(CATBR50)

Introduction

  • Characteristic findings are coagulation necrosis and contraction band necrosis.
  • Majority of myocyte loss occurs by coagulation necrosis.
  • Revised definition of MI (2007 Joint task force)
    • Acute, evolving or recent MI- either of these
      • Typical rise or fall or markers + any one of these
        • Ischemic symptoms
        • Q waves
        • ST elevation or depression
        • New RWMA
        • Imaging evidence of new loss of viable myocardium
      • Pathologic evidence
    • Healing or healed MI- either of these
      • Q waves
      • Pathologic evidence
  • Short term mortality in STEMI
    • With aggressive pharmacological reperfusion in an RCT- 6.5 to 7.5 %.
    • In the community- 15 to 20%.
  • Age above 75 years increases mortality 4 times compared to young.
  • Causes of MI other than coronary atherosclerosis-
    • Coronary arteritis (Takayasu, Kawasaki, luetic, PAN, DLE, rheumatoid, ankylosing spondylitis)
    • Thickening of coronary wall (Hurler, Fabry, amyloid, juvenile intimal sclerosis, contraceptive steroids, post partum, radiation, homocystinuria, PSE)
    • Dynamic causes (Printzmetal, NTG withdrawal)
    • Dissection (aortic, coronary)
    • Trauma
    • Embolism (IE, cardiac mural thrombus, myxoma, angiography, CABG, aortic valve papillary fibroelastoma or fixed thrombus, MVP, prosthetic valve emboli, paradoxical emboli)
    • Hematological (DIC, TTP, PV, thrombocytosis, hypercoagulability states)
    • Congenital coronary anomalies (ALCAPA, LMCA from anterior sinus, coronary AV fistula, coronary-cameral fistula, coronary aneurysm)
    • Myocardial oxygen supply-demand mismatch (AS, AR, CO poisoning, thyrotoxicosis, prolonged hypotension, Takotsubo, incomplete differentiation of aortic valve)
    • Others (cocaine abuse, myocardial contusion)

