CE: Namrta; BCF-17-164; Total nos of Pages: 3;
BCF-17-164
Case report 1
Newly developed left ventricular apical thrombus under dabigatran treatment Adem Adara, Orhan Onalanb and Fahri Cakanb Left ventricular (LV) thrombi are mostly formed in the aneurysmal or akinetic segment of the LV apex. Thromboembolism to the brain is usually fatal. There is not enough information available regarding the use of these new oral anticoagulant agents in LV thrombi. In this case, we present a 56-year-old male patient who was given dabigatran (150 mg, twice a day) for paroxysmal atrial fibrillation after experiencing anterior myocardial infarction. During the use of dabigatran, thrombus formation, which was not present earlier, was observed in the LV apical aneurysm. The dabigatran treatment discontinued and warfarin was initiated and, in the follow-ups, the thrombus was observed to shrink, and complete resolution was seen 6 weeks after treatment with warfarin. The patient did not experience any thromboembolic event. Our case is the first report showing that the treatment of dabigatran 150 mg may not prevent LV thrombus development. Blood Coagul
Fibrinolysis 26:000–000 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.
Blood Coagulation and Fibrinolysis 2017, 27:00–00 Keywords: dabigatran, heart failure, left ventricular thrombus a Karabuk University Training and Research Hospital and bKarabuk University Faculty of Medicine, Department of Cardiology, Karabuk, Turkey
Correspondence to Adem Adar, MD, Karabuk Trainning and Research Hospital, Karabuk University, Karabuk, Turkey Tel: +905072316878; fax: +03704125628; e-mail: [email protected] Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.bloodcoagulation.com). Received 1 June 2017 Revised 21 September 2017 Accepted 26 September 2017
Introduction Left ventricular (LV) thrombi are frequent in patients with low ejection fraction and LV apical aneurysm due to blood stasis, endothelial dysfunction, and hypercoagulable state [1]. Clinical importance of left ventricular apical thrombus (LVAT) depends on potential risk of cardio embolic stroke. Oral anticoagulation with warfarin is currently the gold standard treatment for LVAT [2]. Data are scarce regarding the use of new oral anticoagulant agents instead of warfarin in the prophylaxis and treatment of LVAT. Here, we report a case of newly developed LVAT in a 56-year-old male patient with atrial fibrillation who were receiving dabigatran for stroke prevention.
Fig. 1
Case presentation A 56-year-old patient, who was being treated for coronary artery disease and paroxysmal atrial fibrillation was admitted to our outpatient clinic for routine cardiac examination. He was asymptomatic, his vital signs were stable. Sinus rhythm, ST segment elevation, and T-negativity on V2-6 derivations indicating LV apical aneurysm were positive in his ECG. He experienced anterior myocardial infarction and underwent stent implantation 26 months ago, and after 4 months experienced an episode of paroxysmal atrial fibrillation. He was prescribed perindopril 10 mg, metoprolol 50 mg, atorvastatin 20 mg, spironolactone 25 mg, and dabigatran 150 mg. After having left a ventricular aneurysm, the patient underwent transthoracic echocardiography. In the echocardiography, the ejection fraction was 30%, he was 0957-5235 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.
Admission echocardiographic imaging: LV apical thrombus in dimensions of 22.7 mm 24.9 mm. LV, left ventricular.
DOI:10.1097/MBC.0000000000000671
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: Namrta; BCF-17-164; Total nos of Pages: 3;
BCF-17-164
2 Blood Coagulation and Fibrinolysis
2017, Vol 00 No 00
Fig. 2
2nd week control echocardiographic imaging: decreased LV apical thrombus. LV, left ventricular.
having severe hypokinesia in the anteroseptal wall of the LV, the apex was aneurysmal, and a pedunculated and moving thrombus (22.7 mm 24.9 mm) was present in an aneurysm (Fig. 1, Supplementary Video 1, http:// links.lww.com/BCF/A37). Although using dabigatran treatment for about 20 months, there was no thrombus observed in the left ventricular (LV) apex in his previous echocardiographic control 1 month ago. As the patient developed LV thrombus under dabigatran treatment, the dabigatran treatment was discontinued and warfarin in combination with heparin was initiated. After attaining an International Normalized Ratio (INR) level of greater than 2, heparin was discontinued and the treatment was continued only with warfarin. In the transthoracic echocardiography control after 2 weeks and 4 weeks, considerable shrinkage in the LV apical thrombus (LVAT) was observed (Figs. 2 and 3, Supplementary Video 2, http:// links.lww.com/BCF/A38). The patient continued warfarin treatment and had INR levels of 2 to 3, and in the next echocardiography control, the LVAT was observed to be completely resolved (Fig. 4, Supplementary Video 3, http://links.lww.com/BCF/A39). As the patient had the diagnosis of paroxysmal atrial fibrillation, the warfarin treatment was continued until the end of 3 months. The patient did not show thromboembolism or hemorrhage in follow-ups and is being given warfarin treatment.
