The pain is not sharp (some patients confuse \200\234sharp \200\235 with \200\234severe \200\235). Pain lasts longer than a few seconds and rarely exceeds an hour without varying in severity. Most episodes will last 1 \200\2235 minutes. The response to nitroglycerin, if any, will be almost immediate. Generally, responses taking more than 5 minutes are unlikel y to be related to the drug. Chest wall tenderness suggests musculoskeletal pain and does not accom- pany angina. Dyspnea, fatigue, nausea, and recurrent belching may also represent underlying ischemia and can occur in the absence of the classical central chest pain. The clue to underlying ische mic heart disease (IHD) lies in their precipitation by exertion or emotional stress. Angina is often classi \201 ed according to its temporal pattern and its rela- tion to exertion because this loosely re \202 ects prognosis. \200 Stable angina constant level of exertion. Unstable angina is characterized by pain on minor exertion or at rest, which is either new onset or a dramatic worsening of existing angina. Also, it can present as pain on ever-diminishing levels of exertion, usually over a period of days. is characterized by pain occurring after a relatively The Canadian Cardiovascular Society (CCS) system provides a quantitative means to describe exertional capacity and is divided into four classes: I. Minimal limitation of ordinary activity. Angina occurs with strenuous, rapid, or prolonged exertion at work or recreation. II. Slight limitation of ordinary activity; angina occurs on walking or climb- ing stairs r apidly; walking in cold, in wind, or under emotional stress. III. Marked limitation of ordinary physical activity; angina occurs on walking 50 \200\223100 m on level ground or climbing 1 \202 ight of stairs at a normal pa ce in normal conditions. Inability to perform any physical activity without discomfort; ang ina symptoms may be present at rest. IV. ANGINA PECTORIS 87 Physical examination \200 Measure the pulse rate. This may be slowed by inferior ischemia due to atrioventricular (AV ) node ischemia. A resting tachycardia, if present, usually represents activation of the sy mpathetic nervous system but may be due to an arrhythmia precipitated by ischemia. Blood pr essure measurement is essential to look for evidence of hypertension (predisposing to ather oma) or hypotension (may re \202 ect cardiac dysfunction or overmedication). Precordial ex amination should include palpation for left ventricular hypertrophy (LVH), cardiac enlargem ent, or dyskinesis, and auscultation for added heart sounds (heart failure or acute ischemi a), aortic stenosis, or mitral regurgitation (due to papillary muscle dysfunction). Examine for signs of heart failure by listening for \201 ne, late-inspiratory crackles at the lu ng bases and looking for dependent pitting edema (typically bilateral ankle leg edema, b ut sacral edema may be the only manifestation if the patient has been recumbent for some ti me). Look for evidence of peripheral vascular disease by palpating for aortic aneurysm; fee ling the carotid and limb pulses; listening for carotid, renal, or femoral artery bruits; a nd assessing tissue integrity and capillary re \201 ll of the legs and feet. Examine for s igns of hypercholesterolemia: the eyes for xanthelasmata and corneal arcus, and the skin an d tendons (especially the Achilles) for xanthomata. Differential diagnosis The differential diagnosis of anginal chest pain is wide and include s \200 \200 \200 \200 \200 \200 Anxiety and hyperventilation Musculoskeletal chest wall pain Cervical or thoracic root pain Pneumothorax, pneumonia, or pulmonary embolus Esophageal problem (in \202 ammation/spasm) Other upper gastrointestinal (GI) problem (gastritis, peptic ulcer, pancreatitis, cholecys titis) Pericarditis Aortic dissection Mitral valve prolapse Coronary emboli (LV mural throm bus, atrial myxoma) \200 \200 \200 Investigations Further risk strati \201 cation will add to the diagnostic certainty achiev ed by history and examination. Measure complete blood count (CBC), chemis- tries, a full fa sting lipid pro \201 le (total, LDL and HDL cholesterol and triglyc- eride levels), and bl ood glucose. Chest X-ray (CXR) is not mandatory but should be performed if there is suspicion of heart f ailure, aortic dissection, a pulmonary condition or an abnormality of the bony structures o f the chest wall. CHAPTER 2 Coronary artery disease 88 12 Lead ECG A resting electrocardiogram (ECG) may not con \201 rm the diagnosis but can po int toward ischemic heart disease. The presence of Q waves suggests previous myocardial inj ury. The presence of ST depression and, to a lesser extent, T-wave inversion during pain is a marker of ischemia and patients with these signs should be further investigated. If ST-s egment deviation is observed at rest, an acute coronary syndrome must be excluded. A 