Progress in diagnosing and managing cardiac amyloidosis

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Progress in diagnosing and managing cardiac amyloidosis
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Mazen Hanna, MD
Chetan Huded, MD
E. Rene Rodriguez, MD
Dermot Phelan, MD
Deborah Kwon, MD
Wael Jaber, MD
Jason Valent, MD
Michael Zhen-Yu Tong, MD, MBA

From the Cleveland Clinic Journal of Medicine

This article has been removed from the website. The article was prepared by the editorial staff based on a transcript of the proceedings of a conference, and errors occurred during this process that were subsequently published. A clarification of the errors will be published in a future issue.

A review of this topic was published in the December 2017 issue of the Journal (Donnelly JP, Hanna M. Cardiac amyloidosis: An update on diagnosis and treatment. Cleve Clin J Med 2017;84[12suppl 3]:12–26). doi:10.3949/ccjm.84.s3.02

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Mazen Hanna, MD
Co-Director, Amyloidosis Center, Section of Heart Failure and Cardiac Transplant Medicine, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic

Chetan Huded, MD
Resident Fellow, Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic

E. Rene Rodriguez, MD
Director, Cardiovascular Pathology, Director, Autopsy Pathology, Department of Anatomic Pathology, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Dermot Phelan, MD
Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic

Deborah Kwon, MD
Director of Cardiac MRI Research, Department of Cardiovascular Medicine and Department of Diagnostic Radiology, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Wael Jaber, MD
Department of Cardiovascular Medicine, Heart and Vascular Institute, and Department of Nuclear Medicine, Cleveland Clinic

Jason Valent, MD
Department of Hematology and Medical Oncology Cleveland Clinic

Michael Zhen-Yu Tong, MD, MBA
Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic

Address: Mazen Hanna, MD, Department of Cardiovascular Medicine, Heart and Vascular Institute, J3-4, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; [email protected]

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Mazen Hanna, MD
Chetan Huded, MD
E. Rene Rodriguez, MD
Dermot Phelan, MD
Deborah Kwon, MD
Wael Jaber, MD
Jason Valent, MD
Michael Zhen-Yu Tong, MD, MBA
Author(s)
Mazen Hanna, MD
Chetan Huded, MD
E. Rene Rodriguez, MD
Dermot Phelan, MD
Deborah Kwon, MD
Wael Jaber, MD
Jason Valent, MD
Michael Zhen-Yu Tong, MD, MBA
Author and Disclosure Information

Mazen Hanna, MD
Co-Director, Amyloidosis Center, Section of Heart Failure and Cardiac Transplant Medicine, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic

Chetan Huded, MD
Resident Fellow, Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic

E. Rene Rodriguez, MD
Director, Cardiovascular Pathology, Director, Autopsy Pathology, Department of Anatomic Pathology, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Dermot Phelan, MD
Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic

Deborah Kwon, MD
Director of Cardiac MRI Research, Department of Cardiovascular Medicine and Department of Diagnostic Radiology, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Wael Jaber, MD
Department of Cardiovascular Medicine, Heart and Vascular Institute, and Department of Nuclear Medicine, Cleveland Clinic

Jason Valent, MD
Department of Hematology and Medical Oncology Cleveland Clinic

Michael Zhen-Yu Tong, MD, MBA
Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic

Address: Mazen Hanna, MD, Department of Cardiovascular Medicine, Heart and Vascular Institute, J3-4, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; [email protected]

Author and Disclosure Information

Mazen Hanna, MD
Co-Director, Amyloidosis Center, Section of Heart Failure and Cardiac Transplant Medicine, Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic

Chetan Huded, MD
Resident Fellow, Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic

E. Rene Rodriguez, MD
Director, Cardiovascular Pathology, Director, Autopsy Pathology, Department of Anatomic Pathology, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Dermot Phelan, MD
Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic

Deborah Kwon, MD
Director of Cardiac MRI Research, Department of Cardiovascular Medicine and Department of Diagnostic Radiology, Cleveland Clinic; Assistant Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Wael Jaber, MD
Department of Cardiovascular Medicine, Heart and Vascular Institute, and Department of Nuclear Medicine, Cleveland Clinic

Jason Valent, MD
Department of Hematology and Medical Oncology Cleveland Clinic

Michael Zhen-Yu Tong, MD, MBA
Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic

Address: Mazen Hanna, MD, Department of Cardiovascular Medicine, Heart and Vascular Institute, J3-4, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195; [email protected]

From the Cleveland Clinic Journal of Medicine

This article has been removed from the website. The article was prepared by the editorial staff based on a transcript of the proceedings of a conference, and errors occurred during this process that were subsequently published. A clarification of the errors will be published in a future issue.

A review of this topic was published in the December 2017 issue of the Journal (Donnelly JP, Hanna M. Cardiac amyloidosis: An update on diagnosis and treatment. Cleve Clin J Med 2017;84[12suppl 3]:12–26). doi:10.3949/ccjm.84.s3.02

From the Cleveland Clinic Journal of Medicine

This article has been removed from the website. The article was prepared by the editorial staff based on a transcript of the proceedings of a conference, and errors occurred during this process that were subsequently published. A clarification of the errors will be published in a future issue.

A review of this topic was published in the December 2017 issue of the Journal (Donnelly JP, Hanna M. Cardiac amyloidosis: An update on diagnosis and treatment. Cleve Clin J Med 2017;84[12suppl 3]:12–26). doi:10.3949/ccjm.84.s3.02

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Progress in diagnosing and managing cardiac amyloidosis
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Left ventricular thrombosis can still complicate acute myocardial infarction

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Author(s)
Muhammad Umer Tariq, MD
Ali M. Tariq, MD
Carmela D. Tan, MD
E. Rene Rodriguez, MD
Venu Menon, MD

A 62-year-old man with hypertension, type 2 diabetes mellitus, and hypercholesterolemia presented to the emergency department with substernal chest pain that started about 15 hours earlier while he was at rest watching television.

On examination, his pulse was 92 beats per minute and regular, his blood pressure was 160/88 mm Hg, and he had no evidence of jugular venous distention or pedal edema. Lung examination was positive for bibasilar crackles.

Electrocardiography revealed Q waves with ST elevation in leads I, aVL, V4, V5, and V6 with reciprocal ST depression in leads II, III, and aVF.

His troponin T level on presentation was markedly elevated.

Figure 1. Transthoracic echocardiography, apical four-chamber view, shows thrombus in the left ventricular apical cavity. The blue arrow points to the well-demarcated thrombus adhering to the endocardium.

He underwent heart catheterization and was found to have 100% occlusion of the proximal left anterior descending artery. He underwent successful percutaneous coronary intervention with placement of a drug-eluting stent, and afterward had grade 3 flow on the Thrombolysis in Myocardial Infarction (TIMI) scale.

Echocardiography the next day revealed a mobile echo-dense mass in the left ventricular apex (Figure 1) and a left ventricular ejection fraction of 35%.

THE INCIDENCE OF LEFT VENTRICULAR THROMBOSIS IN ACUTE MI

1. What is the incidence of left ventricular thrombosis after acute myocardial infarction (MI), now that primary percutaneous coronary intervention is common?

  • 0.1%
  • 2%
  • 20%
  • 40%

Left ventricular thrombosis is a serious complication of acute MI that can cause systemic thromboembolism, including stroke.1 Before thrombolytic therapy was available, this complication occurred in 20% to 60% of patients with acute MI.2,3 But early reperfusion strategies, anticoagulation for the first 48 hours, and dual antiplatelet therapy have reduced the incidence of this complication significantly.

In the thrombolytic era, the incidence of left ventricular thrombosis was 5.1% in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI) 3 study, which had 8,326 patients. A subset of patients who had an anterior MI had almost double the incidence (11.5%).3

The incidence has further declined with the advent of primary percutaneous coronary intervention, likely thanks to enhanced myocardial salvage, and now ranges from 2.5% to 15% (Table 1).4–11 The largest observational study, with 2,911 patients undergoing percutaneous coronary intervention, reported an incidence of 2.5% within 3 to 5 days of the MI.7 At our center, the incidence was found to be even lower, 1.8% in 1,700 patients presenting with ST-elevation MI undergoing primary percutaneous coronary intervention. Hence, of the answers to the question above, 2% would be closest.

Large infarct size with a low left ventricular ejection fraction (< 40%), anterior wall MI, hypertension, and delay in time from symptom onset to intervention were independent predictors of left ventricular thrombus formation in most studies.7,12 The risk is highest during the first 2 weeks after MI, and thrombosis almost never occurs more than 3 months after the index event.5,13–16

WHAT IS THE PATHOGENESIS OF LEFT VENTRICULAR THROMBOSIS?

A large transmural infarct results in loss of contractile function, which causes stagnation and pooling of blood adjacent to the infarcted ventricular segment. In addition, endocardial injury exposes tissue factor, which then initiates the coagulation cascade. To make matters worse, MI results in a hypercoagulable state through unclear mechanisms, which completes the Virchow triad for thrombus formation. Elevations of D-dimer, fibrinogen, anticardiolipin antibodies (IgM and IgG), and tissue factor have also been reported after acute MI.17

Figure 2. (A) A cross section of the apical segment of the left ventricle shows a mildly dilated cavity filled with mural thrombus. (B) Photo-micrograph of an acute thrombus shows alternating layers of fibrin and platelet with red and white blood cells (hematoxylin and eosin, original magnification × 200). (C) Organization of a thrombus is characterized by infiltration of fibroblasts and newly formed capillaries (hematoxylin and eosin, original magnification × 200).

