Cardiology Core Curriculum - part 4 pdf

approximately 18 hours, and return to normal in approximately 3 days (Figure 6.5). 6 Cardiac troponins T (cTnT) and I (cTnI) are contractile proteins that are released in response to myocardial necrosis. Like CK and CK-MB, these enzymes are detectable 3–6 hours after the onset of chest pain Cardiology Core Curriculum 180 I aVL V 2 V 5 aVR V 1 V 4 II aVF V 3 V 6 Figure 6.4 Electrocardiographic changes characteristic of pericarditis. Concave (upsloping) ST elevation is seen diffusely, together with PR-segment depression. Importantly, T waves are essentially normal, which is another distinguishing feature from ST-segment elevation myocardial infarction Myoglobin CK/CK-MB Troponin T/I LDH Hours from onset of infarction × Upper limit of normal 0 0 24 48 72 96 120 5 10 15 20 Figure 6.5 Time course of serum marker release in acute myocardial infarction. (See text for details.) CK, creatinine kinase; LDH, lactate dehydrogenase. Adapted with permission from Antman 6 and peak at approximately 14–20 hours (see Figure 6.5). They differ, however, in that they remain elevated for up to 14 days after infarction. This prolonged detection window facilitates the diagnosis of remote infarction (i.e. an infarct that occurred in the days or weeks before presentation) but makes the diagnosis of early recurrent infarction difficult. Because cTnT and cTnI are not found in adult skeletal muscle, they are highly specific for myocardial injury and thus are excellent markers for confirming the diagnosis of MI. The normal reference range for the cardiac troponins is set at a very low level; as a result, troponins are very sensitive for the detection of small amounts of myocardial necrosis. Indeed, it has recently been shown that patients with minor myocardial necrosis, as evidenced by low level troponin elevation in the absence of CK and CK-MB elevation, are at increased risk for the development of adverse clinical outcomes. 7 This finding has led to a revised, more liberal definition of myocardial infarction that now includes patients with low level troponin elevation, even if CK and CK-MB are normal. Myoglobin is a small cytosolic molecule that is rapidly released from ischemic muscle and promptly cleared by the kidney. Serum levels of myoglobin rise earlier than other available markers, and elevated levels can be detected as early as 2 hours after the onset of chest pain. Myoglobin peaks at approximately 6 hours and returns to normal levels within 18–24 hours (see Figure 6.5). Widespread use of serum myoglobin for the detection of MI has been limited by concerns about poor cardiac specificity. Skeletal muscle trauma and renal failure can raise serum myoglobin levels in a non-specific manner. Nevertheless, myoglobin remains a very useful early marker because of its rapid release and renal clearance, and it is more sensitive than CK-MB for detecting MI within the first few hours after presentation. An elevated myoglobin should be confirmed with a more specific marker at a later time point, such as CK-MB, cTnT, or cTnI. 8 Radionuclide imaging New high-resolution agents, such as 99m Tc-sestamibi and 99m Tc- tetrofosmin, are now available for myocardial perfusion imaging. These radionuclides, unlike thallium-201, do not redistribute after their initial deposition. This property allows these agents to be given by intravenous injection during an episode of suspected ischemic pain, with imaging performed following stabilization and/or therapy. The images obtained provide a “snapshot” of myocardial perfusion at the time the tracer was injected. This strategy may be a particularly useful means of excluding ischemia as a cause of prolonged chest pain in patients with a non-diagnostic electrocardiogram. Acute coronary syndromes 181 Initial therapy for acute coronary syndromes All patients should be given oxygen and an aspirin tablet to chew. Morphine is an extremely effective agent to relieve the pain of acute myocardial ischemia and MI; in addition, because morphine dilates venous capacitance vessels, it also relieves symptoms of pulmonary congestion or edema. Beyond this, the initial management of patients with suspected ACS depends on the presenting electrocardiogram (Figure 6.6). Patients with ST-segment elevation are directed to immediate reperfusion therapy, whereas those without ST-segment elevation are treated initially with antiplatelet and antithrombotic therapy, and aggressive antianginal medical therapy to minimize ischemia. Cardiology Core Curriculum 182 Suspected ACS 12-lead ECG ST depression or marked