MINISTRY OF HEALTH OF UKRAINE

MINISTRY OF HEALTH OF UKRAINE

KHARKIV NATIONAL MEDICAL UNIVERSITYDEPARTMENT OF INTERNAL MEDICINE 1 AND CLINICAL PHARMACOLOGY

GUIDELINES FOR STUDENTS

ACADEMIC DISCIPLINE INTERNAL MEDICINE

CONTENTS MODULE #3 CURRENT PRACTICE OF INTERNAL MEDICINE

TopicMANAGEMENT OF PATIENTS WITH ACUTE CORONARY SYNDROME

AuthorYuliya Shaposhnikova

Course 6 th

FacultyFaculty of the foreign students education

APPROVED

Academic Council of HNMU

Protocol number_____

from __________________2010

KHARKIV HNMU 2010

ACUTE CORONARY SYNDROMES

Acute coronary syndromes (ACS) is a term used to describe a group of conditions resulting from acute myocardial ischemia (insufficient blood flow to heart muscle) and ranging from unstable angina (increasing, unpredictable chest pain) to myocardial infarction (heart attack). The conditions are related to varying degrees of narrowing or blockage of single or multiple coronary arteries that provide blood, oxygen, and nutrients to the heart. This life-threatening disorder is a major cause of emergency medical care and hospitalization.

Acute Coronary Syndrome (ACS) is a term that encompasses a spectrum of conditions including unstable angina (UA), the closely related condition non-ST-segment elevation myocardial infarction (NSTEMI), and ST segment elevation myocardial infarction (STEMI).

In general, ACS is caused by an imbalance between myocardial oxygen supply and demand. Most often, ACS is the result of decreased myocardial perfusion that results from coronary artery narrowing caused by atherosclerotic plaque and thrombi formation involved in coronary heart disease.

When patients report anginal chest pain, the goal is to immediately classify them into one of three groups based on their symptoms, ECG findings, and laboratory tests. These determine if the patient is having stable angina, unstable angina, NSTEMI or STEMI.

Acute myocardial infarction (AMI) and unstable angina are part of a spectrum known as the acute coronary syndromes (ACS), which have in common a ruptured atheromatous plaque. Plaque rupture results in platelet activation, adhesion, and aggregation, leading to partial or total occlusion of the artery.

These syndromes include ST-segment elevation MI, non-ST-segment elevation MI, and unstable angina. The ECG presentation of ACS includes ST-segment elevation infarction, ST-segment depression (including nonQ-wave MI and unstable angina), and nondiagnostic ST-segment and T-wave abnormalities. Patients with ST-segment elevation MI require immediate reperfusion, mechanically or pharmacologically.

Clinical evaluation of chest pain and acute coronary syndromes

History. Chest pain is present in 69% of patients with AMI. The pain may be characterized as a constricting or squeezing sensation in the chest. Pain can radiate to the upper abdomen, back, either arm, either shoulder, neck, or jaw. Atypical pain presentations in AMI include pleuritic, sharp or burning chest pain. Dyspnea, nausea, vomiting, palpitations, or syncope may be the only complaints.

Clinical presentation. The clinical presentation of acute coronary syndromes encompasses a wide variety of symptoms. The classic features of typical ischemic cardiac pain are well known and will not be further described here. Traditionally, several clinical presentations have been distinguished: prolonged (>20 min) anginal pain at rest, new onset (de novo) severe (Class III of the Canadian Cardiovascular Society Classification) angina, or recent destabilization of previously stable angina with at least CCS III angina characteristics (crescendo angina). Prolonged pain is observed in 80% of patients while de novo or accelerated angina is observed in only 20%.

However, atypical presentations of acute coronary syndromes are not uncommon. They are often observed in younger (2540 years) and older (>75 years) patients, diabetic patients, and in women. Atypical presentations of unstable angina include pain that occurs predominantly at rest, epigastric pain, recent onset indigestion, stabbing chest pain, chest pain with some pleuritic features, or increasing dyspnoea. In addition, variant angina, which forms part of the spectrum of unstable angina, may not be recognized at initial presentation

Cardiac risk factors include age (male >45 years, female >55 years), hypertension, hyperlipidemia, diabetes, smoking, and a strong family history (coronary artery disease in early or mid-adulthood in a firstdegree relative), low HDL.

