Acute Coronary Syndrome (ACS)

• Cardiovascular refers to the circulatory system

ACS - Agenda

• Includes:
  • Angina
  • Unstable Angina
  • Myocardial Infarction

Acute Coronary Syndrome (ACS)

• Term for when a patient has acute chest pain from myocardial ischemia.
• It’s used when it can’t be immediately determined if the patient has a myocardial infarction (MI) or unstable angina (UA).

ACS Pathophysiology Basics

• Myocardial ischemia occurs due to inadequate perfusion to meet myocardial oxygen demand.
• Myocardial oxygen consumption is determined by heart rate, afterload, contractility, and wall tension.
• Inadequate perfusion usually results from coronary arterial vessel stenosis due to atherosclerotic CAD.
• Ischemic symptoms don't occur at rest until vessel stenosis exceeds 95% obstruction to flow.

Anatomy of Plaque Disruption

• Vulnerable plaques have thin, friable fibrous caps separating a substantial thrombogenic lipid core from blood.
  • Lumen could be well preserved
• Stable plaques have thick fibrous caps protecting thrombogenic lipid core from blood
  • More luminal narrowing

Plaque Rupture, Stenosis, and Thrombosis Progression

• Plaque rupture may lead to occlusive thrombosis, total chronic occlusion, or mural thrombus.
• Over time, the artery may recanalize or the plaque may heal with decreased or increased stenosis.
• Plaque rupture and thrombus can eventually develop AMI or unstable angina
• Complete occlusion can lead to lysis and residual thrombus and disease progression.

Coronary Artery Occlusion: The Evolution of Infarction

• Normal myocardium transitions from an ischemic but viable state to necrosis over time after occlusion.
• Necrosis starts subendocardially in the first 30 minutes.
• Progresses towards subepicardium in 4 hours.
• Involves the whole area between 6-12 hours.

ACS Pathophysiology at the Cellular Level

• Myocardial injury at the cellular level occurs due to inflammation, thrombosis, and debris.
• Debris from occlusive plaque lesions is released and embolizes into the distal vessel.
• The introduction of calcium, oxygen, and cellular elements can happen during ACS.
• Reperfusion injury, prolonged ventricular dysfunction (myocardial stunning), or reperfusion dysrhythmias can also occur.

Stable Angina Overview

• Stable angina pectoris isn't considered a form of ACS.
• It's a transient, episodic chest discomfort resulting from myocardial ischemia.
• Etiology: atherosclerosis, vasospasm, myocardial hypertrophy, tachycardia, severe anemias, respiratory disease with oxygen deficit.
• Transient chest pain occurs when myocardial metabolic demands outpace coronary blood supply
  • Causes myocardial ischemia, lactic acid buildup / inflammation / abnormal stretching of ischemic myocardium.
• Afferent sympathetic fibers enter spinal cord at C3-T4, resulting in varying locations & radiations patterns of chest discomfort.

Stable Angina – Classic Presentation

• Acute onset substernal pain/pressure radiating down the medial aspect of the left arm.
• A clenched fist on sternum / neck / jaw / both arms / back / epigastric - (mistaken for indigestion, dental pain, or shoulder arthritis) may occur
• Nature of Pain: excruciating, constricting, squeezing, vice-like, suffocating, tightness, burning, heavy weight "elephant on chest".
• Associated Signs: diaphoresis, nausea, vomiting, pallor.
• ECG changes: T wave inversion &/or ST depression (subendocardial ischemia), ST elevation in contiguous leads (Variant or transmural ischemia), or unremarkable.

Stable Angina Classification

• The Canadian Cardiovascular Society (CCS) classification is:
  • Class I: no angina with ordinary physical activity.
  • Class II: minimal limitation of normal activity; angina with exertion or emotional stress.
  • Class III: severe limitation of ordinary physical activity; angina with exertion under normal physical conditions.
  • Class IV: inability to perform any physical activity without discomfort even at rest.

Characteristics of Stable Angina

• Predictable and typical, stenosed arteries dilate poorly in response to demand.
• Follows exercise, heavy work, strain, stress, overeating, alcohol consumption, exposure to cold, or infection with fever.
• Relieved by rest and nitroglycerin (causes coronary and peripheral vasodilation workload).

Typical Angina

• Chest pressure or squeezing lasting several minutes.
• Provoked by exercise or emotional stress.
• Relieved by rest or glyceryl trinitrate.
• This symptom complex is most consistently associated with coronary disease

Atypical Angina

• defined as chest discomfort with only two characteristics of typical angina.
• Less predictive of coronary disease than typical angina, but may be more frequent in certain populations (women, diabetes, older people).
• Some guidelines advise against using the term atypical.
• Instead, they suggest using cardiac, possibly cardiac, and ‘non-cardiac' pain, although symptoms alone can not determine the cause of chest pain.

