Regressive Aortic Valve and InfundibularTumors During Idiopathic Hypereosinophilic

SyndromeClaire Dauphin, MD, Pascal Motreff, MD, Marc Ruivard, MD, Virginie Rieu, MD,

Jean-Jacques Cloix, MD, Dominique Lamaison, MD, Jean Cassagnes, MD, and

Jean-René Lusson, MD, Clermont-Ferrand, France

Fibroblastic endocarditis is a classic complica-tion of prolonged hypereosinophilic syndrome,whatever the cause. In France, it is most fre-quently encountered in cases of idiopathic hy-pereosinophilic syndrome. It commonly involvesthe apex of the ventricles, with a clinical picture ofrestrictive cardiomyopathy of unfavorable prog-nosis, and the auriculoventricular valves. We re-port the case of a 77-year-old man in whomatypical cardiac involvement disclosed idiopathichypereosinophilic syndrome. In addition to theusual features of obliteration of the apex and

restrictive cardiomyopathy, echocardiographic

doi:10.1016/j.echo.2004.12.026

e8

examination showed severe left ventricular dys-function and intracardiac tumors, one of whichwas unusually localized to an aortic valve. Treat-ment, which comprised strict control of the eosin-ophilic process, standard treatment for cardiacfailure, and anticoagulation therapy, producedrapid and long-lasting improvement of his clinicalstatus and left systolic and diastolic ventricularfunction, and on echocardiography the intracar-diac tumors had totally disappeared. The patientsuddenly died of septic shock 16 months after firstbeing seen. (J Am Soc Echocardiogr 2005;18:e8-11.)

CASE REPORT

A 77-year-old man was admitted to hospital for investi-gation of generalized heart failure. He had no history ofsurgical procedure. The signs of heart failure had ap-peared gradually over the 3 months before admission,when he presented with impaired general health, asthe-nia, and loss of appetite. Routine examination showed asystolic murmur of mitral regurgitation 2/6. Heart soundswere rapid with gallop rhythm. Painful hepatomegaly andedema of the lower limbs were evocative of right ventric-ular failure. Pulmonary examination was normal. Bloodpressure was 110/70 mm Hg. On electrocardiography therhythm was sinusal (100/min) with incomplete rightbundle-branch block, left axis. Thoracic radiographic pic-ture showed moderate cardiomegaly and small left pleuraleffusion. Laboratory examination showed hypereosino-philia (4000/mm3).

From the Service de cardiologie Professeur Cassagnes, HôpitalGabriel Montpied; and Fédération de Médecine Interne–Maladiesinfectieuses et tropicales–hématologie clinique adulte, Hotel Dieu(M.R., V.R.).Reprint requests: Claire Dauphin, MD, Service de cardiologie PrCassagnes, Hopital Gabriel Montpied, 58 Rue Montalembert,63003 Clermont-Ferrand CEDEX 1, France (E-mail: cdauphin@chu-clermontferrand.fr).0894-7317/$30.00Copyright 2005 by the American Society of Echocardiography.

On transthoracic echocardiography, the left ventriclewas of normal size (telediastolic diameter: 53 mm) withgeneralized, severely impaired kinetics (9% shorteningfraction). Obliteration of the two ventricle apices, typicalof fibroblastic endocarditis, was also observed (Figure 1).On ultrasound, the mitral valve had normal structure witha moderate, functional central leakage. Mitral inflow wasrestrictive (deceleration time: 115 milliseconds) (Figure 2).Right ventricular pressure was estimated to be 50 mm Hg.The inferior vena cava was dilated. The pericardium wasnormal.

A bulky right intraventricular mass was visualized at-tached to the posterior innfundibulum. It was multilobarwith mobile elements and overlapped the pulmonaryvalve during systole, causing color Doppler aliasing withunremarkable gradient, and moderate pulmonary failure.Transesophageal ultrasound yielded no further informa-tion concerning the mass but showed infiltration of thetricuspid pillars and disclosed a round, sessile, well-defined tumor, 8 mm in diameter, attached to the aorticface of the right cusp (Figure 3). The mass was not causingvalvular dysfunction.

Thromboembolism and infectious endocarditis wereruled out by thoracic angioscan and blood culture results.Causative investigations for hypereosinophilic syndrome(HES) were negative, and so a diagnosis of idiopathic HESwas established. Symptomatic treatment of the cardiacfailure, with diuretics and angiotension-converting en-zyme inhibitors, was initiated, associated with corticoste-roid therapy (prednisolone 1 mg/kg) and anticoagulant

agents.

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COURSE

Swift clinical improvement allowed the diuretics tobe discontinued after 1 week of treatment. Trans-thoracic and transesophageal echocardiographic ex-aminations performed from the third week of treat-ment and thereafter showed clear improvement inleft ventricular function (29% shortening fraction),persistence of obliteration of the two apexes withleft predominance, and moderate mitral leaking.Mitral inflow was improved (pseudonormal diastolicfilling, deceleration time: 210 milliseconds) (Figure 2).Pulmonary pressure had returned to normal and thepericardium was dry. There was no longer evidenceof the aortic and infundibular tumors but grade 1aortic leaking was apparent (Figure 3). At 16 monthsafter diagnosis, when the patient’s hemodynamicstatus and echocardiographic findings were stable,he suddenly died of septic shock, as the result ofurinary sepsis to which long-term corticosteroidtherapy had undoubtedly contributed.