Thrombus formation begins with platelet aggregation at the site of endocardial damage, forming a platelet plug, followed by activation of clotting factors. These thrombi are referred to as “mural,” as they adhere to the chamber wall (endocardium). They are composed of fibrin and entrapped red and white blood cells (Figure 2).

The natural course of thrombus evolution is established but variable. A left ventricular thrombus may dislodge and embolize, resulting in stroke or other thromboembolic complications. Alternately, it can dissolve over time, aided by intrinsic fibrinolytic mechanisms. On other occasions, the thrombus may organize, a process characterized by ingrowth of smooth muscle cells, fibroblasts, and endothelium.

 

 

HOW IS LEFT VENTRICULAR THROMBOSIS DIAGNOSED?

2. What is the best imaging test for detecting a thrombus?

  • Transesophageal echocardiography
  • Transthoracic echocardiography
  • Cardiac magnetic resonance imaging (MRI) without gadolinium contrast
  • Cardiac MRI with gadolinium contrast

Evaluation of left ventricular function after acute MI carries a class I indication (ie, it should be performed).18 

Echocardiography is commonly used, and it has a 60% sensitivity to detect a thrombus.19 In patients with poorer transthoracic echocardiographic windows, contrast can be used to better delineate the left ventricular cavity and show the thrombus. Transesophageal echocardiography is seldom useful, as the left ventricular apex is foreshortened and in the far field.

A left ventricular thrombus is confirmed if an echo-dense mass with well-demarcated margins distinct from the endocardium is seen throughout the cardiac cycle. It should be evident in at least two different views (apical and short-axis) and should be adjacent to a hypokinetic or akinetic left ventricular wall. False-positive findings can occur due to misidentified false tendons, papillary muscles, and trabeculae.

Figure 3. Cardiac magnetic resonance imaging with a delayed-enhancement phase-sensitive inversion recovery image, vertical long-axis view. The red arrow points to dense subendocardial delayed enhancement in the apex extending into the mid-inferior wall, consistent with scar in the distal left anterior descending artery territory. The orange arrow shows a nonenhancing mass in the apex, consistent with thrombus.

Cardiac MRI with late gadolinium enhancement is now the gold standard for diagnostic imaging, as it accurately characterizes the shape, size, and location of the thrombus (Figure 3). Gadolinium contrast increases the enhancement of the ventricular cavity, thus allowing easy detection of thrombus, which appears dark. Cardiac MRI with delayed enhancement has 88% to 91% sensitivity and 99% specificity to detect left ventricular thrombosis.20,21 However, compared with echocardiography, routine cardiac MRI is time-intensive, costly, and not routinely available. As a result, it should be performed only in patients with poor acoustic windows and a high clinical suspicion of left ventricular thrombosis.

Delayed-contrast cardiac computed tomography can be used to identify left ventricular thrombosis, using absence of contrast uptake. The need to use contrast is a disadvantage, but computed tomography can be an alternative in patients with contraindications to cardiac MRI.

WHAT COMPLICATIONS ARISE FROM LEFT VENTRICULAR THROMBOSIS?

The most feared complication of left ventricular thrombosis is thromboembolism. Cardioembolic stroke is generally severe, prone to early and long-term recurrence, and associated with a higher death rate than noncardioembolic ischemic stroke.22,23 Thrombi associated with thromboembolism are often acute and mobile rather than organized and immobile.24 They may embolize to the brain,  spleen, kidneys, and bowel.25 In a meta-analysis of 11 studies, the pooled odds ratio for risk of embolization was 5.45 (95% confidence interval [CI] 3.02–9.83) with left ventricular thrombi vs without.26 Before systemic thrombolysis and antiplatelet therapy became available, stroke rates ranged from 1.5% to 10%.27–29

In a meta-analysis of 22 studies from 1978 to 2004, the incidence of ischemic stroke after MI during hospitalization was around 11.1 per 1,000 MIs.30 This study found that anterior MI was associated with a higher risk of stroke, but reported no difference in the incidence of stroke with percutaneous coronary intervention, systemic thrombolysis, or no reperfusion.

In a large prospective cohort study of 2,160 patients,31 259 (12%) had a stroke after MI. In multivariable analysis, age, diabetes, and previous stroke were predictors of stroke after MI. This study reported significantly fewer strokes in patients who underwent percutaneous coronary intervention than with other or no reperfusion therapies.31

ANTICOAGULATION TREATMENT

3. How would you treat a patient who has a drug-eluting stent in the left anterior descending artery and a new diagnosis of left ventricular thrombosis?

  • Warfarin
  • Aspirin and clopidogrel
  • Aspirin, clopidogrel, and warfarin
  • Aspirin and warfarin

The management of left ventricular thrombosis has been summarized in guidelines from the American College of Chest Physicians (ACCP) in 2012,32 and from the American College of Cardiology/American Heart Association in 2013,18 which recommend anticoagulation for at least 3 months, or indefinitely if bleeding risk is low, for all patients developing a left ventricular thrombus.

For patients with acute MI and left ventricular thrombosis, the ACCP guidelines recommend warfarin with a target international normalized ratio of 2.0 to 3.0 plus dual antiplatelet therapy (eg, aspirin plus clopidogrel)  for 3 months, after which warfarin is discontinued but dual antiplatelet therapy is continued for up to 12 months.32

The European Society of Cardiology guidelines33 recommend 6 months of anticoagulation. However, if the patient is receiving dual antiplatelet therapy, they recommend repeated imaging of the left ventricle after 3 months of anticoagulation, which may allow for earlier discontinuation of anticoagulation if the thrombus has resolved and apical wall motion has recovered. Therefore, most experts recommend 3 months of anticoagulation when used in combination with dual antiplatelet therapy and repeating echocardiography at 3 months to safely discontinue anticoagulation. The best answer to the question posed here is aspirin, clopidogrel, and warfarin.

Decisions about antithrombotic therapy may also depend on stent type and the patient’s bleeding risk. With bare-metal stents, dual antiplatelet therapy along with anticoagulation should be used for 1 month, after which anticoagulation should be used with a single antiplatelet agent for another 2 months; after this, the anticoagulant can be discontinued and dual antiplatelet therapy can be resumed for a total of 12 months. Newer anticoagulants such as rivaroxaban, dabigatran, edoxaban, and apixaban may also have a role, but they have not yet been studied for this indication.

Surgical thrombectomy is rarely considered now, given the known efficacy of anticoagulants in dissolving the thrombus. It was done in the past for large, mobile, or protruding left ventricular thrombi, which have a higher potential for embolization.34 Currently, it can be done under very special circumstances, such as before placement of a left ventricular assist device or if the thrombus is large, to prevent embolism.35,36

BLEEDING COMPLICATIONS WITH TRIPLE ANTITHROMBOTIC THERAPY

After stent placement, almost all patients need to be on dual antiplatelet therapy for a specified duration depending on the type and generation of stent used. Such patients end up on “triple” antithrombotic therapy (two antiplatelet drugs plus an anticoagulant), which poses a high risk of bleeding.37 Consideration needs to be given to the risks of stroke, stent thrombosis, and major bleeding when selecting the antithrombotic regimen.38 Triple antithrombotic therapy has been associated with a risk of fatal and nonfatal bleeding of 4% to 16% when used for indications such as atrial fibrillation.39–41

Risks of triple antithrombotic therapy (aspirin 80–100 mg, clopidogrel 75 mg, and warfarin) were compared with those of clopidogrel plus warfarin in the What Is the Optimal Antiplatelet and Anticoagulant therapy in Patients With Oral Anticoagulation and Coronary Stenting Trial,37 which reported a significantly lower risk of  major and minor bleeding with clopidogrel-plus-warfarin therapy than with triple antithrombotic therapy, 14.3% vs 31.7% (hazard ratio 0.40, 95% CI 0.28–0.58, P < .0001).

Additionally, the increased risk of major and minor bleeding associated with triple antithrombotic therapy has been confirmed in many observational studies; other studies found a trend toward lower risk with triple therapy, but this was not statistically significant (Table 2).38,40,42–55 A large multicenter European trial is being conducted to compare dual antiplatelet therapy vs triple antithrombotic therapy in patients with left ventricular thrombosis.

CASE FOLLOW-UP

Our patient was started on warfarin, clopidogrel 75 mg, and aspirin 75 mg at the time of discharge. He was continued on warfarin for 3 months, at which time a follow-up echocardiogram showed no thrombus in the left ventricle. Warfarin was discontinued, and he had no thromboembolic complications.

TAKE-HOME POINTS

Left ventricular thrombosis after an acute MI is very important to detect, as it can lead to serious complications through arterial embolism.

The incidence of left ventricular thrombosis has declined significantly with the use of percutaneous coronary intervention. However, it may still occur in a small number of patients with larger infarcts owing to delay in revascularization or proximal (left main or left anterior descending) occlusions with larger infarct size.

Echocardiography, which is routinely performed after acute MI to assess myocardial function, uncovers most left ventricular thrombi. In high-risk cases, MRI with late gadolinium enhancement can increase the diagnostic yield.

