Ischemic stroke after acute myocardial infarction (AMI) Ischemic stroke after acute myocardial infarction (AMI) is one of the complications of myocardial infarction, and ischemic stroke can occur at the same time or sequentially with AMI. They share many common risk factors and have similar pathophysiologic processes, and often occur at the same time. With advances in medical technology, the survival rate of patients with AMI has improved significantly, and there is limited information on the incidence and risk of concomitant stroke. The optimal therapeutic regimen has not been determined because of the lack of reliable information on the long-term natural course of the disease. Now, we would like to make a review on the risk factors of stroke after AMI and the related research progress. Epidemiology of post-MI ischemic stroke Cerebral infarction is the most common extracardiac complication of AMI.The incidence of post-MI stroke has been poorly reported, and there is a lack of data from large-scale epidemiological surveys. Previous studies have shown that the incidence of ischemic stroke after AMI ranges from 1.1% to 2.0%, with about 1.5% of AMI patients having a stroke early in the hospitalization period, and the incidence tends to increase year by year.1 A pooled analysis and a large-sample clinical study have shown that the incidence of ischemic stroke within 1 month after the onset of AMI is 1.2%, and the incidence within 1 year ranges from 2% to 2.14%.2 In the case of asymptomatic myocardial infarction, stroke is the most common complication of AMI, but it is not the most common complication of AMI. In patients with asymptomatic myocardial infarction (especially with diabetes mellitus), ischemic stroke may be the initial symptom of acute myocardial damage. Most secondary cerebral embolisms occur within days or weeks of AMI, and the risk returns to baseline levels approximately 3 to 6 months after the onset of AMI. A 22-year study in the United States showed that the average incidence of stroke was 22.6/1000 within 30 d after the onset of AMI, which was as much as 44 times higher than that in the normal population; the incidence of stroke was 1.6/1000 between day 31 and 1 year and declined over time, but remained 2-3 times higher than that of the normal population for 3 years, and then dropped to the level of the normal population after 3 years. Stroke after myocardial infarction significantly increases the risk of death in patients with AMI, and the risk of death is higher in patients with concomitant stroke at the beginning of hospitalization than in other AMI patients. Univariate analysis showed that advanced age, female sex, hypertension, diabetes mellitus, atrial fibrillation, Killip classification, and history of previous stroke were associated with post-MI stroke, whereas peak creatine kinase levels, Q-wave changes, and ST-segment elevation were not associated with post-MI stroke. Multivariate analysis showed that independent risk factors for post-MI stroke included advanced age [oddsratio (OR) 1.04, 95% confidence interval (CI) 1.03-1.05], history of previous stroke (OR 2.07, 95% CI 1.44-2.97]), diabetes mellitus (OR 1.68. 95% CI 1.27 to 2.20]), while findings regarding the correlation of myocardial infarction size, site, and severity with post-MI stroke were inconsistent. Systemic inflammatory response similarly increases the risk of AMI complicating cerebral infarction. One study showed that in patients discharged with AMI, stroke onset was associated with chronic atrial fibrillation, advanced age, history of previous myocardial infarction, anterior wall infarction, more than 4-fold elevation of aspartate aminotransferase levels, chronic renal failure, and history of previous stroke. The incidence of stroke in AMI patients with concomitant chronic atrial fibrillation was five times higher than that in the control group. 2, Pathological mechanisms of ischemic stroke after AMI 2.1 Site of AMI and stroke The overall risk of cerebral embolism after AMI is about 1%-6%, with the highest risk being in large anterior wall myocardial infarction, while the incidence of thromboembolic events in patients with inferior wall myocardial infarction is less than 1%. Overseas studies have shown that 76% of post-AMI ischemic strokes occur in patients with anterior wall myocardial infarction. There are aortic arch and carotid sinus pressure receptors in this area. When anterior wall myocardial infarction occurs, especially when the lesion is located on the left side, pathological reflexes are transmitted to the medulla oblongata nucleus of the cranium through the pressure receptors of the aortic arch and carotid sinus, which causes persistent spasm of the intracranial blood vessels, and then results in hypoxic edema of the brain tissues and slowing down of blood flow, and thrombus formation is easy to occur in this process. 