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Journal of Veterinary Cardiology (2012) 14, 453e458

www.elsevier.com/locate/jvc

CASE REPORT

Thrombotic complications associated with atrialfibrillation in three dogs*

Paul J. Usechak, DVM a, Janice M. Bright, BSN, MS, DVM b,*,Thomas K. Day, DVM, MS a

a Louisville Veterinary Specialty and Emergency Services, 13160 Magisterial Drive, Louisville, KY 40223,USAbDepartment of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, ColoradoState University, 300 W. Drake Rd., Fort Collins, CO 80523-1620, USA

Received 15 August 2011; received in revised form 17 February 2012; accepted 2 April 2012

KEYWORDSCanine;Aortic thromboembo-lism;Dilated cardiomyop-athy;Thromboprophylaxis

pect of the Journal of Ved diagnostics. These imom/science/journal/1e Summary Plus link. Te several minutes. Reaenjoy the content. Anpaper which is indicateing author.ess: jmbright@colostat

see front matter ª 201org/10.1016/j.jvc.2012

Abstract Atrial fibrillation (AF) is the most common chronic pathologic arrhythmiain dogs, and whereas thromboembolism is a common complication of AF in humans,this complication has not been previously reported in dogs. This report describesthrombotic complications associated with AF in three dogs. A spherical left atrialmass consistent with a thrombus was identified in two dogs during echocardio-graphic examination. A third dog experienced arterial thromboembolism confirmedwith ultrasound and postmortem examination. These cases provide a unique ante-mortem description of intra-atrial thrombus formation and cardioembolic diseaseassociated with AF in dogs, and raise awareness of the importance of thoroughechocardiographic evaluation of the atria for thrombus prior to pharmacologic car-dioversion or direct current cardioversion.ª 2012 Elsevier B.V. All rights reserved.

terinary Cardiology is the emphasis of additional web-based images permitting the detailing ofages can be viewed (by those readers with subscription access) by going to http://www.

7602734. The issue to be viewed is clicked and the available PDF and image downloading ishe supplementary material for a given article appears at the end of the page. Downloading theders will require at least Quicktime 7 (available free at http://www.apple.com/quicktime/other means to view the material is to go to http://www.doi.org and enter the doi numberd at the end of the manuscript.

e.edu (J.M. Bright).

2 Elsevier B.V. All rights reserved..04.003

Abbreviations

AF atrial fibrillationECG electrocardiogramINR international normalized ratioPT prothrombin time

454 P.J. Usechak et al.

Case 1, a 13 year old, 17 kg spayed female,mixed breed dog was referred for additionaltreatment of congestive heart failure due todegenerative valve disease and severe mitralregurgitation. Heart failure had been managedwith pimobendan (0.3 mg/kg PO q 12 h), benaze-pril (0.6 mg/kg PO q 24 h), and furosemide(1.5 mg/kg PO q 8 h). One week prior to presen-tation, the owner noted onset of weakness andincreased respiratory effort. The dog was taken tothe primary care veterinarian who diagnosed atrialfibrillation (AF) and referred the dog for additionaldiagnostics and treatment.

Physical examination showed a slightly thin dogin no acute distress. The dog was afebrile (98.9 �F)with pale pink mucous membranes. The heart ratewas abnormally rapid (average 180 bpm) witha chaotic rhythm. Heart sounds were of varyingintensity and a grade V/VI holosystolic murmur washeard over the left apex. The dog was tachypneic(60 breaths/min) with increased respiratory effortand decreased respiratory sounds ventrally bilater-ally. Femoral arterial pulses were weak overall withvarying pulse strength and frequent pulse deficits.Jugular venous examination was unremarkable.

Electrocardiographic examination confirmed AFwith a rapid ventricular response (215 bpm).Frequent wide QRS complexes consistent withventricular tachycardia were also present. Thesystolic blood pressure assessed by Dopplersphygmomanometryc was 110 mmHg. Radiographicevaluation of the thorax showed cardiomegaly(vertebral heart score 12.8; normal < 10.5) withsevere left atrial enlargement, an interstitial per-ihilar pattern consistent with pulmonary edema,and pleural effusion. A complete blood count wasnormal. A serum chemistry panel showed mildincreases in blood urea nitrogen or BUN (47 mg/dL,reference interval 7e32 mg/dL), creatine kinase(279 IU/L, reference interval 50e275 IU/L),alanine aminotransferase or ALT (199 IU/L, refer-ence interval 10e110 IU/L), and aspartate amino-transferase or AST (108 IU/L, reference interval16e50 IU/L). The serum chloride concentrationwas slightly low (107 mEq/L, reference interval

c Doppler Flow Detector, Parks Medical Electronics, 19460 SWShaw, Aloha OR 97007 USA.

