Abstract
Aims
Recent years, several studies have suggested that abnormal baseline left ventricular (LV) function and structure are associated with left ventricular thrombus (LVT) formation. Despite this, most studies have given less attention to the potential role of left ventricular reverse remodelling (LVRR), that is, the improvement of LV function and structure, in resolving LVT. In this study, we aim to investigate the clinical characteristics, prognosis, and LVT resolution in patients with LVRR.
Methods and results
This is a retrospective study conducted at The First Affiliated Hospital of Dalian Medical University. Our cohort consists of patients diagnosed with LVT between 1 November 2015 and 31 May 2020. Enrolled patients were categorized into two groups: LVRR and Failure of LVRR. The primary endpoints included LVT resolution and embolic events. A total of 84 patients were included in the study, with 59 patients in the LVRR group and 25 patients in the Failure of LVRR group. In our study, patients in the LVRR group experienced higher incidence of LVT resolution and a lower risk of embolic events. Multivariate logistic analysis revealed that Failure of LVRR was the only independent negative predictor for LVT resolution and positive predictor for embolic events.
Conclusions
Patients with LVRR experience higher incidence of LVT resolution and have lower risk of embolic events, highlighting the significance of identifying and mitigating risk factors that contribute to abnormal LV function and structure in management of patients with LVT.
Keywords: Embolic events, Left ventricular reverse remodelling, Left ventricular thrombus, Thrombus resolution
Introduction
Left ventricular thrombus (LVT) is a common complication caused by ischaemic 1 and non‐ischaemic heart disease, 2 , 3 , 4 , 5 resulting from blood stasis, hypercoagulability related to abnormal platelet and blood coagulation factors, endothelial injury, and inflammation. 6 Despite the continual progress of medical technology in reducing the incidence of LVT, 6 , 7 patients with LVT remain at high risk for cardio embolism and systemic embolic events. 1 Guidelines and specialist consensus have made points about the management of LVT, but they have mainly focused on the choice and duration of antithrombotic therapies. 8 , 9 , 10 , 11 , 12 , 13 What is more, the results of several observational retrospective studies, 14 , 15 randomized controlled trials, 16 and meta‐analysis 17 that compared warfarin with directed oral anticoagulants (DOACs) in resolving thrombi and bleeding risks are inconsistent. Consequently, the management of LVT patients is still unclear. Notably, decreased left ventricular ejection fraction (LVEF) 18 and dilated LV chamber size 19 are independently associated with LVT formation. As LV function and structure can dynamically alter throughout the course of disease, they need regular monitoring. 20 Several studies have confirmed that LV function and structure can recover with guideline‐directed medical therapy (GDMT), invasive or surgical management, defined as left ventricular reverse remodelling (LVRR). 21 Despite previous studies confirming that abnormal baseline LVEF and LV chamber structure could be related to LVT formation, research on the management of LVT has paid less attention to how changes in LV function and structure affect LVT resolution. In this study, we investigate clinical characteristics, prognosis, and LVT resolution in LVRR patients.
Methods
All clinical data and study materials are available upon reasonable request from the Department of Cardiology, The First Affiliated Hospital of Dalian Medical University.
Study population and grouping
This is a retrospective study, which was approved by the institutional review board of The First Affiliated Hospital of Dalian Medical University, and all procedures were performed in accordance with the Declaration of Helsinki and its amendments. Informed consent was obtained from all study participants prior to the collection of clinical data.
This is a real‐world study, which included patients diagnosed with LVT via echocardiography at The First Affiliated Hospital of Dalian Medical University between 1 November 2015 and 31 May 2020. Patients with end‐stage renal failure, left atrial and/or right ventricular thrombus, aortic dissection thrombus, missing echocardiography data, or loss to follow‐up were excluded from this cohort. Considering the validity of anticoagulation, patients who received warfarin but failure to maintain a therapeutic international normalized ratio (INR), which refers to the time in therapeutic range is <50%, were also excluded. In this study, INR target is 2 to 3. All subjects received at least two echocardiography examination, with parameters collected from the first and last examination for those with more than two tests to assess the changes of LV structure and function. The interval time between two echocardiography tests was at least 6 months. LVT participants were divided into two groups: patients who met the criteria for LVRR were included in the LVRR group, while others were included in the Failure of LVRR group. In view of the assessment of LVRR was based on parameter changes between two echocardiography examination, LVRR was confirmed at second echocardiography examination. Baseline demographics, laboratory test results, imaging findings, and therapeutic schedules were collected from Yidu Cloud, one of the largest medical databases in China.
