Hypereosinophilic syndrome with rapid progression of cardiac involvement and early echocardiographic abnormalities

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Fig. 2. Longitudinal TEE view shows left a t r i u m (LA), aortic valve (AOV), and ascending a o r t a (AO). Sessile nonmobile m a s s compatible with clot rises anteriorly.

has been well established.1 Diseases of the a o r t a have figured prominently in this experience. Most important, a t h e r o m a t o u s debris has been closely linked with spontaneous embolic events or events associated with catheterbased interventions or after cardiac surgery. 1-3Protruding, mobile, often frondlike lesions with a n a r r o w base or irregular, immobile lesions with a broad base have been interpreted as atheromatous plaque with or without superimposed thrombus. 3 Pathologic studies of surgical specimens have confirmed variable combinations of plaque fragment and clot. 1 Such lesions have been identifled almost exclusively in the descending aorta, arch, and proximal arch n e a r the junction with the ascending aorta.l-3, 4 Atherosclerotic debris or clot have only r a r e l y been identified in vivo in the ascending a o r t a itself. Using TEE, Horowitz et al. 4 found "mobile, frond-like" projections in the aortic root of only i of 183 p a t i e n t s referred for stroke but in 6 patients at the proximal aortic archascending a o r t a junction. F a r a h and Hawawini 5 detected a mobile m a s s in the ascending aorta of a p a t i e n t with stroke. The m a s s resolved after 6 days of intravenous heparin and was p r e s u m e d to r e p r e s e n t thrombus. Amarenco et al. 3 described six patients with abnormal debris at the junction of the arch and the ascending a o r t a or in the arch itself. None of the debris was a p p a r e n t l y localized to the ascending aorta. In one p a t i e n t a large p r o t r u d i n g mass disappeared and was p r e s u m e d to be thrombus. Two patients with p e r i p h e r a l embolic events and TEEdetected ascending a o r t a thrombi are presented here. In the first, direct histologic verification of thrombus was made. In the second, the histologic identity of the lesion was inferred on the basis of examination of embolic material. Echo a p p e a r a n c e of these lesions was more compatible with mass or clot t h a n with previously described atherosclerotic debris. In case 1, the clot rose from a mild atherosclerotic and myxomatous lesion. No ulceration was described. No evidence of hypercoagulability was initially present. In case 2, volume depletion and metabolic der a n g e m e n t m a y have contributed to hypercoagnlability.

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Although TEE detection of atherosclerotic debris or thrombi in ascending a o r t a is rare, necropsy studies m a y show atherosclerotic changes or ulcerations. 6 Such ulcerations have been linked to stroke, possibly as a result of lesion-related thrombus. These ulcerations occur less commonly in the ascending a o r t a t h a n in the arch, possibly because of different hemodynamic conditions in the nonline a r arch with branch vessel ostia. 1,6 R a r i t y of TEEdetected atherosclerotic debris in the ascending a o r t a compared with debris in the arch or arch-ascending a o r t a junction m a y also be related to this. R a r i t y of both necropsy and TEE detection of lesion-related thrombi m a y be related to the lower frequency of atherosclerotic lesions in the ascending a o r t a and also to fragility of clot adherence to the vessel wall. 1, 6 Embolic events m a y occur as a result of transient, atherosclerotic l e s i o n - r e l a t e d thrombi in the ascending a o r t a t h a t are not subsequently detected. Our findings support the occurrence of ascending a o r t a thrombi and their embolic potential. REFERENCES

