Continuing Education Activity

The pathogenesis of acute myocardial infarction (AMI) and unstable angina is the rupture of the coronary artery plaque, resulting in acute thrombotic occlusion of a coronary artery. Thus, the thrombus forms an integral part of the atherosclerotic coronary plaques. There is a consensus that intracoronary thrombus is a challenging target for revascularization because of its unique characteristics. It has a crucial impact on the performance and outcome of the percutaneous coronary intervention (PCI). This activity reviews the cause and presentation of coronary artery thrombus and highlights the role of the interprofessional team in its management.

Objectives:

• Evaluate the pathophysiology of coronary artery thrombus.

• Identify the evaluation of a patient with coronary artery thrombus.

• Differentiate the treatment options for coronary artery thrombus.

• Communicate interprofessional team strategies for improving care coordination and communication to advance the management of coronary artery thrombi and improve outcomes.

Introduction

Coronary artery thrombus occurs due to rupture or preexisting coronary artery plaque erosion, resulting in the artery's complete occlusion.[1] It manifests clinically as an acute coronary syndrome, including ST-elevation MI, Non-ST elevation myocardial infarction, and unstable angina[2]. The coronary thrombus can occur in both symptomatic and asymptomatic patients with significant or less than 50% stenosis. Coronary thrombus is 1 of the frequent causes of sudden cardiac death[3][4]. The literature review shows that coronary thrombus causes one-third of the sudden cardiac death, completely occluding the culprit artery on autopsy. The amount and duration of coronary thrombus play an essential role in determining the prognosis of acute coronary syndrome patients.[5] The coronary thrombus has a crucial impact on the performance and outcome of percutaneous coronary intervention (PCI).[6] It is a strong predictor of PCI-induced major adverse coronary events, distal embolization, and stent thrombosis.[7] This topic reviews the etiology, epidemiology, pathophysiology, histopathology, history and physical examination, treatment, differential diagnosis, staging, and prognosis of coronary thrombus.

Etiology

The risk factors involved in coronary thrombus initiation include smoking, diabetes mellitus, hypertension, hyperlipidemia, stress, and a family history of atherosclerosis.

Epidemiology

Coronary thrombosis with acute myocardial infarction is a life-threatening condition and is associated with increased morbidity and mortality globally.[8] Coronary thrombus causes death in 200,000 persons a year in the United States, affecting males more than females

Pathophysiology

Understanding the structure of a thrombus and its physical characteristics is essential to make proper treatment choices in the revascularization of atherosclerotic lesions.[9] Following rupturing the plaque's fibrous cap, the internal necrotic core becomes exposed to the arterial lumen. This contact of a highly thrombogenic subendothelial matrix with the circulating platelets and white blood cells activates the coagulation cascade. It activates the platelets and promotes their adhesion and aggregation. Activated platelets release strong mediators of vasoconstriction and aggregation like serotonin, adenosine diphosphate, thromboxane A2, and endothelin, among others. The released tissue factor from the subendothelial matrix directly activates the extrinsic coagulation cascade and results in fibrin accumulation. All this finally accumulates to form a thrombus, which causes acute occlusion and impaired distal flow, with resultant clinical ischemic complications.[10] A thrombus comprises a conglomerate of platelets, red blood cells, vasoconstrictors, and procoagulant anchored to a scaffolding matrix of crisscrossing fibrin fibers. Two distinct types of branching fibrin fibers exist. The dense, thin fibers resist deforming mechanical forces and are poorly dissolved by thrombolytic agents. Thick fibrin fibers are susceptible to external mechanical forces and get dissolved by thrombolytic agents.[11][12]

Histopathology

A thrombus comprises a conglomerate of platelets, red blood cells, vasoconstrictors, and procoagulant anchored to a scaffolding matrix of crisscrossing fibrin fibers. Two distinct types of branching fibrin fibers exist. The dense, thin fibers resist deforming mechanical forces and are poorly dissolved by thrombolytic agents. Thick fibrin fibers are susceptible to external mechanical forces and get dissolved by thrombolytic agents.[11][12]

History and Physical

The clinical features depend on the duration and the severity of ischemia, depending on whether the obstruction is wholly or partially occlusive, transient, or persistent. Coronary artery thrombus presents clinically as sudden cardiac arrest or acute coronary syndrome.[13] The history may include chest pain, shortness of breath, and syncope. Sinus tachycardia is common in patients presenting with acute coronary syndrome.[14] The patient may have hypotension due to low cardiac output and a poor outcome predictor. Tachypnea can occur as a result of congestive heart failure due to left ventricle dysfunction.[15] The patient may have an S4 gallop or S3 on physical examination due to LV dysfunction. Heart murmurs of mitral regurgitation and ventricular septal rupture may present, especially in patients with delayed presentation.[16]

Evaluation

On laboratory tests, an elevated blood level of a cardiac enzyme (troponin)can occur in patients with coronary artery thrombus. An electrocardiogram shows ST elevation in leads, which monitors the artery containing the thrombus. Several imaging modalities are utilized to diagnose intracoronary thrombus. Multiple studies have shown the low sensitivity of angiography, although specificity approaches 99-100% while using multiple angiographic views for verification.[17] Angiography remains the gold standard for recognizing thrombus, showing the classic findings of reduced contrast density, staining, haziness, irregular lesion contour, filling defects, or a smooth convex meniscus at the site of total thrombotic occlusion. Intravascular imaging can help in conditions where the presence of coronary thrombosis is not clear. Intravascular Ultrasound and optical coherence tomography can detect intracoronary thrombus. However, the sensitivity of optical coherence tomography is much higher than intravascular ultrasound for diagnosing intracoronary thrombus compared to angioscopy.[18]

