Ischemic Heart Disease

Question 1

Define Ischemic heart disease.

Answer 1

IHD defined as acute or chronic form of cardiac
disability arising from imbalance between the myocardial supply and demand
for oxygenated blood.

Question 2

Why is ischemic heart disease also called coronary artery disease?

Answer 2

Since narrowing or obstruction of the coronary arterial
system is the most common cause of myocardial anoxia, the alternate term ‘coronary artery disease (CAD)’ is used synonymously with IHD.

Question 3

Etiopathogenesis

Answer 3

1. Coronary Atherosclerosis (90% of cases)
2. Superadded changes in Coronary Atherosclerosis
3. Non-Atherosclerotic causes

Question 4

Coronary Atherosclerosis

Answer 4

DISTRIBUTION

• Atherosclerotic lesions in coronary arteries are distributed in one or more of the three major coronary arterial trunks, the highest incidence being in the anterior descending branch of the left coronary, followed in decreasing frequency, by the right coronary artery and still less in circumflex branch of the left coronary.

LOCATION

• Almost all adults show atherosclerotic plaques scattered throughout the coronary arterial system. However, significant stenotic lesions that may produce chronic myocardial ischaemia show more than 75% (three-fourth) reduction in the cross-sectional area of a coronary artery or its branch.

FIXED ATHEROSCLEROTIC PLAQUES

• The atherosclerotic plaques in the coronaries are more often eccentrically located bulging into the lumen from one side.
• Occasionally, there may be concentric thickening of the wall of the artery.
• Atherosclerosis produces gradual luminal narrowing that may eventually lead to ‘fixed’ coronary obstruction.

Question 5

Eccentric

Answer 5

Not placed centrally or not having its axis or other part placed centrally.

Question 6

Superadded changes in Coronary Atherosclerosis.

Answer 6

ACUTE CHANGES IN CHRONIC ATHEROMATOUS PLAQUE

Though chronic fixed obstructions are the most frequent cause of IHD, acute coronary episodes are often precipitated by sudden changes in chronic plaques such as:

• plaque haemorrhage, fissuring, or ulceration that results in thrombosis and embolisation of atheromatous debris.

CORONARY ARTERY THROMBOSIS

• Transmural acute myocardial infarction is often precipitated by partial or complete coronary thrombosis. T
• he initiation of thrombus occurs due to surface ulceration of fixed chronic atheromatous plaque, ultimately causing complete luminal occlusion.
• The lipid core of plaque, in particular, is highly thrombogenic.

LOCAL PLATELET AGGREGATION AND CORONARY ARTERY SPASM

• Some cases of acute coronary episodes are caused by local aggregates of platelets on the atheromatous plaque, short of forming a thrombus.
• The aggregated platelets release vasospasmic mediators such as thromboxane A2 which may probably be responsible for coronary vasospasm in the already atherosclerotic vessel.

Question 7

Non-Atherosclerotic Causes

Answer 7

These are:

Vasospasm, Stenosis of coronary ostia, Arteritis, Embolism, Thrombotic diseases, Trauma, Aneurysms and Compression.

Question 8

What are the main clinical forms of IHD?

Answer 8

IHD is a consequence of atherosclerosis and develops when the coronary blood flow is inadequate to meet the needs of the myocardium. Ischemia that results from narrowing or obstruction of coronary arteries may be relative or absolute and will present itself in several clinical conditions:

• Asymptomatic state
• Angina pectoris (AP)
• Acute myocardial infarction (MI)
• Chronic ischaemic heart disease (CIHD)/ Ischaemic cardiomyopathy/ Myocardial fibrosis
• Sudden cardiac death

Question 9

Angina Pectoris

Question 10

Stable or typical angina

Answer 10

• This is the most common pattern.
• Stable or typical angina is characterised by attacks of pain following physical exertion or emotional excitement and is relieved by rest.
• The pathogenesis of condition lies in chronic stenosing coronary atherosclerosis that cannot perfuse the myocardium adequately when the workload on the heart increases.
• During the attacks, there is depression of ST segment in the ECG due to poor perfusion of the subendocardial region of the left ventricle but there is no elevation of enzymes in the blood as there is no irreversible myocardial injury.

Question 11

Prinzmetal’s Variant Angina

Answer 11

• This pattern of angina is characterised by pain at rest and has no relationship with physical activity.
• The exact pathogenesis of Prinzmetal’s angina is not known.
• It may occur due to sudden vasospasm of a coronary trunk induced by coronary atherosclerosis, or may be due to release of humoral vasoconstrictors by mast cells in the coronary adventitia.
• ECG shows ST segment elevation due to transmural ischaemia.
• These patients respond well to vasodilators like nitroglycerin.

