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Pathogenesis of ventricular tachycardia and ventricular fibrillation during acute myocardial infarction

Philip J Podrid, MD, FACC
Leonard I Ganz, MD, FHRS, FACC
Section Editor
Bradley P Knight, MD, FACC
Deputy Editor
Brian C Downey, MD, FACC


Life-threatening ventricular arrhythmias — ventricular tachycardia (VT) and ventricular fibrillation (VF) — are infrequent but serious complications of an acute ST-elevation myocardial infarction (MI). The largest experience on the incidence of VT and VF during an acute ST elevation MI comes from the GUSTO-1 trial of 40,895 patients who were treated with thrombolytic therapy [1]. The overall incidence of sustained VT or VF was 10.2 percent: 3.5 percent developed VT, 4.1 percent VF, and 2.7 percent both VT and VF. Approximately 80 to 85 percent of these arrhythmias occurred in the first 48 hours.

Sustained ventricular arrhythmias are less common in patients with an acute non-ST elevation MI or unstable angina, as illustrated in a pooled analysis of four major trials of over 25,000 such patients [2]. The overall incidence of VT or VF was 2.1 percent, lower than the 10.2 percent incidence in GUSTO-1 in STEMI [3]. VT occurred in 0.8 percent, VF in 1 percent, and VT and VF in 0.3 percent. The median time to arrhythmia was 78 hours.

Sustained VT and VF in the setting of myocardial infarction result from the complex interaction of multiple factors, including myocardial ischemia (with resulting local electrolyte abnormalities), necrosis, reperfusion, healing, and scar formation. In addition, there are autonomic changes resulting from the infarction that have an important impact. These events produce the mechanisms that initiate arrhythmias and the substrate for arrhythmia perpetuation. Arrhythmia pathogenesis varies at different stages in this process. For ventricular arrhythmias occurring more than 48 to 72 hours after an acute myocardial infarction (MI), scar formation is of primary importance.

Ventricular arrhythmias during acute MI are typically classified based upon their time of onset. This scheme is useful clinically because VT and VF occurring early (≤24 to 48 hours) have been thought to be epiphenomena of the MI and do not require long-term therapy because they are not associated with a worse prognosis after hospital discharge. In contrast, VT or VF occurring later is generally thought to reflect the development of arrhythmic substrate, and require chronic therapy because of an increased risk of sudden cardiac death. (See "Clinical features and treatment of ventricular arrhythmias during acute myocardial infarction".)

This topic will review the mechanisms of arrhythmogenesis during acute MI, with particular attention to serious ventricular arrhythmias occurring in the first 48 to 72 hours. The clinical features and management of these arrhythmias are discussed separately. (See "Clinical features and treatment of ventricular arrhythmias during acute myocardial infarction".)


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Literature review current through: Dec 2014. | This topic last updated: May 1, 2014.
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  1. Newby KH, Thompson T, Stebbins A, et al. Sustained ventricular arrhythmias in patients receiving thrombolytic therapy: incidence and outcomes. The GUSTO Investigators. Circulation 1998; 98:2567.
  2. Al-Khatib SM, Granger CB, Huang Y, et al. Sustained ventricular arrhythmias among patients with acute coronary syndromes with no ST-segment elevation: incidence, predictors, and outcomes. Circulation 2002; 106:309.
  3. Sobel BE, Corr PB, Robison AK, et al. Accumulation of lysophosphoglycerides with arrhythmogenic properties in ischemic myocardium. J Clin Invest 1978; 62:546.
  4. Hansen DE, Craig CS, Hondeghem LM. Stretch-induced arrhythmias in the isolated canine ventricle. Evidence for the importance of mechanoelectrical feedback. Circulation 1990; 81:1094.
  5. Popović AD, Nesković AN, Pavlovski K, et al. Association of ventricular arrhythmias with left ventricular remodelling after myocardial infarction. Heart 1997; 77:423.
  6. Tansey MJ, Opie LH. Relation between plasma free fatty acids and arrhythmias within the first twelve hours of acute myocardial infarction. Lancet 1983; 2:419.
  7. Janse MJ, Wit AL. Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. Physiol Rev 1989; 69:1049.
  8. Yunus A, Gillis AM, Duff HJ, et al. Increased precordial QTc dispersion predicts ventricular fibrillation during acute myocardial infarction. Am J Cardiol 1996; 78:706.
