An 8-year-old, 4 kg, intact female, domestic shorthaired cat was
referred for tachypnea and pleural effusion. A 24-h Holter recording showed
numerous polymorphic ventricular premature complexes with left and right bundle
branch block morphology. Echocardiographic examination revealed right atrial and
ventricular dilation. The right ventricular free wall was thin and aneurysmal. The
cat died 10 days after initiation of antiarrhythmic therapy. Gross and histopathological
findings were consistent with arrhythmogenic right ventricular cardiomyopathy
(ARVC) associated with severe left ventricular involvement

Basso C

CIARAMELLA, PAOLO

Di Loria A

PIANTEDOSI, DIEGO

English

Archivio della ricerca - Università degli studi di Napoli Federico II

* CorrespondE-mail addr1760-2734/$ -doi:10.1016/j.Journal of Veterinary Cardiology (2009) 11, 41e45www.elsevier.com/locate/jvcArrhythmogenic right ventricular cardiomyopathyassociated with severe left ventricularinvolvement in a catPaolo Ciaramella, DVM a,*, Cristina Basso, MD, PhD b,Antonio Di Loria, DMV, PhD a, Diego Piantedosi, DMV, PhD aa Department of Veterinary Clinical Sciences, Section of Internal Medicine,University of Naples Federico II, Via F. Delpino 1, 80137 Napoli, Italyb Institute of Pathology, University of Padua Medical School, Via A. Gabelli 61, 35121 Padova, ItalyReceived 30 May 2008; received in revised form 19 February 2009; accepted 20 February 2009KEYWORDSFeline;Myocardial disease;ARVC;Left ventricleing author.ess: paociara@unina.itsee front matter ª 200jvc.2009.02.007Abstract An 8-year-old, 4 kg, intact female, domestic shorthaired cat wasreferred for tachypnea and pleural effusion. A 24-h Holter recording showednumerous polymorphic ventricular premature complexes with left and right bundlebranch block morphology. Echocardiographic examination revealed right atrial andventricular dilation. The right ventricular free wall was thin and aneurysmal. Thecat died 10 days after initiation of antiarrhythmic therapy. Gross and histopatholog-ical findings were consistent with arrhythmogenic right ventricular cardiomyopathy(ARVC) associated with severe left ventricular involvement.ª 2009 Elsevier B.V. All rights reserved.An 8-year-old, 4 kg, intact female, domesticshorthaired cat was referred to the VeterinaryTeaching Hospital of Naples University ‘‘FedericoII’’ with a two week history of progressive lethargy,anorexia, and dyspnea. The cat lived indoors, wasregularly vaccinated, and was fed commercialcanned pet food. Treatment initiated by the(P. Ciaramella).9 Elsevier B.V. All rights reserreferring veterinarian included oral furosemide,c6 mg twice daily and oral enrofloxacin,d 20 mgonce daily. This resulted in transient relief ofdyspnea.On physical examination the patient was under-weight, lethargic and moderately (5%) dehydrated.Mucous membranes appeared pale and dry, andcapillary refill time (5 s) was increased. Bothfemoral pulses were palpable. Pulse rate wasc Diuren, Tecknofarma, Turin, Italy.d Baytril, Bayer, Milan, Italy.ved.Figure 1 24-h Holter recording. Note the polymorphicventricular arrhythmias. 25 mm/s.42 P. Ciaramella et al.210 beats/min. Shallow breathing was noted withtachypnea (56 breaths/min) and abdominal effort.Rectal temperature was 38.1 C (100.6 F).Thoracic auscultation revealed muffled lung soundsand heart sounds. Heart murmur was not detected.Systolic and diastolic arterial blood pressuremeasured by an oscillometric methode was withinnormal range (140/100 mmHg). Dilated jugularveins and liver enlargement were detected. Serumbiochemistry abnormalities included increasedblood urea (17.8 mmol/L; normal, 6.5e10.5 mmol/L), creatinine (201 mmol/L; normal, 133e175 mmol/L), and alanine aminotransferase (79 IU/L; normal,15e45 IU/L). Serum total proteins were slightlyreduced (56 g/L; normal, 60e75 g/L). Felineleukemia virus (FeLV) and feline immunodeficiencyvirus (FIV) infections were ruled out by routineantigen serology assay.f Standard 6-lead electro-cardiography (ECG) showed sinus rhythm andnumerous, polymorphic, ventricular prematurecomplexes. A 24-h Holter recording revealedventricular premature complexes with left bundlebranch block (LBBB) morphology (25,920complexes) and right bundle branch block (RBBB)morphology (6480 complexes) (Fig. 1). Ventricularcouplets (4,320) and R-on-T phenomenon (220complexes) were also noted. Average heart rate was213 12 beats/min (median 210, interquartileinterval 201e235). No change in heart rate orseverity of the