T-wave inversion Non-ST-elevation ACS Non-diagnostic ECG ST elevation * ST-elevation MI Serial ECGs and cardiac markers Consider ETT for selected patients Aspirin Unfractionated heparin † β-Blocker Invasive strategy Conservative strategy Primary PCIFibrinolytic therapy Failure Abnormal Normal Abnormal Non-cardiac chest pain Normal Success Failure Success Rescue PCI Aspirin Heparin (either UFH or LMWH) β-Blocker GPllb/llla inhibitors for selected patients Nitrates for angina Long term therapy Aspirin β-Blockers ACE inhibitors Statins Clopidogrel? Figure 6.6 An algorithm for the diagnosis and management of suspected acute coronary syndromes (ACS). Dark boxes indicate diagnostic categories; white boxes indicate diagnostic or therapeutic procedures; and gray boxes indicate interpretation of tests or procedures. * New, or presumed new left bundle branch block should be considered together with ST elevation. † Intravenous unfractionated heparin is not indicated as adjunctive therapy with streptokinase. ACE, angiotensin- converting enzyme; ECG, electrocardiogram; ETT, exercise tolerance test; GP, glycoprotein; LMWH, low molecular weight heparin; MI, myocardial infarction; PCI, percutaneous coronary intervention; UFH, unfractionated heparin Reperfusion therapy for ST-segment elevation myocardial infarction Options for reperfusion therapy include fibrinolytic therapy and primary percutaneous coronary intervention (PCI), either with percutaneous transluminal coronary angioplasty or intracoronary stenting. Primary PCI is the preferred method in centers with sufficient resources and expertise to perform successful PCI within 90 min of presentation to the hospital; however, if the “door to balloon” time is greater than 90 min, then fibrinolytic therapy is preferred. Clinical studies suggest that mortality is slightly lower with primary PCI than with pharmacologic reperfusion therapy when PCI is performed in expert institutions. In addition, recurrent MI and intracranial hemorrhage are observed less frequently with primary PCI than with fibrinolytic therapy. Because of resource limitations, fibrinolytic therapy is much more widely available than PCI, and is the reperfusion method of choice in the majority of hospitals. The speed at which reperfusion therapy is administered is much more important than the choice between PCI and fibrinolytic therapy, or the choice between individual fibrinolytic agents. For each hour earlier that reperfusion therapy is administered, there is an absolute 1% decrease in mortality. 9 All of the fibrinolytic agents currently available are plasminogen activators. Reteplase (recombinant plasminogen activator [rPA]) and tenecteplase have a prolonged half-life and can be given as a bolus injection, as compared with the prolonged infusion required with alteplase (recombinant tissue plasminogen activator [tPA]) and streptokinase. Because tPA, rPA, and tenecteplase are more potent than streptokinase, they are associated with slightly lower mortality at a cost of slightly increased bleeding. The cost/benefit ratio favors these agents over streptokinase in patients presenting early after symptom onset with a large area of injury (for example acute anterior MI) and a low risk for intracranial hemorrhage. In groups with smaller potential for survival benefit and a greater risk for intracranial hemorrhage, streptokinase may be the agent of choice, particularly in view of the cost. Additional considerations include avoiding readministration of streptokinase or anistreplase to patients for at least 4 years (preferably indefinitely) because of a high prevalence of potentially neutralizing antibodies, and because there is a risk of anaphylaxis upon re-exposure to these drugs. There are contraindications to fibrinolytic therapy (Table 6.2). In addition, fibrinolytic therapy is not indicated for patients with non- ST-segment elevation ACS because it increases bleeding complications without a measurable clinical benefit. 10 Acute coronary syndromes 183 Antiplatelet and antithrombotic therapy For patients with both ST-segment elevation and non-ST-segment elevation ACS, aspirin reduces mortality, recurrent ischemia, and MI, and therefore should be given to all patients. 