ISCHEMIC HEART

DISEASES
BY
DR UDO MARK
DEPARTMENT OF ANATOMICAL PATHOLOGY
INTRODUCTION
 ISCHEMIA in the context of heart diseases
refers to: insufficiency of O2 + decreased
availability of substrates + inadequate removal
of metabolites.
 IHD is synonymous with coronary artery
disease (CAD) because 90% of MI is caused by
decreased coronary blood flow due to
atherosclerosis.
 IHD is therefore caused by imbalance b/w
perfusion (supply) and demand of the heart for
O2nated blood.
INTRODUCTION
 CAUSE: Atherosclerosis (90%)  decr coronary blood flow
 RISK of IHD; depends on
 Number/nature of atheroma plaques
 Degree of narrowing
 PATHOGENESIS
 Decreased coronary perfusion relative to myocardial
demand.
 This is due to interactions b/w:
a). Fixed atherosclerotic narrowing
b). Plaque disruption + intraluminal thrombosis +
platelet aggregation  inflammation.
c). Vasospasm
INTRODUCTION
 75% or more narrowing  exercise intolerance.
 90% or more narrowing  angina at rest.
 Causes of acute plaque change:
 Rupture/fissuring of a fixed plaque
 Erosion/ulceration
 Hemorrhage into the atheroma
 N/B; plaque instability (ie plaque change) contributes
more to MI than the degree of narrowing in a fixed
plaque.
 CRP (an acute phase protein) is a predictor of risk of
MI because it is released during inflm phase of
atherosclerosis.
SYNDROMES OF ISCHEMIC HEART
DISEASES
 1. Myocardial Infarction (MI)
 2. Angina Pectoris (AP)
 3. Chronic IHD with heart failure
 4. Sudden cardiac death
 The following order of events is noteworthy;
 Stable angina = demand>> suply
 Unstable angina = sudden change in plaque
morphology  partial occlusion.
 MI = total thrombotic occlusion.
 Sudden death = regional myocardial ischemia
MYOCARDIAL INFARCTION (HEART
ATTACK)
 Death of cardiac muscles due to ischemia.
 Two types of lesions occur:

 A. Transmural infarct (commonest): Ischemic

necrosis involving full or nearly full thickness
of the ventricular wall in the distribution of a
single coronary artery.
MYOCARDIAL INFARCTION (HEART
ATTACK)
 B. Subendocardial (non trasmural) infarct: an
area of ischemic necrosis limited to 1/3 or at
most ½ of the ventricular wall.
 May extend laterally beyond the perfusion

territory of a single coronary artery.

 Note; the subendocardium is the least well

perfused part of the myocardium and d/4

prone to MI.
 Results from; plaque disruption+thrombus,

also from systemic HTN and shock

MYOCARDIAL INFARCTION (HEART
ATTACK)
 INCIDENCE/RISK: Age, gender (F<M); women in
reproductive years are protected, and
predispositions to atherosclerosis eg smoking,
D/M, HTN, genetic etc.
 PATHOGENESIS
 Sudden plaque change  exposed subendothelium
 Platelet adhesion, aggregation, & activation.
 Vasospasm; platelet released mediators.
 Growth of the thrombus: coagulation pathway.
 Complete occlusion of vessel by thrombus growth.
MYOCARDIAL INFARCTION (HEART
ATTACK)
 MECHANISM OF DEATH: Coagulative necrosis.
 Note; “At risk area”= the anatomic area of the

subendocardium supplied by an occluded

major coronary artery.
 MI is potentially reversible in 6 hours.

 INFARCT MODIFICATION
 REPERFUSION: Reperfusion (in the 1st 3-4hrs

of MI) may restore function.

MYOCARDIAL INFARCTION (HEART
ATTACK)
 REPERFUSION INJURY
 A. Stunned myocardium (ie prolonged post

ischemic dysfunction):
 Results from brief ischemia, followed by

reperfusion.
 B. ROS (reactive o2 species) injury from

migrant leukocytes.
 C. Contraction band necrosis of myocytes, ie

when damaged myocytes are exposed

calcium ions from reflow blood.
 MORPHOLOGY OF MI
 Nearly all transmural infarcts involve at least a portion of
the left ventricle.
 Isolated rt ventricular infarction is rare (1-3%)
 There is almost always a narrow rim (approx. 0.1mm) of
preserved subendocardial myocardium sustained by
direct diffusion of oxygen and nutrients from the lumen.
 Frequencies of involvement of the main coronary arteries
in MI are:
 LAD= 40%-50% of infarcts and involves the anterior LV
wall and apex, ant. 2/3 of the ventricular septum
 RCA= 30%-40%, infarct involves inf-post LV wall, post
1/3 of ventr septum and RV wall.
 LCX= 15%-20%, infarcts involve lateral LV wall.
MORPHOLOGY OF MI
 Note; stenosing atherosclerosis or thrombosis of penetrating
intramyocardial branches of the coronary arteries are almost
never encountered.
 Timing is critical in the gross and microscopic appearance of
an infarct
 MI <12hrs old are usually not apparent on gross
examination.
 Areas of infarct can be identified by applying
Triphenyltetrazolium (TTC) chloride solution to sections of
the infarcted myocardium. This imparts a brick-red color to
the non infarcted myocytes where LDH enzymes are
preserved, while the infarcted areas are pale.
MORPHOLOGY OF MI
 Old scarred infarcts are white and glistening.
 After 12hrs-24hrs an infarct can be identified
routinely as areas of red-blue hue as a result
of stagnated trapped blood.
 Later infarcts become yellow-tan colored, more
sharply defined areas of softenong.
 By the 10th day – 2wks, the area is rimmed by a
hyperemic zone of highly vascularized
granulation tissue.
 Over the weeks, the infarcted region evolves
into a fibrous scar.
MI MORPHOLOGY SUMMARY
 LIGHT MICROSCOPY
 1ST 12hrs after MI = no change
 Up to 3 days=coagulative necrosis, neutrophil
 1-2wks = granulation tissues
 >3wks = fine scar
 >2months = dense scar
 EM: Membrane disruption, mitochondrial densities
 SPECIAL STAINS: TTC
 Stains Mahogany-brown with LDH
 Unstained area = infarction
 Mahogany-Brown = viable
 White glistening = scar
CLINICAL FEATURES OF MI
 Rapid weak pulse
 Sweating profusely
 Dyspnoea due to impaired contractility of the