Anticoagulation with warfarin is recommended for at least 3 months. Post-MI patients undergoing stent implantation may need triple antithrombotic therapy, which, however, increases the bleeding risk significantly. Large randomized trials are needed to guide physicians in risk stratification of such patients.

References
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  45. Gao F, Zhou YJ, Wang ZJ, et al. Meta-analysis of the combination of warfarin and dual antiplatelet therapy after coronary stenting in patients with indications for chronic oral anticoagulation. Int J Cardiol 2011; 148:96–101.
  46. Hansen ML, Sorensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010; 170:1433–1441.
  47. Hermosillo AJ, Spinler SA. Aspirin, clopidogrel, and warfarin: is the combination appropriate and effective or inappropriate and too dangerous? Ann Pharmacother 2008; 42:790–805.
  48. Holmes DR Jr, Kereiakes DJ, Kleiman NS, Moliterno DJ, Patti G, Grines CL. Combining antiplatelet and anticoagulant therapies. J Am Coll Cardiol 2009; 54:95–109.
  49. Khurram Z, Chou E, Minutello R, et al. Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding. J Invasive Cardiol 2006; 18:162–164.
  50. Orford JL, Fasseas P, Melby S, et al. Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation. Am Heart J 2004; 147:463–467.
  51. Porter A, Konstantino Y, Iakobishvili Z, Shachar L, Battler A, Hasdai D. Short-term triple therapy with aspirin, warfarin, and a thienopyridine among patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv 2006; 68:56–61.
  52. DeEugenio D, Kolman L, DeCaro M, et al. Risk of major bleeding with concomitant dual antiplatelet therapy after percutaneous coronary intervention in patients receiving long-term warfarin therapy. Pharmacotherapy 2007; 27:691–696.
  53. Ruiz-Nodar JM, Marin F, Hurtado JA, et al. Anticoagulant and antiplatelet therapy use in 426 patients with atrial fibrillation undergoing percutaneous coronary intervention and stent implantation implications for bleeding risk and prognosis. J Am Coll Cardiol 2008; 51:818–825.
  54. Sarafoff N, Ndrepepa G, Mehilli J, et al. Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation. J Intern Med 2008; 264:472–480.
  55. Rossini R, Musumeci GF, Lettieri CF, et al. Long-term outcomes in patients undergoing coronary stenting on dual oral antiplatelet treatment requiring oral anticoagulant therapy. Am J Cardiol 2008; 102:1618–1623.
Article PDF
tariq_leftventricularthrombosis.pdf
Author and Disclosure Information

Muhammad Umer Tariq, MD
Heart and Vascular Institute, MedStar Georgetown/Washington Hospital Center, Washington, DC

Ali M. Tariq, MD
Sheikh Zayed Medical College, Lahore, Pakistan

Carmela D. Tan, MD
Departments of Pathology and Transplantation Center, Cleveland Clinic; Associate Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

E. Rene Rodriguez, MD
Departments of Pathology, Thoracic and Cardiovascular Surgery, Molecular Cardiology, and Transplantation Center, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Venu Menon, MD
Medical Director, Cardiac Intensive Care Unit; Departments of Cardiovascular Medicine and Diagnostic Radiology and Critical Care Center, Heart and Vascular Institute, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Address: Muhammad Umer Tariq, MD, Cardiology Fellow, Washington Hospital Center/Georgetown University, 110 Irving Street NW, Washington, DC 20010; [email protected]

Issue
Cleveland Clinic Journal of Medicine - 83(11)
Publications
Cleveland Clinic Journal of Medicine
Topics
Cardiology
Drug Therapy
Imaging
Vascular
Page Number
819-826
Sections
IM Board Review
Symptoms to Diagnosis
Author(s)
Muhammad Umer Tariq, MD
Ali M. Tariq, MD
Carmela D. Tan, MD
E. Rene Rodriguez, MD
Venu Menon, MD
Author(s)
Muhammad Umer Tariq, MD
Ali M. Tariq, MD
Carmela D. Tan, MD
E. Rene Rodriguez, MD
Venu Menon, MD
Author and Disclosure Information

Muhammad Umer Tariq, MD
Heart and Vascular Institute, MedStar Georgetown/Washington Hospital Center, Washington, DC

Ali M. Tariq, MD
Sheikh Zayed Medical College, Lahore, Pakistan

Carmela D. Tan, MD
Departments of Pathology and Transplantation Center, Cleveland Clinic; Associate Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

E. Rene Rodriguez, MD
Departments of Pathology, Thoracic and Cardiovascular Surgery, Molecular Cardiology, and Transplantation Center, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Venu Menon, MD
Medical Director, Cardiac Intensive Care Unit; Departments of Cardiovascular Medicine and Diagnostic Radiology and Critical Care Center, Heart and Vascular Institute, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Address: Muhammad Umer Tariq, MD, Cardiology Fellow, Washington Hospital Center/Georgetown University, 110 Irving Street NW, Washington, DC 20010; [email protected]

Author and Disclosure Information

Muhammad Umer Tariq, MD
Heart and Vascular Institute, MedStar Georgetown/Washington Hospital Center, Washington, DC

Ali M. Tariq, MD
Sheikh Zayed Medical College, Lahore, Pakistan

Carmela D. Tan, MD
Departments of Pathology and Transplantation Center, Cleveland Clinic; Associate Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

E. Rene Rodriguez, MD
Departments of Pathology, Thoracic and Cardiovascular Surgery, Molecular Cardiology, and Transplantation Center, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Venu Menon, MD
Medical Director, Cardiac Intensive Care Unit; Departments of Cardiovascular Medicine and Diagnostic Radiology and Critical Care Center, Heart and Vascular Institute, Cleveland Clinic; Professor, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH

Address: Muhammad Umer Tariq, MD, Cardiology Fellow, Washington Hospital Center/Georgetown University, 110 Irving Street NW, Washington, DC 20010; [email protected]

Article PDF
tariq_leftventricularthrombosis.pdf
Article PDF
tariq_leftventricularthrombosis.pdf

A 62-year-old man with hypertension, type 2 diabetes mellitus, and hypercholesterolemia presented to the emergency department with substernal chest pain that started about 15 hours earlier while he was at rest watching television.

On examination, his pulse was 92 beats per minute and regular, his blood pressure was 160/88 mm Hg, and he had no evidence of jugular venous distention or pedal edema. Lung examination was positive for bibasilar crackles.

Electrocardiography revealed Q waves with ST elevation in leads I, aVL, V4, V5, and V6 with reciprocal ST depression in leads II, III, and aVF.

His troponin T level on presentation was markedly elevated.

Figure 1. Transthoracic echocardiography, apical four-chamber view, shows thrombus in the left ventricular apical cavity. The blue arrow points to the well-demarcated thrombus adhering to the endocardium.

He underwent heart catheterization and was found to have 100% occlusion of the proximal left anterior descending artery. He underwent successful percutaneous coronary intervention with placement of a drug-eluting stent, and afterward had grade 3 flow on the Thrombolysis in Myocardial Infarction (TIMI) scale.

Echocardiography the next day revealed a mobile echo-dense mass in the left ventricular apex (Figure 1) and a left ventricular ejection fraction of 35%.

THE INCIDENCE OF LEFT VENTRICULAR THROMBOSIS IN ACUTE MI

1. What is the incidence of left ventricular thrombosis after acute myocardial infarction (MI), now that primary percutaneous coronary intervention is common?

  • 0.1%
  • 2%
  • 20%
  • 40%

Left ventricular thrombosis is a serious complication of acute MI that can cause systemic thromboembolism, including stroke.1 Before thrombolytic therapy was available, this complication occurred in 20% to 60% of patients with acute MI.2,3 But early reperfusion strategies, anticoagulation for the first 48 hours, and dual antiplatelet therapy have reduced the incidence of this complication significantly.

In the thrombolytic era, the incidence of left ventricular thrombosis was 5.1% in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI) 3 study, which had 8,326 patients. A subset of patients who had an anterior MI had almost double the incidence (11.5%).3

The incidence has further declined with the advent of primary percutaneous coronary intervention, likely thanks to enhanced myocardial salvage, and now ranges from 2.5% to 15% (Table 1).4–11 The largest observational study, with 2,911 patients undergoing percutaneous coronary intervention, reported an incidence of 2.5% within 3 to 5 days of the MI.7 At our center, the incidence was found to be even lower, 1.8% in 1,700 patients presenting with ST-elevation MI undergoing primary percutaneous coronary intervention. Hence, of the answers to the question above, 2% would be closest.

Large infarct size with a low left ventricular ejection fraction (< 40%), anterior wall MI, hypertension, and delay in time from symptom onset to intervention were independent predictors of left ventricular thrombus formation in most studies.7,12 The risk is highest during the first 2 weeks after MI, and thrombosis almost never occurs more than 3 months after the index event.5,13–16

WHAT IS THE PATHOGENESIS OF LEFT VENTRICULAR THROMBOSIS?

A large transmural infarct results in loss of contractile function, which causes stagnation and pooling of blood adjacent to the infarcted ventricular segment. In addition, endocardial injury exposes tissue factor, which then initiates the coagulation cascade. To make matters worse, MI results in a hypercoagulable state through unclear mechanisms, which completes the Virchow triad for thrombus formation. Elevations of D-dimer, fibrinogen, anticardiolipin antibodies (IgM and IgG), and tissue factor have also been reported after acute MI.17

Figure 2. (A) A cross section of the apical segment of the left ventricle shows a mildly dilated cavity filled with mural thrombus. (B) Photo-micrograph of an acute thrombus shows alternating layers of fibrin and platelet with red and white blood cells (hematoxylin and eosin, original magnification × 200). (C) Organization of a thrombus is characterized by infiltration of fibroblasts and newly formed capillaries (hematoxylin and eosin, original magnification × 200).