LVRR refers to the normalization of chamber geometry and function in failing myocardium, which may additionally encompass the correction of molecular and transcriptional irregularities, and it mainly manifests improved LV structure and function in clinic. 22 The criteria for LVRR was defined as LVEF unchanged or increasing from baseline, or LV mass and end‐diastolic dimension decreasing from baseline. 23
Study endpoints and follow‐up
The deadline for follow‐up is 31 December 2022. The primary endpoints of this study included two independent clinical events, which were LVT resolution, and the occurrence of embolic events. The secondary endpoints included bleeding events, all‐cause death, cardiovascular rehospitalization, and all‐cause rehospitalization. Embolic events were defined as composite outcomes of ischaemic stroke and systematic embolic events, which are characterized as acute vascular occlusion of an extremity or organ. 24 All enrolled patients were encouraged to regularly monitor their condition through outpatient services. For those who did not complete their follow‐up plans, we attempted to contact them by telephone.
Statistical analysis
The statistical analysis was performed by SPSS Statistical Software, Version 26.0 (SPSS Inc, Chicago, IL, USA). Categorical variables were shown as percentage. Continuous variables with normal distribution were expressed as mean ± SD, while continuous variables with nonnormal distribution, median and interquartile range were used. To compare characteristic differences between two groups, chi‐square test, independent‐sample t‐test, and Kruskal–Wallis test were used for categorical, normally distributed, and nonnormally distributed variables, respectively. Kaplan–Meier analysis was performed to describe incidence of clinical adverse events, and the log‐rank test was used to assess statistical differences. Logistic regression analysis was used to confirm the independent factors for predicting primary endpoints. The covariates included in the multivariate logistic analysis were the independent predictors that showed statistical significance in univariate logistic analysis. Additional clinically relevant characteristics, including age and oral anticoagulant (a combination of patients receiving warfarin and DOACs), were adjusted in multivariate logistic regression model to reduce bias, according to the one‐in‐ten rule that revealed that the maximum number of predicting variables in our multivariate logistic model is 6. A two‐sided P value < 0.05 was considered statistically significant.
Results
Baseline demographics and clinical characteristics
Between 1 November 2015 and 31 May 2020, a total of 190 subjects were diagnosed with LVT by echocardiography at The First Affiliated Hospital of Dalian Medical University. Of these, 106 subjects were excluded based on criteria, and 84 subjects were enrolled in our cohort (Figure 1 ), the median length of follow‐up was 47 months (range 40–58 months). Among these, a total of 59 patients (70.2%) were included into the LVRR group, and 25 patients (29.8%) were classified into the Failure of LVRR group. Table 1 shows their baseline characteristics. In general, compared with patients in the Failure of LVRR group, those in the LVRR group had higher diastolic blood pressure, higher alcohol consumption, lower incidence of IHD, lower left ventricular ejection fraction (LVEF) and haemoglobin level, shorter time interval between 2 echocardiography tests, and higher creatine kinase‐MB (CK‐MB) level. Additionally, patients in the LVRR group received less nitrates and percutaneous transluminal coronary intervention (PCI) therapy.
Figure 1.
Flow diagram of inclusion and exclusion of study subjects. LVRR, left ventricular reverse remodelling; LVT, left ventricular thrombus.
Table 1.
