(A) Causes of morbidity
1.Basic etiology
The vast majority (more than 95%) of cases are coronary atherosclerosis, occasionally coronary thrombosis, inflammation, congenital malformation, spasm and coronary artery mouth obstruction, resulting in severe luminal narrowing and insufficient myocardial blood supply, while the collateral circulation is not fully established. On this basis, myocardial infarction can occur once the myocardial blood supply is further sharply reduced or interrupted by the following conditions, resulting in severe and persistent acute ischemia of the myocardium for more than 1h (1) Intraluminal thrombosis of coronary arteries.
(1) Those without a history of angina pectoris before myocardial infarction.
Coronary artery atherosclerosis makes the lumen narrowing generally below 70%, the original lumen is relatively smooth, the area supplied by the artery has no effective collateral circulation, the thrombus makes the lumen suddenly completely blocked, and the myocardium supplied by this vessel is acutely necrotic.
In these patients, the onset of myocardial necrosis is rapid, the symptoms are severe, and the myocardial necrosis often extends from the subendocardium to the epicardium through the entire ventricular wall. The infarcted ventricular wall often becomes thin and dilates outward, and is prone to cardiac rupture within one week of onset, with thrombus blockage in the proximal end of the large branches of the coronary artery, and a wide range of penetrating infarcts, often resulting in acute left heart failure, cardiogenic shock and ventricular wall tumor formation.
②Persons with a history of pre-existing angina pectoris or old myocardial infarction.
Acute thrombus blocking another coronary artery not only causes acute myocardial necrosis at its blood supply site, but also blocks the collateral circulation providing the original ischemic and old myocardial infarction site, making the condition more severe than before.
(iii) Multi-branch coronary atherosclerosis.
If acute thrombotic blockage occurs at a branch of coronary plaque where the lumen has been extremely narrowed, generally there is a history of angina pectoris in the past, but because of the presence of a certain amount of collateral circulation that protects the subepicardial myocardium, myocardial necrosis due to acute blockage may be limited to the subendocardial myocardium, with multiple focal necrosis and a smaller infarct, so cardiac rupture and ventricular wall tumor formation are less likely to occur.
④ Incomplete blockage by thrombosis at the coronary plaque.
Patients often present with unstable angina, which can also lead to acute subendocardial myocardial infarction without abnormal Q waves on ECG, at which time serum myocardial enzymatic examination should be performed to help diagnosis.
(2) Coronary artery spasm.
Some authors performed coronary angiography in a group of patients with acute myocardial infarction within 12 h after the onset of the disease, showing that 40% had coronary spasm. Injection of nitroglycerin into the occluded coronary artery could open or partially open the occluded lumen, indicating that the acute myocardial infarction in this group was caused by coronary spasm.
(3) Bleeding within or under the atherosclerotic plaque.
The thin fibrous covering cap on the surface of lipid-rich soft plaques, together with the shape of the plaque, in which the fatty foci are in an eccentric position, are easily ruptured by blood flow impact. In addition to these vulnerable plaque structures, acute changes in intracavitary pressure by coronary arteries; changes in coronary artery tension; bending and torsion of coronary arteries with each heartbeat and other external factors can cause vulnerable plaque rupture or subintimal bleeding, inducing platelet aggregation thrombosis, causing coronary artery obstruction and leading to myocardial infarction.
(4) Sudden drop in cardiac blood output.
Shock, dehydration, bleeding, surgery or severe arrhythmias cause a sudden drop in cardiac output and a sharp decrease in coronary perfusion.
(5) A surge in myocardial oxygen demand.
Heavy physical activity, elevated blood pressure or emotional excitement lead to a significant increase in left ventricular load, increased secretion of catecholamines, a surge in myocardial oxygen demand, and a significant shortage of coronary artery blood supply, resulting in myocardial cell ischemia and necrosis.
2.Onset factors
For the development of myocardial infarction, as with all coronary heart diseases, hypercholesterolemia (or increased LDL), hypertension and smoking are important risk factors.
(1) Gender and age.
The majority of acute myocardial infarction occurs in middle-aged and elderly people over 40 years of age, accounting for about 95% of the total number of patients according to foreign literature, with individual patients less than 30 years of age, and the incidence increases significantly with age.
