8. Acute coronary syndromes (myocardial infarction, unstable angina pectoris)

Overview of Acute Coronary Syndromes

• Definition: ACS include unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI).

• Pathophysiology: Typically results from the rupture of an atherosclerotic plaque and subsequent thrombus formation, which abruptly reduces or blocks blood flow through a coronary artery.

Risk Factors

• Common: Increasing age, male gender, smoking, and a family history of coronary artery disease.

• Comorbidities: Hypertension, diabetes mellitus, hyperlipidemia, and obesity significantly contribute to the risk of developing ACS.

Alternate Causes of ACS

• Coronary Artery Vasospasm: Can cause transient episodes of chest pain (Prinzmetal angina); triggered by substances like cocaine.

• Coronary Artery Embolism: May result from conditions like atrial fibrillation or the presence of a prosthetic heart valve.

• Takotsubo Cardiomyopathy: Also known as stress-induced cardiomyopathy, it mimics ACS but is typically precipitated by severe emotional or physical stress.

• Myocarditis: Inflammation of the heart muscle, often due to viral infections, which can impair myocardial function and mimic symptoms of ACS.

• Thrombophilia: Increased tendency to form blood clots can lead to coronary thrombosis.

• Vasculitis: Inflammatory destruction of blood vessels, which can include coronary arteries.

• Myocardial Oxygen Supply-Demand Mismatch: Conditions like severe anemia, hypertrophic cardiomyopathy, or aortic stenosis can precipitate myocardial ischemia without coronary artery occlusion.

Pathophysiology of Acute Coronary Syndrome (ACS)

1. Formation and Rupture of Atherosclerotic Plaque:

   • Unstable Atherosclerotic Plaque: The primary cause of ACS is the rupture of an unstable plaque, which is lipid-rich and covered by a thin fibrous cap. This cap is more susceptible to rupture even under minor stress due to its structural weakness.

   • Stable Plaque: In contrast, stable plaques contain fewer lipids and have a thicker fibrous capsule, making them less likely to rupture. However, they can still cause partial occlusion of the coronary artery, typically presenting as stable angina.

2. Role of cdx: These enzymes, secreted by inflammatory cells within the plaque, degrade the structural integrity of the fibrous cap, leading to its eventual rupture.

3. Activation of the Thrombotic Pathway: Once the plaque ruptures, the underlying connective tissues are exposed to the bloodstream, triggering the thrombotic pathway and leading to clot formation.

Consequences of Plaque Rupture

• Partial Occlusion: Leads to conditions such as unstable angina or non-ST-elevation myocardial infarction (NSTEMI). These conditions are characterized by ischemia, particularly affecting the subendocardial layer of the myocardium, which is highly susceptible to reductions in blood supply.

• Complete Occlusion: Results in ST-elevation myocardial infarction (STEMI), where there is a full thickness (transmural) myocardial damage due to the complete interruption of blood supply.

Clinical Presentation and Management of ACS

• Unstable Angina:

  • Definition: A deterioration of previously stable angina where the pain becomes more severe, frequent, and may also occur at rest.

  • Characteristics: Episodes typically last less than 20 minutes. Despite the severe symptoms, myocardial necrosis does not occur, so cardiac biomarkers remain normal.

  • ECG Findings: Can range from normal to showing ST-depression, reflecting myocardial strain rather than damage.

  • Treatment: Includes antiplatelet therapy (aspirin, ticagrelor) and anticoagulation to prevent further thrombus formation. In high-risk cases, more invasive procedures like percutaneous coronary intervention (PCI) may be necessary.

NSTEMI

• Pathophysiology: Characterized by acute myocardial ischemia that leads to myocardial injury, typically due to a partial occlusion of a coronary artery. The subendocardial layer, which is the innermost layer of the heart wall, is particularly affected because it is the most vulnerable to reductions in blood supply.

• Diagnostic Criteria:

  • Cardiac Biomarkers: Elevated levels are indicative of myocardial injury. Common biomarkers include troponins, which are released into the bloodstream from the damaged heart muscle.

  • ECG Changes: Can be non-specific. Typical findings may include ST-segment depression, T-wave inversion, or a loss of R-wave amplitude, reflecting subendocardial ischemia.

• Treatment of NSTEMI:

  • Anticoagulation Therapy: Essential to prevent further clot formation.