Fig. 3
4th week control echocardiographic imaging: LV apical thrombus in dimensions of 9.1 mm 12.5 mm, decreased. LV, left ventricular.
Discussion Despite the advancements in percutaneous coronary intervention and medical treatment, the prevalence of LVAT remains to be 5–15% [3]. Approximately, 13% of the patients develop thromboembolism [4]. In such cases, mortality is high, especially for thromboembolism in the brain. LVAT can be successfully treated with anticoagulant medications. The risk of thromboembolism considerably decreases in the patients treated with an anticoagulant [2]. Warfarin, a vitamin K antagonist, in combination with heparin is used for the treatment of LVAT [5]. Owing to the difficulty of warfarin use and the requirement of INR monitorization, new oral anticoagulants have been introduced. Despite their established efficacy in nonvalvular atrial fibrillation, deep venous thrombosis, and pulmonary embolism [6], there is not enough information regarding the efficacy and safety of these medications in the treatment of LVAT. Dabigatran, being one of the new oral anticoagulants, is a direct thrombin inhibitor. There is not enough information in the literature on the use of dabigatran in the prophylaxis and treatment of LVAT. Dabigatran has been reported to be successful in the treatment of LVAT in a few cases [7]. LV ejection fraction being less than 35%, the history of anterior myocardial infarction, and an advanced age are the predictors identified for the development of LVAT
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: Namrta; BCF-17-164; Total nos of Pages: 3;
BCF-17-164
Left ventricular thrombus under dabigatran treatment Adar et al. 3
Fig. 4
thrombus that could not be prevented with ‘low-dose’ dabigatran treatment. It has also been shown that while dabigatran cannot prevent the thrombus formation in a prosthetic valve, it may also fail to prevent the LVAT development in patients with LV apical aneurysm and low ejection fraction. In conclusion, serial echocardiographic follow-ups for LVAT formation may be beneficial in patients with a LV apical aneurysm and the low ejection fraction if dabigatran was initiated for an indication such as atrial fibrillation.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References 1 2
3
4
6th week control echocardiographic imaging: Completely disappeared LV apical thrombus. LV, left ventricular. 5
[3,8]. In our case, a patient with heart failure and LV apical aneurysm developed a new LV thrombus under the treatment with dabigatran. We believe that in the presence of coronary artery disease, heart failure, and especially LV apical aneurysm, LVAT is developed as a result of stasis, endothelial dysfunction, and hypercoagulation, known as Virchow’s triad [1]. Furthermore, it is the first case report that shows dabigatran treatment may fail especially in the prophylaxis of LVAT. In accordance with our case that Koyama et al. [9] reported a case of atrial fibrillation in which a left atrial appendage
6 7
8
9
Lip GY, Gibbs CR. Does heart failure confer a hypercoagulable state? Virchow’s triad revisited. J Am Coll Cardiol 1999; 33:1424–1426. 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. Solheim S, Seljeflot I, Lunde K, Bjornerheim R, Aakhus S, Forfang 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; 106:1197–200. Stratton JR, Resnick AD. Increased embolic risk in patients with left ventricular thrombi. Circulation 1987; 75:1004–1011. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction–executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation 2004; 110:588–636. Altirriba J, Aparicio P. Oral anticoagulation in primary care. Rev Esp Sanid Penit 2017; 19:19–34. Nagamoto Y, Shiomi T, Matsuura T, Okahara A, Takegami K, Mine D, et al. Resolution of a left ventricular thrombus by the thrombolytic action of dabigatran. Heart Vessels 2014; 29:560–562. Sharma ND, McCullough PA, Philbin EF, Weaver WD. Left ventricular thrombus and subsequent thromboembolism in patients with severe systolic dysfunction. Chest 2000; 117:314–320. Koyama T, Otsuka Y, Kawahara M, Imoto Y, Nakamura K, Kodama S, et al. A left atrial appendage thrombus that developed during prophylactic low-dose dabigatran treatment resolved after switching to apixaban. Clin Case Rep 2017; 5:711–713.
