Disseminated Coccidioidomycosis With Rapid Progression to

Effusive-Constrictive Pericarditis Ronald Oudiz, MD, Paiboon Mahaisavariya, MD, Shi-Kaung Peng, MD, PhD,

Lisa Shane-Yospur, MD, Craig Smith, MD, Fritz Baumgarmer, MD, and Shelley Shapiro, MD, PhD, Torrance, California

This case reports coccidiomycosis presenting as peri- carditis with tamponade rapidly progressing to effusive-constrictive pericarditis and death over 72 hours. Coccidiomycosis pericarditis is a rapidly pro- gressing disease requiring early and complete peri- cardiectomy to avoid the hemodynamics of constric- tion. We illustrate the use of echocardiography in this

case and demonstrate the histopathology. We review the literature and discuss therapy and management. Coccidiomycosis is often clinically unsuspected and unrecognized by the health care worker unfamiliar with the disease process. (J AM Soc ECHOCARDIOGR 1995;8:947-52.)

n r e r i c a r d i a l effusion can occur as a complication of disseminated coccidioidomycosis. However, a rapid clinical progression to effusive-constrictive pericardi- tis leading to death is rare. We report a case of an otherwise healthy adult young man who had cardiac tamponade reqtfiring pericardiocentesis and died of effusive-constrictive pericarditis caused by dissemi- nated coccidioidomycosis:

CASE REPORT

A 24-year-old Samoan man was seen in the emergency department with a 1-week history of fever, dyspnea on exertion, and a nonproductive cough. He had received a stab wound to the chest requiring chest tube placement 1 year before admission to the hospital but had been symp- tom free until 1 week before admission. He had lived in California most of his life and there was no recent travel history.

Physical examination revealed a well-developed man who was diaphoretic and dyspneic. Blood pressure was 147/75 mm Hg, pulse rate was 122 beats/rain, respira- tory rate was 30/rain, and the temperature was 102.6 ~ F. There was jugular venous distention to the angle of the jaw, and a pulsus paradoxus of approximately 20 mm Hg was obtained. The heart sounds were distant and there was

From the Department of Medicine, Division of Cardiology, St. Johns Cardiovascular Research Center, and the Departments of Pathology and Surgery, Harbor-University of California, Los An- geles, Medical Center. Reprint requests: Shelley M. Shapiro, MD, PhD, Department of Medicine, Division of Cardiology, Harbor-UCLA Medical Cen- ter, 1000 W. Carson St., Torrance, CA 90509. Copyright �9 1995 by the American Society of Echocardiography. 0894-7317/95 $5.00 + 0 27/1/63582

a gallop rhythm. Bibasilar crackles were present in both lung fields.

L a b o r a t o r y

The white blood cell count was 1 2 , 2 0 0 / c m 3 with 75% neutrophils and 18% lymphocytes. Liver func- tion test results were mildly elevated. Twelve-lead electrocardiogram showed sinus tachycardia with nonspecific ST and T wave changes. Chest roent- genogram revealed an enlarged cardiac silhouette and a left lower lobe infiltrate with evidence of pul- monary vascular congestion.

Results of initial echocardiography revealed a large pericardial effusion with evidence of right ventricular diastolic and right atrial systolic collapse (Figure 1). Cardiac chambers were normal in size and function. Small fibrinous strands were noted throughout the effusion.

H o s p i t a l C o u r s e

Initial managcmcnt included administration of intra- venous cefuroxime, which was given for prcsumed bacterial infcction, and the patient was placed in respiratory isolation until tuberculosis could be ruled out. Right-sided heart catheterization was per- formed showing near equalization of the pulmonary artery diastolic, pulmonary capillary wedge, and right atrial pressures (pulmonary artery diastolic pressure = 34 m m Hg, pulmonary capillary wedge pressure = 29 m m Hg, and right atrial pressure = 29 m m Hg) .

