Discussion

Current management of left ventricular thrombus

LVT management focuses on reducing thromboembolic complications while balancing bleeding risk. Prompt identification and initiation of anticoagulation remain the cornerstone of therapy because untreated LVT is associated with substantial risks of ischemic stroke, systemic embolization, and adverse cardiovascular outcomes [3,6-8].

Accurate diagnosis is central to management. Transthoracic echocardiography (TTE) remains the first-line imaging modality because of its broad availability and bedside accessibility; however, sensitivity may be limited in patients with apical abnormalities or poor acoustic windows [2,3,10]. Use of contrast-enhanced echocardiography improves endocardial border definition and increases diagnostic yield [10,11]. Cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement remains the reference standard because of superior sensitivity, specificity, and ability to characterize thrombus morphology and myocardial viability [2-4].

Historically, VKAs such as warfarin represented standard therapy due to evidence demonstrating reductions in embolic events and thrombus persistence [7]. Current American Heart Association and American College of Cardiology recommendations generally support initiating therapeutic anticoagulation for approximately three months following LVT diagnosis with repeat imaging to document thrombus resolution [8,11]. For patients with persistent thrombus, severe left ventricular dysfunction, ventricular aneurysm, or recurrent thrombotic risk factors, extended treatment durations of three to six months or longer may be considered through individualized decision-making [8].

Despite these recommendations, optimal anticoagulation duration remains uncertain. Existing guidance largely derives from observational studies and expert consensus rather than prospective randomized trials [8]. Patients with remote myocardial infarction, chronic ischemic cardiomyopathy, or persistent ventricular dysfunction present management challenges because thromboembolic risk may continue beyond apparent thrombus resolution [19,21].

DOACs have increasingly emerged as alternatives to warfarin because of predictable pharmacokinetics, fewer drug and dietary interactions, and lack of routine laboratory monitoring. Multiple observational studies, systematic reviews, and contemporary meta-analyses demonstrate comparable efficacy and safety between DOACs and VKAs for thrombus resolution and prevention of systemic embolization [9,12-20]. More recent prospective and randomized studies further support the non-inferiority of DOAC therapy [14,15,20,22-24]. Ongoing trials, including RELEVENT, may provide additional evidence regarding optimal anticoagulant selection and future treatment approaches [23].

Risk stratification of patients with left ventricular thrombus

Current management of LVT largely relies on thrombus resolution and improvement in ventricular function to guide anticoagulation duration. However, available evidence suggests substantial heterogeneity exists among patients with LVT regarding thrombus persistence, recurrence, and risk of future thromboembolic events [8,19]. This variability suggests that risk stratification models may help identify patient subgroups who could benefit from individualized anticoagulation duration and surveillance strategies.

Recurrence of LVT carries potentially devastating consequences because recurrent thrombus formation has been associated with significantly increased rates of cardioembolic events, particularly ischemic stroke [19]. In patients with post-myocardial infarction LVT, thrombus protrusion, recurrent thrombus formation, and failure of initial thrombus resolution have been identified as independent predictors of subsequent ischemic stroke [16]. Namjouyan et al. additionally demonstrated that despite initial thrombus resolution, approximately 5.2% of patients subsequently experienced acute ischemic stroke, with cardioembolic mechanisms accounting for most events [19]. Multivessel coronary artery disease was similarly associated with greater recurrence risk compared with single-vessel disease [19].

Beyond clinical variables, echocardiographic findings may provide important prognostic information. Studies have demonstrated associations between persistent LVT and larger left ventricular end-diastolic diameter (LVEDD), larger left ventricular end-systolic diameter (LVESD), increased left atrial volume, reduced left ventricular wall-motion scores, and higher rates of apical aneurysm formation [16]. These findings suggest that advanced ventricular remodeling and impaired ventricular mechanics may contribute to thrombus persistence.

Morphologic characteristics of the thrombus may further refine risk assessment. Thrombus size, shape, mobility, and protrusion have all demonstrated associations with both embolic risk and likelihood of thrombus resolution [8,16]. Smaller baseline thrombus size appears associated with an increased probability of thrombus regression, whereas larger thrombus burden may correlate with greater ventricular dysfunction and chamber enlargement. Some studies suggest that each 1 mm increase in thrombus size may be associated with slower rates of thrombus resolution [16].

