Acute Coronary Syndrome BY BATOOL BASYOUNI

Patients with ischemic heart disease (IHD) fall into two large groups:

A. patients with chronic coronary artery disease (CAD) who most commonly present with stable angina (SIHD).

B. patients with acute coronary syndromes (ACSs). The spectrum of ACS includes ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), and unstable angina

PATHOPHYSIOLOGY Acute coronary syndrome (ACS) is an acute manifestation of coronary artery disease (CAD) and, for many patients,

is the first indication that they have CAD. It is most commonly caused by an imbalance between oxygen supply and

oxygen demand resulting from an occluding thrombus forming on a disrupted atherothrombotic coronary plaque

“Vulnerable Plaque” which typically have a lipid-rich core with thin fibrous caps, or on eroded coronary artery

endothelium.

Severe ischemia or myocardial necrosis may occur consequent to the reduction of coronary blood flow caused by the

thrombus.

Atherosclerotic plaques that rupture in patients with ACS tend to be “nonobstructive”, occluding less than 70% of the

luminal diameter.

Thus, patients with nonobstructive plaques may not experience angina symptoms prior to plaque rupture due to

adequate autoregulation to maintain blood flow and oxygen supply in times of increased myocardial oxygen demand.

Therefore, patients are often unaware they have atherosclerotic plaques until the ACS event occurs.

In STEMI, the artery is totally occluded, while in NSTEMI and unstable angina the artery is subtotally occluded.

The thinning of the fibrous cap involves both an increased breakdown of collagen in the fibrous matrix, and a reduction in collagen production to restore the structure of the fibrous cap. Inflammatory processes are involved with both mechanisms

A thinning fibrous cap by itself does not usually produce plaque rupture.

There is typically a connection to physiological or psychological stress which enhances the likelihood of an acute event.

Approximately two-thirds of ACS events occur in the morning. This is likely related to circadian rhythm activation of the sympathetic nervous system and catecholamine release that produces an increase in heart rate, blood pressure, and vasoconstriction.

An increase in catecholamines may occur due to physical and emotional stress. These changes in conjunction with a thin fibrous cap place patients at risk for ruptured atherosclerotic plaque and subsequent ACS.

Upon plaque rupture, the barrier between the necrotic core of the plaque and blood components is breached.

Circulating platelets are initially attracted and adhere to the area of injury

During platelet activation;

1. Granules with high concentrations of platelet activators (eg, thromboxane A2, ADP, serotonin) make their way to the surface of the platelet and release their contents into the circulation

2. Assembly of the tenase and prothrombinase complex that produce most of the activated factor Xa and IIa (thrombin) in the coagulation cascade

3. Expression of active GP IIb/IIIa receptors

The platelet plug by itself is rarely enough to significantly occlude myocardial blood flow and oxygen supply.

A fibrin meshwork then forms within and on top of the platelet plug that more completely traps cellular components such as red blood cells and produces the abrupt reduction in myocardial blood flow.

The formation of this fibrin meshwork involves activation of the clotting cascade.

Thrombus formation in the area of atherosclerotic plaque rupture produces an abrupt reduction in myocardial blood flow and oxygen supply.

This abrupt blockage produces ischemia and, if untreated, potentially infarction which results in myocyte necrosis and cell death

GENERAL CHARACTERISTICS

Unstable angina is characterized by:

1. New-onset (i.e., within the prior 2 weeks) or <6 weeks

2. Rapidly worsening angina (crescendo angina) (i.e., distinctly more severe, prolonged, or frequent than previous episodes),

3. Angina on minimal exertion or angina at rest, in the absence of myocardial damage.

The diagnosis of NSTEMI is established if a patient with these clinical features develops evidence of myocardial necrosis, as reflected in abnormally elevated levels of biomarkers of cardiac necrosis. (cardiac enzymes : Troponin & /Creatinine Kinase)

Myocardial infarction differs from unstable angina, since there is evidence of myocardial necrosis.

Most patients with MI have history of angina, risk factors for CAD, or history of arrhythmias.

CLINICAL PRESENTATION General

The patient is typically in acute distress and may develop or present with hypertensive crisis, acute heart failure, cardiogenic shock, or cardiac arrest.

Symptoms

The classic symptom of ACS is abrupt-onset substernal chest pain or discomfort often described as Intense substernal pressure sensation “crushing” and “an elephant standing on my chest.”, squeezing, heaviness, or tightness that persists for 10 minutes or longer. It is sometimes located in the epigastrium

Symptoms may radiate to the arms, shoulders, back, abdomen, or jaw, commonly to the left side.