2.2 Intracardiac Appendage Thrombosis and Dislodgement Embolism reflects acute myocardial injury and cardiac instability. Embolism is often secondary to ventricular dysfunction, intraventricular thrombosis, or coagulation cascade reactions. Attachment thrombosis is associated with post-MI ventricular remodeling, such as ventricular wall segmental motion abnormalities, ventricular wall tumors, ventricular septal defects, atrial fibrillation, and old massive myocardial infarctions.Post-MI ventricular wall segmental motion abnormalities result in increased autoregulation of pacing rhythm points in different parts of the heart. Atrial fibrillation and segmental wall motion abnormalities are the main factors in the formation of LV appendage thrombi.Bilge et al. concluded that appendage thrombosis is possible even if sinus rhythm is maintained after the onset of AMI. This type of accessory wall thrombus (i.e., ventricular wall tumor) occurs mostly in the apical region, and the incidence of true ventricular wall tumor accounts for 22% of myocardial infarction. Dislodgement of the attached thrombus and rupture of the ventricular mural tumor can lead to embolism.Kelly et al. showed that intracardiac thrombus formation and dislodgement are independent risk factors for ischemic stroke after AMI, which was supported by earlier pooled analyses performed by Vaitkus and Barnathan. Cerebral embolism occurs in approximately 3% of patients with AMI within 4 weeks of onset and is a common cause of cardiac cerebral embolism, accounting for 15% of all cardiac embolisms. Previous studies have shown that the incidence of left ventricular appendage thrombus is 1.5% in patients without a history of myocardial infarction, compared with 28%-34% in those with a history of myocardial infarction. Appendicular thrombus formation and dislodgement has been recognized and demonstrated for many years, but it is only one of several predisposing factors. 2.3 Atherosclerosis and hypoperfusion Atherosclerosis is a common risk factor for cardiovascular disease. Atherosclerosis roughens the endothelial surface of blood vessels, and the loosening of plaque properties and ulcer formation are important mechanisms for the development of successive or simultaneous infarcts in the heart and brain. In some patients, the stroke that occurs after AMI does not originate from a cardiac embolism, but rather from an artery-to-artery embolism. In addition to being a source of emboli, severe atherosclerosis causes severe stenosis or occlusion of the vessel, leading to hypoperfusion and thus ischemia. This hypoperfusion can exacerbate the damaging effects of embolization, and patients with relatively normal perfusion may be asymptomatic after embolization, whereas patients with a hypoperfused state may become symptomatic because perfusion does not recover rapidly. AMI can lead to cardiogenic shock and cardiac insufficiency, which in turn leads to cerebral ischemia and perfusion insufficiency on top of pre-existing cerebral stenosis, or, if vulnerable plaque is present in the vessel wall, to arterial-derived cerebral embolism due to hemodynamic changes after AMI. A pooled analysis showed that events such as left heart insufficiency, reduced ejection fraction, and heart failure can contribute to inadequate cerebral perfusion and are risk factors for stroke after myocardial infarction. AMI (especially inferior wall and right ventricular myocardial infarction) can result in significant fluid loss and hypovolemia due to pain, profuse sweating, nausea and vomiting, which in turn reduces cardiac output. Some medications have a greater effect on blood pressure during treatment, such as nitroglycerin, beta-blockers, and morphine, all of which can cause a drop in blood pressure. Revascularization can also induce a transient decrease in cardiac function, dominated by vagal regulation, resulting in vasodilation, decreased blood pressure and slow blood flow. All of these factors lead to inadequate cerebral perfusion, and patients with AMI who also combine these multiple risk factors have a significantly higher risk of concomitant cerebral infarction. 2.4 Treatment of AMI and Stroke During the acute phase of AMI, monitoring and rational control of blood pressure are extremely important, and care should be taken to prevent insufficient cerebral perfusion caused by too low blood pressure. For AMI patients with combined low blood pressure (<110/70 mm Hg, 1 mmHg=0.133 kPa), in order to prevent complication of ischemic stroke, small doses of blood pressure-raising drugs can be applied to improve cerebral blood circulation and increase cerebral perfusion pressure. Maintaining systolic blood pressure at 140-150 mmHg does not cause neurologic impairment and has minimal effect on cardiac function. Thrombolytic therapy and percutaneous coronary intervention (PCI) are beneficial in saving dying myocardium and reducing infarct size, increasing peripheral blood supply, reducing arrhythmia rates, and preventing ventricular wall tumor formation. In eligible patients, coronary blood flow should be actively restored to correct hypoperfusion, heart failure, the occurrence of malignant arrhythmias, and the restoration of various cardiac functions in a timely