Baseline demographics and clinical characteristics at the time of first echocardiography
| Variables | LVRR, n = 59 | Failure of LVRR, n = 25 | P value |
|---|---|---|---|
| Age, year | 60.32 ± 14.369 | 62.60 ± 12.573 | 0.493 |
| Men, n (%) | 50 (84.7%) | 23 (92.0%) | 0.584 |
| QTc interval, ms | 473.37 ± 39.212 | 460.45 ± 33.303 | 0.197 |
| QRS duration, ms | 101.00 (94.00–113.50) | 98.00 (88.50–108.00) | 0.462 |
| Heart rate, b.p.m. | 82.36 ± 20.368 | 78.44 ± 15.243 | 0.391 |
| SBP, mmHg | 125.37 ± 21.120 | 121.92 ± 18.628 | 0.481 |
| DBP, mmHg | 80.61 ± 12.699 | 74.76 ± 10.713 | 0.047 |
| Smoking, n (%) | 30 (50.8%) | 11 (44.0%) | 0.566 |
| Alcohol consumption, n (%) | 20 (33.9%) | 3 (12.0%) | 0.040 |
| DCM, n (%) | 10 (83.3%) | 2 (16.7%) | 0.465 |
| HCM, n (%) | 4 (6.8%) | 0 (0.0%) | 0.439 |
| DM, n (%) | 19 (32.2%) | 6 (24.0%) | 0.452 |
| Hypertension, n (%) | 33 (55.9%) | 16 (64.0%) | 0.493 |
| Cancer, n (%) | 2 (3.4%) | 2 (8.0%) | 0.729 |
| Stroke, n (%) | 6 (10.2%) | 4 (16.0%) | 0.700 |
| Other thrombus events, n (%) | 5 (8.5%) | 1 (4.0%) | 0.791 |
| IHD, n (%) | 40 (67.8%) | 23 (92.0%) | 0.019 |
| HF, n (%) | 50 (84.7%) | 21 (84.0%) | 1.000 |
| NYHA class III/IV, n (%) | 32 (76.2%) | 15 (88.2%) | 0.494 |
| AF, n (%) | 7 (11.9%) | 5 (20.0%) | 0.527 |
| Conduction block, n (%) | 13 (22.0%) | 5 (20.0%) | 0.835 |
| AMI, n (%) | 17 (28.8%) | 11 (44.0%) | 0.177 |
| Valvular heart disease, n (%) | 51 (86.4%) | 20 (80.0%) | 0.677 |
| Apical ventricular aneurysm, n (%) | 9 (15.3%) | 8 (32.0%) | 0.081 |
| LV dysfunction, n (%) | 55 (93.2%) | 21 (87.5%) | 0.678 |
| Pericardial effusion, n (%) | 21 (35.6%) | 7 (28.0%) | 0.500 |
| Laboratory values | |||
| BNP, pg/mL | 918.23 (375.35–1902.20) | 348.86 (195.28–1806.76) | 0.248 |
| Tbil, μmol/L | 20.72 ± 12.02 | 20.77 ± 13.23 | 0.986 |
| Dbil, μmol/L | 5.80 (2.80–8.80) | 5.20 (3.00–12.60) | 0.902 |
| Lymphocyte, 109/L | 1.78 ± 0.74 | 1.55 ± 0.66 | 0.178 |
| Neutrophil, 109/L | 5.31 ± 2.40 | 5.40 ± 2.59 | 0.889 |
| NLR | 2.95 (2.01–4.42) | 2.84 (2.08–6.30) | 0.676 |
| Monocyte, 109/L | 0.65 ± 0.30 | 0.59 ± 0.20 | 0.435 |
| Platelet, 109/L | 186.00 (160.00–243.00) | 188.50 (175.50–261.75) | 0.433 |
| Haemoglobin, g/dL | 131.90 ± 37.72 | 143.25 ± 11.36 | 0.040 |
| PT, s | 13.50 (11.85–15.55) | 13.00 (11.30–18.50) | 0.848 |
| D‐Dimer, μg/L | 1860.36 ± 2012.89 | 1563.04 ± 1281.65 | 0.515 |
| Fibrinogen, g/L | 3.56 ± 1.36 | 3.19 ± 1.21 | 0.270 |
| CK‐MB, μg/L | 2.46 (1.41–5.12) | 1.52 (0.90–2.86) | 0.018 |
| hs‐cTnI, μg/L | 0.15 (0.48–1.13) | 0.05 (0.03–0.40) | 0.057 |
| Serum potassium, mmol/L | 4.08 ± 0.54 | 3.90 ± 0.47 | 0.179 |
| Creatinine, μmol/L | 89.00 (70.00–106.00) | 81.00 (68.50–113.50) | 0.895 |
| Cholesterol, mmol/L | 4.00 ± 1.02 | 4.33 ± 1.10 | 0.194 |
| Triglyceride, mmol/L | 1.16 ± 0.41 | 1.35 ± 0.65 | 0.125 |
| HDL‐C, mmol/L | 0.97 ± 0.33 | 0.92 ± 0.27 | 0.555 |
| LDL‐C, mmol/L | 2.25 ± 0.66 | 2.59 ± 0.80 | 0.059 |
| Echocardiography parameters | |||
| LVEF | 30.97 ± 10.99 | 36.64 ± 11.33 | 0.035 |
| LAD, mm | 42.53 ± 5.71 | 43.20 ± 5.26 | 0.614 |
