Blood supply of the heart
- The coronary arteries originate from the aorta immediately distal to the aortic valve in the sinuses of Valsalva
- Consist of epicardial coronary arteries and smaller vessels that penetrate the myocardium (intramural arteries). These small arteries yield arterioles and a rich network of capillaries in which there is nearly one vessel adjacent to each myocyte
- The 3 major epicardial coronary arteries are;
- LAD – branches of which are called the diagonal and septal perforators
- Left circumflex – braches of which are the obtuse marginals
- Right coronary artery
- LAD – branches of which are called the diagonal and septal perforators
- Most blood flow to the myocardium is during diastole
Perfusion
- LAD supplies;
- The apex
- The anterior wall of the left ventricle
- Anterior 2/3 of the intraventricular septum
- The apex
- In a right dominant circulation
- The circumflex artery perfuses only the lateral wall of the left ventricle
- The RCA supplies the entire RV free wall and the posterobasal wall of the left ventricle
- The circumflex artery perfuses only the lateral wall of the left ventricle
Ishaemic Heart Disease
- Ischaemia comprises;
- Insufficient oxygen
- Insufficient nutrients
- Inadequate removal of metabolite
- Insufficient oxygen
- The clinical manifestations of IHD can be divided into 4 syndromes;
- Myocardial infarction
- Angina pectoris
- Chronic IHD and heart failure
- Sudden cardiac death
- Acute MI, unstable angina and sudden cardiac death can be referred to as acute coronary syndrome.
Epidemiology
- Leading cause of death for both males and female in the western world
- However since the 1960’s the overall death rate from IHD has decreased by 50%. This has occurred by;
- Prevention – modifiable risk factors such as smoking, high cholesterol and blood pressure
- Diagnostic and therapeutic advances – e.g. thrombolysis, coronary angioplasty, CABG
- Additional factors may be, improved sugar control in diabetes, control of obesity and aspirin prophylaxis
Pathogenesis
- Caused by diminished coronary perfusion relative to myocardial demand due to an interaction between atherosclerotic narrowing of the coronary arteries, intraluminal thrombosis overlying a disrupted atherosclerotic plaque, platelet aggregation and vasospasm
- In >90% of cases the cause is atherosclerosis of the coronary arteries reducing perfusion
- Narrowing of 75% or greater causes symptomatic ischaemia induced by exercise
- 90% stenosis can lead to ischaemia at rest
- Slowly developing occlusions may lead to the development collateral vessels which protect against distant ischaemia and infarction
- Role of acute plaque rupture
- The acute coronary syndromes are frequently initiated by an unpredictable conversion of a stable atherosclerotic plaque to an unstable artherothrombotic lesion, following disruption the following may happen;
- Rupture/fissuring, exposing the highly thrombogenic plaque contents
- Erosion/ulceration, exposing the thrombogenic subendothelial basement membrane to blood
- Haemorrhage into the atheroma, expanding its volume
- Statins are thought to help stabilize plaques
- Role of inflammation
- Inflammation is important in the development of artherosclerosis as T cells and monocytes enter the arterial wall as a consequence of the release of chemokines by endothelial cells and the expression of the adhesion molecules ICAM-1, ICAM-2, P-selectin and E-selectin by these cells. T cells located within the wall produce cytokines such as TNF, IFNγ and IL6 which activate macrophages which become loaded with oxidized LDL
- At later stages the destabilization and weakening of the plaque may involve the secretion of MMP by macrophages
- CRP may serve as a potential marker for atherosclerosis
- Role of coronary thrombus
- Partial or total thrombosis associated with a disrupted plaque is critical to the pathogenesis of acute coronary syndromes
- It may lead to occlusion of may embolise
- Also thrombus is a potent activator of multiple growth related signals in smooth muscle cells which can contribute to artherosclerotic lesions
- Role of vasoconstriction
- Vasoconstriction compromises lumen size and by increasing local mechanical forces can potentiate plaque disruption
- Vasoconstriction may be potentiated by;
- Circulating adrenergic agonists
- Localized released platelet contents
- Impaired secretion of endothelial relaxing factors relative to contracting factors
- Mediators released from perivascular inflammatory cells
Angina pectoris
- Symptom complex of IHD, characterized by paroxysmal and usually recurrent attacks of substernal or precordial chest discomfort caused by transient myocardial ischaemia that falls short of inducing the cellular necrosis that defines infarction
- There are three patterns of angina pectoris;
- Stable
- Prinzmental or variant angina
- Unstable of crescendo angina
- Stable angina
- Appears to be caused by the reduction in coronary perfusion to a critical level by chronic stenosing coronary atherosclerosis
- This renders the heart more susceptible to ischaemia whenever there is increased demand e.g. exercise
- Usually relieved by rest and GTN
- Prizmental angina
- Episodic angina that occurs at rest and is due to coronary artery spasm
- Usually there is ST elevation on the ECG indicating ischaemia
- Generally responds to GTN and calcium channel blockers
- Unstable angina
