Acute Coronary Syndromes: Pathophysiology and Presentation

Author: Jason M Kendall / Editor: Jason M Kendall / Reviewer: Liz Florey, Jolene Rosario / Code: A1Published: 21/10/2021

Before commencing this session you should be able to appropriately interpret ECGs

After completing this session you will be able to:

  • Describe the pathophysiology underlying acute coronary syndromes
  • Define acute myocardial infarction
  • Classify the various presentations within the spectrum of acute coronary syndromes
  • Interpret features of the history, examination and ECG in terms of likelihood ratios that increase or reduce the probability of definitive diagnosis
  • Recognise the need for additional ECG leads where appropriate
  • Describe the role of cardiac markers in patients with acute coronary syndromes

References:

  1. Goodacre S, Cross E, Arnold J, et al. The health care burden of acute chest pain. Heart 2005;91:229-30.
  2. Collinson PO, Premachandram S, Hashemi K. Prospective audit of incidence of prognostically important myocardial damage in patients discharged from emergency department. BMJ. 2000 Jun 24;320(7251):1702-5.
  3. Myocardial infarction redefined A consensus document of The Joint European Society of Cardiology / American College of Cardiology Committee for the Redefiniton of Myocardial Infarction. Eur Heart J. 2000 Sep;21(18):1502-13. doi: 10.1053/euhj.2000.2305. PMID: 10973764.
  4. Norris RM, Caughey DE, Mercer CJ et al. Prognosis after myocardial infarction. Six year follow-up. Br Heart J1974;36:786-790.
  5. de Vreede JJ, Gorgels AP, Verstraaten GM, et al. Did prognosis after acute myocardial infarction change during the past 30 years? A meta-analysis. J Am Coll Cardiol. 1991 Sep;18(3):698-706.
  6. Assessment of the Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet. 2001 Aug 25;358(9282):605-13.
  7. Norris RM. Fatality outside hospital from acute coronary events in three British districts, 1994-5. United Kingdom Heart Attack Collaborative Study Group. BMJ1998;316:1065-70.
  8. Tunstall-Pedoe H, Kuulasmaa K, Mahonen M, et al. Contribution of trends in survival and coronary event rates to changes in coronary heart disease mortality: 10 year results from 37 WHO MONICA project populations. Monitoring trends and determinants in cardiovascular disease. Lancet 1999;353:1547-57.
  9. Kainth A, Hewitt A, Sowden A et al. Systematic review of interventions to reduce delay in patients with suspected heart attack. Emerg Med J 2004;21:506-508.
  10. Swap CJ and Nagurney JT. Value and limitations of chest pain history in the evaluation of patients with suspected acute coronary syndromes. JAMA 2005;294(20):2623-29.
  11. Panju A, Hemmelgarn B, Guyatt G, and Simel D. Is this patient having a myocardial infarction? JAMA1998;280:1256-63.
  12. Mant J, McManus RJ, Oakes RAL, Delaney BC, et al. Systematic review and modelling of the investigation of acute and chronic chest pain presenting in primary care. Health Technology Assessment 2004;Vol 8:No. 2.
  13. Jaeschke R, Guyatt GH, Sackett DL. Users guide to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me cure my patients? The Evidence Based Medicine Working Group. JAMA 1994;271:703-7.
  14. Canto J, Shlipak M, Rogers W, et al. Prevalence, clinical characteristics, and mortality among patients with acute myocardial infarction presenting without chest pain. JAMA 2000;283:3223-3229.
  15. Verheugt F, Gersh B, Armstrong P. Aborted myocardial infarction: a new target for reperfusion therapy. Eur Heart J2006;27:901-904.
  16. Karlson B, Herlitz J, Wiklund O, Richter A, Hjalmarson A. Early prediction of acute myocardial infarction from clinical history, examination and electrocardiogram in the emergency room. Am J Cardiol 1991;68:171-5.
  17. Fibrinolytic Therapy Trialists (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials with more than 1000 patients. Lancet 1994;343:311-22.
