L7 Pathology Ischaemic Heart disease

Overview

Ischaemic heart disease is the clinical manifestation of coronary atherosclerosis: blood supply becomes insufficient relative to myocardial demand. The lecture builds the disease from the vessel wall outwards. It first defines the terminology of ischaemia and infarction, then develops atherosclerosis as a chronic inflammatory and healing response of the arterial wall to endothelial injury, with its morphology from fatty streak to mature plaque to complicated plaque. It then splits the consequences into two mechanisms: chronic mechanical obstruction by a stable plaque, which gives stable angina, versus acute plaque change with superimposed thrombosis, which gives the acute coronary syndromes. The rest of the lecture follows myocardial infarction through diagnosis, the “time is muscle” principle, the gross and microscopic timeline of the healing infarct, and the early and late complications, ending with chronic ischaemic heart disease and congestive heart failure.

Terminology

• Ischaemia: reduced tissue blood flow.
• Hypoxia: oxygen deprivation, which causes cell injury by reducing aerobic oxidative respiration.
• Infarct / infarction: a localised area of ischaemic tissue necrosis (death), usually coagulative necrosis.
• Coagulative necrosis: a form of necrosis in which tissue architecture (the “ghost” outline) is preserved for at least some time.
• Atherosclerosis etymology: “athero” = gruel, “sclerosis” = hardening.
• IHD = CAD (coronary artery disease).

Burden of disease

• Ischaemic heart disease is the leading cause of death globally. WHO (2020) top 10, in rank order: 1 ischaemic heart disease, 2 stroke, 3 chronic obstructive pulmonary disease, 4 lower respiratory infections, 5 neonatal conditions, 6 trachea/bronchus/lung cancers, 7 Alzheimer’s disease and other dementias, 8 diarrhoeal diseases, 9 diabetes mellitus, 10 kidney diseases.
• Comparing 2000 with 2019, ischaemic heart disease has both the largest number of deaths and the largest increase over that period. It is classed as a noncommunicable cause (the other categories used are communicable and injuries).
• In New Zealand it is the number one killer in Māori males and in both non-Māori males and females (age-standardised mortality, 2010 to 2012).

Relevant normal anatomy

• Layers around the heart: pericardium is the outer fibrous sac, epicardium is the yellow-white fatty surface of the heart itself, with the diaphragm below.
• A normal coronary artery in cross-section has a patent (open) lumen and a thin wall. The normal aortic valve has three cusps.
• The three major coronary arteries: RCA (right coronary artery), LCX (left circumflex branch of the left coronary artery), LAD (left anterior descending / anterior interventricular branch of the left coronary artery).
• Normal arterial wall layers, from inside out: lumen, intima, internal elastic lamina, media, adventitia.

Atherosclerosis: risk factors

Non-modifiable (constitutional)	Modifiable
Genetics (e.g. familial hypercholesterolaemia)	Hyperlipidaemia (hypercholesterolaemia)
Family history	Hypertension
Increasing age	Cigarette smoking
Male gender	Diabetes
	Inflammation (increased CRP)

Atherosclerosis: pathogenesis, the response to injury hypothesis

Key points:

• Endothelial injury or dysfunction lies at the heart of Atherosclerosis.
• Definition to know: atherosclerosis is “a chronic inflammatory and healing response of arterial wall to endothelial injury”.
• Vessels affected: elastic arteries (aorta, carotids, iliacs) and large and medium sized muscular arteries (coronaries). Veins and smaller arterioles do not get atherosclerosis because there is not enough pressure.

The endothelial cell has two states:

• Basal state: maintained by normotension, laminar flow and growth factors such as VEGF, giving a non-adhesive, non-thrombogenic surface.
• Activated state: driven by turbulent flow, hypertension, cytokines, complement, bacterial products, lipid products, advanced glycation end-products, hypoxia, acidosis, viruses and cigarette smoke. The activated cell shows increased expression of procoagulants, adhesion molecules and proinflammatory factors, and altered expression of chemokines, cytokines and growth factors.