Question 12

Crescendo or Unstable Angina

Answer 12

• Also referred to as ‘pre-infarction angina’ or ‘acute coronary insufficiency’, this is the most serious pattern of angina.
• It is characterised by more frequent onset of pain of prolonged duration and occurring often at rest. It is thus indicative of an impending acute myocardial infarction.
• Distinction between unstable angina and acute MI is made by ST segment changes on ECG— acute MI characterised by ST segment elevation while unstable angina may have non-ST segment elevation MI.
• Multiple factors are involved in the pathogenesis of unstable angina which include: stenosing coronary atherosclerosis, complicated coronary plaques (e.g. superimposed thrombosis, haemorrhage, rupture, ulceration etc), platelet thrombi over atherosclerotic plaques and vasospasm of coronary arteries.

Question 13

Acute Myocardial Infarction

Answer 13

Acute myocardial infarction (MI) is the most important and feared consequence of coronary artery disease. Many patients may die within the first few hours of the onset, while remainder suffer from effects of impaired cardiac function.

Incidence:

In developed countries, acute MI accounts for 10-25% of all deaths. Due to the dominant etiologic role of coronary atherosclerosis in acute MI, the incidence of acute MI correlates well with the incidence of atherosclerosis in a geographic area.

Age:

Acute MI may virtually occur at all ages, though the incidence is higher in the elderly. About 5% of heart attacks occur in young people under the age of 40 years, particularly in those with major risk factors to develop atherosclerosis like hypertension, diabetes mellitus, cigarette smoking and dyslipidaemia with familial hypercholesterolaemia.

Sex:

Males throughout their life are at a significantly higher risk of developing acute MI as compared to females. Women during reproductive period have remarkably low incidence of acute MI, probably due to the protective influence of oestrogen. After menopause, this sex difference gradually declines but the incidence of disease among women never reaches that among men of the same age.

Question 14

Acute Myocardial Infarction; Etiopathogenesis- Notable features in the development of acute MI are?

Answer 14

1. Myocardial Ischemia.
2. Role of Platelets: Rupture of an atherosclerotic plaque exposes the subendothelial collagen to platelets which undergo aggregation, activation and release reaction. These events contribute to the build-up of the platelet mass that may give rise to emboli or initiate thrombosis.
3. Acute Plaque Rupture: In general, slowly-developing coronary ischaemia from stenosing coronary atherosclerosis of high-grade may not cause acute MI but continue to produce episodes of angina pectoris. But acute complications in coronary atherosclerotic plaques in the form of superimposed coronary thrombosis due to plaque rupture and plaque haemorrhage is frequently encountered in cases of acute MI.
4. Non-atherosclerotic causes:

Question 15

Transmural VS Subendocardial Infarcts

Answer 15

1. Transmural (full thickness) infarcts are the most common type seen in 95% cases. Critical coronary narrowing (more than 75% compromised lumen) is of great significance in the causation of such infarcts. Atherosclerotic plaques with superimposed thrombosis and intramural haemorrhage are significant in about 90% cases, and non-atherosclerotic causes in the remaining 10% cases.
2. Subendocardial (laminar) infarcts have their genesis in reduced coronary perfusion due to coronary atherosclerosis but without critical stenosis (not necessarily 75% compromised lumen), aortic stenosis or haemorrhagic shock. This is because subendocardial myocardium is normally least well perfused by coronaries and thus is more vulnerable to any reduction in the coronary flow.

Question 16

Where are infarcts most frequently located?

Answer 16

1. Infarcts are most frequently located in the left ventricle.
2. Right ventricle is less susceptible to infarction due to its thin wall, having less metabolic requirements and is thus adequately nourished by the thebesian (smallest cardiac vessels) vessels.
3. Atrial infarcts, whenever present, are more often in the right atrium, usually accompanying the infarct of the left ventricle.
4. Left atrium is relatively protected from infarction because it is supplied by the oxygenated blood in the left atrial chamber.

Question 17

Three regions of Myocardial Infarction depending upon the blocked coronary artery trunks:

Answer 17

1. Stenosis of the left anterior descending coronary artery is the most common (40-50%). The region of infarction is the anterior part of the left ventricle including the apex and the anterior two-thirds of the interventricular septum.
2. Stenosis of the right coronary artery is the next most frequent (30-40%). It involves the posterior part of the left ventricle and the posterior one-third of the interventricular septum.
3. Stenosis of the left circumflex coronary artery is seen least frequently (15-20%). Its area of involvement is the lateral wall of the left ventricle.

Question 18

Sequence of macroscopic changes in all myocardial infarcts

Answer 18

1. In 6 to 12 hours old infarcts, no striking gross changes are discernible except that the affected myocardium is slightly paler and drier than normal. However, the early infarcts (3 to 6 hours old) can be detected by histochemical staining for dehydrogenases on unfixed slice of the heart. This consists of immersing a slice of unfixed heart in the solution of triphenyltetrazolium chloride (TTC) which imparts red brown color to the normal heart muscle, while the area of infarcted muscle fails to stain due to lack of dehydrogenases.
2. By about 24 hours, the infarct develops cyanotic, red-purple, blotchy areas of hemorrhage due to stagnation of blood.
3. During the next 48 to 72 hours, the infarct develops a yellow border due to neutrophilic infiltration and thus becomes more well-defined.
4. In 3-7 days, the infarct has hyperemic border while the center is yellow and soft.
5. By 10 days, the periphery of the infarct appears reddish-purple due to growth of granulation tissue.
6. By the end of 6 weeks, the infarcted area is replaced by a thin, grey-white, hard, shrunken fibrous scar which is well developed in about 2 to 3 months. However, the time taken by an infarct to heal by fibrous scar may vary depending upon the size of the infarct and adequacy of collateral circulation.