108e120 mEq/L). A qualitative two dimensionalechocardiographic examination showed degenera-tive changes of the mitral valve leaflets, poor leftventricular contractile function, and severe dila-tion of the left atrium, left auricle, and leftventricle. There was mild pericardial effusion andsevere pleural effusion. An echo-dense sphericalmass consistent with thrombus was identifiedwithin the left auricle near its junction with theleft atrial chamber (Fig. 1, Video 1). Color flowDoppler confirmed severe mitral regurgitation andmoderate tricuspid regurgitation.

To stabilize the dog’s respiratory status, thera-peutic thoracocentesiswas performedwhich yielded600 mL of serosanguinous fluid. The dog was dis-charged from the hospital on the following medica-tions: pimobendan (0.3mg/kg PO q 12 h), benazepril(0.6 mg/kg PO q 24 h), furosemide (1.5 mg/kg PO q8 h), hydrochlorothiazide/spironolactone (0.4 mg/kg/0.4mg/kg PO q 24 h), sustained release diltiazem(5 mg/kg PO q 24 h), amiodarone (12 mg/kg PO q24 h), and warfarin (0.1 mg/kg PO q 24 h1). Recheckexamination in 3 days and cardioversion in 2e4weeks were planned. However, the dog died acutelyapproximately 12 h after discharge. The ownerdeclined postmortem examination.

Case 2, a 5 year old, 53 kg, neutered male,Bernese mountain dog was referred for lethargy,reduced appetite, and vomiting of 48 h duration.On physical examination, the dog appeared thinand slightly depressed. There was an irregularcardiac rhythm with a heart rate of 150 bpm, andvariable arterial pulse strength. An electrocardio-gram (ECG) showed sustained AF. Systolic bloodpressurec was normal (110 mmHg), and no signifi-cant abnormalities were present on thoracicradiographs. Doppler echocardiographic examina-tion showed no structural heart disease. However,an echo-dense spherical mass consistent witha thrombus was noted at the junction of the leftauricle with the body of the left atrium (Video 2).The dog was discharged from the hospital onamiodarone (12 mg/kg PO q 24 h for 14 days, then6 mg/kg PO q 24 h) and with treatment forgastritis. In addition, anticoagulation and anti-platelet therapies were initiated to address theintra-atrial thrombus. Specifically, the dogreceived warfarin (0.08 mg/kg PO q 24 h1) andaspirin (2 mg/kg PO q 24 hr2). The warfarin dosewas adjusted by monitoring the InternationalNormalized Ratio (INR) to maintain a ratiobetween 2.0 and 3.0.d The INR was evaluated 72 h

d PT measurement and INR calculation performed by theClinical Pathology Laboratory, Veterinary Teaching Hospital,Colorado State University, Fort Collins, CO 80523 USA.

Figure 1 A left cranial short axis echocardiographicimage obtained from dog 1 is shown. A sphericalthrombus is visible in the left auricle near its junctionwith the body of the left atrium. LA ¼ left atrium,LAu ¼ left auricle, Ao ¼ aorta.

Thrombotic complications of atrial fibrillation 455

after beginning warfarin administration, and thenweekly. The initial total weekly warfarin dose(28 mg) was increased by 20% (to 33 mg) after thefirst week of treatment. Six weeks later, echocar-diographic imaging showed no evidence of thepreviously noted left atrial thrombus, and sinusrhythm was safely restored with direct currentcardioversion under anesthesia.

Case 3, a 7½ year old, 21 kg, neutered male,Shetland sheepdog was referred for treatment ofcongestive heart failure. The dog had a two weekhistory of a non-productive cough and progressiveloss of appetite with severe exercise intolerance.One day before referral, an arrhythmia wasdetected (ECG not recorded) and treatment withatenolol (1.2 mg/kg PO q 12 h) was initiated by theprimary care veterinarian.

