A patient's coronary angiogram shows 40% stenosis — no symptoms, normal exercise tolerance. An intravascular ultrasound reveals a thin fibrous cap and a large lipid core. How should you interpret this?
AThe lesion is reassuring; mild stenosis cannot cause hemodynamically significant ischemia
BThe lesion is high risk; plaque vulnerability, not degree of stenosis, predicts rupture risk
CThe finding is concerning only because 40% stenosis will restrict flow enough to cause ischemia at peak exercise
DA thin fibrous cap indicates the plaque has already stabilized and is less likely to rupture
This is the central paradox of acute coronary syndromes. Many MI patients have plaques causing only 30–50% stenosis — insufficient to cause symptoms. Rupture risk is determined by structural vulnerability: thin fibrous cap, large lipid-rich necrotic core, and active macrophage infiltration. A 40% stenosis plaque with these features is more dangerous than an 80% stable plaque with a thick cap. Stenosis grade alone is an unreliable predictor of acute MI risk.
Question 2 Multiple Choice
When an atherosclerotic plaque ruptures, what immediately triggers intracoronary thrombus formation?
ARelease of inflammatory cytokines from smooth muscle cells into the coronary lumen
BVasospasm of the coronary artery wall at the rupture site
CExposure of thrombogenic contents — tissue factor, collagen, and von Willebrand factor — to circulating blood
DActivation of the complement cascade by lipid-laden foam cells
Plaque rupture exposes the lipid core contents to flowing blood: tissue factor (activates the extrinsic coagulation pathway), collagen (activates platelets), and von Willebrand factor (anchors platelets). Simultaneous activation of platelet aggregation and the coagulation cascade rapidly produces an occlusive thrombus. Vasospasm can accompany the event but is not the primary trigger.
Question 3 True / False
Most acute myocardial infarctions are caused by rupture of coronary plaques that were previously causing significant (>70%) luminal obstruction.
TTrue
FFalse
Answer: False
Most infarctions originate from plaques causing only mild to moderate stenosis (often 30–50%). These 'vulnerable' plaques appear innocuous on angiography — the lumen is nearly normal — but their structural properties (thin cap, large lipid core, macrophage infiltration) make them prone to rupture. This explains why patients can have a fatal MI with no prior symptoms: their dangerous plaque was never obstructive enough to limit flow or trigger angina.
Question 4 True / False
Aggressive statin therapy reduces heart attack risk partly by stabilizing vulnerable plaques, not just by reducing the degree of luminal obstruction.
TTrue
FFalse
Answer: True
Statins have pleiotropic effects beyond LDL lowering: they reduce macrophage infiltration, decrease metalloproteinase secretion, suppress lipid core growth, and thicken the fibrous cap. These effects reduce plaque vulnerability even when the stenosis percentage does not change significantly. This explains why statins reduce MI risk even in patients with modest stenosis — the target is plaque stability, not lumen diameter.
Question 5 Short Answer
Why does myocardial necrosis progress from the endocardium outward (not from the epicardium inward) following a complete coronary occlusion?
Think about your answer, then reveal below.
Model answer: The subendocardium is furthest from the epicardial blood supply and has the highest metabolic demand. Coronary artery branches penetrate from the epicardial surface inward; the endocardium is perfused by the most distal, highest-resistance branches. When an epicardial coronary is occluded, flow is cut first and most completely in the subendocardium. Additionally, subendocardial tissue has higher oxygen consumption due to greater wall tension. These factors make the subendocardium the first zone to become ischemic and necrotic, with the wavefront progressing outward toward the epicardium over 4–6 hours.
Understanding this progression explains the clinical urgency of reperfusion. Early reperfusion (within 90 minutes) can salvage the epicardial myocardium before the wavefront reaches it. After 6 hours, the full transmural territory is infarcted. This is why 'door-to-balloon time' matters so intensely — every minute represents a layer of potentially salvageable myocardium.