| LVEDD, mm | 58.15 ± 8.61 | 60.92 ± 7.90 | 0.172 |
| E/e′ | 13.23 ± 6.07 | 11.28 ± 4.22 | 0.162 |
| IVS, mm | 10.18 ± 1.67 | 9.38 ± 1.87 | 0.057 |
| LVPWT, mm | 10.00 (9.00–11.00) | 10.00 (8.00–10.00) | 0.080 |
| EDT, mms | 160.43 ± 56.52 | 186.96 ± 55.99 | 0.057 |
| LV mass, g | 238.79 ± 66.19 | 234.41 ± 69.98 | 0.786 |
| Time interval, mo | 11.05 ± 10.99 | 19.12 ± 17.23 | 0.038 |
| Treatment | |||
| Beta‐blockers, n (%) | 46 (78.0%) | 20 (80.0%) | 0.835 |
| RAAS blockers, n (%) | 31 (52.5%) | 15 (60.0%) | 0.530 |
| Spironolactone, n (%) | 39 (67.2%) | 19 (32.8%) | 0.370 |
| Loop diuretic, n (%) | 35 (59.3%) | 15 (60.0%) | 0.954 |
| Nitrates, n (%) | 19 (32.2%) | 15 (60.0%) | 0.018 |
| Statins, n (%) | 40 (67.8%) | 22 (88.0%) | 0.054 |
| ICD, n (%) | 3 (5.1%) | 0 (0.0%) | 0.551 |
| Pacemaker, n (%) | 2 (3.4%) | 0 (0.0%) | 1.000 |
| CRT, n (%) | 1 (1.7%) | 0 (0.0%) | 1.000 |
| PCI, n (%) | 12 (20.3%) | 11 (44.0%) | 0.026 |
| Antiplatelet drugs, n (%) | 32 (54.2%) | 18 (72.0%) | 0.129 |
| Oral anticoagulant, n (%) | 46 (78.0%) | 14 (56.0%) | 0.042 |
| Warfarin, n (%) | 23 (39.0%) | 7 (28.0%) | 0.337 |
| DOACs, n (%) | 23 (39.0%) | 7 (28.0%) | 0.337 |
AF, atrial fibrillation; AMI, acute myocardial infarction; BNP, B‐type natriuretic peptide; CK‐MB, creatine kinase‐MB; CRT, cardiac resynchronization therapy; Dbil, direct bilirubin; DBP, diastolic blood pressure; DCM, dilated cardiomyopathy; DM, diabetes mellitus; DOACs, direct oral anticoagulants; E/e′, mitral Doppler early velocity/mitral annular early velocity; EDT, E peak deceleration time; HCM, hypertrophic cardiomyopathy; HDL‐C, high‐density lipoprotein cholesterol; HF, heart failure; hs‐cTnI, high‐sensitivity troponin I; ICD, implantable cardioverter‐defibrillator; IHD, ischaemic heart disease; IVS, interventricular septal; LAD, left atrium diameter; LDL‐C, low‐density lipoprotein cholesterol; LV, left ventricular; LVEDD, left ventricular end‐diastolic diameter; LVEF, left ventricular ejection fraction; LVPWT, left ventricular posterior wall thickness; NLR, neutrophil to lymphocyte ratio; NYHA, New York Heart Association; PCI, percutaneous transluminal coronary intervention; PT, prothrombin time; RAAS, renin‐angiotensin‐aldosterone system; SBP, systolic blood pressure; Tbil, total bilirubin.
Thrombus resolution and antithrombotic therapies in both groups
In comparison to patients in the Failure of LVRR group, LVRR patients had a higher incidence of thrombus resolution [LVRR group: n = 48, (81.4%) vs. Failure of LVRR group: n = 15, (60.0%), P = 0.039] (Figure 2 ). There is no statistical difference for the time interval of LVT resolution between LVRR and Failure of LVRR group [LVRR group: 10.56 ± 11.28 vs. Failure of LVRR group: 16.33 ± 16.45, P = 0.221]. Although more patients in LVRR group received oral anticoagulant [LVRR group: n = 46, (78.0%) vs. Failure of LVRR group: n = 14, (56.0%), P = 0.042] (Figure 3 ), LVRR was still associated with thrombus resolution when oral anticoagulant was considered as additional covariate and adjusted in multivariate logistic regression model (Table 2 ).
