Left ventricular thrombus after acute myocardial infarction

INTRODUCTION — Left ventricular (LV) thrombus may develop after acute myocardial infarction (MI) and occurs most often with a large, anterior ST-elevation MI (STEMI). However, the use of reperfusion therapies, including percutaneous coronary intervention and fibrinolysis, has significantly reduced the risk. LV thrombus can lead to arterial embolic complications such as stroke. Patients with LV thrombus or those at high risk for development of this complication should receive anticoagulation for at least three months.

This topic will discuss LV thrombus in detail. Other potential causes of arterial emboli originating in the heart are presented elsewhere:

●(See "Clinical features and diagnosis of acute lower extremity ischemia", section on 'Arterial embolism'.)

●(See "Overview of secondary prevention for specific causes of ischemic stroke and transient ischemic attack", section on 'Cardiogenic embolism'.)

PATHOPHYSIOLOGY — LV thrombus is most often seen in patients with large, anterior ST-elevation MI with anteroapical aneurysm. In most cases, these infarcts occur in the distribution of the left anterior descending coronary artery [1]. These anteroapical infarcts have large areas of poorly contracting LV muscle; adjacent intracavitary blood movement is sluggish (stasis) compared with normal areas. This relative stasis of blood is thought to increase the risk of thrombus formation. Many, but not all, of these patients will have an LV apical aneurysm with akinesis or dyskinesis. In most cases, thrombus is located within or adjacent to the LV apex [1] but can also occur with large basal inferolateral infarctions/aneurysms. Contact of blood with the fibrous tissue in the aneurysm rather than normal endocardium is also thought to trigger clot formation.

AT-RISK PATIENTS — Patients with one or more of the following are at risk for the development of LV thrombus. However, we do not routinely anticoagulate patients at risk in the absence of documented LV thrombus.

●Anterior ST-elevation MI by electrocardiographic criteria. (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'Anterior, lateral, and apical MI'.)

●Left anterior descending coronary artery infarct (especially proximal left anterior descending coronary artery infarct).

●Large infarction defined as a LV ejection fraction (LVEF) <30 percent. Many, but not all, of these patients will have an LV aneurysm. (See "Left ventricular aneurysm and pseudoaneurysm following acute myocardial infarction", section on 'Left ventricular aneurysm'.)

●Long delay between onset of symptoms and reperfusion (more than four to six hours) due to the increased risk for an LV aneurysm due to more extensive infarction/systolic dysfunction.

INCIDENCE — Over the past 30 years, the incidence of LV thrombus has decreased as the frequency of early reperfusion therapies has increased. The likely mechanism is that early reperfusion, compared with no or late reperfusion, leads to smaller infarction [1-12]. Its impact may be greatest in patients with anterior infarctions, which tend to be larger than infarcts at other locations. (See 'Pathophysiology' above.)

The incidence of LV thrombi in the prereperfusion era was reported to be as high as 40 percent in patients with anterior infarction [4,7]. Most thrombi developed within the first two weeks (median five to six days) after MI [3,4,7,10,11]. In a series of 30 patients with LV thrombus after an acute anterior MI, 27 percent were present at less than 24 hours, 57 percent at 48 to 72 hours, 75 percent at one week, and 96 percent at two weeks [5].

Data are more limited on the incidence of LV thrombus in the reperfusion era. In two series of ST-elevation MI (STEMI) patients treated with primary percutaneous coronary intervention, the incidence of LV thrombus was about 4 percent [13,14].

However, the true incidence of LV thrombus in the current reperfusion era may be higher than in the above studies, as reported incidence depends on the sensitivity of the diagnostic test used. Cardiovascular magnetic resonance (CMR) imaging with late gadolinium enhancement (LGE) has been shown to be considerably more sensitive than transthoracic echocardiography (TTE) with or without an intravenous endocardial border definition contrast agent. In a study of 201 STEMI patients, of whom 199 were treated with reperfusion, who were evaluated with LGE-CMR, the incidence of LV thrombus was 8 percent [1].

