Discussion:
CE is a non-atherosclerotic cause of AMI that can present as either STEMI or NSTEMI. CE accounts for 4% to 13% of acute MI cases, as observed in angiographic and autopsy studies. The first description of CE-related MI dates back to 1856 by Rudolf Virchow. The primary causes of CE include atrial fibrillation (AF), cardiomyopathy, and malignancy; however, 26.3% of cases have no discernible source8,9.
CE can theoretically arise from three primary sources. The first is direct embolism, occurring from thrombi originating in the left atrial appendage, left ventricle, or heart valves, often due to conditions such as infective endocarditis or cardiac tumors. The second source is paradoxical embolism, which occurs when venous thrombi travel into systemic circulation through openings like a patent foramen ovale or atrial septal defects. The third source is iatrogenic embolism, which can result from medical procedures such as aortic valve replacements or percutaneous coronary interventions (PCI). Although coronary arteries are generally protected from systemic embolisms, risks like coronary air embolism can arise during PCI, potentially leading to vessel occlusion. Furthermore, complications such as device embolization and microthrombi during STEMI interventions can complicate diagnosis, especially when thrombi coexist with underlying atherosclerosis 8.
Diagnosing CE can be challenging due to its clinical presentation, which resembles atherosclerotic acute coronary syndromes (ACS). To help differentiate CE from atherosclerotic coronary artery disease (CAD), Shibata et al. introduced diagnostic criteria based on clinical and angiographic findings, classifying CE as either “definite” or “probable” (Table 1). In CE cases, coronary artery stenosis is typically minimal, aiding in distinguishing it from atherosclerotic causes. Imaging techniques such as angiography, transthoracic echocardiography (TTE), transesophageal echocardiography (TEE), and magnetic resonance imaging (MRI) are essential for identifying embolic sources, with AF being the most commonly implicated risk factor4,9.
Coronary arteries are generally more protected from embolic events than other vascular systems due to several factors, including their smaller diameter, higher vascular resistance, and the anatomical positioning of the aortic valve and sinus of Valsalva, which reduce the likelihood of embolization during systole 4. However, in patients with AF, dilated cardiomyopathy, or prosthetic heart valves, emboli can lodge in the coronary arteries, causing CE 10. Notably, CE preferentially affects the left coronary system, occurring three to four times more frequently than the right, particularly in the left anterior descending artery, due to its anatomical orientation, which makes it more susceptible to embolization. In contrast, coronary vasospasm is more frequently reported in the proximal right coronary artery 1.
It is crucial to emphasize the relationship between MI and the presence of a left intraventricular thrombus. In these instances, CE can either serve as a cause, where MI leads to the formation of the ventricular thrombus, or as a consequence, where CE arises from a pre-existing ventricular thrombus 8.
Cocaine use stimulates the formation of intraventricular thrombus through sympathetic activation, resulting in prolonged coronary vasospasm and direct myocardial injury. Additionally, its prothrombotic effects further elevate the risk of intracardiac thrombus formation6,11.
Left ventricular (LV) thrombus is a significant complication of LV dysfunction, closely associated with systemic embolism, morbidity, and mortality. Heart failure and acute MI, particularly STEMI, are common causes of LV thrombus. Reduced ejection fraction (EF) is prevalent in these cases, with 36% of patients having an EF <20%, 38.7% with an EF between 20% and 30%, and 25.3% with an EF between 30% and 40%. Cases with an EF between 41% and 49% are less common (8%), as are those with an EF ≥50% (5%) 12. The LAD artery is the most frequently involved culprit artery, accounting for 77.8% of cases. In contrast, RCA occlusion, as seen in our patient, is rare. Thrombus formation is significantly related to the region with the most severe functional impairment, often reflecting infarction or scarring. Global LV dysfunction is present in 64.8% of cases, with regional dysfunction commonly affecting the apex (92.7%), anterior (26.8%), septal (26.8%), inferior (14.6%), and lateral (9.8%) regions12,13.
The combination of blood stasis, endothelial injury, and hypercoagulability, collectively known as Virchow’s triad, is essential for thrombus formation. In the context of acute MI, particularly associated with cocaine use, all three components of this triad are evident. Regional wall akinesia and dyskinesia contribute to blood stasis; prolonged ischemia leads to subendocardial tissue injury and inflammation; and cocaine use promotes a hypercoagulable state6,13.