  • Antiplatelet Therapy: Aspirin and P2Y12 inhibitors (e.g., ticagrelor) are standard to reduce the risk of further thrombotic events.

  • Invasive Procedures: High-risk patients may require coronary angiography followed by possible revascularization via percutaneous coronary intervention (PCI).

STEMI

• Pathophysiology: Resulting from a complete occlusion of a coronary artery, leading to transmural infarction where the entire thickness of the heart muscle is affected. This complete blockage is more severe than in NSTEMI and results in extensive myocardial damage.

• Diagnostic Criteria:

  • Cardiac Biomarkers: Similarly to NSTEMI, biomarkers will be elevated but typically to a higher extent due to more significant muscle damage.

  • ECG Findings: Characterized by ST-segment elevations in two contiguous leads or the presence of a new left bundle branch block (LBBB), indicative of a widespread impact on cardiac electrical activity.

• Treatment of STEMI:

  • Immediate Revascularization: Urgent PCI, commonly known as angioplasty with stenting, is the preferred treatment to restore blood flow. In some regions or cases where PCI is not available within the optimal time frame, thrombolytic therapy may be used.

  • Anticoagulation and Antiplatelet Therapy: Similar to NSTEMI, these are used to prevent further clots and stabilize existing ones.

  • Post-Revascularization Care: Continued care with medications such as beta-blockers, ACE inhibitors, or statins to manage risk factors and prevent complications.

Common Clinical Features of Acute Coronary Syndrome

1. Acute Retrosternal Chest Pain:

   • Description: Often described as dull, squeezing, or a pressure-like sensation.

   • Radiation: Commonly radiates to the left arm, shoulder, neck, jaw, back, or epigastrium.

   • Triggers: Typically precipitated by exertion or stress.

   • Timing: Frequently occurs in the morning when circadian variations in blood pressure and coronary arterial tone can predispose to increased plaque rupture.

2. Dyspnea: Shortness of breath is a frequent symptom, reflecting either direct myocardial dysfunction or a consequence of the acute stress response.

3. Pallor: Paleness due to poor perfusion and the body's sympathetic response diverting blood to vital organs.

4. Nausea and Vomiting: These symptoms may be due to the visceral pain referral from the ischemic myocardium or a vagal response.

5. Diaphoresis and Anxiety: Sweating and feelings of anxiety are common and relate to adrenergic activation in the setting of pain and hypoxia.

6. Dizziness or Syncope: Caused by reduced cardiac output and cerebral perfusion during acute events.

Specific Manifestations Based on Infarction Location

1. Inferior Wall Infarction:

   • Cause: Typically results from occlusion of the right coronary artery.

   • Symptoms: Can include bradycardia due to involvement of the sinoatrial or atrioventricular nodes, and epigastric pain, often mistaken for indigestion or gastrointestinal issues.

2. Right Ventricular Infarction:

   • Indicators: Hypotension, elevated jugular venous pressure, and clear lung fields.

   • Importance: Recognizing right ventricular involvement is crucial as these patients may require specific management strategies, including maintenance of adequate right ventricular preload and cautious use of nitrates.

Atypical Presentations

• Minimal or No Chest Pain: Particularly common in patients with diabetes due to diabetic neuropathy, which may mask typical chest pain sensations.

• Elderly and Women: May also present atypically, often due to higher pain thresholds or differences in pain perception. Symptoms in these groups may include fatigue, breathlessness, and general malaise rather than classic chest pain.

Initial Diagnostic Steps of Acute Coronary Syndrome

1. ECG: An immediate ECG is crucial when ACS is suspected. The ECG can show various changes depending on the stage and severity of the myocardial infarction.

2. Cardiac Biomarkers: Measurement of enzymes and proteins such as troponins, which are released into the blood from the damaged heart muscle, helps confirm myocardial injury. Elevated troponin levels are significant indicators of myocardial infarction.

ECG Changes in STEMI

• Acute Stage:

  • Hyperacute T-waves: Peaked T-waves are an early sign but only appear when the MI is ongoing.

  • ST-Elevation: Occurs in two contiguous leads with reciprocal ST-depressions elsewhere. This indicates ongoing myocardial damage due to complete occlusion of a coronary artery.