Thrombus formation begins with platelet aggregation at the site of endocardial damage, forming a platelet plug, followed by activation of clotting factors. These thrombi are referred to as “mural,” as they adhere to the chamber wall (endocardium). They are composed of fibrin and entrapped red and white blood cells (Figure 2).

The natural course of thrombus evolution is established but variable. A left ventricular thrombus may dislodge and embolize, resulting in stroke or other thromboembolic complications. Alternately, it can dissolve over time, aided by intrinsic fibrinolytic mechanisms. On other occasions, the thrombus may organize, a process characterized by ingrowth of smooth muscle cells, fibroblasts, and endothelium.

 

 

HOW IS LEFT VENTRICULAR THROMBOSIS DIAGNOSED?

2. What is the best imaging test for detecting a thrombus?

  • Transesophageal echocardiography
  • Transthoracic echocardiography
  • Cardiac magnetic resonance imaging (MRI) without gadolinium contrast
  • Cardiac MRI with gadolinium contrast

Evaluation of left ventricular function after acute MI carries a class I indication (ie, it should be performed).18 

Echocardiography is commonly used, and it has a 60% sensitivity to detect a thrombus.19 In patients with poorer transthoracic echocardiographic windows, contrast can be used to better delineate the left ventricular cavity and show the thrombus. Transesophageal echocardiography is seldom useful, as the left ventricular apex is foreshortened and in the far field.

A left ventricular thrombus is confirmed if an echo-dense mass with well-demarcated margins distinct from the endocardium is seen throughout the cardiac cycle. It should be evident in at least two different views (apical and short-axis) and should be adjacent to a hypokinetic or akinetic left ventricular wall. False-positive findings can occur due to misidentified false tendons, papillary muscles, and trabeculae.

Figure 3. Cardiac magnetic resonance imaging with a delayed-enhancement phase-sensitive inversion recovery image, vertical long-axis view. The red arrow points to dense subendocardial delayed enhancement in the apex extending into the mid-inferior wall, consistent with scar in the distal left anterior descending artery territory. The orange arrow shows a nonenhancing mass in the apex, consistent with thrombus.

Cardiac MRI with late gadolinium enhancement is now the gold standard for diagnostic imaging, as it accurately characterizes the shape, size, and location of the thrombus (Figure 3). Gadolinium contrast increases the enhancement of the ventricular cavity, thus allowing easy detection of thrombus, which appears dark. Cardiac MRI with delayed enhancement has 88% to 91% sensitivity and 99% specificity to detect left ventricular thrombosis.20,21 However, compared with echocardiography, routine cardiac MRI is time-intensive, costly, and not routinely available. As a result, it should be performed only in patients with poor acoustic windows and a high clinical suspicion of left ventricular thrombosis.

Delayed-contrast cardiac computed tomography can be used to identify left ventricular thrombosis, using absence of contrast uptake. The need to use contrast is a disadvantage, but computed tomography can be an alternative in patients with contraindications to cardiac MRI.

WHAT COMPLICATIONS ARISE FROM LEFT VENTRICULAR THROMBOSIS?

The most feared complication of left ventricular thrombosis is thromboembolism. Cardioembolic stroke is generally severe, prone to early and long-term recurrence, and associated with a higher death rate than noncardioembolic ischemic stroke.22,23 Thrombi associated with thromboembolism are often acute and mobile rather than organized and immobile.24 They may embolize to the brain,  spleen, kidneys, and bowel.25 In a meta-analysis of 11 studies, the pooled odds ratio for risk of embolization was 5.45 (95% confidence interval [CI] 3.02–9.83) with left ventricular thrombi vs without.26 Before systemic thrombolysis and antiplatelet therapy became available, stroke rates ranged from 1.5% to 10%.27–29

In a meta-analysis of 22 studies from 1978 to 2004, the incidence of ischemic stroke after MI during hospitalization was around 11.1 per 1,000 MIs.30 This study found that anterior MI was associated with a higher risk of stroke, but reported no difference in the incidence of stroke with percutaneous coronary intervention, systemic thrombolysis, or no reperfusion.

In a large prospective cohort study of 2,160 patients,31 259 (12%) had a stroke after MI. In multivariable analysis, age, diabetes, and previous stroke were predictors of stroke after MI. This study reported significantly fewer strokes in patients who underwent percutaneous coronary intervention than with other or no reperfusion therapies.31

ANTICOAGULATION TREATMENT

3. How would you treat a patient who has a drug-eluting stent in the left anterior descending artery and a new diagnosis of left ventricular thrombosis?

  • Warfarin
  • Aspirin and clopidogrel
  • Aspirin, clopidogrel, and warfarin
  • Aspirin and warfarin

The management of left ventricular thrombosis has been summarized in guidelines from the American College of Chest Physicians (ACCP) in 2012,32 and from the American College of Cardiology/American Heart Association in 2013,18 which recommend anticoagulation for at least 3 months, or indefinitely if bleeding risk is low, for all patients developing a left ventricular thrombus.

For patients with acute MI and left ventricular thrombosis, the ACCP guidelines recommend warfarin with a target international normalized ratio of 2.0 to 3.0 plus dual antiplatelet therapy (eg, aspirin plus clopidogrel)  for 3 months, after which warfarin is discontinued but dual antiplatelet therapy is continued for up to 12 months.32

The European Society of Cardiology guidelines33 recommend 6 months of anticoagulation. However, if the patient is receiving dual antiplatelet therapy, they recommend repeated imaging of the left ventricle after 3 months of anticoagulation, which may allow for earlier discontinuation of anticoagulation if the thrombus has resolved and apical wall motion has recovered. Therefore, most experts recommend 3 months of anticoagulation when used in combination with dual antiplatelet therapy and repeating echocardiography at 3 months to safely discontinue anticoagulation. The best answer to the question posed here is aspirin, clopidogrel, and warfarin.

Decisions about antithrombotic therapy may also depend on stent type and the patient’s bleeding risk. With bare-metal stents, dual antiplatelet therapy along with anticoagulation should be used for 1 month, after which anticoagulation should be used with a single antiplatelet agent for another 2 months; after this, the anticoagulant can be discontinued and dual antiplatelet therapy can be resumed for a total of 12 months. Newer anticoagulants such as rivaroxaban, dabigatran, edoxaban, and apixaban may also have a role, but they have not yet been studied for this indication.

Surgical thrombectomy is rarely considered now, given the known efficacy of anticoagulants in dissolving the thrombus. It was done in the past for large, mobile, or protruding left ventricular thrombi, which have a higher potential for embolization.34 Currently, it can be done under very special circumstances, such as before placement of a left ventricular assist device or if the thrombus is large, to prevent embolism.35,36

BLEEDING COMPLICATIONS WITH TRIPLE ANTITHROMBOTIC THERAPY

After stent placement, almost all patients need to be on dual antiplatelet therapy for a specified duration depending on the type and generation of stent used. Such patients end up on “triple” antithrombotic therapy (two antiplatelet drugs plus an anticoagulant), which poses a high risk of bleeding.37 Consideration needs to be given to the risks of stroke, stent thrombosis, and major bleeding when selecting the antithrombotic regimen.38 Triple antithrombotic therapy has been associated with a risk of fatal and nonfatal bleeding of 4% to 16% when used for indications such as atrial fibrillation.39–41

Risks of triple antithrombotic therapy (aspirin 80–100 mg, clopidogrel 75 mg, and warfarin) were compared with those of clopidogrel plus warfarin in the What Is the Optimal Antiplatelet and Anticoagulant therapy in Patients With Oral Anticoagulation and Coronary Stenting Trial,37 which reported a significantly lower risk of  major and minor bleeding with clopidogrel-plus-warfarin therapy than with triple antithrombotic therapy, 14.3% vs 31.7% (hazard ratio 0.40, 95% CI 0.28–0.58, P < .0001).

Additionally, the increased risk of major and minor bleeding associated with triple antithrombotic therapy has been confirmed in many observational studies; other studies found a trend toward lower risk with triple therapy, but this was not statistically significant (Table 2).38,40,42–55 A large multicenter European trial is being conducted to compare dual antiplatelet therapy vs triple antithrombotic therapy in patients with left ventricular thrombosis.

CASE FOLLOW-UP

Our patient was started on warfarin, clopidogrel 75 mg, and aspirin 75 mg at the time of discharge. He was continued on warfarin for 3 months, at which time a follow-up echocardiogram showed no thrombus in the left ventricle. Warfarin was discontinued, and he had no thromboembolic complications.

TAKE-HOME POINTS

Left ventricular thrombosis after an acute MI is very important to detect, as it can lead to serious complications through arterial embolism.

The incidence of left ventricular thrombosis has declined significantly with the use of percutaneous coronary intervention. However, it may still occur in a small number of patients with larger infarcts owing to delay in revascularization or proximal (left main or left anterior descending) occlusions with larger infarct size.

Echocardiography, which is routinely performed after acute MI to assess myocardial function, uncovers most left ventricular thrombi. In high-risk cases, MRI with late gadolinium enhancement can increase the diagnostic yield.

