Unstable angina non ST elevation myocardial infarction overview: Difference between revisions

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{{Unstable angina / NSTEMI}}
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{{CMG}}; '''Associate Editors-In-Chief:''' [[Varun Kumar]], M.B.B.S; [[Lakshmi Gopalakrishnan]], M.B.B.S.; {{CZ}}; {{NMG}}; Smita Kohli, M.D.  
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| [[Unstable angina/ NSTEMI resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
|}{{Unstable angina / NSTEMI}}
 
{{CMG}}; {{AOEIC}} [[User:Maheep Sangha|Maheep Singh Sangha, M.B.B.S.]]; [[Varun Kumar]], M.B.B.S; [[Lakshmi Gopalakrishnan]], M.B.B.S.; {{CZ}}; {{NMG}}; Smita Kohli, M.D.
 
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==Overview==
==Overview==
[[Unstable angina]] and Non ST elevation myocardial infarction ([[NSTEMI]]) belong to two different ends of the spectrum of [[acute coronary syndrome]].  Unstable angina is differentiated from NSTEMI by the absence of elevated cardiac biomarkers.  The basic pathology in both the conditions involves a non-occlusive thrombus formation from a previously disrupted atherosclerotic plaque causing inadequate blood supply to the heart muscle.


==The Spectrum of Acute Coronary Syndromes==
==The Spectrum of Acute Coronary Syndromes==
*[[Acute coronary syndrome]]s ([[ACS]]) is a term that encompasses:
[[Acute coronary syndrome]]s ([[ACS]]) is a term that encompasses:
:*[[Unstable angina]] ([[UA]]),  
*[[Unstable angina]] ([[UA]]),  
:*[[Non-ST-segment elevation myocardial infarction]] ([[NSTEMI]]) and  
*[[Non-ST-segment elevation myocardial infarction]] ([[NSTEMI]]), and  
:*[[ST-segment elevation myocardial infarction]] ([[STEMI]]).   
*[[ST-segment elevation myocardial infarction]] ([[STEMI]]).   


*While all three usually result from [[atherosclerotic plaque rupture]] and subsequent [[thrombus|thrombus formation]] in one of the main epicardial coronary arteries, with subsequent inadequate blood supply to meet the oxygen and metabolic demands of the [[myocardium]]. Other possible etiologies of this imbalance such as coronary artery narrowing alone, [[coronary spasm]], or [[coronary dissection]].  
While all three usually result from [[atherosclerotic plaque rupture]] and subsequent [[thrombus|thrombus formation]] in one of the main epicardial coronary arteries, with subsequent inadequate blood supply to meet the oxygen and metabolic demands of the [[myocardium]]. Other possible etiologies of this imbalance such as coronary artery narrowing alone, [[coronary spasm]], or [[coronary dissection]].  


*Unstable angina, [[NSTEMI]] and [[STEMI]] are distinguished pathophysiologically as to whether or not the [[thrombus]] is '''occlusive''' (as in the case of [[STEMI]]) or '''non-occlusive'''(as in the case of [[UA]] and [[NSTEMI]]).   
Unstable angina, [[NSTEMI]] and [[STEMI]] are distinguished pathophysiologically as to whether or not the [[thrombus]] is occlusive (as in the case of [[STEMI]]) or non-occlusive (as in the case of [[UA]] and [[NSTEMI]]).   
:*If an electrocardiogram ([[EKG]]) is performed at the time that an [[occlusive coronary artery thrombus]] is formed, it will usually show [[ST-segment elevation]] in the leads which correspond to the territory of [[myocardium]] in which blood supply has been disrupted (see [[ST Elevation Myocardial Infarction Electrocardiogram|Electrocardiogram]]).   
*If an electrocardiogram ([[EKG]]) is performed at the time that an [[occlusive coronary artery thrombus]] is formed, it will usually show [[ST-segment elevation]] in the leads which correspond to the territory of [[myocardium]] in which blood supply has been disrupted (see [[ST Elevation Myocardial Infarction Electrocardiogram|Electrocardiogram]]).   
:*If an EKG is performed at the time that a [[non-occlusive thrombus]] is formed, it may or may not show signs of [[ischemia]](see [[Unstable angina / NSTEMI ECG|Electrocardiogram]]).   
*If an EKG is performed at the time that a [[non-occlusive thrombus]] is formed, it may or may not show signs of [[ischemia]] (see [[Unstable angina / NSTEMI ECG|Electrocardiogram]]).   


*Frequently, [[Unstable Angina]] and [[NSTEMI]] are indistinguishable on inital evaluation as these two conditions are at different spectrums of [[ischemia]].  If the ischemia is significant to cause myocardial damage, there will be an elevation of Cardiac biomarkers ([[CK-MB]] or [[troponin]]) and would be classified as an [[NSTEMI]](see [[Unstable angina / NSTEMI bio markers|Biomarkers]]).  Often, these may not be detected for up to 12 hours in the bloodstream, which emphasizes the need for thorough evaluation. <ref name="Anderson"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' Circulation 2007 116: e148 – e304. PMID 17679616</ref> <ref name="Anderson2"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. Correction of ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' J Am Coll Cardiol. 2008 Mar 4; 51(9): 974. PMID 17692738 </ref>
Frequently, [[Unstable Angina]] and [[NSTEMI]] are indistinguishable on inital evaluation as these two conditions are at different spectrums of [[ischemia]].  If the ischemia is significant to cause myocardial damage, there will be an elevation of Cardiac biomarkers ([[CK-MB]] or [[troponin]]) and would be classified as an [[NSTEMI]] (see [[Unstable angina / NSTEMI bio markers|Biomarkers]]).  Often, these may not be detected for up to 12 hours in the bloodstream, which emphasizes the need for thorough evaluation.<ref name="Anderson"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' Circulation 2007 116: e148 – e304. PMID 17679616</ref><ref name="Anderson2"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. Correction of ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' J Am Coll Cardiol. 2008 Mar 4; 51(9): 974. PMID 17692738 </ref>


==Definition==
==Definition==
'''Unstable Angina ([[UA]]):'''
====Unstable Angina====
[[Angina pectoris]] is classified as stable when its characteristics are unchanged for 60 days. [[Stable angina pectoris]] usually responds to sublingual [[nitroglycerin]] or rest.  [[Unstable angina]] occurs at rest and may not improve with rest.
Unstable angina is defined as new onset [[angina pectoris]] (or [[chest pain]] which is [[ischemic]] in origin) with the following features: a) occurs at rest or with lesser degrees of exertion than [[stable angina]], b) lasts less than 30minutes, c) follows a crescendo pattern (i.e., occurs more frequently than previous), and d) there no sign of [[myocardial necrosis]] unlike in [[STEMI]] or [[NSTEMI]], and there is no release of biomarkers of myonecrosis ([[CK]] or [[troponin]]). <ref>Ambrose JA, Winters SL, Stern A, et al: Angiographic morphology and the pathogenesis of unstable angina pectoris. J Am Coll Cardiol 1985 Mar; 5(3): 609-16. PMID 3973257</ref><ref>Crea F, Biasucci LM, Buffon A, Liuzzo G, Monaco C, Caligiuri G, et al. Role of inflammation in the pathogenesis of unstable coronary artery disease. Am J Cardiol 1997; 80: 10-6E. PMID 9296463</ref><ref>Biasucci LM, Colizzi C, Rizzello V, Vitrella G, Crea F, Liuzzo G. 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====Non ST Elevation Myocardial Infarction====
Non-ST Elevation MI ([[NSTEMI]]) presents with clinical features of [[UA]] along with the evidence of [[myocardial necrosis]] like elevated serum levels of cardiac [[Unstable angina / NSTEMI bio markers|biomarkers]] (i.e., creatine kinase ([[CK]]), [[MB]] isoenzyme of CK ([[CK-MB]]) and [[Troponin]]s I and T). [[Troponin]]s are fairly sensitive and specific for [[myocardial necrosis]]. For the diagnosis of [[NSTEMI]] to be made, the [[troponin]] elevation must occur in the context of ischemic [[chest pain]], however the diagnosis should not be made based on laboratory findings alone, as there are other possible etiologies for elevated [[troponin]]s.<ref name="Anderson"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' Circulation 2007 116: e148 – e304. PMID 17679616</ref> <ref name="Anderson2"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. Correction of ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' J Am Coll Cardiol. 2008 Mar 4; 51(9): 974. PMID 17692738 </ref>


