The usual cause of an acute coronary syndrome is the rupture of an atherosclerotic plaque (Phalen and Aehlert, 2006, p. 61) Acute Coronary Syndrome

Plaque Rupture

Intraluminal thrombus Growth of thrombus Intraplaque thrombusLipid pool Blood Flow Atherosclerotic Plaque Rupture and Thrombus Formation Adapted from Weissberg PL. Eur Heart J Supplements 1999:1:T13–18

Classifications 1.ST-Segment Elevation Myocardial Infarction 2. Unstable Angina and Non–ST Elevation Myocardial Infarction 3. Stable Ischemic Heart Disease

Acute Coronary Syndrome

Unstable Angina Cause: Thrombus partially or intermittently occludes the coronary artery Diagnostic Findings: ST-segment depression or T-wave inversion Normal Cardiac Markers (Overbaugh, 2009, p. 46)

NSTEMI Cause: Thrombus partially or intermittently the occludes coronary artery Diagnostic Findings: ST-segment depression or T-wave inversion Elevated Cardiac biomarkers (Overbaugh, 2009, p. 46)

Temporal Evolution and Tissue Injury Time is Myocardium

Coronary Disease Progression

Clinical Indicators of Increased Risk in UA/NSTEMI

CAUSES OF ACUTE CHEST PAIN DIAGNOSTIC CONSIDERATIONS IMMEDIATE MANAGEMENT Approach to the Patient with Chest Pain

Acute chest pain is one of the most common reasons for presentation to the emergency department 15% to 25% of patients with acute chest pain actually have ACS The diagnosis of ACS is missed in approximately 2% of patients Mortality for patients with acute myocardial infarction (MI) who are mistakenly discharged from the ED increases twofold ACUTE CHEST PAIN

Myocardial Ischemia or Infarction, Pericardial Disease, Vascular Disease, Pulmonary Conditions, Gastrointestinal Conditions, Musculoskeletal and Other Causes, CAUSES OF ACUTE CHEST PAIN

The most common serious cause of acute chest discomfort Supply of myocardial oxygen is inadequate compared with the demand Usually occurs in the setting of coronary atherosclerosis Myocardial Ischemia or Infarction

Coronary spasm Coronary arteritis, Proximal aortitis, Spontaneous coronary dissection, Proximal aortic dissection, Coronary emboli from infectious or noninfectious endocarditis,thrombus in the left atrium or left ventricle, Myocardial bridge, Congenital abnormality of the coronary arteries Myocardial Ischemia or Infarction Other less common causes

Ischemia May occur as a result of either or both of the following: Demand Ischemia: Increased myocardial O 2 demand (Anemia, hypoxemia, coronary artery narrowing due to a thrombus, vasospasm, or rapid progression of atherosclerosis) Supply Ischemia: Reduced myocardial O 2 supply (Exercise, smoking, heavy meals, fever, HF, tachydysrhythmias, OCM, cocaine, amphetamines, emotional stress, hypertension, cold weather, aortic stenosis, pheochromocytoma, thyrotoxicosis)

Injury Ischemia prolonged more than just a few minutes results in myocardial injury. Injured myocardial cells are still alive but will infarct if the ischemia is not quickly corrected ECG Changes: ST-segment elevation (Injured myocardial cells do not depolarize completely, remaining electrically more positive than the uninjured areas surrounding them)

Infarction A myocardial infarction occurs when blood flow to the heart muscle stops or is suddenly decreased long enough to cause cell death Infarcted cells are without function and cannot respond to electrical stimulus or provide any mechanical function (Thalen and Aehlert, 2006, p, 67) ECG Changes: ST-segment elevation, T-wave inversion, abnormal Q waves

Evaluation of the patient with acute chest pain Hemodynamic instability A 12-lead electrocardiogram (ECG) Initial Assessment

History Physical Examination Electrocardiography Chest Radiography Biomarkers Initial Assessment

Vital signs, Examination of the peripheral vessels – Bruits or absent pulses Identify potential precipitating causes – Uncontrolled hypertension, anemia, hyperthriodism Important comorbid conditions – Chronic obstructive pulmonary disease Evidence of hemodynamic complications – Congestive heart failure, – New mitral regurgitation, hypotension Physical Examination

