Ischemic Heart Disease IHD is caused by myocardial ischemia due to Imbalance between the myocardial oxygen demand and supply from the coronary arteries. Majority of cases due to Reduction in coronary artery blood flow caused by Obstructive atherosclerotic disease. IHD is also known as Coronary artery disease

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Ischemic Heart Disease
IHD

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Ischemic Heart Disease
• IHD is caused by myocardial ischemia due to
– Imbalance between the myocardial oxygen
demand and supply from the coronary
arteries.
• Majority of cases due to
– Reduction in coronary artery blood flow caused
by
• Obstructive atherosclerotic disease.
• IHD is also known as Coronary artery disease

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Ischemic Heart Disease
• Factor responsible for myocardial blood supply:
– Coronary artery blood flow:
• Most important factor
• Provide oxygen to cardiac muscle
• Coronary arteries fill in diastole.
• Sub endocardium gets the least amount of
oxygen from coronary arteries.
• Increasing HR decreases time for filling of
coronary arteries.

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Ischemic Heart Disease
• The coronaries:
1. Left anterior descending ( LAD) coronary
artery:
2. Right coronary artery:
3. Left circumflex coronary artery:
• Left anterior descending ( LAD) coronary
artery:
– Supplies:
• entire anterior portion of LV
• anterior 2/3rd of IVS
– Accounts for 40-50% of coronary artery
thrombosis.

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• Right coronary artery:
– Supplies:
• the entire posterior and inferior part of the
LV
• Posterior 1/3rd of IVS
• the entire RV
• posteromedial papillary muscle in LV
• Both arterioventricular and sinoatrial node
– Accounts for 30% to 40% of coronary artery
thromboses.
• Left circumflex coronary artery:
– Supplies the lateral wall of the LV
– Accounts for 15% to 20% of coronary artery
thromboses.

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CA occlusion
Infarct Zone

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Ischemic Heart Disease
• Epidemiology:
– Major cause of death in US
• (500,000 deaths/year)
– IHD is more common in men
– Peaks in men after age 60 and women
after age 70.
– Death rate has fallen by approx. 50%
since 1963

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Ischemic Heart Disease
• Four types of Ischemic Heart Diseases:
1. Angina pectoris (Most common)
2. Acute Myocardial infarction (AMI)
3. Chronic IHD
4. Sudden cardiac death (SCD)

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Ischemic Heart Disease
• Risk factors:
– Age:
• Most important overall risk factor
• Men 45 yrs old and up and women 55 years old and
up
– Family history of premature CAD or stroke
– Lipid abnormalities:
• LDL (bad cholesterol) above 160 mg/dL
– Oxidized LDL poses an even greater risk for
CAD than native LDL
– Vitamin E neutralizes oxidized LDL
• HDL (good cholesterol) below 35 mg/dL
– Enhances atherosclerosis

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Ischemic Heart Disease
• Smoking tobacco:
– Enhances atherosclerosis – chemicals in smoke
damage endothelial cells.
• Hypertension:
– With blood pressure >140/90 mmHg
– CAD is MC COD in hypertension
• Diabetes mellitus:
– Enhances atherosclerosis
– CAD is MC COD in diabetes

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Angina pectoris
• Literally means chest pain
• Is intermittent chest pain caused by
transient reversible myocardial ischemia.
• Ischemia insufficient to cause death of
myocardium
• Three Types:
1. Stable angina
2. Prinzmetal’s angina (Variant angina)
3. Unstable (crescendo) angina

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Stable angina
• Most common variant
• Recurrent episodes of chest pain brought on by
increased physical activity.
• Causes:
– Severe fixed coronary artery atherosclerosis
( >75%).
• With this narrowing, oxygen supply to heart
is sufficient during rest, but becomes
insufficient on increased demand.
• Pathogenesis:
– Subendocardial ischemia due to decreased
coronary artery blood flow.

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Stable angina
• Clinical features:
– Sudden onset of exercise induced substernal chest
pain lasting 30 seconds to 30 minutes.
– Pain:
• Nature: Described as crushing or squeezing
• Radiation: to left arm or to left jaw
• Relieved by: rest (reducing the demand) or
nitroglycerin
• Diagnosis:
– Stress test:
• shows ST segment depression
– indicating subendocardial ischemia.
– Confirmed by arteriography

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Prinzmetal’s angina
• Angina occuring at rest due to coronary artery
spasm.
• Pathogenesis:
– Intermittent coronary artery vasospasm at
rest.
– Vasoconstriction due to platelet thromboxane
A2.
• Clinical findings:
– Stress ECG reveals ST elevation
• representing transmural ischemia
– Responds to nitoglycerin and calcium channel
blocker (vasodilator)

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Unstable (crescendo) angina
• Characterized by:
– Frequent bouts of chest pain at rest or with
minimal exertion.
– May progress to acute MI therefore, aka
• Pre-infarction angina
• Associated with:
– Disrupted plaques with superimposed partial
thrombosis.
– Severe, fixed, multivessel atherosclerotic
disease
• Diagnosis:
– Stress ECG is unsafe