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ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' Circulation 2007 116: e148 – e304. PMID 17679616</ref> <ref name="Anderson2"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. 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Coronary vasospasm-induced acute coronary syndrome complicated by life-threatening cardia arrhythmias in patients without hemodynamically significant coronary artery disease. ''Int J Cardiol'' 2007; 117:37-44. PMID 16844245</ref> <ref>Yuksel UD, Celik T, Iyisoy A, et al:. Polymorphic ventricular tachycardia induced by coronary vasospasm: A malignant case of variant angina. Int J Cardiol, 2006. E-pubahead of print, Nov. 22, 2006. PMID 17125857 </ref> <ref>Kawano H, Motoyama T, Yasue H, et al: Endothelial function fluctuates with diurnal variation in the frequency of ischemic episodes in patients with variant angina. ''J Am Coll Cardiol'' 2002; 40:266-270. PMID 12106930</ref> <ref>Matsuguchi T, Araki H, Nakamura N, et al: Prevention of vasospastic angina by alcohol ingestion: Report of 2 cases. ''Angiology'' 1988; 39:394-400. PMID 3364807</ref> <ref>Raxwal V, Gupta K: Images in cardiovascular medicine. Coronary artery spasm. ''Circulation'' 2006; 113:e689-e690. PMID 16606795</ref> <ref>Chen HS, Pinto DS: Images in clinical medicine. Prinzmetal's angina. ''N Engl J Med'' 2003; 349:e1. PMID 12840104</ref> <ref>Wang K, Asinger RW, Marriott HJ: ST-segment elevation in conditions other than acute myocardial infarction. ''N Engl J Med'' 2003; 349:2128-2135. PMID 14645641</ref> <ref>Unverdorben M, Haag M, Fuerste T, et al: Vasospasm in smooth coronary arteries as a cause of asystole and syncope. ''Cathet Cardiovasc Diagn'' 1997; 41:430-434. PMID 9258492 </ref> <ref>Lip GY, Gupta J, Khan MM, Singh SP: Recurrent myocardial infarction with angina and normal coronary arteries. ''Int J Cardiol'' 1995; 51:65-71. PMID 8522399</ref> <ref>Pepine CJ, el-Tamimi H, Lambert CR: Prinzmetal's angina (variant angina). ''Heart Dis Stroke'' 1992; 1:281-286. PMID 1344118</ref> <ref>Crea F: Variant angina in patients without obstructive coronary atherosclerosis: a benign form of spasm. ''Eur Heart J'' 1996; 17:980-982. PMID 8809510</ref> <ref>Hirano Y, Ueharfa H, Nakamura H, et al: Diagnosis of vasospastic angina: Comparison of hyperventilation and cold-pressor stress echocardiography, and coronary angiography with intracoronary injection of acetylcholine. ''Int J Cardiol'' 2007; 116:331-337. PMID 16890307</ref> <ref>Nakao K, Ohgushi M, Yoshimura M, et al: Hyperventilation as a specific test for diagnosis of coronary artery spasm. ''Am J Cardiol'' 1997; 80:545-549. PMID 9294979</ref> <ref>Antman E, Muller J, Goldberg S, et al: Nifedepine therapy for coronary artery spasm. Experience in 127 patients.  ''N Engl J Med''  1980; 302:1269-1273. PMID 6767986</ref> <ref>De Cesare N, Cozzi S, Apostolo A, et al: Facilitation of coronary spasm by propranolol in Prinzmetal's angina: Fact or unproven extrapolation?. ''Coron Artery Dis'' 1994; 5:323-330. PMID 8044344</ref> <ref>Tzivoni D, Keren A, Benhorin J, et al: Prazosin therapy for refractory variant angina.''Am Heart J'' 1983; 105:262-266. PMID 6823808 </ref> <ref>Kaski JC: Management of vasospastic angina—role of nicorandil. ''Cardiovasc Drugs Ther 9 Suppl'' 1995; 2:221-227. PMID 7647026</ref> <ref>Kawano H, Motoyama T, Hirai N, et al: Estradiol supplementation suppresses hyperventilation-induced attacks in postmenopausal women with variant angina. ''J Am Coll Cardiol'' 2001; 37:735-740. PMID 11693745</ref> <ref>Tanabe Y, Itoh E, Suzuki K, et al: Limited role of coronary angioplasty and stenting in coronary spastic angina with organic stenosis. ''J Am Coll Cardiol'' 2002; 39:1120-1126. PMID 11923034 </ref> <ref>Meisel SR, Mazur A, Chetboun I, et al: Usefulness of implantable cardioverter-defibrillators in refractory variant angina pectoris complicated by ventricular fibrillation in patients with angiographically normal coronary arteries. ''Am J Cardiol'' 2002; 89:1114-1116. PMID 11988204</ref> <ref>Bory M, Pierron F, Panagides D, et al: Coronary artery spasm in patients with normal or near normal coronary arteries. Long-term follow-up of 277 patients. ''Eur Heart J'' 1996; 17:1015-1021. PMID 8809518</ref> <ref>Shimokawa H, Nagasawa K, Irie T, et al: Clinical characteristics and long-term prognosis of patients with variant angina. A comparative study between western and Japanese populations. ''Int J Cardiol'' 1998; 18:331-349. PMID 3129375</ref> <ref>Tashiro H, Shimokawa H, Koyanagi S, Takeshita A: Clinical characteristics of patients with spontaneous remission of variant angina. ''Jpn Circ J'' 1993; 57:117-122. PMID 8450595 </ref> is defined as new onset [[angina pectoris]] (or [[chest pain]] which is [[ischemic]] in origin) with the following features:
==Classification==
:*occurs at rest or with lesser degrees of exertion than [[stable angina]],
Braunwald in 1989 proposed a classification for [[unstable angina]] based on severity and clinical circumstances.  This classification was employed in various clinical trials and studies to determine its prognostic importance and clinical usefulness.  In recent years with the more detailed understanding of the pathophysiology of unstable angina and the discovery of improved markers of myocardial injury, acute phase proteins and hemostatic markers, especially cardiac [[troponin I]] and [[troponin T]], it was suggested to extend Class IIIB (angina at rest within the past 48 hrs) of the original classification, by subclassifying it into troponin negative and troponin positive patients.
:*lasts less than 30minutes,
:*follows a crescendo pattern (i.e., occurs more frequently than previous)
:*there no sign of [[myocardial necrosis]] unlike in [[STEMI]] or [[NSTEMI]], and there is no release of biomarkers of myonecrosis ([[CK]] or [[troponin]]).  


'''Non-ST Elevation MI ([[NSTEMI]]):'''
==Pathophysiology==
*[[NSTEMI]] presents with clinical features of [[UA]] along with the evidence of [[myocardial necrosis]] like elevated serum levels of cardiac [[Unstable angina / NSTEMI bio markers|Biomarkers]] (i.e., creatine kinase ([[CK]]), [[MB]] isoenzyme of CK ([[CK-MB]]) and [[Troponin]]s I and T).
====Unstable Angina====
*[[Troponin]]s are fairly sensitive and specific for [[myocardial necrosis]].
[[Unstable angina]] occurs when myocardial oxygen demand exceeds myocardial oxygen supply at rest or with minimal exertion. This supply/demand mismatch can be caused by conditions that increase oxygen demand or reduce oxygen supply.<ref>Ambrose JA, Winters SL, Stern A, et al: Angiographic morphology and the pathogenesis of unstable angina pectoris. J Am Coll Cardiol 1985 Mar; 5(3): 609-16. PMID 3973257</ref><ref>Crea F, Biasucci LM, Buffon A, Liuzzo G, Monaco C, Caligiuri G, et al. Role of inflammation in the pathogenesis of unstable coronary artery disease. Am J Cardiol 1997; 80: 10-6E. PMID 9296463</ref><ref>Biasucci LM, Colizzi C, Rizzello V, Vitrella G, Crea F, Liuzzo G. Role of inflammation in the pathogenesis of unstable coronary artery diseases. Scand J Clin Lab Invest Suppl 1999; 230: 12-22 PMID 10389197</ref><ref>Asher CR, Topol EJ, Moliterno DJ, et al: Insights into the pathophysiology of atherosclerosis and prognosis of black Americans with acute coronary syndromes. 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Coronary vasospasm-induced acute coronary syndrome complicated by life-threatening cardia arrhythmias in patients without hemodynamically significant coronary artery disease. ''Int J Cardiol'' 2007; 117:37-44. PMID 16844245</ref><ref>Yuksel UD, Celik T, Iyisoy A, et al:. Polymorphic ventricular tachycardia induced by coronary vasospasm: A malignant case of variant angina. Int J Cardiol, 2006. E-pubahead of print, Nov. 22, 2006. PMID 17125857 </ref><ref>Kawano H, Motoyama T, Yasue H, et al: Endothelial function fluctuates with diurnal variation in the frequency of ischemic episodes in patients with variant angina. ''J Am Coll Cardiol'' 2002; 40:266-270. PMID 12106930</ref><ref>Matsuguchi T, Araki H, Nakamura N, et al: Prevention of vasospastic angina by alcohol ingestion: Report of 2 cases. ''Angiology'' 1988; 39:394-400. PMID 3364807</ref><ref>Raxwal V, Gupta K: Images in cardiovascular medicine. Coronary artery spasm. ''Circulation'' 2006; 113:e689-e690. PMID 16606795</ref><ref>Chen HS, Pinto DS: Images in clinical medicine. Prinzmetal's angina. ''N Engl J Med'' 2003; 349:e1. PMID 12840104</ref><ref>Wang K, Asinger RW, Marriott HJ: ST-segment elevation in conditions other than acute myocardial infarction. ''N Engl J Med'' 2003; 349:2128-2135. PMID 14645641</ref><ref>Unverdorben M, Haag M, Fuerste T, et al: Vasospasm in smooth coronary arteries as a cause of asystole and syncope. ''Cathet Cardiovasc Diagn'' 1997; 41:430-434. PMID 9258492 </ref><ref>Lip GY, Gupta J, Khan MM, Singh SP: Recurrent myocardial infarction with angina and normal coronary arteries. ''Int J Cardiol'' 1995; 51:65-71. PMID 8522399</ref><ref>Pepine CJ, el-Tamimi H, Lambert CR: Prinzmetal's angina (variant angina). ''Heart Dis Stroke'' 1992; 1:281-286. PMID 1344118</ref><ref>Crea F: Variant angina in patients without obstructive coronary atherosclerosis: a benign form of spasm. ''Eur Heart J'' 1996; 17:980-982. PMID 8809510</ref><ref>Hirano Y, Ueharfa H, Nakamura H, et al: Diagnosis of vasospastic angina: Comparison of hyperventilation and cold-pressor stress echocardiography, and coronary angiography with intracoronary injection of acetylcholine. ''Int J Cardiol'' 2007; 116:331-337. PMID 16890307</ref><ref>Nakao K, Ohgushi M, Yoshimura M, et al: Hyperventilation as a specific test for diagnosis of coronary artery spasm. ''Am J Cardiol'' 1997; 80:545-549. PMID 9294979</ref><ref>Antman E, Muller J, Goldberg S, et al: Nifedepine therapy for coronary artery spasm. Experience in 127 patients.  ''N Engl J Med''  1980; 302:1269-1273. PMID 6767986</ref><ref>De Cesare N, Cozzi S, Apostolo A, et al: Facilitation of coronary spasm by propranolol in Prinzmetal's angina: Fact or unproven extrapolation?. ''Coron Artery Dis'' 1994; 5:323-330. PMID 8044344</ref><ref>Tzivoni D, Keren A, Benhorin J, et al: Prazosin therapy for refractory variant angina.''Am Heart J'' 1983; 105:262-266. PMID 6823808 </ref><ref>Kaski JC: Management of vasospastic angina—role of nicorandil. ''Cardiovasc Drugs Ther 9 Suppl'' 1995; 2:221-227. PMID 7647026</ref><ref>Kawano H, Motoyama T, Hirai N, et al: Estradiol supplementation suppresses hyperventilation-induced attacks in postmenopausal women with variant angina. ''J Am Coll Cardiol'' 2001; 37:735-740. PMID 11693745</ref><ref>Tanabe Y, Itoh E, Suzuki K, et al: Limited role of coronary angioplasty and stenting in coronary spastic angina with organic stenosis. ''J Am Coll Cardiol'' 2002; 39:1120-1126. PMID 11923034 </ref><ref>Meisel SR, Mazur A, Chetboun I, et al: Usefulness of implantable cardioverter-defibrillators in refractory variant angina pectoris complicated by ventricular fibrillation in patients with angiographically normal coronary arteries. ''Am J Cardiol'' 2002; 89:1114-1116. PMID 11988204</ref><ref>Bory M, Pierron F, Panagides D, et al: Coronary artery spasm in patients with normal or near normal coronary arteries. Long-term follow-up of 277 patients. ''Eur Heart J'' 1996; 17:1015-1021. PMID 8809518</ref><ref>Shimokawa H, Nagasawa K, Irie T, et al: Clinical characteristics and long-term prognosis of patients with variant angina. A comparative study between western and Japanese populations. ''Int J Cardiol'' 1998; 18:331-349. PMID 3129375</ref><ref>Tashiro H, Shimokawa H, Koyanagi S, Takeshita A: Clinical characteristics of patients with spontaneous remission of variant angina. ''Jpn Circ J'' 1993; 57:117-122. PMID 8450595 </ref>
*For the diagnosis of [[NSTEMI]] to be made, the [[troponin]] elevation must occur in the context of ischemic [[chest pain]], however the diagnosis should not be made based on laboratory findings alone, as there are other possible etiologies for elevated [[troponin]]s. <ref name="Anderson"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' Circulation 2007 116: e148 – e304. PMID 17679616</ref> <ref name="Anderson2"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. Correction of ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' J Am Coll Cardiol. 2008 Mar 4; 51(9): 974. PMID 17692738 </ref>