10 minutes after presentation New persistent or transient ST-segment abnormalities (≥0.1 mV) and T inversion (≥0.2 mV) During a symptomatic episode at rest and resolve Electrocardiography

Usually non-diagnostic Pulmonary edema (ischemia-induced diastolic or systolic dysfunction) Pneumothorax, Pneumonia Chest Radiography

A cardiac troponins (T or I; cTnT or cTnI) Creatine kinase MB isoenzyme (CK- MB, less sensitive) Biomarkers

Biomarkers for Evaluation of Patients with STEMI

Myocarditis, Myocardial contusion, Cardioversion or defibrillation, Left ventricular strain from congestive heart failure Hypertensive crisis, Extreme exercise, Right ventricular strain from pulmonary embolus, Other causes of acute pulmonary hypertension Troponins_True myocardial damage

Patients with renal disease Severe sepsis Troponins_mechanism remains unclear

Blood should be obtained for testing at hospital presentation, and at 6 to 9 hours A normal reference values 0.01 to 0.07 ng/ml Ultrasensitive assays <0.001 ng/ml or <1 pg/ml Serial sampling up to 12 hours after presentation %90 to %95 3 hours of the onset of chest pain 80% to 85% Troponins

Found in – Skeletal muscle, – Tongue, – Diaphragm, – Small intestine, uterus, and prostate Eleveted – Muscular dystrophy – High-performance athletics – Rhabdomyolysis – Alcohol abuse or trauma vs Shorter half-life – Useful for gauging the timing of an MI – Diagnosing reinfarction Creatine Kinase MB Isoenzyme lack of specificity

Serum myoglobin heart-type fatty acid binding protein C-reactive protein serum amyloid A, myeloperoxidase interleukin-6 D-dimer B-type natriuretic peptides Other Markers

 hs-C-reactive protein (prognostic)  D-dimer (PE)  B-type natriuretic peptide (HF, prognostic)

Acute Coronary Syndrome Likelihood That Signs and Symptoms

ST Elevation Myocardial Infarction

Step 1: Assess time and risk. Time since onset of symptoms Risk of STEMI Risk of fibrinolysis Time required for transport to a skilled PCI laboratory Assessment of Reperfusion Options for STEMI Patients

AB CD

Skilled PCI laboratory is available with surgical backup – Skilled PCI laboratory is available, defined by – Medical contact-to-balloon or door-to-balloon less than 90 min High risk from STEMI – Cardiogenic shock – Killip class ≥ 3 Contraindications to fibrinolysis, Late presentation – Symptom onset was more than 3 hr ago An invasive strategy is generally preferred if

Based on Clinical Examination I.Rales and S3 absent II.Crackles, S3 gallop, elevated jugular venous pressure III.Frank pulmonary edema IV.Shock Hemodynamic Classifications of Patients with Acute Myocardial Infarction Modified from Killip T, Kimball J: Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol 20:457, 1967

Based on Invasive Monitoring I.Normal hemodynamics; PCWP 2.2 II.Pulmonary congestion; PCWP > 18 mm Hg, CI > 2.2 III.Peripheral hypoperfusion; PCWP < 18 mm Hg, CI < 2.2 IV.Pulmonary congestion and peripheral hypoperfusion; PCWP > 18 mm Hg, CI < 2.2 Hemodynamic Classifications of Patients with Acute Myocardial Infarction Modified from Forrester J, Diamond G, Chatterjee K, et al: Medical therapy of acute myocardial infarction by the application of hemodynamic subsets. N Engl J Med 295:1356, 1976.

Delay to invasive strategy: – Prolonged transport – Medical contact-to-balloon or door-to-balloon more than 90 min Early presentation (≤3 hr from symptom onset and delay to invasive strategy; see below) Invasive strategy is not an option: – Catheterization laboratory occupied or not available – Vascular access difficulties – Lack of access to a skilled PCI laboratory Fibrinolysis is generally preferred if

Approved Fibrinolytic Agents

Reperfusion Options for STEMI Patients

Post Myocardial Infarction Complications

Post MI Complications Arrhythmias Cardiac Arrest Cardiac Muscle Dysfunction Cardiogenic Shock (Haworth and Pratowski, 2000 p. 90) Heart Failure Mitral Insufficiencies PericarditisThromboembolism GI Complaints