• Intermediate Stage:

  • Necrosis Indicators: The R-wave may disappear, and pathological Q-waves begin to form. T-wave inversions also occur as the injury progresses.

  • Pathological Q-Waves: Defined as having a duration >40 ms, amplitude >0.1 mV, or appearance in leads V1-V3, indicating myocardial necrosis.

• Chronic Stage:

  • Scarring: Persistent, broad, and deep Q-waves indicate the formation of scar tissue where myocardial necrosis occurred. T-wave inversions may remain, and R-waves may not fully recover, showing incomplete healing.

• Sequence of ECG Changes: The progression typically follows this sequence:

  • Hyperacute T-waves → ST-elevation → Pathological Q-wave formation → T-wave inversion → ST normalization → T-wave normalization.

Special Considerations

• Left Bundle Branch Block (LBBB):

  • In patients presenting with new or presumably new LBBB and symptoms suggestive of ACS, it's treated as a STEMI equivalent because it can mask the typical ST-elevations due to underlying ventricular depolarization abnormalities.

ECG Changes in NSTEMI

• NSTEMI Characteristics:

  • Unlike STEMI, NSTEMI does not typically show ST-elevation.

  • ECG may show non-specific changes such as ST-depressions, T-wave inversions, or a loss of R-wave amplitude, reflecting less severe but still significant myocardial injury.

Importance of Timely Diagnosis

• Prompt identification and treatment are crucial to minimize myocardial damage and improve outcomes. The management strategies differ between STEMI and NSTEMI, primarily based on the presence or absence of ST-elevation, with STEMI often requiring more immediate and aggressive interventional treatment.

Localization of Myocardial Infarction by ECG Leads

1. V1-V6 (Chest Leads)

   • V1-V6: Indicates an extensive anterior infarct, typically due to occlusion of the proximal left anterior descending artery (LAD). This artery supplies the anterior wall, the anterior part of the lateral wall, the apex, and the anterior two-thirds of the interventricular septum.

   • V1-V2: Suggests an anteroseptal infarction, indicative of an LAD occlusion affecting the basal part of the septum.

   • V3-V4: Points to an anteroapical infarction, likely due to occlusion of the distal LAD, affecting the apex of the heart.

   • V5-V6: Reflects an anterolateral infarction, which can be caused by occlusion of the distal LAD, a diagonal branch of the LAD, or the left circumflex artery.

2. Limb Leads

   • I, aVL: These leads indicate a lateral wall infarction, typically due to occlusion of the proximal left circumflex artery, which supplies the lateral wall of the left ventricle.

   • II, III, aVF: These leads show an inferior wall infarction. This is most commonly caused by occlusion of the right coronary artery (RCA), which supplies the inferior part of the left ventricle, parts of the right ventricle, and the sinoatrial and atrioventricular nodes. Less commonly, it may be due to occlusion of the distal left circumflex artery.

3. Extended Leads for Posterior Wall

   • V7-V9: These leads are used to detect a posterior wall infarction, typically involving the posterior descending artery. Reciprocal changes (ST-depressions) in leads V1-V3 often accompany true posterior wall MIs.

Localization of Infarction Based on ECG Leads

• V1-V4 (Anterior Leads): These leads view the anterior wall of the heart, predominantly supplied by the left anterior descending artery (LAD). An MI here typically presents with ST elevations in these leads.

• I, aVL, V5-V6 (Lateral Leads): These leads reflect the lateral wall of the left ventricle, primarily supplied by branches of the left circumflex artery (LCX) and the LAD. Changes here indicate a lateral wall MI.

• II, III, aVF (Inferior Leads): These leads view the inferior part of the heart, which is usually supplied by the right coronary artery (RCA). An MI in this area shows ST elevations in these inferior leads.

• III, aVF, V1, V6 (Posterior Leads): Though not typically used to directly visualize the posterior wall, changes in these leads can suggest a posterior MI. Posterior MIs often show reciprocal changes (ST depressions) in V1-V2 and might require additional posterior leads (V7-V9) for direct visualization.

Laboratory Markers for Myocardial Infarction

• Troponin T/I:

  • Timing: Troponins begin to rise 6-8 hours after the onset of MI, peak around 12-24 hours, and return to baseline within 7-10 days.