  18. Newby KH, Pisano E, Rukoff MW, et al. Incidence and clinical relevance of the occurrence of bundle branch block in patients treated with thrombolytic therapy. Circulation 1996;94:2424-8.
  19. Sgarbossa EB, Pinski SL, Barbagelata A, et al. Electrocardiographic diagnosis of evolving myocardial infarction in the presence of left bundle branch block. N Engl J Med 1996;334:481-7.
  20. Reuben AD, Mann CJ. Simplifying thrombolysis decisions in patients with left bundle branch block. Emerg Med J2005;22:617-20.
  21. Bertrand M, Simoons M, Fox K, et al. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. The Task Force on the Management of Acute Coronary Syndromes of the European Society of Cardiology. Eur Heart J 2002;23:1809-40.
  22. Jaffe As, Ravkilde J, Roberts R et al. Its time for a change to a troponin standard. Circulation2000;102:1216-20.
  23. Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T. Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I. New Engl J Med 1997;337:1648-53.
  24. Smith SC, Ladenson JH, Mason JW et al. Elevations of cardiac troponin I associated with myocarditis. Circulation1997;95:163-8.
  25. Giannitsis E, Mller-Bardorff M, Kurowski V, et al. Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism. Circulation. 2000 Jul 11;102(2):211-7.
  26. Frankel WL, Herold DA, Ziegler TW et al. Cardiac troponin is elevated in asymptomatic patients with chronic renal failure. Am J Clin Path 1996;106:118-23.
  27. NICE. Unstable angina and NSTEMI: The early management of unstable angina and non-ST-segment-elevation myocardial infarction.. Clinical Guideline 94. National Institute of Health and Clinical Excellence. London, March 2010.
  28. Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina / non-ST elevation MI. JAMA2000;284:835-42.
  29. Boersma E, Pieper KS, Steyerberg EW, et al. for the PURSUIT Investigators. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. Circulation 2000;101:2557-67.
  30. Granger CB, Goldberg RJ, Dabbous OH, et al. for the Global Registry of Acute Coronary Events Investigators. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med 2003;163:2345-53.
  31. Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischaemic events in unstable angina/non-Q wave myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 11B trial.Circulation 1999;100:1593-601.
  32. Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low molecular weight heparin with unfractionated heparin for unstable coronary disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. ESSENCE. N Engl J Med1997;337:447-52.
  33. Sabatine MS, Antmann EM. The Thrombolysis in Myocardial Infarction Risk Score in Unstable Angina / Non-ST-Segment Elevation Myocardial Infarction. J Am Coll Cardiol 2003;41:89S-95S.
  34. Eagle KA, Lim MJ, Dabbous OH, et al. A validated prediction model for all forms of acute coronary syndrome: estimating the 6 month postdischarge death in an international registry. JAMA 2004;291:2727-2733.
  35. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003 ;361 :13-20.
  36. Gruppo Italiano per lo Studio della Streptochinasi nellInfarto Miocardio (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;1:397-401.
  37. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet1988;2:349-60.
  38. Keeley E, Boura J, Grines C. Comparison of primary and facilitated percutaneous coronary interventions for ST-segment elevation myocardial infarction: quantitative review of randomised trials. Lancet2006;367:579-88.
  39. Bonnefoy E, Lapostolle F, Leizorovicz A et al. Primary angioplasty versus prehospital fibrinolysis in acute myocardial infarction: a randomised study. Lancet 2002;360:825-29.
  40. Armstrong PW; WEST Steering Committee. A comparison of pharmacologic therapy with/without timely coronary intervention vs. primary percutaneous intervention early after ST-elevation myocardial infarction: the WEST (Which Early ST-elevation myocardial infarction Therapy) study. Eur Heart J. 2006 Jul;27(13):1530-8.
  41. Nallamothu B, Antman E, Bates E. Primary Percutaneous Coronary Intervention versus Fibrinolytic therapy in Acute Myocardial Infarction: Does the choice of fibrinolytic agent impact on the importance of time to treatment? Am J Cardiol 2004;94:772-4.
