411 Section 5: Myocardial Infarction (MI)
MYOCARDIAL INFARCTION (MI)
Definition and General Understanding
Myocardial Infarction (MI):
Defined as the development of ischemia, leading to irreversible necrosis (cell death) of the myocardium.
The earliest necrosis occurs in the subendocardium and spreads transmurally.
This condition results from a prolonged obstruction of the coronary arteries, depriving the heart muscle of oxygen.
Cardiac troponin I (cTnI) becomes positive in 3–12 h, peaks at \sim24 h, and stays elevated 4–10 d.
Incidence: Approximately 1.5 million occurrences annually in the US. Rates of MI are seasonal, peaking between Thanksgiving and New Year’s Day.
The Centers for Disease Control and Prevention (CDC) states that about 805,000 MIs occur annually in the US, leading to 500,000 deaths in 2017 and 697,000 in 2022.
MI is the leading cause of death, accounting for 1 in 5 deaths in the adult population, despite a steady decline in coronary heart disease (CHD) incidence from 1997 to 2008 (Parikh et al., 2009). Hospitalization rates are declining.
Acute Myocardial Infarction
Acute Myocardial Infarction (AMI): Often caused by sudden thrombotic occlusion of a coronary artery at the site of an unstable atherosclerotic plaque, which can undergo ulceration of tunica intima, fissuring, or rupture.
Irreversible myocyte death can start within 20–40 min of occlusion, mostl likely sooner; greatest salvage if reperfused within \le6 h.
Consequences:
Heart failure (CHF) may occur if 25% of the left ventricle is infarcted.
Cardiogenic shock is likely with 40% infarction of the left ventricle.
Up to half of inferior wall infarctions display right ventricular ischemia or infarction.
ST-Segment Elevation Myocardial Infarction (STEMI)
STEMI vs. Non-STEMI: More severe than Non-STEMI, determined by ECG results at hospital admission.
It involves the complete occlusion of the blood and oxygen supply to a substantial portion of the myocardium, significantly altering ECG results.
Routine supplemental oxygen in STEMI may increase myocardial injury and arrhythmias.
Comparison of the ST segment at admission with the ST segment after reperfusion therapy can predict the size of the infarct, and patient prognosis is correlated with the rapidity of ST segment resolution.
Based on the reperfusion capacity of the myocardium
the ability to break down the thrombus and to reinfuse it back into the tissues
If a proper breakdown of the thrombus doesn’t happen, it will only cause more blockage
Better ST-segment revolution results in better prognosis/survival rates
Absence of ST-resolution typically indicates failed reperfusion
Acute Coronary Syndromes
Unstable angina
tunica intima is disrupted, and platelets aggregate
Non-ST-segment elevation MI
A thrombus is formed and there’s limited flow
May be able to relax and reduce the metabolic demand of the heart to heal
ST-segment elevation MI
The thrombus grows exponentially
completely blocks the lumin
no blood gets through
Serum Cardiac Markers
Primary Means of Detection
When the myofibers die, they release content into the blood
The amount of concentration of content indicates severity
cTn1/Troponin 1
Becomes positive in 3-12 hours after MI
Peaks at 24 hours
Remans elevated for 4-10 days
Highly sensitive for the early detection of myocardial injury
can be used to help discharge patients with chest pain
Pathophysiology and Etiology of MI
Most patients with MI experience coronary atherosclerosis, where thrombus formation occurs predominantly at atherosclerotic lesions.
It is often triggered by plaque rupture
Most MIs arise from plaque rupture with platelet aggregation and fibrin formation \rightarrow thrombotic occlusion (blockage)
Pathogenesis of Atherosclerosis:
A condition that develops through injury to endothelial cells, leading to an inflammatory response.