  9. Endoh Y, Kasanuki H, Ohnishi S, et al. Influence of early coronary reperfusion on QT interval dispersion after acute myocardial infarction. Pacing Clin Electrophysiol 1997; 20:1646.
  10. Downar E, Janse MJ, Durrer D. The effect of acute coronary artery occlusion on subepicardial transmembrane potentials in the intact porcine heart. Circulation 1977; 56:217.
  11. Guarnieri T, Strauss HC. Intracellular potassium activity in guinea pig papillary muscle during prolonged hypoxia. J Clin Invest 1982; 69:435.
  12. Kléber AG. Resting membrane potential, extracellular potassium activity, and intracellular sodium activity during acute global ischemia in isolated perfused guinea pig hearts. Circ Res 1983; 52:442.
  13. Hill JL, Gettes LS. Effect of acute coronary artery occlusion on local myocardial extracellular K+ activity in swine. Circulation 1980; 61:768.
  14. Hirche H, Franz C, Bös L, et al. Myocardial extracellular K+ and H+ increase and noradrenaline release as possible cause of early arrhythmias following acute coronary artery occlusion in pigs. J Mol Cell Cardiol 1980; 12:579.
  15. Rau EE, Shine KI, Langer GA. Potassium exchange and mechanical performance in anoxic mammalian myocardium. Am J Physiol 1977; 232:H85.
  16. Arnsdorf MF, Sawicki GJ. The effects of lysophosphatidylcholine, a toxic metabolite of ischemia, on the components of cardiac excitability in sheep Purkinje fibers. Circ Res 1981; 49:16.
  17. Clarkson CW, Ten Eick RE. On the mechanism of lysophosphatidylcholine-induced depolarization of cat ventricular myocardium. Circ Res 1983; 52:543.
  18. Corr PB, Cain ME, Witkowski FX, et al. Potential arrhythmogenic electrophysiological derangements in canine Purkinje fibers induced by lysophosphoglycerides. Circ Res 1979; 44:822.
  19. Basset AL, Gelband H, Nilsson K, et al. Electrophysiology following healed experimental myocardial infarction. In: Reentrant Arrhythmias: Mechanisms and Treatment, Kulbertus HE (Ed), MTP Press, Lancaster, England 1979. p.242.
  20. Corr PB, Yamada KA, Creer MH, et al. Lysophosphoglycerides and ventricular fibrillation early after onset of ischemia. J Mol Cell Cardiol 1987; 19 Suppl 5:45.
  21. Katz AM. Membrane-derived lipids and the pathogenesis of ischemic myocardial damage. J Mol Cell Cardiol 1982; 14:627.
  22. Vegh A, Komori S, Szekeres L, Parratt JR. Antiarrhythmic effects of preconditioning in anaesthetised dogs and rats. Cardiovasc Res 1992; 26:487.
  23. Figueras J, Segura R, Bermejo B. Repeated 15-minute coronary occlusions in pigs increase occlusion arrhythmias but decrease reperfusion arrhythmias that are associated with extracellular hypokalemia. J Am Coll Cardiol 1996; 28:1589.
  24. Cinca J, Blanch P, Carreño A, et al. Acute ischemic ventricular arrhythmias in pigs with healed myocardial infarction: comparative effects of ischemia at a distance and ischemia at the infarct zone. Circulation 1997; 96:653.
  25. HARRIS AS. Delayed development of ventricular ectopic rhythms following experimental coronary occlusion. Circulation 1950; 1:1318.
  26. Bigger JT Jr, Dresdale FJ, Heissenbuttel RH, et al. Ventricular arrhythmias in ischemic heart disease: mechanism, prevalence, significance, and management. Prog Cardiovasc Dis 1977; 19:255.
  27. Boineau J, Cox JL. Slow ventricular. A source of re-entrant premature contraction. Circulation 1973; 48:703.
  28. El-Sherif N, Scherlag BJ, Lazzara R, Hope RR. Re-entrant ventricular arrhythmias in the late myocardial infarction period. 1. Conduction characteristics in the infarction zone. Circulation 1977; 55:686.
  29. Kaplinsky E, Ogawa S, Balke CW, Dreifus LS. Two periods of early ventricular arrhythmia in the canine acute myocardial infarction model. Circulation 1979; 60:397.
  30. Scherlag BJ, Helfant RH, Haft JI, Damato AN. Electrophysiology underlying ventricular arrhythmias due to coronary ligation. Am J Physiol 1970; 219:1665.
