - 2733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Roberts and U. Sigwart New Concepts in Hypertrophic Cardiomyopathies, Part II Circulation, October 30, 2001; 104(18): 2249 - 2252. [Full Text] [PDF]
|
|
|
|
 |
|
 X. Jouven and P. Ducimetiere Exercise testing: do frequent premature ventricular depolarizations represent a new criterion of positivity? Eur. Heart J., October 1, 2001; 22(19): 1759 - 1761. [PDF]
|
|
|
|
 |
|
 S. Capomolla, O. Febo, C. Opasich, G. Guazzotti, A. Caporotondi, M. T. La Rovere, M. Gnemmi, A. Mortara, M. Vona, G. D. Pinna, et al. Chronic infusion of dobutamine and nitroprusside in patients with end-stage heart failure awaiting heart transplantation: safety and clinical outcome Eur J Heart Fail, October 1, 2001; 3(5): 601 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Adachi-Akahane and Y. Kurachi New Era for Translational Research in Cardiac Arrhythmias Circ. Res., June 8, 2001; 88(11): 1095 - 1096. [Full Text] [PDF]
|
|
|
|
|
|
S. M. Pogwizd Increased Na+-Ca2+ Exchanger in the Failing Heart Circ. Res., October 13, 2000; 87(8): 641 - 643. [Full Text] [PDF]
|
|
|
|
 |
|
 X. Jouven, M. Zureik, M. Desnos, D. Courbon, and P. Ducimetiere Long-Term Outcome in Asymptomatic Men with Exercise-Induced Premature Ventricular Depolarizations N. Engl. J. Med., September 21, 2000; 343(12): 826 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhuang, K. A. Yamada, J. E. Saffitz, and A. G. Kleber Pulsatile Stretch Remodels Cell-to-Cell Communication in Cultured Myocytes Circ. Res., August 18, 2000; 87(4): 316 - 322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Becker and W. Schoels Re: 'Ventricular arrhythmias induced by endothelin-1 or by acute ischemia: a comparative analysis using three-dimensional mapping' (Cardiovasc Res 2000;45:310-320) Cardiovasc Res, June 1, 2000; 46(3): 606 - 607. [Full Text] [PDF]
|
|
|
|
|
|
P. C. Viswanathan and Y. Rudy Cellular Arrhythmogenic Effects of Congenital and Acquired Long-QT Syndrome in the Heterogeneous Myocardium Circulation, March 14, 2000; 101(10): 1192 - 1198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. I. Goldhaber Sodium-Calcium Exchange : The Phantom Menace Circ. Res., November 26, 1999; 85(11): 982 - 984. [Full Text] [PDF]
|
|
|
|
|
|
S. M. Pogwizd, M. Qi, W. Yuan, A. M. Samarel, and D. M. Bers Upregulation of Na+/Ca2+ Exchanger Expression and Function in an Arrhythmogenic Rabbit Model of Heart Failure Circ. Res., November 26, 1999; 85(11): 1009 - 1019. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Pogwizd, K. Schlotthauer, L. Li, W. Yuan, and D. M. Bers Arrhythmogenesis and Contractile Dysfunction in Heart Failure : Roles of Sodium-Calcium Exchange, Inward Rectifier Potassium Current, and Residual {beta}-Adrenergic Responsiveness Circ. Res., June 8, 2001; 88(11): 1159 - 1167. [Abstract] [Full Text] [PDF]
|
|