Endothelial cells: line chambers of the heart and blood vessel walls
permeable membrane
smooth muscle surface to enhance blood flow
regulate dilation and constriction chemically (NO + prostacyclin, Ang-2 + enodthelin)
“Response to Injury Theory”
Injury to the endothelium
earliest event in atherosclerosis
physical or chemical reasoning
When injury/irritation occurs, endothelial cells secrete cytokines as an inflammatory response
Activated endothelial cells attract leukocytes, which migrate into the intima and differentiate into macrophages, leading to plaque formation.
Injuries:
Common injuries include hypertension, turbulence in blood flow, circulation of reactive substances, and elevated glucose levels.
Physical stress from direct trauma (HTN)
Turbulent blood flow
Circulation of reactive oxygen and nitrogen
Hyperlipidemia
Chronically elevated plasma glucose, resulting in a dangerous concentration level
Homocysteinemia
If an Injury Occurs…
Cytokines attract monocytes
Monocytes adhere to the damaged region due to cell surface adhesion molecules (VCAM-1)
Monocyte migration into the intima between endothelial junctions
When junctions between endothelial cells become weakened…
Increases permeability for lipoproteins to enter into intima
oxidation and mineralization start
monocytes engulf lipoproteins to turn into macrophages
Macrophages take up oxidized LDL and minerals
Macrophages become foam cells
Smooth muscle cells proliferate into the tunica intima, further destabilizing the vessel
Progression of Atherosclerosis:
Involves cellular apoptosis (cell death), mostly smooth muscle cells
destabilizes the vessel
contributes to thrombogenicity (increase in thrombi generation)
connective tissue and plaque calcification
Accounts for approximately 76% of myocardial infarction fatalities.
Thrombogenicity: How does a thrombus actually generate?
Chronic, mild plaque build-up and ruptures with healing, inducing platelet accumulation
Platelets initially limit blood flow
Thrombotic oclusion (blockage), derived from fibrin formation in conjunction with platelet aggregation
How is Fibrin generated?
Activation of proteolytic enzymes synthesized in the liver as a reserve since it is constantly producing enzymes
Blood vessel damage initiates a cascade of enzyme activation based on the inflammatory response
Thromboplastin is released from the damaged wall = prothrombin
Prothrombin is converted into thrombin
Thrombin is an enzyme that converts inactive fibrinogen to fibrin
Coronary Artery Calcium Score
Risk Factors for Myocardial Infarction
80-90% of all MIs stem from a coronary thrombus at the site of a pre-existing stenosic plaque. Major risk factors include:
Smoking (doubles risk)
Cocaine use
Vasculitis: anywhere that has vascular inflammation
Aortic stenosis
Over-exertion in sedentary individuals (particularly in the early morning)
Periodontal diseases and acute respiratory infections
Diabetes leads to elevated Plasminogen Activator Inhibitor-1 (PAI-1), which inhibits t-PA and promotes thrombosis, increasing susceptibility to thrombus formation.
Tissue plasminogen activator helps break down blood clots
Pathophysiological Prinicples
Irreversible damage to the myocardium can begin as early as 20-40 mins after…probably within first few minutes
The dynamic process of infection may not be completed for several hours
Inflammation/edema/altered endothelial integrity/platelet aggregation/ neutrophil infiltration
Can result in reduced tissue perfusion capactiy even upon perfusion restoration
Edema/swelling
Necrosis of tissue appears to occur in a sequential fashion
starts in subendocardial layer of heart
Spreads like a “wavefront” throughout the thickness of the wall of the heart
Dog Study: the shorter the time between coronary occlusion and coronary reperfusion, the greater the amount of myocardial tissue that could be salvaged
Pathogensis
Observe the blood supply to the heart
2 large arteries with multiple branches
L & R coronary arteries
Left circumflex artery
Most common site: left ventricle
Still some shifting and moving on right side
When we wee a heart attack…
Different zones
Zone of infarction:
Region of ischemic damage: denied blood flow
Ischemia and reperfusion with inflammatory response
beased on swelling of tissue, get the spreading to other zones
Zone of Hypoxic Injury:
Immediatley surrownding the zone of infarction is a region that gets damaged from inflammatory response inside from the zone of ifarction
can be reversible if relaxed, and rapid perfusion
Zone of Ischemia:
immediately surrounding zone of hypoxic injury
can be reversible
Papillary Muscle Damage:
Immediately surrounding zone of hypoxic injury
Also reversible…
Size of the Infarction
Several factors determine the size of the resulting infarction based on…
Extent, severity, and duration of the ischemic episode
The size of the vessel involved
The amount of collateral circulation
more branches off vessel feeding, will see less heart damage
The status of the intrinsic fibrinolytic system
body’s ability to produce protiolytic activator (rate at which the thrombus can be removed)
Vascular tone
is there greater constriction or dialation? more dialation = less damage
The metabolic demands of the myocardium at the time of the event
high demand, needs oxygen, greater chance of injury
MIs most often result in damage to the left ventricle, leading to an alteration in left ventricle function
Infarctions can also occur in the right ventricle
Transmural infarction:
Clinical Manifestations
General Symptoms: Sudden pressure or crushing pain in the chest, often radiating to the arm, neck, back or throat; persistent pain lasting over 30 minutes, shortness of breath, pallor, profuse perspiration.