  31. Waldo AL, Kaiser GA. A study of ventricular arrhythmias associated with acute myocardial infarction in the canine heart. Circulation 1973; 47:1222.
  32. Hoffman BF, Rosen MR. Cellular mechanisms for cardiac arrhythmias. Circ Res 1981; 49:1.
  33. Arnar DO, Bullinga JR, Martins JB. Role of the Purkinje system in spontaneous ventricular tachycardia during acute ischemia in a canine model. Circulation 1997; 96:2421.
  34. Coronel R, Wilms-Schopman FJ, deGroot JR. Origin of ischemia-induced phase 1b ventricular arrhythmias in pig hearts. J Am Coll Cardiol 2002; 39:166.
  35. Carlsson L, Abrahamsson T, Almgren O, Svensson L. Ischaemia-induced release of noradrenaline and creatine kinase in the isolated, working rat heart. Acta Physiol Scand 1987; 130:83.
  36. Schömig A, Dart AM, Dietz R, et al. Release of endogenous catecholamines in the ischemic myocardium of the rat. Part A: Locally mediated release. Circ Res 1984; 55:689.
  37. Penny WJ. The deleterious effects of myocardial catecholamines on cellular electrophysiology and arrhythmias during ischaemia and reperfusion. Eur Heart J 1984; 5:960.
  38. Wellens HJ, Düren DR, Lie KI. Observations on mechanisms of ventricular tachycardia in man. Circulation 1976; 54:237.
  39. Campbell RW, Murray A, Julian DG. Ventricular arrhythmias in first 12 hours of acute myocardial infarction. Natural history study. Br Heart J 1981; 46:351.
  40. Northover BJ. Ventricular tachycardia during the first 72 hours after acute myocardial infarction. Cardiology 1982; 69:149.
  41. Sugi K, Karagueuzian HS, Fishbein MC, et al. Spontaneous ventricular tachycardia associated with isolated right ventricular infarction, one day after right coronary artery occlusion in the dog: studies on the site of origin and mechanism. Am Heart J 1985; 109:232.
  42. Peters NS, Coromilas J, Severs NJ, Wit 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. Circulation 1997; 95:988.
  43. Marchlinski FE, Buxton AE, Waxman HL, Josephson ME. Identifying patients at risk of sudden death after myocardial infarction: value of the response to programmed stimulation, degree of ventricular ectopic activity and severity of left ventricular dysfunction. Am J Cardiol 1983; 52:1190.
  44. DiMarco JP, Lerman BB, Kron IL, Sellers TD. Sustained ventricular tachyarrhythmias within 2 months of acute myocardial infarction: results of medical and surgical therapy in patients resuscitated from the initial episode. J Am Coll Cardiol 1985; 6:759.
  45. Stambler BS, Akosah KO, Mohanty PK, et al. Myocardial ischemia and induction of sustained ventricular tachyarrhythmias: evaluation using dobutamine stress echocardiography-electrophysiologic testing. J Cardiovasc Electrophysiol 2004; 15:901.
  46. Shusterman V, Aysin B, Gottipaty V, et al. Autonomic nervous system activity and the spontaneous initiation of ventricular tachycardia. ESVEM Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring Trial. J Am Coll Cardiol 1998; 32:1891.
  47. Saeed M, Link MS, Mahapatra S, et al. Analysis of intracardiac electrograms showing monomorphic ventricular tachycardia in patients with implantable cardioverter-defibrillators. Am J Cardiol 2000; 85:580.
  48. Marrouche NF, Verma A, Wazni O, et al. Mode of initiation and ablation of ventricular fibrillation storms in patients with ischemic cardiomyopathy. J Am Coll Cardiol 2004; 43:1715.
  49. Marchlinski FE, Waxman HL, Buxton AE, Josephson ME. Sustained ventricular tachyarrhythmias during the early postinfarction period: electrophysiologic findings and prognosis for survival. J Am Coll Cardiol 1983; 2:240.
  50. Brugada J, Aguinaga L, Mont L, et al. Coronary artery revascularization in patients with sustained ventricular arrhythmias in the chronic phase of a myocardial infarction: effects on the electrophysiologic substrate and outcome. J Am Coll Cardiol 2001; 37:529.
  51. Gillis AM, Sheldon RS, Wyse DG, et al. Long-term reproducibility of ventricular tachycardia induction in patients with implantable cardioverter/defibrillators. Serial noninvasive studies. Circulation 1995; 91:2605.
