Myocardial infraction

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"myocardial infarction"[MeSH Terms] AND management

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Myocardial Infarction (Heart Attack)

Definition

Myocardial infarction (MI) is the death of cardiac muscle due to prolonged ischemia. In the United States, roughly 800,000 individuals experience an MI each year (nearly one MI every 40 seconds), causing almost 400,000 deaths annually. The major underlying cause is atherosclerosis.

Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 511

Pathogenesis

Coronary Arterial Occlusion

The following sequence underlies most MIs:

An atheromatous plaque is eroded or suddenly disrupted by endothelial injury, intraplaque hemorrhage, or mechanical forces, exposing subendothelial collagen and necrotic plaque contents to blood.
Platelets adhere, aggregate, and release thromboxane A2, ADP, and serotonin - causing further platelet aggregation and vasospasm.
Activation of coagulation by tissue factor adds to the growing thrombus.
Within minutes, the thrombus can fully occlude the coronary artery lumen.

When angiography is performed within 4 hours of MI onset, coronary thrombosis is demonstrated in almost 90% of cases. This has therapeutic implications: early thrombolysis and/or angioplasty can be highly successful in limiting myocardial necrosis.

In approximately 10% of cases, MI occurs without typical coronary atherothrombosis. Other mechanisms include:

Vasospasm (e.g., cocaine or ephedrine use)
Embolism (from left atrial mural thrombus in atrial fibrillation, infective endocarditis vegetations, prosthetic material)
Disorders of small intramural coronary vessels, sickle cell disease, vasculitis, aortic stenosis
Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 511-512

Progression of Necrosis

Progression of myocardial necrosis after coronary artery occlusion - showing area at risk at 0 hr, zone of necrosis at 2 hr, and completed infarct at 24 hr

Fig. 12.10 - Progression of myocardial necrosis after coronary artery occlusion. Necrosis begins in the subendocardial zone and progresses outward as a wavefront over 6-24 hours.

The timeline of ischemic events:

Feature	Time
Onset of ATP depletion	Seconds
Loss of contractility	<2 minutes
ATP reduced to 50% of normal	10 minutes
ATP reduced to 10% of normal	40 minutes
Irreversible cell injury	20-40 minutes
Microvascular injury	>1 hour

Irreversible injury first occurs in the subendocardial zone - the last area to receive blood from epicardial vessels and the area exposed to the highest intramural pressures. With prolonged ischemia, a wavefront of cell death moves centripetally. An infarct usually achieves its full extent within 6 to 12 hours.

Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 512

Morphology and Histology

Microscopic features of myocardial infarction and repair - A: 1-day coagulative necrosis with wavy fibers; B: neutrophil infiltrate at 3-4 days; C: phagocytosis at 7-10 days; D: granulation tissue; E: healed fibrous scar (Masson trichrome)

Fig. 12.13 - Microscopic features of MI and repair. (A) 1-day-old infarct: coagulative necrosis and wavy fibers. (B) 3-4 days: dense neutrophil infiltrate. (C) 7-10 days: macrophage phagocytosis of necrotic myocytes. (D) Granulation tissue with loose collagen and abundant capillaries. (E) Healed infarct: dense collagenous scar (blue, Masson trichrome).

The gross and microscopic changes evolve predictably:

Time	Gross Changes	Microscopic Changes
0-4 hours	None visible	None visible (EM: myofibril relaxation, mitochondrial swelling)
4-12 hours	Dark mottling (early)	Coagulative necrosis begins; wavy myofibers
12-24 hours	Dark mottling	Pyknosis, contraction bands, neutrophil infiltrate begins
1-3 days	Mottling with yellow-tan infarct center	Extensive coagulative necrosis; heavy neutrophil infiltrate
3-7 days	Yellow-tan center, hyperemic border	Neutrophil disintegration; macrophage phagocytosis begins
7-10 days	Maximally yellow-tan, soft, depressed borders	Phagocytosis of necrotic myocytes; granulation tissue
2-8 weeks	Gray-white fibrosis	Fibrous scar formation
>2 months	Dense fibrous scar	Complete scarring; residual myocytes show compensatory hypertrophy

Classification

By ECG pattern:

STEMI (ST-Elevation MI) - transmural infarction (full wall thickness); ST segment elevation in leads overlying the infarct
NSTEMI (Non-ST-Elevation MI) - subendocardial infarction; no ST elevation, but troponin positive

By territory:

Anterior MI - usually left anterior descending (LAD) artery occlusion
Inferior MI - usually right coronary artery (RCA) occlusion
Lateral MI - usually left circumflex artery occlusion

ECG Changes (Ganong's Physiology)

Three major abnormalities cause ECG changes in acute MI:

Defect in Infarcted Cells	Current Flow	ECG Change in Leads over Infarct
Rapid repolarization	Out of infarct	ST segment elevation
Decreased resting membrane potential	Into infarct	TQ segment depression (manifested as ST elevation)
Delayed depolarization	Out of infarct	ST segment elevation

The hallmark of acute MI is ST segment elevation in leads overlying the infarct. Leads on the opposite side show ST segment depression (reciprocal changes).

