PATHOPHYSIOLOGY, INVESTIGATIONS, AND MANAGEMENT OF UNSTABLE ANGINA: A REVIEW
OMAR ELSAKA *
Department of Cardiology, Mansoura University, Faculty of Medicine, Mansoura Manchester Medical Program (MMMP), Mansoura, Egypt.
MONEER AYMAN NOURELDEAN
Department of Cardiology, Mansoura University, Faculty of Medicine, Mansoura Manchester Medical Program (MMMP), Mansoura, Egypt.
MOHAMED ADEL GAMIL
Department of Cardiology, Mansoura University, Faculty of Medicine, Mansoura Manchester Medical Program (MMMP), Mansoura, Egypt.
MOSTAFA TAREK GHAZALI
Department of Cardiology, Mansoura University, Faculty of Medicine, Mansoura Manchester Medical Program (MMMP), Mansoura, Egypt.
ASHRAF HAMADA ABD AL-RAZIK
Department of Cardiology, Mansoura University, Faculty of Medicine, Mansoura Manchester Medical Program (MMMP), Mansoura, Egypt.
DALIA HISHAM
Department of Cardiology, Mansoura University, Faculty of Medicine, Mansoura Manchester Medical Program (MMMP), Mansoura, Egypt.
*Author to whom correspondence should be addressed.
Abstract
Unstable angina pectoris is a phenomenon that disrupts the early recovery phase of acute myocardial infection, the emergence of new ischemic symptoms, the development of more severe pain, usually at rest, or the formation of intermittent ischemic events. ۔ Acute myocardial infarction is the most serious complication of unstable angina pectoris, which can affect up to 25% of patients within three months of the onset of symptoms. Physically, changes in ECG and hemodynamics usually occur before the onset of pain. The following hemodynamic changes and an increase in oxygen demand in the already ischemic heart respond positively, leading to further instability in unstable angina. Hemodynamic changes may be the result of abnormal stress response or excessive chemotherapeutic discharge. While coronary spasm may play a role in the pathogenesis of unstable angina, other factors such as bleeding in the wall of the atherosclerotic plaque, peripheral embolization, alteration, or platelet aggregation in the coronary artery from nearby soft cholesterol "abscess". Feedback should also be considered. Along with medications such as nitrates, calcium antagonists, and warnings, beta-adrenergic blockers are used to stimulate coronary and peripheral vasodilation and reduce cardiac effort. Treatment with aortic counter-pulsating balloons is recommended for those who have failed to respond to pharmacological treatment. Emergency surgery should be performed voluntarily. The full clinical and pathological compatibility of unstable angina pectoris is still unknown. Future issues will revolve around further investigations into entity procedures, treatment and prevention. The purpose of this review is to explain the pathophysiology of unstable angina, highlight changes in ECG in the assessment of unstable angina, and improve the outcome of patients with unstable angina. Consider the need to strengthen the coordination of care within the team.
Keywords: Acute coronary syndrome, mortality, myocardial infarction, troponin, unstable angina pectoris
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American Diabetes Association. Standards of Medical Care in Diabetes-2016 Abridged for Primary Care Providers. Clin Diabetes. 2016 Jan. 34 (1):3-21.
Amsterdam EA, Wenger NK, Brindis RG, et al. For the ACC/AHA Task Force Members. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Dec 23;130(25):e344-426.
Anderson HV, Cannon CP, Stone PH, et al. One-year results of the Thrombolysis in Myocardial Infarction (TIMI) IIIB clinical trial. A randomized comparison of tissue-type plasminogen activator versus placebo and early invasive versus early conservative strategies in unstable angina and non-Q wave myocardial infarction. J Am Coll Cardiol. 1995 Dec;26(7):1643-50.
Basra SS, Virani SS, Paniagua D, Kar B, Jneid H. Acute coronary syndromes: unstable angina and non-ST elevation myocardial infarction. Heart Fail Clin. 2016 Jan;12 (1):31-48.
Bonaca MP, Bhatt DL, Cohen M, et al, for the PEGASUS-TIMI 54 Steering Committee and Investigators. Long-term use of ticagrelor in patients with prior myocardial infarction. N Engl J Med. 2015 May 7;372 (19):1791-800.
Cannon CP, McCabe CH, Stone PH, et al. The electrocardiogram predicts one-year outcome of patients with unstable angina and non-Q wave myocardial infarction: Results of the TIMI III Registry ECG Ancillary Study. Thrombolysis in Myocardial Ischemia. J Am Coll Cardiol. 1997 Jul;30(1):133-40.