Sequence of plaque formation:

1. Chronic endothelial injury (hyperlipidaemia, hypertension, smoking, homocysteine, haemodynamic factors, toxins, viruses, immune reactions) causes endothelial injury and dysfunction, with increased vascular permeability and leukocyte and platelet adhesion.
2. With increased permeability, lipoproteins, mainly LDL and its oxidised form, seep into the vessel wall.
3. Cytokine release from activated endothelial cells attracts monocytes, which adhere, emigrate into the intima, transform into activated macrophages and engulf lipid to become foam cells. A fatty streak forms.
4. Further cytokine and growth factor release from endothelial cells, platelets and macrophages recruits smooth muscle cells from the media or from circulating precursors.
5. Smooth muscle cells proliferate and deposit extracellular matrix (collagen). They also engulf lipid and become foam cells.
6. T cells (T lymphocytes) are also recruited.
7. A fibrolipid atheroma, the atherosclerotic plaque, forms within the intima and physically encroaches on the vascular lumen.

Structure of the atherosclerotic plaque (atheroma)

• Fibrous cap: smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularisation.
• Necrotic centre: cell debris, cholesterol crystals, foam cells, calcium.
• The plaque sits in the intima, above the internal elastic lamina and the media.

Morphology of atherosclerosis, gross and microscopic

• Early: fatty streaks. Gross, flat or slightly raised yellow streaks on the luminal surface. Microscopic, a layer of lipid-filled foamy macrophages in the intima just beneath the endothelial surface.
• Mature plaque. Cross-section shows marked luminal narrowing by plaque. Gross, a raised yellow-white lesion on the opened luminal surface. In coronary arteries, stable plaques appear as narrowed, eccentric lumens surrounded by thickened yellow-white plaque, without thrombus.
• Complicated plaque. A coronary artery almost completely occluded by thrombus due to plaque rupture (acute plaque change). Gross, an opened coronary artery with multiple haemorrhagic or ulcerated plaques along its length. In cross-section, plaque tissue surrounds central dark occluding thrombus.

Stable versus vulnerable plaque

• Vulnerable plaque: large lipid core, thin fibrous cap, inflammatory cells scattered through the cap.
• Stable plaque: smaller lipid core, thick fibrous cap.

Warning

On the trichrome-stained mature plaque histology image the labels “L”, “F” and “C” are single letters with no key given on the slide. From the neighbouring plaque-anatomy slide they most likely mean lumen, fibrous cap and core (necrotic centre), but the slide does not state this.

Complications of atherosclerosis

• Mechanical obstruction of the vessel leading to ischaemia. Critical stenosis is about 70% (given as 70 to 75% on the IHD pathogenesis slide).
• Increased diffusion distance from lumen to media, so the media degenerates and weakens through loss of elastic fibres, leading to aneurysm formation. These occur commonly in the abdominal aorta and common iliac arteries.
• Aneurysms can be saccular or fusiform and commonly contain a mural thrombus. Aneurysms can rupture. Gross appearance of an abdominal aortic aneurysm: a markedly dilated balloon-like segment of abdominal aorta with surrounding haemorrhage, and when opened a large dark thrombus filling the sac.
• Haemorrhage into the plaque, from the new vessels of neovascularisation, leading to plaque expansion or rupture.
• Plaque ulceration, erosion or rupture, leading to thrombosis and partial or complete occlusion of the vessel.

The last two, that is intra-plaque haemorrhage and plaque ulceration/erosion/rupture, are what the lecture calls acute plaque change.

Clinical consequences by arterial territory

• Arteries of the heart: ischaemic heart disease.
• Arteries of the brain: stroke.
• Lower limb arteries: peripheral vascular disease.
• Aorta: abdominal aortic aneurysm.

