CASE REPORT

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non-valvular atrial fibrillation. However, because oflimited dabigatran use in such situations, there are

mid-ventricular obstruction associated with paradoxicaldiastolic flow (Figure 1). Although the global left ventricu-

JOURNAL OF MEDICALCASE REPORTS

Kaku Journal of Medical Case Reports 2013, 7:238http://www.jmedicalcasereports.com/content/7/1/238and amiodarone (200mg/day) were continued for theDivision of Cardiovascular Medicine, Toyama Red Cross Hospital, 2-1-58Ushijima-honmachi, Toyama, Japanrelatively few reports in the literature regarding theefficacy of dabigatran for the resolution of establishedintra-cardiac thrombi. Herein described is the effectivenessof dabigatran for thrombus resolution in a patient with aleft ventricular aneurysm.

Case presentationA 59-year-old Japanese man presented for treatment ofan intra-cardiac thrombus. At 52 years of age, he was

lar ejection fraction was not markedly impaired, aneurysmformation was observed at the left ventricular apex(Figure 1), and technetium (99mTc) tetrofosmin single-photon emission computed tomography demonstratedsevere hypoperfusion in this area (Figure 2). Coronaryangiography was concurrently performed, but revealed noatherosclerotic lesions in the coronary arteries. At 55 yearsof age, the patient developed sustained ventricular tachycar-dia associated with hemodynamic collapse, for which animplantable cardioverter-defibrillator (ICD) was inserted.Although the administration of bisoprolol (5mg/day)

Correspondence: 3kaku@nyc.odn.ne.jpeffective for thrombus resolution in a patient with a left ventricular aneurysm.

Case presentation: A 59-year-old Japanese man with a mid-ventricular obstructive hypertrophiccardiomyopathy-associated apical aneurysm presented with a left ventricular apical thrombus (15.0mm17.0mm).Anti-coagulation therapy with dabigatran (150mg b.i.d. with meals) was initiated. Following dabigatran administration,weekly echocardiographic examinations demonstrated gradual decreases in thrombus size. After three weeks, nothrombus was detected and no systemic thromboembolic events had occurred.

Conclusions: The left ventricular apical thrombus resolved after dabigatran administration. Hence, dabigatran mayrepresent an alternative to warfarin as a therapeutic option in patients with previously detected intra-cardiac thrombus.

Keywords: Dabigatran, Intra-cardiac thrombus, Mid-ventricular obstructive hypertrophic cardiomyopathy

IntroductionIn general, heparin and warfarin are used for the treat-ment of intra-cardiac thrombi. Dabigatran is a novel oralanti-coagulant that has recently been approved for usein the prevention of thromboembolism in patients with

diagnosed with mid-ventricular obstructive hypertrophiccardiomyopathy (HCM) associated with paroxysmal atrialfibrillation. Electrocardiography revealed poor R-wave pro-gression at the V4 and V5 leads, and echocardiographicimages demonstrated asymmetrical septal hypertrophy andpatient with mid-ventricuhypertrophic cardiomyopBunji Kaku

Abstract

Introduction: Although dabigatran, a novel oral anti-coagthromboembolism in patients with non-valvular atrial fibrestablished intra-cardiac thrombi has not been validated.Intra-cardiac thrombus reanti-coagulation therapy 2013 Kaku; licensee BioMed Central Ltd. ThiAttribution License (http://creativecommons.oreproduction in any medium, provided the orOpen Access

olution afterith dabigatran in aar obstructivethy: a case report

lant, has been approved for the prevention oftion, the efficacy of dabigatran for the resolution ofrein is describe a case in which dabigatran wass is an open access article distributed under the terms of the Creative Commonsrg/licenses/by/2.0), which permits unrestricted use, distribution, andiginal work is properly cited.