  42. Hochman JS, Sleeper LA, Webb JG et al, for the Should We Emergently Revascularise Occluded Coronaries for Cardiogenic Shock (SHOCK) Investigators. Early revascularisation in acute myocardial infarction complicated by cardiogenic shock. NEJM 1999;341:625-34.
  43. National Institute for Health and Clinical Excellence. Acute coronary syndromes [NICE guideline NG185]. 18 November 2020.
  44. ACC/AHA Guidelines for the Management of Patients with ST-elevation Myocardial Infarction. A report of the ACC/AHA Task Force on practice guidelines. Circulation 2004;110:588-636.
  45. The Task Force on the Management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology. Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation.Eur Heart J 2008;29:2909-45.
  46. Boersma E, Mass A, Deckers J et al. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet 1996;348:771-75.
  47. Morrison LJ, Verbeek PR, McDonald AC et al. Mortality and pre-hospital thrombolysis for acute myocardial infarction: a meta-analysis. JAMA 2000;283:2686-92.
  48. MINAP Steering Group. How the NHS manages heart attacks. Sixth Public Report 2008.
  49. White H. Thrombolytic therapy in the elderly. Lancet 2000;356:2028-30.
  50. Gershlick AH, Stephens-Lloyd A, Hughes S et al for the REACT Trial Investigators. Rescue Angioplasty after failed Thrombolytic Therapy for Acute Myocardial Infarction. NEJM 2005;353:2758-68.
  51. Fernandez-Avils F, Alonso JJ, Castro-Beiras A, Vzquez N, et al. Routine invasive strategy within 24 hours of thrombolysis versus ischaemia-guided conservative approach for acute myocardial infarction with ST-segment elevation (GRACIA-1): a randomised controlled trial. Lancet. 2004 Sep 18-24;364(9439):1045-53.
  52. The Task Force for Percutaneous Coronary Interventions of The European Society of Cardiology. Guidelines for percutaneous coronary interventions. Eur Heart J 2005;26:804-47.
  53. Verheugt FW. Lyse now, stent later: the grace of GRACIA. Lancet 2004;364:1014-15.
  54. ASSENT-4 PCI Investigators. Primary versus tenecteplase-facilitated percutaneous coronary intervention in patients with ST-segment elevation acute myocardial infarction (ASSENT-4 PCI): randomised trial. Lancet2006;367:569-78.
  55. Anti-thrombotic Trialists Collaboration. Collaborative meta-analysis of randomised trials of anti-platelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86.
  56. Sabatine MS, Cannon CP, Gibson M et al, for the CLARITY-TIMI 28 Investigators. Addition of Clopidogrel to Aspirin and Fibrinolytic Therapy for Myocardial Infarction with ST-Segment Elevation. N Engl J Med2005;352 (25):2647-57.
  57. COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial) Collaborative Group. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: a randomised placebo-controlled trial. Lancet 2005;366:1607-21.
  58. NICE. Prasugrel for the treatment of acute coronary syndromes with percutaneous coronary intervention. NICE Technology Appraisal Guidance 182. National Institute of Health and Clinical Excellence. London, October 2009.
  59. National Institute of Health and Clinical Excellence. Ticagrelor for the treatment of acute coronary syndromes. NICE Technology Appraisal Guidance [TA236]. 26 October 2011.
  60. de Bono D, Simoons ML, Tijssen J et al. Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomised double blind European Cooperative Study Group trial. Br Heart J 1992;67:122-8
  61. Antman EM, Morrow DA, McCabe C et al. for the EXTRACT-TIMI 25 Investigators. Enoxaparin versus Unfractionated Heparin with Fibrinolysis for ST-Elevation Myocardial Infarction. NEJM 2006;354:1477-88.
  62. The Assessment of Safety and Efficacy of a New Thrombolytic Regimen (ASSENT)-3 Investigators. Efficacy and safety of tenecteplase in combination with enoxaparin, abciximab, or unfractionated heparin: the ASSENT-3 randomised trial in acute myocardial infarction. Lancet 2001;358:605-13.
