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Annual Review of Physiology

Volume 87, 2025

Mechanisms and Implications of Electrical Heterogeneity in Cardiac Function in Ischemic Heart Disease

Abstract

A healthy heart shows intrinsic electrical heterogeneities that play a significant role in cardiac activation and repolarization. However, cardiac diseases may perturb the baseline electrical properties of the healthy cardiac tissue, leading to increased arrhythmic risk and compromised cardiac functions. Moreover, biological variability among patients produces a wide range of clinical symptoms, which complicates the treatment and diagnosis of cardiac diseases. Ischemic heart disease is usually caused by a partial or complete blockage of a coronary artery. The onset of the disease begins with myocardial ischemia, which can develop into myocardial infarction if it persists for an extended period. The progressive regional tissue remodeling leads to increased electrical heterogeneities, with adverse consequences on arrhythmic risk, cardiac mechanics, and mortality. This review aims to summarize the key role of electrical heterogeneities in the heart on cardiac function and diseases. Ischemic heart disease has been chosen as an example to show how adverse electrical remodeling at different stages may lead to variable manifestations in patients. For this, we have reviewed the dynamic electrophysiological and structural remodeling from the onset of acute myocardial ischemia and reperfusion to acute and chronic stages post–myocardial infarction. The arrhythmic mechanisms, patient phenotypes, risk stratification at different stages, and patient management strategies are also discussed. Finally, we provide a brief review on how computational approaches incorporate human electrophysiological heterogeneity to facilitate basic and translational research.

Keyword(s): acute myocardial ischemia, arrhythmia, electrocardiogram, myocardial infarction, pathophysiological mechanisms, remodeling
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/content/journals/10.1146/annurev-physiol-042022-020541
2025-02-10
2025-06-19
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Literature Cited

  1. 1.
    Boukens BJ, Sulkin MS, Gloschat CR, Ng FS, Vigmond EJ, Efimov IR. 2015.. Transmural APD gradient synchronizes repolarization in the human left ventricular wall. . Cardiovasc. Res. 108:(1):188–96
     [Crossref] [Google Scholar]
  2. 2.
    Glukhov AV, Fedorov VV, Lou Q, Ravikumar VK, Kalish PW, et al. 2010.. Transmural dispersion of repolarization in failing and nonfailing human ventricle. . Circ. Res. 106:(5):981–91
     [Crossref] [Google Scholar]
  3. 3.
    Khan MA, Hashim MJ, Mustafa H, Baniyas MY, Al Suwaidi SKBM, et al. 2020.. Global epidemiology of ischemic heart disease: results from the Global Burden of Disease Study. . Cureus 12:(7):e9349
     [Google Scholar]
  4. 4.
    Carmeliet E. 1999.. Cardiac ionic currents and acute ischemia: from channels to arrhythmias. . Physiol. Rev. 79:(3):917–1017
     [Crossref] [Google Scholar]
  5. 5.
    Penny WJ, Sheridan DJ. 1983.. Arrhythmias and cellular electrophysiological changes during myocardial “ischaemia” and reperfusion. . Cardiovasc. Res. 17:(6):363–72
     [Crossref] [Google Scholar]
  6. 6.
    Richardson W, Clarke S, Quinn T, Holmes J. 2015.. Physiological implications of myocardial scar structure. . Compr. Physiol. 5:(4):1877–909
     [Crossref] [Google Scholar]
  7. 7.
    Bartos DC, Grandi E, Ripplinger CM. 2015.. Ion channels in the heart. . Compr. Physiol. 5:(3):1423–64
     [Crossref] [Google Scholar]
  8. 8.
    Amos GJ, Wettwer E, Metzger F, Li Q, Himmel HM, Ravens U. 1996.. Differences between outward currents of human atrial and subepicardial ventricular myocytes. . J. Physiol. 491:(Part 1):31–50
     [Crossref] [Google Scholar]
  9. 9.
    Hennis K, Rötzer RD, Piantoni C, Biel M, Wahl-Schott C, Fenske S. 2021.. Speeding up the heart? Traditional and new perspectives on HCN4 function. . Front. Physiol. 12::669029
     [Crossref] [Google Scholar]
  10. 10.
    Li N, Csepe TA, Hansen BJ, Dobrzynski H, Higgins RSD, et al. 2015.. Molecular mapping of sinoatrial node HCN channel expression in the human heart. . Circ. Arrhythmia Electrophysiol. 8:(5):1219–27
     [Crossref] [Google Scholar]
  11. 11.
    Ideker RE, Kong W, Pogwizd S. 2009.. Purkinje fibers and arrhythmias. . Pacing Clin. Electrophysiol. 32:(3):283–85
     [Crossref] [Google Scholar]
  12. 12.
    Camps J, Wang ZJ, Doste R, Holmes M, Lawson B, et al. 2024.. Cardiac digital twin pipeline for virtual therapy evaluation. . arXiv:2401.10029 [cs.CE]
  13. 13.
    Ramanathan C, Jia P, Ghanem R, Ryu K, Rudy Y. 2006.. Activation and repolarization of the normal human heart under complete physiological conditions. . PNAS 103:(16):6309–14
     [Crossref] [Google Scholar]
  14. 14.
    Antzelevitch C. 2006.. Cellular basis for the repolarization waves of the ECG. . Ann. N. Y. Acad. Sci. 1080::268–81
     [Crossref] [Google Scholar]
  15. 15.
    Janse MJ, Coronel R, Opthof T, Sosunov EA, Anyukhovsky EP, Rosen MR. 2012.. Repolarization gradients in the intact heart: Transmural or apico-basal?. Prog. Biophys. Mol. Biol. 109:(1–2):6–15
     [Crossref] [Google Scholar]
  16. 16.
    Szentadrassy N, Banyasz T, Biro T, Szabo G, Toth BI, et al. 2005.. Apico-basal inhomogeneity in distribution of ion channels in canine and human ventricular myocardium. . Cardiovasc. Res. 65:(4):851–60
     [Crossref] [Google Scholar]
  17. 17.
    Cheng J, Kamiya K, Liu W, Tsuji Y, Toyama J, Kodama I. 1999.. Heterogeneous distribution of the two components of delayed rectifier K+ current: a potential mechanism of the proarrhythmic effects of methanesulfonanilide class III agents. . Cardiovasc. Res. 43:(1):135–47
     [Crossref] [Google Scholar]
  18. 18.
    Okada J-I, Washio T, Maehara A, Momomura S-I, Sugiura S, Hisada T. 2011.. Transmural and apicobasal gradients in repolarization contribute to T-wave genesis in human surface ECG. . Am. J. Physiol. Heart Circ. Physiol. 301:(1):H200–8
     [Crossref] [Google Scholar]
  19. 19.
    Liu MB, Ko CY, Song Z, Garfinkel A, Weiss JN, Qu Z. 2016.. A dynamical threshold for cardiac delayed afterdepolarization-mediated triggered activity. . Biophys. J. 111:(11):2523–33
     [Crossref] [Google Scholar]
  20. 20.
    Cheng H, Lederer WJ. 2008.. Calcium sparks. . Physiol. Rev. 88:(4):1491–545
     [Crossref] [Google Scholar]
  21. 21.
    Qu Z, Hu G, Garfinkel A, Weiss JN. 2014.. Nonlinear and stochastic dynamics in the heart. . Phys. Rep. 543:(2):61–162
     [Crossref] [Google Scholar]
  22. 22.
    Fowler ED, Wang N, Hezzell M, Chanoit G, Hancox JC, Cannell MB. 2020.. Arrhythmogenic late Ca2+ sparks in failing heart cells and their control by action potential configuration. . PNAS 117:(5):2687–92
     [Crossref] [Google Scholar]
  23. 23.
    Boyett MR, Honjo H, Kodama I. 2000.. The sinoatrial node, a heterogeneous pacemaker structure. . Cardiovasc. Res. 47:(4):658–87
     [Crossref] [Google Scholar]
  24. 24.
    Grainger N, Guarina L, Cudmore RH, Santana LF. 2021.. The organization of the sinoatrial node microvasculature varies regionally to match local myocyte excitability. . Function 2:(4):zqab031
     [Crossref] [Google Scholar]
  25. 25.