(2) Pre-existing relevant diseases before the onset.
The combination of hypertension in myocardial infarction cases reported in various parts of China accounted for 50% to 90%, and in Beijing from 1972 to 1983, 53.1% to 70.2%, which is generally slightly higher than the combination rate recorded abroad. The number of cases with diabetes mellitus ranged from 3.9% to 7.5%, which is slightly lower than the majority of foreign reports. Nearly half of the patients had a previous history of angina pectoris.
(3) Predisposing factors.
According to domestic data, about 1/2 to 2/3 of the cases have triggers to be found, among which overexertion, emotional excitement or nervousness are the most common, followed by full meals and upper respiratory tract or other infections, a few are surgical hemorrhage or other causes of hypotension, shock and subarachnoid hemorrhage, etc. There are also some patients who have episodes during sleep or complete rest. The number of acute myocardial infarction cases has a clear seasonal pattern, with two peak incidences from November to January and from March to April each year, suggesting that the incidence is related to climate change.
(II) Pathogenesis
1.Pathogenesis
Atherosclerotic lesions in coronary arteries are complicated by atheromatous plaque rupture and bleeding, intravascular thrombosis, subintimal hemorrhage or persistent arterial spasm, resulting in persistent and complete occlusion of the lumen, which can lead to acute myocardial infarction.
(1) Intracoronary thrombosis and myocardial infarction.
The vast majority of acute myocardial infarctions are caused by acute occlusion of the lumen complicated by stenotic atherosclerotic lesions in the coronary arteries, and the cause of this occlusion is mainly arterial thrombosis. Recent studies have also affirmed that acute thrombotic occlusion of coronary arteries is the main cause of acute transmural myocardial infarction. Myocardial ischemia occurs when coronary atheromatous plaque ruptures and its contents are exposed, inducing platelet aggregation, thrombosis and vasospasm, causing a dramatic reduction in coronary blood flow, and severe and persistent ischemia causing myocardial necrosis. In acute myocardial infarction, thrombosis in the coronary arteries can be as high as 90%.
(2) Coronary artery spasm and myocardial infarction.
It was found that 6.8% of patients showed normal coronary arteries, and myocardial infarction was considered to be caused by coronary artery spasm, but natural dissolution of the original coronary thrombus could not be excluded. Prolonged coronary artery spasm can cause acute myocardial infarction. Coronary artery spasm can also cause rupture or subintimal hemorrhage due to compression of the atheromatous plaque, inducing platelet aggregation and release of thromboxane A2 and 5-hydroxytryptamine. Further platelet aggregation and vasospasm can lead to thrombosis, resulting in acute myocardial infarction.
(3) Intra-atherogenic plaque bleeding and ulceration and myocardial infarction.
According to recent studies, there are two ways of thrombus formation after plaque rupture: one is plaque surface erosion, and thrombus occurs at the rupture that is attached to the plaque surface and blocks the blood vessel, leading to myocardial ischemic necrosis; while the other thrombus formation is rupture and bleeding in the deep part of plaque to form thrombus that gradually expands and blocks the blood vessel, causing acute myocardial infarction. In addition, atheromatous plaque material can block the distal coronary artery branches, causing myocardial necrosis.
(4) Sympathetic excitation and myocardial infarction.
Stress, overexertion, and mental tension can stimulate sympathetic excitation, release catecholamines, and induce myocardial infarction. The possible mechanisms of catecholamines induced myocardial infarction are as follows.
①Increased inward flow of calcium ions in cardiac myocytes: increased myocardial contraction and increased myocardial oxygen consumption, causing further damage to the hypoxic myocardium.
(ii) Catecholamines can damage cardiomyocyte mitochondria: reduce ATP production.
③Catecholamines excite α receptors: coronary vasoconstriction, β receptor excitation, and increased heart rate, resulting in increased myocardial cell oxygen consumption and decreased oxygen supply.
④Higher concentration of plasma free fatty acids: prompt platelet aggregation, resulting in vascular occlusion.
2.Pathophysiology
The pathophysiological changes of acute myocardial infarction are mainly manifested as some hemodynamic changes of ventricular involvement, electrophysiological instability and ventricular remodeling occurring in late stages.