11 If a true aspirin allergy is present, then clopidogrel may serve as an effective alternative. For patients with ST-segment elevation MI, intravenous unfractionated heparin (UFH) should be administered as an adjunct to reperfusion therapy with tPA, rPA, and tenecteplase. With streptokinase, on the other hand, there is no clear benefit of adjunctive heparin, and it should not be given routinely. In non-ST-segment elevation ACS, the addition of intravenous UFH to aspirin reduces the rate of death and recurrent infarction, 12 and therefore should be given unless there is a bleeding contraindication or the patient has a history of heparin associated thrombocytopenia. Heparin should be administered as a weight adjusted bolus and infusion, and titrated to a partial thromboplastin time of approximately 2 × control. Recently, several novel antiplatelet and antithrombotic therapies have been introduced that appear to be beneficial in patients with non-ST-segment elevation ACS. Ticlopidine and clopidogrel are thienopyridine agents that block adenosine diphosphate mediated platelet aggregation, and appear to provide protection similar to that with aspirin in patients with established vascular disease. 13 Clopidogrel causes fewer hematologic side effects than does ticlopidine, and thus is the agent of choice in this drug class. The combination of clopidogrel and aspirin has recently been shown to be even more beneficial than either agent alone, and prolonged therapy with these two agents following ACS will probably become commonplace in the near future. Glycoprotein IIb/IIIa inhibitors are intravenous compounds that block the final common pathway of platelet aggregation, namely fibrinogen mediated cross-linking at the glycoprotein IIb/IIIa receptor. These agents Cardiology Core Curriculum 184 Table 6.2 Contraindications to thrombolytic therapy Absolute contraindications Relative contraindications Active internal bleeding Blood pressure consistently Prior intracranial hemorrhage >180/110 mmHg Stroke within past year Stroke or TIA at any time in past Recent head trauma or brain neoplasm Known bleeding diathesis Suspected aortic dissection Proliferative diabetic retinopathy Major surgery or trauma within 2 weeks Prolonged CPR Pregnancy CPR, cardiopulmonary resuscitation; TIA, transient ischemic attack provide platelet inhibition that is several times greater than that with aspirin or clopidogrel. Two of the glycoprotein IIb/IIIa inhibitors, namely tirofiban and eptifibatide, have been shown to reduce the probability of recurrent ischemic events among patients with non-ST- segment elevation ACS. The benefit of these agents is greatest in high risk patients (those with dynamic ST changes or elevated cardiac enzymes) who are managed with an early aggressive strategy, including routine angiography and percutaneous revascularization. 14,15 Low molecular weight heparins (LMWHs) are created by depolymerization of standard UFH and selection of those fragments with lower molecular weight. LMWH is active early in the clotting cascade, inhibiting factor Xa to a greater extent than does UFH, thereby inhibiting both thrombin activity and its generation. The high bioavailability and reproducible anticoagulant response of LMWH allows for subcutaneous administration without monitoring of the anticoagulant effect. In high-risk patients with non-ST-segment elevation ACS, the LMWH heparin compound enoxaparin is associated with modestly lower risk for death and MI versus UFH. 16 Other LMWH compounds appear to be roughly equivalent to UFH. Predominantly because of its ease of use, it is likely that LMWH will replace UFH for most patients with non-ST-segment elevation ACS in the near future. ββ -Blockers β-Blockers exert their beneficial effect in ACS by decreasing myocardial contractility and especially heart rate, thereby improving the balance between oxygen supply and demand. As such, they may reduce infarction size and lower short-term mortality rates. In addition, β-blockers prevent atrial and ventricular arrhythmias in patients following MI, and may prevent ventricular rupture following transmural MI. Long-term therapy is indicated with β-blockers following ACS to prevent recurrent infarction. Angiotensin-converting enzyme inhibitors Angiotensin-converting enzyme (ACE) inhibitors have become a mainstay in the treatment of patients with all types of ACS. Following ST-segment elevation MI, ACE inhibitors are administered because they prevent deleterious left ventricular chamber remodeling and subsequent heart failure. 17 In addition, long-term therapy with ACE inhibitors prevents ischemic events in patients with established coronary artery disease. 