    Maltsev VA, Maltsev AV, Maltsev A, Lakatta EG, Stern MD. 2023.. Sinoatrial node cells and tissue operate via stochastic resonance. . Biophys. J. 122:(3):382a
     [Crossref] [Google Scholar]
  26. 26.
    Maltsev AV, Maltsev VA, Mikheev M, Maltseva LA, Sirenko SG, et al. 2011.. Synchronization of stochastic Ca2+ release units creates a rhythmic Ca2+ clock in cardiac pacemaker cells. . Biophys. J. 100:(2):271–83
     [Crossref] [Google Scholar]
  27. 27.
    Tadros R, Ton A-T, Fiset C, Nattel S. 2014.. Sex differences in cardiac electrophysiology and clinical arrhythmias: epidemiology, therapeutics, and mechanisms. . Can. J. Cardiol. 30:(7):783–92
     [Crossref] [Google Scholar]
  28. 28.
    Rautaharju PM, Zhou SH, Wong S, Calhoun HP, Berenson GS, et al. 1992.. Sex differences in the evolution of the electrocardiographic QT interval with age. . Can. J. Cardiol. 8:(7):690–95
     [Google Scholar]
  29. 29.
    Rabkin SW, Cheng X-BJ, Thompson DJ. 2016.. Detailed analysis of the impact of age on the QT interval. . J. Geriatr. Cardiol. 13:(9):740–48
     [Google Scholar]
  30. 30.
    Locati EH, Zareba W, Moss AJ, Schwartz PJ, Vincent GM, et al. 1998.. Age- and sex-related differences in clinical manifestations in patients with congenital long-QT syndrome: findings from the International LQTS Registry. . Circulation 97:(22):2237–44
     [Crossref] [Google Scholar]
  31. 31.
    Peirlinck M, Sahli Costabal F, Kuhl E. 2021.. Sex differences in drug-induced arrhythmogenesis. . Front. Physiol. 12::708435
     [Crossref] [Google Scholar]
  32. 32.
    Garcia-Elias A, Benito B. 2018.. Ion channel disorders and sudden cardiac death. . Int. J. Mol. Sci. 19:(3):692
     [Crossref] [Google Scholar]
  33. 33.
    Ritchie RH, Abel ED. 2020.. Basic mechanisms of diabetic heart disease. . Circ. Res. 126:(11):1501–25
     [Crossref] [Google Scholar]
  34. 34.
    Kodama I, Wilde A, Janse MJ, Durrer D, Yamada K. 1984.. Combined effects of hypoxia, hyperkalemia and acidosis on membrane action potential and excitability of guinea-pig ventricular muscle. . J. Mol. Cell. Cardiol. 16:(3):247–59
     [Crossref] [Google Scholar]
  35. 35.
    Moréna H, Janse MJ, Fiolet JW, Krieger WJ, Crijns H, Durrer D. 1980.. Comparison of the effects of regional ischemia, hypoxia, hyperkalemia, and acidosis on intracellular and extracellular potentials and metabolism in the isolated porcine heart. . Circ. Res. 46:(5):634–46
     [Crossref] [Google Scholar]
  36. 36.
    Weiss J, Shine KI. 1982.. [ K+]o accumulation and electrophysiological alterations during early myocardial ischemia. . Am. J. Physiol. 243:(2):H318–27
     [Google Scholar]
  37. 37.
    Kraut JA, Madias NE. 2010.. Metabolic acidosis: pathophysiology, diagnosis and management. . Nat. Rev. Nephrol. 6:(5):274–85
     [Crossref] [Google Scholar]
  38. 38.
    Cobbe SM, Poole-Wilson PA. 1980.. The time of onset and severity of acidosis in myocardial ischaemia. . J. Mol. Cell. Cardiol. 12:(8):745–60
     [Crossref] [Google Scholar]
  39. 39.
    Kazbanov IV, Clayton RH, Nash MP, Bradley CP, Paterson DJ, et al. 2014.. Effect of global cardiac ischemia on human ventricular fibrillation: insights from a multi-scale mechanistic model of the human heart. . PLOS Comput. Biol. 10:(11):e1003891
     [Crossref] [Google Scholar]
  40. 40.
    Kléber AG. 1983.. Resting membrane potential, extracellular potassium activity, and intracellular sodium activity during acute global ischemia in isolated perfused guinea pig hearts. . Circ. Res. 52:(4):442–50
     [Crossref] [Google Scholar]
  41. 41.
    Rodríguez B, Trayanova N, Noble D. 2006.. Modeling cardiac ischemia. . Ann. N. Y. Acad. Sci. 1080::395–414
     [Crossref] [Google Scholar]
  42. 42.
    Parham WA, Mehdirad AA, Biermann KM, Fredman CS. 2006.. Hyperkalemia revisited. . Tex. Heart Inst. J. 33:(1):40–47
     [Google Scholar]
  43. 43.
    Campese VM, Adenuga G. 2016.. Electrophysiological and clinical consequences of hyperkalemia. . Kidney Int. Suppl. 6:(1):16–19
     [Crossref] [Google Scholar]
  44. 44.
    Kagiyama Y, Hill JL, Gettes LS. 1982.. Interaction of acidosis and increased extracellular potassium on action potential characteristics and conduction in guinea pig ventricular muscle. . Circ. Res. 51:(5):614–23
     [Crossref] [Google Scholar]
  45. 45.
    Irisawa H, Sato R. 1986.. Intra- and extracellular actions of proton on the calcium current of isolated guinea pig ventricular cells. . Circ. Res. 59:(3):348–55
     [Crossref] [Google Scholar]
  46. 46.
    Mozhayeva GN, Naumov AP, Nosyreva ED. 1984.. A study on the potential-dependence of proton block of sodium channels. . Biochim. Biophys. Acta 775:(3):435–40
     [Crossref] [Google Scholar]
  47. 47.
    Vilin YY, Peters CH, Ruben PC. 2012.. Acidosis differentially modulates inactivation in NaV1.2, NaV1.4, and NaV1.5 channels. . Front. Pharmacol. 3::109
     [Crossref] [Google Scholar]
  48. 48.
    Noma A. 1983.. ATP-regulated K+ channels in cardiac muscle. . Nature 305:(5930):147–48
     [Crossref] [Google Scholar]
  49. 49.
    Coronel R, Wilms-Schopman FJG, deGroot JR. 2002.. Origin of ischemia-induced phase 1b ventricular arrhythmias in pig hearts. . J. Am. Coll. Cardiol. 39:(1):166–76
     [Crossref] [Google Scholar]
  50. 50.
    Jie X, Trayanova NA. 2010.. Mechanisms for initiation of reentry in acute regional ischemia phase 1B. . Heart Rhythm 7:(3):379–86
     [Crossref] [Google Scholar]
  51. 51.
    Kaplinsky E, Ogawa S, Balke CW, Dreifus LS. 1979.. Two periods of early ventricular arrhythmia in the canine acute myocardial infarction model. . Circulation 60:(2):397–403
     [Crossref] [Google Scholar]
  52. 52.
    Martinez-Navarro H, Mincholé A, Bueno-Orovio A, Rodriguez B. 2019.. High arrhythmic risk in antero-septal acute myocardial ischemia is explained by increased transmural reentry occurrence. . Sci. Rep. 9::16803
     [Crossref] [Google Scholar]
  53. 53.
    Martinez-Navarro H, Zhou X, Bueno-Orovio A, Rodriguez B. 2021.. Electrophysiological and anatomical factors determine arrhythmic risk in acute myocardial ischaemia and its modulation by sodium current availability. . Interface Focus 11:(1):20190124
     [Crossref] [Google Scholar]
  54. 54.
    Hausenloy DJ, Yellon DM. 2013.. Myocardial ischemia-reperfusion injury: a neglected therapeutic target. . J. Clin. Investig. 123:(1):92–100
     [Crossref] [Google Scholar]
  55. 55.
    van der Weg K, Prinzen FW, Gorgels AP. 2019.. Editor's choice- reperfusion cardiac arrhythmias and their relation to reperfusion-induced cell death. . Eur. Heart J. Acute Cardiovasc. Care 8:(2):142–52
     [Crossref] [Google Scholar]
  56. 56.
