ISCHEMIC HEART DISEASE

1. Ischemic
Heart
Disease

2. • ISCHEMIC HEART DISEASE
• Introduction
• Pathogenesis
• ANGINA PECTORIS
• MYOCARDIAL INFARCTION
• Introduction
• Epidemiology
• Etiologies and Risk factors
• Pathogenesis
• Morphological changes
• Symptoms
• Complications
• CHRONIC IHD
• DIAGNOSIS

3. INTRODUCTION TO IHD
• Ischemic heart disease (IHD) represents a group of pathophysiologically related
syndromes resulting from myocardial ischemia — an imbalance between myocardial
perfusion and cardiac demand for oxygenated blood.
o Ischemia limits tissue oxygenation (and therefore ATP generation) as well as
availability of nutrients and removal of metabolic wastes.
• >90% myocardial ischemia results from reduced blood flow due to obstructive
atherosclerotic lesions in the EPICARDIAL CORONARY ARTERY.
• IHD usually is synonymous with coronary artery disease (CAD).

4. Causes of IHD
The syndromes of
IHD are the late
manifestations of
coronary
atherosclerosis
(beginning even in
childhood or
adolescence).
90%
10%
• Coronary emboli,
• Myocardial vessel
inflammation,
• Vascular spasm,
• Conditions where
otherwise modest
vascular occlusions
may become
consequential
o Myocardial
hypertrophy,
o Tachycardia
o Hypoxemia, and
o Systemic
hypotension (e.g.,
shock).

5. • ISCHEMIC HEART DISEASE
• Introduction
• Pathogenesis
• ANGINA PECTORIS
• MYOCARDIAL INFARCTION
• Introduction
• Epidemiology
• Etiologies and Risk factors
• Pathogenesis
• Morphological changes
• Symptoms
• Complications
• CHRONIC IHD
• DIAGNOSIS

6. Atherosclerosis of Epicardial coronary artery
Progressive narrowing of lumen
Stenosis
“FIXED OBSTRUCTION”
Acute plaque erosion
or rupture
THROMBOSIS
Compromises blood flow
>70% occlusion Significant CAD (precipitated by exercise)
-90% occlusion Significant CAD even at rest.
STABLE ATHEROSCLEROTIC PLAQUE

7. STABLE ATHEROSCLEROTIC PLAQUE
Unpredictable and
abrupt conversion to
Rupture, or Superficial erosion, or
Ulceration, or Fissuring, or Deep
Hemorrhage
Partially life threatening ATHEROTHROMBOTIC plaque
SUPERIMPOSED THROMBUS
Partially or Completely occludes the artery
IHD

8. Ischemic Heart Disease
No plaque
disruption
STABLE
ANGINA
Plaque
disruption
Thrombosis
+/- Vasoconstriction
+/- Emboli
UNSTABLE
ANGINA
Acute Plaque
Changes
Abrupt
Thrombotic
Occlusion
Myocardial
Necrosis
MI
Regional
myocardial
ischemia
Fatal Ventricular
Arrhythmia
SUDDEN
CARDIAC DEATH

9. • ISCHEMIC HEART DISEASE
• Introduction
• Pathogenesis
• ANGINA PECTORIS
• MYOCARDIAL INFARCTION
• Introduction
• Epidemiology
• Etiologies and Risk factors
• Pathogenesis
• Morphological changes
• Symptoms
• Complications
• CHRONIC IHD
• DIAGNOSIS

10. ANGINA PECTORIS (Chest Pain)
• Angina pectoris is characterized by
paroxysmal and usually recurrent attacks
of substernal or precordial chest discomfort
caused by transient (15 seconds to 15
minutes) myocardial ischemia that is
insufficient to induce myocyte necrosis.
• The pain is described as constricting,
squeezing, choking, or knifelike.
- probably is a consequence of the
ischemia-induced release of adenosine,
bradykinin, and other molecules that
stimulate the vagal and afferent nerves.

11. Myocardial
demand
Myocardial
perfusion
Coronary pathology
Stable
Angina
Prinzmetal
variant
angina
Unstable
Angina

12. STABLE ANGINA
• ‘Typical Angina Pectoris’.
• MC form.
• It is caused by an imbalance in coronary perfusion (due to chronic stenosing coronary
atherosclerosis) relative to myocardial demand, such as that produced by physical activity,
emotional excitement, or any other cause of increased cardiac workload.
• Usually relieved by rest (which decreases demand) or administering nitroglycerin, a strong
vasodilator (which increases perfusion).

