Cardiovascular Emergencies - Part 2 pdf

2.4.1 Non-occlusive thrombus: asymptomatic Disruption of vulnerable plaques occurs relatively frequently, 9 but thrombus does not accumulate on the plaque surface and patients remain asymptomatic with a normal ECG, cardiac enzymes, and troponins. The relatively high frequency with which plaque fissuring occurs indicates the importance of the thrombotic response in determining subsequent clinical events. 2.4.2 Abrupt reduction in luminal diameter: unstable angina The next possibility is that the thrombus produces a reduction in luminal diameter that falls short of complete occlusion. Under these circumstances the luminal clot tends to be platelet rich 10 (and as such, relatively resistant to thrombolysis 11 ). The release of vasoactive substances from these platelets produces spasm of the smooth muscle in the Cardiovascular Emergencies 30 Intraluminal thrombus propagation thrombus blood flow intraplaque thrombus lipid pool partial obstruction distal embolisation transient occlusion persistent occlusion unstable angina ST depression MI ST elevation MI elevated cardiac enzymes elevated troponins Figure 2.3 Clinical syndromes associated with the presence of intracoronary thrombus. Modified from Davies. 1 1318 BMJ Cardio Emergencies 29/5/01 3:46 pm Page 30 adjacent arterial wall which further contributes to luminal narrowing. Luminal obstruction may be sufficient to produce an abrupt reduction in flow or even intermittent (10–20 minutes) occlusion, resulting in unstable angina (Figure 2.3). Several factors then determine the development of myocardial ischaemia. The degree of luminal obstruction caused by the plaque/thombus complex This will vary due to the dynamic interplay between the innate thrombotic and thrombolytic factors active on the plaque’s surface. These tend to produce cyclical variations in the thrombus load. Vascular tone of the adjacent arterial segment Forty per cent of non-stenotic plaques are eccentric and thus there will be segments of arterial wall adjacent to the plaque where vascular tone remains an important determinant of vessel diameter. Platelet aggregation results in intense vasoconstriction of the vessel wall which is not held rigid by the disrupted plaque. Myocardial oxygen demand For a given degree of arterial narrowing the amount of myocardial ischaemia will depend on the myocardial oxygen demand, which will be determined by the product of rate and force of contraction. The combination of these factors produces the characteristically intermittent and apparently unpredictable occurrence of the pain in unstable angina, with variations in arterial supply accounting for around 70% of ischaemic episodes and 30% attributable variations in metabolic demand. Clinical history Abrupt onset or deterioration in exertional angina or of angina occurring at rest. Acute coronary syndromes I 31 1318 BMJ Cardio Emergencies 29/5/01 3:46 pm Page 31 ECG During periods of ischaemia this shows reversible ST depression (Figure 2.4) sometimes associated with T wave inversion which may persist after the resolution of the ischaemic episode. The ECG is frequently normal during pain- free periods (when there is insufficient luminal obstruction to cause ischaemia). The ECG can occasionally be normal during pain if ischaemia occurs in the electrically silent circumflex perfusion zone. Cardiac enzymes Normal. Troponins Normal or elevated (the latter defining a high risk group). 2.4.3 Intermittent occlusion or distal propagation of thrombus: non-Q wave infarction A third possibility is that brief intermittent occlusion of the artery may occur due to luminal obstruction by thrombus for Cardiovascular Emergencies 32 Figure 2.4 Unstable angina/non-ST elevation infarction. ST depression in leads I, II, III, aVF and V4–V6 with T wave inversion in II, III and aVF. Critical circumflex stenosis at angiography. 1318 BMJ Cardio Emergencies 29/5/01 3:46 pm Page 32 < 1 hour followed by spontaneous thrombolysis, or there may be embolisation of thrombus from the plaque surface into the distal coronary bed. 12 Both of these processes result in non-Q wave infarction. The Q wave/non-Q wave differentiation does not necessarily equate with the pathological entities of transmural and non-transmural infarction 13 and these terms are no longer used. Non-Q wave infarction may also result from total coronary occlusion in the presence of collaterals supplying the myocardium which reduce the magnitude of infarction. In a proportion of patients this embolisation of platelet- derived thrombi into the distal coronary circulation results in sudden death and this process appears to be the mechanism in 45% of cases of sudden death. 14 Clinical history Clinically indistinguishable from unstable angina. ECG Appearances are identical to those of unstable angina with reversible ST depression (although this tends to be deeper and more prolonged) with later T wave inversion. Cardiac enzymes and troponins Both elevated. 