IHD: pathogenesis

• Insufficient blood supply relative to myocardial demand. Most cases are due to atherosclerosis of one or more coronary arteries.
• Chronic vascular occlusion by atherosclerosis: 70 to 75% stenosis is considered critical, affecting one or more of LAD, RCA, LCX.
• Acute plaque change: intra-plaque haemorrhage, erosion, rupture, with superimposed thrombosis and possible complete vascular occlusion.
• An element of coronary vasospasm also contributes.

IHD: clinical presentation

One or more of:

1. Angina pectoris (chest pain): ischaemia not severe enough to cause infarction. Can be stable or unstable.
2. Myocardial infarction: (severe) ischaemia causing myocardial necrosis.
3. Sudden cardiac death: ischaemia leading to fatal arrhythmia (ventricular fibrillation).
4. Chronic IHD with heart failure: due to accumulated ischaemic damage.

Unstable angina, MI and sudden cardiac death together make up the acute coronary syndromes, mostly caused by acute plaque change and obstructive thrombosis.

Angina pectoris

• Stable angina (most common): caused by significant coronary occlusion due to atherosclerosis, that is critical stenosis. Triggered by increased oxygen demand such as exercise, stress and emotional excitement, hence “demand angina”. Usually relieved by rest or vasodilators.
• Unstable angina: associated with plaque change and superimposed non-occlusive thrombi and/or vasospasm. Pain is prolonged, more frequent, and occurs even at rest.
• Prinzmetal angina: coronary artery spasm.

Character of the pain of myocardial ischaemia:

• Site and duration: precordial or substernal, chiefly retrosternal and intense, lasting 15 seconds to 15 minutes.
• Descriptions: viselike, constricting, crushing weight and/or pressure, or burning.
• Radiation: most commonly to the left shoulder and/or the ulnar aspect of the left arm and hand. May also radiate to neck, jaw, teeth, back, abdomen or right arm.
• Other manifestations of myocardial ischaemia: fear, shortness of breath, perspiration, nausea and vomiting, weakness, collapse, coma.

Myocardial infarction

• Ischaemia severe enough to cause cardiac myocyte death.
• Caused by acute plaque change with superimposed thrombosis. Vasospasm also occurs, under the effect of platelet-derived mediators. The thrombus can expand to occlude the vascular lumen completely.
• Clinically, severe prolonged chest pain lasting more than 30 minutes, not relieved by rest or vasodilators.

Laboratory diagnosis: cardiac biomarkers. These measure blood levels of proteins that leak out of necrotic myocytes:

• Cardiac-specific troponins T and I (cTnT and cTnI, including high-sensitivity TnT).
• The MB isoform of creatine kinase (CK-MB).

How they reach the blood: (1) onset of myocardial infarction; (2) the plasma membrane of necrotic myocytes becomes leaky, with myosin, actin and troponin free in the cytoplasm and the troponin complex released from the actin filament; (3) these molecules leak out of the cell into the circulation via a nearby blood vessel.

Important

“Time is muscle”. After acute coronary occlusion there is a zone of perfusion (the area at risk). Necrosis begins subendocardially and the zone of necrosis widens until the infarct is transmural (full thickness) by approximately 6 hours, ending as a completed infarct involving nearly the entire area at risk. A transmural infarct corresponds to STEMI on the ECG. The longer the delay, the more muscle is lost, so early diagnosis and intervention salvages muscle.

MI distribution by coronary artery. The region infarcted corresponds to the artery occluded:

• LAD: 40 to 50% of cases, anterior and anteroseptal wall.
• RCA: 30 to 40%, inferior/posterior wall and right ventricle.
• LCX: 15 to 20%, lateral wall of the left ventricle.

MI morphology: gross timeline

Time	Macroscopic picture
Up to 12 hrs	No change
12 to 24 hrs	Dark mottling (reddish-blue discoloration of tissue due to stagnant blood)
1 to 3 days	Mottling with pale yellow infarct centre (coagulation necrosis and infiltration by neutrophils)
3 to 7 days	Central pale yellow-tan infarct with hyperaemic border
10 to 14 days (1 to 2 weeks)	Reddish depressed hyperaemic border (rim of highly vascularised granulation tissue)
2 to 8 weeks	Grey-white scar (collagen)

Gross examples shown: at 12 to 24 hours, dark reddish-blue mottling of the cut heart; at 1 to 2 weeks, a pale yellow-tan central infarct surrounded by a red hyperaemic border; years later, a pale, thinned, white-grey fibrous area of ventricular wall (healed scarred infarct).