Pathology

  • Q is determined more by infarct size than transmural nature.
  • Most patients with NSTEMI develop no Q waves while most patients with STEMI develop Q waves. Crossovers occur in both groups.
  • A small strip of subendocardial myocardium is spared from necrosis due to oxygen diffused from blood.
  • The culprit plaque in STEMI is more complex and irregular compared to other plaques.
  • Thrombus causing STEMI is about 1 cm long.
  • Plaques prone to rupture have metalloproteinases elaborated by macrophages and mast cells.
  • STEMI occurs more in winter, in morning hours and after natural disasters.
  • After STEMI, Q waves may not develop in some. These patients may have loss of R and splintering of QRS.
  • Occlusive thrombus is more likely to cause transmural infarction while non-occlusive thrombus is more likely to cause non-transmural infarction.
  • Viable myocardium is stained red by TTC and blue by NBT.
  • Wavy myocardial fibers are seen at 1 to 3 hours.
  • PMN infiltration occurs at 8 hours.
  • Edema begins at 8 hours.
  • Loss of cross-striations and cytoplasmic clumping occur at 24 hours.
  • Macrophages appear at 4th day.
  • Thinning of ventricular wall starts on day 8.
  • Granulation tissue is present from 10th day to end of first month.
  • The infarcted area becomes a gray scar at 6 weeks.
  • Patterns of myocardial necrosis-
    • Coagulation necrosis- This occurs in the centre of the infarct. It is due to severe ischemia. There is arrest in relaxed state. Cells and myofibrils are stretched. Mitochondrial damage occurs with amorphous or flocculent densities without calcification. Cells are arrested in relaxed state. Healing occurs by phagocytosis.
    • Contraction band necrosis- also called coagulative myocytolysis. Due to severe ischemia followed by reflow. Seen at periphery of infarcts. Seen more in non-transmural than transmural infarcts. Entire infarct shows contraction band necrosis if reperfusion occurs. Myofibrils are contracted with contraction bands due to calcium influx. Mitochondrial damage causes calcification. Marked vascular congestion is present. Cells are arrested in contracted state. Healing occurs by cell lysis.
    • Myocytolysis- Due to prolonged ischemia without necrosis. This is reversible. Myocyte vacuolization occurs. Later, cloudy swelling occurs.
  • Electron microscopy- Earliest changes are seen within 20 minutes and consist of reduction in glycogen granules, intracellular edema and distortion of organelles.
  • Apoptosis or programmed cell death is characterized by cell shrinkage, DNA fragmentation and phagocytosis without inflammatory infiltrate. It mainly occurs in late stages of MI and ventricular remodeling.
  • If reperfusion occurs within 20 minutes, there is no necrosis.
  • Reperfusion causes exaggerated early peaking of CK-MB and troponins.
  • Coronary anatomy- Early angiography shows 90% incidence of total occlusion of IRA. 5% have normal coronaries- here the cause may be embolism, transient platelet thrombus or spasm. Majority of culprit plaques are non-obstructive though obstructive plaques are more likely to cause STEMI than non-obstructive ones. Infarct at a distance occurs due to occlusion of the coronary supplying collaterals to another coronary territory.
  • RV infarction- Incidence is lower due to lower oxygen demand, richer collaterals and thinness of ventricular wall allowing nutrition from blood. After reperfusion, there is better chance of recovery of contractile function.
  • Atrial infarction- This occurs in 10% of STEMIs. It is more common in the right atrium probably because left atrial blood has more oxygen. It is more in the atrial appendages. It can cause thrombosis and rupture. It frequently causes atrial arrhythmias. It reduces ANP secretion.
  • Coronary collaterals are well developed in patients with-
    • More than 75% stenosis in a coronary
    • Chronic hypoxia as in severe anemia, COPD and congenital cyanotic heart disease and
    • LVH.
  • With total occlusion of a coronary supplying a collateral rich area-
    • MI may not occur or
    • MI may occur, but aneurysms may not occur.
  • After cardiac surgery, MI may occur due to air or valvular calcium.
  • Chest wall trauma may cause coronary thrombosis.
  • Coxsackie B viral infection can cause coronary inflammation leading to MI.
  • Cocaine abuse can cause MI in patients with normal coronaries, coronary spasm and coronary atherosclerosis.
  • STEMI with normal coronaries has many causes as already seen. Often this occurs in young smokers without other risk factors and without preceding angina. The cause of MI may be rupture of small plaques or coronary spasm. The patients have RWMA on recovery. But on recovery, further heart failure, re-MI and death are unusual and the long term prognosis is better compared to patients with abnormal coronaries. TMT will be normal and stable angina does not develop.