Anticoagulation with warfarin is recommended for at least 3 months. Post-MI patients undergoing stent implantation may need triple antithrombotic therapy, which, however, increases the bleeding risk significantly. Large randomized trials are needed to guide physicians in risk stratification of such patients.

A 62-year-old man with hypertension, type 2 diabetes mellitus, and hypercholesterolemia presented to the emergency department with substernal chest pain that started about 15 hours earlier while he was at rest watching television.

On examination, his pulse was 92 beats per minute and regular, his blood pressure was 160/88 mm Hg, and he had no evidence of jugular venous distention or pedal edema. Lung examination was positive for bibasilar crackles.

Electrocardiography revealed Q waves with ST elevation in leads I, aVL, V4, V5, and V6 with reciprocal ST depression in leads II, III, and aVF.

His troponin T level on presentation was markedly elevated.

Figure 1. Transthoracic echocardiography, apical four-chamber view, shows thrombus in the left ventricular apical cavity. The blue arrow points to the well-demarcated thrombus adhering to the endocardium.

He underwent heart catheterization and was found to have 100% occlusion of the proximal left anterior descending artery. He underwent successful percutaneous coronary intervention with placement of a drug-eluting stent, and afterward had grade 3 flow on the Thrombolysis in Myocardial Infarction (TIMI) scale.

Echocardiography the next day revealed a mobile echo-dense mass in the left ventricular apex (Figure 1) and a left ventricular ejection fraction of 35%.

THE INCIDENCE OF LEFT VENTRICULAR THROMBOSIS IN ACUTE MI

1. What is the incidence of left ventricular thrombosis after acute myocardial infarction (MI), now that primary percutaneous coronary intervention is common?

  • 0.1%
  • 2%
  • 20%
  • 40%

Left ventricular thrombosis is a serious complication of acute MI that can cause systemic thromboembolism, including stroke.1 Before thrombolytic therapy was available, this complication occurred in 20% to 60% of patients with acute MI.2,3 But early reperfusion strategies, anticoagulation for the first 48 hours, and dual antiplatelet therapy have reduced the incidence of this complication significantly.

In the thrombolytic era, the incidence of left ventricular thrombosis was 5.1% in the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI) 3 study, which had 8,326 patients. A subset of patients who had an anterior MI had almost double the incidence (11.5%).3

The incidence has further declined with the advent of primary percutaneous coronary intervention, likely thanks to enhanced myocardial salvage, and now ranges from 2.5% to 15% (Table 1).4–11 The largest observational study, with 2,911 patients undergoing percutaneous coronary intervention, reported an incidence of 2.5% within 3 to 5 days of the MI.7 At our center, the incidence was found to be even lower, 1.8% in 1,700 patients presenting with ST-elevation MI undergoing primary percutaneous coronary intervention. Hence, of the answers to the question above, 2% would be closest.

Large infarct size with a low left ventricular ejection fraction (< 40%), anterior wall MI, hypertension, and delay in time from symptom onset to intervention were independent predictors of left ventricular thrombus formation in most studies.7,12 The risk is highest during the first 2 weeks after MI, and thrombosis almost never occurs more than 3 months after the index event.5,13–16

WHAT IS THE PATHOGENESIS OF LEFT VENTRICULAR THROMBOSIS?

A large transmural infarct results in loss of contractile function, which causes stagnation and pooling of blood adjacent to the infarcted ventricular segment. In addition, endocardial injury exposes tissue factor, which then initiates the coagulation cascade. To make matters worse, MI results in a hypercoagulable state through unclear mechanisms, which completes the Virchow triad for thrombus formation. Elevations of D-dimer, fibrinogen, anticardiolipin antibodies (IgM and IgG), and tissue factor have also been reported after acute MI.17

Figure 2. (A) A cross section of the apical segment of the left ventricle shows a mildly dilated cavity filled with mural thrombus. (B) Photo-micrograph of an acute thrombus shows alternating layers of fibrin and platelet with red and white blood cells (hematoxylin and eosin, original magnification × 200). (C) Organization of a thrombus is characterized by infiltration of fibroblasts and newly formed capillaries (hematoxylin and eosin, original magnification × 200).

Thrombus formation begins with platelet aggregation at the site of endocardial damage, forming a platelet plug, followed by activation of clotting factors. These thrombi are referred to as “mural,” as they adhere to the chamber wall (endocardium). They are composed of fibrin and entrapped red and white blood cells (Figure 2).

The natural course of thrombus evolution is established but variable. A left ventricular thrombus may dislodge and embolize, resulting in stroke or other thromboembolic complications. Alternately, it can dissolve over time, aided by intrinsic fibrinolytic mechanisms. On other occasions, the thrombus may organize, a process characterized by ingrowth of smooth muscle cells, fibroblasts, and endothelium.

 

 

HOW IS LEFT VENTRICULAR THROMBOSIS DIAGNOSED?

2. What is the best imaging test for detecting a thrombus?

  • Transesophageal echocardiography
  • Transthoracic echocardiography
  • Cardiac magnetic resonance imaging (MRI) without gadolinium contrast
  • Cardiac MRI with gadolinium contrast

Evaluation of left ventricular function after acute MI carries a class I indication (ie, it should be performed).18 

Echocardiography is commonly used, and it has a 60% sensitivity to detect a thrombus.19 In patients with poorer transthoracic echocardiographic windows, contrast can be used to better delineate the left ventricular cavity and show the thrombus. Transesophageal echocardiography is seldom useful, as the left ventricular apex is foreshortened and in the far field.

A left ventricular thrombus is confirmed if an echo-dense mass with well-demarcated margins distinct from the endocardium is seen throughout the cardiac cycle. It should be evident in at least two different views (apical and short-axis) and should be adjacent to a hypokinetic or akinetic left ventricular wall. False-positive findings can occur due to misidentified false tendons, papillary muscles, and trabeculae.

Figure 3. Cardiac magnetic resonance imaging with a delayed-enhancement phase-sensitive inversion recovery image, vertical long-axis view. The red arrow points to dense subendocardial delayed enhancement in the apex extending into the mid-inferior wall, consistent with scar in the distal left anterior descending artery territory. The orange arrow shows a nonenhancing mass in the apex, consistent with thrombus.

Cardiac MRI with late gadolinium enhancement is now the gold standard for diagnostic imaging, as it accurately characterizes the shape, size, and location of the thrombus (Figure 3). Gadolinium contrast increases the enhancement of the ventricular cavity, thus allowing easy detection of thrombus, which appears dark. Cardiac MRI with delayed enhancement has 88% to 91% sensitivity and 99% specificity to detect left ventricular thrombosis.20,21 However, compared with echocardiography, routine cardiac MRI is time-intensive, costly, and not routinely available. As a result, it should be performed only in patients with poor acoustic windows and a high clinical suspicion of left ventricular thrombosis.

Delayed-contrast cardiac computed tomography can be used to identify left ventricular thrombosis, using absence of contrast uptake. The need to use contrast is a disadvantage, but computed tomography can be an alternative in patients with contraindications to cardiac MRI.

WHAT COMPLICATIONS ARISE FROM LEFT VENTRICULAR THROMBOSIS?

The most feared complication of left ventricular thrombosis is thromboembolism. Cardioembolic stroke is generally severe, prone to early and long-term recurrence, and associated with a higher death rate than noncardioembolic ischemic stroke.22,23 Thrombi associated with thromboembolism are often acute and mobile rather than organized and immobile.24 They may embolize to the brain,  spleen, kidneys, and bowel.25 In a meta-analysis of 11 studies, the pooled odds ratio for risk of embolization was 5.45 (95% confidence interval [CI] 3.02–9.83) with left ventricular thrombi vs without.26 Before systemic thrombolysis and antiplatelet therapy became available, stroke rates ranged from 1.5% to 10%.27–29

In a meta-analysis of 22 studies from 1978 to 2004, the incidence of ischemic stroke after MI during hospitalization was around 11.1 per 1,000 MIs.30 This study found that anterior MI was associated with a higher risk of stroke, but reported no difference in the incidence of stroke with percutaneous coronary intervention, systemic thrombolysis, or no reperfusion.

In a large prospective cohort study of 2,160 patients,31 259 (12%) had a stroke after MI. In multivariable analysis, age, diabetes, and previous stroke were predictors of stroke after MI. This study reported significantly fewer strokes in patients who underwent percutaneous coronary intervention than with other or no reperfusion therapies.31

ANTICOAGULATION TREATMENT

3. How would you treat a patient who has a drug-eluting stent in the left anterior descending artery and a new diagnosis of left ventricular thrombosis?

  • Warfarin
  • Aspirin and clopidogrel
  • Aspirin, clopidogrel, and warfarin
  • Aspirin and warfarin

The management of left ventricular thrombosis has been summarized in guidelines from the American College of Chest Physicians (ACCP) in 2012,32 and from the American College of Cardiology/American Heart Association in 2013,18 which recommend anticoagulation for at least 3 months, or indefinitely if bleeding risk is low, for all patients developing a left ventricular thrombus.