2.4.4 Stable occlusion: ST elevation infarction Alternatively, the thrombus can completely occlude the artery, under these circumstances the thrombus tends to be rich in erythrocytes enmeshed in fibrin 10 (Figure 2.5). This results in complete obstruction to coronary flow for >1 hour and usually produces the clinical entity of ST elevation (Figure 2.6), although this is far from absolute and the presence of a collateral circulation may modify the extent of subsequent myocardial necrosis. Again, the process of occlusion is initially cyclical in many patients 15 resulting in a stuttering Acute coronary syndromes I 33 1318 BMJ Cardio Emergencies 29/5/01 3:46 pm Page 33 presentation of pain before occlusion becomes established. Total coronary occlusion also provides the second of the three mechanisms responsible for sudden cardiac death and is responsible for around 30% of cases. 14 Clinical history Continuous pain lasting in excess of half an hour and usually much longer. ECG ST elevation, followed by eventual resolution with loss or R wave voltage and the formation of Q waves. Cardiovascular Emergencies 34 artery occluded by thrombus and expanded plaque plaque expansion by haemorrhage into plaque Figure 2.5 Occlusive plaque haemorrhage. Figure 2.6 ST elevation infarction. ST elevation V2–V5. LAD occlusion at angiography. 1318 BMJ Cardio Emergencies 29/5/01 3:46 pm Page 34 Cardiac enzymes and troponins Elevated. 2.4.5 Acute reperfusion: ST segment resolution/non- resolution Removal of the occlusive thrombus either by the thrombolysis (natural or pharmacological) or using angioplasty may produce restoration of arterial flow and ST segment resolution. However, the presence of platelet microthrombi and myocardial oedema in the capillary bed may prevent reperfusion occurring within the myocardium itself (the “no- reflow phenomenon”). Under these circumstances, the ST elevation persists (Figure 2.7). Conversely, if reperfusion occurs via collaterals despite persistent occlusion at the site of the fissured plaque, ST resolution occurs. The fact that the ECG predicts occlusion at the level of the plaque but reperfusion at the level of the myocardium is initially confusing but provides further useful information as failure of ST resolution is associated with a less favourable prognosis. 16 Acute coronary syndromes I 35 Figure 2.7 Correlating ST segment resolution with arterial pathology. Modified from Davies and Ormerod. 16 1318 BMJ Cardio Emergencies 29/5/01 3:46 pm Page 35 2.5 Chronic resolution of thrombus and plaque remodelling Chronic resolution of the plaque–thrombus complex occurs with a variable degree of incorporation of thrombus into the plaque substance (Figure 2.8). This can result in increases in plaque size (producing stable angina if luminal obstruction is >50%) or a return of the plaque to its previous dimensions and the patient to an asymptomatic state. This ability of plaques to progress rapidly, superimposed on the underlying development of gradual progression, produces the unpredictable variability in the development of atheroma. Following thrombolysis for acute myocardial infarction the average degree of luminal obstruction is >60% 17 and thus symptoms of ongoing ischaemia are not invariable. The clinical correlates of this are that many patients with acute coronary syndromes can be managed medically once the plaque has healed and do not invariably require mechanical intervention to reduce luminal obstruction by the residual plaque. 2.6 Additional factors in the relationship between arterial pathology and clinical presentation Although the above correlations between events on the plaque surface and subsequent clinical events provide a Cardiovascular Emergencies 36 endothelium reseals over plaque surface reduced arterial lumen intramural haemorrhage incorporated into expanded plaque Figure 2.8 Resolution and remodelling following plaque haemorrhage. 1318 BMJ Cardio Emergencies 29/5/01 3:46 pm Page 36 framework for understanding acute coronary syndromes, these mechanisms are an over-simplification and some additional processes need to be taken into account. 2.6.1 Relationship between initial ST shift and Q wave development Classical ECG teaching states that ST elevation occurs when the myocardium nearest to the recording electrode is damaged (“epicardial ischaemia”) whereas ST depression occurs where there is an intervening segment of normal myocardium (“subendocardial ischaemia”). It is tempting to simplify this situation into ST elevation resulting in Q wave infarction and ST depression producing non-Q wave infarction/unstable angina. Unfortunately, there is a crossover population with some patients who initially presented with ST elevation developing non-Q wave infarctions and a minority of those with ST depression subsequently developing Q waves. These inconsistencies in the relationship between arterial pathology and ECG findings tend not to produce problems in clinical practice as the response to the therapeutic strategies available has been defined on the basis of initial ST segment change (see Chapters 3 and 4). 