  • Specificity: Highly specific for myocardial damage. The degree of elevation is generally proportional to the myocardial injury extent, making it a valuable marker for assessing the severity of MI.

  • Sensitivity: Troponin levels are also sensitive, but elevations can occur in other cardiac conditions such as myocarditis or heart failure.

• Myoglobin:

  • Timing: Rises within 1 hour post-MI, peaks between 4-12 hours, and normalizes within 24 hours.

  • Use: Due to its rapid rise and decline, myoglobin can be helpful for early diagnosis of MI and is particularly useful for detecting reinfarction.

• Creatine Kinase (CK-MB):

  • Timing: Begins to rise 4-9 hours after MI onset, peaks at 12-24 hours, and returns to normal within 2-3 days.

  • Use: Previously a standard biomarker for MI, CK-MB is useful for identifying reinfarction due to its relatively short duration in the blood compared to troponins.

• Additional Findings:

  • Leukocytosis: Commonly seen in response to stress and tissue damage.

  • C-Reactive Protein (CRP): Elevated in response to inflammation.

  • Brain Natriuretic Peptide (BNP): Elevated in cases of heart failure which may complicate or result from MI.

  • Lactate Dehydrogenase (LDH) and Aspartate Transaminase (AST): These enzymes can be elevated in MI, but they are less specific than troponin and CK-MB.

Other Diagnostic Methods of Acute Coronary Syndrome

1. Coronary Angiography:

   • Purpose: Considered the gold standard for diagnosing coronary artery disease, coronary angiography directly visualizes the coronary arteries to identify blockages or occlusions.

   • Procedure: Involves the insertion of a catheter into the coronary arteries and the injection of a contrast dye, visualized by X-ray imaging.

   • Indications: Mandatory for acute STEMI and recommended for high-risk ACS patients without STEMI, such as those with dynamic ECG changes or ongoing chest pain.

   • Interventions: Allows for simultaneous interventions like percutaneous coronary intervention (PCI) with stent placement to restore blood flow.

2. Transthoracic Echocardiogram (TTE):

   • Purpose: Used to assess cardiac structure and function, particularly left ventricular function and wall motion abnormalities.

   • Utility: Helps in detecting complications such as ventricular aneurysms, thrombi, or valvular issues. It is an excellent tool for evaluating left ventricular ejection fraction, a key determinant of prognosis.

3. Cardiac Computed Tomography (CT):

   • Indication: An alternative to invasive angiography, especially useful in patients with an intermediate risk of coronary artery disease.

   • Advantages: Non-invasive and capable of visualizing the coronary arteries, cardiac CT can also assess for calcium scoring and other vascular conditions.

   • Limitations: Less suitable in cases of high calcium burden or in patients with arrhythmias, which may affect image clarity.

Risk Assessment Tools

1. TIMI Score:

   • Purpose: Used to assess the risk of death and ischemic events in patients with unstable angina or NSTEMI.

   • Components: Includes factors such as age >65, presence of three or more risk factors for coronary artery disease, known coronary artery stenosis >50%, at least two episodes of angina in the last 24 hours, use of aspirin in the past seven days, recent changes in ST-segment on ECG, and elevated cardiac biomarkers.

   • Scoring: Each factor scores one point. A higher score indicates a higher risk and suggests the need for more aggressive treatment, including early angiography.

Clinical Application

• Low TIMI Score (0-2): Typically managed with medical therapy and non-invasive testing.

• High TIMI Score (>3): Indicates a higher risk and may warrant early invasive strategies such as coronary angiography and potential revascularization.

Gross Morphology of Myocardial Infarction

1. >12 Hours Post-Infarction:

   • Observations: Initially, there may be no visible changes to the myocardial tissue.

2. 12-24 Hours:

   • Appearance: The infarcted area starts to appear pale due to tissue necrosis. A reddish-blue discoloration may develop around the edges due to stagnated blood, often described as dark mottling or red-purplish marbling.

3. 1-3 Days:

   • Changes: The affected area exhibits hyperemia (increased blood flow to the tissue as part of the inflammatory response) and begins to show a yellow pallor indicating the progression of tissue death.

4. 3-14 Days:

   • Description: The central zone of the infarct turns yellow-brown and becomes soft due to necrosis, surrounded by a hyperemic border as the body ramps up inflammatory and healing responses.