Castini D, Centola M, Ferrante G, Cazzaniga S, Persampieri S, Lucreziotti S, Salerno-Uriarte D, Sponzilli C, Carugo S. Comparison of CRUSADE and ACUITY-HORIZONS Bleeding Risk Scores in Patients With Acute Coronary Syndromes. Heart Lung Circ. 2019 Apr;28(4):567-574.
Clark MG, Beavers C, Osborne J. Managing the acute coronary syndrome patient: Evidence based recommendations for anti-platelet therapy. Heart Lung. 2015 Mar-Apr;44(2):141-9.
Damman P, Hirsch A, Windhausen F, Tijssen JG, de Winter RJ. 5-year clinical outcomes in the ICTUS (Invasive versus Conservative Treatment in Unstable coronary Syndromes) trial a randomized comparison of an early invasive versus selective invasive management in patients with non-ST-segment elevation acute coronary syndrome. J Am Coll Cardiol. 2010 Mar 2;55(9):858-64.
De Servi S, Goedicke J, Schirmer A, Widimsky P. Clinical outcomes for prasugrel versus clopidogrel in patients with unstable angina or non-ST-elevation myocardial infarction: an analysis from the TRITON-TIMI 38 trial. Eur Heart J Acute Cardiovasc Care. 2014 Dec;3(4):363-72.
Direct thrombin inhibitors in acute coronary syndromes: principal results of a meta-analysis based on individual patients' data. Lancet. 2002 Jan 26;359(9303):294-302.
Eggers KM, Jernberg T, Lindahl B. Unstable angina in the era of cardiac troponin assays with improved sensitivity-a clinical dilemma. Am J Med. 2017 Dec;130 (12):1423-30.e5.
Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: Primary results of the SYNERGY randomized trial. JAMA. 2004 Jul 7;292(1):45-54.
Fiotti N, Moretti ME, Bussani R, et al. Features of vulnerable plaques and clinical outcome of UA/NSTEMI: Relationship with matrix metalloproteinase functional polymorphisms. Atherosclerosis. 2011 Mar; 215(1):153-9.
Fox KA, Poole-Wilson PA, Henderson RA, et al. 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.
George J, Mathur R, Shah AD, Pujades-Rodriguez M, Denaxas S, Smeeth L, Timmis A, Hemingway H. Ethnicity and the first diagnosis of a wide range of cardiovascular diseases: Associations in a linked electronic health record cohort of 1 million patients. PLoS One. 2017;12(6):e0178945.
Gurses KM, Kocyigit D, Yalcin MU, et al. Enhanced platelet toll-like receptor 2 and 4 expression in acute coronary syndrome and stable angina pectoris. Am J Cardiol. 2015 Dec 1;116 (11):1666-71.
Harrap SB, Zammit KS, Wong ZY, et al. Genome-wide linkage analysis of the acute coronary syndrome suggests a locus on chromosome 2. Arterioscler Thromb Vasc Biol. 2002 May 1;22(5):874-8.
Hedayati T, Yadav N, Khanagavi J. Non-ST-segment acute coronary syndromes. Cardiol Clin. 2018 Feb;36(1):37-52.
Helwani MA, Amin A, Lavigne P, Rao S, Oesterreich S, Samaha E, Brown JC, Nagele P. Etiology of Acute Coronary Syndrome after Noncardiac Surgery. Anesthesiology. 2018 Jun;128(6):1084-1091.
Hoekstra JW, Pollack CV Jr, Roe MT, et al. Improving the care of patients with non-ST-elevation acute coronary syndromes in the emergency department: the CRUSADE initiative. Acad Emerg Med. 2002 Nov;9(11):1146-55.
Ibbotson T, McGavin JK, Goa KL. Abciximab: an updated review of its therapeutic use in patients with ischaemic heart disease undergoing percutaneous coronary revascularisation. Drugs. 2003;63(11):1121-63.
Januzzi JL, Cannon CP, DiBattiste PM, Murphy S, Weintraub W, Braunwald E. Effects of renal insufficiency on early invasive management in patients with acute coronary syndromes (The TACTICS-TIMI 18 Trial). Am J Cardiol. 2002 Dec 1;90(11):1246-9.
Kwong RY, Chan AK, Brown KA, et al. Impact of unrecognized myocardial scar detected by cardiac magnetic resonance imaging on event-free survival in patients presenting with signs or symptoms of coronary artery disease. Circulation. 2006 Jun 13;113(23):2733-43.
Kwong RY, Sattar H, Wu H, et al. Incidence and prognostic implication of unrecognized myocardial scar characterized by cardiac magnetic resonance in diabetic patients without clinical evidence of myocardial infarction. Circulation. 2008 Sep 2;118(10): 1011-20.
