ABSTRACT
Coronary artery disease Narrowing of the lumen of a coronary artery (stenosis) by atheroma may lead to chronic ischaemia of the muscle supplied by that artery. If the myocardium becomes ischaemic, it may also become electrically unstable, predisposing to the development of an abnormal heart rhythm (i.e. an arrhythmia). The oxygen requirement of the myocardium is dependent upon the heart rate; an increase in heart rate – for example during exercise, following a large meal or as a consequence of a sudden adrenaline response to stress, anger, fear or other such emotion – will lead to an increase in myocardial oxygen demand. If the increased oxygen demand cannot be met, owing to restriction of blood flow through the stenotic vessel, the myocardium distal to the stenosis will become ischaemic. Ischaemia does not invariably lead to myocardial infarction, it just has to be sufficiently severe to initiate a fatal arrhythmia and, if the region rendered ischaemic includes one of the pace-making nodes or a major branch of the conducting system, the risk that rhythm abnormalities will develop is greatly increased. Complications of atheromatous plaques may worsen the coronary stenosis and subsequent myocardial ischaemia. Bleeding may occur into a plaque and this can be seen as sub-intimal haemorrhage at autopsy. Sudden expansion of the plaque may lead to
rupture, which may also occur if the plaque ulcerates. When a plaque ruptures, the extruded cholesterol, fat and fibrous debris will be ‘washed downstream’ in the coronary artery and impact distally, often causing multiple mini-infarcts. The endothelial cap of a ruptured plaque may act as a flap valve within the vessel and cause a complete obstruction. An atheromatous plaque is a site for the development of thrombus, which will further reduce the vessel lumen without necessarily fully blocking the vessel. Coronary thrombosis underlies most of the complications of coronary artery atherosclerosis, including unstable angina, acute myocardial infarction and sudden cardiac death but such thrombi are found with variable frequency at autopsy – between 13% and 98% (Figure 6.1). Myocardial infarction occurs when there is severe stenosis or complete occlusion of a coronary artery so that the blood supply is insufficient to maintain
oxygenation of the myocardium. However, if there is adequate collateral circulation, blood can still reach the myocardium by other routes. The fatal effects of an infarct may appear at any time after the muscle has become ischaemic (Figure 6.2). The area of muscle damaged by a myocardial infarction is further weakened by the process of cellular death and the inflammatory response to these necrotic cells. The area of the myocardial infarct is weakest between 3 days and 1 week after the clinical onset of the infarct and it is at this time that the weakened area of myocardium may rupture, leading to sudden death from a haemopericardium and cardiac tamponade. The rupture occasionally occurs through the interventricular septum, resulting in a left-right shunt. If a papillary muscle is infarcted, it may rupture, which will allow part of the mitral
valve to prolapse, which may be associated with sudden death or may present as a sudden onset of valve insufficiency (Figure 6.3). An infarct heals by ‘scarring’ (fibrosis), and fibrotic plaques in the wall of the ventricle or septum may interfere with physical or electrical cardiac function. Cardiac aneurysms may form at sites of infarction; they may calcify and they may rupture. Physical lesions in the cardiac conducting system have been studied intensively in recent years, especially in relation to sudden death. Many different abnormalities have been found; it may be difficult to determine if conduction system lesions are the cause of a fatal arrhythmia or merely an incidental finding but, in the absence of any other abnormality, it may be reasonable to conclude that they were a significant factor in causing the death.