12-lead ECG can also help identify other causes of chest pain (LVH, arrhythmia, pericarditis). Tests for inducible ischemia Tests such as exercise ECG, stress echocardiogram (ECHO), or m yocar- dial perfusion scanning are useful adjuncts to con \201 rm the diagnosis and aid ma nagement. Management Lifestyle Smoking cessation is of paramount importance. Encourage daily aerobic exercise within limits of exercise capacity. Look at the patient \200\231s occupa- tional n eeds and advise adjustment if symptom level is not compatible. Advise a healthy diet, colla borating with dieticians if required. Aspirin Provide aspirin in all cases unless there is active peptic ulcer disease, allergy ( desensitizing may be required), or bleeding diathesis. Those with past peptic ulcer disease may take a gastroprotective agent such as an H2 antagonist or proton pump inhibitor. Anti-anginals B \200 Blockers: First line (e.g., atenolol 25 \200\223100 mg qd or metoprolol 25 \200\22350 mg bi d). Start on suspicion of ischemic heart disease. Avoid only if contraindicated (asthma wit h con \201 rmed B-agonist response (mortality improved in patients with angina and concomi tant COPD if they can tolerate bronchospasm), uncontrolled severe LV dysfunction, bradycard ia, coronary artery spasm). Calcium antagonists contraindicated or concern for vasospasm, c alcium antagonists become the drug of choice. Nitrates (e.g., nitroglycerin): Used for cont rol of breakthrough angina. Long-acting nitrates (e.g., isosorbide mononitrate 60 \200\2231 20 mg qd) are a useful addition to B-blockers for prevention of attacks. (e.g., amlodipine or diltiazem): If B-blocker Statins Statins (HMG-CoA reductase inhibitors) reduce mortality by approxi- mately one-thir d in all risk groups. However, the underlying risk of events must be taken into account whe n considering starting the drug, because absolute risk reduction in young patients with low -risk IHD may be very small, with possible harm of myositis, hepatic failure, and reduced c ompli- ance with other medications. ACUTE CORONARY SYNDROMES 89 Acute coronary syndromes Acute coronary syndrome (ACS) is a term used to describe a constel lation of symptoms resulting from acute myocardial ischemia. An ACS resulting in myocardial injury is termed myocardial infarction (MI). ACS includes the diagnosis of unstable angina (UA), non-ST elevation myocardial infarction (NSTEMI), and ST elevation myocardial infarct ion (STEMI). De \201 nition The current nomenclature divides ACS into two major groups on the basis of delivered treatment modalities (see Fig. 2.1). ST elevation myocardial infarction (STEMI) \200\224an ACS in which patients present with ch est discomfort and ST-segment elevation on ECG. This group of patients must undergo reperfu sion therapy on presentation. Non-ST elevation myocardial infarction (NSTEMI) and unstable angina (UA) \200\224ACS in whi ch patients present with ischemic chest discomfort associated with transient or permanent n on-ST-elevation ischemic ECG changes. If there is biochemical evidence of myocardial injury , the condi- tion is termed NSTEMI, and in the absence of biochemical myocardial injury the condition is termed UA. This group of patients is not treated with thrombolysis. Initial management of ACS \200 All patients with suspected ACS should have continuous ECG monitoring and access to a de \201 brillator. Rapid assessment and stabilization is imperative. Immediate assessment should include \200 Rapid examination murmurs, and identify and treat acute pulmonary edema. Secure IV access. 12 Lead ECG should be obtained and reported within 10 minutes of presentation. Give the fol lowing: \200 Oxygen (initially only 28% if history of COPD) \200 Morphine 2.5 \200\2231 0 mg IV prn for pain relief \200 Aspirin 325 mg po \200 Nitroglycerin, unless hypotensi ve \200 Heparin IV and/or Integrilin \200 Consider addition of Plavix Take blood for th e following: \200 \200 to exclude hypotension, note the presence of \200 CBC/chemistries Glucose Supplement K+ to keep it at 4 \200\2235 mmol/L May be i acutely post-MI, even in nondiabeti cs, re \202 ecting a stress-catecholamine response and may resolve without treatment \200 \200 Biochemical markers of cardiac injury Lipid pro \201 le Serum cholesterol and HDL remain c lose to baseline for 24 \200\22348 hours but fall thereafter and take (cid:116)8 weeks to r eturn to baseline. Total cholesterol, LDL, HDL, triglycerides CHAPTER 2 Coronary artery disease 90 Portable CXR to assess cardiac size and pulmonary edema and to exclude mediastinal enlargem ent. General examination should include peripheral pulses, fundoscopy, and abdominal examin ation for organomegaly and aortic aneurysm. Box 2.1 Conditions mimicking pain in ACS \200 \200 \200 \200 \200 \200 \200 Pericarditis Dissecting aortic aneurysm Pulmonary embolism Esophageal re \202 ux, spasm, o r rupture Biliary