Although atherosclerosis of the coronary arteries is the most common cause of luminal stenosis and coronary heart disease, there are many non-atherosclerotic causes of severe luminal stenosis and associated clinical coronary events such as angina pectoris or acute myocardial infarction. Various non-atherosclerotic coronary artery diseases can reduce or interfere with coronary blood flow through the following mechanisms: ① Fixed lumen obstruction (intrinsic stenosis). ② Lumen involvement due to lesions in the arterial wall or adjacent tissues (exogenous stenosis) or a combination of both. The reduction in coronary blood flow can also be caused by dynamic changes in the nearly normal coronary artery wall (spasm) or by an imbalance in the balance of myocardial oxygen supply and demand. Liu Haibo, Department of Cardiovascular Medicine, Fu Wai Hospital, Beijing, China
This article focuses on non-atherosclerotic factors that cause coronary artery stenosis or obstruction, such as congenital malformations, coronary artery coarctation, inflammatory coronary artery disease, coronary thrombosis (antiphospholipid antibody syndrome), coronary embolism and coronary spasm.
Section I. Congenital malformations
The right and left coronary arteries originate from the same walsalis sinus: the anomalous vessel passes across the base of the heart in front of the pulmonary vascular trunk, behind the aorta, or between the aorta and pulmonary artery. Sudden death and myocardial infarction related to the anomaly occurs in 79% of these patients.
Single coronary artery
Patients with a single coronary artery can be clinically asymptomatic, so the diagnosis is made predominantly by angiography during life. The disease needs to be differentiated from complete obstruction of the opening of one coronary artery due to atherosclerosis or thrombosis. When the main trunk or major branch of a single coronary artery travels between the pulmonary artery and the aorta, mechanical compression of the aorta or pulmonary artery can cause myocardial ischemia or even sudden death.
Coronary artery atresia
In infants and children, atresia of one of the two main coronary arteries can be associated with myocardial ischemia or infarction. The affected vessel is supplied with blood by a collateral branch from the opposite coronary artery.
Coronary artery ectasia
In infants and children, myocardial ischemia and infarction can be caused by ectopic origin of the coronary artery from the pulmonary artery trunk, with the left coronary artery being the ectopic artery in 90% of cases. Patients in this group often present with systolic murmurs or sudden death and abnormal electrocardiograms due to damage to the papillary activated anterior septal myocardium.
Myocardial bridges
A portion of the coronary artery is buried in the myocardium, forming a myocardial bridge. It is found in 0.5% to 7.5% of all patients who undergo coronary angiography for chest pain and has been reported as a cause of sudden death in young athletes. The left anterior descending branch is the most vulnerable to compression by the myocardial bridge. Most patients are asymptomatic, a few patients may have angina pectoris, and very few patients develop myocardial infarction. Myocardial ischemia can be seen as ventricular arrhythmias, and obstruction of the left anterior descending branch and the first penetrating branch can cause a high degree of atrioventricular block, which can lead to sudden death when the dominant proximal coronary artery is compressed. In this group of patients, the gyral branch and right coronary are thin, and there is little collateral circulation, and the damaged coronary supply area is mostly ischemic necrosis.
Coronary artery fistula
Abnormal communication between the coronary artery and its branches and the heart chambers and vessels. It can be seen at any age and is mostly found on coronary angiography. There may be a clinical continuity murmur, angina pectoris, myocardial infarction, sudden death, heart failure, endocarditis, arrhythmia, and superior vena cava syndrome. Right coronary artery fistulas are more common, with 90% of fistulas flowing into the venous circulation, mostly in a single channel.
Coronary artery aneurysms
Congenital coronary aneurysms are most often seen in the right coronary artery, while acquired coronary aneurysms are most often seen in atherosclerosis. Severe coronary artery aneurysms in adults are likely to arise from a history of polyarteritis nodosa, Kawasaki disease or aortitis in early childhood.
Section 2: Coronary artery coarctation
A separation of the middle layer of an artery with or without an intimal tear due to hemorrhage is called coronary artery coarctation. The separation forces the intima-media layer (the wall of the true lumen) to move into the true lumen of the coronary artery, resulting in distal myocardial ischemia or infarction. Coronary artery entrapment can be primary or secondary. Secondary coronary artery entrapment is more common, especially when it is caused by extension of the aortic root entrapment. Primary coronary artery entrapment can be caused by coronary angiography, cardiac surgery, thoracic trauma, or spontaneous.