Figure 2.
Incidence of thrombus resolution in the LVRR and the Failure of LVRR group. LVRR, left ventricular reverse remodelling.
Figure 3.
Antithrombotic therapies in the LVRR and the Failure of LVRR group. LVRR indicates left ventricular reverse remodelling; oral anticoagulant indicates a combination of patients receiving warfarin and direct oral anticoagulants.
Table 2.
Logistic regression analysis to identify predictors of LVT resolution
| Univariate analysis | Multivariate analysis | |||||
|---|---|---|---|---|---|---|
| OR | 95% CI | P value | OR | 95% CI | P value | |
| Age | 0.979 | 0.943–1.017 | 0.283 | 0.998 | 0.946–1.053 | 0.948 |
| Failure of LVRR | 0.344 | 0.122–0.967 | 0.043 | 0.211 | 0.054–0.822 | 0.025 |
| Platelet | 1.010 | 1.001–1.019 | 0.036 | 1.012 | 0.999–1.025 | 0.069 |
| Fibrinogen | 1.977 | 1.068–3.660 | 0.030 | 1.406 | 0.720–2.748 | 0.318 |
| LDL‐C | 2.637 | 1.063–6.537 | 0.036 | 2.471 | 0.824–7.406 | 0.106 |
| Oral anticoagulant | 1.000 | 0.335–2.984 | 1.000 | 0.860 | 0.200–3.691 | 0.839 |
CI, confidence interval; LDL‐C, low‐density lipoprotein cholesterol; LVRR, left ventricular reverse remodelling; oral anticoagulant, a combination of patients receiving warfarin and direct oral anticoagulants; OR, odds ratio.
Secondary endpoints
During the follow‐up period, a total of 65 patients experienced adverse events [LVRR group: n = 44, (74.6%) vs. Failure of LVRR group: n = 21, (84.0%)]. Among them, 13 patients experienced bleeding events [LVRR group: n = 6, (10.2%) vs. Failure of LVRR group: n = 7, (28.0%)], 19 patients died for all‐causes [LVRR group: n = 12, (20.3%) vs. Failure of LVRR group: n = 7, (28.0%)], 54 patients were rehospitalized for cardiovascular causes [LVRR group: n = 36, (61.0%) vs. Failure of LVRR group: n = 18, (72.0%)], and 62 patients were rehospitalized for all‐causes [LVRR group: n = 43, (72.9%) vs. Failure of LVRR group: n = 19, (76.0%)]. Although there were no statistically significant differences in bleeding events, all‐cause death, cardiovascular rehospitalization, and all‐cause rehospitalization between LVRR and Failure of LVRR group, the Kaplan–Meier survival curve indicated that subjects in Failure of LVRR group had higher incidence of all‐cause mortality than those in the LVRR group (Figure 4 ).
Figure 4.
Kaplan–Meier survival curve for adverse events in the LVRR and the Failure of LVRR group. LVRR, left ventricular reverse remodelling.
Independent predictors for left ventricular thrombus resolution and embolic events
In this study, 48 subjects in the LVRR group and 15 in the Failure of LVRR group experienced LVT resolution. Univariate logistic analysis showed that Failure of LVRR (OR, 0.344; 95% CI, 0.122–0.967; P = 0.043), platelet (OR, 1.010; 95% CI, 1.001–1.019; P = 0.036), fibrinogen (OR, 1.977; 95% CI, 1.068–3.660; P = 0.030), and LDL‐C (OR, 2.637; 95% CI, 1.063–6.537; P = 0.036) were independent predictors for LVT resolution. After fully adjusted, multivariate logistic analysis revealed that only Failure of LVRR was a negative independent predictor for LVT resolution (OR, 0.211; 95% CI, 0.054–0.822; P = 0.025) (Table 2 ). A total of six patients in the LVRR group and seven patients in the Failure of LVRR group experienced embolic events during follow‐up. Univariate logistic analysis showed that Failure of LVRR (OR, 3.435; 95% CI, 1.020–11.571; P = 0.046), other thrombus events (OR, 6.800; 95% CI, 1.203–38.453; P = 0.030), and atrial fibrillation (AF) (OR, 5.714; 95% CI, 1.463–22.327; P = 0.012) were independent predictors for embolic events. Multivariate analysis revealed that Failure of LVRR (OR, 4.336; 95% CI, 1.078–17.450; P = 0.039), other thrombus events (OR, 11.726; 95% CI, 1.649–83.396; P = 0.014), and atrial fibrillation (OR, 5.895; 95% CI, 1.325–26.223; P = 0.020) were still positive independent predictors of embolic events (Table 3 ).