MI morphology: microscopic timeline

Time	Microscopic picture
4 to 12 hrs	Early coagulative necrosis, oedema and haemorrhage
12 to 24 hrs	Nuclei dark and small (pyknosis), hypereosinophilia of necrotic myocytes, early infiltration by neutrophils (necrotic muscle elicits acute inflammation)
1 to 3 days	Myocytes lose their nuclei and cross striations, marked interstitial infiltration by neutrophils
3 to 7 days	Infiltration by macrophages, which clear the necrotic debris
10 to 14 days (1 to 2 weeks)	Well established granulation tissue
2 to 8 weeks	Collagenous scar

Histology examples shown:

• Normal myocardium: intact myocyte fibres with visible cross-striations and normally located nuclei.
• 2 to 3 days: dense neutrophil infiltration; necrotic myocytes are small, have no nuclei and lack the striations of normal myocytes.
• 7 to 10 days: granulation tissue with macrophages clearing debris and numerous small capillaries in loose vascularised connective tissue.
• Months old: a band of dense pink collagenous (fibrous) scar between areas of surviving myocardium.

Complications of MI

Early / acute

• Acute heart failure: left side gives hypotension and pulmonary oedema; right side gives peripheral oedema.
• Cardiogenic shock, which accounts for two thirds of deaths in acute MI.
• Arrhythmias of all types, including potentially fatal ventricular fibrillation.
• Myocardial rupture, occurring 5 to 7 days following MI:
  • Ventricular free wall rupture, leading to haemopericardium and cardiac tamponade.
  • Rupture of the interventricular septum, leading to a left to right shunt.
  • Papillary muscle rupture, leading to acute (mitral) valve regurgitation.
• Pericarditis: 1 to 2 days following a transmural infarct; grossly a roughened fibrinous epicardial surface over the infarct.
• Mural thrombus formation: occurs overlying the infarct because of stasis (loss of myocardial contractility) plus endocardial (endothelial) damage. It carries the potential for thromboembolism, and is another reason for antiplatelets and anticoagulants. Grossly, dark thrombus adherent to the endocardium overlying the infarct.

Late

• Ventricular aneurysm formation: occurs late, due to scarring and bulging of the ventricular wall, seen grossly as a thin bulging scarred left ventricular wall. It can itself lead to mural thrombus formation and thromboembolism.
• Ischaemic papillary muscle dysfunction.
• Progressive late heart failure (chronic IHD).

Chronic IHD with heart failure

• Progressive congestive heart failure due to accumulated ischaemic damage over the years, with a history of previous MI in most cases.
• Left sided failure: systolic failure with pooling of blood in the lungs, giving pulmonary oedema, which produces cough, dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea and crepitations. Gross appearance of the lung: a dark red, wet, frothy cut surface.
• Right sided failure: mostly secondary to left sided failure, because increased pressure in the pulmonary circulation causes pressure overload on the right side. It produces systemic venous congestion, giving peripheral oedema, elevated JVP and chronic liver congestion (nutmeg liver). Gross appearance of the liver: a mottled reddish-brown and tan-yellow cut surface resembling nutmeg.

Recommended reading

• Robbins and Cotran Pathologic Basis of Disease, 10th ed (ClinicalKey), Chapter 11 Blood Vessels: atherosclerosis pp. 493 to 504, abdominal aortic aneurysm p. 506.
• Or Robbins and Kumar Basic Pathology, 11th ed (ClinicalKey), Chapter 8 Blood Vessels: atherosclerosis pp. 280 to 288, abdominal aortic aneurysm p. 290.