Physical examination showed expiratory dysp-nea, tachypnea (70 breaths/min), marked bilateralrales, an irregular heart rhythm with a rate of130 bpm, and normal body temperature (101.8 �F).Thorough cardiac auscultation was hindered by theseverity of rales. The dog received aminophylline8 mg/kg IV, morphine 0.1 mg/kg IV, and furose-mide 2 mg/kg IV. Radiographic evaluation of thethorax showed cardiomegaly (vertebral heartscore 12.5, normal < 10.5), left atrial enlarge-ment, and an alveolar pattern consistent withpulmonary edema. Sustained AF was noted on theECG. A brief, two dimensional echocardiographicexamination showed diffuse thickening and nod-ularity of the mitral valve leaflets consistent withdegenerative valvular disease, a markedly dilatedleft atrium, and global left ventricular systolicdysfunction. Treatment was initiated witha loading dose of furosemide (1 mg/kg IV) followed

by an infusion (1 mg/kg/h), enalapril (0.24 mg/kgPO), and pimobendan (0.24 mg/kg PO). After 7 hof treatment, there was notable clinical improve-ment. The dog was alert, responsive, eupneic withdiminished rales, and ambulatory withoutlameness.

Two hours later the dog developed peracutetachypnea, tachycardia (260e280 bpm), hyper-tension (160 mmHg right forelimbc), severe painand hind limb paralysis. Administration of fentanyl(12 mg/kg IV) produced mild pain relief anda decline in heart rate (200e220 bpm). Concurrentright hind limb systolic blood pressurec was120 mmHg. Left hind limb dorsal metatarsal andfemoral pulses could not be detected with eitherpalpation or Doppler flow transducer. This limbwas cool with blanched skin. Hind limb sensationwas present and the dog reacted painfully tohandling. Color Doppler examination revealedabsence of blood flow in the left femoral arteryand negligible femoral venous flow. A large intra-luminal echodense lesion was visible at the aortictrifurcation, occluding the left external iliac artery(Fig. 2).

This dog’s owner chose not to pursue therapy,and a postmortem examination was performedimmediately following euthanasia. On gross exam-ination a large, firm, white thromboembolus wasfound within the aorta occluding the left externaliliac artery and advancing into the right externaliliac artery (Fig. 3). The dog had no history, clinicalsigns, or necropsy findings of chronic non-cardiacillness, and a prior complete blood count andchemistry panel were unremarkable.

Discussion

There are few reports of canine arterial thrombo-embolic disease in the veterinary literature. Insmall animals, the most common forms of macro-vascular thromboembolic disease are aorticthromboembolism in cats and pulmonary throm-boembolism in dogs.3,4 One study identified only 36cases of canine arterial thrombosis or thrombo-embolism from 8000 postmortem examinations(0.45%) over 15 years.5 Antemortem confirmationof thrombotic disease was made in 16 of thesedogs; in these cases, arterial thrombus occurred inassociation with glomerular amyloidosis, chronicinterstitial nephritis, heartworm disease,neoplasia, endocarditis, and prior patent ductusarteriosus surgery. One dog was found to have bothdilated cardiomyopathy and pancreatitis. Amajority of the dogs had slow onset of clinicalsigns, and cardiac arrhythmias were not present.

Figure 3 Photograph obtained during postmortemexaminationof dog 3 showing thecaudal aortawith a largeembolus (arrow head) at the trifurcation. The embolusoccludes the left external iliac artery and extends intothe right external iliac artery. R ¼ right, L ¼ left.

Figure 2 Sagittal ultrasound images of the caudalabdomen of dog 3 without (A) and with (B) powerDoppler showing a large embolus (arrow head) occupyingthe aorta and extending into and occluding the leftexternal iliac artery.

456 P.J. Usechak et al.

In-situ thrombosis of a femoral artery has beenreported in one dog following hind limb entrap-ment.6 Finally, in a descriptive study of heartdisease in Irish wolfhounds, the authors note thatone dog with AF was euthanized because of suddenonset hind limb paralysis; the authors commentthat they have noted thrombi in the left atrium ofwolfhounds with AF.7

In patients with AF, intra-atrial thrombusformation is believed to be triggered by Virchow’striad of stasis of blood flow, endothelial damage,and a hypercoagulable state.8e10 Stasis of bloodflow, particularly in the left auricle, is a feature ofAF, and the left auricle is the typical site ofthrombus formation in people with thisarrhythmia.8,9 Other factors contributing to a pro-thrombotic state in patients with AF includecardiomyopathy-related endomyocardial damage,intracardiac platelet activation, increased platelet

microparticles, and elevated circulating tissuefactor.10e12 Intracardiac platelet activation occursduring AF simultaneously with basal systemicplatelet activity.11 Turbulent blood flow associatedwith mitral valvular regurgitation also incitesplatelet activation.13

In people, left atrial thrombi are found in 5e14%of patients with AF of more than two days durationand 29% of patients with more chronic AF.8,14 Intra-atrial thrombus size may vary from a few milli-meters to approximately 4 cm.8,15 Typically,thromboembolism occurs either during AF orwithin 10 days after conversion to sinus rhythm,causing ischemic stroke; mesenteric, renal orsplenic infarction; or acute limb ischemia includingsaddle embolus. In human patients, atrial thrombiare typically identified by transesophagealechocardiography.10,14e16 Arterial thromboembo-lism is identified by computed tomography,Doppler ultrasonography, or digital subtractionangiography. A cardioembolic event may occureven with optimal management of AF, and earlydiagnosis is considered crucial for therapy andoutcome.