    Wit AL, Friedman PL. 1975.. Basis for ventricular arrhythmias accompanying myocardial infarction: alterations in electrical activity of ventricular muscle and Purkinje fibers after coronary artery occlusion. . Arch. Intern. Med. 135:(3):459–72
     [Crossref] [Google Scholar]
  57. 57.
    Jeck C, Pinto J, Boyden P. 1995.. Transient outward currents in subendocardial Purkinje myocytes surviving in the infarcted heart. . Circulation 92:(3):465–73
     [Crossref] [Google Scholar]
  58. 58.
    Pinto JM, Boyden PA. 1998.. Reduced inward rectifying and increased E-4031-sensitive K+ current density in arrhythmogenic subendocardial Purkinje myocytes from the infarcted heart. . J. Cardiovasc. Electrophysiol. 9:(3):299–311
     [Crossref] [Google Scholar]
  59. 59.
    Boyden PA, Pinto JM. 1994.. Reduced calcium currents in subendocardial Purkinje myocytes that survive in the 24- and 48-hour infarcted heart. . Circulation 89:(6):2747–59
     [Crossref] [Google Scholar]
  60. 60.
    Hirose M, Stuyvers BD, Dun W, ter Keurs HEDJ, Boyden PA. 2008.. Function of Ca2+ release channels in Purkinje cells that survive in the infarcted canine heart: a mechanism for triggered Purkinje ectopy. . Circ. Arrhythm. Electrophysiol. 1:(5):387–95
     [Crossref] [Google Scholar]
  61. 61.
    Lue WM, Boyden PA. 1992.. Abnormal electrical properties of myocytes from chronically infarcted canine heart. Alterations in Vmax and the transient outward current. . Circulation 85:(3):1175–88
     [Crossref] [Google Scholar]
  62. 62.
    Pu J, Boyden PA. 1997.. Alterations of Na+ currents in myocytes from epicardial border zone of the infarcted heart. A possible ionic mechanism for reduced excitability and postrepolarization refractoriness. . Circ. Res. 81:(1):110–19
     [Crossref] [Google Scholar]
  63. 63.
    Jiang M, Cabo C, Yao J, Boyden PA, Tseng G. 2000.. Delayed rectifier K currents have reduced amplitudes and altered kinetics in myocytes from infarcted canine ventricle. . Cardiovasc. Res. 48:(1):34–43
     [Crossref] [Google Scholar]
  64. 64.
    Dun W, Baba S, Yagi T, Boyden PA. 2004.. Dynamic remodeling of K+ and Ca2+ currents in cells that survived in the epicardial border zone of canine healed infarcted heart. . Am. J. Physiol. Heart Circ. Physiol. 287:(3):H1046–54
     [Crossref] [Google Scholar]
  65. 65.
    Baba S, Dun W, Cabo C, Boyden PA. 2005.. Remodeling in cells from different regions of the reentrant circuit during ventricular tachycardia. . Circulation 112:(16):2386–96
     [Crossref] [Google Scholar]
  66. 66.
    Cabo C, Yao J, Boyden PA, Chen S, Hussain W, et al. 2006.. Heterogeneous gap junction remodeling in reentrant circuits in the epicardial border zone of the healing canine infarct. . Cardiovasc. Res. 72:(2):241–49
     [Crossref] [Google Scholar]
  67. 67.
    Ursell PC, Gardner PI, Albala A, Fenoglio JJ, Wit AL. 1985.. Structural and electrophysiological changes in the epicardial border zone of canine myocardial infarcts during infarct healing. . Circ. Res. 56:(3):436–51
     [Crossref] [Google Scholar]
  68. 68.
    Gardner PI, Ursell PC, Fenoglio JJ, Wit AL. 1985.. Electrophysiologic and anatomic basis for fractionated electrograms recorded from healed myocardial infarcts. . Circulation 72:(3):596–611
     [Crossref] [Google Scholar]
  69. 69.
    Spear JF, Michelson EL, Moore EN. 1983.. Cellular electrophysiologic characteristics of chronically infarcted myocardium in dogs susceptible to sustained ventricular tachyarrhythmias. . J. Am. Coll. Cardiol. 1:(4):1099–110
     [Crossref] [Google Scholar]
  70. 70.
    Peters NS, Coromilas J, Severs NJ, Wit AL. 1997.. 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 95:(4):988–96
     [Crossref] [Google Scholar]
  71. 71.
    Yao J-A, Hussain W, Patel P, Peters NS, Boyden PA, Wit AL. 2003.. Remodeling of gap junctional channel function in epicardial border zone of healing canine infarcts. . Circ. Res. 92:(4):437–43
     [Crossref] [Google Scholar]
  72. 72.
    Aggarwal R, Boyden PA. 1995.. Diminished Ca2+ and Ba2+ currents in myocytes surviving in the epicardial border zone of the 5-day infarcted canine heart. . Circ. Res. 77:(6):1180–91
     [Crossref] [Google Scholar]
  73. 73.
    Pinto JMB, Boyden PA. 1999.. Electrical remodeling in ischemia and infarction. . Cardiovasc. Res. 42:(2):284–97
     [Crossref] [Google Scholar]
  74. 74.
    Aggarwal R, Pu J, Boyden PA. 1997.. Ca2+-dependent outward currents in myocytes from epicardial border zone of 5-day infarcted canine heart. . Am. J. Physiol. 273:(3 Part 2):H1386–94
     [Google Scholar]
  75. 75.
    Cabo C, Schmitt H, Wit AL. 2000.. New mechanism of antiarrhythmic drug action: increasing L-type calcium current prevents reentrant ventricular tachycardia in the infarcted canine heart. . Circulation 102:(19):2417–25
     [Crossref] [Google Scholar]
  76. 76.
    Hund TJ, Decker KF, Kanter E, Mohler PJ, Boyden PA, et al. 2008.. Role of activated CaMKII in abnormal calcium homeostasis and INa remodeling after myocardial infarction: insights from mathematical modeling. . J. Mol. Cell. Cardiol. 45:(3):420–28
     [Crossref] [Google Scholar]
  77. 77.
    Zhou X, Wang ZJ, Camps J, Tomek J, Santiago A, et al. 2024.. Clinical phenotypes in acute and chronic infarction explained through human ventricular electromechanical modelling and simulations. . eLife 13::e93002
     [Crossref] [Google Scholar]
  78. 78.
    Wang ZJ, Santiago A, Zhou X, Wang L, Margara F, et al. 2021.. Human biventricular electromechanical simulations on the progression of electrocardiographic and mechanical abnormalities in post-myocardial infarction. . Europace 23:(Suppl. 1):i143–52
     [Crossref] [Google Scholar]
  79. 79.
    Cinca J, Figueras J, Tenorio L, Valle V, Trenchs J, et al. 1981.. Time course and rate dependence of Q-T interval changes during noncomplicated acute transmural myocardial infarction in human beings. . Am. J. Cardiol. 48:(6):1023–28
     [Crossref] [Google Scholar]
  80. 80.
    Arini PD, Valverde ER. 2016.. Beat-to-beat electrocardiographic analysis of ventricular repolarization variability in patients after myocardial infarction. . J. Electrocardiol. 49:(2):206–13
     [Crossref] [Google Scholar]
  81. 81.
    Batchvarov VN, Hnatkova K, Poloniecki J, Camm AJ, Malik M. 2004.. Prognostic value of heterogeneity of ventricular repolarization in survivors of acute myocardial infarction. . Clin. Cardiol. 27:(11):653–59
     [Crossref] [Google Scholar]
  82. 82.
    Swann MH, Nakagawa H, Vanoli E, Lazzara R, Schwartz PJ, Adamson PB. 2003.. Heterogeneous regional endocardial repolarization is associated with increased risk for ischemia-dependent ventricular fibrillation after myocardial infarction. . J. Cardiovasc. Electrophysiol. 14:(8):873–79
     [Crossref] [Google Scholar]
  83. 83.
    Beuckelmann DJ, Näbauer M, Erdmann E. 1992.. Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. . Circulation 85:(3):1046–55
     [Crossref] [Google Scholar]
  84. 84.
