A case report of left ventricular thrombosis in patient with normal ejection fraction
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Key findings
• The formation of left ventricular (LV) thrombus in patients with normal LV ejection fraction (LVEF) is very rare.
• LV thrombosis with normal LVEF in few weeks later after MI was usually easy to be ignored.
What is known and what is new?
• LV thrombus is a well-known complication of acute myocardial infarction (AMI) that can lead to serious thromboembolism. LV thrombus is considered to form in the milieu of significant myocardial dysfunction with low LVEF. The risk of LV thrombus formation after MI may be greatest in the first two weeks. There are no consensus guidelines for the treatment of LV thrombosis in patients with normal LV systolic function.
• We report a case of a 30-year-old man was diagnosed with LV thrombosis in normal LV ejection after AMI. Subsequent renal artery and lower limb artery embolization because of the delayed discovery with LV thrombus and the different choices of anticoagulation therapy. The timing of LV thrombus assessment is crucial, as assessment too soon after the onset of myocardial infarction will miss LV thrombus formation.
What is the implication, and what should change now?
• Follow-up imaging should be strengthened in patients with acute anterior wall MI even with normal LVEF. Attention should be paid to the risk of bleeding in patients with LV thrombosis after AMI who are receiving antiplatelet plus anticoagulation therapy. The choice of anticoagulation regimen should be tailored to the individual patient.
IntroductionOther Section
Left ventricular (LV) thrombus is one of the major complications of acute myocardial infarction (AMI). The incidence of LV thrombus in patients with anterior AMI in the era of primary percutaneous coronary intervention (pPCI) ranged from 4% to 15% (1,2). However, there was a high incidence of systemic arterial embolism in patients with LV thrombus as a whole. The formation of LV thrombus after AMI is associated with a 5.5-fold increased risk of thromboembolic events compared with no thrombus (3). Without anticoagulation, the annual stroke or systemic embolization rate is approximately 10% to 15% per year (4). LV thrombus is a significant and independent predictor of systemic arterial embolism (5). The clinical outcomes are different due to different sites of embolization. Since these thromboembolic events are typically abrupt and without warning, the satisfactory medical approach is adequate management of these high risk patients. We present this case in accordance with the CARE reporting checklist (available at https://jxym.amegroups.com/article/view/10.21037/jxym-24-13/rc).
Case presentationOther Section
A 30-year-old male patient was admitted to the hospital for chest pain for 6 hours. He had no history of previous heart disease. The cardiac examination was normal. The patient’s only cardiovascular risk factor was smoking 40 cigarettes a day for at least 10 years. Electrocardiography revealed prominent ST-segment elevation in V2-V5 (Figure 1). Laboratory measurements upon admission showed elevated levels of myocardial biomarkers (highly sensitive troponin-I >99 ng/mL, creatine kinase-myocardial band >301 ng/mL). Rheumatological and immune-related indicators were negative. Thrombophilia screening and right heart contrast echocardiography revealed no obvious findings. We immediately performed coronary angiography, which suggested total occlusion of the proximal left anterior descending coronary artery with a thrombus shadow (Figure 2). Subsequent percutaneous coronary intervention (PCI) was performed by intracoronary thrombolysis and thrombus aspiration followed by the placement of one stent. The patient was given aspirin (100 mg daily) and ticagrelor (90 mg daily) after PCI. Transthoracic echocardiography showed no ventricular thrombosis and normal LV systolic function before the first hospital discharge. One month later, the patient was admitted to the hospital for right low back pain that had lasted for 6 hours. Preliminary abdominal ultrasound showed no obvious abnormalities, D-dimer was positive, and further whole-abdominal enhanced CT revealed renal artery thrombosis. The cause of the renal artery thrombus was sought, so echocardiography was performed, and the LV thrombus was found. Transthoracic echocardiography showed an apical segment with an obvious thrombus (43 mm × 23 mm), visible shaking with the heart beat, and LV ejection fraction (LVEF) of 56% (Figure 3A). Cardiac magnetic resonance (CMR) showed thinning of the anterior wall