Physical examination. Physical examination is most often normal, including chest examination, auscultation, and measurement of heart rate and blood pressure. The purpose of the examination is to exclude non-cardiac causes of chest pain, non-ischaemic cardiac disorders (pericarditis, valvular disease), potential precipitating extra-cardiac causes, pneumothorax, and finally, to look for signs of potential haemodynamic instability and left ventricular dysfunction. Physical examination may reveal tachycardia or bradycardia, hyper- or hypotension, or tachypnea. Inspiratory rales and an S3 gallop are associated with left-sided failure. Jugulovenous distention (JVD), hepatojugular reflux, and peripheral edema suggest right-sided failure. A systolic murmur may indicate ischemic mitral regurgitation or ventricular septal defect.

Laboratory evaluation of chest pain and acute coronary syndromes

Electrocardiogram (ECG)

1. Significant ST-segment elevation is defined as 0.10 mV or more measured 0.02 second after the J point in two contiguous leads, from the following combinations: (1) leads II, III, or aVF (inferior infarction), (2) leads V1 through V6 (anterior or anterolateral infarction), or (3) leads I and aVL (lateral infarction). Abnormal Q waves usually develop within 8 to 12 up to 24 to 48 hours after the onset of symptoms. Abnormal Q waves are at least 30 msec wide and 0.20 mV deep in at least two leads.

2. A new left bundle branch block with acute, severe chest pain should be managed as acute myocardial infarction pending cardiac marker analysis. It is usually not possible to definitively diagnose acute myocardial infarction by the ECG alone in the setting of left bundle branch block.

Laboratory markers

1. Creatine phosphokinase (CPK) enzyme is found in the brain, muscle, and heart. The cardiacspecific dimer, CK-MB, however, is present almost exclusively in myocardium.

2. CK-MB subunits. Subunits of CK, CK-MB, - MM, and -BB, are markers associated with a release into the blood from damaged cells. Elevated CK-MB enzyme levels are observed in the serum 2-6 hours after MI, but may not be detected until up to 12 hours after the onset of symptoms.

3. Cardiac-specific troponin T (cTnT) is a qualitative assay and cardiac troponin I (cTnI) is a quantitative assay. The cTnT level remains elevated in serum up to 14 days and cTnI for 3-7 days after infarction.

4. Myoglobin is the first cardiac enzyme to be released. It appears earlier but is less specific for MI than other markers. Myoglobin is most useful for ruling out myocardial infarction in the first few hours.

Table 1.

Common Markers for Acute Myocardial Infarction

MarkerInitial elevation after MIMean time to peak elevationsTime to return to baseline

Myoglobin1-4 h6-7 h18-24 h

CTnl3-12 h10-24 h3-10 d

CTnT3-12 h12-48 h5-14 d

CKMB4-12 h10-24 h48-72 h

CKMBiso2-6 h12 h38 h

Differential diagnosis of severe or prolonged chest pain:

Myocardial infarction

Unstable angina

Aortic dissection

Gastrointestinal disease (esophagitis, esophageal spasm, peptic ulcer disease, biliary colic, pancreatitis)

Pericarditis

Chest-wall pain (musculoskeletal or neurologic)

Pulmonary disease (pulmonary embolism, pneumonia, pleurisy, pneumothorax)

Psychogenic hyperventilation syndrome

Table 2.Differential diagnosis of acute MI

Life-threateningAortic dissectionPulmonary embolus

Perforating ulcerTension pneumothoraxBoerhaave syndrome

(esophageal rupture with

mediastinitis)

Other cardiovascular and non-ischemicPericarditisAtypical angina

Early repolarization

Wolff-Parkinson-White syndrome

Deeply inverted T-waves suggestive of a central nervous system lesion or apical hypertrophic cardiomyopathyLV hypertrophy with strainBrugada syndrome

Myocarditis

Hyperkalemia

Bundle-branch blocks

Vasospastic angina

Hypertrophic cardiomyopathy

Other noncardiacGastroesophageal reflux (GERD) and spasmChest-wall pain

Pleurisy

Peptic ulcer disease

Panic attackBiliary or pancreatic painCervical disc or neuropathic pain

Somatization and psychogenic pain disorder

Table 3.