    Beuckelmann DJ, Näbauer M, Erdmann E. 1993.. Alterations of K+ currents in isolated human ventricular myocytes from patients with terminal heart failure. . Circ. Res. 73:(2):379–85
     [Crossref] [Google Scholar]
  85. 85.
    Li G-R, Lau C-P, Leung T-K, Nattel S. 2004.. Ionic current abnormalities associated with prolonged action potentials in cardiomyocytes from diseased human right ventricles. . Heart Rhythm 1:(4):460–68
     [Crossref] [Google Scholar]
  86. 86.
    Glukhov AV, Fedorov VV, Kalish PW, Ravikumar VK, Lou Q, et al. 2012.. Conduction remodeling in human end-stage nonischemic left ventricular cardiomyopathy. . Circulation 125:(15):1835–47
     [Crossref] [Google Scholar]
  87. 87.
    Hegyi B, Bossuyt J, Griffiths LG, Shimkunas R, Coulibaly Z, et al. 2018.. Complex electrophysiological remodeling in postinfarction ischemic heart failure. . PNAS 115:(13):E3036–44
     [Crossref] [Google Scholar]
  88. 88.
    Ambrosi CM, Yamada KA, Nerbonne JM, Efimov IR. 2013.. Gender differences in electrophysiological gene expression in failing and non-failing human hearts. . PLOS ONE 8:(1):e54635
     [Crossref] [Google Scholar]
  89. 89.
    Røe ÅT, Ruud M, Espe EK, Manfra O, Longobardi S, et al. 2019.. Regional diastolic dysfunction in post-infarction heart failure: role of local mechanical load and SERCA expression. . Cardiovasc. Res. 115:(4):752–64
     [Crossref] [Google Scholar]
  90. 90.
    Wei X, Li T, Hagen B, Zhang P, Sanchez PG, et al. 2013.. Short-term mechanical unloading with left ventricular assist devices after acute myocardial infarction conserves calcium cycling and improves heart function. . JACC Cardiovasc. Interv. 6:(4):406–15
     [Crossref] [Google Scholar]
  91. 91.
    Maczewski M, Mackiewicz U. 2008.. Effect of metoprolol and ivabradine on left ventricular remodelling and Ca2+ handling in the post-infarction rat heart. . Cardiovasc. Res. 79:(1):42–51
     [Crossref] [Google Scholar]
  92. 92.
    Mackiewicz U, Mączewski M, Klemenska E, Brudek M, Konior A, et al. 2010.. Brief postinfarction calcineurin blockade affects left ventricular remodeling and Ca2+ handling in the rat. . J. Mol. Cell. Cardiol. 48:(6):1307–15
     [Crossref] [Google Scholar]
  93. 93.
    Jiang MT, Lokuta AJ, Farrell EF, Wolff MR, Haworth RA, Valdivia HH. 2002.. Abnormal Ca2+ release, but normal ryanodine receptors, in canine and human heart failure. . Circ. Res. 91:(11):1015–22
     [Crossref] [Google Scholar]
  94. 94.
    Kolstad TR, van den Brink J, MacQuaide N, Lunde PK, Frisk M, et al. 2018.. Ryanodine receptor dispersion disrupts Ca2+ release in failing cardiac myocytes. . eLife 7::e39427
     [Crossref] [Google Scholar]
  95. 95.
    Biesmans L, Macquaide N, Heinzel FR, Bito V, Smith GL, Sipido KR. 2011.. Subcellular heterogeneity of ryanodine receptor properties in ventricular myocytes with low T-tubule density. . PLOS ONE 6:(10):e25100
     [Crossref] [Google Scholar]
  96. 96.
    Dries E, Santiago DJ, Gilbert G, Lenaerts I, Vandenberk B, et al. 2018.. Hyperactive ryanodine receptors in human heart failure and ischaemic cardiomyopathy reside outside of couplons. . Cardiovasc. Res. 114:(11):1512–24
     [Crossref] [Google Scholar]
  97. 97.
    Høydal MA, Kirkeby-Garstad I, Karevold A, Wiseth R, Haaverstad R, et al. 2018.. Human cardiomyocyte calcium handling and transverse tubules in mid-stage of post-myocardial-infarction heart failure. . ESC Heart Fail. 5:(3):332–42
     [Crossref] [Google Scholar]
  98. 98.
    Mendonca Costa C, Plank G, Rinaldi CA, Niederer SA, Bishop MJ. 2018.. Modeling the electrophysiological properties of the infarct border zone. . Front. Physiol. 9::356
     [Crossref] [Google Scholar]
  99. 99.
    Kimura S, Bassett AL, Gaide MS, Kozlovskis PL, Myerburg RJ. 1986.. Regional changes in intracellular potassium and sodium activity after healing of experimental myocardial infarction in cats. . Circ. Res. 58:(2):202–8
     [Crossref] [Google Scholar]
  100. 100.
    Wong SS, Bassett AL, Cameron JS, Epstein K, Kozlovskis P, Myerburg RJ. 1982.. Dissimilarities in the electrophysiological abnormalities of lateral border and central infarct zone cells after healing of myocardial infarction in cats. . Circ. Res. 51:(4):486–93
     [Crossref] [Google Scholar]
  101. 101.
    Myerburg RJ, Epstein K, Gaide MS, Wong SS, Castellanos A, et al. 1982.. Cellular electrophysiology in acute and healed experimental myocardial infarction. . Ann. N. Y. Acad. Sci. 382::90–115
     [Crossref] [Google Scholar]
  102. 102.
    Kimura S, Bassett AL, Cameron JS, Huikuri H, Kozlovskis PL, Myerburg RJ. 1988.. Cellular electrophysiological changes during ischemia in isolated, coronary-perfused cat ventricle with healed myocardial infarction. . Circulation 78:(2):401–6
     [Crossref] [Google Scholar]
  103. 103.
    Weigand K, Witte R, Moukabary T, Chinyere I, Lancaster J, et al. 2017.. In vivo electrophysiological study of induced ventricular tachycardia in intact rat model of chronic ischemic heart failure. . IEEE Trans. Biomed. Eng. 64:(6):1393–99
     [Crossref] [Google Scholar]
  104. 104.
    Pop M, Sermesant M, Liu G, Relan J, Mansi T, et al. 2012.. Construction of 3D MR image-based computer models of pathologic hearts, augmented with histology and optical fluorescence imaging to characterize action potential propagation. . Med. Image Anal. 16:(2):505–23
     [Crossref] [Google Scholar]
  105. 105.
    Litwin SE, Bridge JH. 1997.. Enhanced Na+-Ca2+ exchange in the infarcted heart. Implications for excitation-contraction coupling. . Circ. Res. 81:(6):1083–93
     [Crossref] [Google Scholar]
  106. 106.
    Lee YS, Chang P-C, Hsueh C-H, Maruyama M, Park HW, et al. 2013.. Apamin-sensitive calcium-activated potassium currents in rabbit ventricles with chronic myocardial infarction. . J. Cardiovasc. Electrophysiol. 24:(10):1144–53
     [Crossref] [Google Scholar]
  107. 107.
    Spear JF, Horowitz LN, Hodess AB, MacVaugh H, Moore EN. 1979.. Cellular electrophysiology of human myocardial infarction. 1. Abnormalities of cellular activation. . Circulation 59:(2):247–56
     [Crossref] [Google Scholar]
  108. 108.
    Dangman KH, Danilo P, Hordof AJ, Mary-Rabine L, Reder RF, Rosen MR. 1982.. Electrophysiologic characteristics of human ventricular and Purkinje fibers. . Circulation 65:(2):362–68
     [Crossref] [Google Scholar]
  109. 109.
    Srinivasan NT, Orini M, Providencia R, Dhinoja MB, Lowe MD, et al. 2019.. Prolonged action potential duration and dynamic transmural action potential duration heterogeneity underlie vulnerability to ventricular tachycardia in patients undergoing ventricular tachycardia ablation. . Europace 21:(4):616–25
     [Crossref] [Google Scholar]
  110. 110.
    Kelemen K, Greener ID, Wan X, Parajuli S, Donahue JK. 2022.. Heterogeneous repolarization creates ventricular tachycardia circuits in healed myocardial infarction scar. . Nat. Commun. 13:(1):830
     [Crossref] [Google Scholar]
  111. 111.