1. Kronzon I, Tunick PA. Transesophageal echocardiography as a tool in the evaluation of patients with embolic disorders. Prog Cardiovasc Dis 1993;1:39-60. 2. Tunick PA, Kronzon I. Protruding atherosclerotic plaque in the aortic arch of patients with systemic embolization: a new finding seen by transesophageal echocardiography. AM HEARTJ 1990;120:658-60. 3. Amarenco P, Cohen A, Baudrimont M, Bousser M-G. Transesophageal echocardiographic detection of aortic arch disease in patients with cerebral infarction. Stroke 1992;23:1005-9. 4. Horowitz DR, Tuhrim S, Budd J, Goldman ME. Aortic plaque in patients with brain ischemia: diagnosis by transesophageal echocardiography. Neurology 1992;42:1602-4. 5. Farah MG, Hawawini H. Thrombus in the ascending aorta as a source of cerebral embolism. Chest 1993;104:1604-5. 6. Amarenco P, Duyckaerts C, Tzourio C, Henin D, Bousser M-G, Hauw J-J. The prevalence of ulcerated plaque in the aortic arch in patients with stroke. N Engl J Med 1992;326:221-5.

Hypereosinophilic syndrome with rapid progression of cardiac involvement and early echocardiographic abnormalities David M. Zientek, MD, David L. King, MD, Stephen J. Dewan, MD, Paul H. Harford, MD, Dudley J. Youman, MD, and Timothy R. Hines, MD Austin, Tex.

In 1936 L6ffier first described a form of restrictive cardiomyopathy now recognized as one manifestation ofhyperFrom the Central Texas Heart Institute and Seton Medical Center. Reprint requests: David M. Zientek, MD, Austin Heart, 1301 W. 38th St., #300, Austin, TX 78705. AM HEARTJ 1995;130:1295-8. Copyright © 1995 by Mosby-Year Book, Inc. 0002-8703/95/$5.00 + 0 4/4/67125

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Fig. 1. A, Two-dimensional echocardiogram demonstrates thickening of endocardium of left ventricular apex (arrows) with normal left atrial size. LA, Left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. B, Two-dimensional echocardiogram demonstrates mass of increased echodensity filling left ventricular apex and extending along lateral wall of left ventricle (arrows). Color Doppler demonstrated mitral regurgitation and LA is now enlarged.

eosinophilic syndrome (HES). 1-4 Patients with cardiac involvement of this syndrome typically have a characteristic echocardiographic and pathologic picture. 1, 3-7 We present a patient with hypereosinophilic syndrome that took an unusually rapid course despite only modest elevation in total eosinophil counts and aggressive therapy. As a result of the rapid course of the disease, our patient demonstrated the progression of echocardiographic findings in the disease. This case represents one of the first characterizations of the cardiomyopathy in this syndrome by transesophageal echocardiography. Case history. A 52-year-old white man had a 1-week history of low-grade fevers, night sweats, myalgias, and mild dyspnea. Examination results and chest radiograph were normal. Repeat radiograph 3 weeks later revealed marked cardiomegaly and no pulmonary infiltrates. White blood cell count (WBC) was 10,300 with 4% eosinophils. One week later the blood pressure was 132/82 m m Hg without paradox. He had no fever. Jugular venous pressure was normal, with lung examination demonstrating no rales. Heart sounds were distant, with no murmur or gallop. Echocardiography revealed normal left ventricular function with mild thickening of the apex and a large pericardial effusion (Fig. 1, A). WBC was 9400 with 18.5% eosinophils. Thyroid function tests were normal, and erythrocyte sedimentation rate was 31 mm/hr. Ibuprofen slightly improved symptoms. Repeat echocardiogram 1 week later was unchanged. Two weeks later the patient noted increasing dyspnea and a nonproductive cough. He was hospitalized with a temperature of 101.2 ° F, jugular venous pressure of 8 cm of water, and no rales on lung auscultation. Cardiac examination revealed a soft $4. The WBC was 9700 with 11% eosinophils. New renal insufficiency was accompanied by a creatinine level of 2.0 mg/dl. Echocardiography revealed normal left ventricular function; however, the previous apical thickening had extended