  63. Wallentin L, Goldstein p, Armstrong P et al. Efficacy and Safety of Tenecteplase in Combination with the Low-Molecular-Weight Heparin Enoxaparin or Unfractionated Heparin in the Prehospital Setting. Circulation 2003;108:135-42.
  64. Fondaparinux in patients with ST-segment elevation acute myocardial infarction not receiving reperfusion treatment. Eur Heart J 2008;29:315-23.
  65. The GUSTO V Investigators. Reperfusion therapy for acute myocardial infarction with fibrinolytic therapy or combined reduced fibrinolytic therapy and platelet glycoprotein IIb/IIIa inhibition: the GUSTO V randomised trial. Lancet2001;375:1905-14.
  66. Theroux P, Ouimet H, McCans J et al. Aspirin, Heparin, or both to treat acute unstable angina.NEJM1988;319:1105-11.
  67. Yusuf S, Zhao F, Mehta SR, et al. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001 Aug 16;345(7):494-502.
  68. Budaj A, Yusuf S, Mehta S et al. Benefit of Clopidogrel in Patients with Acute Coronary Syndromes without ST-Segment Elevation in Various Risk Groups. Circulation 2002;106:1622-26.
  69. NICE. Unstable angina and NSTEMI The early management of unstable angina and non-ST-segment-elevation myocardial infarction. Clinical Guideline 94. National Institute of Health and Clinical Excellence. London, March 2010.
  70. Low-molecular-weight heparin during instability in coronary artery disease, Fragmin during Instability in Coronary Artery Disease (FRISC) study group. Lancet. 1996 Mar 2;347(9001):561-8. PMID: 8596317.
  71. Peterson MD, Mahaffey KW, Hasselblad V et al. Efficacy and Bleeding Complications among Patients Randomised to Enoxaparin or Unfractionated Heparin for Anti-thrombin Therapy in Non-ST-Segment Elevation Acute Coronary Syndromes. A Systematic Overview. JAMA 2004;292:89-96.
  72. Yusuf S, Mehta SR, Chrolavicius S et al. Efficacy and safety of fondaparinux compared to enoxaparin in 20,078 patients with acute coronary syndromes without ST segment elevation. The OASIS (Organisation to Assess Strategies in Acute Ischaemic Syndromes)-5 Investigators. N Engl J Med 2006;354:1464-76.
  73. EPIC Investigators. Use of a monoclonal antibody directed against the platelet Glycoprotein IIB/IIIA receptor inhibitor in high risk angioplasty. N Engl J Med 1994;330:956-61.
  74. EPISTENT Investigators. Randomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with the use of platelet glycoprotein IIB/IIIA blockade. The EPISTENT Investigators. Evaluation of platelet IIB/IIIA Inhibitor for Stenting. Lancet 1998;352:87-92.
  75. ESPRIT. Investigators. Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet 2000;356:2037-44.
  76. CAPTURE Investigators. Randomised placebo-controlled trial of Abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE study. Lancet 1997;349:1429-35.
  77. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. N Engl J Med. 1998 May 21;338(21):1498-505.
  78. PRISM-PLUS. Inhibition of the platelet Glycoprotein IIB/IIIA receptor with tirofiban in unstable angina and non-Q-wave-myocardial infarction. Platelet Receptor Inhibition in Ischaemic Syndrome Mangement in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators. N Engl J Med1998;338:1488-97.
  79. PARAGON Investigators. International, randomised, controlled trial of lamifiban (a platelet glycoprotein IIB/IIIA inhibitor), heparin, or both in unstable angina. The PARAGON Investigators. Platelet IIB/IIIA Antagonism for the Reduction of Acute coronary syndrome events in a Global Organisation Network. Circulation 1998;97:2386-95.
  80. Global Organization Network (PARAGON)-B Investigators. Randomized, placebo-controlled trial of titrated intravenous lamifiban for acute coronary syndromes. Circulation. 2002 Jan 22;105(3):316-21.