Table 3.
Logistic regression analysis to identify predictors of embolic events
| Univariate analysis | Multivariate analysis | |||||
|---|---|---|---|---|---|---|
| OR | 95% CI | P value | OR | 95% CI | P value | |
| Age | 1.000 | 0.957–1.043 | 0.982 | 0.983 | 0.933–1.036 | 0.529 |
| Failure of LVRR | 3.435 | 1.020–11.571 | 0.046 | 4.336 | 1.078–17.450 | 0.039 |
| Other thrombus events | 6.800 | 1.203–38.453 | 0.030 | 11.726 | 1.649–83.396 | 0.014 |
| AF | 5.714 | 1.463–22.327 | 0.012 | 5.895 | 1.325–26.223 | 0.020 |
| Oral anticoagulant | 0.585 | 0.170–2.010 | 0.394 | 0.601 | 0.139–2.599 | 0.496 |
AF, atrial fibrillation; CI, confidence interval; LVRR, left ventricular reverse remodelling; oral anticoagulant, a combination of patients receiving warfarin and direct oral anticoagulants; OR, odds ratio.
Discussion
The main findings of this study are as follows: (i) LVRR patients experienced higher incidence of LVT resolution, and Failure of LVRR was found to be a negative independent predictor of LVT resolution; (ii) LVRR patients had fewer embolic events during follow‐up period.
As mentioned before, abnormal blood flow is one of risk factors of LVT formation. Current research on management of LVT focuses on the efficacy of anticoagulated drugs, with less attention paid to abnormal blood flow. It is worth noting that LV chamber dilation and dysfunction caused by non‐ischaemic and ischaemic heart disease, known as LV structure and function remodelling, can lead to abnormal hemodynamic status. 25 However, LV remodelling can be reversed with GDMT, 26 LV assist device, 27 and invasive/surgical approaches, 28 collectively known as LVRR. 21 Patients with LVRR have better survival rates than those without reverse remodelling. 29 In our study, after adjusting correlated variates, including oral anticoagulant, the results showed that Failure of LVRR is still a negative independent predictor of LVT resolution. Although previous studies have not extensively explored the hemodynamic and other prethrombotic state changes caused by LVRR, several studies have suggested that blood stasis resulting from large apical or anterior LV dyskinesis and LV systolic dysfunction, 18 , 30 and abnormal LV structure 19 are linked to LVT formation. Jonathan et al. found that stepwise deteriorated LV contractile function from basal to apical was associated with LVT, supporting the notion that abnormal blood flow due to LV segmental dysfunction plays a critical role in LVT formation. 31 Sharma et al. reported that an increase in LV internal diastolic dimension (LVIDD) was an independent predictors of LVT formation (OR, 1.10; 95% CI, 1.03–1.18; P = 0.004), and no patients with LVIDD < 60 mm had LVT formation. 19 , 32 Furthermore, we observed that patients with LVRR had a lower incidence of IHD at baseline. Previous research has shown that independent correlates of LVT resolution include non‐ischaemic heart disease (HR, 2.74; 95% CI, 1.43–5.26; P = 0.002) and a smaller baseline thrombus area (HR, 0.66; 95% CI 0.45–0.96; P = 0.031). 33 The key factors for LVT formation after IHD may be blood stasis caused by LV segmental dysfunction, 1 endocardial injury, and inflammation. 34 In summary, the lower prevalence of IHD and improved LV structure and function may explain higher incidence of LVT resolution in patients with LVRR.