Question 19

The ischaemic injury to myocardium is reversible if perfusion is restored within the first ________.

Answer 19

30 min

Question 20

The salvage in early infarcts can be achieved by the following interventions:

Answer 20

1. Institution of thrombolytic therapy with thrombolytic agents such as streptokinase and tissue plasminogen activator (door-to-needle time <30 minutes).
2. Percutaneous transluminal coronary angioplasty (PTCA).
3. Coronary artery stenting
4. Coronary artery bypass surgery

Question 21

Myonecrosis during reperfusion occurs due to?

Answer 21

Myonecrosis during reperfusion occurs due to rapid influx of calcium ions and generation of toxic oxygen free radicals.

Question 22

Electron microscopic changes in early infarcts

Answer 22

Changes by EM examination are evident in less than half an hour on onset of infarction. These changes are:

1. Disappearance of perinuclear glycogen granules within 5 minutes of ischemia.
2. Swelling of mitochondria in 20 to 30 minutes.
3. Disruption of sarcolemma.
4. Nuclear alterations like peripheral clumping of nuclear chromatin.

Question 23

Chemical and histochemical changes in early infarcts.

Answer 23

Analysis of tissues from early infarcts by chemical and histochemical techniques has shown a number of findings. These are as follows:

1. Glycogen depletion in myocardial fibres within 30 to 60 minutes of infarction.
2. Increase in lactic acid in the myocardial fibres.
3. Loss of K+ from the ischaemic fibres.
4. Increase of Na+ in the ischaemic cells.
5. Influx of Ca++ into the cells causing irreversible cell injury.

Question 24

CK-MB; myocardial form?

Answer 24

CK-MB 2

A ratio of CK-MB2: CK-MB1 above 1.5 is highly sensitive for the diagnosis of acute MI after 4-6 hours of onset of myocardial ischaemia. CKMB disappears from blood by 48 hours.

Question 25

LDH; Myocardial form?

Answer 25

LDH too has two isoforms of which LDH-1 is myocardial-specific.

Estimation of ratio of LDH-1: LDH-2 above 1 is reasonably helpful in making a diagnosis. LDH levels begin to rise after 24 hours, reach peak in 3 to 6 days and return to normal in 14 days.

Question 26

Cardiac-specific troponins (cTn)

Answer 26

Both cTnT and cTnI are not found in the blood normally, but after myocardial injury their levels rise very high around the same time when CK-MB is elevated (i.e. after 4-6 hours). Both troponin levels remain high for much longer duration; cTnI for 7-10 days and cTnT for 10-14 days.

Question 27

Why is Myoglobin not used for diagnosis of MI?

Answer 27

Though myoglobin is the first cardiac marker to become elevated after myocardial infarction, it lacks cardiac specificity and is excreted in the urine rapidly. Its levels, thus, return to normal within 24 hours of attack of acute MI.

Question 28

Chronic Ischemic Heart Disease

Answer 28

Chronic ischaemic heart disease, ischaemic cardiomyopathy or myocardial fibrosis, are the terms used for focal or diffuse fibrosis in the myocardium characteristically found in elderly patients of progressive IHD.

Such small areas of fibrous scarring are commonly found in the heart of patients who have history of episodes of angina and attacks of MI some years back.

Question 29

CIHD; Etiopathogenesis.

Answer 29

In majority of cases, coronary atherosclerosis causes progressive ischemic myocardial damage and replacement by myocardial fibrosis. A small percentage of cases may result from other causes such as emboli, coronary arteritis and myocarditis.

Question 30

CIHD; Morphology.

Answer 30

1. There are scattered areas of diffuse myocardial fibrosis, especially around the small blood vessels in the interstitial tissue of the myocardium.
2. Intervening single fibres and groups of myocardial fibres show variation in fibre size and foci of myocytolysis.
3. Areas of brown atrophy of the myocardium may also be present.
4. Coronary arteries show atherosclerotic plaques and may have complicated lesions in the form of superimposed thrombosis.

Question 31

Sudden Cardiac Death

Answer 31

Sudden cardiac death is defined as sudden death within 24 hours of the onset of cardiac symptoms.

The most important cause is coronary atherosclerosis; less commonly it may be due to coronary vasospasm and other non-ischaemic causes. These include: calcific aortic stenosis, myocarditis of various types, hypertrophic cardiomyopathy, mitral valve prolapse, endocarditis, and hereditary and acquired defects of the conduction system.

The mechanism of sudden death by myocardial ischaemia is almost always by fatal arrhythmias, chiefly ventricular asystole or fibrillation.

At autopsy, such cases reveal most commonly critical atherosclerotic coronary narrowing (more than 75% compromised lumen) in one or more of the three major coronary arterial trunks with superimposed thrombosis or plaque-haemorrhage.