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Angina pectoris
• Revascularization procedures:
1. Percutaneous transluminal coronary
angioplasty (PTCA) and stenting
2. Coronary artery bypass graft (CABG)

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Revascularization procedures
• Percutaneous transluminal coronary angioplasty
(PTCA):
– Balloon angioplasty dilates and ruptures the
atheromatous plaque
• Problem with re-stenosis
• Intracoronary stents:
– Decreases the rate of re-stenosis
– MC early complication is a localized
dissection with thrombosis

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Revascularization procedures
• Coronary artery bypass graft (CABG):
– Used for multi-vessel coronary artery
atherosclerosis
1. Internal mammary artery graft
• Best graft patency after 10 years
2. Saphenous vein graft
• Arterialization of the vessel, fibrosis and
occlusion common after 10 years.

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Chronic Ischemic Heart disease
• Repeated infarcts result in replacement of
cardiac tissue by noncontractile fibrous tissue.
– Resulting in progressive CHF due to systolic
dysfunction.
• Clinical findings:
– Biventricular CHF (MC cause of Death)
– Arrythmias

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Sudden cardiac death
• Unexpected death within 1 hour due to cardiac
causes
• In many patients SCD is the first clinical
manifestation of IHD.
• Pathogenesis:
– Severe atherosclerosis underlies most cases.
– Ultimate mechanisms:
• Lethal arrhythmia ( ventricular arrhythmia)
triggered by acute ischemia without infarction.
• Absence of occlusive thrombus* (>80%) of cases.
• Prognosis in those prone to develop SCD improved by
automatic cardioverter defibrillators.

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Myocardial infarction
• Definition:
– Popularly called Heart Attack
– is necrosis of heart muscles resulting from
ischemia
• Due to occlusion of one/more of the three
main trunks of the coronary arteries.
• Major underlying cause of MI is Atherosclerosis.

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Myocardial infarction
• Pathogenesis: Sequence of events:
– Sudden disruption of an atheromatous plaque
– Exposed subendothelial collagen or thrombogenic
necrotic material
– Platelet adhesion , aggregation, activation and
secretion causes
• Eventual formation of a platelet & fibrin
thrombus.
• Thrombus  Occlusion  Ischemia 
Infarction
• Role of Thromboxane A2:
– Platelet aggregator : Contributes to formation of
platelet thrombus
– Vasoconstrictor: Causes vasospasm of the artery.

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Region of Plaque ruptureLumen occluded by thromAtherosclerotic plaque

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Zone of Infarct
Epicardial FatRight VentricleInterventricular SeptumLeft Ventricle Wall

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Progression of myocardial necrosis
after coronary artery occlusion.

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Progression of myocardial necrosis after coronary artery occlusion.

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• Less common causes of acute MI
– Vasculitis (PAN or Kawasaki disease)
– Cocaine use
– Embolization of plaque material
– Thrombosis syndrome (AT III deficiency,
polycythemia).
Myocardial infarction

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Myocardial infarction
• The coronary vessels involved:
– LAD > RCA > LCxA.
• Most MI located in the left ventricle and
IVS.
• Pure right ventricular infarcts are rare

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Types of myocardial infarction
• Transmural infarction (Q wave infarction)
– Involves the full thickness of the myocardium
– New Q wave develops in an ECG
– Occurs due to occlusive thrombi; are larger ;
and have higher mortality
• Subendocardial infarction (non Q wave
infarction):
– Iinvolves the inner third of the myocardium
– Q waves are absent.
– Occurs due to fixed AS; are smaller; reduced
early mortality; increased risk of reinfarction
& sudden cardiac death

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Myocardial Response to Ischemia
• Within seconds: Switch to Anaerobic glycolysis
for ATP
• Less than 2 min: loss of contractility
• 1 - 10 min: Reversible injury
• 20-40 minutes: irreversible damage
• Reperfusion within 40 min. saves muscle.

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Myocardial Infarction
• Reperfusion: can be achieved by
– thrombolytic therapy (e.g tissue plasminogen
activator, streptokinase)
– Angioplasty with or without stents
• Early reperfusion
– salvages some injured but not necrotic
myocytes.
– Improves short and long term function and
survival
• Reperfusion can also cause
– reperfusion injury and
– Changes in necrotic myocardium

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• Reperfusion histologically alters damaged
myocardial cells:
– Produces contraction band necrosis.
– Contraction bands:
• Seen in irreversibly damaged myocytes.
• Are eosinophilic transverse bands.
• Composed of hypercontracted sarcomeres
• Hyper-contraction of myofibrils in dead
cells due to the influx of Ca2+ .