13. PRINZMETAL VARIANT ANGINA
• uncommon from of episodic myocardial ischemia - caused by coronary artery spasm.
• May have significant coronary atherosclerosis, but the anginal attacks are unrelated to
physical activity, heart rate, or blood pressure.
• Can be triggered by alcohol, iced drinks, atrial pacing, cocaine, nicotine and
hyperventilation.
• Responds promptly to vasodilators, such as nitroglycerin and calcium channel blockers.

14. UNSTABLE ANGINA
• “Crescendo Angina”.
• Pattern of increasingly frequent pain, often of prolonged duration, that is precipitated by
progressively lower levels of physical activity or that even occurs at rest.
• Caused by the disruption of an atherosclerotic plaque with superimposed partial (mural)
thrombosis and possibly embolization or vasospasm (or both).
• Unstable angina serves for imminent MI – “Preinfarction Angina”.

15. • ISCHEMIC HEART DISEASE
• Introduction
• Pathogenesis
• ANGINA PECTORIS
• MYOCARDIAL INFARCTION
• Introduction
• Epidemiology
• Etiologies and Risk factors
• Pathogenesis
• Morphological changes
• Symptoms
• Complications
• CHRONIC IHD
• DIAGNOSIS

16. MYOCARDIAL INFARCTION
• “heart attack,”
• Due to necrosis of heart muscle resulting from ischemia.
• It is a diseased condition which is caused by reduced blood flow in a coronary artery due
to atherosclerosis and occlusion of an artery by an embolus or thrombus.
• It is one of the major causes of emergency medical conditions worldwide.

17. EPIDEMIOLOGY
All races equally affected
Any age (10% - before age 40,
and 45% - before age 65)
Men > Women
• Women tend to be remarkably
protected against MI during their
reproductive years.
• Menopause — with declining
estrogen production — is
associated with exacerbation of
coronary artery disease.
• Therefore, IHD is the most
common cause of death in elderly
women.

18. ETIOLOGY AND RISK FACTORS
Myocardial
Infarction
Lifestyle
Genetics
Others
Diseases
Smoking
Lack of Exercise
Job Stress
Dietary Saturated Fat Diet
Family h/o IHD
DM
HTN
LDL
HDL
TG
Obesity

19. • ISCHEMIC HEART DISEASE
• Introduction
• Pathogenesis
• ANGINA PECTORIS
• MYOCARDIAL INFARCTION
• Introduction
• Epidemiology
• Etiologies and Risk factors
• Pathogenesis
• Morphological changes
• Symptoms
• Complications
• CHRONIC IHD
• DIAGNOSIS

20. PATHOGENESIS
Coronary
artery
Occlusion
Myocardial
Response
Myocyte
necrosis
Biochemical changes
Ultrastructural
Changes

21. CORONARY ARTERY OCCLUSION :
An atheromatous plaque is suddenly disrupted by intraplaque
hemorrhage or mechanical forces, exposing subendothelial collagen
and necrotic plaque contents to the blood.
Platelets adhere, aggregate, and are activated, releasing
thromboxane A2, adenosine diphosphate (ADP), and serotonin—
causing further platelet aggregation and vasospasm.
Activation of coagulation by exposure of tissue factor and other
mechanisms adds to the growing thrombus evolve completely to
occlude the coronary artery lumen.

22. BIOCHEMICAL CHANGES
• Cessation of aerobic metabolism (within
seconds).
• Onset of ATP depletion (within seconds)
• To 50% of N in 10 minutes.
• To 10% of N in 40 minutes.
• Accumulation of noxious metabolites (eg.
Lactic Acid).
Myocardial contractility ceases within a
minute.
ULTRASTRUCTURAL CHANGES
• Myofibrillar relaxation.
• Glycogen depletion.
• Cell & Mitochondrial swelling
Develop within a few minutes (Reversible)
Irreversible
Severe Ischemia (Blood
flow is 10% of N)
>20-40 mins.
Myocyte Necrosis
MYOCARDIAL RESPONSE TO ISCHEMIA:

23. ULTRASTRUCTURAL CHANGES
Capillary
Irreversible injured
myocyte
Mitochondrial
swelling

24. location, size, and morphologic features of an acute MI
Size and distribution of the involved vessel
The size of the vascular bed perfused by the obstructed
vessels
Metabolic demands of the myocardium Rate of development and duration of the
occlusion
.
Extent of collateral supply
The presence, site, and severity of
coronary arterial spasm

