Define Ischemic Heart Disease
Imbalance between supply and demand for oxygen and nutrients and removal of metabolites
What is the leading cause of death and disability in the USA?
Ischemic Heart Disease (IHD)
What most commonly causes IHD?
≥ 90%: reduced coronary blood flow due to atherosclerotic narrowing
Causes of decreased blood flow?
- Fixed atherosclerotic narrowing
- Acute plaque change
- Thrombosis overlying ruptured plaque
What coronary arteries are most commonly affected by fixed obstruction?
First several centimeters of the LAD, left circumflex, and entire length or right coronary artery
How does the degree or anatomic narrowing/occlusion lead to different types of ischemia?
Narrowing of >70% causes symptomatic ischemia with exercise
>90% stenosis causes ischemia at rest
What are risks associated with acute plaque change?
Ruptures/fissures/ulcers that can expose underlying thrombogenic substances
Hemorrhage into atheroma
What are some intrinsic factors that influence acute plaque change?
Large areas of foam cells
Thin fibrous cap
Most dangerous leasions are the moderately stenoic, lipid rich atheromas (soft core)
Few smooth muscle cells
What are some extrinsic factors that contribute to acute plaque change?
What is coronary thrombosis?
What are the problems associated with total occlusion vs. incomplete occlusion?
Coronary thrombosis - partial or total occlusion superimposed on a partially stenotic plaque
Total occlusion can cause acute transmural MI or sudden death
Incomplete occlusion (mural thrombus) can lead to unstable angina, acute subendocardial infarction, or sudden death
What can stimulate vasoconstriction?
- Adrenergic agonists in circulation
- Locally released platelet contents
- Endothelial dysfunction leading to impaired secretion of endothelial relaxing factors
- Mediators released from mast cells
Four basic syndromes of IHD?
- Angina pectoris
- Myocardial infarction
- Chronic ischemic heart disease
- Sudden cardiac death
What is Angina Pectoris?
Paroxysmal and recurrent attacks of chest pain caused by transient myocardial ischemia (15 seconds to 15 minutes) - no necrosis
What are the three patterns or Angina Pectoris presentation?
Stable - produced by physical activity or emotional excitement - attributed to chronic stenosis coronary aortic sinus
Prinzmetal - due to coronary artery spasm, at rest
Unstable - occurs with progressively increasing frequency and progressively less effort - often at rest and of prolonged duration
What is often the event that induces Unstable angina pectoris
Induced by disruption of plaque with superimposed partial thrombosis (often a prodrome of acute MI)
What is a Myocardial Infarction?
Death of cardiac muscle due to ischemia
What are risk factors associated with MI?
What are the most common causes of MI?
- Risk factors: increasing age and predisposition to atherosclerosis
- 90% - acute plaque change - thrombosis and occlusion of coronary artery
- 10% - vasospasm, emboli or unexplained
What are the characteristics of a Transmural MI?
- Full thickness of ventricular wall
- Confined to distribution of one vessel
- Fixed coronary obstruction with superimposed acute plaque change and complete obstructive thrombosis
What are the characteristics of a Subendocardial MI?
- Necrosis limited to inner 1/3
- May extend laterally beyond perfusion of one vessel
- Fixed coronary obstruction with acute plaque change but with non-occlusive thrombus or lysis of thrombus or hypotension
What is the myocardial response to...
60 seconds of ischemia?
20-40 minutes of ischemia?
Early thrombolytic therapy (3-4 hours) after ischemia?
Loss of blood supply?
60 seconds of ischemia: loss of contractility
20-40 minutes of ischemia: irreversible damage
Early thrombolytic therapy (3-4 hours) after ischemia: Reperfusion and limited size of infarct
Loss of blood supply? reversible damage in early stages
* Arrhythmias can lead to sudden death
Which area of the blood vessel (in relation to the obstruction) is first to necrose?
The area farthest away from the obstruction
Frequency of involvement of coronary arteries in MI?
LAD: most often (40-50%)
RCA: next most often (30-40%)
LCA (left circumflex): Least common (15-20%)
Myocardial infarction: Gross morphology
<12 hours: pale areas 2-3 hours post occurance
12-24 hours: Dark red-blue mottling (stagnant blood)
1-14 days: early: sharply defined yellow-tan area; late: hyperemic peripheral zone (increased blood flow)
>2 weeks: Gray-white scar begins to form
Histology of MI
12 hours - 7 days:
7 -14 days:
4-12 hours: wavy fibers
12 hours - 7 days: coagulative necrosis (neutrophils, lack of nuclei, macrophages at border)
7 -14 days: Granulation tissue well established
>2 weeks: Progressively more collagen deposition - eventually dense fibrous scar
Reperfusion injury associated with acute MI usually occurs after what treatments? Prevention of necrosis occurs with reperfusion within __ minutes
Thrombolysis, balloon angioplasty, or bypass grafts
Possible causes of reperfusion injury
- Oxygen free radicals released from leukocytes
- Microvascular injury causes hemorrhage and endothelial swelling that occludes capillaries
- Platelet and complement activation
*Microscopically: Necrosis with contraction bands due to influx of calcium
How do you diagnose MI?
Rapid weak pulse, dyspnea due to pulmonary edema
Lab evaluation of cardiac enzymes, C-reactive protein
Approximately 10-15% without symptoms
What are some potential complications of MI?
Cardiogenic shock (pump failure) with damage to 40% or more
Myocardial rupture (shunts)
What types of mycocardial rupture are associated with MI?
Free wall - hemopericardium, tamponade, aneurysm
Ventricular septum - Lt to Rt shunt
Papillary muscle due to mitral regurgitation
What are some later complications of MI?
Progressive heart failure
Papillary muscle dysfunction secondary to scarring
Long term prognosis of acute MI depends on...
Quality of left ventricular function and the extent of vascular obstruction
What makes chronic IHD different than acute IHD?
Usually in elderly patients with progressive heart failure due to ischemic myocardial damage - myocardial dysfunction
What is the morphology associated with Chronic IHD?
Heart is enlarged and heavy with left ventricular hypertrophy and dilation, coronary atherosclerosis, scars, subendocardial myocyte vacuolization
Sudden Cardiac Death is most often due to...
IHD and its first manifestation (80-90%)