Emergent pericardiocentesis was performed, with the removal o f 600 ml hemorrhagic fluid from the

947

lournal of the American Society of Echocardiography 948 Oudiz et al. November-December 1995

Figure 1 Still-frame image of modified apical four-chamber view of heart demonstrates left ventricle (LV) and large pericardial effusion (pcf). Solid arrow points to multiple fibrinous strand seen within effusion. Image was obtained on first hospital day bctbre pericardiocentesis.

pericardial space. A pericardial catheter was left in place for continued drainage. After withdrawal of the initial 600 ml fluid, there was immediate symptom- atic improvement. Intrapericardial pressure dropped from 18 to 6 mm Hg, cardiac output rose from 4.2 to 8.2 L /min , right ventricular end-diastolic pres- sure dropped from 26 to 12 mm Hg, and pulmonary capillary wedge pressure dropped from 26 to 18 mm Hg. Cefuroxime was discontinued, and a new regi- men of antibiotics including erythromycin, isoniazid, rifampin, ethambutol, and pyrazinamide was started. Fluid removal through the pericardial catheter was difficult. Initial results of laboratory examination of the pericardial fluid showed a cell count consistent with an exudative effusion (spun hematocrit level = 23%; white cell count differential included 23% neutrophils, 57% lymphocytes, 16% monocytes, and 4% eosinophils; glucose = 51 mg/d l ; and lactic de- hydrogenase = 843 mU/ml ) . There were no organ- isms seen on Gram stain and no growth was observed in bacterial culture. Smears for acid-fast bacilli were negative.

On the second hospital day, the patient continued to reaccumnlate pericardial fluid rapidly. Repeat echocardiogram show a large, loculated pericardial effusion with thick fibrinous strands (Figure 2). An emergent pericardial window was performed in the operating room with the placement of two large- bore chest tubes into the pericardial space. During surgery, a loculated pericardial effusion was noted and 500 ml bloody fluid was drained. Follow-up echocardiogranl on hospital day 3 revealed a persis-

tent echodense region surrounding thc heart, repre- senting a pericardial effusion with consolidation or clotting within the pericardial space. Only limited drainage from the chest tubes was noted. The patient's right-sided heart pressures had risen modestly; however, the hcmodynamics were not consistent with constrictive pericarditis.

The patient was scheduled for urgent, complete pericardiectomy; however, he suddenly became un- responsive and asystolic approximately 2 hours be- fore surgery. After aggressive attempts at resuscita- tion, the thorax was opened acutely at the patient's bedside and an estimated 400 to 600 ml hemor- rhagic fluid including blood clots and fibrinous ma- terial was evacuated from the pericardial space. Open cardiac pacing and heart massage, however, failed to resuscitate the patient and he died.

Pathology An autopsy was performed, Gross examination re- vcaled no skin lesions or gross dcformities. On open- ing the thorax, the pericardium was found firmly adherent to the heart, parietal pleura of both lungs, and the diaphragm (Figure 3). The pericardium was markedly thickened and hemorrhagic, admixed with yellow-white exudates and firm, fibrous tissue on the surface. In addition, bilateral pleural effusions were noted. Cardiomegaly along with biventricular dila- tion and left ventricular hypertrophy were noted. The lungs had multiple small, tan-white nodules on the pleura] surfaces, and the left lower lobe contained an area of nodular consolidation measuring 4 c m x

Journal of the American Society of Echocardiography Volume 8 Number 6 O u d i z et al. 9 4 9

Figure 2 Still-frame image of modified ai0ical four-chamber view demonstrates reaccumulated pericardial effusion (peJ) with increased strands and loculations demonstrated by solid arrow. Pleural effusion lateral to pericardial effusion can also be seen. (LV, Left ventricle.)

Figure 3 Gross photograph of heart and pericardium. Marked thickening of pericardium can be seen. Also seen are fibrous adhesions and exudates and hemorrhage on visceral surface of pericardium.

4 cm. Several matted paraaortic and mediastinal nodes were found. The liver was passively congested and both the liver and spleen had nodules similar to those seen on the lungs.

Microscopic examination was remarkable for multiple caseous and epithelioid granulomata with multinucleated giant cells found in the lymph nodes, pericardium, lungs, liver, and spleen (Figure 4). Pe-

riodic acid-Schiff and methenamine silver stains o f the paraaortic and mediastinal lymph nodes revealed the presence of fungal spores, which varied from 10 to 50 ~tm in diameter and were located within the granulomata and multinucleated giant cells. The spores were spherical and thick walled, consistent with Coccidioides immit is (Figure 5). There was no evidence of myocarditis, and no organisms were

Journal of the American Society of Echocardiography 950 Oudiz e t ;ti. November-December 1995

Figure 4 Section of paraaortic lymph node. Caseous and epithelioid granulomata are seen. Note Langhans' giant cell (arrow) within granuloma. (Hematoxylin and eosin stain; original magnification x 100.)

Figure 5 Section of paraaortic lymph node. Presence of fungal spores with variable size (arrow) can be seen in caseous granuloma. Note thick wall of each spore. (Methenamine silver stain; original magnification x 200.)