Therapy for Non-ST Segment myocardial infarction and unstable angina

TreatmentRecommendations

Antiplatelet agentAspirin, 325 mg (chewable)

NitratesSublingual nitroglycerin (Nitrostat), one tablet every 5 min for total of three tablets initially, followed by IV form (Nitro-Bid IV, Tridil) if needed

Beta-blocker IV therapy recommended for prompt response, followed by oral therapy. Metoprolol (Lopressor), 5 mg IV every 5 min for three doses

Atenolol (Tenormin) 5 mg IV q5min x 2 doses

Esmolol (Brevibloc), initial IV dose of 50 micrograms/kg/min and adjust up to 200-300 micrograms/kg/min

Heparin80 U/kg IVP, followed by 15 U/kg/hr. Goal: aPTT 50-70 sec

Enoxaparin (Lovenox) 1 mg/kg IV, followed by 1 mg/kg subcutaneously bid

Glycoprotein IIb/IIIa inhibitorsEptifibatide (Integrilin) or tirofiban (Aggrastat) for patients with high-risk features in whom an early invasive approach is planned

Adenosine diphosphate receptor-inhibitorConsider clopidogrel (Plavix) therapy, 300 mg x 1, then 75 mg qd.

Cardiac catheterizationConsideration of early invasive approach in patients at intermediate to high risk and those in whom conservative

Initial treatment of acute coronary syndromes Continuous cardiac monitoring and IV access should be initiated. Morphine, oxygen, nitroglycerin, and aspirin ("MONA") should be administered to patients with ischemic-type chest pain unless contraindicated.

Morphine is indicated for continuing pain unresponsive to nitrates. Morphine reduces ventricular preload and oxygen requirements by venodilation. Administer morphine sulfate 2-4 mg IV every 5-10 minutes prn for pain or anxiety. C.Oxygen should be administered to all patients with ischemic-type chest discomfort and suspected ACS for at least 2 to 3 hours.

Intravenous nitroglycerin Nitroglycerin is an analgesic for ischemic-type chest discomfort. Nitroglycerin is indicated for the initial management of pain and ischemia unless contraindicated by hypotension (SBP 1 mm in 2 contiguous leads have acute myocardial infarction. Immediate reperfusion therapy with thrombolytics or angioplasty is recommended.2.Patients with ischemic-type pain but normal or nondiagnostic ECGs or ECGs consistent with ischemia (ST-segment depression only) do not have ST-segment elevation MI. These patients should not be given fibrinolytic therapy.

3.Patients with normal or nondiagnostic ECGs usually do not have AMI, and they should be further evaluated with serial cardiac enzymes, stress testing and determination of left ventricular function.

Management of ST-segment elevation myocardial infarction.

1. Patients with ST-segment elevation have AMI should receive reperfusion therapy with fibrinolytics or percutaneous coronary intervention.

Reperfusion therapy:

Fibrinolytics Patients who present with ischemic pain and ST-segment elevation (>1 mm in >2 contiguous leads) within 6 hours of onset of persistent pain should receive fibrinolytic therapy unless contraindicated. Patients with a new bundle branch block (obscuring ST-segment analysis) and history suggesting acute MI should also receive fibrinolytics or percutaneous coronary intervention.

Indications and contraindications for thrombolysis.

