By Michael H. Crawford, MD, Editor
SYNOPSIS: Left ventricular thrombus is an uncommon finding but one associated with a high incidence of all-cause mortality, and major adverse cardiac and embolic events. Total regression of left ventricular thrombus on anticoagulant therapy reduced mortality.
SOURCE: Lattuca B, Bouziri N, Kerneis M, et al. Antithrombotic therapy for patients with left ventricular mural thrombus. J Am Coll Cardiol 2020;75:1676-1685.
Left ventricular thrombus (LVT) can be observed in up to one-quarter of patients with ST-elevation myocardial infarction (STEMI) and one-third of patients with dilated cardiomyopathy using optimal imaging techniques. Although guidelines recommend anticoagulation therapy for LVT, there are few data about the optimal course and type of therapy and its efficacy.
In a large Paris hospital, Lattuca et al conducted a retrospective, observational study of echocardiograms that were performed between 2011 and 2017. On each echocardiogram, two independent experts reported LVT. In discordant cases, another imaging modality, such as contrast echo, computed tomography, or magnetic resonance imaging, was performed. Patients with thrombi in other chambers were excluded. Clinical information, including anticoagulant therapy, was obtained by chart review. The study population consisted of 159 patients (mean age 58 years, 18% women, 79% ischemic etiology, and mean LV ejection fraction 32%). Anticoagulation therapy was administered to 99% of the patients: vitamin K antagonists (VKA) in 48%, direct oral anticoagulants (DOAC) in 23%, low molecular weight heparin in 23%, and unfractionated heparin in 5% for a median duration of 508 days.
Total LVT regression was achieved in 62% at a median time of 103 days. Total LVT regression after multivariate adjustment was associated with smaller thrombi (hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.45-0.96; P = 0.03) and non-ischemic etiology (HR, 2.74; 95% CI, 1.43-5.26; P = 0.002). Major adverse cardiac events (MACE) and embolic events occurred in 37% and 22%, respectively. All-cause mortality was 19%, and major bleeding occurred in 30%.
Total LVT regression was associated with fewer deaths (HR, 0.48; 95% CI, 0.23-0.98; P = 0.39), whereas persistent LVT was associated with major bleeding (HR, 0.34; 95% CI, 0.14-0.82; P = 0.011). MACE occurred more commonly in patients with an LV ejection fraction (EF) ≤ 35% (HR, 0.46; 95% CI, 0.23-0.93; P = 0.029) and who were on anticoagulant therapy for less than three months (HR, 0.42; 95% CI, 0.20-0.88; P = 0.021). There were fewer embolic events in patients treated with anticoagulant therapy for longer than three months (HR, 0.46; 95% CI, 0.18-1.14; P = 0.09). The type of anticoagulant used was not associated with outcomes.
The authors concluded LVT was associated with a high risk of MACE, and LVT regression reduced this risk regardless of the anticoagulation regimen.
In my experience, the incidence of LVT decreased markedly after the widespread use of reperfusion therapy for acute STEMI. Lattuca et al needed to peruse 90,000 echocardiograms to find 174 potential cases of isolated LVT. Among these, 14 were eliminated because LVT was not confirmed on other imaging modalities, and one was excluded by review with the second reader. This left 159 patients for this study. This investigation did not permit an assessment of prevalence by diagnosis. Most patients had ischemic heart disease, and 35% had experienced a STEMI. Considering the mean EF of 32%, most had a reduced EF. Almost all the thrombi detected were apical, but only 15% had an aneurysm. Interestingly, 35% of the thrombi were mobile.
LVT are a well-known complication of left-sided heart diseases, and were described as far back as 1847 in autopsy studies.1 Although relatively uncommon today, LVT are associated with an adverse prognosis. In this study, 40% of subjects experienced a cardiovascular event and 20% died over a median follow-up of 1.7 years. These are higher event rates than those seen after a STEMI in general.
Despite its uncommon nature, a LVT is an important finding whose optimal treatment is largely unknown. All major guidelines recommend an echocardiogram in post-MI and cardiomyopathy patients. If a LVT is found, prescribe anticoagulation with a vitamin K antagonist for three to six months. Based on small, observational studies, practitioners often use DOACs.
The Lattuca et al study shows LVT regression, which occurred in two-thirds of their patients, was associated with lower mortality and fewer MACE if treatment was continued for longer than three months. This was at the cost of major bleeding in more than 10% of patients. The efficacy of DOACs was equivalent to vitamin K antagonists, but this study was not powered to answer this question.
The major limitations of the Lattuca et al study were that it was retrospective, observational, and conducted from a single center. Also, contrast echo was not used routinely. I have found contrast echo increases sensitivity for detecting LVT; it should be performed in all post-MI patients and others with low EFs. If a LVT is discovered, my practice is to treat with warfarin (if there are no contraindications) for three months, then re-image. If the LVT is gone, I usually stop anticoagulation; if not, I continue treatment for another three months, and repeat as necessary. A few patients end up on indefinite anticoagulation. Outstanding issues are the role of antiplatelet agents and the comparative efficacy of DOAC, but it is hard to imagine someone conducting a randomized, controlled study of LVT patients.
- Virchow R. Ueber die akute Entzündung der Arterien. Archiv f pathol Anat 1 1847:272-378.