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
BCF-17-164
Case report 1
Newly developed left ventricular apical thrombus under dabigatran treatment Adem Adara, Orhan Onalanb and Fahri Cakanb Left ventricular (LV) thrombi are mostly formed in the aneurysmal or akinetic segment of the LV apex. Thromboembolism to the brain is usually fatal. There is not enough information available regarding the use of these new oral anticoagulant agents in LV thrombi. In this case, we present a 56-year-old male patient who was given dabigatran (150 mg, twice a day) for paroxysmal atrial fibrillation after experiencing anterior myocardial infarction. During the use of dabigatran, thrombus formation, which was not present earlier, was observed in the LV apical aneurysm. The dabigatran treatment discontinued and warfarin was initiated and, in the follow-ups, the thrombus was observed to shrink, and complete resolution was seen 6 weeks after treatment with warfarin. The patient did not experience any thromboembolic event. Our case is the first report showing that the treatment of dabigatran 150 mg may not prevent LV thrombus development. Blood Coagul
Fibrinolysis 26:000–000 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.
Blood Coagulation and Fibrinolysis 2017, 27:00–00 Keywords: dabigatran, heart failure, left ventricular thrombus a Karabuk University Training and Research Hospital and bKarabuk University Faculty of Medicine, Department of Cardiology, Karabuk, Turkey
Correspondence to Adem Adar, MD, Karabuk Trainning and Research Hospital, Karabuk University, Karabuk, Turkey Tel: +905072316878; fax: +03704125628; e-mail: [email protected] Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (www.bloodcoagulation.com). Received 1 June 2017 Revised 21 September 2017 Accepted 26 September 2017
Introduction Left ventricular (LV) thrombi are frequent in patients with low ejection fraction and LV apical aneurysm due to blood stasis, endothelial dysfunction, and hypercoagulable state [1]. Clinical importance of left ventricular apical thrombus (LVAT) depends on potential risk of cardio embolic stroke. Oral anticoagulation with warfarin is currently the gold standard treatment for LVAT [2]. Data are scarce regarding the use of new oral anticoagulant agents instead of warfarin in the prophylaxis and treatment of LVAT. Here, we report a case of newly developed LVAT in a 56-year-old male patient with atrial fibrillation who were receiving dabigatran for stroke prevention.
Fig. 1
Case presentation A 56-year-old patient, who was being treated for coronary artery disease and paroxysmal atrial fibrillation was admitted to our outpatient clinic for routine cardiac examination. He was asymptomatic, his vital signs were stable. Sinus rhythm, ST segment elevation, and T-negativity on V2-6 derivations indicating LV apical aneurysm were positive in his ECG. He experienced anterior myocardial infarction and underwent stent implantation 26 months ago, and after 4 months experienced an episode of paroxysmal atrial fibrillation. He was prescribed perindopril 10 mg, metoprolol 50 mg, atorvastatin 20 mg, spironolactone 25 mg, and dabigatran 150 mg. After having left a ventricular aneurysm, the patient underwent transthoracic echocardiography. In the echocardiography, the ejection fraction was 30%, he was 0957-5235 Copyright ß 2017 Wolters Kluwer Health, Inc. All rights reserved.
Admission echocardiographic imaging: LV apical thrombus in dimensions of 22.7 mm 24.9 mm. LV, left ventricular.
DOI:10.1097/MBC.0000000000000671
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: Namrta; BCF-17-164; Total nos of Pages: 3;
BCF-17-164
2 Blood Coagulation and Fibrinolysis
2017, Vol 00 No 00
Fig. 2
2nd week control echocardiographic imaging: decreased LV apical thrombus. LV, left ventricular.
having severe hypokinesia in the anteroseptal wall of the LV, the apex was aneurysmal, and a pedunculated and moving thrombus (22.7 mm 24.9 mm) was present in an aneurysm (Fig. 1, Supplementary Video 1, http:// links.lww.com/BCF/A37). Although using dabigatran treatment for about 20 months, there was no thrombus observed in the left ventricular (LV) apex in his previous echocardiographic control 1 month ago. As the patient developed LV thrombus under dabigatran treatment, the dabigatran treatment was discontinued and warfarin in combination with heparin was initiated. After attaining an International Normalized Ratio (INR) level of greater than 2, heparin was discontinued and the treatment was continued only with warfarin. In the transthoracic echocardiography control after 2 weeks and 4 weeks, considerable shrinkage in the LV apical thrombus (LVAT) was observed (Figs. 2 and 3, Supplementary Video 2, http:// links.lww.com/BCF/A38). The patient continued warfarin treatment and had INR levels of 2 to 3, and in the next echocardiography control, the LVAT was observed to be completely resolved (Fig. 4, Supplementary Video 3, http://links.lww.com/BCF/A39). As the patient had the diagnosis of paroxysmal atrial fibrillation, the warfarin treatment was continued until the end of 3 months. The patient did not show thromboembolism or hemorrhage in follow-ups and is being given warfarin treatment.