2.6.2 Alternative mechanisms of non-Q wave infarction A second inconsistency is that although the majority of patients with ST depression have either brief arterial occlusion or embolisation of platelet thrombi, in some proportion there is persistent occlusion of the epicardial artery combined with perfusion from collaterals. Importantly, in the setting of multivessel coronary disease, the collaterals themselves may be dependent on a critically stenosed vessel and intermittent ischaemia can then occur despite an occluded culprit vessel. 2.6.3 Unstable angina and no thrombus Although the majority of studies of patients with unstable angina demonstrate intracoronary thrombus either Acute coronary syndromes I 37 1318 BMJ Cardio Emergencies 29/5/01 3:46 pm Page 37 angiographically, angioscopically, or at post mortem, this is not a universal finding. 18 Whilst some of these discrepancies are attributable to the timing of the investigation and the wide clinical spectrum of unstable angina, smooth muscle proliferation in the absence of plaque rupture may account for a proportion of cases 19 particularly in restenosis following angioplasty. Summary Q wave MI Persistent occlusion > 1 hour Non-Q wave MI Transient occlusion < 1 hour Platelet emboli into distal coronary tree Persistent occlusion ϩ collaterals Unstable angina Transient occlusion 10–20 minutes Platelet emboli into distal coronary tree Persistent occlusion ϩ multivessel disease Sudden ischaemic death Persistent occlusion Platelet emboli into distal coronary tree No intramural thrombus – primary arrhythmia References 1 Davies MJ. The pathophysiology of acute coronary syndromes. Heart 2000;83:361–6. 2 Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 1995;92:1355–74. 3 Fuster V. Elucidation of the role of plaque instability and rupture in acute coronary events. Am J Cardiol 1995;76:24C–33C. 4 Mann JM, Davies MJ. Vulnerable plaque. Relation of characteristics to degree of stenosis in human coronary arteries. Circulation 1996;94:928–31. 5 Ambrose JA, Fuster V. The risk of coronary occlusion is not proportional to the prior severity of coronary stenoses. Heart 1998;79;3–4 6 Hangartner JR, Charleston AJ, Davies MJ, Thomas AC. Morphological characteristics of clinically significant coronary artery stenosis in stable angina. Br Heart J 1986;56:501–8. 7 Burke AP, Farb A, Malcolm GT, Liang YH, Smialek J, Virmani R. Coronary risk factors and plaque morphology in men with coronary disease who died suddenly. N Engl J Med 1997;336:1276–82. 8 Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med 1999;340;115–26. Cardiovascular Emergencies 38 1318 BMJ Cardio Emergencies 29/5/01 3:46 pm Page 38 9 Kristensen SD, Ravn HB, Falk E. Insights into the pathophysiology of unstable coronary artery disease. Am J Cardiol 1997;80:5E–9E. 10 Mizuno K, Satomura K, Miyamoto A, et al. Angioscopic evaluation of coronary artery thrombi in acute coronary syndromes. N Engl J Med 1992;326:287–91. 11 Jang IK, Gold HK, Ziskind M, et al. Differential sensitivity of erythrocyte- rich and platelet-rich arterial thrombi to lysis with recombinant tissue- type plasminogen activator. A possible explanation for resistance to coronary thrombolysis. Circulation 1989;79:920–8. 12 Davies MJ, Thomas AC, Knapman PA, Hangartner IR. Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death. Circulation 1986;73:418–27. 13 Phibbs B. “Transmural” versus “subendocardial” myocardial infarction: an electrocardiographic myth. J Am Coll Cardiol 1983;1:561–4. 14 Davies MJ, Bland JM, Hangartner JR, Angelini A, Thomas AC. Factors influencing the presence or absence of acute coronary artery thrombi in sudden ischaemic death. Eur Heart J 1989;10:203–8. 15 Hackett D, Davies G, Chierchia S, Maseri A. Intermittent coronary occlusion in acute myocardial infarction. Value of combined thrombolytic and vasodilator therapy. N Engl J Med 1987;317:1055–9. 16 Davies CH, Ormerod OIM. Diagnosis and management of failed thrombolysis. Lancet 1998;351:1191–6. 17 Hackett D, Davies G, Maseri A. Pre-existing coronary stenoses in patients with first myocardial infarction are not necessarily severe. Eur Heart J 1988;9:1317–23. 18 Waxman S, Mittleman MA, Zarich SW, et al. Angioscopic assessment of coronary lesions underlying thrombus. Am J Cardiol 1997;79:1106–9. 