arrhythmia was observed duringsleep. A right lateral thoracic radiograph revealedpleural effusion. Mild increase in caudal lung lobeopacity was noted and hepatic enlargement waspresent. No abdominal effusion was evident. Thor-acocentesis yielded 120 ml of serous fluid. Cytologywas consistent with modified transudate. B-modeechocardiography showed severe right atrial andright ventricular dilation. The right ventricular wallappeared very thin and hypokinetic. Aneurysmswere detected in apical and subtricuspid regions.Flattening of interventricular septum at end-dias-tole and mild dilation of the pulmonary trunk wereobserved. The left atrium and ventricle appeared tobe unremarkable. M-mode echocardiographyrevealed paradoxic interventricular septal motione MEMOPRINT, Sþ B medVET, Babenhausen, Germany.f Feline SNAP Combo Plus, IDEXX Laboratories, Milan, Italy.which prevented accurate left ventricle measure-ment. The right ventricular chamber was severelydilated (end-diastole, 15.0 mm). Doppler echocar-diography revealed mild tricuspid regurgitation(maximal velocity, 107 cm/s; maximal pressuregradient, 4.54 mmHg) and decreased maximalpulmonary artery velocity (maximal velocity,39.4 cm/s). Based upon physical examination, ECGand 24-h Holter recordings, and echocardiographicfindings, a diagnosis of arrhythmogenic rightventricular cardiomyopathy (ARVC) was made.Initial therapy included administration of furo-semide,c 10 mg subcutaneously every 12 h, ena-lapril,g 1 mg per os every 12 h, and sotalol,h 8 mgper os twice daily. Mild clinical improvement wasobserved during the following four days and theowner continued to treat the pet at home. The catdied suddenly 10 days after initiation of therapy.At post-mortem, gross examination of the heartrevealed severe right ventricular chamber dilationwith infundibular, apical and inferior aneurysms(triangle of dysplasia). At cross section, the rightventricle (RV) free wall was extremely and diffuselythinned (1 mm) and the wall had a ‘‘parchment-like’’ appearance. In the left ventricle (LV) free wallthere were whitish scars in the sub-epicardial layer(Fig. 2). The heart was fixed in 10% phosphate-buffered formalin. Tissue sections were cut 5 mmthick and stained with haematoxylin and eosin andHeidenhain (azan) trichrome stains. They revealedmassive fibrous tissue replacement associated withmild fatty tissue infiltration in the right ventricularfree wall. Similar features were observed on theright side of the interventricular septum. Acircumferential band of replacement-type fibrosiswas also present, confined to the sub-epicardial,outer third of the LV free wall (Fig. 3). This band wasdetected in multiple, serial, cross sections sampledfrom the cardiac base to the mid-portion of the LVchamber. In right ventricular sections patchy,lymphocytic inflammatory infiltrates were presentwith myocyte abnormalities that included dys-metric and dysmorphic nuclei and perinuclear halo(Fig. 4). Focal myocyte apoptotic nuclei were alsoobserved. Collectively, these pathological lesionswere consistent with a diagnosis of ARVC associatedwith severe left ventricular involvement.DiscussionArrhythmogenic right ventricular cardiomyopathyis an uncommon, spontaneous, cardiomyopathywhich has been described in cats, dogs andg Enacard, Merial, Milan, Italy.h Sotalex, Brystol Myers, Rome, Italy.Figure 3 Histology of the right ventricular myocar-dium, antero-lateral free wall. Note the myocardialreplacement by fibrous tissue (blue color) and thepresence of some adipocytes. Trichrome Heidenhainstain; 100.Figure 4 Histology of the right ventricular myocar-dium, antero-lateral free wall. There is waviness andlengthening of myocytes which is suggestive of focalnecrosis (arrowheads). A few round inflammatory cellsare also visible (arrow). Haematoxylineeosin stain;200.Figure 2 (a) Post-mortem transverse cardiac sectionmade at the mid-ventricular level. The right ventricle isgreatly dilated. Note the diffuse thinning of the rightventricular free wall. There are antero-infundibular andinferior aneurysms (arrows). Along the entire circumfer-ence of the left ventricular free wall is evident a whitish,sub-epicardial band (arrowheads); (b) Correspondinghistologic section showing transmural fibro-fatty replace-ment of the right ventricular free wall. A circumferentialband of replacement-type fibrosis is also present and isconfined to the outer layer of the left ventricle andthe right-side of the interventricular septum. LV¼ leftventricle; RV¼ right ventricle.ARVC in a cat 43humans.1e3 It is an unique heart muscle disease,clinically characterized by marked right ventric-ular cavity enlargement with ventricular arrhyth-mias, congestive heart failure and/or suddencardiac death. The remarkable interest in thiscardiomyopathy is associated with difficulty inearly clinical diagnosis, and its propensity to causesudden death in apparently healthy patients.Regarding feline ARVC, the disease was describedfor the first time by Fox et al. in 2000.2 This reportconsisted of a retrospective series of 12 cases offeline ARVC from the USA. In Europe, the incidenceof feline ARVC is unknown and only two cases havebeen reported from the United Kingdom.4Diagnosis of feline ARVC can be challenging. Noage or breed predisposition has been identified.Clinical signs are not distinctive but include dysp-nea/tachypnea, jugular vein distention, abdominaland/or pleural effusion, soft heart murmurs, andarrhythmias. Differential diagnoses include othermyocardial disorders as well as acquired orcongenital diseases affecting the right heart (suchas tricuspid dysplasia and Uhl’s anomaly). Currently,the diagnosis of ARVC is based on the combinationof a family history, the presence of marked rightventricular cavity enlargement, ventricular and/orsupraventricular arrhythmias, and post-mortem44 P. Ciaramella et al.pathologic findings that include right ventriculardilation and fibro-fatty replacement.In the present case the clinical signs wererelated to right sided congestive heart failure,similar to the other clinical reports.2,4 No episodesof syncope were observed. The diagnosis wasbased upon findings from the history, echocardi-ography and radiography suggesting right ventric-ular involvement, and from ECG and 24-h Holterrecordings that revealed extensive ventricularectopy.Arrhythmias are a common finding in felineARVC. In the largest series of reported cases,2recorded arrhythmias included ventricular tachy-cardia in four cats, atrial fibrillation in four cats,supraventricular tachycardia in one cat, andventricular premature complexes in eight cats.First and third degree atrioventricular block werealso recorded.2,4 In the present case the ECG and24-h Holter recording documented a large numberof ventricular arrhythmias. In feline ARVC thefrequency and severity of left ventriculararrhythmia are not well documented. Six of theeight cases reported by Fox et al.2 also includedventricular premature complexes with RBBBmorphology. In the present case the finding ofventricular extrasystoles with RBBB morphologymight be associated with the extensive, sub-epicardial, left ventricular free wall fibrosisdetected in this cat.Arrhythmogenic right ventricular cardiomyop-athy with left ventricular involvement has beendescribed to involve sub-epicardial layers eparticularly the postero-lateral free wall inpeople.1,5 This has been reported in up to 76% ofhuman patients,6 in 48% of boxer dogs,3 and inthe majority of cats reported by Fox et al.2 Morerecently, both clinico-pathologic and magneticresonance investigations showed a similarpattern of left ventricular involvement in ARVCpatients, particularly those linked to desmopla-kin gene mutations.7,8 These findings tend tochallenge the traditional view that left ventric-ular involvement occurs only in late stages ofARVC, and supports the notion of a broader,more inclusive condition that has been termed,‘‘arrhythmogenic cardiomyopathy.’’9Clinical diagnosis of ARVC with left ventricularinvolvement is difficult to ascertain. Left ven-triculography, echocardiography and radionuclideventriculography cannot directly detect thepresence of fibrous and adipose LV tissue.Magnetic resonance imaging and multidetector-row computed tomography methods are consid-ered to be the gold standard for diagnosing leftventricular involvement in human ARVC.10,11These methods are not routinely employed inveterinary cardiology.The echocardiographic findings in this report areconsistent with those reported in other cases offeline ARVC.2,4 Characteristic findings include rightatrial and ventricular dilation, and thin, hypo-kinetic right ventricular wall segments with aneu-rysms, particularly those localized in the apicaland subtricuspid regions. The tricuspid regurgitantjet detected in this cat was mild. This finding isconsistent with the observation of Harvey et al.4In our case, gross and histopathologic lesionswere similar to the hallmark findings described forARVC in humans and