Cohort of Patients With Left Ventricular Thrombus: Management and Outcomes in the Direct Oral Anticoagulants Era (LV-Thrombus)

The investigators' primary objective is to assess whether a difference in the occurrence of bleeding events exist between patients with LVT treated with DOACs as compared to those treated with VKAs.

Study Overview

• Status: Recruiting
• Conditions: Thrombus of Left Ventricle

Detailed Description

Left ventricular thrombus (LVT) is a well-known complication of left ventricle (LV) systolic dysfunction that can be seen in acute systolic dysfunction, i.e. induced by an acute myocardial infarction (AMI) or Takotsubo cardiomyopathy, and in chronic heart failure with reduced ejection fraction (HFrEF), whatever the cause.

Improvements in the management of AMI, particularly with the implementation of primary percutaneous coronary intervention (PCI), have led to a striking reduction in the occurrence of LVT in patients with AMI from about 30% in the thrombolytic era to about 4% nowadays, according to echocardiographic assessment. On the other hand prognosis of patients with LVT didn't change over time: mortality and risk of embolic events associated with this condition are still high.

A limited amount of evidence shows that oral anticoagulation is associated in the majority of patients with both resolution of LVT and reduction in ischemic events. This benefit comes at the cost of bleeding complications, which have been demonstrated to impact on mortality, especially in patients after AMI receiving an oral anticoagulant on top of a dual antiplatelet therapy (so-called triple antithrombotic therapy).

Current European and American guidelines on treatment of myocardial infarction with ST-elevation do not make strong recommendations for the management of LVT, whereas guidelines on treatment of heart failure do not give any. The European Society of Cardiology recommends an anticoagulation treatment for up to 6 months from diagnosis in case of LVT thrombus after AMI and the decision to continue the therapy after 6 months should be taken on the basis of echocardiographic follow-up (class IIa level of evidence C). The American College of Cardiology and American Heart Association (AHA) gives a similar recommendation (IIaC), however specifically mentioning vitamin K antagonists (VKAs) and a target INR (international normalized ratio) 2.0-2.5 for 3 months on top of dual antiplatelet therapy (DAPT). They also propose to consider an anticoagulant therapy for patients with severe anterior wall motion after STEMI but without LVT (IIbC). The AHA and American Stroke Association published in 2014 their last recommendations for secondary stroke prevention, which are in line with the above mentioned guidelines. Direct oral anticoagulants (DOACs) are mentioned as an alternative to VKAs (IIbC).

All guidelines agree that DOACs for LVT treatment cannot be recommended as first-line therapy because of the scarce evidence, based on case reports small case series and only one large retrospective study (RED VELVT study, published on April 22, 2020).

However, in clinical practice because of the establishment of DOACs over VKAs as first-line therapy to prevent embolic events in patients with atrial fibrillation, those are prescribed off-label to a significant number of patients with LVT. DOACs, as compared to VKAs, showed a greater efficacy regarding prevention of ischemic and hemorrhagic stroke and systemic embolic events in atrial fibrillation, but an increased risk of gastrointestinal bleedings.

The pathophysiology of thrombus formation in a left ventricle with regional wall motion abnormalities and in left atrium with atrial fibrillation is very similar and it implies a blood stasis as main mechanism. Thus one could expect that DOACs, which have been demonstrated to be superior to VKAs in term of prevention of embolic events in atrial fibrillation, have a similar effect on treatment of LVT. However, the first large retrospective study including 541 patients with LVT, of which 421 treated with anticoagulation showed an increased risk of embolic events at 1 year among patients with LVT treated with DOACs as compared to those on VKAs; occurrence of bleeding events was not reported.

Beside the above mentioned uncertainty concerning duration and type of treatment (VKAs versus DOACs) in LVT, there are also some issues concerning the imaging modality used for the diagnosis of LVT. Several studies comparing the diagnostic performance of transthoracic echocardiography (TTE) versus cardiac magnetic resonance (CMR) showed a roughly 30% sensitivity of TTE when taking delayed-enhancement CMR (DE-CMR) as gold standard. With the growing use of CMR, an increasing number of patients are diagnosed with small left ventricular thrombi, which would have been missed in usual clinical practice and which seem to be associated with an embolic risk similar to thrombi detected by TTE.

• Study Type: Observational
• Enrollment (Estimated): 550

Contacts and Locations

• Study Contact: Name: Christoph Gräni, Prof. PHD; Phone Number: +41 31 632 4508; Email: christoph.graeni@insel.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Department of Cardiology, University Hospital Bern
    • Contact: Christoph Gräni, Prof. PhD; Phone Number: +41316324508; Email: christoph.graeni@insel.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This is an observational, retrospective and prospective, monocentric study including all patients diagnosed with left ventricular thrombus through different imaging modalities (echocardiography, CT or MRI)

Description

Inclusion Criteria:

• Patients at least 18 years old at enrolment
• With a LVT identified at echocardiography, MRI or CT between January 1st, 2013 and July 31st, 2020
• Treated at least once at the Inselspital or in another site of the Insel Gruppe
• Able to provide a written informed consent

Exclusion Criteria:

• Documented refusal

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients diagnosed with left ventricular thrombus; All patients diagnosed with left ventricular thrombus through different imaging modalities (echocardiography, CT or MRI) and who have been diagnosed and/or treated at the Inselspital or another site of the Insel Gruppe.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The occurrence at 1 year of bleeding	Primary combined endpoint includes the occurrence at 1 year of bleeding BARC (Bleeding Academic Research) Consortium type 2, 3 or 5.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of patients with arterial systemic embolic event	Combined endpoint of arterial systemic embolic event, including ischemic stroke, myocardial infarction, peripheral embolism (e.g. splenic infarction, renal infarction, bowel infarction, acute embolic limb ischemia) at 1, 2 and 5 years.	1, 2 and 5 years
Rate of patients with ischemic stroke	Each arterial systemic embolic event considered separately at 1, 2 and 5 years	1, 2 and 5 years
Rate of patients with myocardial infraction	Each arterial systemic embolic event considered separately at 1, 2 and 5 years	1, 2 and 5 years
Rate of patients with peripheral embolism	Each arterial systemic embolic event considered separately at 1, 2 and 5 years	1, 2 and 5 years
Rate of patients with transient ischemic attack	Transient ischemic attack at 1, 2 and 5 years	1, 2 and 5 years
Rate of patients with pulmonary embolism	Pulmonary embolism at 1, 2 and 5 years	1, 2 and 5 years
All-cause mortality	All-cause mortality at 1, 2 and 5 year(s)	1, 2 and 5 years
LVT size/resolution	LVT size/resolution at follow-up imaging	5 years

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Christoph Gräni, Prof. PHD, Department of Cardiology, University Hospital Bern

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Estimated): February 28, 2026
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: August 25, 2021
• First Submitted That Met QC Criteria: August 25, 2021
• First Posted (Actual): August 31, 2021

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Acute Myocardial Infarction; Direct Oral Anticoagulant; Left Ventricular Assist Device; Dual Antiplatelet Therapy; Left Ventricular or Left Ventricle
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis
• Other Study ID Numbers: 2020-02187

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No