- Refers to a pattern of pain that occurs with progressively increasing frequency, with progressively less effort, often occurs at rest and with prolonged duration
- It may be the prodrome of a subsequent MI
Myocardial infarction
- Death of cardiac muscle resulting from ischaemia
- Leading cause of death in the western world
- Most MI are transmural in which the necrosis involves the full thickness of the ventricular wall in the distribution of a single coronary artery. This pattern is normally associated with coronary artery artherosclerosis, acute plaque change and superimposed thrombosis
- In a subendocardial infarct, the necrosis is limited to the inner 1/3 of the ventrical wall and may extend laterally beyond the territory of a single coronary artery
- A subendocardial infarct can occur due to;
- A plaque disruption followed by coronary thrombus that becomes lysed before necrosis extends across the thickness of the wall
- Prolonged, severe reduction in systemic blood pressure e.g. in shock. In which case the are usually circumferential rather than limited to the distribution of a single coronary artery
Incidence and aetology
- More common with increasing age and when predispositions to atherosclerosis are present;
- Hypertension
- Smoking
- Diabetes
- Hypercholesterolaemia
- Hyperlipoproteinaemia
- Men are more susceptible than women, as women are protected during their reproductive years
Pathogenesis
- Coronary artery occlusion
- In typical MI, the following sequence of events can be proposed;
- The initial event is a sudden change in the morphology of an atheromatous plaque
- Exposed to subendothelial collagen and necrotic plaque contents, platelets undergo adhesion, aggregation, activation and release of potent aggregators including thromboxane A2 and platelet factors 3 and 4
- Vasospasm is stimulated by platelet aggregation and the release of mediators
- Other mediators activate the extrinsic pathway of coagulation adding to the bulk of the thrombus
- Frequently within minutes the thrombus evolves to completely occlude the lumen of the vessel
- In around 10% of cases, transmural acute MI is not associated with atherosclerotic plaque thrombosis. In these situations other mechanisms may be involved;
- Vasospasm – sometimes related to cocaine abuse
- Emboli – from the LA in association with AF, a left sided thrombosis or vegetative endocarditis or paradoxical emboli crossing from the right side of the heart through a patent foramen ovale
- Unexplained – vasculitis, haemoglobinopathies, amyloidosis
Myocardial response
- The principle early consequences of mycocardial ischaemia is the cessation of aerobic glycolysis, and therefore the initiation of anaerobic glycolysis within secs leading to inadequate production of high energy phosphates and the production of potentially noxious breakdown products such as lactic acid
- Myocardial tissue is exceedingly sensitive to ischaemia with a decrease in contractility after only 60 secs which can precipitate heart failure
- Only after 20 -40 mins does irreversible myocyte injury occur
- Classic acute MI occurs when the perfusion of the mycocardium is reduced severely below its needs for an extended interval, usually at least 2 to 3 hours cusing profound, prolonged ischaemia and resulting in permanent loss of function of large regions in which cell death has occurred
- Predominant mechanism of cell death is coagulation necrosis
- If reperfusion follows briefer periods of flow deprivation, loss of cell viability can be prevented
- Myocardial ischaemia can lead to arrhythmias probably die to electrical instability
Approximate time onset of key events in ischaemic cardiac myocytes;
|
Feature |
Time |
|
Onset of ATP depletion |
Seconds |
|
Loss of contractility |
Less than 2 mins |
|
ATP reduced To 50% of normal To 10% of normal |
10 mins 40 mins |
|
Irreversibly injury |
20-40 mins |
|
Microvascular injury |
Less than 1 hour |
- Irreversibly injury occurs first in the sudendocardial zone
- The precise location, size and specific morphological features of an acute MI depends upon;
- The location, severity and rate of development of coronary atherosclerotic obstructions
- The size of the vascular bed perfused by the obstructed vessels
- The duration of the occlusion
- The metabolic/oxygen needs of the myocardium at risk
- The extent of collateral vessels
- The presence, site and severity of coronary arterial spasm
- Other factors such as blood pressure, heart rate and cardiac rhythm
Morphology
- Nearly all transmural infarcts involve a portion of the left ventrical
- Isolated RV infarction occurs in only 1-3% of cases
- Almost always there is a narrow rim of preserved subendocardial myocardium sustained by diffusion of oxygen and nutrients from the lumen
- Lesions on the LAD causes infarction of the anterior wall of the
LV near the apex, the anterior portion of the ventricular septum and the apex itself circumferentially - RCA infarct involves the inferior/posterior wall of the
LV , posterior portion of the ventricular septum and in some cases the inferior/posterior all of the RV - Left circumflex infarct involves the lateral wall of the left ventricle
- The gross appearance of an infarct depends on the survival of the patient following the MI
- Areas of damage undergo a progressive sequence of morphological changes
- Macroscopic
- MI less than 12 hours old are not apparent by gross examination