18 ACE inhibitors should be initiated early (but not emergently) after the presentation of ACS and continued indefinitely. Acute coronary syndromes 185 Nitrates Nitrates favorably effect both myocardial oxygen supply and demand, and thus are of particular value early in ACS. Nitrates dilate both normal and atherosclerotic resistance coronary arteries, and redistribute blood flow from epicardial to ischemic endocardial regions. Central venodilatation and modest peripheral arterial dilatation reduce myocardial oxygen demand. Nitrates are effective in relieving symptoms of ischemia in patients with ACS, and may be particularly useful in patients with concomitant congestive heart failure (CHF) because of the venodilating properties of this class of drugs. In unstable patients intravenous nitroglycerin should be given because it is easily titratable and rapidly reversible. In more stable patients topical or oral nitrates are usually adequate. It is reasonable to use nitroglycerin for the first 24–48 hours in patients with ACS and recurrent ischemia, CHF, or hypertension. Long-term nitrate therapy should only be used in patients with ongoing symptoms of ischemia because there is no evidence that chronic nitrate therapy prevents MI or death. Calcium channel blockers Calcium channel blockers have a limited role in the contemporary management of ACS. Unlike β-blockers and ACE inhibitors, the calcium channel blockers have not been shown to reduce mortality. Thus, they should only be used for patients with contraindications or intolerance to β-blockers and ACE inhibitors, or if refractory hypertension or tachycardia is present. In patients with non-ST- segment elevation ACS diltiazem and verapamil may reduce recurrent ischemia and infarction, but these agents are harmful for patients with left ventricular dysfunction or clinical heart failure. Dihydropyridine calcium channel blockers such as nifedipine should not be used in patients with ACS unless a β-blocker is used in combination to prevent reflex tachycardia. Because of safety concerns, short-acting preparations of nifedipine should not be used. In-hospital management Risk stratification Risk stratification in ACS begins at the moment a patient arrives in the emergency room and should continue through hospital discharge and beyond. When the patient is first seen, history, physical examination, electrocardiogram, and serum marker information are rapidly Cardiology Core Curriculum 186 integrated, both to arrive at a diagnosis and to estimate a patient’s risk for adverse outcome. Older age, presence of diabetes, three or more risk factors, and a history of prior MI or CHF are all associated with increased risk. In addition, tachycardia or bradycardia, hypotension, and evidence for CHF are markers of increased risk that are easily obtained from a focused examination. The electrocardiogram provides incremental prognostic value. An anterior location of infarction (or an inferior infarction with right ventricular extension or anterior ST depression), and a greater amount of ST deviation are associated with larger MI and increased risk. Finally, elevated serum cardiac markers at presentation and ACS despite aspirin use during the past week are associated with an increased risk for morbidity and mortality. Patients are initially triaged based on the presence or absence of ST-segment elevation on the presenting electrocardiogram (see Figure 6.6). Subsequent risk stratification steps should focus on identifying patients at risk for electrical, mechanical, and ischemic complications (see Figure 6.6), and on selecting those patients who will benefit most from particular therapies, such as revascularization. It should be remembered that with many therapies absolute risk reduction is highest in those patients at greatest risk; therefore, the higher the risk in an individual patient, the more aggressive the care should be. Left ventricular function Left ventricular function is the single most important determinant of long-term survival in patients with coronary artery disease. Because of the importance of left ventricular function to risk assessment, most patients should have an ejection fraction measurement following an acute MI. Because reversible left ventricular dysfunction may follow an ischemic insult (myocardial “stunning”), initial measurements may significantly underestimate true left ventricular function. Therefore, unless clinically indicated because of CHF, suspected valvular heart disease, or pericardial effusion, measurement of ejection fraction can be deferred until approximately 5–7 days after the MI. Although echocardiography, contrast ventriculography, and radionuclide angiography are all reliable methods for assessing left ventricular ejection fraction, echocardiography has the advantage of providing structural information