Ischemic Heart Disease

1
Ischemic Heart Disease

• 80 of deaths in the United States by heart
  disease and 30 of total mortality
• Mortality from IHD declined in the United States
  by 40 in the past 20 years

2
IHD Pathogenesis

• Imbalance between myocardial blood flow and the
  metabolic demands of the myocardium
• Coronary artery perfusion pressure differential
  between the ostia (aortic diastolic) and coronary
  sinus (right atrial)

3
Reduction in Coronary Flow

• Decreased aortic diastolic pressure
• Increased intraventricular pressure
• Coronary artery stenosis
• Aortic valve stenosis
• Increased right atrial pressure

4
Coronary Artery Stenosis

• Fixed coronary stenosis
• Acute Plaque change
• Coronary artery thrombosis
• Vasocontriction

5
Coronary Artery Distribution

• LAD (40-50) - anterior wall LV, apex, anterior
  IV septum
• Right (30-40) - posterior wall LV, posterior IV
  septum
• Left circumflex (15-20) - lateral wall LV

6
Increased Myocardial Demands

• Tachycardia
• Hypertrophy
• Hypermetabolism
• Hyperthyroidism
• Drugs

7
Availability of Oxygen in Blood

• Anemia
• Carboxyhemoglobin
• Pulmonary disease
• Right to left shunts

8
Angina Pectoris

• Paroxysmal attacks of chest pain
• Substernal or precordial
• Myocardial ischemia

9
Stable Angina

• Pain related to exertion
• Relieved by rest or vasodilators
• Subendocardial ischemia
• ST-segment depression

10
Variant Angina

• Classically occurs at rest
• Reversible spasm
• ST-segment elevation or depression

11
Unstable Angina

• Prolonged pain or pain at rest
• ST-segment depression

12
Sudden Cardiac Death

• Unexpected death within one hour of cardiac event
• 300,000-400,000 persons per year
• Usually high grade coronary stenosis
• Ventricular electrical instability

13
Myocardial Infarction

• Occlusive intracoronary thrombus
• Vasospasm and platelet aggregation
• Emboli from left sided mural thrombus or
  vegetative endocarditis

14
Coronary artery with thrombus
15
Subendocardial Infarct

• Multifocal areas of necrosis confined to inner
  1/3-1/2 of LV wall
• Infarct evolution different than transmural
  infarct

16
Transmural Infarct

• Endocardium to epicardium
• Usually involving LV anterior and posterior free
  wall or septum with extension into RV wall in
  15-30 of cases

17
RRecent Co
Recent transmural infarct
18
MI Early (0-2 hours)

• Electron microscopy shows mitochondrial matrix
  clearing, relaxation of contractile proteins,
  nuclear chromatin margination
• Decreased glycogen, dehydrogenases, oxidases,
  phosphorylases and potassium
• Increased sodium and calcium

19
Mitochondrion with ischemia in an early infarct
20
MI - Microscopic Appearance

• 1-3 hrs - Wavy fibers
• 2-3 hrs - Tetrazolium dye staining defect
• 4-12 hrs - Coagulation necrosis
• 18-24 hrs - Pyknosis, contraction bands
• 24-72 hrs - Neutrophils, loss of striations
• 3-7 days - Macrophages and fibrosis
• 7 weeks and beyond - Fibrosis

21
Contraction bands in an early infarct. They are
dark pink, and consist of greatly contracted,
ineffective actin and myosin fibrils.
22
Wavy fibers are another sign of an early infarct.
23
Loss of nuclear basophilia in early infarct. Some
contraction bands also present.
24
Coagulative necrosis (24h after infarct)
25
Coagulative necrosis and a few inflammatory cells
26
Coagulative necrosis, interstitial bleeding, and
a few inflammatory cells.
27
Coagulative necrosis plus many neutrophils (2-3
day old infarct).
28
Coagulative necrosis with neutrophils and nuclear
debris (2-3 day old infarct).
29
Infarct with numerous macrophages (slightly
older, 7 days).
30
Macrophages and granulation tissue ( 10-day-old
infarct)
31
Mostly macrophages and granulation tissue. Note
the hemosiderin (brown). 10-14-day-old infarct.
32
MI - Gross Appearance

• 18-24 hrs - Pallor
• 24-72 hrs - Pallor and hyperemia
• 3-7 days - Hyperemic border with central
  yellowing
• 10-21 days - Maximally yellow with soft vascular
  margins
• 7 weeks and beyond - White fibrosis

33
Pale area in recent infarct
34
Pale area in recent infarct
35
Two areas of pale, recent infarction
36
Large, pale areas of infarction, including
papillary muscle that ruptured
37
Old infarct. It is a firm scar
38
Old infarct with scar and organizing thrombus.
39
LV aneurysm with thrombus.
40
MI - Complications