Sympathetic Activation: Causes peripheral vasoconstriction affecting blood pressure.
In Women: Symptoms may present atypically, including unexplained fatigue, pain in mid-thoracic spine, neck or shoulder pain, stomach pain, nausea, unexplained anxiety, and silent MIs without symptoms.
Post-Infarction Complications
Over 90% of MI survivors may endure arrhythmias, which stem from ischemia, electrolyte imbalance, and altered conduction pathways. Other complications include:
Congestive heart failure (CHF)
Cardiogenic shock
Rupture of the heart or valves
Pericarditis, albeit less frequently.
Exercise Considerations Following MI
Contraindications to exercise within 1-2 days of MI include unstable angina, signs of MI, oxygen saturation <85%, recent pulmonary embolism, or uncontrolled diabetes.
Treatment and Rehabilitation: Focus on reestablishing blood flow, pain control, reducing vasoconstriction, and preventing further thrombosis. Interventions include angioplasty and cardiac rehabilitation. Exercise, when done appropriately, can increase survivors' exercise tolerance, reduce dependency on medication, and limit cardiac risk factors.
Beta-blockers (\beta‑blockers) blunt exercise HR; therefore, use Rating of Perceived Exertion (RPE) or adjusted targets for exercise intensity.
Pharmacology in Post-MI Care
Medications: Include ACE inhibitors, beta-blockers (notably extending life post-MI), statins, anticoagulants, and calcium channel blockers aimed at regulating arrhythmias.
Reperfusion Injury
This refers to the damage that occurs upon blood flow restoration after ischemia, initiating inflammation and possibly exacerbating myocardial damage through ionic shifts and harmful chemical production.
Clot Formation and Breakdown
Clot Formation: Initiated post-vessel damage through enzyme activation that leads to thrombin conversion of fibrinogen to fibrin, ultimately forming a stable clot.
Clot Breakdown: Tissue plasminogen activator (t-PA) is pivotal in converting plasminogen to plasmin, dissolving clots, underscoring the balance required between clot formation and breakdown to prevent excessive clotting that can escalate thrombus events.
plasminogen activator, urokinase
fibrinosylin, enzyme breaks down fibrin
breaks down fibrin mesh, TPA
Pharmacology
Antitrombotic: platelet side of the “equation” - inhibit platelet/clotting - “blood thinner”, “plavix”, arteriole
Anticoagulants: fobrin mesh side, limits function and synthesis of clotting factors, does not convert to fibrin - no meshwork for thrombus formation
venous issue, heparin- bypass first pass effect
Heparin warfarin(coumadin)
Thrombolytic drugs: facilitate the breakdown - actually break it down, prevent all the things making plasminogen to plasma
Throbolytic Therapy
Conclusion
Assessment of MI Incidence: Proper management and understanding of myocardial infarction's etiology, risk factors, and clinical implications are crucial for effective prevention and treatment strategies.