DISCUSSION

Idiopathic HES is characterized by a marked, sus-tained (� 6 months), unexplained increase in eosin-ophilic polynuclears (�1500/L) accompanied byorgan involvement.1 Cardiac involvement is classi-cally described in the form of endomyocardial fibro-sis. It is secondary to direct toxicity of the eosino-phils, as confirmed by experimental studies,2 andoccurs during prolonged HES, irrespective of thecause. Lesions develop in 3 stages3,4: early, necrotic“myocarditis” phase; thrombotic phase; and a finalstage resulting in endocardial fibrosis. These abnor-malities are most frequently located in the apices of

Figure 1 Transthoracic echocardiography n°1: apical4-chamber view. Obliteration of two apices.

the ventricles but may also involve the inflow tract,

pillars, and chordae of the atrioventricular valvesand impede their normal function.5-7

Prognosis for this cardiopathy is unfavorable, withdeath occurring in 30% to 50% of cases in the first 2years after diagnosis, most commonly as a result ofcongestive heart failure.8 Management consists incausative treatment of the HES, anticoagulation, andsymptomatic treatment of the cardiac failure.5,6 Inthe late stages, endocardial resection may be per-formed if medical treatment is insufficient.9

A team from the Mayo Clinic, Rochester, Minn,7

made a retrospective study of the medical records of94 patients with HES including 51 with idiopathicHES. In 29 of the latter, echocardiographic exami-nation typically showed endomyocardial fibrosis:obliteration of the ventricular apices, intracavitarythrombus, endocardial thickening, or involvementof the posterior mitral leaflet. Progression varied

Figure 2 Mitral inflow (Pulsed Doppler: Doppler windowwas located at top of mitral valve.) Transthoracic echocar-diography (TTE) n°1: restrictive diastolic transmitral fill-ing. Deceleration time (DCT) � 135 milliseconds. Down:TTE at 6 months: mitral inflow. DCT � 210 milliseconds.

widely. Two patients had regression of intracavitary

Journal of the American Society of Echocardiographye10 Dauphin et al July 2005

thrombotic mass with mobile elements after treat-ment.

There have been reports of HES presenting atyp-ically as myocardial infarction,10,11 myocarditis,12,13

dilated cardiomyopathy,14 giant ventricular throm-bi,15 or in an unusually localized form.16

Cardiac involvement can occur rapidly both inpatients with long-standing HES16 and in those withrecent onset.17

Observations of postoperative progress after mi-tral valve replacement suggest that bioprosthesesshould be used because of the high susceptibilitytoward thrombus formation with mechanicalvalves.16,18

Hendren et al16 reported the case of a 36-year-oldman with HES diagnosed 5 years previously who hadaortic stenosis and, 3 months later, mitral stenosisleading to pulmonary edema. Both aortic and mitralvalves were replaced by St Jude prostheses. Atoperation, the patient’s aortic cusps were describedas being deeply embedded in a thick, cheesy mate-rial. Histologic examination showed the material tobe a mixture of fibrin, fibroblasts, and eosinophils.Three days postoperatively, the patient underwentfurther operation for acute prosthetic valve stenosis:the hinges were encased with the same materialfound at the first operation. The mechanical valveswere replaced by Carpentier-Edwards bioprosthe-ses. Two months later obstruction of the aortic valveled to renewed heart failure. Chemotherapy wasintensified and his symptoms improved.

To our knowledge, our observation is only thesecond reported case of aortic valve involvement,with the semilunar valves being classically unaf-fected. It was difficult to determine the nature of theinvolvement because the localization was unusual

Figure 3 Up left and down left: transesophageal echocar-diography (TEE) n°1: round tumor of aortic surface ofright cusp. Up right and down right: TEE n°2 at 3 weeks:disappearance of aortic tumor.

for a thrombus or vegetation (aortic surface). The

diagnosis of a small papilloma-type tumor was dis-counted when regression was achieved by cortico-steroid therapy and anticoagulant agents.

The absence of valvular lesion and improvementon treatment suggested the presence of inflamma-tory and/or thrombotic deposits. Valve involvementof this kind was reported in a child in whom strandsattached to the anterior leaflet of the mitral valveresolved after anticoagulant treatment.11 A compar-ison of these findings with those of the patientoperated on in the report by Hendren et al16 and theabnormalities observed in patients undergoing earlyrepeated operation for prosthetic valve thrombo-sis18 lends weight to this explanation. The othersuggestion is that patients with HES should first betreated medically, because the lesions can regress ona medical regimen and because postoperativeprogress can be complicated.16 The infundibularmass, which was of the same echogenicity as that ofthe aortic valve, also regressed after treatment andwas very likely of the same nature. The otherfeatures of our observation were those classicallyfound elsewhere.