• None 10-20
• Arrhythmias 75-95
• CHF, pulmonary edema 60
• Cardiogenic shock 10-15
• Pericarditis 50
• Mural thrombosis 40
• Rupture ventricle or papillary muscle 4-8

41
Ruptured papillary muscle in recent MI.
42
Mitral valve
Recent infarct with mural thrombus.
43
Recent infarct with perforation
44
Another Rupture in an acute MI. This typically
happens 3-5 days after the infarct.
45
Recent infarct with rupture (arrow).
46
Recent infarct with mural thrombus (arrow to
thrombus).
47
Infarct with mural thrombus
48
Recent infarct with huge mural thrombus
49
Chronic Ischemic Heart Disease

• LV Dilatation, atherosclerosis, focal scars
• Myocyte hypertrophy, myocytolysis, focal small
  interstitial scars
• Slow progressive heart failure with or without
  previous MI or angina
• 40 of mortality in IHD
• Ischemic cardiomyopathy

50
Congestive failure in chronic ischemic heart
disease
51
Diffuse fibrosis in chronic ischemic heart
disease. There is also myocyte hypertrophy and a
decrease in small vessels.
52
MI - Therapeutic Modalities

• Infarct modification by thrombolysis
• PTCA - balloon dilatation
• Directional atherectomy
• Coronary bypass surgery

53
Coronary artery bypass graft (saphenous).
54
Coronary artery bypass graft (Dacron).
55
Creatine Kinase - CK Isoenzyme
Tissue BB MB MM
Muscle 0 2 98
Heart 0 15-40 60-85
Brain 90 0 10
Bladder 95 0 5
Bowel 100 0 0
56
Lactate Dehydrogenase - LD
LD-1 HHHH 19-9 Heart, RBC Kidney
LD-2 HHHM 25-30 Kidney, RBC
LD-3 HHMM 16-31 Lung
LD-4 HMMM 2-9 Muscle
LD-5 MMMM 2-17 Liver, Muscle
57
Lactate Dehydrogenase - LD

• Normally LD-1/LD-2 less than 1.0
• LD-2 most abundant, LD-1, LD-3, LD-4, LD-5 least
  abundant

58
Temporal Sequence of Enzymes
Enzyme Appear Peak Duration
CK-MB 2-8 hr 6-8 hr 1-3 day
Total CK 4-8 hr 18-24 hr 1-3 day
LD-1 4-8 hr 12-24 hr 5-14 day
Total LD 12-24 hr 48-96 hr 5-14 day
AST 6-8 hr 24-48 hr 3-5 day
59
Troponin for Acute MI

• Troponin - regulatory protein release when
  cardiac cell necrosis occurs
• Serum levels within 4 hours of AMI
• Troponin I - inhibits myosin ATPase
• Troponin T - binds to tropomyosin
• Troponin C - binds to calcium

60
Hyperhomocysteinemia

• Homocysteine levels are often elevated by 15-40
  in patients with coronary artery disease
• Normal levels are less than 16 micromols/liter
• Treated with folic acid, pyridoxine or vitamin B12

61
BNP - Brain Natriuretic Peptide

• Neurohormone produced in the LV in response to
  pressure and volume
• Up-regulated in patients with heart failure
• Resulting in vasodilation and diuresis/natriuresis
  
• Elevated BNP - hypertension, tachycardia,
  cardiomyopathy, MI, mitral and aortic stenosis

62
BNP Brain Natriuretic Peptide

• Detect asymptomatic CHF
• Objectively assess heart failure severity -
  correlating with NYHA classification
• Monitor therapy and disease progression
• Predict 30-day and 10-month mortality after AMI

63
BNP - Brain Natriuretic Peptide

• BNP lt 100 pg/ml - no heart failure
• BNP 100-300 pg/ml - heart failure present
• BNP 300-600 pg/ml - mild heart failure
• BNP 600-1000 pg/ml - moderate heart failure
• BNP gt 1000 pg/ml - severe heart failure

64
hs-C Reactive Protein(hs high sensitivity)

• Independent risk factor for first MI and ischemic
  stroke in healthy people
• Not associated with risk of venous thrombosis
• Short term risk factor in patients with unstable
  angina and long term risk factor in patients for
  MI and ischemic stroke occurring six or more
  years later

65
hs-C Reactive Protein

• Inflammation mediated by a chronic process and
  excludes undetected acute illness
• Aspirin and other antiinflammatory agents may
  have a role in preventing cardiovascular disease
• May predict patients who will benefit from
  aspirin or other antiinflammatory therapy