Li Z, Liu X, Wang J, et al. Analysis of urinary metabolomic profiling for unstable angina pectoris disease based on nuclear magnetic resonance spectroscopy. Mol Biosyst. 2015 Dec 10;11 (12):3387-96.
Lippi G, Favaloro EJ. Myocardial Infarction, Unstable Angina, and White Thrombi: Time to Move Forward? Semin Thromb Hemost. 2019 Feb;45(1):115-116.
Lu MT, Ferencik M, Roberts RS, Lee KL, Ivanov A, Adami E, Mark DB, Jaffer FA, Leipsic JA, Douglas PS, Hoffmann U. Noninvasive FFR Derived From Coronary CT Angiography: Management and Outcomes in the PROMISE Trial. JACC Cardiovasc Imaging. 2017 Nov;10(11):1350-1358.
Luepker RV. WHO MONICA project: what have we learned and where to go from here?. Public Health Rev. 2012;33(2):373-96.
Accessed: May 8, 2013.
Manzoli A, Andreotti F, Varlotta C, et al. Allelic polymorphism of the interleukin-1 receptor antagonist gene in patients with acute or stable presentation of ischemic heart disease. Cardiologia. 1999 Sep;44(9):825- 30.
Maroo A, Lincoff AM. Bivalirudin in PCI: an overview of the REPLACE-2 trial. Semin Thromb Hemost. 2004 Jun;30(3):329-36.
Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med. 2009 Jan 22;360(4):354-62.
Mehta SR, Granger CB, Eikelboom JW, et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial. J Am Coll Cardiol. 2007 Oct 30;50(18):1742-51.
Meune C, Balmelli C, Twerenbold R, et al. Patients with acute coronary syndrome and normal high-sensitivity troponin. Am J Med. 2011 Dec;124(12):1151-7.
Misra D, Leibowitz K, Gowda RM, Shapiro M, Khan IA. Role of N-acetylcysteine in prevention of contrast-induced nephropathy after cardiovascular procedures: A meta-analysis. Clin Cardiol. 2004 Nov;27(11):607-10.
Murphy SA, Cannon CP, Wiviott SD, McCabe CH, Braunwald E. Reduction in recurrent cardiovascular events with intensive lipid-lowering statin therapy compared with moderate lipid-lowering statin therapy after acute coronary syndromes from the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) trial. J Am Coll Cardiol. 2009 Dec 15;54(25):2358-62.
Neumann FJ, Kastrati A, Pogatsa-Murray G, et al. Evaluation of prolonged antithrombotic pretreatment ("cooling-off" strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial. JAMA. 2003 Sep 24;290(12):1593-9.
Nisbet BC, Zlupko G. Repeat Wellens' syndrome: case report of critical proximal left anterior descending artery restenosis. J Emerg Med. 2010 Sep;39(3):305-8.
Nowak R, Mueller C, Giannitsis E, et al. High sensitivity cardiac troponin T in patients not having an acute coronary syndrome: results from the TRAPID-AMI study. Biomarkers. 2017 Dec;22 (8):709-14.
O'Connor FF, Shields DC, Fitzgerald A, Cannon CP, Braunwald E, Fitzgerald DJ. Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes. Blood. 2001 Dec 1;98(12):3256-60.
Pare G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med. 2010 Oct 28;363(18):1704-14.
Park KW, Kim HS. Options to overcome clopidogrel response variability. Circ J. 2012;76(2):287-92.
Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation. 2003 Oct 7;108(14):1682-7.
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. 2001 Dec 4;104(23): 2767-71.
Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016 Jan 14;37 (3):267-315.
Rottger E, de Vries-Spithoven S, Reitsma JB, et al. Safety of a 1-hour rule-out high-sensitive troponin T protocol in patients with chest pain at the emergency department. Crit Pathw Cardiol. 2017 Dec;16(4):129-34.
Sabatine MS, Giugliano RP, Keech AC, et al, for the FOURIER Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017 May 4;376(18):1713-22.
Schwartz GG, Olsson AG, Ezekowitz MD, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: The MIRACL study: A randomized controlled trial. JAMA. 2001 Apr 4;285(13):1711-8.
Shah AP, Nathan S. Challenges in Implementation of Institutional Protocols for Patients With Acute Coronary Syndrome. Am J Cardiol. 2018 Jul 15;122(2):356-363.
Simoons ML. Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial. Lancet. 2001 Jun 16;357(9272):1915-24.