- To highlight areas of necrosis after 2-3 hours following infarct, immerse the tissue in triphenyltetrazolium chloride, which stains areas with intact dehydrogenase enzymes red with infracted areas showing up as unstained pale zone
- After 12-24hr an infarct can be identified as a red/blue hue caused by stagnated blood
- Progressively the unfarct becomes more sharply defined and yellowish in colour, within a weak it develops a hyperaemic zone of highly vascularised granulation tissue
- From around 2 weeks scar tissue forms
- Histological changes
- Typical changes of coagulation necrosis are evident from 4-12 hours with wav fibres being present at the periphery of the infarct, where viably fibres have tugged on the dead fibres during systole, stretching an buckling them
- In the infarct margin there may be vacuolar degeneration (which is potentially reversible)
- The necrotic tissue elicits acute inflammation (within 2-3 days), thereafter macrophages remove necrotic myocytes and the damaged zone is progressively replaced with highly vascular granulation tissue which progressively becomes less vascularised and more fibrous (scars forming within 6 weeks)
- Infarct healing occurs from the periphery towards the centre
- Once a lesion has completely healed it is impossible to determine its age
- Electron microscopy
- Within 30mins there is relaxation of the myofibrils, glycogen loss and mitochondrial swelling
- Between ½ to 4 hours there is sarcolemmal disruption and mitochondrial amorphous densities
Clinical features
- Classically diagnosed by typical symptoms, biochemical changes and by the ECG pattern
- 10-15% may be an asymptomatic MI – more common in the elderly and diabetics
- Troponins are proteins that regulate calcium mediated contraction of cardiac and skeletal muscle, they have near complete tissue specificity and high sensitivity. TnI and TnT rise at 2-4hrs after event and stay high for 7-10 days after acute event
- Levels are increased in patients who have had reperfusion due to washing out of the enzyme from the necrotic tissue
Consequences and complications of MI
- Poor prognosis is associated with;
- Advanced age
- Female gender
- Diabetes
- Previous MI
- Nearly ¾ of patients have one or more complication following an MI. These include;
- Contractile dysfunction
- MI’s produce abnormalities in ventricular function approximately proportional to their size
- May result in hypotension and pulmonary oedema e.g. cardiogenic shock
- Arrhythmias
- Conduction disturbance and myocardial irritability following an MI
- Myocardial rupture
- Cardiac rupture syndromes result from the mechanical weakening that occurs in necrotic and inflamed myocardium;
- Rupture of the ventricular wall resulting in cardiac tamponade
- Rupture of the ventricular septum resulting in left-right shunt
- Papillary muscle rupture resulting in acute onset mitral regurgitation
- Pericarditis
- A fibrinous or fibrohaemorrhagic pericarditis usually develops about the second or third following a transmural infarct and generally resolves over time
- Right ventricular infarction
- Infarction of the right ventricle often accompanies ischaemic injury of the adjacent posterior left ventricle and the ventricular septum
- Infarct extension
- New necrosis may occur adjacent to the existing infarct
- Infarct expansion
- Owing to weakening of the necrotic muscle there may be disproportionate stretching, thinning and dilation of the infarct region
- Mural thrombus
- With any infarct the combination of local myocardial contraction abnormalities and endocardial damage can result in mural thrombus and potentially thromboembolism
- Ventricular aneurism
- Complications of which are mural thrombus, arrhythmias and heat failure
- Papillary muscle dysfunction
- Progressive late heart failure – chronic IHD
- Contractile dysfunction
- Large transmural infarcts more commonly lead to;
- Cardiogenic shock
- Arrhythmias
- Chronic IHD
- Patients with anterior transmural infarct are at increased risk of;
- Free wall rupture
- Expansion
- Mural thombi
- Aneurism
- Posterior transmural infarcts are associated with;
- Conduction defects
- Right ventricular involvement
- Ventricular septal defects
Prognosis
- Total mortality rate within the first year is 30%
- Thereafter there is a 3-4% mortality among survivors with each passing year
Chronic Ischaemic Heart Disease
- Describes progressive heart failure as a consequence of ischaemic myocardial damage
- Also called ischaemic cardiomyopathy
- In most cases there is a history of prior MI and sometime CABG or other intervention
- Usually constitutes post infaction cardiac decompensation due to exhaustion of the compensatory hypertrophy of non infracted myocardium
- Patients normally have
LV hypertrophy and dilation
Sudden cardiac death
- Defined as unexpected death from cardiac causes early after symptom onset (within 1hr) or without symptoms
- May be the first clinical manifestation of IHD
- Generally causes a lethal arrhythmia
- 80-90% caused by atherosclerosis
- With decreasing age, other non atherosclerotic causes of sudden cardiac death are more likely, such as;
- Congenital structural or coronary artery abnormalities
- Aortic valve stenosis
- Mitral valve prolapse
- Myocarditis
- Dilated or hypertrophic cardiomyopathy
- Pulmonary hypertension
- Increased cardiac mass – seen in atheletes