    Callans DJ, Donahue JK. 2022.. Repolarization heterogeneity in human post-infarct ventricular tachycardia. . JACC Clin. Electrophysiol. 8:(6):713–18
     [Crossref] [Google Scholar]
  112. 112.
    Holmes JW, Borg TK, Covell JW. 2005.. Structure and mechanics of healing myocardial infarcts. . Annu. Rev. Biomed. Eng. 7::223–53
     [Crossref] [Google Scholar]
  113. 113.
    Donahue JK, Chrispin J, Ajijola OA. 2024.. Mechanism of ventricular tachycardia occurring in chronic myocardial infarction scar. . Circ. Res. 134:(3):328–42
     [Crossref] [Google Scholar]
  114. 114.
    Rog-Zielinska EA, Norris RA, Kohl P, Markwald R. 2016.. The living scar—cardiac fibroblasts and the injured heart. . Trends Mol. Med. 22:(2):99–114
     [Crossref] [Google Scholar]
  115. 115.
    Saba S, Mathier MA, Mehdi H, Liu T, Choi B-R, et al. 2008.. Dual-dye optical mapping after myocardial infarction: Does the site of ventricular stimulation alter the properties of electrical propagation?. J. Cardiovasc. Electrophysiol. 19:(2):197–202
     [Crossref] [Google Scholar]
  116. 116.
    Dhanjal TS, Lellouche N, von Ruhland CJ, Abehsira G, Edwards DH, et al. 2017.. Massive accumulation of myofibroblasts in the critical isthmus is associated with ventricular tachycardia inducibility in post-infarct swine heart. . JACC Clin. Electrophysiol. 3:(7):703–14
     [Crossref] [Google Scholar]
  117. 117.
    Ripplinger CM, Lou Q, Li W, Hadley J, Efimov IR. 2009.. Panoramic imaging reveals basic mechanisms of induction and termination of ventricular tachycardia in rabbit heart with chronic infarction: implications for low-voltage cardioversion. . Heart Rhythm 6:(1):87–97
     [Crossref] [Google Scholar]
  118. 118.
    Pogwizd SM, Hoyt RH, Saffitz JE, Corr PB, Cox JL, Cain ME. 1992.. Reentrant and focal mechanisms underlying ventricular tachycardia in the human heart. . Circulation 86:(6):1872–87
     [Crossref] [Google Scholar]
  119. 119.
    Kostin S, Rieger M, Dammer S, Hein S, Richter M, et al. 2003.. Gap junction remodeling and altered connexin43 expression in the failing human heart. . Mol. Cell. Biochem. 242:(1–2):135–44
     [Crossref] [Google Scholar]
  120. 120.
    Smith JH, Green CR, Peters NS, Rothery S, Severs NJ. 1991.. Altered patterns of gap junction distribution in ischemic heart disease. An immunohistochemical study of human myocardium using laser scanning confocal microscopy. . Am. J. Pathol. 139:(4):801–21
     [Google Scholar]
  121. 121.
    Ng FS, Kalindjian JM, Cooper SA, Chowdhury RA, Patel PM, et al. 2016.. Enhancement of gap junction function during acute myocardial infarction modifies healing and reduces late ventricular arrhythmia susceptibility. . JACC Clin. Electrophysiol. 2:(5):574–82
     [Crossref] [Google Scholar]
  122. 122.
    Ruiz-Hurtado G, Li L, Fernández-Velasco M, Rueda A, Lefebvre F, et al. 2015.. Reconciling depressed Ca2+ sparks occurrence with enhanced RyR2 activity in failing mice cardiomyocytes. . J. Gen. Physiol. 146:(4):295–306
     [Crossref] [Google Scholar]
  123. 123.
    Li Y, Xue Q, Ma J, Zhang C, Qiu P, et al. 2004.. Effects of imidapril on heterogeneity of action potential and calcium current of ventricular myocytes in infarcted rabbits. . Acta Pharmacol. Sin. 25:(11):1458–63
     [Crossref] [Google Scholar]
  124. 124.
    Liu N, Niu H, Li Y, Zhang C, Zhou Q, et al. 2004.. The changes of potassium currents in rabbit ventricle with healed myocardial infarction. . J. Huazhong Univ. Sci. Technol. Med. Sci. 24:(2):128–31
     [Google Scholar]
  125. 125.
    Zhang H, Makarewich CA, Kubo H, Wang W, Duran JM, et al. 2012.. Hyperphosphorylation of the cardiac ryanodine receptor at serine 2808 is not involved in cardiac dysfunction after myocardial infarction. . Circ. Res. 110:(6):831–40
     [Crossref] [Google Scholar]
  126. 126.
    Pennock GD, Spooner PH, Summers CE, Litwin SE. 2000.. Prevention of abnormal sarcoplasmic reticulum calcium transport and protein expression in post-infarction heart failure using 3, 5-diiodothyropropionic acid (DITPA). . J. Mol. Cell. Cardiol. 32:(11):1939–53
     [Crossref] [Google Scholar]
  127. 127.
    Cox MM, Berman I, Myerburg RJ, Smets MJ, Kozlovskis PL. 1991.. Morphometric mapping of regional myocyte diameters after healing of myocardial infarction in cats. . J. Mol. Cell. Cardiol. 23:(2):127–35
     [Crossref] [Google Scholar]
  128. 128.
    Taggart P, Sutton PM, Opthof T, Coronel R, Trimlett R, et al. 2000.. Inhomogeneous transmural conduction during early ischaemia in patients with coronary artery disease. . J. Mol. Cell. Cardiol. 32:(4):621–30
     [Crossref] [Google Scholar]
  129. 129.
    Sutton P, Taggart P, Opthof T, Coronel R, Trimlett R, et al. 2000.. Repolarisation and refractoriness during early ischaemia in humans. . Heart 84:(4):365–69
     [Crossref] [Google Scholar]
  130. 130.
    ten Tusscher KHWJ, Panfilov AV. 2006.. Alternans and spiral breakup in a human ventricular tissue model. . Am. J. Physiol. Heart Circ. Physiol. 291:(3):H1088–100
     [Crossref] [Google Scholar]
  131. 131.
    Nash MP, Mourad A, Clayton RH, Sutton PM, Bradley CP, et al. 2006.. Evidence for multiple mechanisms in human ventricular fibrillation. . Circulation 114:(6):536–42
     [Crossref] [Google Scholar]
  132. 132.
    Liu Y-B, Pak H-N, Lamp ST, Okuyama Y, Hayashi H, et al. 2004.. Coexistence of two types of ventricular fibrillation during acute regional ischemia in rabbit ventricle. . J. Cardiovasc. Electrophysiol. 15:(12):1433–40
     [Crossref] [Google Scholar]
  133. 133.
    Janse MJ, Kléber AG. 1981.. Electrophysiological changes and ventricular arrhythmias in the early phase of regional myocardial ischemia. . Circ. Res. 49:(5):1069–81
     [Crossref] [Google Scholar]
  134. 134.
    Janse MJ, van Capelle FJ. 1982.. Electrotonic interactions across an inexcitable region as a cause of ectopic activity in acute regional myocardial ischemia. A study in intact porcine and canine hearts and computer models. . Circ. Res. 50:(4):527–37
     [Crossref] [Google Scholar]
  135. 135.
    Janse MJ, van Capelle FJ, Morsink H, Kléber AG, Wilms-Schopman F, et al. 1980.. Flow of “injury” current and patterns of excitation during early ventricular arrhythmias in acute regional myocardial ischemia in isolated porcine and canine hearts. Evidence for two different arrhythmogenic mechanisms. . Circ. Res. 47:(2):151–65
     [Crossref] [Google Scholar]
  136. 136.
    Coronel R, Wilms-Schopman FJ, Opthof T, van Capelle FJ, Janse MJ. 1991.. Injury current and gradients of diastolic stimulation threshold, TQ potential, and extracellular potassium concentration during acute regional ischemia in the isolated perfused pig heart. . Circ. Res. 68:(5):1241–49
     [Crossref] [Google Scholar]
  137. 137.