Most spontaneous coronary artery occlusion occurs in younger women (usually in the postpartum period). The left anterior descending branch (or left main trunk) is often involved. The right coronary artery is also susceptible to involvement in men. The etiology of spontaneous coronary artery coarctation is unknown. These patients can be roughly divided into 3 groups: ① Those with underlying atherosclerotic lesions. (2) Those with postpartum-related disease. (iii) Those who are idiopathic. Systemic hypertension is not a risk factor for spontaneous coarctation. In some patients with spontaneous coronary artery coarctation, the presence of small cytosolic lumina in the middle layer of the affected coronary artery was seen at autopsy, which may be one of the etiologies. It has been suggested that eosinophil infiltration of the coronary artery wall may also be a cause of spontaneous coronary artery coarctation. By releasing proteases from their granules, eosinophils destroy the collagen, elastin, or smooth muscle of the coronary artery, which eventually leads to the development of the coarctation.
Spontaneous coronary artery entrapment can lead to sudden death or acute myocardial infarction. Patients who survive the initial event of spontaneous coronary artery entrapment have a better prognosis, with a survival rate of up to 80% at 4 years. The treatment of spontaneous coronary artery entrapment is uncertain. In most patients with relatively stable disease, aspirin, calcium antagonists, and nitrates are associated with better outcomes. Coronary artery bypass grafting (CABG) and/or percutaneous intervention (PCI) may be effective in patients with left main artery lesions, multiple lesions, uncontrollable medications, and unstable disease.
Section III Coronary arteritis (vasculitis)
Coronary arteritis, referred to as coronary arteritis (vasculitis), is a rare event that has been reported in a variety of conditions. Coronary artery injury can lead directly to myocardial ischemia or myocardial infarction (MI), with or without thrombosis of the coronary artery in question. Some authors (Baroldi) have usefully classified coronary arteritis according to the route of infiltration into the coronary arteries. Coronary arteritis can be caused directly by infection of adjacent organs or tissues (e.g. epicardial or myocardial abscesses due to aortic valve, endocarditis, epicardial tuberculosis). In this case, the outer wall of the coronary artery is first involved; coronary arteritis can also be caused by transmission from the coronary lumen or trophoblastic vessels via a blood source, in which case the intimal layer is first involved. For some other vasculitis, the exact mechanism of the source of dissemination is not known. Some morphologic histologic manifestations have also been used as markers of coronary arteritis as follows: ① limited arterial necrosis with or without calcification. (ii) Acute coronary thrombosis or mechanized thrombus recanalization without underlying atherosclerosis. ③ Vascular rupture unrelated to injury or intervention. ④ Coronary artery wall thickening with secondary lumen narrowing. ⑤ Wall thinning with aneurysm formation. Specific coronary lesions may also be seen in specific systemic diseases (e.g., polyarteritis nodosa).
Tuberculosis
Tuberculous vasculitis is seen mainly in patients with epicardial and myocardial lesions. Atopic coronary sarcoidosis may involve the outer (outer) layer of the vessel, the inner membrane, or the entire vessel.
Polyarteritis nodosa
Nodular polyarteritis is probably the most common cause of coronary artery vasculitis. It is a systemic necrotizing vasculitis affecting small and medium-sized vessels.Holsinger et al. reported 66 patients, 41 (62%) with coronary artery involvement and 41 with varying degrees of myocardial infarction. Coronary artery lesions were identical to necrotizing vasculitic lesions at other sites. The early phase is characterized by disintegration of the middle and inner elastic membranes, while the repair phase is characterized by intimal hyperplasia and scar formation. Coronary arteries can also dilate to form ventral coronary aneurysms, which can be occluded or ruptured by thrombosis (leading to fatal pericardial tamponade).
Giant cell arteritis
Giant cell arteritis primarily involves the temporal lobe and other cranial arteries. However, cases of coronary artery involvement and myocardial infarction have been reported. The arterial wall lesion is a granulomatous inflammatory reaction accompanied by infiltration of giant cells along the disintegrating internal elastic membrane. The intima will be extremely thickened, and eventually the vessel transforms into a fibrous stripe. Intraluminal thrombosis may also occur. Of the 16 patients with temporal lobe arteritis reported by Harrison, only 1 had coronary artery involvement.
Systemic lupus erythematosus
Pericardial and myocardial involvement is a common complication of SLE. Multiple young lupus patients without atherosclerosis developed acute myocardial infarction, and autopsy of coronary arteries in these patients revealed intimal fibrotic hyperplasia, which may be a manifestation of arteritis after repair. Analysis of a 16-year-old female lupus patient found that her acute myocardial infarction was due to a recent thrombotic occlusion of 3 major coronary arteries. A study of a 29-year-old woman with lupus and AMI who also had severe coronary atherosclerosis may suggest that the development of coronary atherosclerosis may be accelerated by lupus or other arteritis-causing diseases. In patients with diffuse fibrous necrosis and fibrosing vasculitis, finer intracardiac coronary arteries are often involved.
