Coronary Artery Disease, Myocardial Ischemia, and Acute Coronary Syndromes

Coronary Artery Anatomy

• Coronary arteries and veins are essential for heart function.
• Normal left coronary and circumflex arteries are critical for supplying blood to the heart muscle.

Coronary Artery Disease

• Definition: Any vascular disorder that narrows or occludes a coronary artery or arteries.
• Most common cause: Atherosclerosis
• Atherosclerosis:
  • Localized accumulation of lipid and fibrous tissue within the coronary arteries.
  • Coronary vessel obstruction > 75% when lesions begin producing myocardial ischemia and dysfunction.

Progression of Atherosclerosis

1. Endothelial damage
2. Fatty streak
3. Fibrous plaque
4. Complicated lesion

Coronary Artery Disease Risk Factors

Conventional Modifiable

• Dyslipidemia
• Hypertension
• Cigarette smoking
• Diabetes mellitus
• Obesity/sedentary lifestyle

Conventional Non-modifiable

• Age
• Male sex
• Female post-menopause
• Family history

Non-traditional Risk Factors

• High-sensitivity C-reactive protein elevation
• Chronic kidney disease
• Air pollution and ionizing radiation
• Medications - NSAIDS
• The microbiome - innate and adaptive immunity

Myocardial Ischemia versus Acute Coronary Syndromes

Myocardial Ischemia

• Local, temporary deprivation of the coronary artery blood supply.
• Stable angina: Recurrent, predictable chest pain often due to activity.
  • Pain may be a feeling of heaviness or pressure, ranging from mild to moderately severe.
  • Pain is due to lactic acid buildup in the myocardium or myocardial nerve fibers irritated by excessive stretching of ischemic myocardium.
  • Occurs when myocardial oxygen demand exceeds oxygen supply.
  • Episodes tend to be similar and brief.
  • Can be relieved by rest or medication.
• Prinzmetal’s angina (vasospastic):
  • Unpredictable, results from coronary vasospasm rather than atherosclerotic disease.
  • Can occur at rest, often during sleep.
  • Usually specific to a particular coronary artery site, which may or may not have atherosclerosis.
• Silent ischemia:
  • Temporary decrease in blood supply to a specific area of the heart.
  • The patient does not experience angina or other detectable symptoms.

Unstable Angina (Acute Coronary Syndrome)

• Significant substernal chest pain that may be new onset or can occur during activity, rest, or sleep.
• Increasing in severity or frequency.

Pathophysiology of Acute Coronary Syndromes

Acute Coronary Syndrome: Myocardial Infarction

• Oxygen demand > Oxygen supply.
• Cellular injury.
  • Ischemia lasting up to ~20 minutes.
  • EKG changes apparent within 30-60 seconds.
• Cellular death.
  • Ischemia lasting > 20 minutes.
  • Prolonged ischemia resulting in myocardial necrosis.
• Non-ST elevation MI (NSTEMI) – partial occlusion.
• ST elevation MI (STEMI) – total occlusion by thrombus.

Myocardial Infarction - Etiology

• Death of myocardial cells due to a prolonged imbalance between myocardial oxygen supply and demand.
• Rapid formation of thrombus within coronary artery(ies).
• Often begins with the subendocardial layer and moves outward through the layers of the heart wall.
• Cellular damage proceeds transmurally (through the wall, from inside to outside).
• Sometimes, not all layers are affected.

Acute MI Diagnosis

• Diagnosis cannot be made on clinical presentation alone.
• EKG changes
  • STEMI vs. non-STEMI
• Cardiac biomarkers
  • Serum cardiac troponin I – Gold standard
    • Increases within 2-4 hours of symptoms
  • Creatine kinase MB
    • Increases within 4-8 hours and for 2-3 days after acute MI

Unstable Angina (UA)/ Non-ST segment elevation myocardial infarction (NSTEMI)

• Unstable angina is the first step in an advancing continuum of ischemia-related myocardial injury.
• Pain is usually different, and more severe than previously experienced.
• UA – hs Troponin I is often slightly increased.
• NSTEMI – Cardiac Troponin I is elevated within 2-4 hours.
• EKG changes - ST segment depression and inverted T wave.
• With UA, EKG changes may resolve as pain resolves.
• Can evolve into ST-segment elevation myocardial infarction (STEMI) and/or death.

ST Segment elevation myocardial infarction (STEMI)

• Often sudden, severe chest pain that is not relieved by rest or nitroglycerin.
• Can involve breathing difficulty.
• Skin is cool and diaphoretic.
• Nausea/vomiting.
• Frothy pink sputum related to pulmonary edema.
• Serum biomarker present - Cardiac Troponin I.
• Sudden shift from aerobic to anaerobic metabolism in the myocardium.
• Infarction area.
• Sudden death can occur within 1 hour.

Myocardial Infarction - Clinical manifestations

• Signs/symptoms are related to inadequate blood perfusion (i.e., oxygen and nutrients) to various organs/tissues. In other words, DECREASED CARDIAC OUTPUT.
• Severe chest pain unrelieved by rest/nitroglycerin.
• Fever.
• Nausea/vomiting.
• Diaphoresis.
• Sternal pressure.
• Decreased BP.
• HR increased or decreased.
• Pain spreads to arms, neck, jaws, head, mid-back.

MI in Females

• Often non-specific symptoms.
• Unusual and/or persistent GI symptoms.
• Pain in back/shoulders.
• May or may not have chest pain.

Myocardial Infarction: Metabolic Effects of MI

Glycolysis

• Glycogen depletion

Anaerobic metabolism

• ↑ Lactic Acid & H^+
• Acidosis

Cellular depletion

• K^+
• Ca^{++}
• Mg^{++}

↓ Contractility

• ↓ Pumping ability

Angiotensin II release

Catecholamine release

• Epinephrine
• Norepinephrine
  • ↑ Myocardial workload
  • Peripheral vasoconstriction
  • Fluid retention
  • ↓ Contractility

Release: glycogen, glucose, stored lipids

• ↑ FFA - Hyperglycemia
• ↑ damage to cardiac cell membranes
• Coronary artery spasm
• ↓ Coronary blood flow
• Myocardial Ischemia/infarction

Acute MI Functional Changes

# Myocardial Infarction: Acute and Chronic Complications

• Arrhythmias
  • Permanent EKG changes
  • Multiple sites of origin
  • Vary in seriousness (mild → fatal)
• Left ventricular failure
  • Decreased cardiac output
• Cardiogenic shock