Journal of the American Society of Echocardiography Volume 8 Number 6 Oudiz et al. 9 5 1

found in the other organs mentioned above. The liver parenchyma revealed passive congestion but was otherwise normal.

DISCUSSION

Coccidioidomycosis, a fungal disease endemic to the desert Southwest of the United States, 1 is caused by (2. immi t i s . It is a dimorphic fungus that exists in the soil as an arthrospore and in human tissue as a spher- ule with endospores. Sporadic cases of coccidioido- mycosis are relatively rare in other parts of the United States; however, there has been a tenfold increase in the number of cases of coccidioidomyco- sis reported in California since 1992. 2

Infection is through inhalation, and person-to- person traalsmission has not been documented. It causes a wide spectrum of illnesses, ranging from mild, self-limited, and clinically unrecognized infec- tion to widely disseminated and potentially life- threatening disease. 3 Several patient groups are at increased risk for the development of severe and disseminated forms of coccidioidomycosis. 1 At?ican- Americans, Latinos, and Filipinos have higher risk as do immunocompromised patients, including those with human immunodeficiency virus infection and women in the late stages of pregnancy. Patients with type B or AB blood are also at increased risk.

A review of 50 autopsy cases o f disseminated coc- cidioidomycosi s4 showed that the myocardium was the eleventh most frequently involved organ, and the pericardium was the sixteenth, with lungs and skin being the most common. Pericarditis was found in seven of the 50 cases and appeared to have resulted from the eruption of a superficial granulomatous

l e s i on located in or just beneath the epicardium. 5 Despite the frequency of autopsy reports of coccid- ioidomycosis, reports of clinical cardiac involvement are relatively infrequent, 6"r with rare reports of peri- cardial involvement2 "s'7 H

The treatment of pericarditis caused by coccidio- idomycosis is difficult and rarely successful even if diagnosed correctly. Schwartz et al.s reported a case of recurrent cardiac tamponade despite appropriate antifungal therapy. Creation of a pericardial window failed to improve the recurrent symptomatic tampon- ade. Effusive-constrictive pericarditis documented by cardiac catheterization developed during 1 week. A total pericardiectomy was performed, after which the

patient rccovcrcd but was not discharged until after 1 month of continued antifungal therapy. Unfortu- nately, coccidioidomycosis is often clinica/ly unsus- pccted and unrecognized by the health-care worker unfamiliar with the disease process.

Our patient had lived in California most of his life. He had obvious evidence of pericardial tamponadc on physical examination; however, he had no cuta- neous manifestations or laboratory findings specific for coccidioidomycosis, nor had he lived in an en- dcmic area.

The literature is limited in identifying the out- comes for patients with cardiac involvement of coccidioidomycosis; however, the echocardiographic appearance of the patient's pericardial effusion pro- vided clues to the underlying process leading to this patient's rapid decompensation. Dense loculations as sccn in this patient shortly after initial removal of pericardial fluid suggested a rapidly progressive effusive-constrictive pericarditis. Echocardiography and right-sided heart catheterization were able to demonstrate clearly the failure o f both pericardiocen- tesis and the subxiphoid pericardiotomy in the acute management o f our patient. Given the rapid progres- sion of the disease, we suggest that the initial proce- dure in cases o f documented pericardial &fusion and tamponade caused by coccidioidomycosis should be pericardioccntcsis in addition to appropriate intrave- nous antifungal therapy followed by completec pericardiectomy to treat the combined effusive- constructive picture that developed. Furthermore, in patients with the echocardiographic developments of consolidation of the pericardial space and a pericar- dial peal, repeat pericardiocentesis is futile and peri- cardiectomy is urgent.

REFERENCES

1. Ample NM, Wiedcn MA, Galgiani JN. Coccidioidomycosis: clinical update. Rev Infect Dis 1989;11:897-911.

2. Coccidioidomycosis-Unitcd States, 1991-1992. MMWR Morb Mortal Wkly Rep 1993;42:21-4.

3. Pappagianis D. Coccidiomycosis. Semin Dermatol 1993;12: 301--9.

4. Forbus WD, Besterbreurtje AM. Coccidioidomycosis: a study of 95 cases of the disseminated type with special reference to the pathogenesis of the disease. Mil Surgeon 1946;99:653- 719.

5. Schwartz EL, Waldmann EB, Payne RM, Golfarb D, Kinard SA, Dietrich EB. Coccidioidal pericarditis. Chest 1976; 70:670-2.