Finally, some of these studies may have underestimated the true incidence, as patients at high risk for LV thrombus (severe heart failure and systolic blood pressure below 100 mmHg) were excluded. (See 'Diagnosis' below.)

DIAGNOSIS — Most patients with acute ST-elevation MI (STEMI) should undergo (noncontrast) TTE to assess LV systolic function before discharge with specific evaluation of anteroapical systolic function, aneurysm, and the presence of an LV thrombus (algorithm 1). In most patients, the diagnosis of an LV thrombus will be made using TTE (image 1 and movie 1). (See 'At-risk patients' above.)

TTE performed very early after an anteroapical infarction may show an LVEF <30 percent; however, repeat TTE 48 hours after reperfusion may show significant improvement in LV systolic function. (See 'Incidence' above.)

When the sonographer is screening for LV thrombus, particular attention should be paid to the LV apex (or for any aneurysm or dyskinetic segment). In addition to reporting the presence of an aneurysm and wall motion in that region, the presence or absence of thrombus should be noted in the report. TTE characteristics of LV thrombus include a mural or pedunculated echodensity often of similar acoustic properties to myocardium (movie 2A-B). (See "Echocardiography in detection of cardiac and aortic sources of systemic embolism", section on 'Left ventricular thrombi'.)

TTE image quality may be suboptimal due to conditions such as chronic pulmonary disease or obesity. Distinguishing thrombus from normal trabeculations may also be difficult. Near-field artifact may also give the appearance of apical thrombus. The sonographer should use an intravenous endocardial border definition contrast agent whenever an apical aneurysm is identified [15,16]. With contrast injection, LV thrombus appears as a filling defect within the ventricular cavity. (See "Contrast echocardiography: Clinical applications", section on 'Rest echocardiography'.)

In patients where there remains uncertainty regarding the presence or absence of thrombus, CMR with gadolinium contrast using a long inversion time should be considered. We consider transesophageal echocardiography (TEE) inferior to long inversion time late gadolinium enhancement (LGE) CMR for the diagnosis of LV thrombus since the apex is often not well visualized by the former test, but may be considered when CMR is not available. Contrast-enhanced cardiac computed tomography is another option.

CMR is considered the gold standard for the noninvasive diagnosis of LV thrombus. Long inversion time LGE-CMR has a greater sensitivity than TTE and a similarly high specificity for the detection of LV thrombus in an ischemic cardiomyopathy population [17-19]. However, it is not used to screen for LV thrombus in all patients with an anteroapical aneurysm due to issues of cost and availability. (See "Clinical utility of cardiovascular magnetic resonance imaging".)

In a retrospective study of 160 patients with a remote prior MI who had surgical and/or pathological confirmation of the presence (48 patients [30 percent]) or absence of LV thrombus, all patients underwent nonsimultaneous preoperative LGE-CMR, TTE, and intraoperative TEE [17]. CMR was significantly more sensitive (88 versus 23 and 40 percent with TTE and TEE, respectively). All imaging modalities had specificities of 96 percent or greater.

In another study, 201 patients were evaluated with noncontrast and contrast TTE, cine-CMR, and LGE-CMR 7 to 30 days after STEMI [1]. Using LGE-CMR as the gold standard for determining the presence of absence of LV thrombus, the following findings were noted:

●LV thrombus was present in 17 patients (8 percent).

●The sensitivity of noncontrast and contrast TTE was only 35 and 64 percent, respectively.

●The specificity of noncontrast and contrast TTE was 98 and 99 percent, respectively.

●Only 12 percent of patients with thrombus had a LVEF ≤30 percent, and LV aneurysm was present in only 24 percent.

●On both noncontrast and contrast TTE, a high apical wall motion score, as measure of apical dysfunction, was strongly correlated with the presence of LV thrombus.

Differential diagnosis — In addition to MI, true LV thrombus may occur in other conditions such as stress cardiomyopathy or myocarditis. However, in a patient with documented acute STEMI, the odds are in favor of the infarct being causative.