25. LAD – Left Anterior Descending Artery
~ 40-50% cases
ARTERY ZONE OF PERFUSION
RCA – Right Coronary Artery
~ 30-40% cases
LCX – Left Circumflex Artery
~ 15-20% cases

26.  Inner 1/3rd gets affected first (farthest)
If blood supply is restored – Outer 2/3rd gets
reperfused.
“SUBENDOCARDIAL INFARCT”
 Other causes:
• Severe Atherosclerosis
• Hypotension
• Shock superimposed on coronary stenosis.
After 3-6 hours
Zone of necrosis extends through the entire wall
thickness.
“TRANSMURAL INFARCT”

27. • ISCHEMIC HEART DISEASE
• Introduction
• Pathogenesis
• ANGINA PECTORIS
• MYOCARDIAL INFARCTION
• Introduction
• Epidemiology
• Etiologies and Risk factors
• Pathogenesis
• Morphological changes
• Symptoms
• Complications
• CHRONIC IHD
• DIAGNOSIS

28. MORPHOLOGICAL CHANGES
• Nearly all transmural infarcts affect at least a portion of the left ventricle and/or
interventricular septum.
• 15% to 30% of MIs that involve the posterior or posteroseptal wall also extend into the
right ventricle.
• Isolated right ventricle infarcts occur in only 1% to 3% of cases.
• Myocardial infarcts less than 12 hours old usually are not grossly apparent.
• Infarcts more than 3 hours old can be visualized by exposing myocardium to vital stains,
such as triphenyltetrazolium chloride, a substrate for lactate dehydrogenase.
• By 12 to 24 hours after MI, an infarct usually can be grossly identified by a red-blue
discoloration caused by stagnated, trapped blood.
• Thereafter, infarcts become progressively better delineated as soft, yellow-tan areas; by
10 to 14 days, infarcts are rimmed by hyperemic (highly vascularized) granulation tissue.
• Over the succeeding weeks, the infarcted tissue evolves to a fibrous scar.

29. Acute myocardial infarct,
predominantly of the
posterolateral left ventricle,
demonstrated
histochemically by a lack of
staining by
triphenyltetrazolium chloride
in areas of necrosis (arrow).
Note the myocardial
hemorrhage at one edge
of the infarct that was
associated with cardiac
rupture, and the anterior
scar (arrowhead),
indicative of old infarct.

30. • The microscopic appearance also undergoes a characteristic sequence of changes:
• Typical features of coagulative necrosis become detectable within 4 to 12 hours of
infarction. “Wavy fibers” also can be present at the edges of an infarct reflecting the
stretching and buckling of noncontractile dead fibers.
• Sublethal ischemia can also induce intracellular myocyte vacuolization.
• Necrotic myocardium elicits acute inflammation (typically most prominent 1 to 3 days
after MI), followed by a wave of macrophages that remove necrotic myocytes and
neutrophil fragments (most pronounced by 5 to 10 days after MI).
• The infarcted zone is progressively replaced by granulation tissue (most prominent
1 to 2 weeks after MI), which in turn forms the provisional scaffolding upon which
dense collagenous scar forms.
• In most instances, scarring is well advanced by the end of the sixth week. Healing
requires the migration of inflammatory cells and ingrowth of new vessels from the
infarct margins.
• Thus, an MI heals from its borders toward the centre, and a large infarct may not heal
as fast or as completely as a small one.

32. Microscopic features of myocardial infarction and its repair
A, One-day-old infarct showing
coagulative necrosis and wavy
fibers (elongated and narrow, as
compared with adjacent normal
fibers at right).
 Widened spaces between
the dead fibers contain
edema fluid and scattered
neutrophils.
B, Dense
polymorphonuclear
leukocytic infiltrate in
area of acute
myocardial infarction of
3 to 4 days' duration.
C, Nearly complete removal
of necrotic myocytes by
phagocytosis (approximately
7 to 10 days).
D, Granulation tissue characterized
by loose collagen and abundant
capillaries.
E, Well-healed myocardial infarct
with replacement of the necrotic
fibers by dense collagenous scar. A
few residual cardiac muscle cells
are present.

