127 Ischemic Heart Disease

Question 1

Anterior view of coronary arteries

Answer 1

• nOriginate from aorta in or above sinus of Valsalva
• nSubepicardial location
• nLeft bifurcates – LAD, LC
• nRight is dominant artery – Posterior descending artery (90%)
• nLAD – anterior LV, anterior septum
• nLC – lateral LV
• nRC – RV, posterior LV, posterior septum

Question 2

Ischemia/reperfusion injury

Answer 2

• Ischemia=The mismatch between oxygen supply (coronary blood flow and oxygen extraction) and the oxygen demand (determined by the workload, wall stress, and inotropic state of the heart)
• Reperfusion injury=Reversible or irreversible injury caused by stunning, arrhythmia, microvascular injury and irreversible cell damage (necrosis/apoptosis)

Question 3

Ischemic Heart Disease

Answer 3

• nMost common disease of the heart
• nSecond leading cause of death in US (750k/yr)
• n90% associated with atherosclerosis
• nPresents as:
  
  • nAngina pectoris
  • nChronic ischemic heart disease
  • nMyocardial infarct
  • nSudden death

Question 4

Sudden Cardiac Death

Answer 4

Definitions:

• Unexpected death from cardiac causes early after symptom onset (usually within 1 hour) or without the onset of symptoms
• Strikes 300,000 to 400,000 individuals annually in US; accounts for 50% of all cardiac deaths
• Often the first clinical manifestation of IHD
• Coronary atherosclerotic heart disease is the most common structural abnormality associated with SCD
  
  • Up to 80% of all SCD’s in the US are due to consequences of coronary atherosclerosis
• Cardiomyopathies account for 10-15% of SCD’s
• Remaining diverse etiologies account for only 5-10% of SCD’s

Question 5

Risk factors IHD

Answer 5

Question 6

Cardiac Ischemia

Answer 6

• nATP loss begins in seconds
  
  • n50% depletion in 10 min
  • n90% depletion in 40 min
• nContractility diminished less than 2 min
• nIrreversible cell injury in 20-40 minutes
• nMicrovascular injury in 1 hour

Question 7

Pathology/progression of MI:

Answer 7

• 1-4 hours – usually not apparent; wavy fiber change
  
  • non contracting myocardium, 1st sign of ischemia, could be reversible up to 40 minutes
• 4-24 hours – pale; swelling, coagulation necrosis, contraction band necrosis, PMNs
  
  • hydropic swelling (ions move from ECM into cells and H2O follows to swell)
  • coag necrosis: nuclei dissapear
  • band necrosis: Ca+2 rushes in and Zlines condense, from reperfusion injury
• 3-5 days – mottled, yellow, red; hemorrhage, heavy PMNs
  
  • danger time for reperfusion injury, maximal softening of tissue occurs, no repair happens yet, inflammatory cells and macrophages arrive
• n5-7 days – mottled; macrophages, fibroblasts
• n2-4 weeks – mottled; granulation tissue
• n5-8 weeks - scarring

Question 8

Pathogenesis of acute MI (big picture)

Answer 8

• n1 Stenosing atherosclerosis of the coronary arteries
• n2 Platelet aggregation with formation of intraluminal thrombus
• n3 Coronary vasospasm
• n4 Nonatherogenic coronary disease (trauma, vasculitis, etc.)
• n5 Hemodynamic derangements

Question 9

Factors affecting infarct size and location

Answer 9

• nSpecific coronary artery affected and anatomy of individual
• nSize of vascular bed affected (proximal vs distal)
• nTime course of obstruction
• nDuration of occlusion
• nOxygen needs of myocardium at risk
• nExtent of collaterals
• nExtent of spasm
• nBlood pressure, heart rate and rhythm

Question 10

Possible complications of acute MI

Answer 10

Question 11

Why, after years of indolent growth, does atherosclerosis suddenly become complicated by life-threatening thrombosis?

Answer 11

• Answer: Plaque disruption with superimposed thrombosis
• The composition and vulnerability of plaque rather than its volume or the consequent severity of stenosis are determinants of MI.
  
  • Mature plaques typically consist of two main components: soft, lipid-rich atheromatous “gruel” and hard, collagen-rich sclerotic tissue.
• Lipid-rich and soft plaques are more dangerous than collagen-rich and hard plaques because they are more unstable and rupture-prone and highly thrombogenic after disruption.

Question 12

Concentric vs eccentric coronary artery stenosis

Answer 12

concentric: usually more stable

Question 13

Plaque characteristics

cracked

Answer 13

• The usually less voluminous atheromatous component is the more dangerous component, because the soft atheromatous gruel destabilizes plaques, making them vulnerable to rupture, whereby the highly thrombogenic gruel is exposed to the flowing blood, leading to thrombosis—a potentially life-threatening event.
• Serial angiographic studies indicate that the more obstructive a plaque is, the more frequently it progresses to coronary occlusion and/or gives rise to myocardial infarction.
• However, although an individual severe stenosis becomes occluded more frequently than did a less severe stenosis, less obstructive plaques (<80% stenosis at baseline) give rise to more occlusions than do the severely obstructive plaques because of their much greater number.
• Thus, coronary occlusion and myocardial infarction most frequently evolve from mild to moderate stenoses.
• •Age, male sex, hypercholesterolemia, hypertension, smoking, and diabetes correlate with the coronary plaque burden (extent of “plaquing”) found at autopsy
• •Plaques containing a soft atheromatous core are unstable and may rupture. Such disrupted plaques are found beneath about 75% of the thrombi responsible for acute coronary syndromes.
• •Vulnerability to rupture depends on (1) size and consistency of the atheromatous core, (2) thickness and collagen content of the fibrous cap covering the core, (3) inflammation within the cap, and (4) cap “fatigue.”
• •Coronary plaques are constantly stressed by a variety of mechanical and hemodynamic forces that may precipitate or “trigger” disruption of vulnerable plaques.

Question 14

MI Tx: stenting

Answer 14

angioplasty causes tearing and usually when effectie causes dissection, stents are thrombogenic

Question 15

MI Tx: Saphenous vein graft

Answer 15

Complication: vein grafts undergo arterialization

Question 16

MI Tx: Allograft

Answer 16

can loose heart transplanted due to diffuse arteriosclerosis

• nCAV is a major cause of death following cardiac transplantation as soon as 1 year following engraftment
• nMany allograft transplants fail to reinervate. Typical anginal sx uncommon hence clinical presentation often arrhythmias, CHF, or sudden death
• nCAV affects intramural and epicardial coronary arteries and veins.
• nThought to result from repeated endothelial injury followed by repair response
• nInciting agents: autoimmune response to allograft; CMV; ischemia reperfusion injury; baseline HLD, HTN; role of MHC complex incompatibility still unclear
• nEarly after transplant: diffuse fibrous intimal thickening or a vasculitis
• nLate: focal atherosclerotic plaques, diffuse intimal thickening, or a mixture of both
• nSmaller branches are often occluded before the larger epicardial arteries, resulting in small, stellate infarcts
• nmedia of the vessel is rarely thickened and sometimes becomes narrower
• ncellular infiltrate of intimal proliferative lesions consists of modified smooth muscle cells, macrophages/monocytes, and T lymphocytes