as well. Coronary angiography and revascularization Routine adjunctive percutaneous coronary intervention following fibrinolysis has not been shown to improve clinical outcomes. Acute coronary syndromes 187 However, selected patients with ST-segment elevation MI should be managed with an early invasive strategy, including routine catheterization and revascularization if the coronary anatomy is suitable. Urgent catheterization is indicated for patients with cardiogenic shock and those with evidence of failed fibrinolysis (i.e. those without resolution of ST elevation 90–180 min after fibrinolytic therapy). Elective catheterization should be considered for patients at high risk, including those with significant left ventricular dysfunction and those with spontaneous ischemia or ischemia that is inducible on a predischarge exercise test. Patients with non-ST-segment elevation ACS have lower initial mortality rates than do patients with ST-segment elevation MI, but have higher rates of recurrent ischemia and reinfarction, so that at the end of 1 year outcomes are similar. There has been considerable controversy as to whether an early invasive or early conservative management strategy is preferred for patients with non-ST-segment elevation ACS. Recent studies suggest that in the modern interventional era, with the use of coronary stents, glycoprotein IIb/IIIa inhibitors, low molecular weight heparins, and careful attention to groin hemostasis, an early invasive approach is associated with modestly lower rates of recurrent ischemic events (MI and recurrent ischemia) but not mortality. In addition to preventing morbidity, an early invasive approach may shorten the hospital stay and is not associated with excess overall costs. The advantages of an early invasive approach appear to be limited to patients at intermediate or high risk for ischemic complications, such as those with dynamic electrocardiographic changes and those with elevation in cardiac enzymes. A more conservative approach utilizing vigorous medical therapy may be appropriate in low risk patients, especially those who have never previously received antianginal medication. After a “cool-off” period with antiplatelet and antithrombotic therapy, treadmill exercise testing with or without adjunctive imaging may help to define patient management further. If the pattern of angina remains unstable or if electrocardiographic changes suggest ongoing ischemia, then coronary angiography is warranted. In addition, significant ischemia on the predischarge exercise test is considered an indication for coronary angiography and revascularization. Risk factor modification Because hospitalization for an ACS is such a significant event in the life of a patient, the hospital stay presents a unique opportunity to address lifestyle factors that contribute to the development and Cardiology Core Curriculum 188 progression of coronary atherosclerosis (Table 6.3). Smoking cessation and weight loss should be emphasized, and patients can begin cardiac rehabilitation before leaving the hospital. Treatment of diabetes and hypertension should be optimized. Most importantly, lipid lowering therapy should be initiated for virtually all patients with ACS, regardless of low-density lipoprotein level. Although diet (either a low fat, low cholesterol diet, or a Mediterranean diet) should be instituted, the benefit of statin therapy has been unequivocally demonstrated in patients with established coronary artery disease; therefore, statins are the agents of choice for treating hyperlipidemia following ACS (Table 6.4). Complications of acute myocardial infarction The mechanical and electrical complications of acute MI are summarized in Tables 6.5 and 6.6, respectively. Infarct expansion and remodeling Following a large MI, the infarct area may expand and cause thinning of the necrotic myocardium. Over weeks to months, the left ventricular cavity may enlarge and assume a more globular shape. This process is termed left ventricular remodeling, and frequently leads to clinical congestive heart failure. Angiotensin-converting Acute coronary syndromes 189 Table 6.3 Risk factor modification following admission for acute coronary syndromes Risk factor Goal of therapy Treatment options Smoking Permanent smoking Behavioral therapy; cessation pharmacotherapy; hypnosis Obesity BMI <25 kg/m 2 Diet; exercise; anorexigen drug therapy as last resort Diabetes Hemoglobin A 1C <7·0% Insulin; oral sulfonylureas; metformin; insulin sensitizing agents; diet Hypertension Blood pressure Drug therapy; diet; exercise <130/85 mmHg Hyperlipidemia LDL <100 mg/dl Drug therapy with statins (<2·6 mmol/l) or fibrates; low fat, low cholesterol, or Mediterranean diet BMI, body mass index; LDL, low-density lipoprotein [...]