  52. El-Sherif N, Smith RA, Evans K. Canine ventricular arrhythmias in the late myocardial infarction period. 8. Epicardial mapping of reentrant circuits. Circ Res 1981; 49:255.
  53. Wit AL, Allessie MA, Bonke FI, et al. Electrophysiologic mapping to determine the mechanism of experimental ventricular tachycardia initiated by premature impulses. Experimental approach and initial results demonstrating reentrant excitation. Am J Cardiol 1982; 49:166.
  54. Ursell PC, Gardner PI, Albala A, et al. Structural and electrophysiological changes in the epicardial border zone of canine myocardial infarcts during infarct healing. Circ Res 1985; 56:436.
  55. Kanaan N, Robinson N, Roth SI, et al. Ventricular tachycardia in healing canine myocardial infarction: evidence for multiple reentrant mechanisms. Pacing Clin Electrophysiol 1997; 20:245.
  56. St John Sutton M, Lee D, Rouleau JL, et al. Left ventricular remodeling and ventricular arrhythmias after myocardial infarction. Circulation 2003; 107:2577.
  57. Schwartz PJ, Stone HL, Brown AM. Effects of unilateral stellate ganglion blockade on the arrhythmias associated with coronary occlusion. Am Heart J 1976; 92:589.
  58. Schwartz PJ, Vanoli E, Stramba-Badiale M, et al. Autonomic mechanisms and sudden death. New insights from analysis of baroreceptor reflexes in conscious dogs with and without a myocardial infarction. Circulation 1988; 78:969.
  59. Boyden PA, Cranefield PF, Gadsby DC. Noradrenaline hyperpolarizes cells of the canine coronary sinus by increasing their permeability to potassium ions. J Physiol 1983; 339:185.
  60. Nademanee K, Taylor R, Bailey WE, et al. Treating electrical storm : sympathetic blockade versus advanced cardiac life support-guided therapy. Circulation 2000; 102:742.
  61. Freemantle N, Cleland J, Young P, et al. beta Blockade after myocardial infarction: systematic review and meta regression analysis. BMJ 1999; 318:1730.
  62. La Rovere MT, Specchia G, Mortara A, Schwartz PJ. Baroreflex sensitivity, clinical correlates, and cardiovascular mortality among patients with a first myocardial infarction. A prospective study. Circulation 1988; 78:816.
  63. Farrell TG, Paul V, Cripps TR, et al. Baroreflex sensitivity and electrophysiological correlates in patients after acute myocardial infarction. Circulation 1991; 83:945.
  64. Cripps TR, Malik M, Farrell TG, Camm AJ. Prognostic value of reduced heart rate variability after myocardial infarction: clinical evaluation of a new analysis method. Br Heart J 1991; 65:14.
  65. Cao JM, Fishbein MC, Han JB, et al. Relationship between regional cardiac hyperinnervation and ventricular arrhythmia. Circulation 2000; 101:1960.
  66. Iwasaki T, Suzuki T, Tateno M, et al. Dual-tracer autoradiography with thallium-201 and iodine-125-metaiodobenzylguanidine in experimental myocardial infarction of rat. J Nucl Med 1996; 37:680.
  67. Nishimura T, Oka H, Sago M, et al. Serial assessment of denervated but viable myocardium following acute myocardial infarction in dogs using iodine-123 metaiodobenzylguanidine and thallium-201 chloride myocardial single photon emission tomography. Eur J Nucl Med 1992; 19:25.
  68. Stanton MS, Tuli MM, Radtke NL, et al. Regional sympathetic denervation after myocardial infarction in humans detected noninvasively using I-123-metaiodobenzylguanidine. J Am Coll Cardiol 1989; 14:1519.
  69. Inoue H, Zipes DP. Results of sympathetic denervation in the canine heart: supersensitivity that may be arrhythmogenic. Circulation 1987; 75:877.
  70. Herre JM, Wetstein L, Lin YL, et al. Effect of transmural versus nontransmural myocardial infarction on inducibility of ventricular arrhythmias during sympathetic stimulation in dogs. J Am Coll Cardiol 1988; 11:414.
  71. Hartikainen J, Kuikka J, Mäntysaari M, et al. Sympathetic reinnervation after acute myocardial infarction. Am J Cardiol 1996; 77:5.
  72. Goldstein JA, Butterfield MC, Ohnishi Y, et al. Arrhythmogenic influence of intracoronary thrombosis during acute myocardial ischemia. Circulation 1994; 90:139.