of the apical segment with a thrombus (34 mm × 16 mm) and slight hypokinesia, and the thrombus was connected to the muscular trabecula and penetrated into the cardiac cavity. The LVEF was 51.2% (Figure 3B). Renoarteriography revealed total occlusion of the right renal artery with a thrombotic shadow (Figure 4). His right renal artery showed no significant stenosis after thrombus aspiration. Considering the course of myocardial infarction (MI) with LV thrombosis at one month and the risk of bleeding, the patient was started on triple antithrombotic therapy with aspirin (100 mg daily), clopidogrel (75 mg daily), and rivaroxaban (15 mg daily). After 3 months of triple antithrombotic therapy, repeat echocardiography indicated a LV thrombus (24 mm × 13 mm). Because the thrombus did not dissipate, rivaroxaban (15 mg daily) was replaced with warfarin [international normalised ratio (INR) kept at 2.0–3.0]. Unfortunately, the patient did not adhere to the outpatient follow-up INR during treatment and developed right lower extremity pain. Lower extremity arteriography revealed that the right femoral artery was completely occluded (Figure 5). The patient was treated with thrombolysis and thrombus aspiration of the right femoral artery. This patient had only one stent implanted in the proximal segment of the left anterior descending coronary artery (PCI <1 year, dual antiplatelet therapy >6 months) and had a low risk of cardiac ischemia (SYNTAX score =20, low-risk group). The patient had poor coordination with oral warfarin and could not reach the standard therapeutic dose, so we decided to increase the dose of rivaroxaban. He was administered clopidogrel (75 mg daily) plus rivaroxaban (20 mg daily), after which the LV thrombus gradually shrank until it disappeared during this period of treatment. Rivaroxaban was discontinued only after one year of anticoagulation because of systemic embolization due to thrombosis recurrence. Since then, the patient has had no more thromboembolic events.
All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
DiscussionOther Section
LV regional wall akinesia and dyskinesia after AMI resulting in blood stasis, prolonged ischemia leading to subendocardial tissue injury with inflammatory changes and a hypercoagulable state are consistent with Virchow’s triad, resulting in LV thrombus formation. There are several risk factors for the development of LV thrombus, such as a large infarct, severe apical asynergy, LV aneurysm and anterior MI (6). Patients with LVEF <40% are also prone to developing LV thrombi (7). In this case report, the patient had acute anterior wall MI at the first hospitalization. Echocardiography and CMR revealed slight hypokinesia in the apical-anterior segments with active thrombosis. Surprisingly, the patient did not develop a ventricular aneurysm and had a normal LVEF. Many clinical studies have been published on LV thrombi in AMI patients with significantly reduced EF (<45%) (7,8), but none has compared LV thrombi between patients with preserved ejection fraction and those with reduced ejection fraction. In a study of more than 8,000 patients with ST-elevation MI (GISSI-3 study), the incidence of LV thrombus was higher in patients with LVEF ≤40% (10.5% vs. 4%, P<0.0001). In the GISSI-3 study, patients with anterior AMI had a higher incidence of LV thrombi than patients with AMI in other regions (11.5% vs. 2.3%, P<0.0001). In patients with anterior AMI and LVEF ≤40%, this percentage was 17.8%. The incidence of LV thrombi was 4% in patients with LVEF >40%. Although they are rare, LV thrombi may form in patients with a normal ejection fraction. There have only been several case reports of patients with a prior history of MI who presented with LV thrombus in the setting of preserved LV systolic function (9). Therefore, follow-up imaging for all patients with acute anterior MI regardless of LVEF is necessary. After anterior wall MI, reduced ejection fraction is a significant risk factor for thrombus formation, and most thrombi occur in the area of apical wall motion abnormalities in hypokinetic, akinetic, or dyskinetic (aneurysmal) segments. Regional LV dysfunction and reduced and abnormal kinetic energy flow patterns within the LV can predispose patients to LV thrombi even in the setting of only normal to moderate LV systolic dysfunction (10,11). In our case, timely and effective revascularization by PCI likely contributed to the small range of LV dysfunction, and reduced abnormal kinetic energy flow patterns within the LV can predispose patients to LV thrombi even if they have normal to moderate LV systolic dysfunction.