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Gross and Microscopic findings in acute MI
• During 0 to 24 hrs
– No Gross changes until 24 hrs after MI
– Microscopy:
• Coagulation necrosis without neutrophil
infiltrate within 12 to 24 hrs

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12 to 24 hrs
Coagulation necrosis
Normal

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Gross and Microscopic findings in
acute MI
• During 1-3 days
– Gross:
• shows pallor of infarcted myocardium
– Microscopy:
• Myocyte nuclei and striations disappear
• Infiltration by neutrophils***
• Neutrophils lyse dead myocardial cells

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Pale area of infarction
1-3 days old infarct

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This is normal
myocardium
1-3 days

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1-3 days
Infiltration by
Neutrophils
Lysis of dead cells
1-3 days

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Gross and Microscopic findings in acute MI
• During 4 to 7 days
– Red granulation tissue surrounds area of infarction
– Macrophages begin removal of necrotic debris
– Period of maximal softness
– Time for rupture******
• During 7 to 10 days
– Necrotic area is bright yellow
– Granulation tissue and collagen formation are well
developed
• During 2 months:
– Infarcted tissue replaced by white, patchy,
noncontractile scar tissue

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Red granulation tissue
Area of infarction
4 to 7 days
7 to 10 days

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Granulation tissue formation
7 to 10 days
Scar tissue
2-3 months

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White patchy areas represent fibrosis
2-3 months

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0-24 hrs 1-3 days
4-7 days 7-10 days 2-3 months

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Clinical findings
• Sudden onset of severe retrosternal pain
– Lasts more than 30 -45 minutes
– Not relieved by nitroglycerin
– Radiates down the left arm into the shoulder
or into the jaw or epigastrium.
– Associated with sweating (diaphoresis), anxiety
and hypotension.
• “Silent” Acute MI:
– May occur in elderly and in individuals with DM
– Due to high pain threshold or problems with
nervous system.

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AMI Complications
• Arrhythmias
– Ventricular premature contractions (MC)
– MC COD is ventricular fibrillation
• Frequently associated with cardiogenic shock
• Congestive heart failure:
– Usually occurs within first 24 hours
– If greater than 40% of ventricle infarcted.

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AMI Complications
• Rupture:
– Most common on 3rd to 7th day
• Anterior wall rupture:
– Causes cardiac tamponade
– Associated with thrombosis of the LAD
• Posteromedial papillary muscle rupture:
– Associated with RCA thrombosis
– Acute onset of mitral valve regurgitation and
LHF
• Interventricular septum rupture:
– Associated with thrombosis of LAD
– Produces left to right shunt causing RHF.

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Anterior myocardial rupture
Rupture of the ventricular septum
Rupture papillary muscle

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Hemopericardium

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AMI Complications
• Mural thrombus:
– Most often associated with LAD coronary artery
thrombosis
– Danger of embolization.

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AMI Complications
• Fibrinous pericarditis with or without effusion:
– Days 1-7* of trans-mural acute MI
• Substernal chest pain relieved by leaning
forward
• Precordial friction rub is present.
– Due to increased vessel permeability in
the pericardium.
• Autoimmune pericarditis: (Dressler’s syndrome)
– Develops 6 to 8 weeks* after an MI
– Autoantibodies are directed against pericardial
antigens
– Systemic S/S: Fever. Joint pain and
pericardial friction rub

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Fibrinous pericarditis

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AMI Complications
• Ventricular aneurysm:
– Clinically recognized within 4 to 8 weeks
– Precordial bulge during systole
• Blood enters the aneurysm causing anterior
chest wall movement.
– Complications due to aneurysms:
• CHF due to lack of contractile tissue
• Danger of embolization of clot material
• Rupture is uncommon****

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Laboratory diagnosis of Acute MI
• For confirming AMI:
1. Electrocardiogram (ECG) and
2. Cardiac enzymes
• Are released when myocytes are damaged
1. Creatine kinase and isoenzyme CK-MB
2. Troponin
3. Lactate dehydrogenase and its
isoenzymes
4. Aspartate aminotransferase (AST)

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Laboratory Diagnosis of Acute MI
• Creatine Kinase isoenzyme MB (CK-MB):
– Appears within 4-8 hours
– Peaks in 24 hrs
– Disappears in 1.5-3 days
– Reappearance of CK MB>3 days is a
reinfarction.
• Cardiac Troponins I (cTnI) and T (cTnT):
– Appear within 3-6 hours
– Peak at 24 hours
– Disappear within 7-10 days*
– Are gold standard for diagnosis of acute MI
• More specific for myocardial tissue than CK
–MB and last longer

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• Lactate dehydrogenase (LDH)1-2 “flip”:
– LDH2 is normally > LDh1
• In acute MI LDH1 in cardiac muscle is
released causing the “flip”
– LDH1-2
• Appears within 10 hours;
• peaks at 2-3 days;
• disappears within 7 days
• Mainly used to identify MI after 3 days.
Laboratory Diagnosis of Acute MI

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• Correlation of ECG changes with microscopic
changes:
– Inverted T waves:
• Correlates with areas of ischemia.
– Elevated ST segment:
• Correlates with injured myocardial cells.
– New Q waves:
• Correlates with the area of infarction with
cell death.
Laboratory Diagnosis of Acute MI

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Treatment of AMI
• Aims of treatment:
– Relief of pain (Morphine)
– Coronary thrombolysis (tPA)
– Prophylaxis for arryhythmias (lidocaine)
– Low flow oxygen
– Aspirin (reduce risk of thrombosis)
– Reduce afterload ( beta blockers)
– Reudce preload (diuretics)