ischemic myocardium
 Resultant pulmonary congestion and edema.
 Onset can be entirely asymptomatic in about

10%-15% of patients. Such silent MIs are

common in elderly patients and in DM.
MYOCARDIAL INFARCTION (HEART
ATTACK)
 LABORATORY EVALUATION OF ACUTE MI
(BIOCHEMICAL MARKERS)

 1. Troponin I and T (TnI & TnT): levels rise in bld 2-

4hrs after MI and remain for 10 days. (specific for
MI)
 2. Creatine Kinase M & B: 2-4hrs after MI, peaks at
24hrs.
 CK-MM = specific for sk muscles
 CK-BB = specific for the brain
 CK-MB = for myocardium (though some amounts are
seen in sk muscles).
LABORATORY EVALUATION OF ACUTE
MI (BIOCHEMICAL MARKERS) contd.

 3. Others:
 CRP: 3mg/dl and above is associated with

high risk of cardiovascular dx

 LDH: Not specific to MI
 Note: Females of child bearing age are

protected from MI due to estrogen. MI rate

increases after menopause.
COMPLICATIONS OF MI
 Contractile dysfunction  pump failure
(cardiogenic shock)
 Arrythmias
 Myocardial rupture
 Pericarditis
 Mural thrombi
 Ventricular aneurysm
 Papillary muscle dysfunction  post

infarction mitrial regurgitation

 Progressive heart failure
ANGINA PECTORIS
 Presents as a recurrent precordial chest pain often
described as squeezing/knife-like/choking pain, caused
by transient (15 secs – 15 mins) myocardial ischemia.
 Three overlapping patterns:

 1. Stable (or typical) angina:

 Most common
 Chronic stenosing coronary aterosclerosis.
 Increased cardiac workload/demand precipitates attack.
Eg physical activity, emotional excitement etc.
 Usually relieved by rest (decreased demand), or
Nitroglycerin (a strong vasodilator).
ANGINA PECTORIS
 2. Prinzmetal Angina
 An uncommon pattern of episodic angina
 Occurs at rest.
 Caused by coronary artery spasm
 Attacks are unrelated to physical activity,

heart rate, or blood pressure, although

patients have significant coronary
atherosclerosis.
 Responds to vasodilators (Nitroglycerin and

Ca-channel blockers.
ANGINA PECTORIS
 3. Unstable (crescendo or pre-infarction) Angina

 Pain occurs with progressively increasing frequency.

 Occurs at rest, and is more prolonged.
 Caused by:
-Plaque disruption
-Vasospasm
-Thrombosis +/- embolization
 The ischemia that causes unstable angina fall short of causing
a detectable infarction.
 It is therefore a prodrome of subsequent acute MI.
 Hence it is refered to as pre infarction angina, and lies in b/w
stable angina on the one hand, and MI in the spectrum of IHD.
CHRONIC ISCHEMIC HEART DISEASE
 This describes cardiac findings in patients who
develop progressive heart failure as a
consequence of ischemic myocardial damage,
ie post infarction cardiac decompensation.
 Or in those without previous MI, a diffuse

myocardial dysfunction.
 Eg, many transplant patients have chronic IHD
 Morphology: enlarged heart, heavy (LV

hypertrophy & dilation), stenosing

atherosclerosis of the coronary arteries.
SUDDEN CARDIAC DEATH
 Unexpected death from cardiac causes soon after
symptoms develop (usually within 1hr), or without onset of
symptoms.
 Usually a sequale of IHD in adults due to atherosclerosis

(90%)
 In younger age groups, non atherosclerotic causes become

significant. Eg
-Congenital structural or coronary arterial abnormalities.
-Aortic valve stenosis
-Mitrial valve prolapse
-Myocarditis
-Dilated or hypertrophic cardiomyopathy
-Pulmonary hypertension
SUDDEN CARDIAC DEATH
 Increased cardiac mass is an independent risk factor for
SCD.
 Thus some young patients, including athlets who died
suddenly, have hypertensive hypertophy, or unexplained
increased cardiac mass as the only finding.
 Mechanism of death in SCD is most often, a lethal
arrhythmia (v. fibrillation), triggered by electrical
irritability of the myocardium.
 Morphology: marked coronary atherosclerosis with
critical (>75%) stenosis involving 1 or more of the 3
major vessels is present in 80%-90% of SCD victims.
 Acute plaque disruption, healeed or new infarct are
common.