==Incidence==
====Non ST Elevation Myocardial Infarction====
*In 2004, there were 1,565,000 hospitalizations for [[acute coronary syndrome]] (896,000 for [[MI]]; 669,000 for [[unstable angina]].<ref name="Rosamond"> Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, McDermott M, Meigs J, Moy C, Nichol G, O'Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.'' Circulation. 2007 Feb 6;115(5):e69-171. Epub 2006 Dec 28. PMID 17194875</ref>
As alluded to in prior sections, [[unstable angina]] and [[NSTEMI]] are at different ends of the spectrum of the same disease.  While there is no way to determine which patients presenting with unstable angina will ultimately progress to NSTEMI, the distinction between the two entities is clear.   Often, for patients presenting prior to the four hour window before [[cardiac biomarkers]] are positive (namely [[CK-MB]]), the [[EKG]] in context of the patient's chest pain will be marker for whether patient has [[STEMI]] versus UA/NSTEMI and needs to urgently undergo [[percutaneous revascularization]].
*Women have higher incidence of [[unstable angina]]/[[NSTEMI]] and are older with increased prevalence of [[HTN]], [[DM]], [[CHF]] than men.
*Men tend to have a higher incidence of [[STEMI]] and [[revascularization]] than women.


==Pathophysiology==
==Epidemiology and Demographics==
These conditions are characterized by an inadequate blood supply to meet the oxygen and metabolic demands of the [[myocardium]].
Over 9 million patients in the United States alone have angina. An estimated 80,700,000 American adults (one in three) have one or more types of cardiovascular disease (CVD), of whom 38,200,000 are estimated to be age 60 or older. Except as noted, the estimates were extrapolated to the U.S. population in 2005 from NHANES 1999–2004.
:*The most common cause of [[UA]]/[[NSTEMI]] is reduced [[myocardial]] perfusion that results from coronary artery narrowing caused by a [[thrombus]] that developed on a disrupted [[atherosclerotic plaque]] and is usually [[nonocclusive]].
 
:*Arterial inflammation which activates the macrophages and T lymphocytes located at the shoulder of a plaque increase the expression of enzymes such as metalloproteinases that cause thinning and disruption of the plaque, which in turn can lead to [[UA]]/[[NSTEMI]].  
==Risk Stratification==
:*An [[occlusive thombus]] or plaque can also cause this syndrome in the presence of extensive collateral supply.  
There are several scoring systems which have been devised as methods of identifying high-risk patients presenting with acute coronary syndrome (ACS).  These include, among others, the ''Braunwald classification system'',<ref>Lee, DS & Roe, MT (2004). Unstable angina and non-ST-elevation myocardial infarction, In Griffin & Topol Eds, Manual of Cardiovascular Medicine, 2nd ed. Lippincott Williams & Williams: Philadelphia, PA, pp 27-44. ISBN 9780781759984</ref> the ''Rizik classification system'',<ref name="Rizik"> Rizik DG, Healy S, Margulis A, Vandam D, Bakalyar D, Timmis G, Grines C, O'Neill WW, Schreiber TL. A new clinical classification for hospital prognosis of unstable angina pectoris. Am J Cardiol. 1995 May 15;75(15):993-7. PMID 7747701</ref> the ''TIMI risk score'',<ref> Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA 2000; 284: 835–42. PMID 10938172 </ref><ref name="Pollack"> Pollack CV Jr, Sites FD, Shofer FS, Sease KL, Hollander JE. Application of the TIMI risk score for unstable angina and non-ST elevation acute coronary syndrome to an unselected emergency department chest pain population. Acad Emerg Med. 2006 Jan;13(1):13-8. Epub  2005 Dec 19. PMID 16365321</ref> the ''GRACE risk score'' <ref>Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van De Werf F, Avezum A, Goodman SG, Flather MD, Fox KA; Global Registry of Acute Coronary Events Investigators. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med. 2003 Oct 27;163(19):2345-53. PMID 14581255</ref><ref>Eagle KA, Lim MJ, Dabbous OH, Pieper KS, Goldberg RJ, Van de Werf F, Goodman SG, Granger CB, Steg PG, Gore JM, Budaj A, Avezum A, Flather MD, Fox KA; GRACE Investigators. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. JAMA. 2004 Jun 9;291(22):2727-33. PMID 15187054</ref> and the ''PURSUIT risk score''.<ref name="Boersma">Boersma E, Pieper KS, Steyerberg EW, Wilcox RG, Chang WC, Lee KL, Akkerhuis KM, Harrington RA, Deckers JW, Armstrong PW, Lincoff AM, Califf RM, Topol EJ, Simoons ML. Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators. Circulation. 2000 Jun 6;101(22):2557-67. PMID 10840005</ref><ref>Lindahl B, Diderholm E, Lagerqvist B, et al: Mechanisms behind the prognostic value of troponin T in unstable coronary artery disease: A FRISC II substudy. J Am Coll Cardiol  2001; 38:979-986.* Lenderink T, Boersma E, Heeschen C, et al: Elevated troponin T and C-reactive  protein predict impaired outcome for 4 years in patients with refractory unstable angina, and  troponin T predicts benefit of treatment with abciximab in combination with  PTCA.  Eur Heart J  2003; 24:77-85. PMID 11583868</ref><ref>Heeschen C, Hamm CW, Bruemmer J, Simoons ML, for the Chimeric c7E3 AntiPlatelet Therapy in Unstable  angina REfractory to standard treatment trial (CAPTURE) Investigators: Predictive value of C-reactive protein and troponin T in patients with unstable angina: A  comparative analysis. J Am Coll Cardiol  2000; 35:1535-1542. PMID 10807457</ref><ref>Gibson CM, Pinto DS, Murphy SA, et al: Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent  mortality. J Am Coll Cardiol 2003; 42:1535-1543. PMID 14607434</ref><ref>The RISC Group: Risk of myocardial infarction and death during treatment with  low-dose aspirin and intravenous heparin in men with unstable coronary artery  disease. Lancet 1990; 336:827-830. PMID 1976875</ref> This evaluation is helpful in selecting the site of care and type of therapy. Physician should document their opinion of the likelihood of [[ACS]] in one of the three categories of low, intermediate or high likelihood. Patients with high risk score and/or hemodynamic instability should be managed in [[coronary care unit]] while those with intermediate to low risk score and hemodynamic stability can be managed in a [[step down unit]]. A continuous ECG monitoring (telemetry) should be used to monitor for [[arrythmias]]. Patients with [[UA]] have lower short term mortality than [[NSTEMI]] or [[STEMI]]. Early risk stratification is, therefore, recommended and is based on the initial history, physical exam, [[ECG]], assessment of [[renal function]] and [[cardiac biomarkers]].
:*Secondary [[UA]] can occur in conditions that increase myocardial oxygen requirements(such as [[fever]], [[tachycardia]] or [[thyrotoxicosis]]), reduce coronary blood flow(such as [[hypotension]]) or reduce myocardial oxygen delivery(such as [[anemia]] or [[hypoxemia]]).
 
:*A less common cause of [[UA]] is [[Prinzmetal angina]] where in a there is focal spasm of a segment of an epicardial coronary artery caused by smooth muscle hypercontractility and/or endothelial dysfunction resulting in dynamic obstruction.
==Natural History, Complications and Prognosis==
:*Some patients with progressive [[atherosclerosis]] or with re[[stenosis]] after a [[PCI]] can also cause [[UA]] by severe narrowing without [[spasm]] or [[thrombus]].  
[[Unstable angina]] / [[NSTEMI]] are signs of more severe heart disease.  Natural history is complicated by the development of [[arrhythmia]]s and [[heart failure]].  In a study it was shown that 14% of the cases of unstable angina can progress to [[MI]].  [[Sudden death]] is an infrequent sequel of both UA and NSTEMI.
 
==Special Groups==
===Women===
Although women are traditionally at lower risk for [[CAD]] as compared to men at all ages, [[UA]]/[[NSTEMI]] is still common amongst this group and importantly, women can manifest CAD somewhat differently than men. It is also important to keep in mind that women with CAD are, on average, older than men and are more likely to have comorbidities such as [[hypertension]], [[diabetes mellitus]], and [[heart failure]] with preserved systolic function; to manifest [[angina]] rather than [[MI]]; and, to have atypical symptoms of angina and MI.
 
===Diabetic Patients===
75% of all deaths among diabetic patients are due to [[coronary artery disease]].  Diabetic patients with [[unstable angina]] or [[NSTEMI]] tend to have a more severe disease with worse outcomes.  Long term morbidity and mortality in diabetic patients with no previous cardiovascular disease are the same as that of nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease.<ref name="pmid10961966">{{cite journal |author=Malmberg K, Yusuf S, Gerstein HC, ''et al.'' |title=Impact of diabetes on long-term prognosis in patients with unstable angina and non-Q-wave myocardial infarction: results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry |journal=Circulation |volume=102 |issue=9 |pages=1014–9 |year=2000 |month=August |pmid=10961966 |doi= |url=}}</ref>
 
===Post-CABG Patients===
Post-CABG patients with [[unstable angina]] or [[NSTEMI]] are associated with a more severe coronary artery disease compared to the patients who have not undergone a bypass surgery.  Medical treatment in this patient population should follow the same guidelines as for UA/NSTEMI in non–post CABG patients.
 