Transthoracic echocardiography is the standard imaging technique for the detection of LV thrombus based on its availability and affordability. Often, the LV apex cannot be clearly defined, and the presence or absence of a thrombus may be difficult to establish, leading to a missed diagnosis of LV thrombus by echocardiography. CMR remains the optimal imaging modality for diagnosing and assessing the shape, size and location of LV thrombi. Because of its avascular composition, LV thrombi do not take up gadolinium. Therefore, late gadolinium enhancement (LGE)-CMR not only enhances the ability to detect and characterize LV thrombi [mural or protuberant thrombi (3)] but also has demonstrated value in identifying structural risk factors for LV thrombus formation, particularly myocardial scar burden and infarct size (12). Several studies have demonstrated that protuberant LV thrombi are associated with a higher rate of embolization than are thrombi without these features (13). In this case, the ventricular thrombus was connected to the trabecular muscle, penetrated into the cardiac cavity, and showed visible shaking with the heart beat. It was an active thrombus that caused thromboembolism in the renal and femoral arteries.
In the era of pPCI, oral anticoagulation (OAC) drug therapy in addition to dual antiplatelet therapy is recommended for AMI patients with LV thrombi (4). Long-term anticoagulation combined with antiplatelet treatment (triple antithrombotic therapy) can significantly increase the risk of bleeding (14). However, it is uncertain whether long-term triple antithrombotic therapy reduces the incidence of systemic embolism without increasing the number of bleeding events. Current guidelines generally recommend vitamin K antagonists (VKAs, warfarin) for patients with LV thrombus after MI (15,16). OAC with warfarin, however, requires dietary consistency, frequent INR monitoring, and vigilance against drug-food (and drug-drug) interactions, which significantly increases the difficulty of anticoagulation in patients. Failure to maintain a therapeutic INR (TTR <50%) causes a significantly increased risk of thromboembolism. A Scientific Statement from the AHA (4) indicated that direct OACs (DOACs) are considered by this writing group to be a reasonable alternative to VKA in patients with LV thrombus and may be particularly attractive as a therapy in patients in whom a therapeutic INR range is difficult to achieve consistently. A meta-analysis (4) revealed no differences in therapeutic efficacy or safety in the treatment of LV thrombus between DOAC and VKA treatment in stroke or systemic embolization [odds ratio (OR), 0.9; 95% confidence interval (CI): 0.70–1.25; P=0.65], as well as in all-cause mortality [OR, 0.92 (95% CI: 0.64–1.30); P=0.63], thrombus resolution [OR, 1.21 (95% CI: 0.89–1.64); P=0.22], or bleeding complications [OR, 0.79 (95% CI: 0.56–1.11); P=0.17]. Thus, DOAC seems to be a reasonable alternative to VKA. However, large prospective trials on the use and dosage of different DOACs for treating LV thrombi are currently lacking, and low or overdose DOACs can have adverse consequences for patients. Large registries of patients with LV thrombi may be needed to observe whether one particular DOAC is superior to others (17). In this case, because the patient had poor compliance, we did not choose warfarin at the beginning of treatment. However, there is no specific recommended dose of new oral anticoagulants to treat the formed LV thrombus in recent guidelines. Considering the risk of bleeding from triple anticoagulation therapy, 15 mg of rivaroxaban daily was chosen, but the results were not ideal. Therefore, we changed to warfarin anticoagulation, as recommended by the guidelines, and strengthened the education of warfarin-related precautions, but the patient still had difficulty adhering to it and failed to maintain a therapeutic INR. Anticoagulation failed with warfarin. The patient had dual antiplatelets for >6 months with a low risk of cardiac ischemia at this time and an increased rivaroxaban dose of 20 mg daily plus one antiplatelet therapy. Strengthening anticoagulation and simplified treatment regimens are more conducive to patient medication.