Treatment / Management

Treatment for coronary artery thrombus involves medications and revascularization to improve myocardial perfusion. Pharmacologic therapy for managing thrombus-containing lesions includes aspirin, thienopyridines (clopidogrel, prasugrel, ticagrelor), and unfractionated heparin.[19][20] However, in the case of persistent thrombus, drugs such as GP IIb/IIIa inhibitors and vasodilators can help improve epicardial and myocardial blood flow.[21][22] Percutaneous devices such as aspiration catheters and embolic protectors decrease distal embolization and improve myocardial blood flow and clinical outcomes.[23][24] The aspiration catheter manual minimizes the thrombus burden, while the embolic protector targets catching the debris released during PCI. Following the publication of several landmark studies, a rekindled interest in mechanical thrombus extraction arose, especially for STEMI management. One can categorize contemporary mechanical thrombus removal or dissolution devices into 4 main types according to their activation mode:

1. Manual aspiration catheters
2. Power-sourced thrombectomy
3. Ultrasound-induced sonication
4. Embolic protection.

Manual thrombus aspiration of the infarct-related vessel is useful for rapidly decreasing the thrombotic burden, preventing the distal embolization of the thrombus, preserving the microvascular integrity, and reducing infarct size. Manual thrombectomy, therefore, improves myocardial perfusion grade. The TAPAS trial showed a mortality reduction, which led the guidelines to recommend routine manual aspiration.[25] However, the latest trials have shown no clear-cut benefit of routine manual aspiration in acute myocardial infarction.[26][27][26] Increased thrombus burden may influence stent opposition, leading to low TIMI flow and poor outcomes. The best method of primary percutaneous intervention in the setting of coronary thrombus has been reported in the SINCERE database.[28] According to it, direct stenting may be adequate if the thrombus size is small. If the thrombus burden is greater, it is wise to perform aspiration thrombectomy before stenting to minimize distal embolization and no-reflow. If the thrombus burden is vast, more aggressive thrombectomy devices such as Angio jet Rt are better for removing the thrombus.

Differential Diagnosis

The differential diagnoses based on symptoms include pulmonary embolism, acute peptic ulcer, pericarditis, and herpes zoster. The differential diagnoses based on angiography include coronary artery dissection, coronary calcification, and no-reflow phenomenon.

Staging

Grading systems are essential for adequately assessing thrombus burden to assist management decisions before and during interventions. The TIMI Study Group introduced the most commonly used thrombus grading classification. Their method is based on a visual angiographic assessment of the thrombus size using a score that ranges from grade 0 to grade 5.[29]

• Grade 0: No angiographic characteristic of thrombus
• Grade 1: Possibility of thrombus on angiography, decreased density, haziness, irregular lesion contour
• Grade 2: Definite thrombus, significant filling defects, the greatest dimension is 1/2 of vessel diameter
• Grade 3: Definite thrombus with the greatest dimension is greater than 1/2 to less than 2 vessel diameter
• Grade 4: Definite large thrombus with the greatest dimension greater than 2 vessel diameter
• Grade 5: Complete thrombotic occlusion

Prognosis

The existence of coronary thrombus on angiogram is a negative predictor associated with higher MACE (major adverse cardiovascular events).[30] The coronary thrombus can occlude the coronary artery and its branches, impairing epicardial and myocardial blood flow. The thrombus size and consistency are also important prognostic markers of distal embolization. Multiple studies have shown that distal embolization is associated with an increase in mortality.

Complications

Complications associated with coronary thrombus include sudden cardiac death, congestive heart failure, and cardioembolic stroke.

Consultations

Consultations that are typically requested for patients with this condition include the following:

• Interventional cardiologist 
• Intensivist
• Cath lab technician
• Staff nurse
• Nutritionist
• Physiotherapist

Deterrence and Patient Education

The cardiac team should explain to patients that they should come to the emergency department as early as possible if symptoms such as chest pain and shortness of breath develop. Besides, they should:

• Avoid salt and use the Mediterranian diet
• Quit smoking and avoid excessive alcohol
• Take medications as prescribed
• Maintain regular exercise
• Maintain control of risk factors such as hypertension, diabetes, and dyslipidemia

Pearls and Other Issues

Thrombus plays a significant role in acute coronary syndrome pathophysiology. The formation of a thrombus within a coronary artery with obstruction of coronary blood flow and reduction in oxygen supply to the myocardium produces several acute coronary syndromes. It is essential to understand the structural components and burden of the thrombus to decide on revascularization strategies. Strategies combining dietary, pharmacologic-medical, and interventional-surgical therapies have successfully prevented and treated major cardiovascular events. These regimens focus on inhibiting the various pathways involved in thrombus generation. Novel strategies based on the knowledge of platelet aggregation's biochemistry, the coagulation processes, and the geometric conditions encountered in the circulation are in different stages of development and clinical trials. Advances in noninvasive imaging techniques help identify plaques at risk and reduce thrombosis's clinical impact.

Enhancing Healthcare Team Outcomes

Many interventional cardiologists widely use thrombus aspiration during percutaneous coronary intervention in STEMI patients. However, recent trials (TASTE and TOTAL) have raised doubts over its value and safety. As a result, the current guidelines do not recommend the routine use of thrombus aspiration in STEMI patients.