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Myocardial Infarction - Complete Review

Definition

Myocardial infarction (MI), commonly called a "heart attack," is necrosis of cardiac muscle resulting from prolonged ischemia. The 2018 joint task force of U.S. and European Cardiology groups defines it as "the presence of acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischemia."

Classification

By ECG Pattern (Clinically Most Used)

Type	ECG	Pathology
STEMI (ST-elevation MI)	ST segment elevation	Transmural infarct; complete coronary occlusion
NSTEMI (Non-ST-elevation MI)	No ST elevation	Subendocardial / partial thickness; incomplete occlusion
Unstable Angina	May be normal	No biomarker rise; ischemia without necrosis

STEMI is invariably due to complete coronary artery occlusion and requires urgent thrombolysis or stenting. NSTEMI can often be managed conservatively.

By Depth

Transmural MI - full thickness of myocardial wall involved; corresponds to STEMI
Subendocardial MI - limited to inner 1/3 to 1/2 of myocardial wall; corresponds to NSTEMI

Fourth Universal Definition (Type Classification)

Type	Cause
Type 1	Spontaneous MI from atherothrombosis (plaque rupture/erosion)
Type 2	MI due to supply-demand mismatch (e.g., vasospasm, tachycardia, anemia)
Type 3	MI causing death before biomarkers can be confirmed
Type 4a/b	Percutaneous coronary intervention (PCI)-related MI
Type 5	CABG surgery-related MI

By Territory (based on coronary artery affected)

LAD occlusion - anterior, anteroseptal, anterolateral wall of LV (most common; "widow maker")
RCA occlusion - posterior, inferior wall of LV; right ventricle
LCx occlusion - lateral wall of LV

Etiopathogenesis

Risk Factors

Non-modifiable: Age, male sex, family history; approximately 10% of MIs occur below age 40
Modifiable: Hypertension, hyperlipidemia, diabetes, smoking, obesity, sedentary lifestyle
Women are protected during reproductive years due to estrogen; risk rises post-menopause

Pathogenesis Sequence (Atherothrombotic, ~90% of cases)

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 activate - releasing thromboxane A2, ADP, and serotonin, causing further aggregation and vasospasm
Coagulation is activated by tissue factor exposure, adding to the growing thrombus
Within minutes, the enlarging thrombus completely occludes the coronary lumen

Angiography within 4 hours of MI onset shows coronary thrombosis in ~90% of cases.

Non-atherothrombotic Causes (~10%)

Coronary artery vasospasm (cocaine, ephedrine use)
Embolism from mural thrombus (atrial fibrillation), valvular vegetations, paradoxical embolism
Vasculitis, amyloid deposition, sickle cell disease (small vessel occlusion)

Myocardial Response to Ischemia

Time	Event
Seconds	ATP depletion begins; aerobic metabolism ceases
< 2 min	Loss of contractility
10 min	ATP reduced to 50% of normal
20-40 min	Irreversible cell injury begins (necrosis threshold)
40 min	ATP reduced to 10% of normal
> 1 hour	Microvascular injury
6-12 hours	Progressive necrosis becomes complete

The critical window is 20-40 minutes - severe ischemia lasting beyond this leads to irreversible myocyte death. The rationale for rapid reperfusion is to salvage as much at-risk myocardium as possible ("time is myocardium").

Necrosis begins in the subendocardial zone (most distal from epicardial vessels, exposed to high intramural pressures) and spreads as a "wavefront" toward the epicardium with prolonged ischemia.

Pathology: Morphology / Sequential Changes Over Time

(Robbins & Kumar Basic Pathology)

Time Frame	Gross Appearance	Light Microscopy	EM Findings
0-½ hr	None	None	Myofibril relaxation; glycogen loss; mitochondrial swelling
½-4 hr	None	Usually none; wavy fibers at border	Sarcolemmal disruption; mitochondrial amorphous densities
4-12 hr	Occasionally dark mottling	Onset of coagulation necrosis; edema; hemorrhage	-
12-24 hr	Dark mottling	Ongoing coagulation necrosis; pyknotic nuclei; hypereosinophilic myocytes; marginal contraction band necrosis; early neutrophilic infiltrate	-
1-3 days	Mottling with yellow-tan infarct center	Coagulation necrosis with loss of nuclei and striations; increased neutrophils	-
3-7 days	Hyperemic border; central yellow-tan softening	Neutrophil disintegration; early macrophage phagocytosis at border	-
7-10 days	Maximally yellow-tan and soft; depressed red-tan margins	Well-developed macrophage phagocytosis; early granulation tissue at margins	-
10-14 days	Red-gray depressed infarct borders	Well-established granulation tissue with new vessels and collagen deposition	-
2-8 weeks	Gray-white scar, progressing from border to core	Increased collagen deposition; decreased cellularity	-
> 2 months	Scarring complete	Dense collagenous scar	-

Key Microscopic Features

Wavy fibers (½-4 hrs): stretching and buckling of non-contractile dead fibers at infarct edges
Coagulation necrosis: preservation of cell outlines but loss of nuclei (4-12 hrs onward)
Contraction band necrosis: particularly seen in reperfused infarcts - intense eosinophilic transverse bands formed by hypercontracted sarcomeres due to calcium influx
Neutrophil infiltration: peaks 1-3 days
Macrophage phagocytosis: peaks 5-10 days
Granulation tissue: appears 1-2 weeks
Dense collagenous scar: complete by 6 weeks