Pathophysiology

Left ventricular function

  • Systolic function-
    • Early changes-
      • Infarct territory-
        • With coronary occlusion, contractility of the affected territory is immediately lost. In sequence, dyssynchrony, hypokinesis, akinesis and dyskinesis occurs. Dyskinesis, if present, leads to decrease in stroke volume.
        • ESV may increase. Increase in ESV is the most powerful hemodynamic predictor of mortality.
        • Ventricle may dilate. If so, Laplace’s law increases wall stress setting up a vicious cycle.
        • Even small infarcts produce diastolic dysfunction. Typically, diastolic dysfunction appears before systolic dysfunction.
        • With affection of
          • More than 15% of myocardium- ejection fraction declines.
          • More than 25%- clinical heart failure.
          • More than 40%- cardiogenic shock.
      • Non-infarcted territory-
        • The non-infarcted areas become hyperkinetic early in MI due to sympathetic stimulation and activation of Frank-Starling mechanism. This hyperkinesis lasts for 2 weeks.
        • The uninfarcted areas may show hypokinesia if
          • these areas were previously infarcted,
          • these areas are supplied by stenotic coronaries or
          • these areas are supplied by collaterals from the IRA.
    • Post early stage changes-
      • Infarct territory-
        • Infarct expansion may occur (see ventricular remodeling below).
        • RWMA may improve due to recovery of stunned myocardium.
        • First edema and later fibrosis may increase stiffness of infarct preventing dyskinesia.
      • Non-infarcted territory-
        • After 2 weeks, hypercontractility disappears.
  • Diastolic function- Diastolic dysfunction is proportional to infarct size. It leads to an initial increase in LVEDP which normalizes over weeks as EDV rises.
  • Circulatory regulation-
    • Decreased coronary perfusion pressure due to decreased stroke volume leads to myocardial ischemia.
    • MI produces systemic inflammation leading to increases in inflammatory cytokines which stimulate iNOS leading to increased NO and peroxynitrite which causes systemic vasodilation. This further decreases coronary perfusion pressure.
  • Laplace’s law- Due to loss of contractile myocardium, LV cannot empty normally. This leads to ventricular dilation. The increased EDV (increased preload) leads to normalization of stroke volume (EDV x EF=SV). With ventricular dilation wall stress increases (increased afterload) by Laplace’s law- this leads to increased myocardial oxygen demand leading to myocardial ischemia.
  • Ventricular remodeling-
    • Infarct expansion-
      • Definition- dilation and thinning of infarct not due to additional myocardial necrosis.
      • Mechanisms-
        • Slippage between muscle bundles
        • Myocyte disruption and
        • Tissue loss.
      • Pathology- Stretching of infarct before scar formation. It occurs due to elevated ventricular pressure. Since apex is the thinnest portion, it is most likely to occur at the apex. Preexisting hypertrophy and patent IRA protects from this. Glucocorticoids and NSAIDs in early MI increases infarct expansion while RAAS inhibitors protect from this.
      • Clinical features- Deterioration of systolic function leading to S3 and basal crepitations.
      • Prognosis- Increases heart failure, aneurysm formation and mortality.
    • Non-infarct area
      • Ventricular dilation-Dilation of non-infarcted area. This starts immediately after MI and continues for years. It is due to shift of PV curve to right. It is a compensatory mechanism to increase stroke volume.
      • Ventricular hypertrophy- Hypertrophy of non-infarcted area. Due to extra load. Leads to hemodynamic improvement.

Other organs

  • Lungs
    • Interstitial edema- This causes
      • Hypoxia due to bronchiolar compression,
      • Reduced lung compliance,
      • Decreased diffusion capacity and
      • Decrease in all lung volumes.
    • Hyperventilation with respiratory alkalosis may occur in anxious patients.
    • Apical redistribution of pulmonary venous blood leads to altered V-P relation.
    • In patients with LV failure, increased erythrocyte 2,3-DPG causes increase in P50 of Hb. So affinity of Hb for oxygen is decreased. This is a compensatory mechanism.
  • Pancreas
    • Hyperglycemia occurs due to
      • Decreased pancreatic blood flow due to splanchnic vasoconstriction leading to decreased insulin secretion and
      • Increased catecholamines decreasing insulin secretion.
    • Insulin deficiency is deleterious because insulin is needed for uptake of glucose into cells and glucose is a more favorable energy source for ischemic myocardium than free fatty acids as ATP can be produced by anaerobic glycolysis.
  • Adrenal medulla-
    • Catecholamines rise maximum in the first hour and remains at peak in the first day.
    • Catecholamine levels correlate with
      • Serious arrhythmias
      • Extent of myocardial damage
      • Incidence of cardiogenic shock and
      • Early and late mortality.
    • Adverse effects are due to
      • Increased myocardial oxygen demand
      • Increased FFA (deleterious) and
      • Platelet aggregation with TXA2 generation causing vasoconstriction.
  • RAAS activation
    • This occurs in non-infarcted areas. This stimulates growth factors leading to hypertrophy. This releases AT II producing coronary vasoconstriction.
  • Natriuretic peptides
    • Peak at 16 hours.
    • ANF is increased and is secreted by atria.
    • BNP is increased and is secreted by both atria and ventricles. The levels correlate with infarct size, ventricular dysfunction and mortality.
  • Adrenal cortex