Non-Specific Angina Symptoms

• Epigastric discomfort
• Jaw pain
• Arm pain
• Dyspnea on exertion
• Nausea / vomiting
• Diaphoresis
• Fatigue
• Hypoxia
• Tachycardia
• Heart sounds
• Bibasilar rales
• Diminished peripheral pulses
• Signs of AAA
• Xanthomas or xanthelasma

Risk Factors for Angina/ACS

• Age and sex
• Smoking
• Hypertension
• Dyslipidemia
• Diabetes
• Inactivity
• Diet
• Race, ethnicity, geography
• Psychological factors and social determinants of health
• Chronic kidney disease (CKD)
• Inflammatory and other diseases
• Obesity
• Substance misuse
• Family history
• Pollution

Differential Diagnosis for Angina

• Pneumonia with pleurisy
• Esophagitis
• Esophageal spasm
• GERD
• Biliary colic
• Peptic ulcer disease
• Costochondritis
• Fibromyalgia
• Rib fracture
• Sternoclavicular arthritis
• Herpes zoster virus infection
• Anxiety disorders and panic attacks

Unstable Angina – Overview

• Pre-infarction angina unpredictable
• Less stress/exercise to initiate, duration > 20 min at rest.
• Incomplete relief with nitroglycerin symptoms at rest.
• Angina can happen with ST changes, S3, or crackles.
• New onset precursor to an AMI

Suspecting Acute Myocardial Infarction

• Suspect it if the patient is clinically unstable, which isn't likely in unstable angina.
• Includes patients with ongoing or recurrent pain despite treatment.
• Hemodynamic instability (low blood pressure or shock).
• Dynamic ECG changes
• Left ventricular failure;
• A life-threatening arrhythmia (ventricular tachycardia or ventricular fibrillation) or cardiac arrest after presentation;
• Mechanical complications like new-onset mitral regurgitation.

Associated Symptoms with Unstable Angina

• Marked sweating
• Epigastric pain
• Dyspnea
• Syncope
• Back pain

Differentials for Unstable Angina

• Stable angina
• Prinzmetal (variant or vasospastic) angina
• Non-ST-elevation myocardial infarction
• ST-elevation myocardial infarction
• Congestive heart failure
• Chest wall pain
• Pericarditis
• Myocarditis
• Aortic dissection
• Pulmonary embolism
• Pleuritis
• Pneumothorax
• Perforated abdominal viscus

Variant or Vasospastic Angina (Prinzmetal's)

• Occurs at rest, often nocturnal, cyclic pattern (e.g. same time each day, or can be unpredictable but is not related to stress or physical activity).
• Peak incidence 2-3 hrs after getting up and early evening ( sympathetic activity); also on a weekly basis Monday morning shows peak occurrence
• Coronary vasospasm responds well to calcium channel blockers, which inhibit vascular smooth muscle contraction

Myocardial Infarction - Overview

• Myocardial ischemia is insufficient delivery of oxygenated blood to the myocardium (mismatch between supply & demand).
• Metabolic needs exceed available supply, dysfunction in cardiac pumping & predisposes to dysrhythmias.
• Severe or prolonged ischemia leads to myocardial infarction (irreversible necrosis and death of cardiac cells).
• ATP levels fall to ½ normal within 10 min of occlusion.
• Irreversible cell injury begins within 30 - 40 min of complete occlusion.
• Ischemic necrosis begins in subendocardial zone.
• Spreads across ventricular wall toward epicardial tissues (greatest collateral network of arterial vessels).

Acute Myocardial Infarction Classifications

• Type 1 involved Spontaneous MI related to ischemia resulting from a primary coronary event.
• Type 2 MI is secondary to ischemia caused by increased oxygen demand or decreased supply.
• Type 3 is Sudden unexpected cardiac death, including cardiac arrest, often with symptoms suggestive of myocardial ischemia.
  • Accompanied by presumably new ST segment elevation or new left bundle branch block (LBBB) pattern.
• Type 4 MI is associated with coronary instrumentation, such as occurring after percutaneous coronary intervention (PCI).
• Type 5 MI is associated with coronary artery bypass grafting (CABG).