===Elderly===
Elderly patients represent a group of patients who have more comorbidities and who are both at risk for both [[CAD]] as well as for associated complications. However, they do derive equivalent or greater benefit from intervention when compared to younger patients. This group is likely to present with atypical symptoms like [[dyspnea]] and [[confusion]] rather than [[chest pain]].  
On the other hand, presence of noncardiac comorbidities such as [[chronic obstructive lung disease]], [[gastroesophageal reflux disease]], upper-body musculoskeletal symptoms, [[pulmonary embolism]], and [[pneumonia]] is also higher, thus making the diagnosis of [[UA]]/[[NSTEMI]] challenging.
Secondly, they are more likely to have altered or abnormal cardiovascular anatomy, increased cardiac [[afterload]] due to decreased arterial compliance and [[arterial hypertension]], [[orthostatic hypotension]], cardiac hypertrophy, and ventricular dysfunction, especially [[diastolic dysfunction]].
Thirdly, elderly patients generally have other cardiac comorbidities and risk factors, such as [[hypertension]], prior [[MI]], [[HF]], cardiac conduction abnormalities, prior [[CABG]], peripheral and cerebrovascular disease, [[diabetes mellitus]], [[renal insufficiency]], and [[stroke]].
As a result, they are on mulitple medications and hence at risk for drug interactions and polypharmacy. When considering revascularization procedures, general medical and cognitive status, bleeding risk and other risk of interventions, anticipated life expectancy, and patient or family preferences must be considered.
 
===Chronic Kidney Disease===
Chronic kidney disease (CKD) constitutes a risk factor for adverse outcomes after [[MI]]. It is a coronary artery disease equivalent as well as a risk factor for progression of [[CAD]].
 
===Drug and Substance Abusers===
[[Cocaine]] and [[methamphetamine]] are common drugs associated with [[MI]].
 
===Prinzmetal's Angina===
Prinzmetal's angina, also known as variant angina or angina inversa, is chest pain at rest that occurs in periodic cycles. It is unrelated to exertion although can occur with exertion.
Prinzmetal's angina is caused by vasospasm, a narrowing of the coronary arteries caused by contraction of the smooth muscle tissue in the vessel walls rather than fixed narrowings of the coronary arteries due to atherosclerosis.  
Attacks can be precipitated by an emotional [[stress]], [[hyperventilation]], [[exercise]], or exposure to cold. A circadian variation in the episodes of angina is most often present, with most attacks occurring in the early morning.
It is characterized by transient ST-segment elevation that spontaneously resolves or resolves with [[NTG]] use without progression to [[MI]]. The majority of patients have normal exercise tolerance, and stress testing may be negative.
Because the anginal discomfort usually occurs at rest without a precipitating cause, it may simulate [[UA]]/[[NSTEMI]] secondary to [[coronary atherosclerosis]].
 
===Cardiovascular Syndrome X===
Cardiovascular syndrome X refers to patients with [[angina]] or angina-like discomfort with exercise, [[ST-segment depression]] on exercise testing, and normal or nonobstructed coronary arteries on angiography.  This entity should be differentiated from the metabolic syndrome X or [[metabolic syndrome]], which describes patients with [[insulin resistance]], hyperinsulinemia, [[dyslipidemia]], [[hypertension]], and abdominal [[obesity]].  It also should be differentiated from noncardiac chest pain.
 
==Diagnosis==
===History and Symptoms===
A person with unstable angina pectoris (UAP) will have a history of angina that has increased in frequency or intensity at the same level of exertion. Anginal pain can manifest in many forms ranging from [[chest pain]] to chest pressure to [[shortness of breath]] to [[epigastric pain]]. UAP is part of the spectrum of acute coronary syndromes ([[ACS]]) and requires immediate assessment and management by a qualified physician. The history and symptoms described by a patient with unstable angina can be identical to the symptoms of either [[NSTEMI]] or [[STEMI]], both of which carry a poorer prognosis.<ref>Ambrose JA, Winters SL, Stern A, et al: Angiographic morphology and the pathogenesis of unstable angina pectoris. J Am Coll Cardiol 1985 Mar; 5(3): 609-16. PMID 3973257</ref><ref>Crea F, Biasucci LM, Buffon A, Liuzzo G, Monaco C, Caligiuri G, et al. Role of inflammation in the pathogenesis of unstable coronary artery disease. Am J Cardiol 1997; 80: 10-6E. 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Coronary vasospasm-induced acute coronary syndrome complicated by life-threatening cardia arrhythmias in patients without hemodynamically significant coronary artery disease. ''Int J Cardiol'' 2007; 117:37-44. PMID 16844245</ref><ref>Yuksel UD, Celik T, Iyisoy A, et al:. Polymorphic ventricular tachycardia induced by coronary vasospasm: A malignant case of variant angina. Int J Cardiol, 2006. E-pubahead of print, Nov. 22, 2006. PMID 17125857 </ref><ref>Kawano H, Motoyama T, Yasue H, et al: Endothelial function fluctuates with diurnal variation in the frequency of ischemic episodes in patients with variant angina. ''J Am Coll Cardiol'' 2002; 40:266-270. PMID 12106930</ref><ref>Matsuguchi T, Araki H, Nakamura N, et al: Prevention of vasospastic angina by alcohol ingestion: Report of 2 cases. ''Angiology'' 1988; 39:394-400. PMID 3364807</ref><ref>Raxwal V, Gupta K: Images in cardiovascular medicine. Coronary artery spasm. ''Circulation'' 2006; 113:e689-e690. 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PMID 8809510</ref><ref>Hirano Y, Ueharfa H, Nakamura H, et al: Diagnosis of vasospastic angina: Comparison of hyperventilation and cold-pressor stress echocardiography, and coronary angiography with intracoronary injection of acetylcholine. ''Int J Cardiol'' 2007; 116:331-337. PMID 16890307</ref><ref>Nakao K, Ohgushi M, Yoshimura M, et al: Hyperventilation as a specific test for diagnosis of coronary artery spasm. ''Am J Cardiol'' 1997; 80:545-549. PMID 9294979</ref><ref>Antman E, Muller J, Goldberg S, et al: Nifedepine therapy for coronary artery spasm. Experience in 127 patients.  ''N Engl J Med''  1980; 302:1269-1273. PMID 6767986</ref><ref>De Cesare N, Cozzi S, Apostolo A, et al: Facilitation of coronary spasm by propranolol in Prinzmetal's angina: Fact or unproven extrapolation?. ''Coron Artery Dis'' 1994; 5:323-330. PMID 8044344</ref><ref>Tzivoni D, Keren A, Benhorin J, et al: Prazosin therapy for refractory variant angina.''Am Heart J'' 1983; 105:262-266. 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====Unstable Angina====
[[UA]] can have typical or atypical presentations. The 3 classic forms of presentation are: a) Rest [[angina]] (angina commencing when the patient is at rest); b) New onset (less than 2 months) severe angina (at least CCS class II); or c) Increasing angina-previously diagnosed angina that has become distinctly more frequent, longer in duration, or lower in threshold (i.e., increased by 1 or more CCS class to at least CCS class III severity).
 
====Non ST Elevation Myocardial Infarction====
[[NSTEMI]] generally presents as prolonged, more intense rest angina or angina equivalent. Patients with suspected [[ACS]] must be evaluated rapidly. Evaluation should not be done over the phone but in person and in a place where a 12 lead [[ECG]] can be obtained. A focused history, examination, [[ECG]] and [[cardiac biomarkers]] are helpful to determine where the patient will be managed and whether the patient needs to be transferred or referred to a different hospital/setting. Physical examination should focus on identifying the precipitating factors, comorbid conditions, rule out alternative diagnosis and assess hemodynamic status of the patient.
 
===Physical Examination===
Patients with suspected [[ACS]] must be evaluated rapidly. The objectives of the initial evaluation are first to identify signs of immediate life-threatening instability and then to ensure that the patient is moved rapidly to the most appropriate setting for the level of care needed based on diagnostic criteria and an estimation of the need for intervention. It is recommended that patients with a suspected [[ACS]] with chest discomfort or other ischemic symptoms at rest for more than 20 min, hemodynamic instability, or recent syncope or presyncope to be referred immediately to an ED or a specialized chest pain unit.<ref name="pmid17692738">{{cite journal |author=Anderson JL, Adams CD, Antman EM, ''et al'' |title=ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine |journal=JACC |volume=50 |issue=7 |pages=e1–e157 |year=2007 |month=August |pmid=17692738 |doi:10.1016/j.jacc.2007.02.013 |url=}}</ref>
 
===Laboratory Findings===
====Blood Studies====
Laboratory findings for the diagnosis of [[unstable angina]] and [[NSTEMI]] include some baseline tests like complete blood count, electrolytes, serum creatinine and measurement of acute-phase proteins.
 
====Biomarkers====
Cardiac markers are biomarkers that are measured to evaluate heart function.  Their levels increase in blood when the heart muscle is necrosed, as in [[MI]]. Clinically the most commonly used  cardiac markers include [[troponin]]s and [[Creatine kinase|creatine kinase-MB]] ([[CK-MB]]).  Other markers are [[lactate dehydrogenase]], [[aspartate transaminase]], [[myoglobin]], ischemia modified albumin, pro-brain natriuretic peptide and glycogen phosphorylase isoenzyme.  Cardiac biomarker measurement is one of the initial tests in a patient with heart attack. [[Unstable angina]] is associated with negative cardiac biomarkers whereas [[NSTEMI]] is associated with elevated cardiac biomarkers.


==Presentation and Diagnosis==
===Electrocardiogram===
[[UA]] can have typical or atypical presentations. The 3 classic forms of presentation are:
The EKG in patients with [[unstable angina]] can be variable. In some cases, no changes on EKG will be appreciated. In other cases, a resting EKG may show flipped or [[inverted T wave]]s, [[ST segment depression]], or non-specific ST-T changes.  It is the first line of assessment in any patient suspected of having unstable angina.
:*Rest [[angina]](angina commencing when the patient is at rest)
:*New onset (less than 2 months) severe angina(at least CCS class II),or  
:*Increasing angina-previously diagnosed angina that has become distinctly more frequent, longer in duration, or lower in threshold (i.e., increased by 1 or more CCS class to at least CCS class III severity)


[[NSTEMI]] generally presents as prolonged, more intense rest angina or [[angina equivalent]].
===Chest X-Ray===
:*Patients with suspected [[ACS]] must be evaluated rapidly.  
When suspecting [[UA]]/[[NSTEMI]] a chest X-ray is critical to aid in the exclusion of [[aortic dissection]]. A [[mediastinal mass]] consistent with a cancer may be present, but it is unlikely to present with a syndrome of accelerating chest pain. It is also used to evaluate other causes of chest pain or discomfort like pulmonary infection, [[pneumothorax]], [[pulmonary hypertension]] etc.
:*Evaluation should not be done over the phone but in person and in a place where a 12 lead [[ECG]] can be obtained.  
:*A focused history, examination, [[ECG]] and [[cardiac biomarkers]] are helpful to determine where the patient will be managed and whether the patient needs to be transferred or referred to a different hospital/setting.
:*Physical examination should focus on identifying the precipitating factors, comorbid conditions, rule out alternative diagnosis and assess hemodynamic status of the patient.  