Skolnick AH, Alexander KP, Chen AY, et al. Characteristics, management, and outcomes of 5,557 patients age > or =90 years with acute coronary syndromes: Results from the CRUSADE Initiative. J Am Coll Cardiol. 2007 May 1;49(17):1790-7.
Smith R, Frazer K, Hyde A, O'Connor L, Davidson P. Heart disease never entered my head: Women's understanding of coronary heart disease risk factors. J Clin Nurs. 2018 Nov;27(21-22):3953-3967.
Soukoulis V, Boden WE, Smith SC Jr, O'Gara PT. Nonantithrombotic medical options in acute coronary syndromes: old agents and new lines on the horizon. Circ Res. 2014 Jun 6;114(12):1944-58.
Stamou SC, Camp SL, Stiegel RM, Reames MK, Skipper E, Watts LT, Nussbaum M, Robicsek F, Lobdell KW. Quality improvement program decreases mortality after cardiac surgery. J Thorac Cardiovasc Surg. 2008 Aug;136(2):494-499.e8.
Steinhubl SR, Berger PB, Mann JT 3rd, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: A randomized controlled trial. JAMA. 2002 Nov 20;288(19):2411-20.
Stone GW, Maehara A, Lansky AJ, et al. A prospective natural-history study of coronary atherosclerosis. N Engl J Med. 2011 Jan 20;364(3):226-35.
Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med. 2006 Nov 23;355(21):2203-16.
Susilovic Grabovac Z, Bakovic D, Lozo M, Pintaric I, Dujic Z. Early changes in platelet size and number in patients with acute coronary syndrome. Int J Angiol. 2017 Dec;26 (4):249-52.
Szarek M, White HD, Schwartz GG, et al. For the Odyssey Outcomes Committees and Investigators. Alirocumab reduces total nonfatal cardiovascular and fatal events: The ODYSSEY OUTCOMES Trial. J Am Coll Cardiol. 2019 Feb 5;73 (4):387-96.
Taguchi I, Iimuro S, Iwata H, Takashima H, Abe M, Amiya E, et al. High-Dose Versus Low-Dose Pitavastatin in Japanese Patients With Stable Coronary Artery Disease (REAL-CAD): A Randomized Superiority Trial. Circulation. 2018 May 08;137(19):1997-2009.
Tanindi A, Erkan AF, Ekici B. Epicardial adipose tissue thickness can be used to predict major adverse cardiac events. Coron Artery Dis. 2015 Dec;26 (8):686-91.
Tegn N, Abdelnoor M, Aaberge L, et al, for the After Eighty study investigators. Health-related quality of life in older patients with acute coronary syndrome randomised to an invasive or conservative strategy. The After Eighty randomised controlled trial. Age Ageing. 2018 Jan 1;47 (1):42-7.
Than M, Cullen L, Reid CM, et al. A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): A prospective observational validation study. Lancet. 2011 Mar 26;377(9771):1077-84.
Theroux P, Waters D, Lam J, Juneau M, McCans J. Reactivation of unstable angina after the discontinuation of heparin. N Engl J Med. 1992 Jul 16;327(3):141-5.
Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Eur Heart J. 2012 Oct;33(20):2551-67.
Tocci G, Figliuzzi I, Presta V, Miceli F, Citoni B, Coluccia R, Musumeci MB, Ferrucci A, Volpe M. Therapeutic Approach to Hypertension Urgencies and Emergencies During Acute Coronary Syndrome. High Blood Press Cardiovasc Prev. 2018 Sep;25(3):253-259.
Tziakas DN, Chalikias GK, Antonoglou CO, et al. Apolipoprotein E genotype and circulating interleukin-10 levels in patients with stable and unstable coronary artery disease. J Am Coll Cardiol. 2006 Dec 19; 48(12):2471-81.
Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57.
Wallentin L, Lagerqvist B, Husted S, Kontny F, Stale E, Swahn E. Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. FRISC II Investigators. Fast Revascularisation during Instability in Coronary artery disease. Lancet. 2000 Jul 1;356(9223):9-16.
White AJ, Duffy SJ, Walton AS, et al. Matrix metalloproteinase-3 and coronary remodelling: implications for unstable coronary disease. Cardiovasc Res. 2007 Sep 1. 75(4):813-20.
Willerson JT. Systemic and local inflammation in patients with unstable atherosclerotic plaques. Prog Cardiovasc Dis. 2002 May-Jun;44(6):469-78.
Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK. 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.
Zhao YH, Xu Y, Gu YY, Li Y, Zhang JY, Su X. Functional effect of platelet membrane glycoprotein ia gene polymorphism in the pathogenesis of unstable angina pectoris. J Int Med Res. 2011;39(2):541-8.