Left ventricular thrombus (LVT), a severe consequence of ventricular dysfunction, is linked to a significant risk of major adverse cardiac and cerebrovascular events (MACCE) [1]. The temporal incidence of LVT after myocardial infarction may be decreasing due to improved percutaneous coronary intervention (PCI) [1, 2], however the risk of LVT cannot be overlooked [3]. Recommendations for drug treatment of LVT are based on evidence from the ST-segment elevation myocardial infarction (STEMI) guidelines in acute myocardial infarction (AMI) patients [4, 5]. However, the etiology of LVT has changed—heart failure is now the most common cause of LVT [6]. A recent scientific statement [7] recommended anticoagulation in patients with LVT in the presence of dilated cardiomyopathy for at least 3–6 months, with discontinuation if the ejection fraction improves to $>$35% or if major bleeding occurs. For patients with ischemic heart disease, the long-term prognosis of patients with heart failure is significantly worse than that of patients with an AMI [8]. Although Virchow’s triad is present in patients with heart failure [9], the negative results of the Zannad et al. [10] do not provide any justification for left ventricular ejection fraction (LVEF) $\le$40% in patients who underwent anticoagulation of rivaroxaban. Compared to no anticoagulation or subtherapeutic anticoagulation, there is limited evidence that anticoagulant therapy is more likely to resolve LVT and reduce embolic risk [7]. There are still questions regarding the treatment of LVT [11]. The purpose of this study was to review the causes of LVT and changes in antithrombotic therapy over the past 12 years and assess the impact of anticoagulant treatment from a single center’s experience.

To the best of our knowledge, our study is the largest LVT cohort. The study’s key conclusions include the following: (i) heart failure with reduced ejection fraction overtook AMI as the leading cause of LVT; (ii) currently, an increasing proportion of patients with LVT are receiving anticoagulant therapy at discharge; (iii) since 2020, rivaroxaban has displaced warfarin as the most popular OAC for LVT patients; (iv) a trend towards better prognosis in the no anticoagulation group can be noted from survival curves; (v) from multivariable, matching and weighting analysis, no improvement in prognosis was observed with anticoagulant therapy; (vi) diabetes mellitus, eGFR 60 mL/min/1.73 m${}^2$, prior stroke, and LVEF $\le$40% were predictors of increased risk of MACCE.

Previous research has often added the qualifier of AMI to LVT [1, 2, 16, 17] while ignoring $\ge$50% of the heart failure population with LVT. Our study confirms that heart failure, rather than AMI, is the most common cause of LVT. McCarthy et al. [6] also reported this finding. There is more robust evidence for anticoagulation in LVT caused by AMI. However, in our study, the actual incidence of anticoagulation was lower in patients with AMI than in those without AMI (43.3% vs. 61.1%, p 0.001). A potential explanation is the increased risk of bleeding caused by combined antiplatelet and anticoagulant treatment. Nearly half (399/909) of patients with a newly diagnosed LVT were not treated with OAC on discharge in our study. In European [16] and American [18] studies, almost all patients with LVT were treated with anticoagulation. This reflects the poor anticoagulation status of LVT in China. Anticoagulant therapy for LVT has not received much attention. The good news is that this proportion is increasing year by year. Prior research has shown that DOAC comprise an increasing fraction of OAC used to treat LVT, whereas VKA remain the most commonly used agent [1, 6, 12, 16]. The same trend was observed in our data, but our off-label application of DOAC was more aggressive, and rivaroxaban exceeded warfarin.

Lemaitre et al. [19] found all-cause mortality occurred in 10% of patients with LVT and heart failure, while symptomatic emboli occurred in 15% and major bleeding occurred in 5% during a median follow-up of 8.7 years. This differs from the findings in our current study. In our cohort, the risk of SE and major bleeding was lower, while the risk of all-cause mortality was higher. Compared with the study findings of Lattuca et al. [18], LVEF was similar in our population (31.9% vs. 38.0%), but the proportion of mobile LVT was lower (34.6% vs. 8.5%), and the proportion of calcified LVT (1.3% vs. 18.4%) was higher. The risk of embolism in patients with LVT is closely related to two morphologic features: movement and protrusion [2]. Differences in LVT characteristics may be a possible explanation for the lower risk of embolism in our population. The major bleeding was higher in the no anticoagulation arm (2.3% vs. 1.2%). This may be due to the fact that the proportion of dual antiplatelet therapy in the no-anticoagulation group was much higher than that in the anticoagulation group (73.4% vs. 22.0%, p 0.001). Our results corroborate the findings of Lee et al. [20], who found that in patients with LV aneurysms and LVT, the benefit of oral anticoagulation with warfarin was not observed (HR, 1.38; 95% CI, 0.32–5.97; p = 0.66). A short course of low-dose rivaroxaban helps prevent LVT formation in patients with an anterior STEMI after primary PCI [21]. This finding may be explained by the fact that all patients received PCI and had a relatively normal LVEF (54%). A retrospective study from Croatia [22] involving more than 4000 patients with COVID-19 found that arterial thrombi were independently associated with less severe COVID-19 but higher comorbidity burden. Since our study covered a longer time period, we did not consider the influence of COVID-19 patients on thrombotic events.