[[Unstable angina]] is associated with negative cardiac biomarkers whereas [[NSTEMI]] is associated with elevated cardiac biomarkers.
===Echocardiogram===
Depending on the patient's symptoms and degree of suspicion for [[ACS]], early [[coronary angiography]] can be performed to make a definitive diagnosis.
Left ventricular function and wall motion abnormalities can be assessed promptly using an echocardiogram.  It can also be used to exclude other possible causes of like [[aortic stenosis]] and [[hypertrophic obstructive cardiomyopathy]]. Valvular or mechanical complications from [[MI]] warrant an immediate [[transesophageal echocardiography]].


==Risk Stratification==
===Coronary Angiography===
*Patients with [[UA]] have lower short term mortality than [[NSTEMI]] or [[STEMI]].  
One other image modality that can be used in diagnosing and treating [[UA]]/[[NSTEMI]] is CT [[coronary angiography]]. This is a superior imaging technique with a sensitivity and specificity of 90% and 95% respectively.<ref name="pmid16442357">{{cite journal |author=Fine JJ, Hopkins CB, Ruff N, Newton FC |title=Comparison of accuracy of 64-slice cardiovascular computed tomography with coronary angiography in patients with suspected coronary artery disease |journal=[[The American Journal of Cardiology]] |volume=97 |issue=2 |pages=173–4 |year=2006 |month=January |pmid=16442357 |doi=10.1016/j.amjcard.2005.08.021 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9149(05)01746-7 |accessdate=2011-04-08}}</ref><ref name="pmid16053973">{{cite journal |author=Raff GL, Gallagher MJ, O'Neill WW, Goldstein JA |title=Diagnostic accuracy of noninvasive coronary angiography using 64-slice spiral computed tomography |journal=[[Journal of the American College of Cardiology]] |volume=46 |issue=3 |pages=552–7 |year=2005 |month=August |pmid=16053973 |doi=10.1016/j.jacc.2005.05.056 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(05)01314-8 |accessdate=2011-04-08}}</ref> Depending on the patient's symptoms and degree of suspicion for [[ACS]], early [[coronary angiography]] can be performed to make a definitive diagnosis. If there is no evidence of either calcified or noncalcified plaque on coronary angiogram, then it is highly unlikely that the patient’s symptoms are due to UA/NSTEMI.
*Early risk stratification is, therefore, recommended and is based on the initial history, physical exam, [[ECG]], assessment of [[renal function]] and [[cardiac biomarkers]].  
*Various models to calculate risk score and determine prognosis are available for example TIMI score, PURSUIT risk model, GRACE risk score etc. This evaluation is helpful in selecting the site of care and type of therapy.
*Physician should document their opinion of the likelihood of [[ACS]] in one of the three categories of low, intermediate or high likelihood. Patients with high risk score and/or hemodynamic instability should be managed in [[coronary care unit]] while those with intermediate to low risk score and hemodynamic stability can be managed in a [[step down unit]].  
*A continuous ECG monitoring([[telemetry]]) should be used to monitor for [[arrythmias]].


==Treatment==
==Treatment==
Immediate management is directed towards relief of [[chest pain]].  
===Primary Prevention===
*[[Nitrates]], [[ASA]] and morphine are recommended to control the symptoms from possible [[ACS]].  
Major risk factors for development of coronary heart disease have been established from several long term epidemiological studies.<ref name="pmid12485966">{{cite journal |author= |title=Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report |journal=[[Circulation]] |volume=106 |issue=25 |pages=3143–421 |year=2002 |month=December |pmid=12485966 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=12485966 |accessdate=2011-04-11}}</ref> <ref name="pmid16461820">{{cite journal |author=Lloyd-Jones DM, Leip EP, Larson MG, D'Agostino RB, Beiser A, Wilson PW, Wolf PA, Levy D |title=Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age |journal=[[Circulation]] |volume=113 |issue=6 |pages=791–8 |year=2006 |month=February |pmid=16461820 |doi=10.1161/CIRCULATIONAHA.105.548206 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=16461820 |accessdate=2011-04-11}}</ref> Various clinical trials have demonstrated that development of coronary diseases can be prevented or the risk of experiencing [[UA]]/[[NSTEMI]] in patients who have [[coronary heart disease]] can be lowered by modifying the main risk factors.<ref name="pmid10448784">{{cite journal |author=Ross SD, Allen IE, Connelly JE, Korenblat BM, Smith ME, Bishop D, Luo D |title=Clinical outcomes in statin treatment trials: a meta-analysis |journal=[[Archives of Internal Medicine]] |volume=159 |issue=15 |pages=1793–802 |year=1999 |pmid=10448784 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=10448784 |accessdate=2011-04-12}}</ref><ref name="pmid10761958">{{cite journal |author=Wilson K, Gibson N, Willan A, Cook D |title=Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies |journal=[[Archives of Internal Medicine]] |volume=160 |issue=7 |pages=939–44 |year=2000 |month=April |pmid=10761958 |doi= |url=http://archinte.ama-assn.org/cgi/pmidlookup?view=long&pmid=10761958 |accessdate=2011-04-12}}</ref><ref name="pmid11571256">{{cite journal |author=Smith SC, Blair SN, Bonow RO, Brass LM, Cerqueira MD, Dracup K, Fuster V, Gotto A, Grundy SM, Miller NH, Jacobs A, Jones D, Krauss RM, Mosca L, Ockene I, Pasternak RC, Pearson T, Pfeffer MA, Starke RD, Taubert KA |title=AHA/ACC Scientific Statement: AHA/ACC guidelines for preventing heart attack and death in patients with atherosclerotic cardiovascular disease: 2001 update: A statement for healthcare professionals from the American Heart Association and the American College of Cardiology |journal=[[Circulation]] |volume=104 |issue=13 |pages=1577–9 |year=2001 |month=September |pmid=11571256 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11571256 |accessdate=2011-04-12}}</ref>
*[[Beta blockers]], thienopyridines(like [[Clopidogrel]] and [[prasugrel]]) should be administered in the absence of contraindication to their use.  
 
*Based on the suspicion for likelihood of [[ACS]], [[anticoagulants]] and [[GP IIb/IIIa inhibitors]] can be started early in the course of presentation.  
===Immediate Management===
*Two strategies in the treatment are early invasive or conservative strategies. Most trials have shown benefit of early invasive therapy with cardiac [[catheterization]] and [[revascularisation]] procedures. Early invasive therapy is now recommended for patients with [[UA]]/[[NSTEMI]] and [[ST segment]] changes at presentation and/or positive [[troponins]] during first 24hrs of presentation.
Initial management of acute coronary syndrome (ACS) begins with differentiating between the spectrum of [[ACS]] which includes [[STEMI]], [[Unstable angina pathophysiology & etiology|unstable angina]] and [[Non ST elevation myocardial infarction pathophysiology & etiology|Non-ST Elevation Myocardial Infarction]]. Because the symptoms for all these can be similar, a medical evaluation is necessary as mentioned in other sections (see [[UA / NSTEMI prehospital care | Pre-hospital Care]] and [[Unstable angina / non ST elevation myocardial infarction initial therapy | Initial Therapy]]). Information from the history, physical examination, 12-lead [[ECG]], and initial cardiac [[biomarker]] tests can help in differentiating between the above three categories as well as categorize the patient into probable or definite [[ACS]], [[chronic stable angina]] or non-cardiac cause of [[chest pain]]. Patients with [[STEMI]] must be evaluated for immediate reperfusion therapy (see [[ST Elevation Myocardial Infarction Reperfusion Therapy|Reperfusion Therapy (Overview of Fibrinolysis and Primary PCI)]]). Patients with [[unstable angina]]/[[NSTEMI]], recurrent symptoms suggestive of [[ACS]] and/or [[Unstable angina / NSTEMI ECG|electrocardiogram]] ST-segment deviations, or positive cardiac [[Unstable angina / NSTEMI bio markers|biomarkers]] who are hemodynamically stable should be admitted to an inpatient unit for bed rest with continuous rhythm monitoring and careful observation for [[recurrent ischemia]] and managed with either an invasive or conservative strategy (see [[Unstable angina / non ST elevation myocardial infarction initial conservative versus initial invasive strategies|initial conservative versus initial invasive strategies)]]. Immediate management is directed towards relief of [[chest pain]]. [[Nitrates]], [[ASA]] and morphine are recommended to control the symptoms from possible [[ACS]]. [[Beta blockers]], thienopyridines (like [[clopidogrel]] and [[prasugrel]]) should be administered in the absence of contraindication to their use. Based on the suspicion for likelihood of [[ACS]], [[anticoagulants]] and [[GP IIb/IIIa inhibitors]] can be started early in the course of presentation. Two strategies in the treatment are early invasive or conservative strategies. Most trials have shown benefit of early invasive therapy with cardiac [[catheterization]] and revascularisation procedures. Early invasive therapy is now recommended for patients with [[UA]]/[[NSTEMI]] and [[ST segment]] changes at presentation and/or positive [[troponin]]s during first 24hrs of presentation.
 
===Antithrombin Therapy===
Anticoagulation, traditionally with [[unfractionated heparin]] (UFH), is a cornerstone of therapy for patients with [[unstable angina]]/[[NSTEMI]].
Some of the agents available in this category include [[unfractionated heparin]], [[low molecular weight heparin]], direct thrombin Inhibitors (e.g.,[[bivalirudin]]) factor Xa Inhibitors (e.g.,[[fondaparinux]]),  and [[warfarin]]. These agents are also sometimes referred to as [[antithrombin]]s, although, it should be noted that they often inhibit one or more proteins in the coagulation cascade before [[thrombin]].
 
