The Challenge of Managing Left Ventricular Thrombus: Questions and Answers

Left ventricular (LV) thrombus is a relatively common condition that can result in thromboembolism including devastating stroke. Over the past 50 years, there have been over 6,600 studies that appear in a PubMed search of “left ventricular thrombus,” documenting substantial evolution of susceptible patient populations, diagnostic imaging techniques, and treatment options. In part because of a paucity of high level evidence from randomized trials, there has been relatively little guideline recommendation about the management of this condition. In recent years, there have been substantial advances in the understanding of left ventricular thrombus and evidence to guide its management. Thus, this thoughtful and measured Scientific Statement from the American Heart Association is a timely and welcome contribution.

The Statement makes 8 practical management suggestions (summarized graphically in Figure 5) for patients at risk for or with LV thrombus, outlined here. (1) For anterior ST elevation myocardial infarction (MI) treated with reperfusion therapy, the benefit of oral anticoagulation (OAC) to prevent LV thrombus is uncertain given the risks. (2) Patients with LV thrombus post MI should receive OAC, “typically” for 3 months. (3) Patients with dilated cardiomyopathy should not be treated with prophylactic OAC, with possible exception of those specific cardiomyopathies with higher risk, like Takotsubo syndrome, LV non-compaction, and peripartum cardiomyopathy where OAC “could be considered.” (4) The authors “suggest that” patients with non-ischemic cardiomyopathy with LV thrombus be treated with OAC for “at least 3-6 months,” with discontinuation if LV ejection fraction improves or if bleeding occurs. (5) “It may be prudent” to treat newly diagnosed mural thrombus with OAC as one would for protruding thrombus. (6) Cardiac magnetic resonance (MR) imaging “may be most appropriate” when echocardiography suggests thrombus but is not diagnostic even with contrast imaging as well as when echocardiography does not show thrombus but suspicion is high for thromboembolism. (7) For treatment of LV thrombus, direct acting oral anticoagulants (DOACs) “seems a reasonable alternative” to warfarin. (8) For persistent LV thrombus, “particularly if protruding,” “a trial of an alternate OAC or low molecular weight heparin is not unreasonable,” nor is it unreasonable to stop OAC if the thrombus becomes “organized or calcified.”

Uncertainty behind the management suggestions

These suggestions cover the most important questions asked by providers, and each suggestion is supported by a comprehensive review of the available literature. However, most of the data come from observational studies with all of the attendant limitations, and thus most of the suggestions are carefully worded to acknowledge uncertainty and need for clinical judgement in applying them to assess risk and benefit. For example, the common question of how long anticoagulation should be continued when an LV thrombus is detected in a patient with dilated cardiomyopathy cannot be answered due to “insufficient study data.” Clinical judgement might lead one to favor longer term oral anticoagulation if an LV thrombus is large and mobile or if is detected in the setting of an acute (presumably embolic) stroke in a patient with a chronic dilated cardiomyopathy. In the setting of acute anterior MI, particularly with delayed presentation or with no reperfusion therapy, not only is the method of imaging important, but so is the timing of imaging. One study of patients treated with primary percutaneous coronary intervention found that 7 of 18 patients with LV thrombus had it develop between the first and fifth day after presentation of acute MI (1). This suggests that in such patients, the typical timing of echocardiography imaging on the first day is not enough to detect many of the thrombi that will develop. This Scientific Statement suggests that a repeat echocardiogram in 2 weeks “might be considered.”

Use of warfarin versus DOAC

There is only one small randomized trial, published in 1990, of warfarin versus placebo for treating LV thrombus in the setting of acute MI, and LV thrombus resolution was not significantly lower with warfarin than with aspirin (2). Observational studies, summarized in this Scientific Statement, strongly suggest that warfarin decreases thromboembolic events in these patients. Moreover, observational studies have reported comparable rates of clinical events and of thrombus resolution with DOACs versus warfarin. But modest differences may well exist that cannot be reliably estimated with observational studies. Thus, the three small randomized trials in patients with LV thrombus of warfarin versus rivaroxaban in patients with cardiomyopathy (3), warfarin versus apixaban in acute MI (4), and warfarin versus apixaban in heart failure (5) are important. Each found comparable rates of LV thrombus resolution with DOAC versus warfarin. Since DOACs are known to have lower rates of bleeding, and in particular intracranial hemorrhage, and lower mortality than warfarin for chronic use in atrial fibrillation (6), DOACs would seem to have advantages over warfarin for most patients with LV thrombus. Since the typical treatment for LV thrombus is for 3 months, and since warfarin has lower time in therapeutic INR range with warfarin as it is initiated, less predictable effects during the early period when the risk of stroke is highest is a drawback for warfarin. The Scientific Statement takes a conservative approach to suggesting that DOAC “seems a reasonable alternative” to warfarin, pending further trial results.

Future research needs

The Scientific Statement underscores that with management of LV thrombus mainly guided by observational study results, clinical trials are needed to define the patient populations who derive greater benefit than risk for prevention of LV thrombus. Also, trials are needed to determine if treatment should be tailored to LV thrombus morphology, to determine if OAC is needed for post-MI thrombus compared to dual antiplatelet therapy, to determine if OAC has greater benefit than risk for LV thrombus in patients with dilated cardiomyopathy, and to determine which oral anticoagulants are optimal for various settings. Until we have this much-needed additional evidence, this Scientific Statement is the best available guide to the management of this important medical condition.