Incidentally discovered LV thrombus — An uncommon patient may present with incidentally discovered LV thrombus during a cardiac imaging study done for other reasons. We treat with oral anticoagulant (OAC) for three months and then reevaluate the thrombus. If there is evidence of thrombus resolution, we stop OAC and reevaluate with echocardiography in another three months.

OUTCOMES — Newly diagnosed LV thrombi may undergo complete resolution, partial resolution, or endothelialization. Prior to one of these end points, embolization may occur.

The risk of embolization in patients with a documented LV thrombus who are not treated with anticoagulant therapy has been reported to be 10 to 15 percent. In a series of 85 patients with LV thrombus (most of whom had a recent MI) followed for almost two years, an embolic event occurred in 11 (13 percent) of those with thrombi compared with only 2 of 91 (2 percent) in a matched control group [20]. In another study of patients with an anterior MI, the presence of an LV mural thrombus identified by noncontrast TTE increased the incidence of an embolic event (odds ratio 5.5, 95% CI 3.0-9.8) [21]. Most embolic events occur within the first three to four months [2,5,6,20-23], although some occur later [20].

Two major echocardiographic risk factors for embolization have been identified: thrombus mobility and thrombus protrusion [2,6,20,24]. In one report, embolization occurred in 22 percent of 119 patients with an LV thrombus after acute MI [2]. Free mobility of the thrombus was present in 58 percent of patients with embolization compared with 3 percent without embolization; among the 18 patients with free thrombus mobility, embolization occurred in 15 (83 percent compared with 11 percent without mobility). Protrusion of the thrombus into the LV cavity was present in 88 percent of those patients with clinical thromboembolism compared with 18 percent without; among the 40 patients with thrombus protrusion, embolization occurred in 23 (58 percent compared with 4 percent without protrusion).

An observational study of 159 patients with a confirmed LV thrombus, most of whom were anticoagulated, found the following at a median follow-up of 103 days [25]:

●A reduction of the thrombus area from baseline was observed in 76 percent, with total regression in 62 percent.

●During a median follow-up of 632 days, death occurred in 18 percent, stroke in 13 percent, and major bleeding in 13 percent.

●A LVEF ≥35 percent and anticoagulation therapy >3 months were independently associated with lower rates of major adverse cardiovascular outcomes.

PREVENTION OF EMBOLIC EVENTS — The following is our approach to the prevention of stroke and systemic embolic events in at-risk patients:

●In all patients being considered for anticoagulant therapy, the benefit must be weighed against the risk of bleeding. This is particularly important since many patients will be receiving treatment with one or two oral antiplatelet agents for some period of time. (See "Coronary artery disease patients requiring combined anticoagulant and antiplatelet therapy", section on 'Discharge to 12 months'.)

●We anticoagulate most MI patients with documented LV thrombus [26]. (See 'Diagnosis' above.)

Some of our contributors will consider anticoagulation in the absence of LV thrombus if apical or basal inferior akinesis/dyskinesis with aneurysm is present. This is a particularly high-risk group for the development of LV thrombus. (See 'At-risk patients' above.)

●There are no large prospective or direct comparison data of direct-acting oral anticoagulants (DOAC; also referred to as non-vitamin K antagonist oral anticoagulants [NOAC]) versus warfarin for prophylaxis for LV thrombus. We consider using DOAC rather than warfarin due to convenience and achievement of therapeutic anticoagulation so long as there is no specific indication for warfarin (eg, prosthetic heart valve).

●For patients in whom warfarin is chosen rather than DOAC, we recommend starting parenteral anticoagulation with unfractionated heparin or a low molecular weight heparin as soon as LV thrombus after acute MI is identified. The goal activated partial thromboplastin time is two to three times the control value. Parenteral anticoagulation should be continued until effective anticoagulation with warfarin (target international normalized ratio [INR] 2 to 3) has been achieved. This recommendation may need to be modified based on the specific antithrombotic requirements of patients treated with primary percutaneous coronary intervention or fibrinolytic therapy. (See "Acute ST-elevation myocardial infarction: Management of anticoagulation", section on 'Summary and recommendations'.)