Among imaging characteristics, thrombus mobility appears particularly important. Oh et al. demonstrated that mobility represented the strongest independent predictor of early thrombus resolution [16]. Mobile protuberant thrombi may provide a greater surface area for interaction with endogenous fibrinolytic pathways and anticoagulant agents. Round thrombi projecting into the ventricular cavity similarly demonstrated earlier resolution compared with mural thrombi, potentially reflecting differences in thrombus mobility and exposed surface area [16].

Collectively, integration of clinical characteristics, ventricular remodeling parameters, and thrombus morphology may provide the foundation for future predictive models capable of identifying low- and high-risk LVT subgroups. Such risk stratification tools may ultimately facilitate individualized anticoagulation duration and surveillance strategies beyond current generalized recommendations.

Artificial intelligence, genomics, and future directions

Current LVT management relies primarily on thrombus resolution and recovery of ventricular function to guide anticoagulation duration. However, clinical characteristics, thrombus morphology, and advanced imaging findings may help identify patients at increased risk for persistence, recurrence, and thromboembolic events. Emerging artificial intelligence (AI) applications may improve standardization of image acquisition and analysis, enabling more consistent assessment of thrombus burden, ventricular remodeling, and high-risk imaging features [25,26]. In parallel, genomic technologies such as next-generation sequencing (NGS) and polygenic risk scores (PRS) have shown promise in cardiovascular risk prediction and may eventually contribute to individualized thrombotic risk assessment [6,27-31]. Although evidence supporting routine use of AI, genetic testing, or pharmacogenomics in LVT remains limited, integration of imaging, clinical, and genomic data may offer future opportunities for personalized anticoagulation strategies and improved risk stratification [8,22,30-32].

Use of pharmacogenetics in DOAC prescriptions

DOACs have a broad therapeutic index and generally demonstrate improved safety profiles compared with VKAs; however, clinically significant bleeding and subtherapeutic anticoagulation remain important concerns despite their increasing use in LVT management [12-15,17,18,20,24]. As anticoagulation strategies continue to evolve, precision medicine approaches such as pharmacogenomics may eventually provide additional tools for individualized risk reduction. Interindividual variability in drug metabolism and response remains incompletely understood and may contribute to differences in anticoagulant efficacy and adverse events. In addition to conventional clinical factors, genetic variants, epigenetic mechanisms, and environmental influences may contribute to variability in therapeutic response. Future investigations integrating genomic data with clinical characteristics may improve individualized anticoagulation selection and treatment strategies in patients with LVT [8,22].

Table 1 presents proposed high-risk features associated with left ventricular thrombus and their potential clinical significance.

Category | High-risk feature | Potential clinical significance | References
Thrombus morphology | Mobile or protruding thrombus | Increased embolic potential and higher risk of systemic thromboembolism | [5,7,16]
Thrombus characteristics | Large thrombus burden | Greater likelihood of thrombus persistence and embolic complications | [1,7,8]
Thrombus characteristics | Persistent LVT despite anticoagulation | Associated with delayed resolution and recurrent adverse events | [19,21]
Thrombus characteristics | Recurrent LVT apparent resolution | Increased risk of future thromboembolic events | [19,21]
Ventricular function | Severely reduced LVEF (<30%-35%) | Promotes blood stasis and thrombus formation | [1,4,8]
Ventricular remodeling | Apical akinesis/dyskinesia or LV aneurysm | Creates regions of stagnant flow favoring thrombus development | [1,4,6]
Clinical history | Prior stroke or systemic embolic events | May indicate increased future embolic risk | [5,7]
Anticoagulation factors | Premature cessation or inadequate anticoagulation | Increased risk of thrombus persistence or recurrence | [19,21]
Imaging findings | Delayed thrombus resolution on serial imaging | May identify patients requiring prolonged therapy | [8,16]
Emerging risk markers | Artificial intelligence-derived imaging features | Potential future enhancement of imaging standardization and risk prediction | [25,26]
Emerging risk markers | Genomic or polygenic risk profiles | Potential individualized prediction of recurrence and treatment response | [6,8,27-33]

This case report has several limitations. As a retrospective case report of a single patient, its findings are not generalizable. In addition, objective measures of anticoagulant adherence and comprehensive serial imaging data were unavailable, limiting definitive conclusions regarding direct oral anticoagulant treatment failure. Finally, the discussion of artificial intelligence, genomics, and pharmacogenetics is intended to highlight emerging areas of investigation rather than approaches validated by this case.