(1) Hemodynamic alterations.
The severity of the hemodynamic alterations of ventricular involvement mainly depends on the infarct extent and site.
(1) Left ventricular function.
When antegrade blood flow interruption occurs in the coronary artery, the myocardium supplied by the vessels below the obstruction site loses its contractile capacity and is unable to complete contraction, and four abnormal forms of contraction of the myocardium occur in sequence.
A. Dyskinesia, in which adjacent myocardial segments do not contract at the same time.
B. Weak contraction, i.e., a decrease in the range of myocardial contraction.
C, absence of contraction, in which myocardial contraction is aborted.
D, paradoxical, with systolic bulge. At the same time as functional abnormalities occur at the infarct site, the residual normal myocardium shows excessive motion in the early phase as a result of acute compensations, including increased sympathetic nervous system activity and the Frank-Starling mechanism. Some of the compensatory over-exercise is ineffective work due to paradoxical motion in the infarcted area caused by contraction of the non-infarcted segment of myocardium. The excessive motion in the noninfarcted area gradually disappears within 2 weeks of infarction, while some degree of contraction recovery occurs at the infarct site, especially when there is reperfusion at the infarct site and myocardial stenosis is reduced, the faster and more pronounced these conditions appear.
Over time, edema, cellular infiltration, and fibrosis occur at the site of ischemic necrosis, and this change can increase the stiffness of the myocardium. The increased stiffness of the infarcted area prevents contradictory systolic ventricular wall motion and therefore helps to improve ventricular function.
Unless an extremely severe myocardial infarction occurs, wall motion can be improved during the healing period due to the gradual restoration of tonoplast function. Regardless of the duration of infarction, 20% to 25% of patients with motion abnormalities in the left ventricle may exhibit hemodynamic signs of left ventricular failure.
Infarcted and necrotic myocardium can alter left ventricular diastolic function, causing left ventricular compliance to increase and then decrease. After an initial increase in left ventricular end-diastolic pressure over several weeks, end-diastolic volume increases and diastolic pressure begins to decrease and normalize. Just as myocardial necrosis is accompanied by impairment of systolic function, the degree of abnormal diastolic function is also related to the extent of infarction.
② Regulation of circulatory function.
Abnormalities in circulatory regulation occur in AMI and begin when anatomic or functional stenosis occurs in the coronary vascular bed. The stenosis can lead to regional myocardial ischemia and, if sustained, to MI, and if the extent of infarction reaches a certain level, the entire left ventricular function is inhibited, resulting in a decrease in left ventricular stroke volume and an increase in filling pressures. A significant decrease in left ventricular beat volume will eventually decrease aortic pressure and coronary perfusion pressure.
This condition can exacerbate myocardial ischemia and cause a vicious cycle. Impaired left ventricular emptying capacity increases the preload, allowing the part of the left ventricle that is well perfused to function normally to dilate. This compensatory mechanism restores the beat-to-beat volume to normal, but decreases the ejection fraction. The dilated left ventricle also increases afterload, which not only depresses left ventricular beat volume but also exacerbates myocardial ischemia. When the area of malfunctioning myocardium is small and the rest of the left ventricle is functioning normally, compensatory mechanisms can maintain function throughout the left ventricle. Once the majority of the left ventricle is necrotic, the entire left ventricular function is inhibited to maintain normal circulation and pump failure occurs despite the expansion of the remaining surviving portion of the ventricle.
(2) Electrophysiological changes.
Myocardial cell edema, necrosis and inflammatory cell infiltration in the infarcted area can cause electrocardiographic instability. Activation of atrial and ventricular intramyocardial receptors caused by ischemic necrotic tissue increases sympathetic nerve activity and increases the concentration of catecholamines in circulating blood and the amount of catecholamines released locally from nerve endings within the heart. Catecholamine release may also be a direct result of ischemic injury to sympathetic neurons. Moreover, ischemic myocardium may be hypersensitive to the arrhythmogenic effects of norepinephrine, and there is great variability in the effects produced by different concentrations of catecholamines in different parts of the ischemic myocardium.