The timing of LV thrombus assessment is crucial, and premature assessment after the onset of MI can miss LV thrombus formation. Unfortunately, LV thrombosis was not detected by echocardiography at the first hospital discharge. An LV thrombus was identified at a repeat visit for renal artery embolization. It is also important to note that imaging assessments conducted too late can also miss LV thrombus formations. Spontaneous or anticoagulant-induced resolution is relatively common in LV thrombus formation after AMI (6). This is probably due to more aggressive anticoagulation therapies in the acute phase (e.g., the use of heparin), smaller infarctions, and improved LV remodeling. The recovery of ventricular function after treatment increases blood flow and lessens stasis, whereas the resolution of myocardial inflammation slows thrombus expansion (18). Several studies have shown an increased incidence of LV thrombus detection by transthoracic echocardiography (or CMR) at 1–2 weeks after MI (compared to the first several days after MI) (19-21). After MI with anteroapical akinesis or dyskinesis in which no LV thrombus is present in the early stage, patients may be considered for focused follow-up echocardiography or CMR. The current evidence for anticoagulation strategies to prevent LV thrombus is limited. Recently, an randomised controlled trial (RCT) indicated that low-dose anticoagulation (rivaroxaban 2.5 mg twice daily for 30 days) in addition to dual anti-platelet therapy (DAPT) could decrease the risk of LV thrombus compared with DAPT alone (22). Nonetheless, studies of combination antiplatelet and anticoagulant therapy in patients with other indications for OAC (most commonly atrial fibrillation) have clearly demonstrated a several-fold increased risk of bleeding (23,24). Considering the pros and cons of prophylactic anticoagulant therapy to prevent LV thrombus in this setting on a patient-by-patient basis seems prudent. Therapeutic anticoagulation therapy should be initiated for the treatment of LV thrombi after AMI, typically for 3 months, with follow-up imaging at this time point. Patients with a history of more distant MI (or ischemic cardiomyopathy) who develop LV thrombi are advised to initiate OAC therapy for at least 3 to 6 months (4).
ConclusionsOther Section
Follow-up imaging should be strengthened in patients with acute anterior wall MI even with normal LVEF, and prophylactic anticoagulation does not seem to be desirable. Active anticoagulant therapy should prevent the occurrence of systemic embolism after the formation of an LV thrombus in patients. Attention should be paid to the risk of bleeding in patients with LV thrombosis after AMI who are receiving antiplatelet plus anticoagulation therapy. If LV function or movement returns to normal, discontinuation of anticoagulation therapy can be considered. The choice of anticoagulation regimen should be tailored to the individual patient.
AcknowledgmentsOther Section
Funding: This work was supported by
FootnoteOther Section
Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://jxym.amegroups.com/article/view/10.21037/jxym-24-13/rc
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Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jxym.amegroups.com/article/view/10.21037/jxym-24-13/coif). All authors received research support fees from High Quality Development Fund Project of West China Guang’an Hospital of Sichuan University. The authors have no other conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
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ReferencesOther Section
- Shacham Y, Leshem-Rubinow E, Ben Assa E, et al. Frequency and correlates of early left ventricular thrombus formation following anterior wall acute myocardial infarction treated with primary percutaneous coronary intervention. Am J Cardiol 2013;111:667-70. [Crossref] [PubMed]
- Solheim S, Seljeflot I, Lunde K, et al. Frequency of left ventricular thrombus in patients with anterior wall acute myocardial infarction treated with percutaneous coronary intervention and dual antiplatelet therapy. Am J Cardiol 2010;106:1197-200. [Crossref] [PubMed]
- Vaitkus PT, Barnathan ES. Embolic potential, prevention and management of mural thrombus complicating anterior myocardial infarction: a meta-analysis. J Am Coll Cardiol 1993;22:1004-9. [Crossref] [PubMed]
- Levine GN, McEvoy JW, Fang JC, et al. Management of Patients at Risk for and With Left Ventricular Thrombus: A Scientific Statement From the American Heart Association. Circulation 2022;146:e205-23. [Crossref] [PubMed]