Similar to angina pectoris in character and distribution but much more severe and lasts longer. Unlike in angina, pain typically does not respond to nitroglycerin.

Nausea, vomiting, diaphoresis, or shortness of breath may also be present.

Up to one-third of patients are likely to be asymptomatic; painless infarcts or atypical presentations more likely in postoperative patients, older adults aged 75 years or greater, women, and patients with diabetes, impaired renal function, and dementia.

SIGNS

No physical findings are specific for ACS.

Nonspecific findings include;

1. S4 or paradoxical splitting of S2 on auscultation.

2. Patients with ACS may present with signs of acute decompensated HF including jugular venous distention, pulmonary edema, and an S3 on auscultation.

3. Patients with ischemia-related papillary muscle dysfunction may present with a new murmur of mitral regurgitation.

4. Patients may also present with arrhythmias, including tachycardia or bradycardia, as well as heart block.

5. Hemodynamic abnormalities may include hypertension and hypotension or shock.

LABORATORY TESTS 1) Cardiac troponin (cTn, either cTnI or cTnT) currently the diagnostic gold standard for myocardial injury, is measured at the time of presentation and repeated 3 to 6 hours later to detect myocardial injury; and 6 hours of symptoms onset in patients intermediate to high-risk features of ACS but normal cTn levels during serial measurements

Elevated levels in a patient with ACS symptoms, ischemic changes on ECG, or other diagnostic evidence of ischemia confirm the diagnosis of MI.

For patients with ACS symptoms who do not have ST-segment elevation on ECG but an elevated cTn, NSTEMI is the appropriate diagnosis.

Patients' ACS symptoms with ischemic changes on ECG but normal cTn may have unstable angina (UA) or an alternative diagnosis.

Troponin I can be falsely elevated in patients with renal failure, PE, Tachycardia, post-PCI, SEPSIS, amyloidosis & pericarditis ; thus following trend of levels is important.

2) CK-MB—less commonly used, Increases within 4 to 8 hours and returns to normal in 48 to 72 hours; reaches a peak in 24 hours. When measured within 24 to 36 hours of onset of chest pain, has greater than 95% sensitivity and specificity. Most helpful in detecting recurrent infarction given quicker return to baseline than troponin.

2. Blood chemistry tests are performed with particular attention given to potassium and magnesium, which may affect heart rhythm.

3. SCr is measured and CrCl is used to identify patients who are at high risk of morbidity and mortality—dosage adjustments for renally cleared medications may be necessary.

4. Baseline complete blood count (CBC) and coagulation tests (aPTT or anti-Xa levels, INR) should be obtained; most patients will receive antithrombotic therapy and these tests are useful in monitoring for complications related to antithrombotic therapy, including bleeding.

5.Fasting lipid panel.

OTHER DIAGNOSTIC TESTS The 12-lead ECG is the first step in evaluating a patient with ACS. Patients are risk-stratified into two groups: those with ST-segment elevation or its equivalent (STEMI) and those without (NSTE-ACS). Patients with NSTE-ACS may have other ischemic ECG changes including ST-segment depression or T-wave inversion.

Patients with STEMI, intermediate- to high-risk ACS, and those with recurrent chest discomfort are likely to undergo coronary angiography via a left heart catheterization to diagnose CAD and may be treated with PCI during the procedure.

Prior to hospital discharge, an assessment of left ventricular (LV) function via echocardiogram or equivalent modality should be performed to identify patients with LV dysfunction (LV ejection fraction [LVEF] less than 40% [0.40]) who are at high risk of death and candidates for guideline-directed medical therapy and device therapy.

- ECG changes will give you an idea of the site of the infarction:

ST segment elevation is considered significant only if present in 2 or more adjacent leads (this applies to most ECG abnormalities)

ST elevation is significant when the elevation is more than 1 mm in limb leads and 2 mm in precordial leads

ST elevation in anterior and lateral leads: the artery most probably involved is LAD or left main.

ST elevation in Lead II, III, aVF: inferior infarct (right coronary artery)

ST elevation in Lead I, aVL, V5, and V6: lateral wall infarct (left circumflex)

ST elevation in V2-V4: anteroseptal infarct

Prominent R wave and ST segment depression in leads V1-V2: posterior wall infarct

RISK STRATIFICATION

A risk assessment that incorporates the clinical presentation, past medical history, ECG, and cTn should be performed to identify high-risk patients and guide therapeutic interventions

Several risk scoring tools have been developed that predict both short-term and long-term event rates, such as mortality, in patients with ACS

Because they have been well-studied and can be easily applied in the clinical setting, the most common among these risk calculators are the Thrombolysis in Myocardial Infarction (TIMI) risk score for NSTE-ACS and the Global Registry of Acute Coronary Events (GRACE) score

TREATMENT

Treatment decisions for patients with ACS are made based on the initial and ongoing risk.