animals. Histological exami-nation of the right ventricle showed severeatrophy of the myocardium, which was replaced byfibro-fatty tissue (presumed to represent a repar-ative process), and myocyte death. Myocyte deathwas associated with inflammatory infiltrates(‘‘myocarditis’’). This finding was reported in 75%and 83% of human and feline ARVC cases respec-tively.6,2 Inflammation may be a reactive processfollowing cell death, or alternatively, couldrepresent immune or infectious mechanisms.12Finally, the mild clinical improvement observed inthe present case did not seem to be associatedwith a change in arrhythmia severity. In humanswith ARVC, different antiarrhythmic drugs havebeen employed. The use of sotalol has beenreported to be associated with complete or partialefficacy in 68% of ARVC patients.13ARVC is a recently recognized disorder ofuncertain origin in feline patients, and is charac-terized by fibro-fatty replacement of rightventricular myocardium. Although it more typi-cally involves segmental regions of the rightventricle, the present case illustrates that it canalso involve substantial regions of the left ventricleas well. In the cat reported here, 24-h Holterrecording revealed extensive ventricular arrhyth-mias, which may have contributed to sudden,unexpected death of this patient.AcknowledgmentsThe authors wish to thank Dr. Antonio Calamo andDr. Giuseppe Marzatico for their technicalassistance.References1. Thiene G, Corrado D, Basso C. Arrhythmogenic rightventricular cardiomyopathy/dysplasia. Orphanet J Rare Dis2007;2:45e60.ARVC in a cat 452. Fox PR, Maron BJ, Basso C, Liu S, Thiene G. Spontaneouslyoccurring arrhythmogenic right ventricular cardiomyopathyin the domestic cat. A new animal model similar to thehuman disease. Circulation 2000;102:1863e1870.3. Basso C, Fox PR, Meurs KM, Towbin JA, Spier AW,Calabrese F, Maron BJ, Thiene G. Arrhythmogenic rightventricular cardiomyopathy causing sudden cardiac death inboxer dogs: a new animal model of human disease. Circu-lation 2004;109:1180e1185.4. Harvey AM, Battersby IA, Faena M, Fews PG, Darke G,Ferasin L. Arrhythmogenic right ventricular cardiomyopathyin two cats. J Small Anim Pract 2005;46:151e156.5. Thiene G, Basso C. Arrhythmogenic right ventricular cardio-myopathy: an update. Cardiovasc Pathol 2001;10:109e117.6. Corrado D, Basso C, Thiene G, McKenna WJ, Davies MJ,Fontaliran F, Nava A, Silvestri F, Blomstrom-Lundqvist C,Wlodarska EK, Fontaine G, Camerini F. Spectrum of clini-copathologic manifestations of arrhythmogenic rightventricular cardiomyopathy/dysplasia: a multicenter study.J Am Coll Cardiol 1997;30:1512e1520.7. Bauce B, Basso C, Rampazzo A, Beffagna G, Daliento L,Frigo G, Malacrida S, Settimo L, Danieli G, Thiene G,Nava A. Clinical profile of four families with arrhythmogenicright ventricular cardiomyopathy caused by dominant des-moplakin mutations. Eur Heart J 2005;26:1666e1675.8. Norman M, Simpson M, Mogensen J, Shaw A, Hughes S,Syrris P, Sen-Chowdhry S, Rowland E, Crosby A,McKenna WJ. Novel mutation in desmoplakin causesarrhythmogenic left ventricular cardiomyopathy. Circula-tion 2005;112:636e642.9. Basso C, Corrado D, Marcus F, Nava A, Thiene G. Arrhythmo-genic right ventricular cardiomyopathy. Lancet 2009;373:1289e1300.10. Sen-Chowdhry S, Syrris P, Ward D, Asimaki A, Sevdalis E,McKenna WJ. Clinical and genetic characterization offamilies with arrhythmogenic right ventricular dysplasia/-cardiomyopathy provides novel insights into patterns ofdisease expression. Circulation 2007;115:1710e1720.11. Matsuo S, Sato Y, Nakae I, Masuda D, Yomota M, Ashihara T,Horie M. Left ventricular involvement in arrhythmogenicright ventricular cardiomyopathy demonstrated by multi-detector-row computed tomography. Int J Cardiol 2007;115:129e131.12. Calabrese F, Basso C, Carturan E, Valente M, Thiene G.Arrhythmogenic right ventricular cardiomyopathy/dysplasia:is there a role for viruses? Cardiovasc Pathol 2006;15:11e17.13. Wichter T, Paul M, Eckardt L, Gerdes P, Kirchhof P,Bocker D, Breithardt G. Arrhythmogenic right ventricularcardiomyopathy. Antiarrhythmic drugs, catheter ablation,or ICD? Herz 2005;30:91e101.Available online at www.sciencedirect.com

Arrhythmogenic right ventricular cardiomyopathy associated with severe left ventricular involvement in a cat.

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Arrhythmogenic right ventricular cardiomyopathy associated with severe left ventricular involvement in a cat.

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