tract disease Perforated peptic ulcer Pancreatitis Acute coronary syndromes No ST elevation ST elevation No enzyme rise NSTEMI Unstable angina NQ-MI QwMI Figure 2.1 Nomenclature of ACS. Patients with ACS may present with or without ST elevation on the ECG. Most patients with ST elevation (large arrows) ultimately develop Q-wave MI (Qw MI), whereas a minority (small arrow) develop a non-Q-wave MI (NQ-MI). Patients without ST elevation are experiencing either unstable angina or an NSTEMI depending on the absence or presence of cardiac enzymes (e.g., troponin) detected in the blood. This \201 gure was pu blished in Libby et al., Braunwald \200\231s Heart Disease, 8th edition. Copyright Elsevier 2007. ST ELEVATION MYOCARDIAL INFARCTION (STEMI) 91 ST elevation myocardial infarction (STEMI) Patients with ACS who have ST-segment elevation or new left bundle branch block (LBBB) on their presenting ECG bene \201 t signi \201 can tly from immediate reperfusion and are treated as one group under the term ST elevation myo cardial infarction (STEMI). Presentation \200 Chest pain is usually similar in nature to angina, but of greater sever ity and longer duration and is not relieved by sublingual (SL) nitroglycerin. Associated fe atures are nausea and vomiting, sweating, breathlessness, and extreme distress. The pain ma y be Diabetics and elderly or hypertensive patients may suffer painless ( \200\234silent \200\235 infarcts) and/or atypical infarction. Presenting features include breathlessness f rom acute pulmonary edema, syncope or coma from arrhythmias, acute confusional states (mani a/psychosis), diabetic hyperglycemic crises, hypotension or cardiogenic shock, central nerv ous system (CNS) manifestations resembling stroke secondary to sudden reduction in cardiac output, and peripheral embolization. \200 atypical (e.g., epigastric) or radiate to the back. Management Diagnosis is normally made on presentation followed by rapid stabiliza- tion to ensure institution of reperfusion therapy without delay. This is in contrast to NSTEMI/UA, where diagnosis may evolve over a period of 24 \200\22372 hours. Management principles of t he various stages are outlined below and expanded subsequently (see also Box 2.2). Stabilizing measures are generally similar for all ACS patients. \200 All patients with suspected STEMI should have continuous ECG monitoring in an area with ful l resuscitation facilities. Patients should receive immediate aspirin 325 mg po (if no cont raindications), analgesia, and oxygen. Secure IV access. Conduct rapid examination to exclu de hypotension, note the presence of murmurs, and identify and treat acute pulmonary edema. Right ventricular failure (RVF) out of proportion to left ventricular failure (LVF) sugges ts RV infarction. Diagnosis must be made on the basis of history, ECG (ST elevation/new LBBB), and biochemica l markers of myocardial injury. (Reperfusion must not be delayed to wait for biochemical ma rkers.) \200 Blood for CBC, biochemical pro \201 le, markers of cardiac injury, lipid pro \201 le, and glucose, and portable CXR. Treatment \200 \200 General medical measures (p. 96) Reperfusion (p. 98). CHAPTER 2 Coronary artery disease 92 All patients with STEMI should be admitted to an intensive care unit (ICU), e.g., coronary ICU (CICU). Discharge and risk prevention Box 2.2 Factors associated with a poor prognosis \200 \200 \200 \200 \200 \200 \200 \200 Age >70 years Previous MI or chronic stable angina Anterior MI or right ventricular infarct ion Left ventricular failure at presentation Hypotension (and sinus tachycardia) at present ation Diabetes mellitus Mitral regurgitation (acute) Ventricular septal defect STEMI: DIAGNOSIS 93 STEMI: diagnosis STEMI diagnosis is based on a combination of history, ECG, and bio- chemic al markers of cardiac injury. In practice, history and ECG changes are normally diagnostic, resulting in immediate reperfusion and medical treatment. Biochemical markers of cardiac i njury usually become available later and help recon \201 rm the diagnosis and provide prog nostic information (magnitude of rise). ECG changes \200 ST-segment elevation 2 weeks. ST elevation of (cid:116)2 mm in adjacent chest leads and (ci d:116)1 mm in adjacent limb leads is necessary to ful \201 ll thrombolysis criteria. Persi sting ST elevation after 1 month suggests formation of LV aneurysm. Infarction site can be localized from ECG changes as indicated in Table 2.1. Pathological Q waves conduction but a re not synonymous with irreversible myocardial damage. In the context of a \200\234transmu ral infarction \200\235 the Q waves may take hours or days to develop and usually remain in de \201 nitely. In the standard leads, the Q wave should be (cid:116)25% of the R wave, 0. 