===Antiplatelet Agents===
====Aspirin====
Antiplatelet therapy plays a major role in the management of [[unstable angina]]/[[NSTEMI]]. This class of medication is directed towards one of the following three pathways: decreasing [[thromboxane A2]] formation ([[aspirin]]), inhibiting the P2Y12 component of the [[adenosine diphosphate]] (ADP) receptor pathway ([[thienopyridines]]), direct inhibitors of platelet aggregation ([[GP IIb/IIIa inhibitors]]).
 
====Thienopyridines====
Thienopyridines are a class of drugs that inhibit [[ADP receptor]]/P2Y 12 and function as antiplatelet agents.
 
====Glycoprotein IIb/IIIa Inhibitor====
[[Glycoprotein IIb/IIIa]] (Gp IIb/IIIa) is an integrin complex present on the surface of the platelets.  This complex aids in [[platelet aggregation]] during the clotting process by acting as a receptor for fibrinogen.  Gp IIb/IIIa inhibitors are a class of antiplatelet agents that prevent platelet aggregation and [[thrombus]] formation by inhibiting the integrin complex.
 
===Mechanical Reperfusion===
====Initial Conservative Versus Initial Invasive Strategies====
Two approaches to the use of [[cardiac catheterization]] and [[revascularization]] in [[UA]]/[[NSTEMI]] include an initial invasive strategy, involving routine early [[cardiac catheterization]] and [[revascularization]] with [[percutaneous coronary intervention]] (PCI) or [[coronary bypass grafting]] (CABG) and a second more conservative approach with initial medical management with [[catheterization]] and [[revascularization]] only for recurrent [[ischemia]] either at rest or on a noninvasive [[stress test]].  The objective of this is to provide a strategy that has the most potential to yield the best clinical outcome and improve long-term prognosis.
 
====PCI====
[[Coronary angiography]] is useful for defining the coronary artery anatomy in patients with [[UA]]/[[NSTEMI]] and for identifying subsets of high-risk patients who can benefit from early [[revascularization]]. The benefits of early invasive strategy have been discussed in previous section (see [[Unstable angina / non ST elevation myocardial infarction initial conservative versus initial invasive strategies | Initial Conservative Versus Initial Invasive Strategies]]).  Coronary [[revascularization]] with either [[PCI]] or [[CABG]] helps improve prognosis, relieve symptoms, prevent [[ischemic]] complications, and improve functional capacity. In recent years, increased utilization of [[PCI]] has been noticed mainly secondary to technical advancements and as a result of this, less complications associated with the procedure.
 
====CABG====
For patients with [[UA]]/[[NSTEMI]], when [[revascularization]] is required, the choice is between [[PCI]] and [[CABG]]. In general, the indications for [[PCI]] and [[CABG]] in [[UA]]/[[NSTEMI]] are similar to those for [[stable angina]]. Based on the results of multiple randomized trials, [[CABG]] is recommended for patients with disease of the [[left main coronary artery]] and [[CAD|multivessel]] disease and impaired [[left ventricular function]]. However, recent advance in techniques and less complications with [[PCI]] have led to use of PCI for isolated [[left main]] disease.


==Discharge care==
===Complications of Bleeding and Transfusion===
*Discharge care after [[UA]]/[[NSTEMI]] must include a medication reconciliation of inpatient and discharge medications, life style modification counselling and instructions on smoking cessation, cardiac rehabilitation and arrangements for follow-up.
*Patients with UA/NSTEMI diagnosis should be discharged home on an [[ASA]], [[clopidogrel]], [[beta blocker]], [[nitrates]], [[ACE inhibitors]] and [[statins]], unless contraindicated.
*Cardiac rehab has been shown to improve exercise tolerance, improve patient compliance and assist in lifestyle modification and all patient should be referred for this.
*Both patient and family should be informed about the treatment plan and a what to do if symptoms recur.


==Related Chapters==
Advancements in the efficacy and increased utilization of synergistic [[anti-platelet]] agents, [[anticoagulant]] therapies, and invasive risk stratification in high-risk patients with [[unstable angina]] and non-ST-segment elevation myocardial infarction ([[NSTEMI]]) has led to a 40% decrease in mortality from [[coronary artery disease]] (CAD) over the preceding 20 years.<ref name="Anderson"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' Circulation 2007 116: e148 – e304. PMID 17679616</ref><ref name="Anderson2"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. Correction of ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' J Am Coll Cardiol. 2008 Mar 4; 51(9): 974. PMID 17692738 </ref>  The advanced management of [[NSTEMI]] minimizes [[ischemic]] events; however the paradigm is that it also increases the risk of bleeding and necessitation for blood transfusion.<ref>Boersma E, Harrington RA, Moliterno DJ, White H, Théroux P, Van de Werf F, de Torbal A, Armstrong PW, Wallentin LC, Wilcox RG, Simes J, Califf RM, Topol EJ, Simoons ML. Platelet glycoproteinIIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet. 2002;359:189-98</ref><ref>James S, Armstrong P, Califf R, Husted S, Kontny F, Niemminen M, Pfisterer M, Simoons ML, Wallentin L. Safety and efficacy of abciximab combined with dalteparin in treatment of acute coronary syndromes. Eur Heart J. 2002;23:1538–45.</ref><ref name="Anderson"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' Circulation 2007 116: e148 – e304. PMID 17679616</ref><ref name="Anderson2"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. Correction of ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' J Am Coll Cardiol. 2008 Mar 4; 51(9): 974. PMID 17692738 </ref> Recent analyses and randomized controlled trials demonstrate an independent association between bleeding complications, [[blood transfusion]]s, and poor outcomes among [[NSTEMI]] patients.<ref>Rao SV, O'Grady K, Pieper KS, Granger CB, Newby LK, Mahaffey KW, Moliterno DJ, Lincoff AM, Armstrong PW, Van de Werf F, Califf RM, Harrington RA. A comparison of the clinical impact of bleeding measured by two different classifications among patients with acute coronary syndromes. J Am Coll Cardiol. 2006;47:809–16.</ref><ref>Eikelboom JW, Mehta SR, Anand SS, Xie C, Fox KAA, Yusuf S. Adverse impact of bleeding on prognosis in patients with acute coronary syndromes. Circulation. 2006;114:774–82.</ref><ref name="Anderson"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' Circulation 2007 116: e148 – e304. PMID 17679616</ref><ref name="Anderson2"> Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr, Chavey WE II, Fesmire FM, Hochman JS, Levin TN, Lincoff AM, Peterson ED, Theroux P, Wenger NK, Wright RS. Correction of ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction).'' J Am Coll Cardiol. 2008 Mar 4; 51(9): 974. PMID 17692738 </ref> Clinical trials of [[antithrombotic]] therapies associated with decreased bleeding complications have demonstrated improvements in short-term and long-term survival.


* [[The Living Guidelines: UA/NSTEMI]]
===Discharge Care===
* [[Chronic stable angina]]
====Medical Regimen====
* [[Non ST Elevation Myocardial Infarction]]
In most cases, the inpatient anti-ischemic medical regimen used in the nonintensive phase should be continued after discharge, and the [[antiplatelet]]/[[anticoagulant]] medications should be changed to an outpatient/oral regimen. The selection of a medical regimen should be individualized to the specific needs of each patient based on the in-hospital findings and events, the risk factors for [[CAD]], drug tolerability, and recent procedural interventions.
* [[ST Elevation Myocardial Infarction]]
 
====Post-Discharge Follow-Up====
Patients with [[UA]]/[[NSTEMI]], specially those with high risk factors during hospital stay, have high mortality which can be as high as 14 fold compared to those with absence of risk factors.
 
===Long-Term Medical Therapy and Secondary Prevention===
Similar to patients with [[STEMI]], patients with [[UA]]/[[NSTEMI]] also require secondary prevention at the time of discharge. Patients and their families should be educated regarding the specific targets for [[LDL]] cholesterol and [[HDL]] cholesterol, [[blood pressure]], [[body mass index]] ([[BMI]]), physical activity, and other appropriate lifestyle modifications.


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
{{WH}}
{{WS}}


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Latest revision as of 21:03, 5 December 2022
Resident
Survival
Guide

Acute Coronary Syndrome Main Page

Unstable angina / NSTEMI Microchapters

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Patient Information

Overview

Classification

Pathophysiology

Unstable Angina
Non-ST Elevation Myocardial Infarction

Differentiating Unstable Angina/Non-ST Elevation Myocardial Infarction from other Disorders

Epidemiology and Demographics

Risk Stratification

Natural History, Complications and Prognosis

Special Groups

Women
Heart Failure and Cardiogenic Shock
Perioperative NSTE-ACS Related to Noncardiac Surgery
Stress (Takotsubo) Cardiomyopathy
Diabetes Mellitus
Post CABG Patients
Older Adults
Chronic Kidney Disease
Angiographically Normal Coronary Arteries
Variant (Prinzmetal's) Angina
Substance Abuse
Cardiovascular "Syndrome X"

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Blood Studies
Biomarkers

Electrocardiogram

Chest X Ray

Echocardiography

Coronary Angiography

Treatment

Primary Prevention

Immediate Management

Anti-Ischemic and Analgesic Therapy

Cholesterol Management

Antitplatelet Therapy

Antiplatelet therapy recommendations
Aspirin
Thienopyridines
Glycoprotein IIb/IIIa Inhibitor

Anticoagulant Therapy

Additional Management Considerations for Antiplatelet and Anticoagulant Therapy

Risk Stratification Before Discharge for Patients With an Ischemia-Guided Strategy of NSTE-ACS

Mechanical Reperfusion

Initial Conservative Versus Initial Invasive Strategies
PCI
CABG

Complications of Bleeding and Transfusion

Discharge Care

Medical Regimen
Post-Discharge Follow-Up
Cardiac Rehabilitation

Long-Term Medical Therapy and Secondary Prevention

ICD implantation within 40 days of myocardial infarction

ICD within 90 days of revascularization

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Unstable angina non ST elevation myocardial infarction overview On the Web

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Maheep Singh Sangha, M.B.B.S.; Varun Kumar, M.B.B.S; Lakshmi Gopalakrishnan, M.B.B.S.; Cafer Zorkun, M.D., Ph.D. [2]; Neil Gheewala, M.D. [3]; Smita Kohli, M.D.


Overview

Unstable angina and Non ST elevation myocardial infarction (NSTEMI) belong to two different ends of the spectrum of acute coronary syndrome. Unstable angina is differentiated from NSTEMI by the absence of elevated cardiac biomarkers. The basic pathology in both the conditions involves a non-occlusive thrombus formation from a previously disrupted atherosclerotic plaque causing inadequate blood supply to the heart muscle.