Kaku Journal of Medical Case Reports 2013, 7:238 Page 2 of 5http://www.jmedicalcasereports.com/content/7/1/238suppression of ventricular tachycardia after ICD implant-ation, anti-coagulation therapy was not initiated becauseno thrombus was detected on two echocardiographicexaminations of the patient at 52 and 55 years of age.During the most recent echocardiographic examination,however, an asymptomatic thrombus (15.0mm17.0mm)was detected in the apical aneurysm (Figure 3). Therefore,hospital admission was recommended for anti-coagulationtherapy with continuous heparin infusion and warfarinadministration. However, because the patient obstinatelydeclined hospital admission and requested the continuationof medical treatment at an ambulatory clinic, dabigatran

Mid-ventricular obstruction

Aneurysmal formation

Figure 1 Echocardiographic images demonstrate asymmetrical septalparadoxical diastolic flow.administration (150mg b.i.d.) was initiated. Coagulationmarkers were measured before the commencement of anti-coagulation therapy, and all were within the normal range(Figure 4). Following dabigatran administration, an approxi-mately two-fold increase in activated partial thromboplastintime (measured four hours after dabigatran administrationwith meals) was observed and the prothrombin timeinternationalized ratio (PT-INR) was increased (Figure 4).However, the levels of D-dimer, thrombin-anti-thrombin IIIcomplex (TAT) and fibrinogen were not significantlyaltered (Figure 4). Moreover, weekly echocardiographicexaminations demonstrated a gradual decrease in thrombus

Systolic phase

Diastolic phase

Systolic phase

Diastolic phase

Pulsed Wave Doppler

hypertrophy and mid-ventricular obstruction associated with

Kaku Journal of Medical Case Reports 2013, 7:238 Page 3 of 5http://www.jmedicalcasereports.com/content/7/1/238size (Figure 3). Echocardiographic examinations performedone week after initial dabigatran administration showed

Figure 2 Technetium-99m tetrofosmin single-photon emissioncomputed tomography scan demonstrates an area of severehypoperfusion at the left ventricular apex (arrows).that thrombus size had decreased to 10.0mm9.0mm.Thrombus size had further decreased to 6.8mm6.0mmafter two weeks, and no thrombus was detected afterthree and four weeks. During the four-week treatmentperiod, no systemic thromboembolic events occurred.Thus, the thrombus appears to have been resolved afterdabigatran administration. However, dabigatran administra-tion was continued even after thrombus resolution.

DiscussionMid-ventricular obstructive hypertrophic cardiomyopathyis a rare form of HCM, accounting for approximately 5%of all HCM cases [1]. However, it is sometimes associatedwith apical aneurysms without significant atheroscleroticcoronary artery stenosis [2]. The annual incidence ofadverse cardiovascular events, including sudden death,appropriate ICD discharges, thromboembolic stroke andprogressive heart failure, has been reported to be 10.5% inpatients with HCM-associated apical aneurysms [2].Maron et al. reported the clinical courses of 28 patientswith HCM-associated apical aneurysms over a meanfollow-up period of 4.13.7 years, in which embolic strokeor left ventricular apical thrombus was detected in fourpatients [2]. On the basis of these results, they re-commended prophylactic anti-coagulation therapy for theprevention of embolic stroke in patients with apicalaneurysms. In the present case, no apical thrombus wasdetected on echocardiographic examinations of thepatient at 52 and 55 years of age, and anti-coagulationtherapy was not initiated. However, despite the patientsbeing asymptomatic, left ventricular apical thrombus wasdetected on his echocardiographic examination performedat 59 years of age.Dabigatran is a reversible direct thrombin inhibitor which

has been approved for the prevention of thromboembolismin patients with non-valvular atrial fibrillation [3] and inthose with thromboembolism after hip and knee replace-ment surgeries [4]. Thrombin is a key factor in the coagu-lant process because it converts fibrinogen into fibrin andactivates platelets and factors V, VII, VIII, IX and XIII.Following oral administration, dabigatran etexilate is rapidlyhydrolyzed into dabigatran and subsequently absorbedfrom the gastrointestinal tract. Dabigatran inactivates freethrombin and fibrin-bound thrombin in a concentration-dependent manner [5]. The efficacy and safety of dabigatranfor the prevention of stroke or systemic embolism inpatients with non-valvular atrial fibrillation was shown inthe Randomized Evaluation of Long-term AnticoagulationTherapy trial [3]. In that trial, dabigatran administration at110mg b.i.d. was associated with similar rates ofstroke and systemic embolism, but with a lower rateof major bleeding than that associated with warfarin.At 150mg b.i.d., dabigatran was associated with lowerrates of stroke and systemic embolism, but similarrates of major bleeding, compared with those of warfarin.Furthermore, the incidence of intra-cranial bleeding wassignificantly lower during the anti-coagulation therapywith both dabigatran doses compared with those ofwarfarin. In patients with non-valvular atrial fibrillation, inwhom atrial thrombus was identified on transesophagealechocardiography, the atrial thrombus was resolved byfour weeks of warfarin administration in approximately80% to 90% of cases [6,7].In contrast, the efficacy of the oral anti-coagulant