Left atrial thrombus formation and systemicembolization, although common in people with AF,are quite rare in dogs. This difference may reflect,at least in part, an increase of associated riskfactors in human patients, such as previous stroke,diabetes, and chronic hypertension.17 However,left ventricular dysfunction and left atrialenlargement are also risk factors for arterialthromboembolism. These additional risk factorsare often present in dogs with AF, suggestingspecies differences in thrombosis as well asdifferences in risk factors.

Table of Videos.

Video 1 Dog 1Echo

Short axis, two dimensionalechocardiogram recorded using aleft cranial transducer positionreveals a spherical thrombus in theleft auricle near its junction withthe body of the left atrium.

Video 2 Dog 2Echo

Tipped, long axis, two dimensionalechocardiogram recorded from theright hemithorax showing aspherical thrombus adjacent to theleft atrial wall.

Thrombotic complications of atrial fibrillation 457

Other than a thrombus, the main differentialdiagnosis for the echodense left atrial massesnoted in the first two cases is intracardiacneoplasia. However, the left atrial chamber isa very uncommon location for cardiac neoplasia indogs,18 and neoplasia is considerably less likely tobe found in association with AF than thrombus.Furthermore, the severity of the structural heartdisease in Case 1 and the resolution of the masswith anticoagulation in Case 2 support the workingdiagnosis of intra-atrial thrombus.

None of the dogs described in this report had anexhaustive diagnostic evaluation to eliminate non-cardiac causes of a prothrombotic state andintravascular thrombus formation; therefore,a causal relationship between AF and thrombuscannot be proven. However, history and routinebloodwork in all three dogs showed no indicationof significant renal disease, hypoproteinemia,neoplasia, sepsis, trauma, or pancreatitis.

Case 2 received chronic antithrombotic therapyconsisting of aspirin and warfarin. An antiplateletdose of aspirin was used,2 and warfarin wasadministered for anticoagulation using an initialstandard dose followed by dose adjustment usingcoagulation monitoring to achieve and maintaina safe yet effective level of anticoagulation.1 Theinitial warfarin dose and the warfarin doseadjustment were done according to a standardizedprotocol of oral warfarin therapy adapted fromhuman medicine19 and successfully used in caninepatients at Colorado State University.1 Specifically,the prothrombin time (PT) was measured and usedto calculate the INR using the International Sensi-tivity Index of the thromboplastin and the meancanine normal PT in our laboratory.d An INRbetween 2 and 3 was considered an ideal targetbased on recommendations for human patientswith AF19 and for canine patients with chronicdistal aortic thrombus.1 After one week, the totalweekly warfarin dose was increased by 20%,allowing for a smaller increase than if the dailydose had been altered.

Initiation of warfarin therapy in humans hasbeen associated with a brief hypercoagulableperiod due to the more rapid drop in protein Clevels compared to functional vitamin K-depen-dent coagulation factors. Therefore, it is consid-ered standard therapy in humans to overlapheparin and warfarin for several days when initi-ating warfarin. However, the importance of over-lapping heparin and warfarin in dogs has not beenconfirmed. In Case 2, preventing a transient pro-coagulant affect of warfarin was not deemedessential; however, the concurrent use of heparinduring initiation of warfarin treatment may be

more important in canine patient populations withgreater prothrombotic risk.

Although left atrial thrombus does not occurwith enough frequency in dogs with AF to justifyroutine transesophageal echocardiographic exam-ination or routine use of antithrombotic therapy,the association of AF with thrombus and throm-boembolism in some dogs illustrates the impor-tance of thorough transthoracic echocardiographicevaluation of the atria (particularly of the leftauricle) and the need to tailor treatment inaffected dogs to prevent embolization.

Conflict of interest

No conflicts of interest declared.

Supplementary data

Supplementary data related to this article canbe found online at http://dx.doi.org/10.1016/j.jvc.2012.04.003.

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