along the posterior wall of the left ventricle, and its echodensity was different from that of the myocardium (Fig. 1, B). Doppler study demonstrated new mitral regurgitation. The pericardial effusion had decreased significantly. Right heart catheterization revealed a right ventricular pressure of 60/0 m m Hg, with a pulmonary artery pressure of 60/24 mm Hg and wedge pressure of 24 m m Hg. Cardiac output was normal. Right ventricular endomyocardial biopsy revealed mild endocardial thickening with occasional hemosiderin-laden macrophages and no increase in eosinophils. Bone marrow biopsy was normocellular, with slight eosinophil hyperplasia. Blood cultures had no growth, stool and sputum specimens demonstrated no parasites, and an HIV test result was negative. A diagnosis of liES was made, and the patient was given high-dose prednisone and interferon. Eosinophil counts decreased to <2% throughout the remainder of the hospital course. Despite therapy, radiograph showed pulmonary infiltrates, and episodes of nonsustained ventricular tachycardia developed. Congestive failure did not improve with aggressive diuresis, and renal function continued to deteriorate. Renal biopsy revealed a focal microthrombus in one glomerular capillary, with no vasculitis. Electron microscopy revealed deposits in the subendothelium of the glomerular capillaries consistent with chronic immune complex deposition. Percutaneous biopsy of the left ventricular mass revealed fibrinous exudate focally infiltrated with macrophages and fibroblasts. Because of refractory pulmonary edema, the patient underwent surgical stripping of the endocardium and mitral valve replacement. Intraoperative transesophageal echocardiography was used to guide the extent of endocardial resection and to determine whether mitral valve repair would be possible or whether valve replacement would be required. End-diastolic frames demonstrated an intracavitary mass to be obliterating the left ventricular apex and extending along

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Fig. 2. A, Transesophageal echocardiogram demonstrates echodense mass obliterating left ventricular apex and extending along septum and lateral wall as far as mitral valve and involving subvalvular apparatus (arrows). LA, Left atrium; LV, left ventricle; RV, right ventricle. B, Transesophageal echocardiogram in immediate postsystolic frame demonstrates opening of anterior mitral leaflet with fixed posterior leaflet (arrows). Also shown is persistence of near obliteration of left ventricular cavity by echodense mass at beginning of diastole. the posterior wall to the mitral annulus (Fig. 2, A). Systolic frames demonstrated no evidence for mitral leaflet prolapse; however, these images demonstrated poor coaptation of the leaflets as a result of the posterior mitral leaflet being fixed by the endocardial mass (Fig. 2, B). No residual effusion was found. The heart was entered via the left atrium, the mitral valve resected, and a 3 to 5 mm-thick tan fibrous mass adherent to the endocardium was resected in multiple fragments. Histologic examination revealed organizing fibrin. The adherent endocardium was thickened and contained hemosiderin, chronic inflammatory cells, and numerous plasma cells. The ventricular cavity was extensively irrigated, and a valve (MedtronicHall, Medtronic, Minneapolis, Minn.) was placed. Postoperatively, oxygenation and hemodynamics iraproved; however, renal function continued to deteriorate, requiring dialysis. Initially, the patient required paralysis and sedation to maintain oxygenation. Anticoagulation was delayed for several days because of postoperative thrombocytopenia. After sedation was withdrawn, the patient remained unresponsive. Electroencephalograms were consistent with anoxic encephalopathy. The patient died 19 days after surgery, 3.5 months from initial examination. At autopsy the heart weighed 670 gm and had concentric hypertrophy. The endocardium was granular in appearance, with some residual fibrin mass along the septum. Microscopy revealed hypertrophy with focal fibrosis of the myocardium, especially of the inner half of the wall, with no eosinophilic infiltrate. The kidneys were mildly enlarged, with dilatation of the proximal convoluted tubules. The brain revealed normal architecture grossly, with widespread anoxic changes. HES has been defined by the presence of a peripheral eosinophilia of at least 1500 eosinophils/mm 3 for at least 6 months or if death occurs before 6 months by signs and symptoms of organ involvement and a lack of evidence for