For patients with acute MI and left ventricular thrombosis, the ACCP guidelines recommend warfarin with a target international normalized ratio of 2.0 to 3.0 plus dual antiplatelet therapy (eg, aspirin plus clopidogrel)  for 3 months, after which warfarin is discontinued but dual antiplatelet therapy is continued for up to 12 months.32

The European Society of Cardiology guidelines33 recommend 6 months of anticoagulation. However, if the patient is receiving dual antiplatelet therapy, they recommend repeated imaging of the left ventricle after 3 months of anticoagulation, which may allow for earlier discontinuation of anticoagulation if the thrombus has resolved and apical wall motion has recovered. Therefore, most experts recommend 3 months of anticoagulation when used in combination with dual antiplatelet therapy and repeating echocardiography at 3 months to safely discontinue anticoagulation. The best answer to the question posed here is aspirin, clopidogrel, and warfarin.

Decisions about antithrombotic therapy may also depend on stent type and the patient’s bleeding risk. With bare-metal stents, dual antiplatelet therapy along with anticoagulation should be used for 1 month, after which anticoagulation should be used with a single antiplatelet agent for another 2 months; after this, the anticoagulant can be discontinued and dual antiplatelet therapy can be resumed for a total of 12 months. Newer anticoagulants such as rivaroxaban, dabigatran, edoxaban, and apixaban may also have a role, but they have not yet been studied for this indication.

Surgical thrombectomy is rarely considered now, given the known efficacy of anticoagulants in dissolving the thrombus. It was done in the past for large, mobile, or protruding left ventricular thrombi, which have a higher potential for embolization.34 Currently, it can be done under very special circumstances, such as before placement of a left ventricular assist device or if the thrombus is large, to prevent embolism.35,36

BLEEDING COMPLICATIONS WITH TRIPLE ANTITHROMBOTIC THERAPY

After stent placement, almost all patients need to be on dual antiplatelet therapy for a specified duration depending on the type and generation of stent used. Such patients end up on “triple” antithrombotic therapy (two antiplatelet drugs plus an anticoagulant), which poses a high risk of bleeding.37 Consideration needs to be given to the risks of stroke, stent thrombosis, and major bleeding when selecting the antithrombotic regimen.38 Triple antithrombotic therapy has been associated with a risk of fatal and nonfatal bleeding of 4% to 16% when used for indications such as atrial fibrillation.39–41

Risks of triple antithrombotic therapy (aspirin 80–100 mg, clopidogrel 75 mg, and warfarin) were compared with those of clopidogrel plus warfarin in the What Is the Optimal Antiplatelet and Anticoagulant therapy in Patients With Oral Anticoagulation and Coronary Stenting Trial,37 which reported a significantly lower risk of  major and minor bleeding with clopidogrel-plus-warfarin therapy than with triple antithrombotic therapy, 14.3% vs 31.7% (hazard ratio 0.40, 95% CI 0.28–0.58, P < .0001).

Additionally, the increased risk of major and minor bleeding associated with triple antithrombotic therapy has been confirmed in many observational studies; other studies found a trend toward lower risk with triple therapy, but this was not statistically significant (Table 2).38,40,42–55 A large multicenter European trial is being conducted to compare dual antiplatelet therapy vs triple antithrombotic therapy in patients with left ventricular thrombosis.

CASE FOLLOW-UP

Our patient was started on warfarin, clopidogrel 75 mg, and aspirin 75 mg at the time of discharge. He was continued on warfarin for 3 months, at which time a follow-up echocardiogram showed no thrombus in the left ventricle. Warfarin was discontinued, and he had no thromboembolic complications.

TAKE-HOME POINTS

Left ventricular thrombosis after an acute MI is very important to detect, as it can lead to serious complications through arterial embolism.

The incidence of left ventricular thrombosis has declined significantly with the use of percutaneous coronary intervention. However, it may still occur in a small number of patients with larger infarcts owing to delay in revascularization or proximal (left main or left anterior descending) occlusions with larger infarct size.

Echocardiography, which is routinely performed after acute MI to assess myocardial function, uncovers most left ventricular thrombi. In high-risk cases, MRI with late gadolinium enhancement can increase the diagnostic yield.

Anticoagulation with warfarin is recommended for at least 3 months. Post-MI patients undergoing stent implantation may need triple antithrombotic therapy, which, however, increases the bleeding risk significantly. Large randomized trials are needed to guide physicians in risk stratification of such patients.