04 s in duration, with negative T waves. In the precordial leads, Q waves in V4 should be > 0.4 mV (4 small sq) and in V6 >0.2 mV (2 small sq), in the absence of LBBB (QRS width <0.1 s or 3 small sq). ST-segment depression ST-segment elevation) is secondary to ischemia in a territory other than the area of infarction (often indicative of multivessel disease) or r eciprocal electrical phenomena. Overall, it implies a poorer prognosis. occurs within minutes and may last for up to indicate signi \201 cant abnormal electrical in a second territory (in patients with Table 2.1 Localization of infarcts from ECG changes Anterior ST elevation and/or Q waves in V1 \200\223V4/V5 Anteroseptal ST elevation and/or Q waves in V1 \200\223V3 Anterolateral ST elevation and/or Q waves in V1 \200\223V6 and I and aVL Lateral ST elevation and/or Q waves in V5 \200\223V6 and T-wave inversion/ST elevation/Q waves in I and aVL Inferolateral ST elevation and/or Q waves in II, III, aVF, and 5 \200\223V6 (sometimes I and aVL) Inferior ST elevation and/or Q waves in II, III, and aVF Inferoseptal ST elevation and/or Q waves in II, III, aVF, V1 \200\223V3 True posterior Tall R waves in V1 \200\223V2 with ST depression in V1 \200\223V3. T waves remain upright i n V1 \200\223V2. This can be con \201 rmed with an esophageal lead if available (method si milar to an NG tube). This usually occurs in conjunction with an inferior or lateral infarc t RV infarction ST-segment elevation in the right precordial leads (V3R \200\223V4R). Usually found in conj unction with inferior infarction. This may only be present in the early hours of infarction CHAPTER 2 Coronary artery disease 94 Box 2.3 Conditions that may mimic ECG changes of a STEMI \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 \200 Left or right ventricular hypertrophy LBBB or left anterior fascicular block Wolff \200\223 Parkinson \200\223White syndrome Pericarditis or myocarditis Cardiomyopathy (hypertrophic o r dilated) Trauma to myocardium Cardiac tumors (primary and metastatic) Pulmonary embolus P neumothorax Intracranial hemorrhage Hyperkalemia Cardiac sarcoid or amyloid Pancreatitis and alterations in the contour of PR-segment elevation/depression the P wave are generally indicative of atrial infarction. Most patients will also have abnormal atrial rhythms such as atrial \201 brillation (AF) or \202 utter, wandering atrial pacemaker, and AV nodal rhythm. T-wave inversion after the ST elevation has resolved. Nondiagnostic changes, LBBB o r RBBB, tachyarrhythmias, transient tall-peaked T waves or T-wave inversion, axis shift (ex treme left or right), or AV block. may be immediate or delayed and generally persists but ones that may be ischemic, include new Biochemical markers of cardiac injury Serial measurements evaluating a temporal rise and fa ll should be obtained to allow a more accurate diagnosis. Creatine kinase (CK) and CK-MB fr om a skeletal muscle source tend to remain elevated for a greater time period in comparison to levels from a cardiac source. CK (creatine kinase) \200 \200 Levels twice the upper limit of normal are considered abnormal. Serum levels rise within 4 \200\2238 hours post-STEMI and fall to normal within 3 \200\2234 days. The peak level occur s at about 24 hours but may be earlier (12 hours) and higher in patients who have had reper fusion (thrombolysis or percutaneous coronary intervention [PCI]). False-positive rates of 15% occur in patients with alcohol intoxication, muscle disease or trauma, vigorous exerci se, convulsions, IM injections, hypothyroidism, pulmonary embolism (PE), and thoracic outle t syndrome. CK-MB isoenzyme is more speci \201 c for myocardial disease. Levels may be elevated despit e a normal total CK. However, CK-MB is also present in small quantities in other tissues (s keletal muscle, tongue, diaphragm, uterus, and prostate) and trauma or surgery may lead to false-positive results. If there is doubt about myocardial injury with CK-MB levels obtaine d, a cardiac troponin must be measured. STEMI: DIAGNOSIS 95 Cardiac troponins (TnT, TnI) \200 Both TnT and TnI are highly sensitive and speci \201 c markers of cardiac injury. Serum le vels start to rise by 3 hours post-MI and elevation may persist up to 7 \200\22314 days. Th is is advantageous for diagnosis of late MI. In most STEMI cases, the diagnosis can be made using a combination of the clinical picture and serial CK/CK-MB levels. In the event of no rmal CK-MB levels and suspected noncardiac sources of CK, troponins can be used. Troponins can also be elevated in nonischemic myocyte damage, such as myocarditis, cardiomyopathy, an d pericarditis. Other markers There are multiple other markers, but with increasing clinical availability o f troponins, measurements of these markers are not recommended. These include aspartamine t ransferase (AST) (rise 18 \200\22336 hours post-MI) and lac- tate dehydrogenase (LDH) (rise 24 \200\22336 hours post-MI). The time course of the various markers is seen in Figure 2.2. Cardiac enzymes \227 50 Trop CK CK \200\223MB AST LDH Trop Creatine kinase CK cardiac isoenzyme Aspartate transaminase Lactate dehydrogenase Cardiac t roponin CK \227 5 l e v e CK \200\223MB \227 4 l e m y z n e m u r e S \227 3 LDH \227 2 AST \227 1 0 1 2 3 4 5 6 Days 7 8 9 10 Figure 2.2 Graph of the appearance of cardiac markers in the blood vs. time of onset of sym ptoms. Peak A: Early release of myoglobin or CK-MB isoforms after acute myocardial infarcti on (AMI). Peak B: Cardiac troponin after AMI. Peak C: CK-MB after AMI. Peak D: Cardiac trop onin after unstable angina. Reprinted with permission from Wu AH, et al. (1999). Clin Chem 45(7):1104 \200\2231121. CHAPTER 2 Coronary artery disease 96 STEMI: general measures 1. Immediate stabilizing measures are as outlined on p. 89 for all ACS. 2. Control of cardiac pain \200 Morphine 2.5 \200\22310 mg IV is the drug of choice and may be repeated to ensure adequate pain relief, unless there is evidence of emerging toxicity (hypotension, respiratory depres sion). Nausea and vomiting should be treated with metoclopramide (10 mg IV) or a phenothiaz ine. Oxygen should be administered at 2 \200\2235 L/min for at least 2 \200\2233 hours. Hyp oxemia is frequently seen post-MI due to ventilation \200\223perfusion abnormalities second ary to LVF. In patients with refractory pulmonary edema, endotracheal intubation may be nec essary. Beware of CO2 retention in patients with COPD. Nitrates that the patient is not hyp otensive. These drugs should be used cautiously in inferior STEMI, especially with right ve ntricular infarction, as venodilation may decrease RV \201 lling and precipitate hypotens ion. Nitrate therapy has no demonstrated effect on mortality (ISIS-4). may lessen pain and can be given (sublingual or IV) provided 3. Correction of electrolytes Both low potassium and low magnesium may be arrhythmogenic an d must be supplemented, especially in the context of arrhythmias. 4. Strategies to limit in farct size (B-blockers, angiotensin-converting enzyme [ACE] inhibitors, and reperfusion). B -Blockade Early B-blockade has been shown to be bene \201 cial by limiting infarct size, r educing mortality, and decreasing early malignant arrhythmias. All patients (including prim ary PCI and thrombolysis patients) should have early B-blockade. Patients with the followin g features may bene \201 t most from B-blocker therapy: \200 \200 \200 Hyperdynamic state (sinus tachycardia, hypertensive) Ongoing or recurrent pain or reinfarct ion Tachyarrhythmias such as AF Absolute contraindications: heart rate (HR) <50, systolic blood pressure (SBP) <90 mmHg, mo derate to severe heart failure, AV conduction defect, severe airways disease. Relative contraindications: asthma, current use of calcium channel blocker and/or B-blocker , severe peripheral vascular disease with critical limb ischemia, large inferior MI involvi ng the right ventricle. Use a short-acting agent IV initially (metoprolol 5 mg at a time repeated at 5-minute inter vals to a maximum dose of 15 mg) under continuous ECG and BP monitoring. Aim for a HR of 60 beats per minute (bpm) and SBP 100 \200\223110 mmHg. If hemodynamic stability continues 15 \200\22330 minutes after the last IV dose, start metoprolol 50 mg po bid. Esmolol is an ul tra-short- acting IV B-blocker, which may be tried if there is concern whether the patient will tolerate B-blockers. STEMI: GENERAL MEASURES 97 ACE inhibitors After receiving aspirin, B-blockade (if appropriate), and reperfusion, all p atients with STEMI/LBBB infarction should receive an ACE inhibitor within the \201 rst 24 hours of presentation. \200 Patients with high risk or large infarcts, particularly with an anterior STEMI, a previous MI, heart failure, and impaired LV function on imaging, will bene \201 t most. The effect of ACE inhibitors appears to be a class effect; therefore, one may use the drug that the ph ysician is familiar with. CHAPTER 2 Coronary artery disease 98 STEMI: reperfusion therapy (thrombolysis) Rapid reperfusion is the cornerstone of current m anagement of STEMI and is marked by normalization of ST segments on ECG. Primary percu- tan eous intervention (PCI, or angioplasty) and thrombolysis are the main reperfusion modalitie s. The best long-term outcome is achieved with pri- mary PCI. Time is of paramount importance and thrombolysis should be admin- istered as soon as possib le. Reperfusion occurs in 50% \200\22370% of patients who receive thrombolysis within 4 hou rs of onset of pain. Thrombolysis reduces mortality, LV dysfunction, heart failure, cardiog enic shock, and arrhythmias. However, the magnitude of the bene \201 ts obtained with thrombolysis is smaller than with PCI. Furthermore, often patients must undergo cardiac catheterization to delineate their c oronary anatomy before further revas- cularization (whereas this is achieved at the same ti me with primary PCI). Indications for thrombolysis \200 Typical