19 Flugelman MY, Virmani R, Correa R, et al. Smooth muscle cell abundance and fibroblast growth factors in coronary lesions of patients with nonfatal unstable angina. A clue to the mechanism of transformation from the stable to the unstable clinical state. Circulation 1993;88:2493–500. Acute coronary syndromes I 39 1318 BMJ Cardio Emergencies 29/5/01 3:46 pm Page 39 [...]... difference GISSI-1 28 ISIS -2 1 4 GISSI -2 ISIS-3 17 16 GUSTO-1 20 53 Cardiovascular Emergencies Box 3.4 Thrombolytic dosage schedules Streptokinase 1.5 million units in 50 ml 5% dextrose infused over one hour Alteplase 15 mg bolus 50 mg over 30 minutes (0.75 mg/kg) 35 mg over 60 minutes (0.5 mg/kg) followed by Heparin 5000 units bolus Heparin infusion for 48 hours (aiming for KCCT of 1.5 2 control) Streptokinase.. .Cardiovascular Emergencies 3: Acute coronary syndromes II: myocardial infarction with ST elevation CH DAVIES,Y BASHIR 3.1 3 .2 3.3 3.4 3.5 Introduction Correlations between site of infarction and ECG abnormalities 3 .2. 1 Anterior infarction 3 .2. 2 Inferior infarction 3 .2. 3 Posterior infarction 3 .2. 4 Right ventricular infarction 3 .2. 5 Infarction with few ECG changes 3 .2. 6 Assessing infarct... 1,30 GUSTO 2b29 Possibly Immediate Immediately following ESCG, 32 TAMI 533 No Rescue Following failed thrombolysis RESCUE34 Early 24 hours – all patients TOPS37 56 Yes No Acute coronary syndromes II 3.4.4 Use of ␤-blockers The benefits of ␤-blockers are less significant than those of thrombolysis (6 lives saved per 1000) Although the TIMI-2B trial demonstrated... infarcts, hypotension (< 120 mmHg), or tachycardia (>100/min) .22 Table 3 .2 Summary of key thrombolytic trials Name Therapy Result SK vs placebo SK beneficial SK vs placebo SK beneficial SK vs alteplase vs anistreplase No difference SK vs alteplase vs anistreplase No difference Front loaded alteplase vs SK Small benefit for alteplase GUSTO-2B29 Alteplase vs PTCA Small benefit for PTCA GUSTO-318 Alteplase vs... therapy in the general clinical setting In particular the use of combination 59 Cardiovascular Emergencies (SKϩtPA) thrombolysis was not associated with clinical benefit in GUSTO-1 (administered non-selectively to all patients and not specifically targeted at those who failed to reperfuse) but was associated with a doubling of the intracranial haemorrhage rate .20 This provides clear evidence of the potential... block, AV block 42 Acute coronary syndromes II 3 .2. 2 Inferior infarction Inferior infarction results in ST elevation in leads II, III, and atrioventricular fibrillation (VF) The diagnostic uncertainty in inferior infarction stems from the fact that the inferior surface of the heart is supplied by the right coronary artery (RCA) in two-thirds of patients, whilst in approximately one-third the inferior... resulted in serious harm The importance of aspirin is sometimes underplayed: the mortality reduction in ISIS -2 associated with aspirin was similar to that obtained with streptokinase (20 lives saved per 1000).14 The dose of aspirin must be in excess of 150 mg (as an approximation to the 165 mg of ISIS -2 ) and there is some pharmacokinetic data to support the use of 300 mg as the initial dose to ensure early... various mechanical complications of infarction is also dependent upon the site of infarction 41 Cardiovascular Emergencies Two-thirds of post-infarction ventricular septal defects follow anterior infarction (as a greater proportion of the intraventricular septum’s supply is derived from the LAD) whereas three-quarters of cases of papillary muscle rupture occur in the setting of inferior infarction Free... below) 3.5 .2 Management of bradycardia and sinus tachycardia Bradycardia This is discussed in Chapter 12 Sinus tachycardia This is frequently a manifestation of an extensive infarct7, 52 and it is a mistake under these circumstances to ␤-block the patient without first performing a chest x ray to exclude occult pulmonary oedema Other causes of tachycardia to consider are volume depletion (in particular... GUSTO-1 study20 (7.3% to 6.3% – about one life saved per hundred treated) It may be that the benefits observed owe more to the differences in the infusion regimen rather than any differences in pharmacology21 and this level of benefit seems insufficient to justify the routine use of alteplase given its increased cost and the increased rate of haemorrhagic stroke (an additional 3 per 1000 patients .20 . Engl J Med 1997;336: 127 6– 82. 8 Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med 1999;340;115 26 . Cardiovascular Emergencies 38 1318 BMJ Cardio Emergencies 29 /5/01 3:46 pm Page. Introduction 3 .2 Correlations between site of infarction and ECG abnormalities 3 .2. 1 Anterior infarction 3 .2. 2 Inferior infarction 3 .2. 3 Posterior infarction 3 .2. 4 Right ventricular infarction 3 .2. 5 Infarction. Engl J Med 19 92; 326 :28 7–91. 11 Jang IK, Gold HK, Ziskind M, et al. Differential sensitivity of erythrocyte- rich and platelet-rich arterial thrombi to lysis with recombinant tissue- type plasminogen