known causes of eosinophilia. 1-4 Although multiple organ systems may be involved, the most common cause of morbidity and mortality is cardiac involvement with extensive fibrous thickening of the endomyocardium and overlying thrombus. 1-5 Patients may have congestive failure caused by restrictive cardiomyopathy or regurgitant lesions of the atrioventricular valves, and they frequently have multiple emboli from thrombus in the left ventricle. Although our patient had cardiac findings typically associated with HES, his clinical course had many unusual aspects. He had minimal elevations in total WBC with only modest eosinophilia, which varied from 4% to 18.5% before treatment. Historic reviews have found an average survival rate of 9 months; however, the use of corticosteroids, cytotoxic agents, and surgical intervention has significantly improved the prognosis for these patients. 1, 5. s Despite having modest eosinophilia, our patient had rapid progression to death within 3.5 months despite therapy with corticosteroids and normalization of his eosinophil count. It has been postulated that cardiac involvement in HES has several phases, beginning with either acute myocarditis or damage to the endocardium by circulating eosinophil proteins.i, 6 This stage is followed by formation of a mural thrombus, typically at the apex of one or both ventricles and propagating toward the ventricular inflow tracts. Often the subvalvar apparatus is involved, leading to atrioventricular valve incompetence. 1,6, 7 Finally, there is organization and fibrosis of the thrombus, with the typical echocardiographic finding of an echodense mass that obliterates one or both ventricular cavities with preserved systolic function. 6 Our patient illustrates this progression. His initial echocardiogram revealed thickening of the left ventricular apex, with no clearly delineated filling defect. This finding most likely represents the earliest phase of thrombus deposition over the injured endocardium and is among the earliest echocardiographic findings reported in

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HES. I n addition, on initial examination the patient had a large pericardial effusion t h a t rapidly diminished during his course of treatment. Effusions occur in up to one third of patients, but are usually chronic. 3 Our patient progressed to the typical apical obliteration and mitral regurgitation over a period of only 1 month. Transesophageal echocardiography was useful in identifying involvement of the subvalvar apparatus and guiding surgical intervention. Our patient is among the first with HES characterized by this modality. When compared to the transthoracic echocardiograms, these images much more clearly demonstrated that there was no prolapse of the mitral leaflets to explain the mitral regurgitation. Rather, the involvement of the subvalvar apparatus appeared to result in a fixed posterior mitral leaflet and poor coaptation of the leaflets in systole. Finally, in our patient, renal biopsy found a microthrombus in one glomerular capillary with electron microscopy, revealing evidence of chronic i m m u n e complex deposition. It is unclear whether the progressive renal failure was the result of showers of microemboli or a chronic i m m u n e process associated with the hypereosinophilia. The findings of diffuse anoxic encephalopathy in the absence of prolonged hypotension or hypoxia raises the question of possible showers of microemboli after endocardial stripping because anticoagnlation was delayed in our patient. Thus our p a t i e n t demonstrates that the early laboratory and echocardiographic findings of the HES can be subtle and the progression of disease rapid. Even with modest eosinophilia and equivocal echocardiographic findings, a high index of suspicion and rapid institution of therapy, including anticoagnlation, m a y improve the outcome of these patients. In patients requiring surgical intervention, transesophageal echocardiography is particularly helpful. We thank Dr. Joseph Parillo for his assistance during the care of this patient.