34. • ISCHEMIC HEART DISEASE
• Introduction
• Pathogenesis
• ANGINA PECTORIS
• MYOCARDIAL INFARCTION
• Introduction
• Epidemiology
• Etiologies and Risk factors
• Pathogenesis
• Morphological changes
• Symptoms
• Complications
• CHRONIC IHD
• DIAGNOSIS

35. SYMPTOMS
• Light-headedness
• Palpitation
• Anxiety
• Insomnia
• Hyper/hypertension
• Arrhythmias
• Chest pain
• Dyspnoea
• Fatigue
• Increased sweating
• Weakness
• Nausea
• Vomiting

36. COMPLICATIONS
• Contractile dysfunction.
• Papillary muscle dysfunction
• Right ventricular infarction.
• Myocardial rupture.
• Congestive heart failure
• Cardiogenic shock
• Arrhythmias
• Pericarditis
• Rupture
• Chamber dilation.
• Mural thrombus
• Thromboembolism
• Ventricular aneurysm
• Cardiac(Ventricular)Aneurysm

37. • ISCHEMIC HEART DISEASE
• Introduction
• Pathogenesis
• ANGINA PECTORIS
• MYOCARDIAL INFARCTION
• Introduction
• Epidemiology
• Etiologies and Risk factors
• Pathogenesis
• Morphological changes
• Symptoms
• Complications
• CHRONIC IHD
• DIAGNOSIS

38. CHRONIC ISCHEMIC HEART DISEASE
• Chronic IHD, also called ischemic cardiomyopathy, is essentially progressive heart failure
secondary to ischemic myocardial damage.
• In most instances, there is a history of previous MI.
• In this setting, chronic IHD appears when the compensatory mechanisms (e.g., hypertrophy) of
residual viable myocardium begin to fail.
• In other cases, severe obstructive CAD can cause diffuse myocardial dysfunction without frank
infarction.
• Clinical Features:
• Severe, progressive heart failure characterizes chronic IHD
• Occasionally punctuated by new episodes of angina or infarction.
• Arrhythmias, CHF, and intercurrent MI account for most of the associated morbidity and
mortality.

39. MORPHOLOGY:
• Patients with chronic IHD typically exhibit left ventricular
dilation and hypertrophy, often with discrete areas of gray-
white scarring from previous healed infarcts.
• There is moderate to severe atherosclerosis of the coronary
arteries, sometimes with total occlusion.
• The endocardium generally shows patchy, fibrous thickening
and mural thrombi may be present.
• Microscopic findings include myocardial hypertrophy, diffuse
sub-endocardial myocyte vacuolization, and fibrosis from
previous infarction.

40. • ISCHEMIC HEART DISEASE
• Introduction
• Pathogenesis
• ANGINA PECTORIS
• MYOCARDIAL INFARCTION
• Introduction
• Epidemiology
• Etiologies and Risk factors
• Pathogenesis
• Morphological changes
• Symptoms
• Complications
• CHRONIC IHD
• DIAGNOSIS

41. DIAGNOSIS
Clinical
Symptoms
Laboratory
investigationsECG

42. Cardiac Biomarkers
• The laboratory evaluation of MI is based on measuring blood levels of macromolecules
that leak out of injured myocardial cells through damaged cell membranes
I. Myoglobin
II. Cardiac troponins T and I (TnT, TnI)
III. Creatine kinase (CK) (specifically the myocardial isoform, CK-MB)
IV. Lactate dehydrogenase

43. Troponins and CK-MB have high specificity and sensitivity for myocardial damage.
Total CK activity is not a reliable marker of cardiac injury since various isoforms of CK are also found in
brain, myocardium, and skeletal muscle.
CK-MB isoform—principally derived from myocardium, but also present at low levels in skeletal
muscle—is the more specific indicator of heart damage.
TnI and TnT normally are not found in the circulation; however, detectable after acute MI.
Cardiac troponin and CK-MB are equally sensitive markers of the early stages of an MI, persistence of
elevated troponin levels for approximately 10 days allows the diagnosis of an acute MI long after CK-MB
levels have returned to normal.
With reperfusion, both troponin and CK-MB levels may peak earlier owing to more rapid washout of the
enzyme from the necrotic tissue.

44. Protein elevation in serum after MI
Serum Protein 1st elevation
(hours)
Peak elevation
(hours)
Duration of
elevation (days)
AST/SGOT 2-4 2-4 3 (2-3x normal only)
LDH 2-4 6-9 1
CK 4-6 18-36 3 (2-3xnormal only)
CKMB 2-4 24 3 (2-3xnormal only)
Myoglobin 2-3 6-9 1
Troponin I and T 4-6 24-36 Trop I 7-10
Trop T 10-14

46. Other
markers
Carbonic Anhydrase III
Glycogen Phosphorylase
Heart Fatty Acid–Binding Protein
Myosin
Ischemia-Modified Albumin

47. THANK YOU