Reperfusion Injury

Restoring blood flow to ischemic tissue can cause additional damage. Mechanisms include:

Mitochondrial dysfunction (membrane permeability → swelling → apoptosis)
Myocyte hypercontracture (calcium overload)
Free radical generation (superoxide, H2O2, peroxynitrite)
Leukocyte aggregation causing microvascular "no-reflow" phenomenon

Laboratory Diagnosis (Cardiac Biomarkers)

The basis is measurement of intracellular proteins that leak from necrotic myocytes through damaged sarcolemmal membranes into the circulation.

Biomarker Kinetics

(Robbins & Kumar Basic Pathology, Fig. 9.13 - Acute increases in Troponin I, CK-MB, and Myoglobin following MI)

Enzyme/Biomarker Changes Summary

Marker	Rise	Peak	Returns to Normal	Notes
Myoglobin	1-4 hrs	6-9 hrs	24-36 hrs	Earliest to rise; low cardiac specificity
CK-MB (creatine kinase-MB isoform)	2-4 hrs	24-48 hrs	~72 hrs	Traditionally used; now largely replaced by troponins
Troponin I (cTnI)	2-4 hrs	~48 hrs	7-10 days	High cardiac specificity and sensitivity; preferred marker
Troponin T (cTnT)	2-4 hrs	~48 hrs	7-14 days	High cardiac specificity; same kinetics as TnI
LDH (LDH-1 isoform)	24-48 hrs	3-5 days	10-14 days	Useful for late diagnosis; LDH-1 > LDH-2 = "flipped LDH"
AST	12-24 hrs	36-48 hrs	3-5 days	Non-specific; less used now

Key points:

TnI and TnT are normally absent from the circulation - any detectable level is significant
Troponin is the gold-standard marker - persists 7-10 days, allowing late diagnosis
With reperfusion: both troponin and CK-MB peak earlier due to rapid washout from necrotic tissue
CK-MB returns to normal days earlier than LDH, making LDH useful for confirming an older infarct

Other Diagnostic Tools

ECG: ST elevation (STEMI), ST depression/T-wave inversion (NSTEMI), new Q-waves (transmural necrosis), bundle branch block
Echocardiography: Regional wall motion abnormalities (hypokinesis, akinesis, dyskinesis)
Coronary angiography: Gold standard for identifying culprit artery; guides PCI
Radionuclide scanning: Technetium-99m sestamibi perfusion imaging
MRI: Most sensitive for detecting myocardial necrosis and viability

Complications of Myocardial Infarction

Nearly three-fourths of patients experience one or more complications. Three are potentially lethal:

Mechanical Complications (most dangerous)

Complication	Timing	Details
Ventricular free wall rupture	3-7 days (peak)	Least common but most fatal; causes hemopericardium and cardiac tamponade
Ventricular septal rupture (VSD)	3-7 days	Most common rupture; harsh new systolic murmur
Papillary muscle rupture	3-7 days	Causes acute severe mitral regurgitation; flash pulmonary edema

Rupture timing: 3-7 days after MI when lysis of necrotic myocardium is maximal and the infarct has been converted to soft, friable granulation tissue (maximum vulnerability).

Functional Complications

Contractile dysfunction / Cardiogenic shock: Proportional to extent of LV damage; cardiogenic shock occurs in ~10% of transmural MIs, typically when >40% of LV is damaged
Papillary muscle dysfunction: Ischemia (without rupture) causes mitral regurgitation
Right ventricular infarction: Isolated in 1-3% of MIs; right-sided failure, systemic hypotension

Arrhythmias

Most common complication; major cause of early (pre-hospital) death
Ventricular fibrillation: leading cause of death within first hour of MI
Ventricular tachycardia, heart block, atrial fibrillation, sinus bradycardia (especially with inferior MIs via vagal stimulation)

Late / Chronic Complications

Complication	Mechanism
Pericarditis (Dressler syndrome)	Autoimmune reaction 2-10 weeks post-MI; fibrinous epicardial inflammation
Mural thrombus	Wall motion abnormality over infarcted zone; risk of systemic embolism
Left ventricular aneurysm	Scar tissue bulges outward with each contraction; associated with persistent ST elevation
Progressive heart failure	Ventricular remodeling with myocyte hypertrophy and chamber dilation
Ventricular remodeling	Infarct expansion + reactive hypertrophy of non-infarcted segments

Clinical Presentation (Brief)

Classic: crushing/squeezing chest pain >30 minutes, radiating to left arm/jaw, diaphoresis, nausea/vomiting, dyspnea
~25% are entirely asymptomatic (especially diabetics with neuropathy) - discovered by ECG or biomarkers
Posterior-inferior MI: nausea/vomiting predominant (vagal stimulation)

Sources: Robbins & Kumar Basic Pathology, pp. 358-360; Robbins, Cotran & Kumar Pathologic Basis of Disease, pp. 511-516

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