Asian Cardiovasc Thorac Ann 2004;12:95-98
© 2004 Asia Publishing EXchange Ltd
Fungal Endocarditis: An Autopsy Study
Sundaram Challa, MD,
Aruna Kumari Prayaga, MD,
Laxmi Vemu, MD,
Jaishankar Sadasivan, MD,
Murali Krishna Murthy Jagarlapudi, MD,
Raghunadharao Digumarti, MD,
Rajagopal Prabhala, MS
Nizam’s Institute of Medical Sciences, Hyderabad, India Institute of Neurological Sciences Care Hospital, Hyderabad, India
For reprint information contact: Sundaram Challa, MD Tel: 91 40 2332 0332 Fax: 91 40 2331 0076 Email: challa_sundaram{at}yahoo.com Nizam’s Institute of Medical Sciences, Panjagutta, Hyderabad 500 082, Andhra Pradesh, India.
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ABSTRACT
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Between 1990 and 2002, 237 hearts were examined at autopsy, including 16 with infective endocarditis; 6 showed fungal endocarditis. The preceding pathology was chronic rheumatic heart disease in 2 patients, one of whom had undergone double valve replacement, 2 patients had been treated for acute lymphoblastic leukemia, and one had protein-energy malnutrition. The underlying cause was unknown in one case. The organisms isolated were Aspergillus in 3 patients, Zygomycota in 1, Candida in 1, and both Candida tropicalis and Aspergillus in 1 patient. Immunosuppressed states are a cause of fungal endocarditis in India, although chronic rheumatic heart disease is the preceding pathology in the majority of patients.
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INTRODUCTION
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Fungal endocarditis is an uncommon entity but it is being diagnosed more frequently with the increasing role of surgery and use of prosthetic valves, as well as the growing number of immunosuppressed individuals. A rheumatic valvular lesion is the major preceding pathology for infective endocarditis (IE) in India.1 However, the pattern and spectrum of IE is changing. We report 6 cases of fungal endocarditis diagnosed at autopsy in a University Hospital in South India.
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METHODS
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All autopsies performed between 1990 and 2002 were reviewed, and cases diagnosed as fungal endocarditis were studied. The age, sex, preceding cardiac pathology, and immunological status of the patient were noted along with the clinical, echocardiographic, and autopsy findings. The antemortem and postmortem blood culture reports were checked.
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RESULTS
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During the study period, 317 autopsies were conducted and 237 hearts were examined. There were 20 cases of congenital heart disease and 21 of rheumatic heart disease with valvular involvement. Infective endocarditis was observed in 16 cases (6.75% of all hearts) including 6 of fungal etiology. In these 6 cases, 4 of the patients were male and 2 were female, with ages ranging from 5 to 30 years. The preceding pathology included chronic rheumatic heart disease with valvular involvement in 2 patients, one of whom had undergone double valve replacement and subsequently developed prosthetic valve endocarditis. Four others has native valve endocarditis, 2 of whom had been treated for acute lymphoblastic leukemia, 1 had protein-energy malnutrition, and the etiology was unknown in 1 patient. The presenting features are listed in Table 1
. The patient (No. 6) with unknown etiology presented with jaundice, fever and a urinary tract infection, and subsequently developed neurological manifestations. Blood and urine culture grew Candida tropicalis. Endocarditis was not suspected clinically and two-dimensional echocardiography did not show any vegetation antemortem. Echocardiography revealed vegetations or thrombi in the other 5 patients (Figures 1 & 2). The autopsies showed infarct or abscess in the lungs, spleens, and kidneys, as well as hemorrhage, infarct, or abscess in the brain. Myocardial granulomas were seen in 3 cases, in addition to endocarditis; 1 with Candida and 2 with Aspergillus (Figure 3).
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Figure 3. Photomicrograph showing myocardial granuloma with giant cells. Hematoxylin stain, original magnification x40.
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Histology of the vegetations or thrombi showed septate hyphae with acute-angle branching consistent with Aspergillus in 4 patients (Figure 4), broad aseptate hyphae with right-angle branching consistent with Zygomycota in 1, and the thin filaments and pseudohyphae of Candida in 1 patient. Culture from the vegetations at autopsy was positive in 4 cases and sterile in 2. Blood cultures antemortem were positive for Aspergillus in 1 patient and for Candida in 2, but they were negative for fungi in the other 3. Death was due to neurological involvement in 2 patients, and to fungemia in 4.
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Figure 4. Photomicrograph showing branching septate hyphae of Aspergillus species. Silver methenamine stain, original magnification x40.