5. >2 Weeks to Months:

   • Later Stages: The necrotic tissue is gradually replaced by grayish-white fibrous scar tissue, signifying the formation of a permanent scar as the final stage of healing.

Microscopic Morphology of Myocardial Infarction

1. 4-12 Hours:

   • Initial Changes: Early signs of coagulative necrosis appear alongside oedema and hemorrhage within the tissue. Neutrophils infiltrate the area, and myofibrils show hypercontraction, evident as wavy fibers.

2. 12-24 Hours:

   • Cellular Changes: Pyknosis (condensation and shrinkage) of nuclei occurs, and contraction band necrosis develops if reperfusion occurs. This type of necrosis is characterized by hypercontraction of sarcomeres, typical of reperfusion injury.

3. 1-3 Days:

   • Tissue Response: There is extensive coagulative necrosis characterized by the loss of nuclei and striations in cardiac muscle cells. Inflammatory response intensifies in the surrounding tissue.

4. 3-14 Days:

   • Healing Process: The presence of dying neutrophils diminishes, while macrophages infiltrate to phagocytize dead cells. Granulation tissue starts to form, initiating the healing and repair process.

5. >2 Weeks to Months:

   • Scar Formation: Over time, granulation tissue is replaced by collagenous scar tissue. This fibrous tissue lacks the contractile function of myocardium, affecting the overall function of the heart depending on the size and location of the scar.

Monitoring and Initial Assessment

• ECG Monitoring: Continuous ECG monitoring is crucial for detecting cardiac rhythm abnormalities and assessing the effectiveness of treatments.

• Troponin Measurement: Regular measurement of troponin levels helps to confirm the diagnosis of MI and assess the extent of myocardial damage.

Symptom Management

• Nitroglycerin: Administered sublingually or intravenously, nitroglycerin is effective for relieving chest pain by dilating blood vessels and reducing myocardial oxygen demand. While it helps with symptom relief, it does not have a direct impact on long-term prognosis.

• Morphine: Given intravenously or subcutaneously, morphine is used to manage severe pain and anxiety, which can also help reduce the cardiac workload and oxygen consumption.

Pharmacologic Therapies

• Beta-Blockers: Should be administered within the first 24 hours post-infarction to decrease heart rate, blood pressure, and myocardial oxygen demand, thereby reducing the risk of further heart damage. Caution is advised in patients with signs of heart failure, marked bradycardia, or hypotension.

• Statins: High-intensity statin therapy, such as atorvastatin 80 mg daily, is recommended to reduce cholesterol levels and stabilize atherosclerotic plaques, thus decreasing the risk of another MI.

• Loop Diuretics: Drugs like furosemide are used to manage volume overload conditions such as pulmonary edema or overt heart failure by promoting the excretion of excess fluid.

Supportive Treatments

• IV Fluids: Important in patients with an inferior MI and resultant right ventricular (RV) dysfunction. Adequate fluid administration helps increase preload and supports RV function, which is crucial due to the RV's dependency on preload for optimal performance.

• Oxygen Therapy: Administered to patients with signs of hypoxia, such as cyanosis and severe dyspnea, to improve oxygen saturation and alleviate symptoms of hypoxemia.

Additional Considerations

• Anticoagulation and Antiplatelet Therapy: Essential components of MI management, typically involving aspirin and other platelet inhibitors to prevent further thrombosis. Anticoagulants may be used to prevent clot propagation and new clot formation.

• Revascularization Procedures: Percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) may be indicated based on the extent of coronary artery blockage and the patient’s overall stability.

TREATMENT FOR STEMI

Revascularization Techniques

1. Percutaneous Coronary Intervention (PCI):

   • Timing: The preferred method for treating STEMI, PCI should be performed within 90 minutes of medical contact, known as the 'door-to-balloon' time.

   • Procedure: Involves the insertion of a catheter with a balloon at its tip through the arterial system to the blocked coronary artery. The balloon is inflated to open the artery, and a stent is usually placed to keep the artery open.

   • Benefits: Directly addresses the occlusion, restoring blood flow more effectively and with better long-term outcomes compared to other methods.

2. Thrombolytic Therapy:

   • Indications: Used when PCI is not available within the ideal time frame. It’s most effective when administered within the first few hours after the onset of symptoms.

