Ischemic Heart Disease

Definition and Pathogenesis

• Ischemic heart disease is really an umbrella term for four interrelated clinical syndromes.
  • Angina pectoris
  • Acute myocardial infarction, the focus of this portion of the lecture
  • Chronic ischemic heart disease – ischemic cardiomyopathy
  • Sudden cardiac death
• All four syndromes are connected by the underlying cause of myocardial ischemia. Simply put, there is too much demand and too little supply of oxygenated blood to heart tissue.
• This lack of perfusion to the heart muscle is most frequently due to atherosclerosis of the epicardial coronary arteries (as mentioned above).
  • This leads to the common use of coronary artery disease or coronary heart disease as a synonym for ischemic heart disease.
• Of the four syndromes listed above, unstable or crescendo angina pectoris, Acute myocardial infarction, and sudden cardiac death are acute coronary syndromes.
• Several structural abnormalities underlie all ischemic heart disease, particularly acute myocardial infarction.
  • Those individuals with acute symptoms usually have atherosclerotic coronary arteries that are 50-75% occluded.
  • Greater than 75% obstruction is called critical stenosis.
    • Even with vasodilation of the affected artery the supply to the heart muscle will be insufficient to meet even modest increases in demand.
  • In the absence of sudden change, these lesions are known as fixed plaques.
  • Of course, the lesions are constantly growing and evolving, and as the lesions change, bad things can happen.
    • Plaque fissures, ruptures, and intraplaque hemorrhages can further stenose the vessel and reduce flow.
    • Thrombosis and vasospasm can achieve the same results.
    • The problems listed above are known as dynamic plaque changes.

Acute Myocardial Infarction (Heart Attack)

• The root of the word infarction means “to stuff in.” What exactly are we stuffing in? An occlusive thrombosis, of course!
• Acute myocardial infarctions are characterized by localized death of myocardial tissue due to ischemia.
• The vast majority of Acute myocardial infarctions are caused by occlusive thrombosis, but there are other, rarer causes as well.
  • Prolonged vasospasm of a vessel. A vessel can be spastic (it’s ok, I giggled a little myself) and prevent adequate blood from reaching heart muscle.
  • Thromboembolism from fibrin-platelet clots that can form on the mitral or aortic valve leaflets. These thrombi on the leaflets are called verrucae (like the derm name for warts) or vegetations. If the break off and wind up in the coronary circulation they can occlude a vessel.
  • Prolonged hypertensive episodes can cause Acute myocardial infarctions as well, but the explanation for this was not given.
  • There are some instances in which the cause is just not known.

• They then sweep outward on a “wave of necrosis” through the myocardium, commonly involving the full thickness of a ventricular wall.
• A full thickness infarct is known as a transmural or full-thickness infarction.
• More limited infarctions are known as subendocardial infarcts.
  
  This can occur if you treat an Acute myocardial infarction early enough and prevent the infarction from spreading using thrombolytic drugs.
   

• Even a full-thickness infarct is not truly full-thickness because the lining of the chamber is in direct contact with systemic blood and can be sustained with diffused oxygen from the ventricle.

• Various factors affect the size and location of an infarct.
  • The specific anatomy of a patient’s coronary circulation plays a role. Do they have right or left dominant circulations?
    • Right dominant circulation is when the posterior wall of the left ventricle receives blood supply from the right coronary artery. Left is the reverse.
  • The site of the occlusion is important as well. In descending order of frequency of occlusion are the LAD, RCA, LCX, and LCA. The LCA is extremely rare. Distal vs proximal occlusion will also be important.
    • Occlusion of the RCA = posterior inferior myocardial infarction.
    • Occlusion of the LAD = anteroseptal infarction.
    • Most infarctions involve the interventricular septum in one way or another.
    • Occlusion of the LCX =  lateral wall infarction
    • Occlusion of the LCA = massive anterolateral infarction
  • The degree of collateral circulation is important in limiting the extent of an infarction.
  • The duration of ischemia is also important in determining the extent of infarction.
• The course of an infarct is as follows:
  • In the first 12 hours of an infarct there are no visible findings upon autopsy.
    • The only way to see the infarction is to paint transverse sections the heart with triphenyl tetrazolium chloride. This chemical reacts with viable dehydrogenases (from previously living tissue) and turn the heart dark brick red. Areas of infarction will not react, leaving that region pale.
  • From 12-24 hours the region will grossly look pale due to early coagulative necrosis. There may be some mottling due to ruptured capillaries.
    • Coagulative necrosis is the hallmark of ischemia
    • Upon histological examination one can see intense eosinophilia and loss of cross-striation in the heart muscle. There is pyknosis, karyorrhexis, and karyolysis and absence of nuclei. Early inflammatory cells (neutrophils) can be seen.
    • Lipofuscin can be seen.
    • Contraction band necrosis occurs when a myofibril is hypercontracted as it dies. This is due to leaky cell membranes allowing calcium into the cell and causing extreme contraction.
  • From 24-72 hours neutrophils give way to macrophages, there is increasing pallor and softness of the tissue because coagulative necrosis has fully developed.
  • In three to 14 days the macrophages have taken over entirely and now phagocytize necrotic tissue making way for new collagenous granuloma material to be laid down.
    • Granulation tissue is very vascular at the beginning so budding capillaries will be seen at first.
    • This time is critical for the patient because the infarcted wall is at its weakest at this point and may rupture.
    • This will develop into a dense collagenous scar in 8 weeks or so.
• Complications from Acute myocardial infarction are numerous. So you aren’t out of the woods even if you survive your Acute myocardial infarction.
  • Many of the complications occur during the weakest time (3-14 days).
    • Rupture will lead to hemopericardium and cardiac tamponade. This is a medical emergency that must be treated immediately or death will rapidly follow.
    • If the infarct involves the septum (as it frequently does) this can rupture as well creating a left-to-right shunt in the heart (pressures are higher on the left so blood is forced to the right.
    • Papillary muscle can rupture as well, causing mitral valve insufficiency which we will talk about next week.
  • A mural thrombus can develop over the area of infarction. These thrombi can break off and move distally to areas like the brain, causing stroke.
  • A ventricular aneurysm is a very late complication of Acute myocardial infarction.
    • This occurs once collagenous scar tissue has formed.
    • Collagen is rigid but not elastic. It can stretch and stretch creating a bubble in the ventricular wall – aneurysm. Mural thrombi can develop here as well.
  • Arrythmias are the most common problem of those that survive Acute myocardial infarctions.

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