dabigatran in the resolution of previously detectedthrombus has not been extensively reported. Vidal et al.[8] reported the first documented case of thrombusresolution following dabigatran administration. In theirreport, after dabigatran administration (150mg b.i.d.) foreight weeks, a large left atrial appendage thrombus wasresolved with no concomitant thromboembolic events. Inthe present case, on the basis of weekly echocardiographicexaminations, the size of the apical aneurysm thrombusgradually decreased. After dabigatran administration forthree weeks, the apical aneurysm thrombus disappearedwithout any thromboembolic events. The absence ofclinical events made migration of the thrombus anunlikely explanation for its disappearance. Because plasmalevels of fibrinogen and TAT did not increase, systemic

coagulation activities did not increase, despite thepresence of a left ventricular thrombus. Before and

020406080

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before treatment after 1 week after 3 weeks after 4 weeks

aPTT

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before treatment after 1 week after 3 weeks after 4 weeks

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before treatment after 2 weeks after 4 weeks

D-dimer

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before treatment after 2 weeks after 4 weeks

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before treatment after 2 weeks after 4 weeks

FIB

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Figure 4 Serial changes in coagulation markers before and after anti-coagulation therapy with dabigatran (150mg b.i.d.). aPTT,activated partial thromboplastin time; PT-INR, prothrombin time internationalized ratio; TAT, thrombin-anti-thrombin III complex; FIB, fibrinogen.

1517mm

Before treatment A

109 mm

1 week after treatment

B

6.86.0

mm

2 weeks after treatment C

3 weeks after treatment 4 weeks after treatment

ED

Figure 3 Thrombic progression in apical aneurysm (thrombus indicated by arrows). (A) Prior to anti-coagulation therapy, thrombus sizewas 15.0mm17.0mm. (B) One week after initial dabigatran administration (150mg b.i.d.), thrombus size was 10.0mm9.0mm. (C) Two weeksafter initial dabigatran administration (150mg b.i.d.), thrombus size was 6.8mm6.0mm. (D) Three weeks after initial dabigatran administration(150mg b.i.d.), thrombus was undetectable. (E) Four weeks after initial dabigatran administration (150mg b.i.d.), thrombus was still undetectable.

Kaku Journal of Medical Case Reports 2013, 7:238 Page 4 of 5http://www.jmedicalcasereports.com/content/7/1/238

natural history of left ventricular apical aneurysms in hypertrophiccardiomyopathy. Circulation 2008, 118:15411549.

3. Connolly SJ, Ezekoxitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A, PogueJ, Reilly PA, Themeles E, Varrone J, Wang S, Alings M, Xavier D, Zhu J, Diaz R,Lewis BS, Darius H, Diener HC, Joyner CD, Wallentin L, RE-LY SteeringCommittee and Investigators: Dabigatran versus warfarin in patients withatrial fibrillation. N Engl J Med 2009, 361:11391151.

4. Gmez-Outes A, Terleira-Fernndez AI, Surez-Gea ML, Vargas-Castrilln E:Dabigatran, rivaroxaban, or apixaban versus enoxaparin forthromboprophylaxis after total hip or knee replacement: systematic