There are no studies that have evaluated the optimal timing of parenteral anticoagulation. We believe it is reasonable to start therapy as soon as an at-risk patient is identified and to discontinue parenteral therapy when effective anticoagulation with warfarin has been achieved (INR of 2 to 3) or the diagnosis has been excluded. Early studies of patients treated with warfarin found that anticoagulation with heparin, if started early and continued for more than 48 hours, lowers the risk of thrombus formation [21]. Other studies suggested benefit from parenteral anticoagulation for up to 14 days [27-29]. However, we do not recommend prolonged parenteral therapy, as early initiation of oral warfarin therapy in appropriate patients is likely to be as effective and is more practical.

●If indicated, oral anticoagulant therapy should be started early after MI and continued for at least three months, as most embolic events occur within the first three to four months. (See 'Outcomes' above.)

In patients who do not have a specific indication for warfarin (eg, mechanical heart valve), we often prefer a DOAC due to convenience in dosing and more rapid achievement of therapeutic anticoagulation.

●Concomitant antiplatelet therapy is indicated in all these patients, as they have sustained an MI. The use of combined anticoagulant and antiplatelet therapy is discussed separately. (See "Coronary artery disease patients requiring combined anticoagulant and antiplatelet therapy", section on 'Discharge to 12 months'.)

●Our approach to the use of antiplatelet therapy after termination of anticoagulation is presented separately. (See "Acute ST-elevation myocardial infarction: Antiplatelet therapy", section on 'Duration of dual antiplatelet therapy'.)

Evidence for anticoagulation — The approach to prevention of stroke and systemic emboli in high-risk acute MI patients is based on limited evidence:

●Older, observational studies provide support for a recommendation to anticoagulate reperfused patients with documented LV thrombus after MI to reduce the risk of embolization [7,21-23]. There are no randomized trials evaluating the efficacy of prolonged oral anticoagulation, compared with no anticoagulation, in the present reperfusion era.

●There are no studies that have compared anticoagulation with no anticoagulation in MI at-risk patients without LV thrombus. (See 'At-risk patients' above.)

●There are no randomized studies that have compared warfarin to DOAC for the prevention of thrombus formation in patients at high risk or for the treatment of LV thrombus. However, in case series of DOAC use in patients with documented LV thrombi, some with recent ST-elevation MI, DOAC use was associated with thrombus resolution [30-34] and was more effective than warfarin [35].

One retrospective cohort study of 514 patients with echocardiographically detected LV thrombi included 300 who received warfarin and 185 who received a DOAC [36]. After a median follow-up of nearly one year, anticoagulation with DOAC was associated with a higher risk of stroke or systemic embolism on multivariable analysis (hazard ratio 2.64, 95% CI 1.28-5.43).

Based on this one study, we consider performing a follow-up TTE with an endocardial border definition agent after two to four weeks of DOAC to assess thrombus resolution. If there is no resolution, we consider switching to warfarin.

Concomitant antiplatelet therapy — All decisions regarding the prolonged use of anticoagulant therapy in these patients must take into account the concurrent risk of bleeding. Bleeding is a particularly important issue, as most of these patients have an indication for intense dual antiplatelet therapy (in addition to anticoagulant therapy) due to the placement of an intracoronary stent after an acute coronary syndrome. (See "Acute non-ST-elevation acute coronary syndromes: Early antiplatelet therapy", section on 'Summary and recommendations' and "Long-term antiplatelet therapy after coronary artery stenting in stable patients", section on 'Duration and Type of Antiplatelet Treatment' and "Coronary artery disease patients requiring combined anticoagulant and antiplatelet therapy" and "Acute ST-elevation myocardial infarction: Antiplatelet therapy".)

While it is biologically plausible that intense antiplatelet therapy could protect against the formation and embolization of LV thrombus, this has not been studied, and we do not recommend it as a substitute for oral anticoagulation to prevent embolization of LV thrombus. Finally, there are no high-quality studies that address the issue of the optimal antithrombotic regimen in these patients with LV thrombus who are not stented. Specifically, the role of P2Y₁₂ receptor blockers has not been evaluated in randomized trials.