history of cardiac pain within previous 12 hours and ST elevation in two contiguous ECG leads (>1 mm in limb leads or >2 mm in V1 \200\223V6). Cardiac pain with newly presume d new LBBB on ECG. If ECG is equivocal on arrival, repeat at 15- to 30-minute intervals to monitor progression. Thrombolysis should not be given if the ECG is normal or if there is i solated ST depression (true posterior infarct must be excluded as described above). \200 Timing of thrombolysis \200 Greatest bene \201 t is achieved with early thrombolysis (especially if given within 1 1/2 hours of onset of \201 rst pain; see Box 2.4). Patients presenting between 12 and 24 hou rs from onset of pain should undergo thrombolysis only with persisting symptoms and ST-segm ent elevation. Elderly patients (>65 years) presenting within the 12- to 24-hour time perio d with symptoms are best managed by primary PCI, as thrombolysis has been demonstrated to r esult in increased incidence of cardiac rupture. Choice of thrombolytic agent \200 \200 This is partly determined by each center \200\231s local thrombolysis strategy. Allergic re actions and episodes of hypotension are greater with streptokinase (SK). Bolus agents are e asier and quicker to administer, with a decrease in drug errors in comparison to \201 rst -generation infusions. STEMI: REPERFUSION THERAPY (THROMBOLYSIS) 99 Recombinant tissue-type plasminogen activator (rtPA) has a greater reperfusion capacity and a marginally higher 30-day survival bene \201 t than that of SK, but this agent has been associated with an increased risk of hemorrhage. More recent rtPA derivatives have demonstr ated a higher 90-minute TIMI-III (coronary reperfusion scale) \202 ow rate, but have show n similar 30-day mortality bene \201 ts to those with rtPA. An rtPA derivative (rather tha n SK) should be considered for any patient with any of the following: \200 \200 Large anterior MI, especially if within 4 hours of onset Previous SK therapy or recent stre ptococcal infection (as this has been shown to be a risk factor for allergic reactions to S K) Hypotension (systolic BP <100 mmHg) Low risk of stroke (age <55 years, systolic BP <144 mmHg) Reinfarction during hospitalization where immediate PCI facilities are not available \200 \200 The characteristics of the major thrombolytic agents are on p. 100. Complications of thromb olysis \200 Bleeding is seen in up to 10% of patients. Most incidents are minor and at sites of vascula r puncture. Local pressure is generally suf \201 cient to stop this bleeding but occasiona lly transfusion may be required. In extreme cases, SK may be reversed by tranexamic acid (1 0 mg/kg slow IV infusion). Hypotension during the infusion is common with SK. Treatment con sists of placing the patient in a supine position and slowing/stopping infusion until the b lood pressure rises. Treatment with cautious (100 \200\223500 mL) \202 uid challenges may be required, especially in inferior/ RV infarction. Hypotension is not necessarily evidenc e of an allergic reaction and may not warrant treatment as such. Allergic reactions are com mon with SK and include a low-grade fever, rash, nausea, headaches, \202 ushing, and, rar ely (0.1%), anaphylaxis. Give hydrocortisone 100 mg IV with chlorpheniramine 10 mg IV. Intr acranial hemorrhage is seen in 0.3% of patients treated with SK and in 0.6% with rtPA. Re perfusion arrhythmias (most commonly a short, self-limiting run of idioventricular rhythm) may occur. Systemic embolization may occur from lysis of thrombus within the left atrium, L V, or aortic aneurysm. Box 2.4 Patients with greatest bene \201 t from thrombolysis \200 \200 \200 \200 \200 \200 Anterior infarct Marked ST elevation Age >75 years Impaired LV function or LBBB Systolic BP <100 mmHg Patients presenting within 1 hour of onset of pain CHAPTER 2 Coronary artery disease 100 Absolute contraindications to thrombolysis \200 \200 \200 \200 \200 \200 \200 Active internal bleeding Suspected aortic dissection Recent head trauma and/or intracranial neoplasm Previous hemorrhagic stroke at any time Previous ischemic stroke within the past 1 year Previous allergic reaction to \201 brinolytic agents Trauma and/or surgery within past 2 weeks at risk of bleeding Relative contraindications to thrombolysis \200 \200 \200 \200 Trauma and/or surgery more than 2 weeks previously Severe uncontrolled hypertension (BP >18 0/110) Nonhemorrhagic stroke over 1 year ago Known bleeding diathesis or current use of ant icoagulation within therapeutic range (INR (cid:116)2) Prolonged (>10 minutes) cardiopulmon ary resuscitation Prior exposure to SK (if planning to give SK, especially previous 6 \200 \2239 months) Pregnancy or postpartum Lumbar puncture within previous 1 month Menstrual ble eding or lactation History of chronic severe hypertension Noncompressible vascular puncture s (e.g., subclavian central venous lines) \200 \200 \200 \200 \200 Box 2.5 Doses and administration of thrombolytic agents Streptokinase (SK) \200 \200 Give as 1.5 million units in 100 mL normal saline IV over 1 hour. There is no indication fo r routine heparinization after SK; there is no clear mortality bene \201 t and there is a small increase in risk of hemorrhage. Recombinant tissue-type plasminogen activator (rtPA, alteplase) \200 The GUSTO trial suggested that the \200\234front-loaded \200\235 or accelerated rtPA is th e most effective dosage regimen. Give 15 mg bolus IV then 0.75 mg/kg over 30 minutes (not t o exceed 50 mg), then 0.5 mg/kg over 60 minutes (not to exceed 35 mg). This should be follo wed by IV heparin. Reteplase \200 Give two IV bolus doses of 10 units 10 minutes apart. Tenectaplase \200 Give as injection over 10 seconds at 30 \200\22350 mg according to body weight (500 \200 \223600 g/kg). Maximum dose is 50 mg. APSAC (anistreplase) \200 Give as an IV bolus of 30 mg over 2 \200\2235 minutes. STEMI: REPERFUSION BY PRIMARY PCI 101 STEMI: reperfusion by primary PCI Time is of the essence for reperfusion, and each institut ion should have its recommended protocol. It is imperative that there are no delays in both the decision-making and implementation processes for reperfusion. In centers where primary PCI is chosen, a rapid response network should be in place such that one telephone call fr om the triage unit should ensure rapid assembly of the PCI team for treatment of the patien t. Primary PCI Primary PCI is the current gold-standard reperfusion strategy for treat- ment o f STEMI. Primary PCI requires signi \201 cant coordination among emergency serv- ices, community ho spitals, and invasive centers. It must only be performed if 1) a primary PCI program is ava ilable and 2) the patient presents to an invasive center and can undergo catheterization wi thout delay. Indication for primary PCI \200 All patients with chest pain and ST-segment elevation or new LBBB ful \201 ll primary PCI criteria (compare with indications for thrombolysis). This includes a group of patients in whom ST-segment elevation may not ful \201 ll all criteria for thrombolysis. In general, p atients in whom thrombolysis is contraindicated should be managed by primary PCI. Patients in whom there is signi \201 cant risk of bleeding must be managed individually. Outcome in primary PCI \200 Data from over 10 large randomized trials demonstrate a superior outcome in patients with S TEMI who are treated with primary PCI in comparison to outcomes with thrombolysis. There is a signi \201 cant short-term, as well as long-term, reduction in mortality and major adve rse cardiac events (MACE) (death, nonfatal reinfarction, and nonfatal stroke) in STEMI pati ents treated with primary PCI. Furthermore, primary PCI patients have overall better LV fun ction, a higher vessel patency rate, and less recurrent myocardial ischemia. Multiple studi es (including PRAGUE-2 and DANAMI-2) have also demonstrated that interhospital transportati on for primary PCI (community hospital to invasive center) is safe, and primary PCI remains superior to thrombolysis despite the time delays involved. Complications \200 Bleeding from arterial puncture site, stroke, recurrent infarction, need for emergency coro nary artery bypass grafting (CABG), and death are similar in frequency to that in nonemerge nt high-risk PCI cases ( 1%). The best results are obtained from high-volume centers with s igni \201 cant experience in primary PCI. Each primary PCI center will have its own policy for management of cases, including the use of low-molecular-weight (LMW) or unfractionated (UF) heparin, antiplatelet agents (e.g., gpIIb/IIIa inhibitors), etc. It is generally acce pted that in the acute phase only CHAPTER 2 Coronary artery disease 102 the \200\234culprit \200\235 lesion(s) and vessel(s) will be treated. The pattern of disea se in the remainder of the vessels will determine whether further revascularization should be performed as an inpatient or an elective case in the future. STEMI patients treated with uncomplicated primary PCI can often be discharged safely within 72 hours of admission with out the need for further risk strati \201 cation. Primary PCI is more cost-effective in th e long term than thrombolysis with signi \201 cant savings from fewer days in the hospital , less need for readmission, and less heart failure. Post-discharge care, secondary prevent ion, and rehabilitation remain identical to that for other MI cases. Rescue PCI Rescue PCI may be performed as an adjunct to thrombolysis but should be reserved for patients who remain symptomatic post-thrombolysis (failure to reperfuse) or develop ca rdiogenic shock. We recommend that all patients who continue to have post-thrombolysis symp toms and/or ongoing ST-elevation with or without symptoms be discussed with the local invas ive cardiac center for urgent catheterization