Kaku Journal of Medical Case Reports 2013, 7:238 Page 5 of 5http://www.jmedicalcasereports.com/content/7/1/238after anti-coagulation therapy with dabigatran, the plasmaD-dimer level, which is a fibrinolysis marker, did notincrease. After dabigatran administration, activated partialprothrombin time was moderately prolonged and PT-INRwas slightly extended. These findings suggest that, insituations in which dabigatran suppresses thrombinactivity without the activation of fibrinolysis, endogenousfibrinolysis and the prevention of new thrombus for-mation by dabigatran administration may be the pri-mary mechanism of thrombus resolution. Some patientsshowed resistance to anti-coagulation therapy withwarfarin [8], which also inhibits vitamin K-dependent-carboxylation of proteins C and S. Therefore, warfarinalso has a potential thrombogenic effect by inhibiting theactivities of these anti-coagulant proteins. It was consideredthat the initiation of warfarin therapy without the additionof heparin at the ambulatory clinic may have triggered thiswarfarin-induced proteins C and S paradox. Therefore,dabigatran may present some advantages over warfarin.The patient had the habit of ardently eating natto, atraditional Japanese fermented soybean dish. Natto con-tains a large quantity of vitamin K; thus, consumption ofeven a small quantity of natto can strongly reverse theeffects of warfarin. Upon initiation of anti-coagulationtherapy with warfarin, patients must completely avoidconsuming vitamin K-rich foods such as natto. Thepatient did not adhere to this suggestion, although he wasinformed that the success of the treatment was dependenton his not consuming natto. In contrast, dabigatranefficacy is not limited by this type of food. If dabigatranefficacy in the resolution of intra-cardiac thrombus can beconfirmed in other cases, dabigatran may represent analternative therapeutic option to warfarin in patients withpreviously detected intra-cardiac thrombus.

ConclusionsBecause thrombus resolution was successful in the presentcase, dabigatran may have the potential to be used asan alternative to warfarin in patients with establishedintra-cardiac thrombus. However, additional cases areneeded to determine if dabigatran is effective for theresolution of intra-cardiac thrombus.

ConsentWritten informed consent was obtained from the patientfor publication of this case report and accompanyingimages. A copy of the written consent is available forreview by the Editor-in-Chief of this journal.

AbbreviationsPT-INR: Prothrombin time internationalized ratio; TAT: Thrombin-anti-thrombin III complex.Competing interestsThe author declares that he has no competing interests.review, meta-analysis, and indirect treatment comparisons. BMJ 2012,344:e3675.

5. Wienen W, Stassen JM, Priepke H, Ries UJ, Hauel N: In-vitro profile andex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatranand its orally active prodrug, dabigatran etexilate. Thromb Haemost 2007,98:155162.

6. Collins LJ, Silverman DI, Douglas PS, Manning WJ: Cardioversion ofnonrheumatic atrial fibrillation: reduced thromboembolic complicationswith 4 weeks of precardioversion anticoagulation are related to atrialthrombus resolution. Circulation 1995, 92:160163.

7. Corrado G, Tadeo G, Beretta S, Tagliagambe LM, Manzillo GF, Spata M,Santarone M: Atrial thrombi resolution after prolonged anticoagulation inpatients with atrial fibrillation. Chest 1999, 115:140143.

8. Vidal A, Vanerio G: Dabigatran and left atrial appendage thrombus.J Thromb Thrombolysis 2012, 34:545547.

doi:10.1186/1752-1947-7-238Cite this article as: Kaku: Intra-cardiac thrombus resolution afteranti-coagulation therapy with dabigatran in a patient with mid-ventricular obstructive hypertrophic cardiomyopathy: a case report.Journal of Medical Case Reports 2013 7:238.

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Research which is freely available for redistributionAuthors contributionBK analyzed and interpreted the patient data and wrote the manuscript.

Received: 17 March 2013 Accepted: 29 August 2013Published: 8 October 2013

References1. Gao XJ, Kang LM, Zhang J, Dou KF, Yuan JS, Yang YJ: Mid-ventricular

obstructive hypertrophic cardiomyopathy with apical aneurysm andsustained ventricular tachycardia: a case report and literature review.Chin Med J (Engl) 2011, 124:17541757.

2. Maron MS, Finley JJ, Bos M, Hauser TH, Manning WJ, Haas TS, Lesser JR,Udelson JE, Ackerman MJ, Maron BJ: Prevalence, clinical significance, andSubmit your manuscript at www.biomedcentral.com/submit

AbstractIntroductionCase presentationConclusions

IntroductionCase presentationDiscussionConclusionsConsentAbbreviationsCompeting interestsAuthors contributionReferences

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