Our cohort is the largest LVT cohort reported, allowing us to perform some sensitivity analyses. With a prevalence inversely associated with LVEF [23], LVT has been documented in 11–44% of patients with heart failure [24]. Anticoagulation failed to produce positive results, even in patients with LVEF $>$40%. Anticoagulation did not seem to improve cardiovascular outcomes for patients with LVT. There are several possible explanations. First, the baseline features of the anticoagulant and non-anticoagulant groups were different. The anticoagulation group had a significantly higher proportion of dilated cardiomyopathy than the non-anticoagulation group with a lower LVEF. In terms of thrombosis morphology, the anticoagulant group had a higher proportion of mobile, round and multiple thrombi than those without anticoagulation. In short, patients in the anticoagulant group had worse cardiac function and a higher risk of embolic thrombi. Therefore, it is not surprising that a clear trend towards a better prognosis in the non-anticoagulant group has been observed (Fig. 3). Multivariable, matching and weighting analysis revealed there was no significant difference in prognosis between the two groups. A second possible explanation is that different types and dosages of anticoagulants may impair their effectiveness. Our study confirms that DOAC is used in a variety of doses to treat LVT. In addition, we found the DOAC group had a higher risk of SE than the other two groups. Low doses of DOAC increase mortality and the risk of embolism without reducing the risk of bleeding [25, 26]. Third, the time in the therapeutic range (TTR) of warfarin and thrombus status are unknown, and these factors are closely related to prognosis [7]. When individuals with LVT don’t keep their international normalized ratio (INR) at a therapeutic level (TTR 50%), they seem to be at a higher risk for stroke [17]. Whole LVT regression, according to Lattuca et al. [18], was linked to lower mortality. We did not observe a greater benefit in the anticoagulation group. Our study does not negate the efficacy of anticoagulation but suggests the need to strengthen the management of anticoagulation in order to achieve better efficacy.

This study included the largest cohort of LVT patients to date and was a retrospective observational analysis. However, this study had several limitations. The main limitation of this study is that it is a retrospective study. We attempted to collect various factors that might influence prognosis for multivariate analysis. However, data on medication adherence and switching medications were not collected during the follow-up. In addition, imaging follow-up data on patients were difficult to obtain, so we did not conduct a relevant analysis. Our results should be viewed as exploratory because we realize that the comparison between the two groups was constrained by the disparate baseline characteristics. We cannot conclude whether anticoagulation improves cardiovascular outcomes for patients with LVT. Our study only suggests that the management of anticoagulation should be strengthened to achieve better results. Not all of the patients in our study who had LVT as determined by different imaging tests had a CMR. This may introduce heterogeneity issues. Finally, the low incidence of embolism and bleeding in our cohort may limit the validity of the findings in other races. Asian populations have a different risk of bleeding and ischemia, as demonstrated in the coronary heart disease population [27].

In this retrospective analysis, we examined the temporal patterns in the causes, courses of therapy, and results among Asian LVT patients. We found that heart failure, rather than AMI, was the primary cause of LVT. Additionally, there has been an increase in OAC utilization among patients discharged with LVT. Moreover, rivaroxaban has surpassed warfarin as the most popular first-line anticoagulant among patients with LVT since 2020. A trend towards better prognosis in the no anticoagulation group was noted from the survival curves. From multivariable, matching and weighting analysis, no improvement in prognosis was observed with anticoagulant therapy. Our study does not negate the efficacy of anticoagulation but suggests the need to strengthen the management of anticoagulation in order to achieve better efficacy.

AMI, acute myocardial infarction; DOAC, direct oral anticoagulants; LVT, left ventricular thrombus; LVEDD, left ventricular end diastolic dimension; LVEF, left ventricular ejection fraction; MACCE, major adverse cardiac and cerebrovascular events; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; VKA, vitamin K antagonists.

The data used in our study is not publicly available but is available from corresponding author on reasonable request.

BS, YS, LM, LJ, DY, HW, WF, KFD, and WS—study design and interpretation of results. BS—data collection. BS, YS, LM, XT, JL, RZ, CS—data analysis. BS, YS, LM, XT, JL, RZ, CS, LJ, DY, HW—manuscript preparation. BS, YS, LM, XT, JL, RZ, CS, LJ, DY, HW, WF, WS, KFD—manuscript revision. All authors contributed to editorial changes in the manuscript. All authors read and approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

The study protocol was approved by the Fuwai Hospital Ethics Committee (2021-1644) and was conducted according to the Declaration of Helsinki. Written consent was waived due to the low patient risk. Oral consent was obtained during the telephonic interview.

Not applicable.

This work was supported by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences [2021-I2M-1-008 and 2020-I2M-C&T-B-056].

The authors declare no conflict of interest.