... (years) No symptoms (%) Non-anginal pain (%) M F M F M F 35 45 45 –55 55–65 65–75 4 8 11 11 1 2 5 11 11 21 28 28 3 7 13 17 81 91 94 94 45 68 84 95 Typical angina (%) F, female; M, male From Diamond2 Physical examination Inspection Inspection of the eyes may reveal a corneal arcus (the size of a corneal arcus appears to correlate positively with age and levels of cholesterol and low-density lipoproteins),.. .Cardiology Core Curriculum Table 6 .4 Summary of treatments for patients with acute coronary syndromes Treatment ST-segment elevation MI Non-ST-segment elevation ACS Oxygen Morphine +++ ++ +++ ++ Antiplatelet therapy Aspirin Clopidogrel ++++ ? ++++ +++ ++ +++ +++ +++ ? +++ Reperfusion therapy Fibrinolytic therapy Primary PCI β-Blockers ++++ ++++ ++++ NO + +++ ACE... results from all randomised trials of more than 1000 patients Lancet 19 94; 343 :311–22 10 The TIMI-IIIB Investigators Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction Results of the TIMI IIIB trial Circulation 19 94; 89:1 545 –56 11 Antiplatelet Trialist' Collaboration Collaborative overview of randomised... 19 94; 308:81–106 12 Oler A, Whooley MA, Oler J, Grady D Adding heparin to aspirin reduces the incidence of myocardial infarction and death in patients with unstable angina A meta-analysis JAMA 1996;276:811–15 203 Cardiology Core Curriculum 13 CAPRIE Steering Committee A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) Lancet 1996; 348 :1329–39 14. .. which the wall is composed of myocardial tissue, the 193 Cardiology Core Curriculum I aVR V1 V4 II aVL V2 V5 III aVF V3 V6 Figure 6.7 Right ventricular infarction ST-segment elevation is present in the inferior leads (II, III, and aVF), indicating inferior myocardial infarction Right sided precordial leads demonstrate ST-segment elevation in lead V4R, which is indicative of right ventricular involvement... et al .4 Exercise test predictors of multivessel coronary artery disease include exercise-induced hypotension, ST-segment changes of greater than 2 mm, a low work load capacity (Table 7 .4) ,4 or a limited duration of exercise (which reflects the functional state of the left ventricle) and persistent ST-segment depressions In outpatients with suspected coronary artery disease, treadmill exercise scores... 1996; 348 :1329–39 14 The PRISM-PLUS Trial Investigators Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction N Engl J Med 1998;338: 148 8–97 15 The Pursuit Trial Investigators Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes N Engl J Med 1998;339: 43 6 43 16 Antman EM, Cohen M,... long-term anticoagulation 197 Cardiology Core Curriculum Pericarditis Fibrinous pericarditis may occur in the first few weeks following transmural infarction, and is often confused with recurrent angina or infarction The pain of pericarditis is usually pleuritic, positional, and often radiates to the shoulder A pericardial friction rub may be present Aspirin should be given, but non-steroidal anti-inflammatory... Intravenous β-blockers (B) Oral diltiazem (C) Intravenous morphine (D) A chewed aspirin (E) Low molecular weight heparin Following the initiation of aspirin, low molecular weight heparin, β-blockers, and nitroglycerin, the patient becomes pain-free and the ST depressions resolve Cardiac enzymes are sent from a sample of blood collected 8 hours after the onset of chest pain 201 Cardiology Core Curriculum. .. or D 199 Cardiology Core Curriculum 5 Which of the following tests or procedures is indicated to diagnose and treat this patient? (A) Doppler echocardiography (B) Placement of a pulmonary artery catheter to measure oxygen saturations in the right atrium and right ventricle (C) Placement of an intra-aortic balloon pump (D) Urgent surgery (E) All of the above Answers Answer to question 1 C ST-segment . minimize ischemia. Cardiology Core Curriculum 182 Suspected ACS 12-lead ECG ST depression or marked T-wave inversion Non-ST-elevation ACS Non-diagnostic ECG ST elevation * ST-elevation MI Serial. to 10–15% of patients by hospital Cardiology Core Curriculum 190 Table 6 .4 Summary of treatments for patients with acute coronary syndromes ST-segment Non-ST-segment Treatment elevation MI elevation. necrosis. Like CK and CK-MB, these enzymes are detectable 3–6 hours after the onset of chest pain Cardiology Core Curriculum 180 I aVL V 2 V 5 aVR V 1 V 4 II aVF V 3 V 6 Figure 6 .4 Electrocardiographic