Our patient made rapid progress. One year on, itwas hoped that his stable cardiac status would bemaintained. However, mild corticosteroid therapyhad to be continued to keep the eosinophilia understrict control, and was very likely the cause of theurinary infection complication that led to his death.

Conclusion

This observation of unusual cardiac involvementsecondary to idiopathic HES is a good illustration ofmany features of the syndrome. It shows that thetoxicity of the eosinophils can involve any of thecardiac segments or valves. It also shows that anti-coagulation agents and normalization of the eosino-phil count can achieve regression of the lesionscaused by toxicity provided they are diagnosedbefore the fibrosis stage. These findings argue infavor of early, regular, systematic screening forcardiac localization once HES has been disclosed, allthe more because cardiac involvement can occurrapidly and be dangerous and lead, for example, toheart failure or complications caused by embolism.

Owing to the high incidence of obstructive throm-bosis, valve replacement in this category of patientsis often accompanied by postoperative complica-tions and so first-line treatment should be a medicalregimen and strict control of the eosinophilic pro-cess. If there is no alternative to valve replacement,the use of a bioprosthesis is recommended, but onlyafter attempts have been made to bring the hypere-osinophilia under control.

REFERENCES

1. Weller PF, Bubley GJ. The idiopathic hypereosinophilic syn-

drome. Blood 1994;83:2759-79.

Journal of the American Society of EchocardiographyVolume 18 Number 7 Dauphin et al e11

2. Schaffer SW, Dimayuga ER, Kayes SG. Development andcharacterization of a model of eosinophil-mediated cardiomy-opathy in rats infected with Toxocara canis. Am J Physiol1992;262:H1428-34.

3. Olsen EG, Spry CJ. Relation between eosinophilia and endo-myocardial disease. Prog Cardiovasc Dis 1985;27:241-54.

4. Prunier F, Delepine S, Victor J, De Gentile L, Moreau C,Laporte J, et al. Endocardite fibroblastique de Löffler: a pro-pos d’un cas compliquant une toxocarose. Arch Mal CoeurVaiss 2001;94:226-30.

5. Cabane J. Syndrome hyperéosinophilique. In: Cohen A, Bel-matoug N, editors. Coeur et médecine interne. Paris: Estem;2002. p. 1623-7.

6. Wynne J, Braunwald E. The cardiomyopathies and myocarditis;toxic, chemical, and physical damage of the heart. In: BraunwaldE, editor. Heart disease–a textbook of cardiovascular medicine.4th ed. Philadelphia: WB Saunders Co; 1992. p. 1394-450.

7. Ommen SR, Seward JB, Tajik AJ. Clinical and echocardio-graphic features of hypereosinophilic syndromes. Am J Car-diol 2000;86:110-3.

8. Felice PV, Sawiski J, Anto J. Endomyocardial disease andeosinophilia. Angiology 1993;44:869-74.

9. Dubost C, Chapelon C, Deloche A, Piette JC, Chauvaud S,Fabiani JN, et al. Chirurgie de la fibrose endomyocardique: apropos de 32 cas. Arch Mal Coeur Vaiss 1990;83:481-6.

10. Mor A, Segev A, Hershkovits R, Lew S, Mekori Y. Hypereosi-nophilic syndrome presenting as acute myocardial infarction.

Allergy 2000;55:899-900.

11. Eapen RS, Lemler MS, Ramaciotti C. Serial echocardio-graphic changes in a child with hypereosinophilia syndrome.Pediatr Cardiol 2001;22:426.

12. Debonne JM, Touze JE, Mouly A, Scheiner C, Blin D, Van deWalle JP , et al. La myocardite aigue éosinophilique: une entitéoriginale au sein des complications du syndrome hyperéosi-nophilique. Ann Med Interne (Paris) 1991;142:625-7.

13. Fourcade L, Heno P, Paule P, Braem L, Quilici J, Bonnet D,et al. Myocardite aigüe et pneumopathie à éosinophiles: évo-lution favorable après traitement médical et suivi à long terme;a propos d’un cas. Arch Mal Coeur Vaiss 2004;97:61-6.

14. De Pace NL, Nestico PF, Morganroth J, Ross J, Fox R, KotlerMN, et al. Dilated cardiomyopathy in the idiopathic hypere-osinophilic syndrome. Am J Cardiol 1983;52:1359-60.

15. Naito H, Nakatsuka M, Yuki K. Giant left ventricular thrombiin the hypereosinophilic syndrome: report of two cases. J Car-diogr 1986;16:475-88.

16. Hendren WG, Jones EL, Smith MD. Aortic and mitral valvereplacement in idiopathic hypereosinophilic syndrome. AnnThorac Surg 1988;46:570-1.

17. Cathebras P, Bouchou K, Bouvet L, Mahul P, Rousset H.Complications cardiaques et neurologiques fulminantes aucours d’un syndrome hyperéosinophilique. Presse Med 1993;22:1745-6.

18. Watanabe K, Tournilhac O, Camillieri L. Recurrent thrombo-sis of prosthetic mitral valve in idiopathic hypereosinophilic

syndrome. J Heart Valve Dis 2002;11:447-9.