ROLE OF FOLLOW-UP IMAGING — TTE with contrast or long inversion time late gadolinium enhancement CMR imaging can be used to monitor resolution of thrombus with anticoagulation [2,4,6,7,12]. Most patients are followed by TTE, with CMR reserved only for situations in which TTE is technically suboptimal.

Based on a limited amount of evidence, we believe it is reasonable to get a follow-up TTE (if the thrombus was previously visualized on TTE) to determine if the thrombus identified on the first TTE has resolved or organized or to assess the degree of left ventricular (LV) remodeling. We obtain this follow-up TTE between two and three months after initial thrombus identification.

The findings of persistent pedunculation of the thrombus may reasonably lead to a decision to prolong anticoagulation beyond the recommended time; the finding of significant improvement of the LVEF and resolution of the apical wall motion abnormality may reasonably lead to a decision to shorten the duration of anticoagulation.

In three series in which serial TTE was performed, thrombus resolution was seen in 14 of 29 patients (47 percent) at six months, 24 of 51 (47 percent) at one year, and 16 of 21 (76 percent) at two-year follow-up [4,6,12]. As noted below, only a small number of late persistent thrombi are associated with embolic events, as most embolic events occur within the first four months. (See 'Prevention of embolic events' above.)

The predictors of LV thrombus resolution are not well defined. In one report, the only independent predictor of thrombus resolution was the absence of apical dyskinesis at six weeks after MI [12]. This observation is consistent with apical dyskinesis or akinesis being a risk factor for thrombus formation [3]. Although warfarin therapy appears to reduce the rate of embolization, it may not increase the rate of thrombus resolution [7].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: ST-elevation myocardial infarction (STEMI)" and "Society guideline links: Non-ST-elevation acute coronary syndromes (non-ST-elevation myocardial infarction)".)

SUMMARY AND RECOMMENDATIONS

●Pathophysiology – Left ventricular (LV) thrombus is a major cause of embolic stroke after acute myocardial infarction (MI). Patients with large anterior MI are at the highest risk for the development of LV thrombi; these patients usually have an LV ejection fraction (LVEF) less than 30 percent and a severe anteroapical or basal inferolateral wall motion abnormality with aneurysm on an imaging study. (See 'Pathophysiology' above.)

●Diagnosis – For patients at risk of LV thrombus, we obtain a transthoracic echocardiogram with echo contrast to screen for LV thrombus in those with an aneurysm. (See 'Diagnosis' above.)

●Treatment – Our recommendations for the use of anticoagulation are as follows:

•Documented thrombus – For patients with MI and documented LV thrombus, we recommend anticoagulation (Grade 1B). Most of our contributors prefer direct-acting oral anticoagulants (DOAC; also referred to as non-vitamin K antagonist oral anticoagulants) to warfarin for prophylaxis for LV thrombus. (See 'Prevention of embolic events' above.)

In patients treated with warfarin, parenteral anticoagulation with unfractionated heparin or low molecular weight heparin should be started as soon as possible and continued until effective oral anticoagulation has been achieved. Warfarin should be started soon after initiation of parenteral anticoagulation; the goal of therapy is an international normalized ratio of 2 to 3.

•Low left ventricular ejection fraction – For patients with MI and no clear thrombus but an LVEF less than 30 with anteroapical or basal inferior/inferolateral wall akinesis/dyskinesis and aneurysm, we suggest prophylactic anticoagulation (Grade 2C). (See 'Prevention of embolic events' above.)

For patients with MI and an LVEF between 30 and 40 percent with a severe anteroapical hypokinesis on imaging but no dyskinesis or aneurysm or thrombus on imaging, we suggest not treating with prophylactic anticoagulation (Grade 2C).

The relative benefits and risks of anticoagulation need to be weighed carefully in these two groups.

For those prescribed anticoagulation with warfarin or DOAC, we suggest continuing anticoagulation for three months rather than a longer duration (Grade 2C). We consider longer duration if there is residual thrombus after three months.

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Scott Solomon, MD, who contributed to earlier versions of this topic review.