6. Reingold IM. Myocardial lesions in disseminated coccidio- idomycosis. Am J Clin Pathol 1950;20:1044-9.

Journal of the American Society of Echocardiography Dobberfin, Warnes, and Seward November-December 1995

7. Chapman MG, ICaplan L. Cardiac involvement in coccidio- idomycosis. Am J Med 1957;23:87-98.

8. Larson R, Scherb R. Coccidiodal pericarditis. Circulation 1953;7:211-7.

9. Bayer AS, Yoshikawa TT, Galpin JE, Guze LB. Unusual syndromes ofcoccidioidomycosis: diagnostic and therapeutic

considerations: a report of 10 cases and review of the English literature. Medicine 1976;55:131-52.

10. Tudbury PA. The electrocardiogram in primary coccidioido- mycosis. Cal Med 1955;83:89-90.

11. Chowdhury JK, Habibzadeh MA. Disseminated coccidioido- mycosis with pericardiris. Chest 1977;71:533-5.

Cor Triatriatum Dexter in an Adult Diagnosed by Transesophageal Echocardiography: A

Case Report Alexander Dobbertin, MD,* Carole A. Warnes, MD, MRCP, and

James B. Seward, MD, FACC, Rochesteg Minnesota

Cor triatriatum dexter is a rare congenital heart mal- formation in which a persistent right sinus venosus valve divides the right atrium into two chambers. Be- fore echocardiography, this anomaly has been rarely diagnosed before surgery or death. This is a case o f co t triatriatum dexter in an adult with lifelong exertional cyanosis and dyspnea. A definitive diagnosis o f cor

C o r triatriatum dexter is a rare congenital hear t defect in which a membrane divides the r ight atrium into two chambers ) The membrane represents a persistence o f the r ight valve o f the sinus venosus (RSV). I t can begin in several ways, 2,a such as a simple muscle bar, fenestrated or nonfenestrated membrane , or Chiafi 's network.

A remnant r ight embryonic sinus venosus valve (depending on the stage o f the embryogenesis 4) is no t u n c o m m o n but rarely causes clinical manifesta- tions. 2 The hemodynamic effects o f the membrane and c o m m o n l y associated fight-sided heart abnor- malities (atrial septal defect, pu lmonary atresia, tri- cuspid atresia, and hypoplastic f ight ventricle 4's) de- termine the symptoms at bir th or later in life) "s'6 The an temor tem diagnosis can be difficult and the pres-

From the Division of Cardiovascular Diseases and Internal Medi- cine, Mayo Clinic and Mayo Foundation. Reprint requests: James B. Seward, MD, FACC, 200 First St. S.W., Rochester, MN 55905. *Current address: University Clinic Essen, Division of Internal Medicine, Iffufelandstrasse 55, D-45122 Essen, Germany. Copyright �9 1995 by the American Society of Echocardiography. 0894-7317/95 $5.00 + 0 27/4/65450

triatriatum dexter with associated heart defects was best made by transesophageal echocardiography at 47 years o f age. Subsequent surgical intervention con- firmed all o f the echocardiographic findings and suc- cessful correction o f the defects was performed. (J AM SOC ECHOCARDIOGR 1995;8:952-7.)

ence o f a significant membrane is often found only at autopsy. 7 Current ly the diagnosis o f cor triatriatum dexter is best established by two-dimensional trans- thoracic echocardiography (TTE) 7-~~ or transesoph- ageal echocardiography ( T E E ) ? ~

In this case repor t we describe the clinical history and management o f a patient with cor triatriatum dexter f rom birth to surgical correct ion at age o f 47 years. The preoperative diagnosis was suggested by two-dimensional T T E and then made definitively by TEE.

CASE REPORT

A 47-year-old man was referred to the Mayo Clinic for evaluation of right-sided heart failure, atrial arrhythmia, and the questionable significance of a right atrial mem- brane suggested by TTE. The patient was born at term in 1946 as a "blue baby" after an unremarkable pregnancy. The cyanosis gradually disappeared after the fourth month of life. However, digital clubbing and dusky nail beds persisted. During childhood, he was found to be both mentally and physically retarded. A decreased exercise tol- erance (exertional fatigue and cyanosis) and the chronic clubbing of fingers and toes prompted a pediatric cardiol- ogy examination at age 15 years. On an otherwise unre- markable physical examination, a soft late systolic murmur in the pulmonic area and a variably split $2 with accentu-

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