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DISCUSSION
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There has been a decline in the incidence and a change in the spectrum of IE in the West due to the reduced incidence of rheumatic heart disease, early detection and surgical correction of congenital and acquired valvular lesions, and prophylactic antibiotic therapy.2,3 However, the spectrum of IE seen in India is quite different with rheumatic heart disease (42%) being the most frequent underlying condition, followed by congenital heart disease (33%), and native valve endocarditis (9%).1 Fungal endocarditis constitutes 1.3% to 6% of IE in the West.4,5 Culture-negative endocarditis is more common in India, varying from 47% to 54.5% in clinical series. Fungal endocarditis is reported to constitute only 1.1% to 2.7% of IE in India.1,6,7 There are very few autopsy studies of IE available from India.8–13 Although rheumatic valvular disease is the leading cause of underlying cardiac lesions in IE in clinical studies, immunosuppressed states and cardiac surgery have been demonstrated in this study as preceding pathology for fungal endocarditis.
Patients who have undergone cardiac surgery are at increased risk of fungal endocarditis.14 In a recent review of fungal endocarditis by Pierrotti and Baddour,15 the predisposing factors were identified as underlying cardiac abnormalities (47.3%), prosthetic valves (44.6%), central venous catheters (30.4%), and use of injected drugs (4.1%). Infection in a prosthetic valve may result from a paravalvular leak or other factors such as cloth wear, turbulence, stasis, or platelet aggregation forming thrombi that act as a nidus for infection.14 There has been a marked increase in the number of immunosuppressed patients in the last two decades because of the increasing number of patients with acquired immunodeficiency syndrome, organ transplant recipients, and those receiving aggressive therapy for hematologic and solid malignancies.16 Although IE is not a frequent complication in patients with depressed immunity, despite bacteremia and fungemia, infections of the heart are increasing.14,16–18 In our cases of acute lymphoblastic leukemia on treatment, there were large masses attached to the atrium which showed Aspergillus on histology and culture. There was no myocardial or pericardial involvement. Malnutrition, seen in one of our patients, is known to result in an immunosuppressed state, although fungal endocarditis in protein-energy malnutrition has rarely been documented. All 3 of these patients had native valve endocarditis.
Candida is the most common causative organism of fungal endocarditis in both normal and immunosuppressed hosts.15,16 Usually, it causes prosthetic valve endocarditis, but it can also cause native valve endocarditis in intravenous drug abusers, patients with prolonged exposure to antibiotics and corticosteroids, those with severe burns, as well as patients undergoing gynecological procedures, urethral manipulations, or oral surgery.16 Candidal infections in immunosuppressed states are due to neutrophil disorders leading to defects in chemotaxis or microbicidal dysfunction.14 In this series, candidal endocarditis was associated with myocardial granuloma; similar involvement has been reported earlier.19 Systemic and visceral involvement other than the heart was seen in our patient with candidal endocarditis. Aspergillus is the second most common cause of fungal carditis.15 Aspergillus involved the myocardium more often than the endocardium, and it was more invasive than Candida.14,17 Aspergillus involves both native and prosthetic valves, and cardiac manifestations are caused by myocardial necrosis produced by coronary arteritis.20 Neutropenia is the major risk factor.18 The incidence of Aspergillus infection among the immunosuppressed is approaching that of Candida as a result of the success of candidal prophylaxis with fluconazole.21 Involvement of the heart by other fungi is much less often reported and mucormycosis constitutes approximately 4.35% of cardiac infections.22 Mucormycosis produces endocarditis in patients with prosthetic valves and those with acquired immunodeficiency syndrome, and similar to aspergillosis, it involves the coronary arteries.23
The rarity of fungal endocarditis and lack of positive results on culture make the diagnosis difficult.15 Large vegetations as seen in 3 of our patients, characterize fungal endocarditis, and transthoracic echocardiography is useful for antemortem diagnosis.15 Culture positivity is greater for yeast fungi than mold fungi, as also seen in this study.15 The mortality rate for fungal endocarditis is high (56.6%) and the patients in this study were diagnosed etiologically only at autopsy. The mortality rate for yeast-related IE (82.1%) is greater than for mold-related IE (40.3%).15 The role of surgery in addition to medical treatment for yeast endocarditis is controversial, and long-term suppressive therapy is advocated.14,15 This autopsy study emphasizes the significance of fungal endocarditis in India. Although rheumatic valvular disease is the most common preceding pathology of IE in India, the pattern in other cases is the same as in the West.
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ACKNOWLEDGMENTS
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The authors thank Mrs Y V Radhika for her secretarial assistance.
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REFERENCES
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ABSTRACT
INTRODUCTION