References
  1. Lip GY, Piotrponikowski P, Andreotti F, et al; Heart Failure Association (EHFA) of the European Society of Cardiology (ESC) and the ESC Working Group on Thrombosis. Thromboembolism and antithrombotic therapy for heart failure in sinus rhythm: an executive summary of a joint consensus document from the ESC Heart Failure Association and the ESC Working Group on Thrombosis. Thromb Haemost 2012; 108:1009–1022.
  2. Turpie AG, Robinson JG, Doyle DJ, et al. Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction. N Engl J Med 1989; 320:352–357.
  3. Chiarella F, Santoro E, Domenicucci S, Maggioni A, Vecchio C. Predischarge two-dimensional echocardiographic evaluation of left ventricular thrombosis after acute myocardial infarction in the GISSI-3 study. Am J Cardiol 1998; 81:822–827.
  4. Kalra A, Jang IK. Prevalence of early left ventricular thrombus after primary coronary intervention for acute myocardial infarction. J Thromb Thrombolysis 2000; 10:133–136.
  5. Nayak D, Aronow WS, Sukhija R, McClung JA, Monsen CE, Belkin RN. Comparison of frequency of left ventricular thrombi in patients with anterior wall versus non-anterior wall acute myocardial infarction treated with antithrombotic and antiplatelet therapy with or without coronary revascularization. Am J Cardiol 2004; 93:1529–1530.
  6. Rehan A, Kanwar M, Rosman H, et al. Incidence of post myocardial infarction left ventricular thrombus formation in the era of primary percutaneous intervention and glycoprotein IIb/IIIa inhibitors. A prospective observational study. Cardiovasc Ultrasound 2006;4:20.
  7. Zielinska M, Kaczmarek K, Tylkowski M. Predictors of left ventricular thrombus formation in acute myocardial infarction treated with successful primary angioplasty with stenting. Am J Med Sci 2008; 335:171–176.
  8. Osherov AB, Borovik-Raz M, Aronson D, et al. Incidence of early left ventricular thrombus after acute anterior wall myocardial infarction in the primary coronary intervention era. Am Heart J 2009; 157:1074–1080.
  9. Solheim S, Seljeflot I, Lunde K, et al. Frequency of left ventricular thrombus in patients with anterior wall acute myocardial infarction treated with percutaneous coronary intervention and dual antiplatelet therapy. Am J Cardiol 2010; 106:1197–1200.
  10. Shacham Y, Leshem-Rubinow E, Ben Assa E, et al. Comparison of C-reactive protein and fibrinogen levels in patients having anterior wall ST-segment elevation myocardial infarction with versus without left ventricular thrombus (from a primary percutaneous coronary intervention cohort). Am J Cardiol 2013; 112:57–60.
  11. Gianstefani S, Douiri A, Delithanasis I, et al. Incidence and predictors of early left ventricular thrombus after ST-elevation myocardial infarction in the contemporary era of primary percutaneous coronary intervention. Am J Cardiol 2014; 113:1111–1116.
  12. Shacham Y, Birati EY, Rogovski O, Cogan Y, Keren G, Roth A. Left ventricular thrombus formation and bleeding complications during continuous in-hospital anticoagulation for acute anterior myocardial infarction. Isr Med Assoc J 2012; 14:742–746.
  13. Asinger RW, Mikell FL, Elsperger J, Hodges M. Incidence of left-ventricular thrombosis after acute transmural myocardial infarction. Serial evaluation by two-dimensional echocardiography. N Engl J Med 1981; 305:297–302.
  14. Nihoyannopoulos P, Smith GC, Maseri A, Foale RA. The natural history of left ventricular thrombus in myocardial infarction: a rationale in support of masterly inactivity. J Am Coll Cardiol 1989; 14:903–911.
  15. Weinreich DJ, Burke JF, Pauletto FJ. Left ventricular mural thrombi complicating acute myocardial infarction. Long-term follow-up with serial echocardiography. Ann Intern Med 1984; 100:789–794.
  16. Greaves SC, Zhi G, Lee RT, et al. Incidence and natural history of left ventricular thrombus following anterior wall acute myocardial infarction. Am J Cardiol 1997; 80:442–448.
  17. Solheim S, Seljeflot I, Lunde K, et al. Prothrombotic markers in patients with acute myocardial infarction and left ventricular thrombus formation treated with pci and dual antiplatelet therapy. Thromb J 2013; 11:1.
  18. O’Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 127:e362–e425.
  19. Weinsaft JW, Kim HW, Crowley AL, et al. LV thrombus detection by routine echocardiography: insights into performance characteristics using delayed enhancement CMR. JACC Cardiovasc Imaging 2011; 4:702–712.
  20. Mollet NR, Dymarkowski S, Volders W, et al. Visualization of ventricular thrombi with contrast-enhanced magnetic resonance imaging in patients with ischemic heart disease. Circulation 2002; 106:2873–2876.
  21. Srichai MB, Junor C, Rodriguez LL, et al. Clinical, imaging, and pathological characteristics of left ventricular thrombus: a comparison of contrast-enhanced magnetic resonance imaging, transthoracic echocardiography, and transesophageal echocardiography with surgical or pathological validation. Am Heart J 2006; 152:75–84.
  22. Eriksson SE, Olsson JE. Survival and recurrent strokes in patients with different subtypes of stroke: a fourteen-year follow-up study. Cerebrovasc Dis 2001; 12:171–180.
  23. Grau AJ, Weimar C, Buggle F, et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German Stroke Data Bank. Stroke 2001; 32:2559–2566.
  24. Keren A, Goldberg S, Gottlieb S, et al. Natural history of left ventricular thrombi: their appearance and resolution in the posthospitalization period of acute myocardial infarction. J Am Coll Cardiol 1990; 15:790–800.
  25. Jordan RA, Miller RD, Edwards JE, Parker RL. Thrombo-embolism in acute and in healed myocardial infarction. I. Intracardiac mural thrombosis. Circulation 1952; 6:1–6.
  26. Vaitkus PT, Barnathan ES. Embolic potential, prevention and management of mural thrombus complicating anterior myocardial infarction: a meta-analysis. J Am Coll Cardiol 1993; 22:1004–1009.
  27. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2:349–360.
  28. Cabin HS, Roberts WC. Left ventricular aneurysm, intraaneurysmal thrombus and systemic embolus in coronary heart disease. Chest 1980; 77:586–590.
  29. Keating EC, Gross SA, Schlamowitz RA, et al. Mural thrombi in myocardial infarctions. Prospective evaluation by two-dimensional echocardiography. Am J Med 1983; 74:989–995.
  30. Witt BJ, Ballman KV, Brown RD Jr, Meverden RA, Jacobsen SJ, Roger VL. The incidence of stroke after myocardial infarction: a meta-analysis. Am J Med 2006; 119:354.e1–354.e9.
  31. Witt BJ, Brown RD Jr, Jacobsen SJ, Weston SA, Yawn BP, Roger VL. A community-based study of stroke incidence after myocardial infarction. Ann Intern Med 2005; 143:785–792.
  32. Vandvik PO, Lincoff AM, Gore JM, et al; American College of Chest Physicians. Primary and secondary prevention of cardiovascular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(suppl):e637S–e68S.
  33. Steg G, James SK, Atar D, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33:2569–2619.
  34. Nili M, Deviri E, Jortner R, Strasberg B, Levy MJ. Surgical removal of a mobile, pedunculated left ventricular thrombus: report of 4 cases. Ann Thorac Surg 1988; 46:396–400.
  35. Kanemitsu S, Miyake Y, Okabe M. Surgical removal of a left ventricular thrombus associated with cardiac sarcoidosis. Interact Cardiovasc Thorac Surg 2008; 7:333–335.
  36. Engin C, Yagdi T, Balcioglu O, et al. Left ventricular assist device implantation in heart failure patients with a left ventricular thrombus. Transplant Proc 2013; 45:1017–1019.
  37. Dewilde WJ, Oirbans T, Verheugt FW, et al; WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013; 381:1107–1115.
  38. Faxon DP, Eikelboom JW, Berger PB, et al. Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting: a North American perspective: executive summary. Circ Cardiovasc Interv 2011; 4:522–534.
  39. Hansen ML, Sorensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010; 170:1433–1441.
  40. Karjalainen PP, Porela P, Ylitalo A, et al. Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting. Eur Heart J 2007; 28:726–732.
  41. Doyle BJ, Rihal CS, Gastineau DA, Holmes DR Jr. Bleeding, blood transfusion, and increased mortality after percutaneous coronary intervention: implications for contemporary practice. J Am Coll Cardiol 2009; 53:2019–2027.
  42. Azoulay L, Dell’Aniello S, Simon T, Renoux C, Suissa S. The concurrent use of antithrombotic therapies and the risk of bleeding in patients with atrial fibrillation. Thromb Haemost 2013; 109:431–439.
  43. Deshmukh A, Hilleman DE, Del Core M, Nair CK. Antithrombotic regimens in patients with indication for long-term anticoagulation undergoing coronary interventions-systematic analysis, review of literature, and implications on management. Am J Ther 2013; 20:654–663.
  44. Fosbol EL, Wang TY, Li S, et al. Warfarin use among older atrial fibrillation patients with non-ST-segment elevation myocardial infarction managed with coronary stenting and dual antiplatelet therapy. Am Heart J 2013; 166:864–870.
  45. Gao F, Zhou YJ, Wang ZJ, et al. Meta-analysis of the combination of warfarin and dual antiplatelet therapy after coronary stenting in patients with indications for chronic oral anticoagulation. Int J Cardiol 2011; 148:96–101.
  46. Hansen ML, Sorensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010; 170:1433–1441.
  47. Hermosillo AJ, Spinler SA. Aspirin, clopidogrel, and warfarin: is the combination appropriate and effective or inappropriate and too dangerous? Ann Pharmacother 2008; 42:790–805.
  48. Holmes DR Jr, Kereiakes DJ, Kleiman NS, Moliterno DJ, Patti G, Grines CL. Combining antiplatelet and anticoagulant therapies. J Am Coll Cardiol 2009; 54:95–109.
  49. Khurram Z, Chou E, Minutello R, et al. Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding. J Invasive Cardiol 2006; 18:162–164.
  50. Orford JL, Fasseas P, Melby S, et al. Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation. Am Heart J 2004; 147:463–467.
  51. Porter A, Konstantino Y, Iakobishvili Z, Shachar L, Battler A, Hasdai D. Short-term triple therapy with aspirin, warfarin, and a thienopyridine among patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv 2006; 68:56–61.
  52. DeEugenio D, Kolman L, DeCaro M, et al. Risk of major bleeding with concomitant dual antiplatelet therapy after percutaneous coronary intervention in patients receiving long-term warfarin therapy. Pharmacotherapy 2007; 27:691–696.
  53. Ruiz-Nodar JM, Marin F, Hurtado JA, et al. Anticoagulant and antiplatelet therapy use in 426 patients with atrial fibrillation undergoing percutaneous coronary intervention and stent implantation implications for bleeding risk and prognosis. J Am Coll Cardiol 2008; 51:818–825.
  54. Sarafoff N, Ndrepepa G, Mehilli J, et al. Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation. J Intern Med 2008; 264:472–480.
  55. Rossini R, Musumeci GF, Lettieri CF, et al. Long-term outcomes in patients undergoing coronary stenting on dual oral antiplatelet treatment requiring oral anticoagulant therapy. Am J Cardiol 2008; 102:1618–1623.
References
  1. Lip GY, Piotrponikowski P, Andreotti F, et al; Heart Failure Association (EHFA) of the European Society of Cardiology (ESC) and the ESC Working Group on Thrombosis. Thromboembolism and antithrombotic therapy for heart failure in sinus rhythm: an executive summary of a joint consensus document from the ESC Heart Failure Association and the ESC Working Group on Thrombosis. Thromb Haemost 2012; 108:1009–1022.
