Pathophysiology
Summary
Coronary artery disease (CAD) is the predominant cause of ischemic heart disease. Fixed coronary plaques with >70% stenosis will present clinically as stable angina, characterized by predictable episodes of chest pain and pressure that worsens with exertion. Stable angina involves transient subendocardial ischemia, with typical symptoms including chest pressure/pain radiating to the left arm, diaphoresis, and dyspnea; however, elderly, diabetic, and women may exhibit minimal/atypical symptoms. Relief for stable angina is found with rest or nitroglycerin, usually within < 30 minutes. On ECG, stable angina shows ST-segment depression due to transient subendocardial ischemia.
On the other hand, vasospastic (Prinzmetal) angina occurs at rest, more commonly at night, and is caused by transient coronary vasospasm likely due to smooth muscle hyper-reactivity in the coronary artery wall. This vasospasm commonly occurs over a stable atherosclerotic coronary plaque, but may also occur in disease-free vessels. Nitroglycerin can improve symptoms of vasospastic angina, with calcium channel blockers being the first-line therapy for long-term management, as they vasodilate and decrease spasticity. Major risk factors for Prinzmetal angina include smoking, as well as agents like sumatriptan and sympathomimetics (e.g., cocaine). A detrimental progression in CAD is plaque rupture, which exposes thrombogenic substances, activating the platelet and coagulation pathways leading to luminal thrombus formation. Such ruptures are common with repeated cycles of plaque disruption and repair while usually remaining subclinical, yet with persistent pathologic Q waves that mark the area of a previous infarct. On ECG, vasospastic angina presents with transient ST-segment elevations from transient transmural ischemia.
The clinical spectrum of acute coronary syndrome (ACS) includes unstable angina, NSTEMI, and STEMI, all of which are triggered by acute plaque destabilization due to rupture or erosion, exposing prothrombotic surfaces leading to occlusive luminal thrombus formation, which in turn causes cardiac ischemia or infarction. NSTEMI involves a transient or partially occlusive thrombus, presenting with unstable symptoms like new onset angina or angina with less exertion or at rest, and often showing ST segment depressions on ECG due to subendocardial ischemia. In contrast, STEMI involves a fully occlusive or prolonged thrombus, leading to transmural infarction or cell death with ECG showing ST segment elevations indicative of transmural involvement. The progression of ECG changes seen in STEMI can be described in four steps: hyperacute T waves within seconds of ischemia, to ‘tombstone' shaped ST elevations within minutes, followed by negative Q waves corresponding to the area of necrosis, and finally, T-wave inversions. New-onset left bundle branch block is also diagnostic of STEMI.
Myocardial necrosis occurs rapidly owing to the high oxygen demand of the heart, and is reflected in the final three ECG alterations. Death and rupture of cardiac myocytes in NSTEMI and STEMI lead to spillage of cellular enzymes, one of which is troponin. troponins and CK-MB (creatine kinase, isoform MB) are vital serum markers for infarction, with troponin I being more specific for cardiac muscle damage and troponin T being more sensitive. CK-MB is valuable for diagnosing reinfarctions due to its relatively short time course of elevation and return to baseline. Serum troponin levels peak around ~24 hours post MI and remain elevated for ~7 days, while serum CK-MB levels also peak in ~24 hours but fall within ~48hrs. NSTEMI and STEMI both result in myocardial cell death and the release of cardiac enzymes into the serum, aiding in the diagnostic process.
Lesson Outline
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FAQs
Stable angina is caused by fixed atherosclerotic plaques leading to more than 70% stenosis in the coronary artery, and results in predictable episodes of chest pain and pressure that typically worsens with exertion. It involves transient subendocardial ischemia. On the other hand, vasospastic, or prinzmetal angina, is due to transient coronary vasospasm, typically occurring over a stable atherscleotic coronary plaque. Its symptoms occur at rest, more commonly at night, and involves episodes of transient transmural ischemia.
Acute coronary syndrome (ACS) encompasses a spectrum of conditions—unstable angina (UA), non-ST-segment-elevation myocardial infarction (NSTEMI), and ST-segment-elevation myocardial infarction (STEMI). All are precipitated by disrupted coronary plaque, which leads to thrombus formation and subsequent cardiac ischemia or infarction. Unstable angina is characterized by transient or partially occlusive thrombi, causing subendocardial ischemia. It manifests as new or worsening angina, often with minimal exertion or even at rest. NSTEMI and STEMI represent a progression from ischemia to infarction and necrosis of myocardial cells. In NSTEMI, this is due to a partially occlusive thrombus, while in STEMI, a fully occlusive thrombus is responsible.
STEMI and NSTEMI are reflected in ECG as ST segment elevations or depressions respectively in leads corresponding to the region of infarcted myocardium. The death and rupture of cardiac myocytes in NSTEMI and STEMI lead to spillage of cellular enzymes like creatine kinase, isoform MB (CK-MB), and troponins. These are cardiac-specific serum markers used to detect infarction. Troponin I is more specific for cardiac muscle damage and Troponin T is more sensitive. Serum troponin levels peak about 24 hours after MI and remain elevated for around 7 days, whereas serum CK-MB levels peak in about 24 hours and fall over the next 24 hours.
Vasospastic angina can be precipitated by factors like cigarette smoking and the use of certain drugs. Major risk factor includes cigarette smoking and agents like sumatriptan and sympathomimetic agents (e.g. cocaine) can also cause vasospastic angina.
The rupture of atheromatous plaque exposes underlying thrombogenic materials, thereby activating platelet aggregation and the coagulation cascade. This event, often occurring in a cycle of repeated plaque disruptions and repairs, is a critical precursor to acute coronary syndrome (ACS). The exposure of these prothrombotic surfaces results in the formation of a luminal thrombus, which can lead to either partial or complete occlusion of the coronary artery, resulting in cardiac ischemia or infarction depending on the extent of the blockage.