Warning

The final slide of the deck is decorative and off-topic (a news item about an artist crocheting wire into an anatomically correct heart sculpture). It carries no pathology content.

Self-test

1. Define ischaemia, hypoxia and infarction.
2. Describe coagulative necrosis and explain why it is the relevant pattern in myocardial infarction.
3. State the lecture’s one-sentence definition of atherosclerosis.
4. List the types of artery affected by atherosclerosis and explain why veins and smaller arterioles are spared.
5. List the non-modifiable and the modifiable risk factors for atherosclerosis.
6. Distinguish the basal from the activated state of the endothelial cell, giving the maintaining factors of one and the triggers and consequences of the other.
7. Describe the steps by which chronic endothelial injury produces an atherosclerotic plaque.
8. Explain what a foam cell is and name the two cell types that can become one.
9. Describe the components of the fibrous cap and of the necrotic centre of a mature plaque.
10. Describe the gross and microscopic appearance of a fatty streak.
11. Distinguish a vulnerable from a stable plaque.
12. What degree of stenosis is regarded as critical, and what does it produce clinically?
13. Atherosclerosis is a disease of the intima, so explain how it leads to aneurysm formation, and state where aneurysms commonly occur, what shapes they take and what they commonly contain.
14. List the changes that constitute acute plaque change and state their immediate consequence.
15. List the clinical consequence of atherosclerosis in each of four arterial territories.
16. List the four clinical presentations of IHD, and state which three make up the acute coronary syndromes and what drives them.
17. Distinguish stable angina from unstable angina in terms of mechanism, trigger and relief.
18. What is Prinzmetal angina?
19. Describe the site, duration, character and radiation of the pain of myocardial ischaemia, and list four other manifestations.
20. Distinguish MI pain from stable anginal pain.
21. Name the cardiac biomarkers used to diagnose MI and explain how they reach the blood.
22. Explain “time is muscle”, including where necrosis starts, how long full-thickness necrosis takes, and the corresponding ECG finding.
23. Give the three coronary arteries with their share of MIs and the region of myocardium each supplies.
24. Describe the gross appearance of a myocardial infarct at 12 to 24 hours, at 3 to 7 days, at 1 to 2 weeks and at 2 to 8 weeks.
25. Describe the microscopic appearance of a myocardial infarct at 12 to 24 hours, at 1 to 3 days, at 3 to 7 days and at 2 to 8 weeks.
26. A patient collapses and dies 6 days after a transmural MI, with blood in the pericardial sac at autopsy. Explain what happened and why the timing fits.
27. List the early complications of MI, and state which accounts for two thirds of deaths in acute MI.
28. Explain why a mural thrombus forms over an infarct, and what it risks.
29. Explain how a ventricular aneurysm forms after MI and what further complication it can cause.
30. Describe the features of left sided and of right sided failure in chronic IHD, including the appearance of the lung and of the liver.
31. Integrative: trace the sequence from a modifiable risk factor such as hypertension through to chronic congestive heart failure, naming the key event at each stage.