  2. Turpie AG, Robinson JG, Doyle DJ, et al. Comparison of high-dose with low-dose subcutaneous heparin to prevent left ventricular mural thrombosis in patients with acute transmural anterior myocardial infarction. N Engl J Med 1989; 320:352–357.
  3. Chiarella F, Santoro E, Domenicucci S, Maggioni A, Vecchio C. Predischarge two-dimensional echocardiographic evaluation of left ventricular thrombosis after acute myocardial infarction in the GISSI-3 study. Am J Cardiol 1998; 81:822–827.
  4. Kalra A, Jang IK. Prevalence of early left ventricular thrombus after primary coronary intervention for acute myocardial infarction. J Thromb Thrombolysis 2000; 10:133–136.
  5. Nayak D, Aronow WS, Sukhija R, McClung JA, Monsen CE, Belkin RN. Comparison of frequency of left ventricular thrombi in patients with anterior wall versus non-anterior wall acute myocardial infarction treated with antithrombotic and antiplatelet therapy with or without coronary revascularization. Am J Cardiol 2004; 93:1529–1530.
  6. Rehan A, Kanwar M, Rosman H, et al. Incidence of post myocardial infarction left ventricular thrombus formation in the era of primary percutaneous intervention and glycoprotein IIb/IIIa inhibitors. A prospective observational study. Cardiovasc Ultrasound 2006;4:20.
  7. Zielinska M, Kaczmarek K, Tylkowski M. Predictors of left ventricular thrombus formation in acute myocardial infarction treated with successful primary angioplasty with stenting. Am J Med Sci 2008; 335:171–176.
  8. Osherov AB, Borovik-Raz M, Aronson D, et al. Incidence of early left ventricular thrombus after acute anterior wall myocardial infarction in the primary coronary intervention era. Am Heart J 2009; 157:1074–1080.
  9. Solheim S, Seljeflot I, Lunde K, et al. Frequency of left ventricular thrombus in patients with anterior wall acute myocardial infarction treated with percutaneous coronary intervention and dual antiplatelet therapy. Am J Cardiol 2010; 106:1197–1200.
  10. Shacham Y, Leshem-Rubinow E, Ben Assa E, et al. Comparison of C-reactive protein and fibrinogen levels in patients having anterior wall ST-segment elevation myocardial infarction with versus without left ventricular thrombus (from a primary percutaneous coronary intervention cohort). Am J Cardiol 2013; 112:57–60.
  11. Gianstefani S, Douiri A, Delithanasis I, et al. Incidence and predictors of early left ventricular thrombus after ST-elevation myocardial infarction in the contemporary era of primary percutaneous coronary intervention. Am J Cardiol 2014; 113:1111–1116.
  12. Shacham Y, Birati EY, Rogovski O, Cogan Y, Keren G, Roth A. Left ventricular thrombus formation and bleeding complications during continuous in-hospital anticoagulation for acute anterior myocardial infarction. Isr Med Assoc J 2012; 14:742–746.
  13. Asinger RW, Mikell FL, Elsperger J, Hodges M. Incidence of left-ventricular thrombosis after acute transmural myocardial infarction. Serial evaluation by two-dimensional echocardiography. N Engl J Med 1981; 305:297–302.
  14. Nihoyannopoulos P, Smith GC, Maseri A, Foale RA. The natural history of left ventricular thrombus in myocardial infarction: a rationale in support of masterly inactivity. J Am Coll Cardiol 1989; 14:903–911.
  15. Weinreich DJ, Burke JF, Pauletto FJ. Left ventricular mural thrombi complicating acute myocardial infarction. Long-term follow-up with serial echocardiography. Ann Intern Med 1984; 100:789–794.
  16. Greaves SC, Zhi G, Lee RT, et al. Incidence and natural history of left ventricular thrombus following anterior wall acute myocardial infarction. Am J Cardiol 1997; 80:442–448.
  17. Solheim S, Seljeflot I, Lunde K, et al. Prothrombotic markers in patients with acute myocardial infarction and left ventricular thrombus formation treated with pci and dual antiplatelet therapy. Thromb J 2013; 11:1.
  18. O’Gara PT, Kushner FG, Ascheim DD, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 127:e362–e425.
  19. Weinsaft JW, Kim HW, Crowley AL, et al. LV thrombus detection by routine echocardiography: insights into performance characteristics using delayed enhancement CMR. JACC Cardiovasc Imaging 2011; 4:702–712.
  20. Mollet NR, Dymarkowski S, Volders W, et al. Visualization of ventricular thrombi with contrast-enhanced magnetic resonance imaging in patients with ischemic heart disease. Circulation 2002; 106:2873–2876.
  21. Srichai MB, Junor C, Rodriguez LL, et al. Clinical, imaging, and pathological characteristics of left ventricular thrombus: a comparison of contrast-enhanced magnetic resonance imaging, transthoracic echocardiography, and transesophageal echocardiography with surgical or pathological validation. Am Heart J 2006; 152:75–84.
  22. Eriksson SE, Olsson JE. Survival and recurrent strokes in patients with different subtypes of stroke: a fourteen-year follow-up study. Cerebrovasc Dis 2001; 12:171–180.
  23. Grau AJ, Weimar C, Buggle F, et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: the German Stroke Data Bank. Stroke 2001; 32:2559–2566.
  24. Keren A, Goldberg S, Gottlieb S, et al. Natural history of left ventricular thrombi: their appearance and resolution in the posthospitalization period of acute myocardial infarction. J Am Coll Cardiol 1990; 15:790–800.
  25. Jordan RA, Miller RD, Edwards JE, Parker RL. Thrombo-embolism in acute and in healed myocardial infarction. I. Intracardiac mural thrombosis. Circulation 1952; 6:1–6.
  26. Vaitkus PT, Barnathan ES. Embolic potential, prevention and management of mural thrombus complicating anterior myocardial infarction: a meta-analysis. J Am Coll Cardiol 1993; 22:1004–1009.
  27. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988; 2:349–360.
  28. Cabin HS, Roberts WC. Left ventricular aneurysm, intraaneurysmal thrombus and systemic embolus in coronary heart disease. Chest 1980; 77:586–590.
  29. Keating EC, Gross SA, Schlamowitz RA, et al. Mural thrombi in myocardial infarctions. Prospective evaluation by two-dimensional echocardiography. Am J Med 1983; 74:989–995.
  30. Witt BJ, Ballman KV, Brown RD Jr, Meverden RA, Jacobsen SJ, Roger VL. The incidence of stroke after myocardial infarction: a meta-analysis. Am J Med 2006; 119:354.e1–354.e9.
  31. Witt BJ, Brown RD Jr, Jacobsen SJ, Weston SA, Yawn BP, Roger VL. A community-based study of stroke incidence after myocardial infarction. Ann Intern Med 2005; 143:785–792.
  32. Vandvik PO, Lincoff AM, Gore JM, et al; American College of Chest Physicians. Primary and secondary prevention of cardiovascular disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(suppl):e637S–e68S.
  33. Steg G, James SK, Atar D, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2012; 33:2569–2619.
  34. Nili M, Deviri E, Jortner R, Strasberg B, Levy MJ. Surgical removal of a mobile, pedunculated left ventricular thrombus: report of 4 cases. Ann Thorac Surg 1988; 46:396–400.
  35. Kanemitsu S, Miyake Y, Okabe M. Surgical removal of a left ventricular thrombus associated with cardiac sarcoidosis. Interact Cardiovasc Thorac Surg 2008; 7:333–335.
  36. Engin C, Yagdi T, Balcioglu O, et al. Left ventricular assist device implantation in heart failure patients with a left ventricular thrombus. Transplant Proc 2013; 45:1017–1019.
  37. Dewilde WJ, Oirbans T, Verheugt FW, et al; WOEST study investigators. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013; 381:1107–1115.
  38. Faxon DP, Eikelboom JW, Berger PB, et al. Antithrombotic therapy in patients with atrial fibrillation undergoing coronary stenting: a North American perspective: executive summary. Circ Cardiovasc Interv 2011; 4:522–534.
  39. Hansen ML, Sorensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010; 170:1433–1441.
  40. Karjalainen PP, Porela P, Ylitalo A, et al. Safety and efficacy of combined antiplatelet-warfarin therapy after coronary stenting. Eur Heart J 2007; 28:726–732.
  41. Doyle BJ, Rihal CS, Gastineau DA, Holmes DR Jr. Bleeding, blood transfusion, and increased mortality after percutaneous coronary intervention: implications for contemporary practice. J Am Coll Cardiol 2009; 53:2019–2027.
  42. Azoulay L, Dell’Aniello S, Simon T, Renoux C, Suissa S. The concurrent use of antithrombotic therapies and the risk of bleeding in patients with atrial fibrillation. Thromb Haemost 2013; 109:431–439.
  43. Deshmukh A, Hilleman DE, Del Core M, Nair CK. Antithrombotic regimens in patients with indication for long-term anticoagulation undergoing coronary interventions-systematic analysis, review of literature, and implications on management. Am J Ther 2013; 20:654–663.
  44. Fosbol EL, Wang TY, Li S, et al. Warfarin use among older atrial fibrillation patients with non-ST-segment elevation myocardial infarction managed with coronary stenting and dual antiplatelet therapy. Am Heart J 2013; 166:864–870.
  45. Gao F, Zhou YJ, Wang ZJ, et al. Meta-analysis of the combination of warfarin and dual antiplatelet therapy after coronary stenting in patients with indications for chronic oral anticoagulation. Int J Cardiol 2011; 148:96–101.
  46. Hansen ML, Sorensen R, Clausen MT, et al. Risk of bleeding with single, dual, or triple therapy with warfarin, aspirin, and clopidogrel in patients with atrial fibrillation. Arch Intern Med 2010; 170:1433–1441.
  47. Hermosillo AJ, Spinler SA. Aspirin, clopidogrel, and warfarin: is the combination appropriate and effective or inappropriate and too dangerous? Ann Pharmacother 2008; 42:790–805.
  48. Holmes DR Jr, Kereiakes DJ, Kleiman NS, Moliterno DJ, Patti G, Grines CL. Combining antiplatelet and anticoagulant therapies. J Am Coll Cardiol 2009; 54:95–109.
  49. Khurram Z, Chou E, Minutello R, et al. Combination therapy with aspirin, clopidogrel and warfarin following coronary stenting is associated with a significant risk of bleeding. J Invasive Cardiol 2006; 18:162–164.
  50. Orford JL, Fasseas P, Melby S, et al. Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation. Am Heart J 2004; 147:463–467.
  51. Porter A, Konstantino Y, Iakobishvili Z, Shachar L, Battler A, Hasdai D. Short-term triple therapy with aspirin, warfarin, and a thienopyridine among patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv 2006; 68:56–61.
  52. DeEugenio D, Kolman L, DeCaro M, et al. Risk of major bleeding with concomitant dual antiplatelet therapy after percutaneous coronary intervention in patients receiving long-term warfarin therapy. Pharmacotherapy 2007; 27:691–696.
  53. Ruiz-Nodar JM, Marin F, Hurtado JA, et al. Anticoagulant and antiplatelet therapy use in 426 patients with atrial fibrillation undergoing percutaneous coronary intervention and stent implantation implications for bleeding risk and prognosis. J Am Coll Cardiol 2008; 51:818–825.
  54. Sarafoff N, Ndrepepa G, Mehilli J, et al. Aspirin and clopidogrel with or without phenprocoumon after drug eluting coronary stent placement in patients on chronic oral anticoagulation. J Intern Med 2008; 264:472–480.
  55. Rossini R, Musumeci GF, Lettieri CF, et al. Long-term outcomes in patients undergoing coronary stenting on dual oral antiplatelet treatment requiring oral anticoagulant therapy. Am J Cardiol 2008; 102:1618–1623.
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Cleveland Clinic Journal of Medicine - 83(11)
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Cleveland Clinic Journal of Medicine - 83(11)
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