and revascularization. SURGERY FOR ACUTE STEMI 103 Surgery for acute STEMI Emergency surgical revascularization (CABG) cannot be widely applie d to patients who suffer an MI outside the hospital. CABG in uncomplicated STEMI patients a fter 6 hours from presentation is contraindicated second- ary to signi \201 cant hemorrhag e into areas of infarction. Unstable patients have a very high rate of perioperative mortal ity. CABG in the context of an acute STEMI is of value in the following situations: \200 High-risk coronary anatomy on catheterization (left main stenosis, left anterior descending [LAD] ostial disease). Complicated STEMI (acute mitral regurgitation, or ventricular ruptu re) STEMI patients (with or without successful thrombolysis) with additional coronary lesio ns whose anatomy is best served by CABG on prior or subsequent catheterization \200 CHAPTER 2 Coronary artery disease 104 STEMI: additional measures Low-molecular-weight and unfractionated heparin UFH \200 \200 There is no indication for \200\234routine \200\235 IV heparin following SK. IV heparin (4 000 U/max IV bolus followed by 1000 U/hr max adjusted for an aPTT ratio of 1.5 \200\2232.0 times control) should be used routinely following rtPA and its derivatives for 24 \200\2234 8 hours. LMWH \200 There is clinical trial data supporting the use of LMWH and thrombolysis (e.g., enoxaparin 30 mg IV bolus, then 1 mg/kg SC q12h). As an alternative to UFH, LMWH can be used at a prop hylactic dose to prevent thromboembolic events in high-risk patients. Clopidogrel \200 This should be administered to all patients undergoing primary PCI (loading dose 300 \200 \223600 mg po followed by 75 mg qd). The length of therapy is determined by the type of ste nt used. Drug- eluting stents require longer term use of clopidogrel than bare-metal stents (current guidelines for ACS is 1 year of Plavix). Glycoprotein (gp) IIb/IIIa inhibitors \200 There are multiple ongoing trials to evaluate the role of these agents in combination with thrombolysis and/or LMWH. These are recommended routinely in the context of STEMI patients treated with primary PCI. Lower doses of LMWH/UFH should be used (consult manufacturers inf ormation sheet for individual agents). They can also be used in the context of rescue PCI s ubsequent to failed thrombolysis, although there is a greater risk of bleeding. Current cli nical use is determined on a case-by-case basis in most centers. Calcium antagonists \200 \200 These are best avoided, especially in the presence of LV impairment. Diltiazem and verapami l started after day 4 \200\2235 in post-MI patients with normal LV function may have a smal l bene \201 cial effect. Amlodipine is safe to use in patients with poor LV function post- MI. Nifedipine has been shown to increase mortality and should be avoided. \200 RIGHT VENTRICULAR (RV) INFARCTION 105 Right ventricular (RV) infarction RV infarction results in elevated right-sided pressures ( RA and RVEDP) and low left-sided pressures (resulting in low BP and cardiac output [CO]). I t is common in inferior STEMI. Diagnosis \200 Clinical: Kussmaul \200\231s sign, and pulsus paradoxus) with absence of p ulmonary edema in the context of a low output state (dBP, cold extremities) ECG: in patient s with inferior STEMI a 0.1 mV (>1 mm) ST-segment elevation in any one of leads V4R \200 \223V6R is highly sensitive and speci \201 c for RV infarction. See Figure 2.3 for differe nt ECG patterns identi \201 ed in right-sided precordial leads. Changes may be transient a nd present in the early stages only. ECHO: signs of right heart failure (elevated jugular venous pulsations, look for RV dilation and wall motion abnormalities. Management \200 Aim to maintain a high RV preload. \200 \200 Initially give 1 \200\2232 L of IV \202 uids rapidly. Avoid use of nitrates and diuretics as they reduce preload and can worsen hypotension. In patients requiring pacing, AV synchr ony must be maintained to ensure maximal CO (requires atrial and ventricular wires). Cardio vert any arrhythmias (e.g., AF/ \202 utter or ventricular rhythms). Reduce afterload. \200 \200 \200 This is particularly important if there is concomitant LV dysfunction. Insert intra-aortic balloon pump (IABP) Arterial vasodilators can be used with caution (Na nitroprusside, hydra lazine) or ACE inhibitors. Inotropic support should ideally be avoided and used only if all other measures fail to res tore hemodynamic status. Reperfusion of the right coronary artery (RCA) (PCI and thrombolys is) has been demonstrated to improve RV function and reduce mortality. In extreme cases, su rgically implantable right ventricular assist devices (RVAD) may be used. CHAPTER 2 Coronary artery disease 106 ST-segment elevation \211 1 mm and positive T wave Proximal occlusion of right coronary artery Distal occlusion of right coronary artery No ST-segment elevation and positive T wave