Indications

1. ST in greater than or equal to 2 contiguous leads; greater than or equal to 1mm in limb leads,

or greater than or equal to 2 mm in precordial leads,

or new or presumably new LBBB;

ST segment depression of greater than or equal to 2 mm in V1 V2 (true posterior infarction), and

2. Anginal chest pain greater than 30 minutes but less than 12 hours unrelieved with NTG SL

Absolute contraindications:

1. Previous hemorrhagic stroke at any time; other strokes or cerebrovascular events within one year

2. Known intracranial neoplasm

3. Active internal bleeding (does not include menses)

4. Suspected aortic dissection

Relative contraindications:

1. Severe uncontrolled hypertension on presentation (greater than 180/110 mmHg)

2. History of prior cerebrovascular accident or known intracerebral pathology not covered in above absolute contraindications

3. Current use of anticoagulants in therapeutic doses (INR greater than or equal to 2.0-3.0); known bleeding diathesis

4. Recent trauma (including head trauma) within 2-4 weeks

5. Major surgery in past 3-6 months

6. Noncompressible vascular punctures

7. Recent internal bleeding

8. For streptokinase/anistreplase: prior exposure (especially within 5 days to 2 years) or prior allergic reaction

9. Pregnancy

10. Active peptic ulcer

11. History of chronic hypertension

Table 5.

Treatment recommendations for ST-segment myocardial infarction.

Supportive care for chest pain: All patients should receive supplemental oxygen, 2 L/min by nasal canula, for a minimum of three hours;

Two large-bore IVs should be placed

Analgesic morphine sulfate

Peripheral venous and arterial dilation; Blocks sympathetic efferent discharge at CNS level; reduces preload and afterload - good with CHF

Side effects - hypotension and bradycardia occur rarely; respiratory depression with severe COPD rare in setting of severe chest pain or pulmonary edema

Good dose response, easily reversible; 2- 5mg every 5-30 min (sometimes >30mg)

Aspirin:

InclusionExclusion RecommendationClinical symptoms or suspicion of AMI Aspirin allergy, active GI bleeding

Chew and swallow one dose of1 60-325 mg, then orally qd

Thrombolytics:

InclusionExclusion

RecommendationAll patients with ischemic pain and ST-segment elevation (>1 mm in >2 contiguous leads) within 6 hours of onset of persistent pain, age 100 bpm, and SBP 0.1 ng/mL)

New ST-segment depression

Sustained ventricular tachycardia

Pulmonary edema, most likely due to ischemia

New or worsening mitral regurgitation murmur

S3 or new/worsening rales

Hypotension, bradycardia, tachycardia

Age >75 years

TIMI Risk Score: A simple, effective tool for initial risk assessment. Patients with ACS who are diagnosed as having UA/NSTEMI, present with varying degrees of ischemic risk. A multivariate analysis that adjusts for several prognostic variables simultaneously provides a more accurate tool for risk stratification. In addition, the prognostic scoring system must be readily applicable using standard patient features that are part of the routine, initial medical evaluation. The TIMI risk score, developed to address this need, has been shown to predict the risk of ischemic eventsTable 8.

TIMI risk score for STEMIHISTORICALPOINTS

Age ( ( 75 65-7432

DM or HTN or angina1

EXAM

SBP < 100 mmHg3

HR >100 bpm2

Killip II-IV2

Weight < 67 kg (150 lb)1

PRESENTATION

Anterior STE or LBBB1

Time to Rx > 4 hrs1

RISK SCORE = Total points (0 -14)Because of the complex profiles of these patients, clinicians individually assess prognosis to formulate plans for treatment. The TIMI risk score may be used as a basis for therapeutic decision-making. Prognostication of patient risk allows clinicians to triage patients to the optimum location for medical care, such as the ICU vs hospital ward vs outpatient care. The TIMI risk score also helps identify patients for whom antithrombotic therapies would be especially effective, even those in whom the treatment benefit may be smaller. As demonstrated in the charts below, the TIMI risk score demonstrates that the higher the score, the greater the risk of death or ischemic events. Therefore, patients with higher risk scores may be candidates for early, aggressive treatment.

An early invasive approach is most beneficial for patients presenting with elevated levels of cardiac markers, significant ST-segment depression, recurrent angina at a low level of activity despite medical therapy, recurrent angina and symptoms of heart failure, marked abnormalities on noninvasive stress testing, sustained ventricular tachycardia, recent percutaneous coronary intervention, or prior CABG.