    Downar E, Janse MJ, Durrer D. 1977.. The effect of acute coronary artery occlusion on subepicardial transmembrane potentials in the intact porcine heart. . Circulation 56:(2):217–24
     [Crossref] [Google Scholar]
  138. 138.
    Valderrábano M, Lee MH, Ohara T, Lai AC, Fishbein MC, et al. 2001.. Dynamics of intramural and transmural reentry during ventricular fibrillation in isolated swine ventricles. . Circ. Res. 88:(8):839–48
     [Crossref] [Google Scholar]
  139. 139.
    Wilensky RL, Tranum-Jensen J, Coronel R, Wilde AA, Fiolet JW, Janse MJ. 1986.. The subendocardial border zone during acute ischemia of the rabbit heart: an electrophysiologic, metabolic, and morphologic correlative study. . Circulation 74:(5):1137–46
     [Crossref] [Google Scholar]
  140. 140.
    Siogas K, Pappas S, Graekas G, Goudevenos J, Liapi G, Sideris DA. 1998.. Segmental wall motion abnormalities alter vulnerability to ventricular ectopic beats associated with acute increases in aortic pressure in patients with underlying coronary artery disease. . Heart 79:(3):268–73
     [Crossref] [Google Scholar]
  141. 141.
    Zhang H, Yu H, Walcott GP, Rogers JM. 2022.. Ectopic foci do not co-locate with ventricular epicardial stretch during early acute regional ischemia in isolated pig hearts. . Physiol. Rep. 10:(20):e15492
     [Crossref] [Google Scholar]
  142. 142.
    Fujimatsu T, Nitta T, Osawa H, Shimizu K. 2010.. Serial changes in epicardial electrograms during and after a coronary artery occlusion. . Gen. Thorac. Cardiovasc. Surg. 58:(7):323–30
     [Crossref] [Google Scholar]
  143. 143.
    Luqman N, Sung RJ, Wang C-L, Kuo C-T. 2007.. Myocardial ischemia and ventricular fibrillation: pathophysiology and clinical implications. . Int. J. Cardiol. 119:(3):283–90
     [Crossref] [Google Scholar]
  144. 144.
    Qu Z, Weiss JN, Garfinkel A. 1999.. Cardiac electrical restitution properties and stability of reentrant spiral waves: a simulation study. . Am. J. Physiol. Heart Circ. Physiol. 276:(1):H269–83
     [Crossref] [Google Scholar]
  145. 145.
    Samie FH, Jalife J. 2001.. Mechanisms underlying ventricular tachycardia and its transition to ventricular fibrillation in the structurally normal heart. . Cardiovasc. Res. 50:(2):242–50
     [Crossref] [Google Scholar]
  146. 146.
    Massé S, Farid T, Dorian P, Umapathy K, Nair K, et al. 2009.. Effect of global ischemia and reperfusion during ventricular fibrillation in myopathic human hearts. . Am. J. Physiol. Heart Circ. Physiol. 297:(6):H1984–91
     [Crossref] [Google Scholar]
  147. 147.
    Wiggers CJ. 1930.. Studies of ventricular fibrillation caused by electric shock: II. Cinematographic and electrocardiographic observations of the natural process in the dog's heart. Its inhibition by potassium and the revival of coordinated beats by calcium. . Am. Heart J. 5:(3):351–65
     [Crossref] [Google Scholar]
  148. 148.
    Wu T-J, Lin S-F, Weiss JN, Ting C-T, Chen P-S. 2002.. Two types of ventricular fibrillation in isolated rabbit hearts: importance of excitability and action potential duration restitution. . Circulation 106:(14):1859–66
     [Crossref] [Google Scholar]
  149. 149.
    Ristagno G, Mauri T, Cesana G, Li Y, Finzi A, et al. 2015.. Amplitude spectrum area to guide defibrillation: a validation on 1617 patients with ventricular fibrillation. . Circulation 131:(5):478–87
     [Crossref] [Google Scholar]
  150. 150.
    Bradley CP, Clayton RH, Nash MP, Mourad A, Hayward M, et al. 2011.. Human ventricular fibrillation during global ischemia and reperfusion: paradoxical changes in activation rate and wavefront complexity. . Circ. Arrhythm. Electrophysiol. 4:(5):684–91
     [Crossref] [Google Scholar]
  151. 151.
    Sattler SM, Skibsbye L, Linz D, Lubberding AF, Tfelt-Hansen J, Jespersen T. 2019.. Ventricular arrhythmias in first acute myocardial infarction: epidemiology, mechanisms, and interventions in large animal models. . Front. Cardiovasc. Med. 6::158
     [Crossref] [Google Scholar]
  152. 152.
    Janse MJ, Wit AL. 1989.. Electrophysiological mechanisms of ventricular arrhythmias resulting from myocardial ischemia and infarction. . Physiol. Rev. 69:(4):1049–169
     [Crossref] [Google Scholar]
  153. 153.
    Fenoglio JJ, Pham TD, Harken AH, Horowitz LN, Josephson ME, Wit AL. 1983.. Recurrent sustained ventricular tachycardia: structure and ultrastructure of subendocardial regions in which tachycardia originates. . Circulation 68:(3):518–33
     [Crossref] [Google Scholar]
  154. 154.
    de Bakker JM, van Capelle FJ, Janse MJ, Tasseron S, Vermeulen JT, et al. 1993.. Slow conduction in the infarcted human heart. “Zigzag” course of activation. . Circulation 88:(3):915–26
     [Crossref] [Google Scholar]
  155. 155.
    Almer J, Jennings RB, Maan AC, Ringborn M, Maynard C, et al. 2016.. Ischemic QRS prolongation as a biomarker of severe myocardial ischemia. . J. Electrocardiol. 49:(2):139–47
     [Crossref] [Google Scholar]
  156. 156.
    Almer J, Elmberg V, Bränsvik J, Nordlund D, Khoshnood A, et al. 2018.. Ischemic QRS prolongation as a biomarker of myocardial injury in STEMI patients. . Ann. Noninvasive Electrocardiol. 24:(1):e12601
     [Crossref] [Google Scholar]
  157. 157.
    Samson WE, Scher AM. 1960.. Mechanism of S-T segment alteration during acute myocardial injury. . Circ. Res. 8::780–87
     [Crossref] [Google Scholar]
  158. 158.
    Vogel B, Claessen BE, Arnold SV, Chan D, Cohen DJ, et al. 2019.. ST-segment elevation myocardial infarction. . Nat. Rev. Disease Primers 5::39
     [Crossref] [Google Scholar]
  159. 159.
    Reindl M, Reinstadler SJ, Feistritzer H-J, Niess L, Koch C, et al. 2017.. Persistent T-wave inversion predicts myocardial damage after ST-elevation myocardial infarction. . Int. J. Cardiol. 241::76–82
     [Crossref] [Google Scholar]
  160. 160.
    Topal DG, Lønborg J, Ahtarovski KA, Nepper-Christensen L, Fakhri Y, et al. 2020.. Early Q-wave morphology in prediction of reperfusion success in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention—a cardiac magnetic resonance imaging study. . J. Electrocardiol. 58::135–42
     [Crossref] [Google Scholar]
  161. 161.
    Moon JCC, De Arenaza DP, Elkington AG, Taneja AK, John AS, et al. 2004.. The pathologic basis of Q-wave and non-Q-wave myocardial infarction: a cardiovascular magnetic resonance study. . J. Am. Coll. Cardiol. 44:(3):554–60
     [Crossref] [Google Scholar]
  162. 162.
    Norda S, van der Weg K, Vos R, Gorgels APM. 2015.. Electrocardiographic prediction of lateral involvement in acute non-anterior wall myocardial infarction. . J. Electrocardiol. 48:(4):527–32
     [Crossref] [Google Scholar]
  163. 163.
    Tiller C, Reindl M, Holzknecht M, Innerhofer L, Wagner M, et al. 2019.. Relationship between admission Q waves and microvascular injury in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. . Int. J. Cardiol. 297::1–7
     [Crossref] [Google Scholar]
  164. 164.