- Maniwa N, Fujino M, Nakai M, et al. Anticoagulation combined with antiplatelet therapy in patients with left ventricular thrombus after first acute myocardial infarction. Eur Heart J 2018;39:201-8. [Crossref] [PubMed]
- Delewi R, Zijlstra F, Piek JJ. Left ventricular thrombus formation after acute myocardial infarction. Heart 2012;98:1743-9. [Crossref] [PubMed]
- Chiarella F, Santoro E, Domenicucci S, et al. Predischarge two-dimensional echocardiographic evaluation of left ventricular thrombosis after acute myocardial infarction in the GISSI-3 study. Am J Cardiol 1998;81:822-7. [Crossref] [PubMed]
- Meurin P, Brandao Carreira V, Dumaine R, et al. Incidence, diagnostic methods, and evolution of left ventricular thrombus in patients with anterior myocardial infarction and low left ventricular ejection fraction: a prospective multicenter study. Am Heart J 2015;170:256-62. [Crossref] [PubMed]
- Liao SF, Lee CH, Wu LS, et al. Left ventricular thrombus and systemic embolism after painless myocardial infarction in a young female. Hong Kong Journal of Emergency Medicine 2018;25:110-2. [Crossref]
- Weinsaft JW, Kim J, Medicherla CB, et al. Echocardiographic Algorithm for Post-Myocardial Infarction LV Thrombus: A Gatekeeper for Thrombus Evaluation by Delayed Enhancement CMR. JACC Cardiovasc Imaging 2016;9:505-15. [Crossref] [PubMed]
- Garg P, van der Geest RJ, Swoboda PP, et al. Left ventricular thrombus formation in myocardial infarction is associated with altered left ventricular blood flow energetics. Eur Heart J Cardiovasc Imaging 2019;20:108-17. [Crossref] [PubMed]
- Weinsaft JW, Kim HW, Shah DJ, et al. Detection of left ventricular thrombus by delayed-enhancement cardiovascular magnetic resonance prevalence and markers in patients with systolic dysfunction. J Am Coll Cardiol 2008;52:148-57. [Crossref] [PubMed]
- Haugland JM, Asinger RW, Mikell FL, et al. Embolic potential of left ventricular thrombi detected by two-dimensional echocardiography. Circulation 1984;70:588-98. [Crossref] [PubMed]
- Lopes RD, Hong H, Harskamp RE, et al. Safety and Efficacy of Antithrombotic Strategies in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Network Meta-analysis of Randomized Controlled Trials. JAMA Cardiol 2019;4:747-55. [Crossref] [PubMed]
- Kleindorfer DO, Towfighi A, Chaturvedi S, et al. 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack: A Guideline From the American Heart Association/American Stroke Association. Stroke 2021;52:e364-467. [Crossref] [PubMed]
- Ibanez B, James S, Agewall S, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 2018;39:119-77. [Crossref] [PubMed]
- Kwok CS, Bennett S, Borovac JA, et al. An evidence-based evaluation of left ventricular thrombus treatment, outcomes, and resolution: a systematic review, pooled analysis and meta-analysis. Coron Artery Dis 2023;34:260-73. [Crossref] [PubMed]
- Camaj A, Fuster V, Giustino G, et al. Left Ventricular Thrombus Following Acute Myocardial Infarction: JACC State-of-the-Art Review. J Am Coll Cardiol 2022;79:1010-22. [Crossref] [PubMed]
- Küpper AJ, Verheugt FW, Peels CH, et al. Left ventricular thrombus incidence and behavior studied by serial two-dimensional echocardiography in acute anterior myocardial infarction: left ventricular wall motion, systemic embolism and oral anticoagulation. J Am Coll Cardiol 1989;13:1514-20. [Crossref] [PubMed]
- Greaves SC, Zhi G, Lee RT, et al. Incidence and natural history of left ventricular thrombus following anterior wall acute myocardial infarction. Am J Cardiol 1997;80:442-8. [Crossref] [PubMed]
- Gellen B, Biere L, Logeart D, et al. Timing of Cardiac Magnetic Resonance Imaging Impacts on the Detection Rate of Left Ventricular Thrombus After Myocardial Infarction. JACC Cardiovasc Imaging 2017;10:1404-5. [Crossref] [PubMed]
- Zhang Z, Si D, Zhang Q, et al. Prophylactic Rivaroxaban Therapy for Left Ventricular Thrombus After Anterior ST-Segment Elevation Myocardial Infarction. JACC Cardiovasc Interv 2022;15:861-72. [Crossref] [PubMed]
- Hansen ML, Sørensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010;170:1433-41. [Crossref] [PubMed]
- Dans AL, Connolly SJ, Wallentin L, et al. Concomitant use of antiplatelet therapy with dabigatran or warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. Circulation 2013;127:634-40. [Crossref] [PubMed]
Cite this article as: Gou C, Yang H, Wen J. A case report of left ventricular thrombosis in patient with normal ejection fraction. J Xiangya Med 2024;9:20.