Myocardial Oxygen Supply & Demand Factors

• Oxygen Demand Factors: tachycardia / contractility (preload) / hypertension (afterload) / ventricular dilation and hypertrophy (CHF - cardiomegaly)
• Hemodynamic Factors: Hypotension – blocked sympathetic innervation (bradycardia) and hypovolemic shock coronary perfusion
• Cardiac Factors: Diastolic filling (SVT's or VT) / ejection fraction (valvular incompetence) / coronary vasospasms
• Hematologic Factors: O2 in blood (severe anemias / high altitude / CO poisoning)

Clinical Pearl - CAD and Physical Activity

• CO required for short term physical activity (e.g. lifting) increases SV with little initial HR.
• Pts with Hx of CHD won't be able to compensate with only SV (will have to increase HR significantly).
• Increased HR is myocardial O2 and stress.
• All pts with suspected AMI should not be made to walk or do any physical activity
• Up to 75% of O2 is used by myocardium with little reserve; coronary dilation (absence of disease) blood flow 5X resting levels; compromised artery will not be able to dilate.

Typical AMI Event – Pathophysiology

• Ulcerated/cracked/ruptured fibrotic plaque in coronary artery allows platelets to adhere, activating clotting cascade.
• Thrombosis occludes coronary artery, leading to localized myocardial ischemia and anaerobic metabolism.
• Anaerobic metabolism causes lactic acid buildup, inflammatory response, and abnormal stretching of myocardium.
• Chest pain, anxiety and apprehension, and epi and norepinephrine release happen.
• Pale, diaphoretic, tachycardia happens which increases myocardial O2 demands.
• All result adds to additional myocardial ischemia

Myocardial Infarction - PUMP and RHYTHM Factors

• PUMP ATP levels affects contractility and SV ejection fraction, also coronary blood flow and myocardial perfusion.
• Can lead to risk of cardiogenic shock, PVCs, V-tach, V-fib cardiac arrest.
• RHYTHM ATP levels affect cellular action potential and irritability threshold.
• Abnormalities are Ischemic ECG changes and increased risk of dysrhythmias (tachy or brady-arrhythmias).
• Abnormalities can affect coronary blood flow and myocardial perfusion, also increased risk of cardiogenic shock, PVCs, V-tach, V-fib cardiac arrest

Myocardial Injury - Progression and Reversibility

• Anaerobic metabolism occurs (> 30 min). Causes changes in cell structure (glycogen / mitochondrial swelling / lysosomal release of enzymes.
• Necrosis occurs (irreversible cell damage) with injury, ECG changes (ST segment elevation)
• Causes release of serum cardiac enzymes
• Myoglobin [1 hr]
• Creatine kinase CK-MB [4 hrs.] helps convert ADP to ATP
• Peak 12 – 20 hrs
• Troponin complex I & T [peaks 24 – 48 hrs]
• Proteins that regulate calcium-mediated contractile process in striated muscle & not found in skeletal muscle

Factors Affecting Extent of Infarction

• Location & area of involvement which can be:
  • Endocardium
  • Myocardium
  • Epicardium
• Transmural infarct is most common.
• It represents a more prolonged and complete thrombosis
  • Affects (left ventrical & interventricular septum)
• Subendocardial infarct affects inner 1/3 −1/2
  • Lower mortality rate and complications
  • Higher incidence of subsequent ischemia and reinfarction
• Complete or partial occlusion
• Duration of occlusion
• Metabolic needs of affected tissue with consideration for underlying cardiac rhythm and BP
• Glycogen depletion and mitochondrial swelling develop within minutes but are reversible if blood flow is restored
• Extent of collateral circulation built up
• Time to Treatment
• [Figure is not included for now]

Myocardial Physiology - Coronary Arteries

• R coronary: Conus, marginal artery, posterior interventricular artery
  • Supplies (R atrium / RV / inferior wall LV / 1/3 septum)
  • SA node 55% of persons / AV node 90% – crux of the heart
• LAD - anterior interventricular artery (LV / 2/3 Septum)
  • LAD anastomoses with posterior branch of R coronary artery
• Circumflex (L atrium / posterolateral wall L ventricle / SA node 45% of persons / AV node 10% of persons)
  • Circumflex continues around atrioventricular sulsus where it anastomoses with R coronary artery

Potential Problems associated with Coronary Artery Occlusion

• R coronary - Potentiates conduction problems – dysrhythmias
• L coronary – Potentiates mechanical problems – pump failure

Coronary Artery-Perfusion

• Coronary blood flow occurs during diastole and during systole / anastomoses
• L & R arteries merge at apex location.
• Collateral circulation and 3000 + capillaries help perfusion per square millimeter
• 1 capillary per muscle fiber.