The Spectrum of Acute Coronary Syndromes

Acute coronary syndromes (ACS) is a term that encompasses:

While all three usually result from atherosclerotic plaque rupture and subsequent thrombus formation in one of the main epicardial coronary arteries, with subsequent inadequate blood supply to meet the oxygen and metabolic demands of the myocardium. Other possible etiologies of this imbalance such as coronary artery narrowing alone, coronary spasm, or coronary dissection.

Unstable angina, NSTEMI and STEMI are distinguished pathophysiologically as to whether or not the thrombus is occlusive (as in the case of STEMI) or non-occlusive (as in the case of UA and NSTEMI).

Frequently, Unstable Angina and NSTEMI are indistinguishable on inital evaluation as these two conditions are at different spectrums of ischemia. If the ischemia is significant to cause myocardial damage, there will be an elevation of Cardiac biomarkers (CK-MB or troponin) and would be classified as an NSTEMI (see Biomarkers). Often, these may not be detected for up to 12 hours in the bloodstream, which emphasizes the need for thorough evaluation.[1][2]

Definition

Unstable Angina

Unstable angina is defined as new onset angina pectoris (or chest pain which is ischemic in origin) with the following features: a) occurs at rest or with lesser degrees of exertion than stable angina, b) lasts less than 30minutes, c) follows a crescendo pattern (i.e., occurs more frequently than previous), and d) there no sign of myocardial necrosis unlike in STEMI or NSTEMI, and there is no release of biomarkers of myonecrosis (CK or troponin). [3][4][5][6][7][8][9][10] [11][1] [2][12][13] [14][15][16][17] [18][19][20][21][22] [23][24][25][26][27][28][29][30][31] [32][33][34][35][36][37][38][39][40][41][42][43] [44][45][46][47][48][49][50][51][52][53][54][55][56] [57][58][59][60][61][62][63][64][65] [66][67][68][69][70][71][72][73][74][75][76][77] [78][79][80][81][82] [83][84][85][86][87][88][89][90][91] [92][93][94]

Non ST Elevation Myocardial Infarction

Non-ST Elevation MI (NSTEMI) presents with clinical features of UA along with the evidence of myocardial necrosis like elevated serum levels of cardiac biomarkers (i.e., creatine kinase (CK), MB isoenzyme of CK (CK-MB) and Troponins I and T). Troponins are fairly sensitive and specific for myocardial necrosis. For the diagnosis of NSTEMI to be made, the troponin elevation must occur in the context of ischemic chest pain, however the diagnosis should not be made based on laboratory findings alone, as there are other possible etiologies for elevated troponins.[1] [2]

Classification

Braunwald in 1989 proposed a classification for unstable angina based on severity and clinical circumstances. This classification was employed in various clinical trials and studies to determine its prognostic importance and clinical usefulness. In recent years with the more detailed understanding of the pathophysiology of unstable angina and the discovery of improved markers of myocardial injury, acute phase proteins and hemostatic markers, especially cardiac troponin I and troponin T, it was suggested to extend Class IIIB (angina at rest within the past 48 hrs) of the original classification, by subclassifying it into troponin negative and troponin positive patients.

Pathophysiology

Unstable Angina

Unstable angina occurs when myocardial oxygen demand exceeds myocardial oxygen supply at rest or with minimal exertion. This supply/demand mismatch can be caused by conditions that increase oxygen demand or reduce oxygen supply.[95][96][97][98][99][100][101][102][103][1][2][104][105][106][107][108][109][110][111][112][113][114][115][116][117][118][119][120][121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141][142][143][144][145][146][147][148][149][150][151][152][153][154][155][156][157][158][159][160][161][162][163][164][165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182][183][184][185][186]

Non ST Elevation Myocardial Infarction

As alluded to in prior sections, unstable angina and NSTEMI are at different ends of the spectrum of the same disease. While there is no way to determine which patients presenting with unstable angina will ultimately progress to NSTEMI, the distinction between the two entities is clear. Often, for patients presenting prior to the four hour window before cardiac biomarkers are positive (namely CK-MB), the EKG in context of the patient's chest pain will be marker for whether patient has STEMI versus UA/NSTEMI and needs to urgently undergo percutaneous revascularization.

Epidemiology and Demographics

Over 9 million patients in the United States alone have angina. An estimated 80,700,000 American adults (one in three) have one or more types of cardiovascular disease (CVD), of whom 38,200,000 are estimated to be age 60 or older. Except as noted, the estimates were extrapolated to the U.S. population in 2005 from NHANES 1999–2004.

Risk Stratification

There are several scoring systems which have been devised as methods of identifying high-risk patients presenting with acute coronary syndrome (ACS). These include, among others, the Braunwald classification system,[187] the Rizik classification system,[188] the TIMI risk score,[189][190] the GRACE risk score [191][192] and the PURSUIT risk score.[193][194][195][196][197] This evaluation is helpful in selecting the site of care and type of therapy. Physician should document their opinion of the likelihood of ACS in one of the three categories of low, intermediate or high likelihood. Patients with high risk score and/or hemodynamic instability should be managed in coronary care unit while those with intermediate to low risk score and hemodynamic stability can be managed in a step down unit. A continuous ECG monitoring (telemetry) should be used to monitor for arrythmias. Patients with UA have lower short term mortality than NSTEMI or STEMI. Early risk stratification is, therefore, recommended and is based on the initial history, physical exam, ECG, assessment of renal function and cardiac biomarkers.

Natural History, Complications and Prognosis

Unstable angina / NSTEMI are signs of more severe heart disease. Natural history is complicated by the development of arrhythmias and heart failure. In a study it was shown that 14% of the cases of unstable angina can progress to MI. Sudden death is an infrequent sequel of both UA and NSTEMI.

Special Groups

Women

Although women are traditionally at lower risk for CAD as compared to men at all ages, UA/NSTEMI is still common amongst this group and importantly, women can manifest CAD somewhat differently than men. It is also important to keep in mind that women with CAD are, on average, older than men and are more likely to have comorbidities such as hypertension, diabetes mellitus, and heart failure with preserved systolic function; to manifest angina rather than MI; and, to have atypical symptoms of angina and MI.

Diabetic Patients

75% of all deaths among diabetic patients are due to coronary artery disease. Diabetic patients with unstable angina or NSTEMI tend to have a more severe disease with worse outcomes. Long term morbidity and mortality in diabetic patients with no previous cardiovascular disease are the same as that of nondiabetic patients with established cardiovascular disease after hospitalization for unstable coronary artery disease.[198]

Post-CABG Patients

Post-CABG patients with unstable angina or NSTEMI are associated with a more severe coronary artery disease compared to the patients who have not undergone a bypass surgery. Medical treatment in this patient population should follow the same guidelines as for UA/NSTEMI in non–post CABG patients.

Elderly

Elderly patients represent a group of patients who have more comorbidities and who are both at risk for both CAD as well as for associated complications. However, they do derive equivalent or greater benefit from intervention when compared to younger patients. This group is likely to present with atypical symptoms like dyspnea and confusion rather than chest pain. On the other hand, presence of noncardiac comorbidities such as chronic obstructive lung disease, gastroesophageal reflux disease, upper-body musculoskeletal symptoms, pulmonary embolism, and pneumonia is also higher, thus making the diagnosis of UA/NSTEMI challenging. Secondly, they are more likely to have altered or abnormal cardiovascular anatomy, increased cardiac afterload due to decreased arterial compliance and arterial hypertension, orthostatic hypotension, cardiac hypertrophy, and ventricular dysfunction, especially diastolic dysfunction. Thirdly, elderly patients generally have other cardiac comorbidities and risk factors, such as hypertension, prior MI, HF, cardiac conduction abnormalities, prior CABG, peripheral and cerebrovascular disease, diabetes mellitus, renal insufficiency, and stroke. As a result, they are on mulitple medications and hence at risk for drug interactions and polypharmacy. When considering revascularization procedures, general medical and cognitive status, bleeding risk and other risk of interventions, anticipated life expectancy, and patient or family preferences must be considered.

Chronic Kidney Disease

Chronic kidney disease (CKD) constitutes a risk factor for adverse outcomes after MI. It is a coronary artery disease equivalent as well as a risk factor for progression of CAD.

Drug and Substance Abusers

Cocaine and methamphetamine are common drugs associated with MI.

Prinzmetal's Angina

Prinzmetal's angina, also known as variant angina or angina inversa, is chest pain at rest that occurs in periodic cycles. It is unrelated to exertion although can occur with exertion. Prinzmetal's angina is caused by vasospasm, a narrowing of the coronary arteries caused by contraction of the smooth muscle tissue in the vessel walls rather than fixed narrowings of the coronary arteries due to atherosclerosis. Attacks can be precipitated by an emotional stress, hyperventilation, exercise, or exposure to cold. A circadian variation in the episodes of angina is most often present, with most attacks occurring in the early morning. It is characterized by transient ST-segment elevation that spontaneously resolves or resolves with NTG use without progression to MI. The majority of patients have normal exercise tolerance, and stress testing may be negative. Because the anginal discomfort usually occurs at rest without a precipitating cause, it may simulate UA/NSTEMI secondary to coronary atherosclerosis.

Cardiovascular Syndrome X

Cardiovascular syndrome X refers to patients with angina or angina-like discomfort with exercise, ST-segment depression on exercise testing, and normal or nonobstructed coronary arteries on angiography. This entity should be differentiated from the metabolic syndrome X or metabolic syndrome, which describes patients with insulin resistance, hyperinsulinemia, dyslipidemia, hypertension, and abdominal obesity. It also should be differentiated from noncardiac chest pain.

Diagnosis

History and Symptoms

A person with unstable angina pectoris (UAP) will have a history of angina that has increased in frequency or intensity at the same level of exertion. Anginal pain can manifest in many forms ranging from chest pain to chest pressure to shortness of breath to epigastric pain. UAP is part of the spectrum of acute coronary syndromes (ACS) and requires immediate assessment and management by a qualified physician. The history and symptoms described by a patient with unstable angina can be identical to the symptoms of either NSTEMI or STEMI, both of which carry a poorer prognosis.[199][200][201][202][203][204][205][206][207][1][2][208][209][210][211][212][213][214][215][216][217][218][219][220][221][222][223][224][225][226][227][228][229][230][231][232][233][234][235][236][237][238][239][240][241][242][243][244][245][246][247][248][249][250][251][252][253][254][255][256][257][258][259][260][261][262][263][264][265][266][267][268][269][270][271][272][273][274][275][276][277][278][279][280][281][282][283][284][285][286][287][288][289][290]

Unstable Angina

UA can have typical or atypical presentations. The 3 classic forms of presentation are: a) Rest angina (angina commencing when the patient is at rest); b) New onset (less than 2 months) severe angina (at least CCS class II); or c) Increasing angina-previously diagnosed angina that has become distinctly more frequent, longer in duration, or lower in threshold (i.e., increased by 1 or more CCS class to at least CCS class III severity).