Rapid identification and delineation of ACS subtype (STEMI, NSTE-ACS) is imperative as treatment goals and timeframes for intervention differ slightly based upon the clinical presentation and subsequent risk of death or complications from the index event (eg, patient with STEMI).

When ACS is suspected, the patient should be immediately referred to an ED, chest pain unit, or equivalent facility for evaluation which should include 12-lead ECG and cTn such that expeditious treatment can be initiated.

GENERAL APPROACH TO TREATMENT The general treatment approach to ACS includes rapid diagnostic triage to determine an appropriate management strategy.

1. Patients with STEMI are of the highest priority and should be emergently referred to the cardiac catheterization lab for primary PCI with the goal of mechanically restoring blood flow to the infarct-related artery as quickly as possible.

2. Patients with NSTE-ACS will undergo additional risk stratification to determine the best approach,

a) Early invasive approach (eg, PCI) for intermediate- and high-risk patients or

b) Conservative, ischemia-guided management plan without planned PCI for those with either the lowest risk for coronary event or contraindications to the invasive procedure itself

GENERAL APPROACH TO TREATMENT Regardless of treatment strategy planned (early invasive approach or ischemia-guided approach), general treatment measures for intermediate- and high-risk patients include

i. Admission to the hospital, (ICU, CCU)

ii. Oxygen administration (if oxygen saturation is <90% [0.90])

iii. Bed rest with continuous multi-lead ST-segment monitoring for arrhythmias and ischemia

iv. Frequent measurement of vital signs

v. Ischemic pain relief

vi. Prompt initiation of antithrombotic therapy

Check word

ACUTE SUPPORTIVE CARE THROMBINS2

1. Thienopyridine (Clopidogrel or prasugrel),

2. Heparin

3. Renin-angiotensin-aldosterone system

4. Oxygen

5. Morphine

6. β-blocker

7. Intervention [eg, PCI]

8. Nitroglycerin

9. Statin/Salicylate [eg, aspirin]

Early interventions to consider in patients with ACS

Fibrinolysis

When primary PCI for patients with STEMI is not possible within a timely fashion, fibrinolysis is an important means of reperfusion.

• Recent guidelines state that fibrinolysis is indicated and should be administered when PCI cannot be performed due to;

1. Immediate contraindications to receiving contrast dye,

2. When patients present to a facility unable to perform PCI and transfer time would exceed 120 minutes

3. When patients present at off-peak hours when the catherization laboratory is not adequately staffed

Fibrinolytic therapy is associated with a slight but statistically significant risk for stroke, and largely attributed to intracranial hemorrhage (ICH)

Thrombolytics are divided into several generations. The best are 3rd generation thrombolytics such as tenecteplase*. Tenecteplase can be given as an IV bolus. Older generations need to be given as infusions.

- With thrombolytics, there is a high risk for an anaphylactic reaction

- Do not give thrombolytics in patients with active bleeding, CVA, CPR, ST depression.

- One of the worst complications of thrombolytics is the creation of emboli:

- MI’s can be complicated with formation of thromboemboli which can be lodged anywhere in the body. Due to stagnation of blood in the left ventricle, a clot might form. There is a high risk that this clot can cause a CVA

COMPLICATIONS OF ACUTE MI 1. Pump failure (CHF)

a. If mild, treat medically (ACE inhibitor, diuretic)

b. If severe, may lead to cardiogenic shock; invasive hemodynamic monitoring may be indicated.

2. Arrhythmias

a. premature ventricular contractions (pvcs)—conservative treatment (observation) indicated; no need for antiarrhythmic agents

b. atrial fibrillation (AFib)

c. ventricular tachycardia (vt)-sustained VT requires treatment: If patient is hemodynamically unstable, electrical cardioversion is indicated. If patient is hemodynamically stable, start antiarrhythmic therapy (IV amiodarone).

d. VFib—immediate unsynchronized defibrillation and CPR are indicated.

e. accelerated idioventricular rhythm does not affect prognosis; no treatment needed in most cases

F. paroxysmal supraventricular tachycardia (psvt).

*The most common cause of death in MI patient is arrest due to ventricular fibrillation

g. sinus tachycardia

• May be caused by pain, anxiety, fever, pericarditis, medications, etc.