  81. PURSUIT Investigators. Inhibition of Platelet glycoprotein IIB/IIIA with eptifibatide in patients with acute coronary syndromes. The PURSUIT Trial Investigators. Platelet Glycoprotein IIB/IIIA in Unstable Angina: Receptor Suppression using Integrilin Therapy. N Engl J Med 1998;339:436-43.
  82. GUSTO-IV ACS Investigators. Effect of glycoprotein IIB/IIIA receptor blocker abciximab on outcome of patients with acute coronary syndromes without early revascularisation: The GUSTO-IV ACS randomised trial. Lancet2001;357:1915-24.
  83. Boersma E, Harrington R, Moliterno D et al. Platelet Glycoprotein IIB/IIIA inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 2002;359:189-198.
  84. Roffi M, Chew DP, Mukherjee D et al. Platelet glycoprotein IIB/IIIA inhibitors reduce mortality in diabetic patients with Non-ST segment elevation acute coronary syndromes. Circulation. 2002.;105:316-21.
  85. Technology Appraisal Guidance Number 47. National Institute for Clinical Excellence. Guidance on the use of GpIIB/IIIA receptor inhibitors in the treatment of acute coronary syndromes. September 2002.
  86. Curfman G, Heinsimir J, Lozner E et al. Intravenous nitroglycerin in the treatment of spontaneous angina pectoris: a prospective randomised trial. Circulation 1983;67:276-82.
  87. Dellborg M, Gustafsson G, Swedberg K. Buccal versus intravenous nitroglycerin in unstable angina pectoris. Eur J Clin Pharmacol 1991;41:5-9.
  88. Yusuf S, Wittes J, Friedman L. Overview of results of randomised clinical Calcium channel blockerstrials in heart disease. Unstable angina, heart failure, primary prevention with aspirin, and risk factor modification. JAMA 1988;260:2259-63.
  89. Theroux P, Taeymans Y, Morissette et al. A randomised study comparing proranolol and diltiazem in the treatment of unstable angina. J Am Coll Cardiol 1985;5:717-22.
  90. Held P, Furberg C. Calcium channel blockers in acute myocardial infarction and unstable angina: an overview. Br Med J 1989;299:1187-92.
  91. Mehta SR, Yusuf S, Peters RJ et al. Effects of pre-treatment with clopidogrel and aspirin followed by long term therapy in patients undergoing percutaneous coronary intervention: the PERI-CURE Study. Lancet2001;358:527-33.
  92. Cannon C, Weintraub W, Demopoulos L et al. for the TACTICS-Thrombolysis in Myocardial Infarction 18 Investigators. Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with glycoprotein IIB/IIIA inhibitor tirofiban. N Engl J Med 2001;344:1879-87.
  93. FRISC II Investigators. Invasive compared with non-invasive treatment in unstable coronary artery disease: FRISC II prospective randomised multicentre study. Fragmin and Fast Revascularisation during InStability in Coronary artery disease investigators. Lancet 1999;354:708-15.
  94. Fox K, Poole-Wilson P, Henderson R et al. Randomized Intervention Trial of unstable Angina Investigators. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Randomized Intervention Trial of unstable Angina. Lancet. 2002 Sep 7;360(9335):743-51.
  95. Hoenig MR, Doust JA, Aroney CN, et al. Early invasive versus conservative strategies for unstable angina and non-ST-elevation myocardial infarction in the stent era. Cochrane Database Syst Rev 2006;3:CD004815.
  96. Hochman JS, Sleeper LA, Webb JG et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. N Engl J Med. 1999 Aug 26;341(9):625-34.
  97. Becker RC, Hochman JS, Cannon CP et al. Fatal cardiac rupture among patients treated with thrombolytic agents and adjunctive thrombin antagonists: observations from the TIMI 9 study. J Am Coll Cardiol 1999;33:479-87.
  98. National Institute for Health and Clinical Excellence. Recent-onset chest pain of suspected cardiac origin: assessment and diagnosis [NICE guideline CG95]. Updated: 30 November 2016.
  99. Resuscitation Council (UK) May 2021 Advanced Life Support Course Provider Manual is in the 8th Edition.

Leave a Reply