    Kochav JD, Okin PM, Wilson S, Afroz A, Renilla A, Weinsaft JW. 2013.. Usefulness of Q-wave area for threshold-based stratification of global left ventricular myocardial infarct size. . Am. J. Cardiol. 112:(2):174–80
     [Crossref] [Google Scholar]
  165. 165.
    Plein S, Younger JF, Sparrow P, Ridgway JP, Ball SG, Greenwood JP. 2008.. Cardiovascular magnetic resonance of scar and ischemia burden early after acute ST elevation and non-ST elevation myocardial infarction. . J. Cardiovasc. Magn. Reson. 10::47
     [Crossref] [Google Scholar]
  166. 166.
    Wong C-K, White HD. 2020.. In the transition from fibrinolysis to primary PCI, the HERO trials help refine STEMI ECG interpretation and Q wave analysis potentially alters future management. . Eur. Heart J. Acute Cardiovasc. Care 9:(Suppl. 1):26–33
     [Crossref] [Google Scholar]
  167. 167.
    Taylor GJ, Crampton RS, Gibson RS, Stebbins PT, Waldman MT, Beller GA. 1981.. Prolonged QT interval at onset of acute myocardial infarction in predicting early phase ventricular tachycardia. . Am. Heart J. 102:(1):16–24
     [Crossref] [Google Scholar]
  168. 168.
    Ahnve S. 1985.. QT interval prolongation in acute myocardial infarction. . Eur. Heart J. 6:(Suppl. D):85–95
     [Crossref] [Google Scholar]
  169. 169.
    Galluzzo A, Gallo C, Battaglia A, Frea S, Canavosio FG, et al. 2016.. Prolonged QT interval in ST-elevation myocardial infarction: predictors and prognostic value in medium-term follow-up. . J. Cardiovasc. Med. 17:(6):440–45
     [Crossref] [Google Scholar]
  170. 170.
    Doroghazi RM, Childers R. 1978.. Time-related changes in the Q-T interval in acute myocardial infarction: possible relation to local hypocalcemia. . Am. J. Cardiol. 41:(4):684–88
     [Crossref] [Google Scholar]
  171. 171.
    Andersen MP, Terkelsen CJ, Sørensen JT, Kaltoft AK, Nielsen SS, et al. 2010.. The ST injury vector: electrocardiogram-based estimation of location and extent of myocardial ischemia. . J. Electrocardiol. 43:(2):121–31
     [Crossref] [Google Scholar]
  172. 172.
    Sarafoff N, Schuster T, Vochem R, Fichtner S, Martinoff S, et al. 2013.. Association of ST-elevation and non-ST-elevation presentation on ECG with transmurality and size of myocardial infarction as assessed by contrast-enhanced magnetic resonance imaging. . J. Electrocardiol. 46:(2):100–6
     [Crossref] [Google Scholar]
  173. 173.
    Zellweger MJ, Weinbacher M, Zutter AW, Jeger RV, Mueller-Brand J, et al. 2003.. Long-term outcome of patients with silent versus symptomatic ischemia six months after percutaneous coronary intervention and stenting. . J. Am. Coll. Cardiol. 42:(1):33–40
     [Crossref] [Google Scholar]
  174. 174.
    Hansen R, Frydland M, Møller-Helgestad OK, Lindholm MG, Jensen LO, et al. 2017.. Association between QRS duration on prehospital ECG and mortality in patients with suspected STEMI. . Int. J. Cardiol. 249::55–60
     [Crossref] [Google Scholar]
  175. 175.
    Sato A, Hiroe M, Nozato T, Hikita H, Ito Y, et al. 2008.. Early validation study of 64-slice multidetector computed tomography for the assessment of myocardial viability and the prediction of left ventricular remodelling after acute myocardial infarction. . Eur. Heart J. 29:(4):490–98
     [Crossref] [Google Scholar]
  176. 176.
    St. John Sutton M, Lee D, Rouleau JL, Goldman S, Plappert T, et al. 2003.. Left ventricular remodeling and ventricular arrhythmias after myocardial infarction. . Circulation 107:(20):2577–82
     [Crossref] [Google Scholar]
  177. 177.
    Sievers B, John B, Brandts B, Franken U, van Bracht M, Trappe H-J. 2004.. How reliable is electrocardiography in differentiating transmural from non-transmural myocardial infarction? A study with contrast magnetic resonance imaging as gold standard. . Int. J. Cardiol. 97:(3):417–23
     [Crossref] [Google Scholar]
  178. 178.
    Yalın K, Gölcük E, Teker E, Yılmaz R, Dursun M, et al. 2014.. No association between scar size and characteristics on T-wave alternans in post-myocardial infarction patients with relatively preserved ventricular function presented with nonsustained ventricular tachycardia. . Anadolu Kardiyol Derg 14:(5):442–47
     [Crossref] [Google Scholar]
  179. 179.
    Yan AT, Shayne AJ, Brown KA, Gupta SN, Chan CW, et al. 2006.. Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post–myocardial infarction mortality. . Circulation 114:(1):32–39
     [Crossref] [Google Scholar]
  180. 180.
    Schmidt A, Azevedo CF, Cheng A, Gupta SN, Bluemke DA, et al. 2007.. Infarct tissue heterogeneity by magnetic resonance imaging identifies enhanced cardiac arrhythmia susceptibility in patients with left ventricular dysfunction. . Circulation 115:(15):2006–14
     [Crossref] [Google Scholar]
  181. 181.
    Roes SD, Borleffs CJW, van der Geest RJ, Westenberg JJM, Marsan NA, et al. 2009.. Infarct tissue heterogeneity assessed with contrast-enhanced MRI predicts spontaneous ventricular arrhythmia in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillator. . Circ. Cardiovasc. Imaging 2:(3):183–90
     [Crossref] [Google Scholar]
  182. 182.
    Raphael CE, Cooper R, Parker KH, Collinson J, Vassiliou V, et al. 2016.. Mechanisms of myocardial ischemia in hypertrophic cardiomyopathy. . J. Am. Coll. Cardiol. 68:(15):1651–60
     [Crossref] [Google Scholar]
  183. 183.
    Park KE, Richard Conti C. 2016.. Prognostic significance of asymptomatic myocardial ischemia in women versus men. . Curr. Pharm. Des. 22:(25):3871–76
     [Crossref] [Google Scholar]
  184. 184.
    Kujime S, Sakurada H, Saito N, Enomoto Y, Ito N, et al. 2017.. Outcomes of Brugada syndrome patients with coronary artery vasospasm. . Intern. Med. 56:(2):129–35
     [Crossref] [Google Scholar]
  185. 185.
    Aliot E, Capucci A, Crijns HJ, Goette A, Tamargo J. 2011.. Twenty-five years in the making: flecainide is safe and effective for the management of atrial fibrillation. . Europace 13:(2):161–73
     [Crossref] [Google Scholar]
  186. 186.
    Cardiac Arrhythmia Suppression Trial II Investigators. 1992.. Effect of the antiarrhythmic agent moricizine on survival after myocardial infarction. . N. Engl. J. Med. 327:(4):227–33
     [Crossref] [Google Scholar]
  187. 187.
    Hondeghem LM, Katzung BG. 1984.. Antiarrhythmic agents: the modulated receptor mechanism of action of sodium and calcium channel-blocking drugs. . Annu. Rev. Pharmacol. Toxicol. 24::387–423
     [Crossref] [Google Scholar]
  188. 188.
    Greenberg HM, Dwyer EM, Hochman JS, Steinberg JS, Echt DS, Peters RW. 1995.. Interaction of ischaemia and encainide/flecainide treatment: a proposed mechanism for the increased mortality in CAST I. . Br. Heart J. 74:(6):631–35
     [Crossref] [Google Scholar]
  189. 189.
    Chen W, Du B, Liu K, Yu Z, Wang X, Yang P. 2022.. Nilotinib related acute myocardial infarction with nonobstructive coronary arteries: a case report and literature review. . BMC Cardiovasc. Disorders 22:(1):46
     [Crossref] [Google Scholar]
  190. 190.
    McFadyen JD, Schaff M, Peter K. 2018.. Current and future antiplatelet therapies: emphasis on preserving haemostasis. . Nat. Rev. Cardiol. 15:(3):181–91
     [Crossref] [Google Scholar]
  191. 191.