REFERENCES

1. FauciAS, HarleyJB, RobertsWC, Ferrans VJ, GarlnickHR, Bjornson BH. The idiopathichypereosinophilicsyndrome:clinical,pathophysiologic, and therapeutic considerations.Ann Intern Med 1982;97:78-92. 2. SchooleyRT, Flaum MA, GarlnickHR, Fauci AS. A clinicopathologic correlation of the idiopathichypereosinophilicsyndrome.II. Clinical manifestations.Blood 1981;58:1021-6. 3. ParilloJE, BorerJS, HenryWL, WolfSM, FauciAS. The cardiovascular manifestations of the hypereosinophilicsyndrome. Am J Med 1979;67:572-82. 4. ChusidMJ, Dale DC, West BC, WolffSM. The hypereosinophilicsyndrome: analysisof fourteen cases with review of the literature. Medicine 1975;54:1-27. 5. Sol]eyGo,MaldonadoJE, GleichGJ, GiulianiER, HoaglandHC, Pierre RV,BrownAL.Endomyocardiopathywitheosinophilia.MayoClinProc 1976;51:697-707. 6. AcquatellaH, SchillerNB. Echocardiographicrecognitionof Chagas' disease and endomyocardialfibrosis.J Am Soc Echo 1988;1:60-8. 7. RodgersJC, IrvineKG, Lerski RA. Echocardiographyin Loeffier'sendocarditis. Br Heart J 1981;46:110-2. 8. BoustanyCW,MurphyGW,HicksGL. Mitralvalvereplacementin idiopathichypereosinophilicsyndrome.AnnThoracSurg1991;51:1007-9.

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Massive pericardiac hematoma with severe constrictive pathophysiologic complications after insertion of an epicardial pacemaker Isidre Vilacosta, MD, a Jorge GSmez, MD, b Jesfis Domlnguez, MD, a Lourdes Domlnguez, MD, a Camino Bafiuelos, MD, a Joaquln FerreirSs, MD, c J u a n Arrazola, MD, c and Luis S ~ c h e z - H a r g u i n d e y , MD a Madrid, Spain

The safety and efficacy of p e r m a n e n t cardiac pacemakers has been well established. However, several u n u s u a l complications can occur. 1, 2 We present a case of massive pericardiac hematoma with symptoms and signs of severe constrictive pericarditis after insertion of a p e r m a n e n t epicardial pacemaker. This report illustrates the value of noninvasive testing in the diagnosis of pericardiac hem a t o m a as the cause of constrictive symptoms. A 64-year-old woman with a mitral valve prosthesis was referred to our institution for evaluation of congestive heart failure and fever. She had been healthy until 14 months before referral, when fatigue, dyspnea on exertion, and peripheral edema had gradually developed. A history of rheumatic fever and heart m u r m u r was elicited, and she was diagnosed as having severe rheumatic mitral stenosis and atrial fibrillation. A percutaneous mitral balloon valvotomy 6 months after the onset of symptoms was unsuccessful. She u n d e r w e n t mitral valve replacement with a Bjork-Shiley prosthesis. The postoperative convalescence was without complications except for a very low ventricular rate, and a p e r m a n e n t transvenous pacemaker was required. Six months after surgery she had fever, rigors, orthopnea, and mild peripheral edema and was transferred to our hospital. An echocardiogram on admission was consistent with prosthetic mitral valve vegetations, and three blood cultures grew Staphylococcus coagulase negative. Therefore, with the clinical diagnosis of prosthetic mitral valve endocarditis, she was sent to surgery for valve replacement. A new Bjork-Shiley prosthesis was placed in the mitra] position, and the transvenous pacemaker was replaced by an epicardial electrode. In the immediate postoperative period, a routine echocardiogram showed a normally functioning prosthetic mitral valve, good left ventricular function, and no pericardial effusion. One week

From the Departments of aCardiologyand CRadiology,Hospital Universitario de San Carlos; and the bDepartment of Radiology, Hospital de la Princesa. Reprint requests: Isidre Vilacosta, MD, Departmentof Cardiology,Hospital Universitariode San Carlos, Serrano 46, 28001 Madrid, Spain. AMHEARTJ 1995;130:1298-300. Copyright © 1995 by Mosby-YearBook, Inc. 0002-8703/95/$5.00 + 0 4/4/67126