Burger’s disease (thromboembolic vasculitis occulta)
In a very small number of patients with Burger disease, polymorphonuclear leukocytes, histiocytes, and giant cell infiltrates are seen in the coronary arteries with or without coronary thrombosis; or just coronary thrombosis without cellular infiltration. In the 30 patients reported by Saphir, only 1 coronary artery was involved. In contrast, in the 19 patients studied by Averbuck and Silbert, there were 6 cases of coronary thrombosis.
Wegener’s granulomatosis
Wegener’s granulomatosis is a necrotizing vasculitis that often involves the renal and pulmonary vascular systems, and Parrillo and Fauci reported that fibrous necrosis was seen in small and medium-sized coronary arteries. Gatenly et al. reported that large coronary arteries can also be occluded, even leading to myocardial infarction.
Infectious (infectious) diseases
Many infectious (contagious) diseases are associated with coronary arteritis, such as syphilis, infective endocarditis, salmonellosis, typhus, and leprosy. Syphilis is one of the most frequent infectious diseases involving the coronary arteries. About one quarter of patients with stage III syphilis develop stenosis at the beginning (opening) of the coronary arteries. The beginning 3-4 mm of the left or right coronary artery is often infiltrated and presents as occlusive arteritis. In rare cases, coronary artery lesions present as syphilitic aneurysms. Angina pectoris and acute myocardial infarction can be caused by syphilitic coronary artery lesions. Plasmodium and Plasmodium-containing red blood cells can block larger coronary arteries. Schistosomiasis can also lead to myocardial infarction.
Conjunctival cutaneous lymph node syndrome (Kawasaki disease)
This acute febrile disease often affects infants and young children. In about 20% of patients, vasculitis of the trophoblastic vessels of the coronary arteries leads to coronary aneurysm formation, thrombosis, and myocardial infarction. 1-2% of patients die from myocardial infarction or ventricular arrhythmias. In advanced stages, thrombosis in the aneurysm may also cause myocardial infarction. Occasionally, aneurysm rupture may lead to death.
Takayasu disease (pulselessness, aortitis)
This condition can lead to granulomatous total arteritis and fibrosis of the aorta and its large branches, leading to luminal narrowing. In several case reports, the disease has been shown to involve the coronary artery openings and the proximal major coronary arteries. This coronary artery lesion can lead to angina pectoris and acute myocardial infarction.
Rheumatoid disease
In rare cases, arteritis and intimal thickening caused by rheumatoid disease can result in severe narrowing of the major coronary arteries. More commonly, diffuse coronary arteritis is common in 10% to 20% of patients with rheumatoid arthritis at autopsy in the smaller coronary arteries, including the traffic vessels. Severe stenosis can occur in the smaller intracardiac coronary arteries of patients with ankylosing spondylitis. A case of complete occlusion of the left main stem in a patient with ankylosing spondylitis has been reported.
Section 4: Coronary artery thrombosis (antiphospholipid antibody syndrome)
Antiphospholipid antibodies syndrome (APS) presents with recurrent arterial and venous thrombosis, cardiac or cerebral ischemia, habitual abortion, thrombocytopenia, and heart valve damage, either singly or in combination. These symptoms may be present singly or in combination with autoimmune diseases, and lupus anticoagulant (LA) or anticardiolipid antibodies (aCL) may be detected in the patient’s serum. Antiphospholipid antibodies (APA) may initially be found in patients with diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), or in patients without connective tissue disease. The main clinical categories are primary APS and secondary APS, and an extremely rare clinical type, called malignant APS, which presents with a short period of progressive and widespread thrombosis involving multiple vital organs, which can result in organ failure and death. The basic pathological changes of the disease are intravascular thrombosis, involving all levels of arteries, veins, endocardium and placenta.
4.1 Clinical manifestations
4.1.1 Coronary lesions The main clinical manifestations of APS are myocardial ischemic symptoms due to coronary thrombosis, and fatal and fatal myocardial infarction, which is the main cause of death.