  73. Coronel R, Wilms-Schopman FJ, Janse MJ. Profibrillatory effects of intracoronary thrombus in acute regional ischemia of the in situ porcine heart. Circulation 1997; 96:3985.
  74. McHowat J, Corr PB. Thrombin-induced release of lysophosphatidylcholine from endothelial cells. J Biol Chem 1993; 268:15605.
  75. Gressin V, Louvard Y, Pezzano M, Lardoux H. Holter recording of ventricular arrhythmias during intravenous thrombolysis for acute myocardial infarction. Am J Cardiol 1992; 69:152.
  76. Gorgels AP, Vos MA, Letsch IS, et al. Usefulness of the accelerated idioventricular rhythm as a marker for myocardial necrosis and reperfusion during thrombolytic therapy in acute myocardial infarction. Am J Cardiol 1988; 61:231.
  77. Goldberg S, Greenspon AJ, Urban PL, et al. Reperfusion arrhythmia: a marker of restoration of antegrade flow during intracoronary thrombolysis for acute myocardial infarction. Am Heart J 1983; 105:26.
  78. Miller FC, Krucoff MW, Satler LF, et al. Ventricular arrhythmias during reperfusion. Am Heart J 1986; 112:928.
  79. Yoshida Y, Hirai M, Yamada T, et al. Antiarrhythmic efficacy of dipyridamole in treatment of reperfusion arrhythmias : evidence for cAMP-mediated triggered activity as a mechanism responsible for reperfusion arrhythmias. Circulation 2000; 101:624.
  80. Wehrens XH, Doevendans PA, Ophuis TJ, Wellens HJ. A comparison of electrocardiographic changes during reperfusion of acute myocardial infarction by thrombolysis or percutaneous transluminal coronary angioplasty. Am Heart J 2000; 139:430.
  81. Hackett D, McKenna W, Davies G, Maseri A. Reperfusion arrhythmias are rare during acute myocardial infarction and thrombolysis in man. Int J Cardiol 1990; 29:205.
  82. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet 1988; 2:349.
  83. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). Lancet 1986; 1:397.
  84. Berger PB, Ruocco NA, Ryan TJ, et al. Incidence and significance of ventricular tachycardia and fibrillation in the absence of hypotension or heart failure in acute myocardial infarction treated with recombinant tissue-type plasminogen activator: results from the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial. J Am Coll Cardiol 1993; 22:1773.
  85. Matsumura K, Jeremy RW, Schaper J, Becker LC. Progression of myocardial necrosis during reperfusion of ischemic myocardium. Circulation 1998; 97:795.
  86. Opie LH. Reperfusion injury and its pharmacologic modification. Circulation 1989; 80:1049.
  87. Opie LH, Coetzee WA. Role of calcium ions in reperfusion arrhythmias: relevance to pharmacologic intervention. Cardiovasc Drugs Ther 1988; 2:623.
  88. Lee JA, Allen DG. Changes in intracellular free calcium concentration during long exposures to simulated ischemia in isolated mammalian ventricular muscle. Circ Res 1992; 71:58.
  89. Coetzee WA, Opie LH. Effects of components of ischemia and metabolic inhibition on delayed afterdepolarizations in guinea pig papillary muscle. Circ Res 1987; 61:157.
  90. Hearse DJ, Tosaki A. Free radicals and calcium: simultaneous interacting triggers as determinants of vulnerability to reperfusion-induced arrhythmias in the rat heart. J Mol Cell Cardiol 1988; 20:213.
  91. Ambrosio G, Weisfeldt ML, Jacobus WE, Flaherty JT. Evidence for a reversible oxygen radical-mediated component of reperfusion injury: reduction by recombinant human superoxide dismutase administered at the time of reflow. Circulation 1987; 75:282.
  92. Lafont A, Marwick TH, Chisolm GM, et al. Decreased free radical scavengers with reperfusion after coronary angioplasty in patients with acute myocardial infarction. Am Heart J 1996; 131:219.
  93. Saman S, Coetzee WA, Opie LH. Inhibition by simulated ischemia or hypoxia of delayed afterdepolarizations provoked by cyclic AMP: significance for ischemic and reperfusion arrhythmias. J Mol Cell Cardiol 1988; 20:91.
  94. Harada K, Komuro I, Hayashi D, et al. Angiotensin II type 1a receptor is involved in the occurrence of reperfusion arrhythmias. Circulation 1998; 97:315.