manner, thus ensuring cerebral blood supply. However, it is still controversial whether patients with high risk factors for appendage thrombosis such as atrial fibrillation should receive thrombolysis and invasive therapy, because appendage thrombus may dislodge after thrombolysis or invasive therapy and lead to cerebral embolism. The incidence of intracardiac appendage thrombosis in patients with AMI is 45.0%, and anticoagulation significantly reduces intracardiac thrombosis and prevents further infarction development, reinfarction, and ischemic stroke. In patients with AMI, prolonged anticoagulation reduces the risk of stroke by 40% within 3 years, but the risk of bleeding is relatively high.The 2008 ACC/AHA/ESC guidelines for the management of atrial fibrillation recommend that anticoagulation be given for at least 3 months to patients with left ventricular (LV) dysfunction, extensive ventricular (V) wall dyskinesia, or evidence of LV appendage thrombosis after AMI. In patients with AMI who have contraindications to anticoagulation, antiplatelet therapy has also been shown to be effective, significantly reducing the incidence of stroke during hospitalization. Imaging of ischemic stroke after AMI The presentation of stroke after AMI is not significantly different from that of common stroke. If AMI and cerebral infarction occur at the same time or successively, due to the existence of autonomic dysfunction in the former, dizziness, transient syncope, nausea, vomiting, eructation, shoulder-hand syndrome and other manifestations may occur, and sometimes it is not easy to distinguish from brainstem stroke. Imaging examination can clarify the diagnosis of cerebral infarction after AMI. For cerebral infarction due to embolic mechanism, echocardiography can detect intraventricular thrombus or appendage thrombus, and the detection rate of appendage thrombus by transesophageal echocardiography is better than that by transthoracic echocardiography, especially the display of left atrial structures, which can predict the risk of concomitant embolism. Embolic foci are often multiple, with infarcts varying in size depending on the size of the embolus, vascular status, and blood flow velocity (Figure 1A); hemorrhagic infarcts are more common because of the ease with which emboli can fragment and allow revascularization, as well as because of the antithrombotic therapy that is often administered after myocardial infarction (Figure 1B).Excessive post-MI decompensation, dehydration, or comorbid cardiogenic shock can result in cerebral hypoperfusion, which can cause watershed infarcts on top of pre-existing cerebral arterial stenosis. In addition to the existing cerebral arterial stenosis, watershed infarction can be caused, which can be manifested as anterior and posterior watershed and subcortical watershed infarction (Figure 1C). If the condition permits, transcranial Doppler (TCD), magnetic resonance angiography, and CT angiography can be used to evaluate the degree and location of stenosis, as well as to detect the nature of atherosclerotic plaques and to track microembolic signals in the blood flow. increased blood viscosity and increased secretion of inflammatory mediators after AMI can lead to in situ thrombus formation on the basis of the existing atherosclerotic plaques in cerebral arteries. In situ thrombosis on the basis of pre-existing atherosclerotic plaques can involve both anterior and posterior circulation, but it is more common in the internal carotid artery system and tends to be progressive, and the prognosis is usually poor. Figure 1 Imaging manifestations of stroke after AMI A: multiple infarct lesions in cardiac stroke; B: hemorrhagic transformation after anticoagulation in cardiac stroke: C: watershed infarction 4. Prevention and treatment of ischemic stroke after AMI AMI and stroke share common risk factors and pathophysiological bases, therefore the prevention of stroke should be emphasized while treating AMI. To control the risk factors of ischemic stroke complicated by AMI, including reasonable control of blood pressure, anti-atherosclerosis, regulation of blood lipids, blood sugar, etc.; actively treating cardiac diseases, including anti-thrombosis, controlling ventricular rate, resetting cardiac rhythm, improving cardiac function. Once cerebral infarction occurs, attention should be paid to balancing the treatment of brain complications and primary diseases, and the impact on AMI treatment should be noted when treating cerebral infarction. In addition, it is also important to control other complications such as fever and infection. 5, Conclusion Once ischemic stroke is concomitant after AMI, the prognosis of patients is usually worse, and its morbidity and mortality rate is two times higher than that of patients with AMI alone, and the morbidity and mortality rate within 6 months is as high as 27%. Therefore, the prevention of stroke in AMI patients should be emphasized. However, there are few clinical studies at home and abroad, and there is a lack of large-scale clinical trials.