• Worsens ischemia (increases myocardial oxygen consumption)

• Treat underlying cause (analgesics for pain, aspirin for fever, etc.)

h. sinus bradycardia

• A common occurrence in early stages of acute MI, especially right-sided/inferior MI

• May be a protective mechanism (reduces myocardial oxygen demand)

• No treatment is required other than observation. If bradycardia is severe or symptomatic (hemodynamic compromise), atropine may be helpful in increasing HR

i. asystole

• Very high mortality.

• Treatment should begin with electrical defibrillation for VFib, which is more common in cardiac arrest and may be difficult to clearly differentiate from asystole.

• If asystole is clearly the cause of arrest, transcutaneous pacing is the appropriate treatment.

j. AV block

• Associated with ischemia involving conduction tracts.

• First-degree and second-degree (type I) blocks do not require therapy.

• Second-degree (type II) and third-degree blocks: Prognosis is dire in the setting of an anterior MI—emergent placement of a temporary pacemaker is indicated (with later placement of a permanent pacemaker). In inferior MI, prognosis is better, and IV atropine may be used initially. If conduction is not restored, a temporary pacemaker is appropriate.

3. Recurrent infarction (extension of existing infarction or reinfarction of a new area)

a. Both short-term and long-term mortality are increased.

b. Diagnosis is often difficult.

• Cardiac enzymes are already elevated from the initial infarction. Troponin levels remain elevated for a week or more, so are not useful here. CK-MB returns to normal faster, and so a reelevation of CK-MB after 36 to 48 hours may be due to recurrent infarction.

• If there is repeat ST segment elevation on ECG within the first 24 hours after infarction, suspect recurrent infarction.

c. Treatment: Repeat thrombolysis or urgent cardiac catheterization and PCI. Continue standard medical therapy for MI.

4. Mechanical complications

a. Free wall rupture

• A catastrophic, usually fatal event that occurs during the first 2 weeks after MI (90% within 2 weeks, most commonly 1 to 4 days after MI)

• 90% mortality rate

• Usually leads to hemopericardium and cardiac tamponade

• Treatment: Hemodynamic stabilization, immediate pericardiocentesis, and surgical repair.

b. Rupture of interventricular septum

• Greater potential for successful therapy than with a free wall rupture, although this is also a critical event; emergent surgery is indicated

• Occurs within 10 days after MI

• Likelihood of survival correlates with size of defect

c. Papillary muscle rupture

• Produces MR (presents with new murmur)

• If suspected, obtain an echocardiogram immediately

• Emergent surgery is needed (mitral valve replacement is usually necessary), as well as afterload reduction with sodium nitroprusside or intra-aortic balloon pump (IABP)

d. Ventricular pseudoaneurysm

• Incomplete free wall rupture (myocardial rupture is contained by pericardium)

• Bedside echocardiogram may show the pseudoaneurysm

• Surgical emergency because ventricular pseudoaneurysms tend to become a free wall rupture

e. Ventricular aneurysm

• Rarely rupture (in contrast to pseudoaneurysms)

• Associated with a high incidence of ventricular tachyarrhythmias

• Medical management may be protective

• Surgery to remove aneurysm may be appropriate in selected patients

5. Acute pericarditis

a. The incidence has decreased sharply since the introduction of revascularization techniques.

b. Treatment consists of aspirin (which is already standard in treatment of MI).

c. NSAIDs and corticosteroids are contraindicated (may hinder myocardial scar formation).

6. Dressler syndrome (“postmyocardial infarction syndrome”)

a. Immunologically based syndrome consisting of fever, malaise, pericarditis, leukocytosis, and pleuritis, occurring weeks to months after an MI

b. Aspirin is the most effective therapy. Ibuprofen is a second option

Differential diagnosis: *Aortic dissection:

- Severe tearing pain

- Mimics pain of MI, especially if it involves the ascending aorta (type A dissection).

- The difference between MI pain and dissection pain is that the peak of the dissection pain is right from the start. While in MI, the pain usually progresses

- Dissection type B: usually the pain is in the back (interscapular)

*Massive pulmonary embolism

*Acute pericarditis

*Pneumonia

- High mortality rate in MI up to 20%

- The commonest cause of death outside the hospital is ventricular fibrillation

- The commonest cause of death inside the hospital is cardiogenic shock

Secondary Prevention of Ischemic Events