After days to weeks, the ST segment abnormalities subside. Dead muscle becomes electrically silent. The hallmark of old MI is the appearance or deepening of Q waves - abnormal Q waves are 0.04 s or wider and/or deeper than 25% of the R wave in the same lead.

Ganong's Review of Medical Physiology, p. 534

Biomarkers

Cardiac Troponins T and I (cTnT, cTnI): Most clinically useful. Rise in 2-4 hours, peak at 24-48 hours, remain elevated for 7-10 days. With reperfusion, may peak earlier ("washout" pattern).
CK-MB: Rises in 4-6 hours, peaks at 24 hours, normalizes in 48-72 hours - useful for detecting reinfarction.
Myoglobin: Earliest to rise (1-4 hours) but non-specific.

Importantly, low-level troponin elevation can occur in other conditions (CHF, pulmonary embolism, renal failure, sepsis), so serial measurements and clinical context are essential.

Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 517

Treatment

Immediate (STEMI) - "Time is Myocardium"

Reperfusion is the cornerstone of STEMI treatment:

Primary PCI (percutaneous coronary intervention): Goal door-to-balloon time <90 minutes (or <120 minutes from first medical contact). Preferred when available.
Fibrinolysis (e.g., tPA, streptokinase): If PCI not available within 120 minutes of first medical contact. Goal door-to-needle time <30 minutes.

Pharmacological therapy:

Morphine 2-4 mg IV every 5 min - for pain relief (watch for hypotension, bradycardia)
Oxygen - if SaO2 <90% or respiratory distress
Nitrates - for vasodilation and relief of vasospasm
Aspirin (162-325 mg chewed immediately) + P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) - dual antiplatelet therapy (DAPT)
Anticoagulation - unfractionated heparin, LMWH, bivalirudin, or fondaparinux
Beta-blockers (e.g., metoprolol 5 mg IV every 2-5 min x3 doses, then oral 50 mg every 6h) - reduce O2 demand, decrease risk of VF and reinfarction. Avoid in acute HF, low output state, cardiogenic shock, bradycardia, or high-degree AV block.
ACE inhibitors / ARBs - started within 24 hours, especially with anterior MI, reduced EF, hypertension, or diabetes
Statins - high-intensity statin therapy immediately

Harrison's Principles of Internal Medicine 22E, p. 2162

Consequences and Complications

Complication	Time of Onset	Notes
Arrhythmias (VF, VT, heart block)	Hours to days	Most common cause of death; VF most common in first hour
Cardiogenic shock	Hours to days	LV pump failure; mortality ~50-80% without support
Left ventricular failure / Pulmonary edema	Hours to days	Related to infarct size
Myocardial rupture (free wall)	3-7 days	Catastrophic; pericardial tamponade
Ventricular septal defect (VSD)	3-7 days	Harsh holosystolic murmur; may need surgical repair
Papillary muscle rupture / Mitral regurgitation	3-5 days	Acute MR; sudden pulmonary edema
Pericarditis (Dressler syndrome)	Days to weeks	Autoimmune; treated with NSAIDs
Left ventricular aneurysm	Weeks to months	Risk of mural thrombus and systemic emboli
Mural thrombus + systemic embolism	Days to weeks	Risk of stroke; anticoagulate
Ventricular remodeling / Chronic HF	Weeks to months	Infarct expansion, hypertrophy of remaining myocardium

Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 501-502

Reperfusion Injury

Although restoring blood flow is beneficial, it can cause additional damage:

Mitochondrial dysfunction - ischemia alters mitochondrial membrane permeability, leading to swelling and release of pro-apoptotic contents
Myocyte hypercontracture - calcium overload during ischemia causes contraction band necrosis on reperfusion
Oxygen free radicals - generated on reperfusion
Reperfusion arrhythmias

Up to 50% or more of the ultimate infarct size may be attributed to reperfusion injury. Clinical trials to prevent it have not yet been successful.

Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 514

Recent Evidence Update

A 2025 meta-analysis (Chi et al., Eur J Prev Cardiol, PMID 39298680) found that beta-blockers for secondary prevention after MI in patients without reduced ejection fraction or heart failure may have a more limited benefit than previously assumed - an important update to the traditional blanket recommendation for post-MI beta-blockade in all patients.

A 2024 pooled cohort meta-analysis (Peek et al., Eur Heart J, PMID 39378245) highlighted that sudden cardiac death risk post-MI remains a major concern and can be stratified using individual patient data.

Sources: Robbins, Cotran & Kumar Pathologic Basis of Disease | Braunwald's Heart Disease | Harrison's Principles of Internal Medicine 22E | Ganong's Review of Medical Physiology | PubMed 2024-2025

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