4.1.2 Other arteriovenous thrombosis Clinical manifestations depend on the type, location and size of the involved vessels. Deep vein thrombosis of the lower extremities is the most common clinical manifestation. Thrombosis of hepatic and inferior vena cava veins causes Budd-Chaiari syndrome, cerebral artery thrombosis causes transient ischemic attack and stroke in young people, renal artery thrombosis causes proteinuria, nephrotic syndrome and hematuria, etc.; embolism of limb or internal cavity artery causes ischemic necrosis of extremity, various organs including liver, intestine, adrenal gland and heart, secondary organ The retinal arteries and veins can also be involved. Reticular cyanosis can be the skin manifestation of deep macrovascular lesions, and cyanotic vasculopathy is caused by the blockage of small superficial skin arteries causing superficial skin ulceration, necrosis and atrophy.
4.1.3 Habitual abortion Thrombosis of the placental vessels can lead to placental insufficiency, resulting in habitual abortion, pre-eclampsia, intrauterine distress, fetal growth retardation or stillbirth.
4.1.4 Thrombocytopenia Thrombocytopenia is another important clinical manifestation of APS.
4.2 Ancillary tests
The specific laboratory tests for APS are positive for LA and positive for aCL, which are moderate to high and low. Primary APS often has normal laboratory parameters, except for increased sedimentation and immunoglobulins. The laboratory indexes of secondary APS are similar to those of the primary disease.
4.3 Other tests
CT, MRI, digital subtraction angiography, angiography and other examinations can be done according to the site involved in the thrombus.
4.4 Clinical diagnosis
APS should be considered in young patients with no clear clinical risk factors, a history of previous thrombosis, myocardial ischemia or myocardial infarction, and if necessary, specific clinical tests should be performed to clarify the diagnosis. The exact proportion of all patients with coronary artery disease in whom APS is the primary cause is not known. Early clinical diagnosis does present some difficulties, but clinicians should be aware that APS is associated with coronary artery disease and should try to achieve early detection and early treatment to save lives to the greatest extent possible.
4.5 Treatment
The treatment of thrombosis in APS can be divided into acute treatment, organ blood circulation reconstruction and treatment to prevent thrombus re-formation.
4.5.1 Acute treatment
For myocardial infarction, thrombolytic or interventional treatment should be taken as early as possible. Antithrombotic therapy can be used to block the continued formation of thrombus with normal heparin or low molecular heparin, and the INR should be maintained at 2-2.5 times the normal value.
4.5.2 Intermediate and long-term treatment
Attention should be paid to the prevention of thrombus re-formation. Subcutaneous injection of low-molecular heparin or oral treatment with high-dose warfarin will maintain the INR between 2.6 and 3.5. Retinal arteriovenous thrombosis, cerebrovascular thrombosis and habitual abortion can be treated with low-dose warfarin and low-dose aspirin, and the INR should be between 2.5 and 3.0. Low-molecular heparin can be added.
Section V. Coronary embolism
Coronary embolism should be clinically suspected in patients with severe chest pain (acute myocardial infarction) due to: the presence of a left heart prosthetic valve; active infective endocarditis; in situ left heart valve stenosis; atrial fibrillation; left ventricular ventricular wall tumor; dilated cardiomyopathy; known cardiac tumor; during cardiac catheterization or cardiac surgery. The etiology of coronary embolism can be divided into: natural causes, medical factors, and those of unknown origin. Coronary embolism most often involves the left anterior descending branch. At autopsy, coronary embolism should be suspected as the cause when the myocardial necrosis is large and discrete (in which case there is insufficient time to establish effective collateral circulation). Embolic coronary lesions can degrade completely and spontaneously. This is one of the explanations for the finding of completely normal coronary arteries on coronary angiography several months after acute myocardial infarction.
The consequences of coronary embolism depend on two main factors: the size of the embolus and the size of the lumen of the involved coronary artery. The smaller the embolus, the more likely it is to rush to a small distal coronary segment, and the less likely it is that a myocardial infarction or fatal arrhythmia will occur. If the embolus is extremely small, it may affect only a single small intra-mural vessel, which may be clinically asymptomatic and found only at autopsy. The underlying condition of the coronary lumen prior to embolization also determines the outcome of myocardial infarction. If the coronary artery is normal before embolization, the embolus will easily migrate to the distal coronary artery and may produce only focal myocardial infarction. Embolization of a diseased coronary artery is most likely to affect the proximal coronary artery. Left main stem embolism is rare but usually fatal.
Section 6: Coronary artery spasm
Coronary artery spasm can be involved in or trigger an acute myocardial infarction. The causes of coronary artery spasm include smoking, alcohol consumption, high-fat meals, drug use (marijuana, cocaine, etc.), and strenuous exercise.