   • Medications: Tissue plasminogen activator (tPA) is a common choice.

   • Contraindications: Includes recent major surgery, bleeding disorders, history of cerebral hemorrhage, uncontrolled hypertension, and recent ischemic stroke. Not recommended if the onset of myocardial infarction was over 24 hours previously.

3. Coronary Artery Bypass Grafting (CABG):

   • Indications: Considered if PCI is not successful or if the patient has multiple vessel diseases that are not amenable to PCI.

   • Timing: Generally not used immediately in the acute setting unless there are compelling indications like failed PCI or ongoing ischemia despite maximal non-surgical intervention.

Pharmacological Management

1. Antiplatelet Therapy:

   • Aspirin: Administered immediately, continued indefinitely.

   • P2Y12 Inhibitors: Such as clopidogrel or ticagrelor, recommended to be used in combination with aspirin for at least 12 months post-PCI to prevent stent thrombosis and reduce arterial clot formation.

2. Glycoprotein IIb/IIIa Receptor Antagonists:

   • Examples: Tirofiban or eptifibatide, often used during PCI to reduce acute thrombotic complications. Administered pre-PCI, especially in high-risk patients or those with large thrombus loads.

3. Anticoagulation:

   • Heparin: Unfractionated heparin is commonly used during the initial management and during PCI. Low molecular weight heparins, such as enoxaparin, are alternatives that provide more stable anticoagulant effects with subcutaneous administration.

Treatment for Unstable Angina/NSTEMI

1. Antiplatelet Therapy:

   • Critical for all patients diagnosed with UA/NSTEMI to prevent further thrombus formation.

   • Commonly includes aspirin and a P2Y12 inhibitor such as clopidogrel, prasugrel, or ticagrelor, which help to inhibit platelet aggregation.

2. Anticoagulation:

   • Heparin (unfractionated or low molecular weight heparin) is typically administered to prevent clot propagation.

   • Anticoagulation is crucial for reducing the overall thrombotic burden within the coronary arteries.

3. Revascularization:

   • Indicated for patients with persistent chest pain, significant troponin elevation, or ST-segment changes despite medical therapy.

   • Percutaneous coronary intervention (PCI) is preferred, but coronary artery bypass grafting (CABG) may be considered based on coronary anatomy and patient stability.

Complications Post-Myocardial Infarction

Immediate to Early Phase (Days 1-14):

• Reperfusion Injury: Can occur upon restoring blood flow, characterized by oxidative stress and further damage to the myocardial cells.

• Sudden Cardiac Death, Arrhythmias, Acute Heart Failure, and Cardiogenic Shock: These are acute complications that can occur within the first 24 hours.

• Infarct-Associated Pericarditis: Typically presents within days 1-3 as chest pain that may worsen with inspiration and improve with sitting forward.

• Structural Complications: Include papillary muscle rupture, ventricular septal defect, and left ventricular free wall rupture, generally occurring within days 3-14.

Late Phase (Weeks to Months):

• Aneurysm Formation: Both atrial and ventricular aneurysms can develop due to the weakening of the myocardial tissue.

• Post-Myocardial Infarction Syndrome (Dressler’s Syndrome): An immune-mediated pericarditis occurring weeks to months after the initial MI.

• Congestive Heart Failure and Re-Infarction: Long-term risks that require ongoing management.

Prevention Strategies

1. Primary Prevention:

   • Aimed at individuals without diagnosed heart disease to prevent the onset of coronary artery disease.

   • Includes lifestyle interventions such as smoking cessation, maintaining a healthy diet, engaging in regular physical activity, and considering low-dose aspirin for certain individuals at higher risk.

2. Secondary Prevention:

   • Targets patients with existing cardiovascular disease to prevent the progression and recurrence of events.

   • Involves a combination of medications:

     • Aspirin and P2Y12 inhibitors: For ongoing antiplatelet effects.

     • Beta-Blockers: Reduce myocardial oxygen demand and counteract the effects of adrenaline, thus protecting against arrhythmias.

     • Statins: Lower cholesterol levels and stabilize plaques.

     • ACE Inhibitors or Angiotensin Receptor Blockers (ARBs): Recommended for patients with reduced ejection fraction or signs of heart failure to improve long-term cardiac function and survival.