Sympathetic stimulation of the heart also increases autoregulation of Purkinje fibers, and catecholamines accelerate calcium-mediated conduction of slow ion flow responses, and stimulation of ischemic myocardium by catecholamines relying on these currents can induce arrhythmias.
In addition, transmural MI blocks the afferent and efferent branches that innervate the sympathetic nerves distal to the infarcted myocardium. Moreover, in addition to the autonomic nerve’s ability to coordinate changes in various cardiovascular reflexes, an imbalance in its regulation can contribute to arrhythmogenesis. This may explain why beta-blockers are equally effective in the treatment of ventricular arrhythmias, and are particularly effective when ventricular arrhythmias are accompanied by other manifestations of excessive increase in adrenergic activity.
Ventricular enlargement and remodeling after AMI can easily cause ventricular depolarization inconsistencies and foldback, leading to fatal arrhythmias. Electrolyte disturbances such as hypokalemia, hypomagnesemia, and acidosis can increase the concentration of free fatty acids in the blood, and the oxygen radicals generated can also cause arrhythmias to develop. The severity of these lesions, the size of the infarct and the status of infarct-related arterial perfusion determine the patient’s risk of developing severe arrhythmias-primary ventricular fibrillation (i.e., ventricular fibrillation presenting in the absence of congestive heart failure or cardiogenic shock).
(3) Ventricular remodeling.
After myocardial infarction, the left ventricular size, geometry, and thickness of the infarcted and noninfarcted segments are altered, and these changes are collectively referred to as ventricular remodeling. The remodeling process includes infarct expansion and ventricular enlargement, both of which can affect ventricular function and prognosis. Ventricular load status and the degree of patency of the infarct-related artery are important factors affecting left ventricular expansion. Increased ventricular pressure leads to increased wall tension and risk of infarct expansion, whereas patency of the infarct-related artery accelerates scar formation, increases tissue filling in the infarcted area, and reduces the risk of infarct expansion and ventricular dilatation.
①Infarct extension.
Acute expansion and thinning of the infarct zone that cannot be explained by additional myocardial necrosis, resulting in an increase in the extent of the infarct zone, is called infarct expansion. The reasons for this are: sliding between myofascicles reduces the number of ventricular myocytes throughout the thickness of the wall; rupture of normal myocytes; and loss of tissue in the necrotic zone. It is characterized by disproportionate thinning and expansion of the infarcted area, followed by the formation of a firm fibrotic scar. The degree of infarct expansion is related to the thickness of the pre-infarct ventricular wall. Prior myocardial hypertrophy prevents myocardial thinning. The apical ventricular wall is the thinnest and is the most vulnerable area to infarct expansion injury.
The occurrence of infarct extension not only increases the rate of death, but also the incidence of nonfatal complications such as heart failure and ventricular wall tumors is significantly higher. More than 3/4 of patients who die from AMI have myocardial infarct extension, and 1/3 to 2/3 are anterior wall ST-segment elevation infarcts. Echocardiography is the best means of diagnosing infarct extension and can detect a prolongation of the anechoic zone of the ventricle. When the extension is severe, the most typical clinical signs are the presence of a loud gallop rhythm and the development of pulmonary stasis or worsening of the original pulmonary stasis. Ventricular rupture is the most serious consequence of infarct extension.
(ii) Ventricular dilatation.
In addition to infarct expansion, dilatation of the surviving portion of the ventricle is also importantly associated with remodeling. Ventricular dilatation begins immediately after the onset of infarction and continues for months or even years thereafter. The dilation of the non-infarcted region can be considered as a compensatory mechanism oriented toward the maintenance of the beat volume in a large infarct, and the additional burden on the residual functional myocardium may be responsible for myocardial hypertrophy.
Hypertrophy of the myocardium helps to compensate for the functional impairment produced by the infarction. This is responsible for the hemodynamic improvement seen in some patients several months after MI. The surviving myocardium is eventually damaged, leading to further myocardial expansion, overall myocardial dysfunction, and eventually heart failure. This spherical dilatation in the non-infarcted zone, although partially compensating for the maintenance of cardiac function, also tends to inconsistently depolarize the myocardium, leaving the patient vulnerable to fatal arrhythmias.