Non ST Elevation Myocardial Infarction

NSTEMI generally presents as prolonged, more intense rest angina or angina equivalent. Patients with suspected ACS must be evaluated rapidly. Evaluation should not be done over the phone but in person and in a place where a 12 lead ECG can be obtained. A focused history, examination, ECG and cardiac biomarkers are helpful to determine where the patient will be managed and whether the patient needs to be transferred or referred to a different hospital/setting. Physical examination should focus on identifying the precipitating factors, comorbid conditions, rule out alternative diagnosis and assess hemodynamic status of the patient.

Physical Examination

Patients with suspected ACS must be evaluated rapidly. The objectives of the initial evaluation are first to identify signs of immediate life-threatening instability and then to ensure that the patient is moved rapidly to the most appropriate setting for the level of care needed based on diagnostic criteria and an estimation of the need for intervention. It is recommended that patients with a suspected ACS with chest discomfort or other ischemic symptoms at rest for more than 20 min, hemodynamic instability, or recent syncope or presyncope to be referred immediately to an ED or a specialized chest pain unit.[291]

Laboratory Findings

Blood Studies

Laboratory findings for the diagnosis of unstable angina and NSTEMI include some baseline tests like complete blood count, electrolytes, serum creatinine and measurement of acute-phase proteins.

Biomarkers

Cardiac markers are biomarkers that are measured to evaluate heart function. Their levels increase in blood when the heart muscle is necrosed, as in MI. Clinically the most commonly used cardiac markers include troponins and creatine kinase-MB (CK-MB). Other markers are lactate dehydrogenase, aspartate transaminase, myoglobin, ischemia modified albumin, pro-brain natriuretic peptide and glycogen phosphorylase isoenzyme. Cardiac biomarker measurement is one of the initial tests in a patient with heart attack. Unstable angina is associated with negative cardiac biomarkers whereas NSTEMI is associated with elevated cardiac biomarkers.

Electrocardiogram

The EKG in patients with unstable angina can be variable. In some cases, no changes on EKG will be appreciated. In other cases, a resting EKG may show flipped or inverted T waves, ST segment depression, or non-specific ST-T changes. It is the first line of assessment in any patient suspected of having unstable angina.

Chest X-Ray

When suspecting UA/NSTEMI a chest X-ray is critical to aid in the exclusion of aortic dissection. A mediastinal mass consistent with a cancer may be present, but it is unlikely to present with a syndrome of accelerating chest pain. It is also used to evaluate other causes of chest pain or discomfort like pulmonary infection, pneumothorax, pulmonary hypertension etc.

Echocardiogram

Left ventricular function and wall motion abnormalities can be assessed promptly using an echocardiogram. It can also be used to exclude other possible causes of like aortic stenosis and hypertrophic obstructive cardiomyopathy. Valvular or mechanical complications from MI warrant an immediate transesophageal echocardiography.

Coronary Angiography

One other image modality that can be used in diagnosing and treating UA/NSTEMI is CT coronary angiography. This is a superior imaging technique with a sensitivity and specificity of 90% and 95% respectively.[292][293] Depending on the patient's symptoms and degree of suspicion for ACS, early coronary angiography can be performed to make a definitive diagnosis. If there is no evidence of either calcified or noncalcified plaque on coronary angiogram, then it is highly unlikely that the patient’s symptoms are due to UA/NSTEMI.

Treatment

Primary Prevention

Major risk factors for development of coronary heart disease have been established from several long term epidemiological studies.[294] [295] Various clinical trials have demonstrated that development of coronary diseases can be prevented or the risk of experiencing UA/NSTEMI in patients who have coronary heart disease can be lowered by modifying the main risk factors.[296][297][298]

Immediate Management

Initial management of acute coronary syndrome (ACS) begins with differentiating between the spectrum of ACS which includes STEMI, unstable angina and Non-ST Elevation Myocardial Infarction. Because the symptoms for all these can be similar, a medical evaluation is necessary as mentioned in other sections (see Pre-hospital Care and Initial Therapy). Information from the history, physical examination, 12-lead ECG, and initial cardiac biomarker tests can help in differentiating between the above three categories as well as categorize the patient into probable or definite ACS, chronic stable angina or non-cardiac cause of chest pain. Patients with STEMI must be evaluated for immediate reperfusion therapy (see Reperfusion Therapy (Overview of Fibrinolysis and Primary PCI)). Patients with unstable angina/NSTEMI, recurrent symptoms suggestive of ACS and/or electrocardiogram ST-segment deviations, or positive cardiac biomarkers who are hemodynamically stable should be admitted to an inpatient unit for bed rest with continuous rhythm monitoring and careful observation for recurrent ischemia and managed with either an invasive or conservative strategy (see initial conservative versus initial invasive strategies). Immediate management is directed towards relief of chest pain. Nitrates, ASA and morphine are recommended to control the symptoms from possible ACS. Beta blockers, thienopyridines (like clopidogrel and prasugrel) should be administered in the absence of contraindication to their use. Based on the suspicion for likelihood of ACS, anticoagulants and GP IIb/IIIa inhibitors can be started early in the course of presentation. Two strategies in the treatment are early invasive or conservative strategies. Most trials have shown benefit of early invasive therapy with cardiac catheterization and revascularisation procedures. Early invasive therapy is now recommended for patients with UA/NSTEMI and ST segment changes at presentation and/or positive troponins during first 24hrs of presentation.

Antithrombin Therapy

Anticoagulation, traditionally with unfractionated heparin (UFH), is a cornerstone of therapy for patients with unstable angina/NSTEMI. Some of the agents available in this category include unfractionated heparin, low molecular weight heparin, direct thrombin Inhibitors (e.g.,bivalirudin) factor Xa Inhibitors (e.g.,fondaparinux), and warfarin. These agents are also sometimes referred to as antithrombins, although, it should be noted that they often inhibit one or more proteins in the coagulation cascade before thrombin.

Antiplatelet Agents

Aspirin

Antiplatelet therapy plays a major role in the management of unstable angina/NSTEMI. This class of medication is directed towards one of the following three pathways: decreasing thromboxane A2 formation (aspirin), inhibiting the P2Y12 component of the adenosine diphosphate (ADP) receptor pathway (thienopyridines), direct inhibitors of platelet aggregation (GP IIb/IIIa inhibitors).

Thienopyridines

Thienopyridines are a class of drugs that inhibit ADP receptor/P2Y 12 and function as antiplatelet agents.

Glycoprotein IIb/IIIa Inhibitor

Glycoprotein IIb/IIIa (Gp IIb/IIIa) is an integrin complex present on the surface of the platelets. This complex aids in platelet aggregation during the clotting process by acting as a receptor for fibrinogen. Gp IIb/IIIa inhibitors are a class of antiplatelet agents that prevent platelet aggregation and thrombus formation by inhibiting the integrin complex.

Mechanical Reperfusion

Initial Conservative Versus Initial Invasive Strategies

Two approaches to the use of cardiac catheterization and revascularization in UA/NSTEMI include an initial invasive strategy, involving routine early cardiac catheterization and revascularization with percutaneous coronary intervention (PCI) or coronary bypass grafting (CABG) and a second more conservative approach with initial medical management with catheterization and revascularization only for recurrent ischemia either at rest or on a noninvasive stress test. The objective of this is to provide a strategy that has the most potential to yield the best clinical outcome and improve long-term prognosis.

PCI

Coronary angiography is useful for defining the coronary artery anatomy in patients with UA/NSTEMI and for identifying subsets of high-risk patients who can benefit from early revascularization. The benefits of early invasive strategy have been discussed in previous section (see Initial Conservative Versus Initial Invasive Strategies). Coronary revascularization with either PCI or CABG helps improve prognosis, relieve symptoms, prevent ischemic complications, and improve functional capacity. In recent years, increased utilization of PCI has been noticed mainly secondary to technical advancements and as a result of this, less complications associated with the procedure.

CABG

For patients with UA/NSTEMI, when revascularization is required, the choice is between PCI and CABG. In general, the indications for PCI and CABG in UA/NSTEMI are similar to those for stable angina. Based on the results of multiple randomized trials, CABG is recommended for patients with disease of the left main coronary artery and multivessel disease and impaired left ventricular function. However, recent advance in techniques and less complications with PCI have led to use of PCI for isolated left main disease.

Complications of Bleeding and Transfusion

Advancements in the efficacy and increased utilization of synergistic anti-platelet agents, anticoagulant therapies, and invasive risk stratification in high-risk patients with unstable angina and non-ST-segment elevation myocardial infarction (NSTEMI) has led to a 40% decrease in mortality from coronary artery disease (CAD) over the preceding 20 years.[1][2] The advanced management of NSTEMI minimizes ischemic events; however the paradigm is that it also increases the risk of bleeding and necessitation for blood transfusion.[299][300][1][2] Recent analyses and randomized controlled trials demonstrate an independent association between bleeding complications, blood transfusions, and poor outcomes among NSTEMI patients.[301][302][1][2] Clinical trials of antithrombotic therapies associated with decreased bleeding complications have demonstrated improvements in short-term and long-term survival.

Discharge Care

Medical Regimen

In most cases, the inpatient anti-ischemic medical regimen used in the nonintensive phase should be continued after discharge, and the antiplatelet/anticoagulant medications should be changed to an outpatient/oral regimen. The selection of a medical regimen should be individualized to the specific needs of each patient based on the in-hospital findings and events, the risk factors for CAD, drug tolerability, and recent procedural interventions.

Post-Discharge Follow-Up

Patients with UA/NSTEMI, specially those with high risk factors during hospital stay, have high mortality which can be as high as 14 fold compared to those with absence of risk factors.

Long-Term Medical Therapy and Secondary Prevention

Similar to patients with STEMI, patients with UA/NSTEMI also require secondary prevention at the time of discharge. Patients and their families should be educated regarding the specific targets for LDL cholesterol and HDL cholesterol, blood pressure, body mass index (BMI), physical activity, and other appropriate lifestyle modifications.

References

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