Answers

Reveal answers

1. Ischaemia is reduced tissue blood flow. Hypoxia is oxygen deprivation, which causes cell injury by reducing aerobic oxidative respiration. Infarction is a localised area of ischaemic tissue necrosis, usually coagulative necrosis.
2. Coagulative necrosis is a form of necrosis in which tissue architecture, the ghost outline of the tissue, is preserved for at least some time. It is the usual pattern of necrosis in an infarct, so infarcted myocardium retains recognisable architecture early on.
3. Atherosclerosis is “a chronic inflammatory and healing response of arterial wall to endothelial injury”.
4. Elastic arteries such as the aorta, carotids and iliacs, and large and medium sized muscular arteries such as the coronaries. Veins and smaller arterioles do not get atherosclerosis because there is not enough pressure.
5. Non-modifiable: genetics (e.g. familial hypercholesterolaemia), family history, increasing age, male gender. Modifiable: hyperlipidaemia (hypercholesterolaemia), hypertension, cigarette smoking, diabetes, inflammation (increased CRP).
6. Basal state: maintained by normotension, laminar flow and growth factors such as VEGF, giving a non-adhesive, non-thrombogenic surface. Activated state: triggered by turbulent flow, hypertension, cytokines, complement, bacterial products, lipid products, advanced glycation end-products, hypoxia, acidosis, viruses and cigarette smoke, producing increased procoagulants, adhesion molecules and proinflammatory factors, and altered chemokine, cytokine and growth factor expression.
7. Chronic endothelial injury causes dysfunction with increased permeability and leukocyte and platelet adhesion; LDL and oxidised LDL seep into the wall; cytokines from activated endothelial cells attract monocytes that enter the intima, become activated macrophages and engulf lipid as foam cells, forming a fatty streak; further cytokines and growth factors from endothelial cells, platelets and macrophages recruit smooth muscle cells from the media or circulating precursors; these proliferate and deposit extracellular matrix and also become foam cells; T cells are recruited; a fibrolipid atheroma forms in the intima and encroaches on the lumen.
8. A foam cell is a lipid-engorged cell within the plaque. Both macrophages (derived from recruited monocytes) and smooth muscle cells can engulf lipid and become foam cells.
9. Fibrous cap: smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans and neovascularisation. Necrotic centre: cell debris, cholesterol crystals, foam cells and calcium.
10. Grossly, flat or slightly raised yellow streaks on the luminal surface. Microscopically, a layer of lipid-filled foamy macrophages in the intima just beneath the endothelial surface.
11. A vulnerable plaque has a large lipid core, a thin fibrous cap and inflammatory cells scattered through the cap. A stable plaque has a smaller lipid core and a thick fibrous cap.
12. Critical stenosis is about 70%, given as 70 to 75% for the coronary arteries. It causes mechanical obstruction with ischaemia of the territory supplied, presenting as stable or demand angina.
13. The plaque increases the diffusion distance from lumen to media, so the media degenerates and weakens through loss of elastic fibres; under arterial pressure the wall stretches and an aneurysm forms. They commonly occur in the abdominal aorta and common iliac arteries, can be saccular or fusiform, and commonly contain a mural thrombus. They can rupture.
14. Haemorrhage into the plaque from its new vessels, causing plaque expansion or rupture; and plaque ulceration, erosion or rupture. These trigger thrombosis with partial or complete occlusion of the vessel.
15. Arteries of the heart: ischaemic heart disease. Arteries of the brain: stroke. Lower limb arteries: peripheral vascular disease. Aorta: abdominal aortic aneurysm.
16. Angina pectoris (stable or unstable), myocardial infarction, sudden cardiac death from fatal arrhythmia (VF), and chronic IHD with heart failure. Unstable angina, MI and sudden cardiac death are the acute coronary syndromes, mostly caused by acute plaque change with obstructive thrombosis.
17. Stable angina is due to significant fixed coronary occlusion (critical stenosis), triggered by increased oxygen demand such as exercise, stress or emotional excitement, and is usually relieved by rest or vasodilators. Unstable angina is associated with plaque change plus superimposed non-occlusive thrombus and/or vasospasm, and the pain is prolonged, more frequent and occurs even at rest.
18. Angina caused by coronary artery spasm.