Patients who are not appropriate candidates for revascularization because of significant or extensive comorbidities should undergo conservative management.

Management of patients with a nondiagnostic ECG/ Patients with a nondiagnostic ECG who have an indeterminate or a low risk of MI should receive aspirin while undergoing serial cardiac enzyme studies and repeat ECGs. Treadmill stress testing and echocardiography is recommended for patients with a suspicion of coronary ischemia.

Question:

1. Define acute coronary syndrome (ACS).

2. Describe the differing criteria for unstable angina (UA), non-ST-segment elevated myocardial infarction (NSTEMI), and ST-segment myocardial infarction (STEMI)

3. Compare and contrast the various types of angina.

4. Discuss the underlying pathophysiology of coronary artery disease and acute coronary syndrome.

5. Explain the various complications that can result from ACS when treatment is not implemented or not effective.

6. Perform a thorough assessment of chest pain by using focused questions.

7. Describe the data regarding chest pain description and the patients history and physical examination to assist in ruling out alternative causes for chest pain.

8. Identify unique anginal characteristics of the elderly.

9. Identify abnormal ECG patterns indicative of CAD (Coronary Artery Disease) for a patient who is experiencing angina.

10. Compare and contrast the lab tests used in evaluating suspected ACS.

11. Differentiate between the noninvasive diagnostic tests (echocardiogram and stress tests) that are used to evaluate suspected ACS.

12. Compare and contrast the pharmacologic therapies that are commonly used for patients with ACS including antiplatelet agents, heparin, nitrates, beta-blockers and calcium-channel blockers.

COMPLICATIONS OF ACUTE MIA variety of complications can occur after myocardial infarction even when treatment is initiated promptly.

Complications of the acute period of the myocardial infarction: Arrhythmia and conduction disturbances

Acute left ventricular failure (cardiac asthma, pulmonary oedema)

Cardiogenic shock

Acute aneurysm of heart

Ventricular septal rupture (VSR) Papillary muscle rupture or dysfunction (causing mitral regurgitation)

Cardiac free wall rupture Pericarditis

Tromboembolic episodes

Acute erosions and ulcers of the gastrointestinal tract Complications of the subacute period of the myocardial infarction: Arrhythmia and conduction disturbances

Chronic heart failure

Chronic aneurysm of the heart

Tromboembolic episodes

Postmyocardial infarction syndrome (Dressler's syndrome )

ostmyocardial infarction stenocardiaVentricular tachyarrhythmia post Ml1Accelerated idioventricular rhythm Common (up to 20%) in patients with early reperfusion in first 48 hours. Usually self limiting and short lasting with no haemodynamic effects If symptomatic, accelerating sinus rate with atrial pacing or atropine may be of value. Suppressive anti-arrhythmic therapy (lignocaine, amiodarone) is only recommended with degeneration into malignant ventricular tachyarrhythmias.2Ventricular premature beats (VPB) Common and not related to incidence of sustained VT/VF Generally treated conservatively. Aim to correct acid-base and electrolyte abnormalities (aim K + >4.0mmol/L and Mg2+>1.0mmol/L) Peri-infarction -blockade reduces VPB.3Non-sustained and monomorphic ventricular tachycardia (VT) Associated with a worse clinical outcome

Correct reversible features such as electrolyte abnormalities and acid-base balance DC cardioversion for haemodynamic instability Non-sustained VT and haemodynamically stable VT (slow HR 0.20s) is a contraindication to -blockade.2Second-degree AV blockThis indicates a large infarction affecting conducting systems and mortality is generally increased in this group of patients Mobitz type I is self-limiting with no symptoms. Generally, requires no specific treatment. If symptomatic or progression to complete heart block will need temporary pacing Mobitz type II, 2:1, 3:1 should be treated with temporary pacing regardless of whether it progresses to complete heart block.3Third-degree AV block In the context of an inferior Ml can be transient and does not require temporary pacing unless there is haemodynamic instability or an escape rhythm of