Myocardial Physiology – Ventricular Blood Flow

• Ventricular blood flow (Pre-load): end-diastolic volume; pressure generated at end of diastole; filling pressure; vol of blood stretching resting heart muscle (reflective of venous return)
• After-load: resistance to ejection; aortic and systemic pressure
• Wall tension must be over come - force that contracting heart must generate to eject blood

Frank-Starling mechanism

• Starling's law: Pre-load = SV

  • Diastolic filling helps stretch myocardial fibers.
  • The Length of muscle fiber affects cross bridging between actin & myosin.
  • Strength determined Sarcomere length and Inotropic effect, and the final End diastolic volume

• Point of no return is beyond the optimal length.

• disengaging of cross-bridges will weaken contracting

  • Like a rubber band, only stretches so far..

Myocardial Deterioration During Ischemia

• Loss of Functional patterns of proper muscle movement
  • 4 progressive types of failure
• Dyssynchrony – dissociation in time with adjacent muscle fibers of myocardium
• Hypokinesis – reduction in extent of muscle fibers shortening with contraction
• Akinesis – cessation of shortening of muscle fibers with systolic contraction
• Dyskinesis – paradoxical expansion of infarcted tissue, occurs with systole
• Stunned myocardium refers to area of ischemia (associated with dyssynchrony) & area of injury (associated with hypokinesis) that is in the process of recovering"

Myocardial Infarction - Acute Symptoms

• Acute crushing substernal pain radiating to left arm-neck-jaw, and or unrelieved by rest/nitro can occur
• Contains visceral pain fibers that enter spinal cord at multiple levels. Maps to areas on parietal cortex.
• Visceral pain fibers are difficult to describe and imprecisely localized.
• Can appear as discomfort, heaviness, and aching terms, often with known referred locations
• Has a Recent onset of chest pain and is distressing
• Terms describe a general overall pressure, tightness, squeezing sensation, etc

MI Atypical presentation

• Vague chest discomfort (often with females)
• Silent MI with known absence of pain/discomfort or Asymptomatic MI is common.
• Possible autonomic neuropathy (like diabetics)
• Can include Shortness of breath (most often described in that category)
• Generally seen w age 80+ adults
• Syncope and palpitations occur.

MI associated complaints - general

• Include epigastric pain and belching/hiccups; circumoral cyanosis; heavy diaphoresis
• Possible tachycardia
• Restfullness
• Base crackles
• Pulmonary congestion is also potentially related

AMI Differential Diagnosis

• Cardiovascular:

  • Acute myocardial infarction
  • Stable, unstable or variant angina
  • Mitral valve prolapse
  • Thoracic aortic aneurysm
  • Pericarditis
  • Myocarditis
  • Endocarditis
  • Hypertropic cardiomyopathy
  • Cardiac contusion

• Pulmonary origin:

  • Pulmonary embolism
  • Pneumonia
  • Pneumothorax
  • Pleurisy
  • Pulmonary contusion
  • Lung tumor

• Gastrointestinal:

  • Esophageal reflux,
  • Rupture
  • Varices
  • Diaphragmatic or Hiatal hernia
  • Gallbladder disease
  • Peptic ulcer
  • Pancreatic disease

• Musculoskeletal:

  • Muscle tear or bruising
  • Costochondritis
  • Resuscitation injury

Treatment - Oxygen

• Consider medication, one with significant potential to benefit and harm the patient with ACS
• Respiratory compromise can occur during ACS. Happens as a result of acute pulmonary edema or exacerbation of chronic pulmonary disease.
• Oxygen therapy delivered to normoxic ACS patients can increase both myocardial injury and infarct size
• Hyperoxia develops as a result of excessive supplemental oxygen therapy. Can potentiate coronary vasoconstriction and increase oxidative stress, worsening outcomes in these patients.

Treatment – Nitroglycerin

• Nitrates decrease myocardial preload and, to a lesser extent, afterload.
• Increases venous capacitance which induces venous pooling, decreasing preload and myocardial oxygen demand.
• Direct vasodilation of coronary arteries increases collateral blood flow to the ischemic myocardium
• Very Beneficial in patients with significant, symptomatic coronary vasospasm
• Limit use in the presence of a STEMI

Antiplatelet Treatment - Aspirin

• Prototypical antiplatelet agent
• Cost-effective treatment in ACS care
• irreversibly acetylates platelet cyclooxygenase, removing all activity for the life span of the platelet (8 to 10 days).
• it stops the production of pro-aggregatory thromboxane A2
• P2Y 12 inhibitors include clopidogrel, ticagrelor and prasugrel, which are more potent platelet inhibitors than aspirin

Treatment - Glycoprotein IIb/IIIa Receptor Inhibitors

• Potent antiplatelet agents;
  • Abciximab,
  • Eptifibatide, and
  • Tirofiban can be administered
• Clinical usefulness is limited to subset ACS patients undergoing PCI as a reperfusion strategy.
• This class of medications is not usually given in the ED setting; other antiplatelet agents (P2Y 12 receptor inhibitors) are preferred for administration in the care of ACS.