    Thibault H, Piot C, Staat P, Bontemps L, Sportouch C, et al. 2008.. Long-term benefit of postconditioning. . Circulation 117:(8):1037–44
     [Crossref] [Google Scholar]
  192. 192.
    Engstrøm T, Kelbæk H, Helqvist S, Høfsten DE, Kløvgaard L, et al. 2017.. Effect of ischemic postconditioning during primary percutaneous coronary intervention for patients with ST-segment elevation myocardial infarction: a randomized clinical trial. . JAMA Cardiol. 2:(5):490–97
     [Crossref] [Google Scholar]
  193. 193.
    Buske M, Desch S, Heusch G, Rassaf T, Eitel I, et al. 2023.. Reperfusion injury: how can we reduce it by pre-, per-, and postconditioning. . J. Clin. Med. 13:(1):159
     [Crossref] [Google Scholar]
  194. 194.
    Piot C, Croisille P, Staat P, Thibault H, Rioufol G, et al. 2008.. Effect of cyclosporine on reperfusion injury in acute myocardial infarction. . N. Engl. J. Med. 359:(5):473–81
     [Crossref] [Google Scholar]
  195. 195.
    Lønborg J, Vejlstrup N, Kelbæk H, Bøtker HE, Kim WY, et al. 2012.. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. . Eur. Heart J. 33:(12):1491–99
     [Crossref] [Google Scholar]
  196. 196.
    Vaduganathan M, Claggett BL, Chatterjee NA, Anand IS, Sweitzer NK, et al. 2018.. Sudden death in heart failure with preserved ejection fraction: a competing risks analysis from the TOPCAT Trial. . JACC Heart Fail. 6:(8):653–61
     [Crossref] [Google Scholar]
  197. 197.
    Solomon SD, Zelenkofske S, McMurray JJV, Finn PV, Velazquez E, et al. 2005.. Sudden death in patients with myocardial infarction and left ventricular dysfunction, heart failure, or both. . N. Engl. J. Med. 352:(25):2581–88
     [Crossref] [Google Scholar]
  198. 198.
    Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, et al. 2015.. 2015 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). . Eur. Heart J. 36:(41):2793–867
     [Crossref] [Google Scholar]
  199. 199.
    Gatzoulis KA, Tsiachris D, Arsenos P, Antoniou C-K, Dilaveris P, et al. 2019.. Arrhythmic risk stratification in post-myocardial infarction patients with preserved ejection fraction: the PRESERVE EF study. . Eur. Heart J. 40:(35):2940–49
     [Crossref] [Google Scholar]
  200. 200.
    Curley D, Lavin Plaza B, Shah AM, Botnar RM. 2018.. Molecular imaging of cardiac remodelling after myocardial infarction. . Basic Res. Cardiol. 113:(2):10
     [Crossref] [Google Scholar]
  201. 201.
    Jenča D, Melenovský V, Stehlik J, Staněk V, Kettner J, et al. 2020.. Heart failure after myocardial infarction: incidence and predictors. . ESC Heart Fail. 8:(1):222–37
     [Crossref] [Google Scholar]
  202. 202.
    Ghanem RN, Jia P, Ramanathan C, Ryu K, Markowitz A, Rudy Y. 2005.. Noninvasive electrocardiographic imaging (ECGI): comparison to intraoperative mapping in patients. . Heart Rhythm 2:(4):339–54
     [Crossref] [Google Scholar]
  203. 203.
    Rudy Y. 2017.. Noninvasive ECG imaging (ECGI): Mapping the arrhythmic substrate of the human heart. . Int. J. Cardiol. 237::13–14
     [Crossref] [Google Scholar]
  204. 204.
    Cuculich PS, Schill MR, Kashani R, Mutic S, Lang A, et al. 2017.. Noninvasive cardiac radiation for ablation of ventricular tachycardia. . N. Engl. J. Med. 377:(24):2325–36
     [Crossref] [Google Scholar]
  205. 205.
    Zhou X, Bueno-Orovio A, Schilling RJ, Kirkby C, Denning C, et al. 2019.. Investigating the complex arrhythmic phenotype caused by the gain-of-function mutation KCNQ1-G229D. . Front. Physiol. 10::259
     [Crossref] [Google Scholar]
  206. 206.
    Coleman JA, Doste R, Ashkir Z, Coppini R, Sachetto R, et al. 2024.. Mechanisms of ischaemia-induced arrhythmias in hypertrophic cardiomyopathy: a large-scale computational study. . Cardiovasc. Res. 120:(8):914–26
     [Crossref] [Google Scholar]
  207. 207.
    Passini E, Britton OJ, Lu HR, Rohrbacher J, Hermans AN, et al. 2017.. Human in silico drug trials demonstrate higher accuracy than animal models in predicting clinical pro-arrhythmic cardiotoxicity. . Front. Physiol. 8::668
     [Crossref] [Google Scholar]
  208. 208.
    Riebel LL, Wang ZJ, Martinez-Navarro H, Trovato C, Camps J, et al. 2024.. In silico evaluation of cell therapy in acute versus chronic infarction: role of automaticity, heterogeneity and Purkinje in human. . Sci. Rep. 14::21584
     [Crossref] [Google Scholar]
  209. 209.
    Corral-Acero J, Margara F, Marciniak M, Rodero C, Loncaric F, et al. 2020.. The ‘Digital Twin’ to enable the vision of precision cardiology. . Eur. Heart J. 41:(48):4556–64
     [Crossref] [Google Scholar]
  210. 210.
    Arevalo HJ, Vadakkumpadan F, Guallar E, Jebb A, Malamas P, et al. 2016.. Arrhythmia risk stratification of patients after myocardial infarction using personalized heart models. . Nat. Commun. 7::11437
     [Crossref] [Google Scholar]
  211. 211.
    Camps J, Berg LA, Wang ZJ, Sebastian R, Riebel LL, et al. 2024.. Digital twinning of the human ventricular activation sequence to clinical 12-lead ECGs and magnetic resonance imaging using realistic Purkinje networks for in silico clinical trials. . Med. Image Anal. 94::103108
     [Crossref] [Google Scholar]
  212. 212.
    Galappaththige S, Gray RA, Costa CM, Niederer S, Pathmanathan P. 2022.. Credibility assessment of patient-specific computational modeling using patient-specific cardiac modeling as an exemplar. . PLOS Comput. Biol. 18:(10):e1010541
     [Crossref] [Google Scholar]
  213. 213.
    Antoniades C, Patel P, Antonopoulos AS. 2023.. Using artificial intelligence to study atherosclerosis, predict risk and guide treatments in clinical practice. . Eur. Heart J. 44:(6):437–39
     [Crossref] [Google Scholar]
  214. 214.
    Mincholé A, Camps J, Lyon A, Rodríguez B. 2019.. Machine learning in the electrocardiogram. . J. Electrocardiol. 57S::S61–64
     [Crossref] [Google Scholar]
  215. 215.
    Banerjee A, Camps J, Zacur E, Andrews CM, Rudy Y, et al. 2021.. A completely automated pipeline for 3D reconstruction of human heart from 2D cine magnetic resonance slices. . Philos. Trans. A 379:(2212):20200257
     [Google Scholar]
  216. 216.
    Martinez-Navarro H, Bertrand A, Doste R, Smith H, Tomek J, . 2024.. ECG analysis of ventricular fibrillation dynamics reflects ischaemic progression subject to variability in patient anatomy and electrode location. . Front. Cardiovasc. Med. 11::1408822
     [Crossref] [Google Scholar]
  217. 217.
    Zhou X, Levesque P, Chaudhary K, Davis M, Rodriguez B. 2024.. Lower diastolic tension may be indicative of higher proarrhythmic propensity in failing human cardiomyocytes. . Sci. Rep. 14::17351
     [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-physiol-042022-020541
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Mechanisms and Implications of Electrical Heterogeneity in Cardiac Function in Ischemic Heart Disease
Annual Review of Physiology 87, 25 (2025); https://doi.org/10.1146/annurev-physiol-042022-020541
/content/journals/10.1146/annurev-physiol-042022-020541
/content/journals/10.1146/annurev-physiol-042022-020541
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