Fig. 3
4th week control echocardiographic imaging: LV apical thrombus in dimensions of 9.1 mm 12.5 mm, decreased. LV, left ventricular.
Discussion Despite the advancements in percutaneous coronary intervention and medical treatment, the prevalence of LVAT remains to be 5–15% [3]. Approximately, 13% of the patients develop thromboembolism [4]. In such cases, mortality is high, especially for thromboembolism in the brain. LVAT can be successfully treated with anticoagulant medications. The risk of thromboembolism considerably decreases in the patients treated with an anticoagulant [2]. Warfarin, a vitamin K antagonist, in combination with heparin is used for the treatment of LVAT [5]. Owing to the difficulty of warfarin use and the requirement of INR monitorization, new oral anticoagulants have been introduced. Despite their established efficacy in nonvalvular atrial fibrillation, deep venous thrombosis, and pulmonary embolism [6], there is not enough information regarding the efficacy and safety of these medications in the treatment of LVAT. Dabigatran, being one of the new oral anticoagulants, is a direct thrombin inhibitor. There is not enough information in the literature on the use of dabigatran in the prophylaxis and treatment of LVAT. Dabigatran has been reported to be successful in the treatment of LVAT in a few cases [7]. LV ejection fraction being less than 35%, the history of anterior myocardial infarction, and an advanced age are the predictors identified for the development of LVAT
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CE: Namrta; BCF-17-164; Total nos of Pages: 3;
BCF-17-164
Left ventricular thrombus under dabigatran treatment Adar et al. 3
Fig. 4
thrombus that could not be prevented with ‘low-dose’ dabigatran treatment. It has also been shown that while dabigatran cannot prevent the thrombus formation in a prosthetic valve, it may also fail to prevent the LVAT development in patients with LV apical aneurysm and low ejection fraction. In conclusion, serial echocardiographic follow-ups for LVAT formation may be beneficial in patients with a LV apical aneurysm and the low ejection fraction if dabigatran was initiated for an indication such as atrial fibrillation.
Acknowledgements Conflicts of interest
There are no conflicts of interest.
References 1 2
3
4
6th week control echocardiographic imaging: Completely disappeared LV apical thrombus. LV, left ventricular. 5
[3,8]. In our case, a patient with heart failure and LV apical aneurysm developed a new LV thrombus under the treatment with dabigatran. We believe that in the presence of coronary artery disease, heart failure, and especially LV apical aneurysm, LVAT is developed as a result of stasis, endothelial dysfunction, and hypercoagulation, known as Virchow’s triad [1]. Furthermore, it is the first case report that shows dabigatran treatment may fail especially in the prophylaxis of LVAT. In accordance with our case that Koyama et al. [9] reported a case of atrial fibrillation in which a left atrial appendage
6 7
8
9
Lip GY, Gibbs CR. Does heart failure confer a hypercoagulable state? Virchow’s triad revisited. J Am Coll Cardiol 1999; 33:1424–1426. 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. Solheim S, Seljeflot I, Lunde K, Bjornerheim R, Aakhus S, Forfang 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; 106:1197–200. Stratton JR, Resnick AD. Increased embolic risk in patients with left ventricular thrombi. Circulation 1987; 75:1004–1011. Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction–executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). Circulation 2004; 110:588–636. Altirriba J, Aparicio P. Oral anticoagulation in primary care. Rev Esp Sanid Penit 2017; 19:19–34. Nagamoto Y, Shiomi T, Matsuura T, Okahara A, Takegami K, Mine D, et al. Resolution of a left ventricular thrombus by the thrombolytic action of dabigatran. Heart Vessels 2014; 29:560–562. Sharma ND, McCullough PA, Philbin EF, Weaver WD. Left ventricular thrombus and subsequent thromboembolism in patients with severe systolic dysfunction. Chest 2000; 117:314–320. Koyama T, Otsuka Y, Kawahara M, Imoto Y, Nakamura K, Kodama S, et al. A left atrial appendage thrombus that developed during prophylactic low-dose dabigatran treatment resolved after switching to apixaban. Clin Case Rep 2017; 5:711–713.
Copyright © 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