Post MI: Common Arrhythmias Atrial Fibrillation Premature Ventricular Contractions Ventricular Tachycardia Accelerated Idioventricular Rhythm Ventricular Fibrillation Atrioventricular Block (Haworth and Pratowski, 2000 p. 91)

Unstable Angina and Non–ST Elevation Myocardial Infarction

Unstable Angina Cause: Thrombus partially or intermittently occludes the coronary artery Diagnostic Findings: ST-segment depression or T-wave inversion Normal Cardiac Markers (Overbaugh, 2009, p. 46)

NSTEMI Cause: Thrombus partially or intermittently the occludes coronary artery Diagnostic Findings: ST-segment depression or T-wave inversion Elevated Cardiac biomarkers (Overbaugh, 2009, p. 46)

Clinical Indicators of Increased Risk in UA/NSTEMI

Treatment UA Oxygen to maintain O 2 sat > 90% NTG or MSO4 to control pain BB’s, CCB’s, ACEI’s, statins, clopidogrel, unfractionated heparin or LMWH, glycoprotein IIb/IIIa inhibitorsNSTEMI Same as UA plus: Cardiac cath & possible PCI for patients with ongoing CP, hemodynamic instability, or increased risk of worsening clinical condition Cardiac cath & possible PCI for patients with ongoing CP, hemodynamic instability, or increased risk of worsening clinical condition

Antiplatelet Therapy Anticoagulant Therapy Control of Cardiac Pain – Analgesics – Nitrates – Beta Blockers – Oxygen Limitation of Infarct Size – Early reperfusion – Reduction of myocardial energy demand General Treatment Measures

Aspirin – mg, nonenteric-coated ASA to be chew – maintenance of mg daily Antiplatelet Therapy

Clopidogrel mg loading 75 mg/day Prasugrel oral loading dose of 60 mg and 10 mg orally daily Ticagrelor a loading dose of 180 mg and 90 mg twice daily Antiplatelet Therapy

Heparin activated partial thromboplastin time (aPTT) target of 1.5 to 2 times that of control Low-Molecular- Weight Heparins Bivalirudin (STMI) Anticoagulant Therapy

– Analgesics meperidine, pentazocine, and morphine Morphine 2 to 8 mg/ 5 to 15 minutes --until the pain is relieved or there is evident toxicity – Nitrates sublingual nitrates, intravenous nitroglycerin systolic pressure <90 mm Hg right ventricular infarction Control of Cardiac Pain

– Beta Blockers Killip class II or higher (precipitating cardiogenic shock) Patients with heart failure (rales > 10 cm up from diaphragm), hypotension (blood pressure < 90 mm Hg), bradycardia (heart rate < 60 beats/min), Control of Cardiac Pain

Oxygen – pulse oximetry – Sao2 < 90% – 2 to 4 liters/min of 100% oxygen – 6 to 12 hours Control of Cardiac Pain

Early reperfusion Routine Measures for Infarct Size Limitation – Beta blocker (HR 50-70) – Inhibitors of the renin-angiotensin- aldosterone system (RAAS) – Arterial oxygenation Limitation of Infarct Size

Angiotensin-converting enzyme (ACE) inhibitor – Start ACE inhibitor orally in patients with pulmonary congestion or LVEF <40% – if the following are absent: hypotension (SBP <100 mm Hg or <30 mm Hg below baseline) or known contraindications to this class of medications. Angiotensin receptor blocker (ARB) – Start ARB orally in patients who are intolerant of ACE inhibitors and with either clinical or radiologic signs of heart failure or LVEF <40% Limitation of Infarct Size

Risk factor control, particularly smoking, must be stringent. Antiplatelet therapy is indicated indefinitely. Dual antiplatelet therapy is indicated up to 12 months. Oral treatment with beta-blockers is indicated in patients with heart failure or left ventricular dysfunction. A fasting lipid profile must be obtained in all patients. A high-dose statin should be initiated or continued early after admission in all patients without contraindication or history of intolerance. ACE inhibitors are indicated in patients with heart failure, LV systolic dysfunction diabetes or an anterior infarct. An ARB is an alternative to ACE inhibitors. Aldosterone antagonists are indicated if EF ≤40% or heart failure or diabetes, provided there is no renal failure or hyperkalaemia. Long term therapies