19. Precordial or substernal, chiefly retrosternal and intense, lasting 15 seconds to 15 minutes; described as viselike, constricting, a crushing weight and/or pressure, or burning; radiating most commonly to the left shoulder and/or the ulnar aspect of the left arm and hand, and possibly to neck, jaw, teeth, back, abdomen or right arm. Other manifestations include fear, shortness of breath, perspiration, nausea and vomiting, weakness, collapse and coma.
20. MI pain is severe and prolonged, lasting more than 30 minutes, and is not relieved by rest or vasodilators, whereas stable anginal pain lasts 15 seconds to 15 minutes and is usually relieved by rest or vasodilators.
21. Cardiac-specific troponins T and I (cTnT and cTnI, including high-sensitivity TnT) and the MB isoform of creatine kinase (CK-MB). At the onset of infarction the plasma membrane of necrotic myocytes becomes leaky, with myosin, actin and troponin free in the cytoplasm and troponin released from the actin filament, and these molecules then leak out of the cell into the circulation through a nearby blood vessel.
22. After acute coronary occlusion there is a zone of perfusion, the area at risk. Necrosis begins in the subendocardium and the zone of necrosis widens until it is transmural by approximately 6 hours, giving a completed infarct involving nearly the entire area at risk. Transmural infarction corresponds to STEMI on the ECG. Delay therefore costs muscle, so early diagnosis and intervention salvages myocardium.
23. LAD, 40 to 50% of cases, anterior and anteroseptal wall. RCA, 30 to 40%, inferior/posterior wall and right ventricle. LCX, 15 to 20%, lateral wall of the left ventricle.
24. 12 to 24 hours: dark mottling, a reddish-blue discoloration from stagnant blood. 3 to 7 days: a central pale yellow-tan infarct with a hyperaemic border. 1 to 2 weeks: a reddish depressed hyperaemic border formed by a rim of highly vascularised granulation tissue. 2 to 8 weeks: a grey-white collagenous scar. (Up to 12 hours there is no gross change.)
25. 12 to 24 hours: pyknotic dark small nuclei, hypereosinophilic necrotic myocytes and early neutrophil infiltration. 1 to 3 days: myocytes lose nuclei and cross striations, with marked interstitial neutrophil infiltration. 3 to 7 days: macrophage infiltration clearing necrotic debris. 2 to 8 weeks: collagenous scar. (At 4 to 12 hours there is early coagulative necrosis, oedema and haemorrhage; at 10 to 14 days, well established granulation tissue.)
26. Rupture of the infarcted left ventricular free wall, producing haemopericardium and cardiac tamponade. Myocardial rupture characteristically occurs 5 to 7 days after MI, when the necrotic wall is at its weakest, with neutrophil and macrophage clearance of debris and granulation tissue not yet established.
27. Acute heart failure (left sided giving hypotension and pulmonary oedema, right sided giving peripheral oedema), cardiogenic shock, arrhythmias of all types including fatal VF, myocardial rupture (free wall, interventricular septum, papillary muscle), pericarditis 1 to 2 days after a transmural infarct, and mural thrombus. Cardiogenic shock accounts for two thirds of deaths in acute MI.
28. Because of stasis over the non-contracting infarcted segment (loss of myocardial contractility) combined with endocardial, that is endothelial, damage. It risks thromboembolism, which is another reason for antiplatelet and anticoagulant treatment.
29. It occurs late, from scarring and bulging of the ventricular wall at the healed infarct. The aneurysmal segment can in turn lead to mural thrombus formation and thromboembolism.
30. Left sided: systolic failure with pooling of blood in the lungs and pulmonary oedema, giving cough, dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea and crepitations; the cut lung is dark red, wet and frothy. Right sided: mostly secondary to left sided failure through raised pulmonary pressure causing right-sided pressure overload, giving systemic venous congestion with peripheral oedema, elevated JVP and chronic liver congestion; the cut liver has a mottled reddish-brown and tan-yellow nutmeg appearance.
31. Hypertension injures and activates the coronary endothelium; LDL seeps into the intima and a chronic inflammatory and healing response follows, with foam cell formation, smooth muscle proliferation and matrix deposition, producing an atherosclerotic plaque; once stenosis reaches 70 to 75% the patient gets demand angina; acute plaque change with superimposed thrombosis then occludes the artery, causing myocardial infarction with myocyte necrosis in that artery’s territory; the infarct heals by neutrophil infiltration, macrophage debris clearance, granulation tissue and finally collagenous scar, which does not contract; accumulated ischaemic damage over the years leaves progressive congestive heart failure, that is chronic IHD, with pulmonary oedema from left sided failure and systemic venous congestion from secondary right sided failure.