Cocaine is emerging as a significant cause of MI through both coronary vasospasm and thrombosis. It increases platelet aggregation and induces vasoconstriction, leading to thrombus formation within the coronary arteries. The drug’s ability to enhance norepinephrine activity heightens sympathetic activation, resulting in coronary vasospasm that can lead to ischemia and MI. Cocaine not only enhances thromboxane A2 production, a promoter of platelet aggregation and vasoconstriction, but also reduces the release of prostacyclin, which normally inhibits platelet aggregation. These imbalances promote a prothrombotic state, while cocaine also increases platelet sensitivity to aggregating agents such as adenosine diphosphate (ADP) and epinephrine, further heightening platelet activity. The combination of endothelial dysfunction and increased platelet activation raises the risk of coronary thrombosis and MI, even in the absence of atherosclerotic disease. Additionally, chronic cocaine use can lead to premature atherosclerosis, cardiomyopathy, and conduction abnormalities, further elevating the risk of MI 6(p1),14.
The combination of smoking and cocaine use, as observed in our patient, amplifies the risk of cardiovascular events due to their combined impact on endothelial function and thrombotic pathways. Both substances cause endothelial injury and impair prostacyclin production, exacerbating platelet aggregation. Smoking also increases oxidative stress and inflammatory markers, further contributing to endothelial dysfunction6(p1),14. Additionally, chronic smokers have elevated fibrinogen levels, which, when combined with cocaine’s effects, enhance platelet aggregation and increase the risk of thrombus formation. Moreover, the effects of cocaine can be exacerbated by concomitant alcohol consumption, which may also be relevant to our patient6.
Aortic dissection is one of the cardiac manifestations that cocaine can induce, and it should be highly suspected in patients presenting with chest pain radiating to the back following cocaine use. In such cases, a CT angiogram can be utilized to rule out the condition. Cocaine has several pathophysiological effects that may increase the risk of aortic dissection. By inhibiting catecholamine reuptake, cocaine stimulates the autonomic nervous system, resulting in elevated heart rate and blood pressure. Additionally, cocaine acts synergistically with alpha agonists to induce vasoconstriction. Chronic cocaine consumption can alter the elastic properties of the aorta, leading to decreased strain, reduced distensibility, and increased aortic stiffness. Furthermore, the sudden and severe elevation of blood pressure induced by cocaine produces increased shear stress in the aorta, contributing to intimal disruption that allows the blood column to enter the media and leads to subsequent antegrade or retrograde propagation of the medial hematoma15.
In terms of management, coronary interventions for CE differ from those for atherosclerotic MI. Thrombus aspiration and balloon angioplasty are preferred approaches, often eliminating the need for stent implantation4. Aoun et al. proposed a comprehensive algorithm for managing CE 16. In cases of small, distal CE without hemodynamic instability, the recommended approach is anticoagulation therapy alone. However, in the presence of high intracoronary thrombus burden accompanied by instability, thrombus aspiration should be prioritized. If angiography indicates CE and the coronary anatomy is favorable, thrombectomy may be attempted. While the efficacy of intracoronary thrombolysis or glycoprotein IIb/IIIa inhibitors has not been established through randomized clinical trials, their use is frequently reported in clinical cases. Notably, Popovic et al. found that interventional procedures for CE involved significantly higher utilization of glycoprotein IIb/IIIa inhibitors compared to non-CE cases (73.9% vs. 37.7%), alongside a markedly lower rate of angioplasty (45.3% vs. 95.5%) 10. In instances where thrombus aspiration results in a TIMI flow grade of less than 2, primary stenting may be considered. Conversely, if TIMI flow is 2 or greater following thrombus aspiration, intravascular ultrasound or optical coherence tomography may be employed to investigate potential plaque erosion. A minimalistic revascularization strategy aimed at achieving TIMI flow grade 3 is preferred, ideally without the need for stenting8.
The Penumbra CAT RX has demonstrated significant efficacy and safety in thrombus removal in acute settings, without the heightened risk of systemic emboli associated with manual aspiration thrombectomy. Approved for coronary use in 2017, this device features an atraumatic catheter combined with a sustained vacuum source, providing consistent power aspiration throughout the procedure. Clinical outcomes reveal that after the use of the CAT RX, 88% of patients achieved a post-procedure TIMI flow of 3, 9% attained TIMI 2 flow, and 3% experienced TIMI 0 flow17.
In conclusion, this case underscores the critical need for heightened awareness of coronary embolism (CE) as a potential cause of acute myocardial infarction (AMI), particularly in younger patients with a history of substance abuse, such as cocaine use. The interplay between cocaine’s thrombogenic effects, the formation of a left ventricular thrombus, and subsequent coronary artery embolism highlights the complexities of diagnosing and managing such cases. Successful aspiration thrombectomy in this patient not only restored coronary blood flow but also emphasizes the importance of tailored therapeutic approaches in managing CE, differing from conventional treatment strategies for atherosclerotic causes. Clinicians should consider CE in the differential diagnosis of AMI, especially in patients with risk factors associated with thrombus formation, and remain vigilant for potential complications arising from both substance use and cardiovascular pathology.