Several studies have investigated the embolic risk in patients receiving different antithrombotic therapies, but the results have been inconsistent. Hansa et al. found no statistically significant differences in the incidence of stroke (2% vs. 0%, P = 0.55) or other thrombotic events (2% vs. 0%, P = 0.55) between patients receiving VKA and DOACs. 35 Abdelnabi et al. reported that DOACs were associated with lower risk of embolism in LVT patients compared with warfarin (0% vs. 15%, P = 0.01). 16 However, other studies have drawn the opposite conclusions. For example, Austin et al. demonstrated that the risk of systemic embolism was significantly higher in patients receiving DOACs than in those receiving warfarin, according to univariable (HR for DOAC vs. warfarin, 2.71; 95% CI, 1.31–5.57; P = 0.01) and multivariable (HR for DOAC vs. warfarin, 2.64; 95% CI, 1.17–3.66; P = 0.01) Cox regression analysis. 36 The inconsistency of clinical outcomes creates challenges when selecting antithrombotic therapy for LVT patients. In our research, multivariable logistic regression analysis found that patients with atrial fibrillation or past history of thrombus events experienced higher risk of embolic events, which have been consistent with previous researches. 37 , 38 What is more, Failure of LVRR, characterized by a lack of reverse remodelling of the heart's structure and function, was an independent predictor for embolic events. Although it requires further prospective studies to validate this finding, LV systolic dysfunction and chamber dilation 19 appear to be independent predictors of embolic events. Nagaraja et al. confirmed that lower LVEF (OR, 0.91; 95% CI, 0.82–1.00, P = 0.04) was an independent predictor of systemic embolization, and patients with increasing ventricular chamber size (incidence of systemic embolic events in patients with LVIDD < 60 mm vs. LVIDD > 60 mm, 4% vs. 14.3%, P < 0.05) tended toward higher risk of embolism. 19 In summary, although large multicentre trials with strong quality are needed to confirm this finding, LVRR patients may experience lower risk of embolic events due to improved LV structure and function.
Optimal selection and usage of anticoagulation is the key for management of thrombus. However, the causes of LVT formation in patients can vary significantly, and abnormal LV function and structure play a significant role in promoting LVT formation. In our study, we found that Failure of LVRR, rather than different antithrombotic therapies, was a negative independent predictor of LVT and a positive independent predictor of embolic events. Therefore, clinicians should aim to identify and eliminate risk factors that contribute to abnormal LV function and structure during LVT treatment. Future clinical trials are needed to provide stronger evidence regarding the role of LVRR in the management of LVT.
Limitations
This study has several limitations. First, due to its retrospective nature, selection bias may be unavoidable. Second, the LVT patients were diagnosed via echocardiography, which has lower sensitivity compared with cardiac magnetic resonance (CMR), potentially leading to missed diagnosis. Third, the lack of statistically significant differences in secondary endpoints between the two groups in survival analysis may be attributed to the small sample size and single‐center design of the study. Additionally, we realized that different types of cardiovascular diseases met different clinical outcomes, and IHD might affect the incidence of LVRR and LVT resolution. However, considering its retrospective nature, the cause of LVT was hard to determination. That is why we discuss the role of LVRR in the whole population including patients with ischaemic and non‐ischaemic heart disease. In order to enhance reliability of results, we considered IHD as a covariate and adjusted it in multivariate logistic analysis. Future prospective studies need to identify specific group and confirm our findings.
Conclusions
Our study found that Failure of LVRR was a negative independent predictor of LVT resolution and a positive independent predictor of embolic events. These findings suggest that clinicians should be vigilant in identifying potential risks related to LV structural modification and dysfunction during the management of LVT.
Conflict of interest
There is no conflict of interest regarding the publication in this article.
Funding
This work was supported by the National Natural Science Foundation of China (No. U1908209 and No. 82170385).
Acknowledgements
The authors thank all staff for their outstanding efforts in this work.
Chen, X. , Zhang, X. , Yang, Y. , Sun, Y. , Si, J. , Jiang, S. , Hu, Y. , Ding, Z. , Xia, Y. , Chen, Y. , and Liu, Y. (2024) Left ventricular reverse remodelling as a promising strategy for resolving left ventricular thrombus. ESC Heart Failure, 11: 2214–2222. 10.1002/ehf2.14781.
Xuefu Chen and Xinxin Zhang contributed equally to this work and shared first authorship.
Contributor Information
Yanwei Chen, Email: chenyanweile@163.com.
Ying Liu, Email: yingliu.med@gmail.com.
Data availability statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.