Treatment - Anticoagulant Options

• Include Heparin (UFH),
• Low-molecular-weight heparin (LMWH) (enoxaparin),
• Direct thrombin inhibitors (bivalirudin), and
• Factor Xa inhibitors (fondaparinux).

Treatment - Rapid reperfusion through using Fibrinolytics

• Rapidly reestablishing perfusion in the infarct-related coronary artery promotes the opportunity for myocardial salvage. Resulting in reductions in mortality with rapid increases in patient quality of life post-MI.
• Predict improved survival rates.
• Used to preserve left ventricular function.

###AMI Complications - Sudden Death

• 30% - 50% from ventricular fibrillation secondary to PVC's occurs within first 4 hrs of onset, often within 1st hr

AMI Complications - Dysrhythmias

• 90% have an arrhythmia (ischemia / necrosis / inflammation in conduction tissue).
• Types include sinus tachycardia, PSVT/SVT, VT, heart blocks and PVCS

AMI Complications - Congestive Heart Failure

• LV ejection fraction can lead to rupture of papillary muscles (usually 3-5 days post MI) and valvular insufficiency

AMI Complications - Spontaneous coronary artery dissection (SCAD)

• SCAD is defined as a separation of the layers of an epicardial coronary artery.
• A wall by intramural hemorrhage causes chest pain that often radiates to the arms, shoulders or back.
• Approximately 90% of patients with SCAD are women aged 47 to 53 years.

AMI Complications - Ventricular Aneurysm

• Transmural infarction is followed by the loss of necrotic fibers, resulting in thinning.
• Wall or interventricular septum weakens and balloons out on systole increasing chance of rupture
• Possible sudden death in 1-2 weeks

AMI Complications - Cardiogenic Shock

• 40%+ Loss of LV
• Mortality can be 80+ %
• Rate: 1st; treat with 2nd Volume and then 3rd Pump:
• Possible Dopamine
• Dobutamine is for patients in CO w pulmonary congestion. No significant improvement can be seen.

AMI Complications, Laws

• Extreme hypotension can cause the Law of Laplace
• Falling pressure in a blood vessel lowers the force, causing the radius and resistance to fall off.
• Eventually pressure may drop below 20 mmHg (critical closing pressure).
• Blood Vessel opens, and Cardiovascular collapse occurs

AMI Complications - Pericarditis

• Sharp chest pain aggregated w deep inspiration
• Also by sharp jabbing chest pain
• Occurs 2-3 days post infection after inflamed Epicardium.
• Fluid and blood can enter pericardial sac
• Possible fluid build-up, with PEA.

AMI Complications - Dressler's syndrome

• Develops a few weeks post infection
• Often related w Pleurisy, Pneumoniae
• Patients with M.I and detected Pericardial friction are more likely to have issues that inferior to that in the chest wall area, with only 10-20% of patients complaining.

AMI Complications - additional possible risks

• Thromboembolism/stroke/ PE's
• Electrolyte related M.I's w Potassium
• M.I pt's on loop Diuretics due to Hypokalemia
• S.V risk

Treatment - ASA

• Indications include suspected cardiac ischemia.
• Allergy or sensitivity to NSAIDs is a contraindication
• Cannot administer to those who are asthmatic and have no prior use of ASA
• PO Route at a dose of 160-162 mg once

Treatment - nitroglycerin

• Indication: Suspected cardiac ischemia.
• Contraindications include sensitivity to nitrates and hypotension
• Perform 12-lead ECG (ensure compatible with right ventricular MI).
• If SBP drops by one-third or more of its initial value after nitroglycerin is administered, the drug should not be given.
• Also it is contraindicated if Phosphodiesterase inhibitor was taken within the previous 48 hours

Treatment - 0.9% NaCl Fluid Bolus

• Indications include STEMI-positive 12-lead ECG + Cardiogenic shock.
• Route is IV through Infusion. Given at 10 ml/kg
• Fluid overload is a contraindication
• Reassess every 250 ml.
• Max total volume is 1, 000 ml.

Test your knowledge of Acute Coronary Syndrome (ACS) treatments. Questions cover nitroglycerin, aspirin, P2Y12 inhibitors, Glycoprotein IIb/IIIa receptor inhibitors, and anticoagulants. Also includes diagnosis of chest pain and Prinzmetal's angina.