A Case of Aspergillus Pericarditis in the Setting of Invasive Aspergillosis: The Role of Surgery in a Multi-modal Treatment.

We report the case of an immunocompromised patient admitted for chest pain secondary to pericardial effusion. Pericardiocentesis liquid analysis revealed an Aspergillus pericarditis. Advanced multimodality imaging later revealed invasive aspergillosis. The patient was treated with pericardectomy and long-term antifungal therapy. Novel teaching points are as follows: Pericardectomy is an efficient treatment for Aspergillus pericarditis. Disease control can be obtained without local relapse with pericardectomy and long-term antifungal therapy.

Cardiac fungal infections are rare and are most commonly caused by Candida albicans, Aspergillus fumigatus, and Cryptococcus.1, 2, 3 Cardiac aspergillosis often involves the endocardium and myocardium. Pericardial involvement is rare and is usually diagnosed postmortem. We report a case of an Aspergillus fumigatus pericarditis in a patient with long-term immunosuppressive therapies for seropositive erosive polyarthritis and a history of chronic lymphoblastic leukemia (CLL) with myeloproliferative syndrome.

Case

A 78-year-old female patient complaining of inspirational epigastric pain was transferred to our hospital with the suspicion of non-ST-elevation myocardial infarction. Her medical history included the following: (i) CLL associated with JAK2-positive myeloproliferative syndrome that was stable (white blood cell count of 15.9 G/L with 14 G/L lymphocytes); (ii) seropositive erosive polyarthritis for which she received intravenous golimumab (100 mg every 8 weeks) and methotrexate (20 mg orally once a week); (iii) leukocytoclastic vasculitis; and (iv) hypertension.

On admission, she did not present with any fever, chills, or sweats. Her electrocardiogram showed inverted T waves in the lateral and inferior leads. Her troponin and lactate dehydrogenase levels were normal, but her C-reactive protein level was elevated at 161 mg/L. Chest x-ray showed an increased cardiothoracic index of 0.63 (Supplemental Fig. S1). Her white blood cell counts were elevated at 19.6 G/L, with lymphocytes and erythroblasts counts, respectively, at 17 g/L and 0.05 g/L. Flow cytometry was in favour of CLL (cluster of differentiation [CD]5+, CD19+, CD23+, CD43+). Malignant transformation was ruled out. Transthoracic echocardiography (TTE) on admission showed a circumferential pericardial effusion ranging from 15 to 20 mm, without signs of cardiac tamponade. Left and right ejection fractions were normal. Mild-to-moderate mitral and tricuspid regurgitation were present, with pulmonary systolic pressures of 35 mm Hg, and a central venous pressure of 15-20 mm Hg. Medical treatment with prednisone at 25 mg orally daily, colchicine at 0.6 mg orally daily, surveillance, and repeat echocardiography were recommended.

Two days after admission, she developed symptomatic de novo atrial fibrillation (AF). The pericardial effusion had increased, with signs of cardiac tamponade and fibrinous pericardial images on the left ventricle (LV) lateral wall (Fig. 1A). Intravenous amiodarone was administered, and emergent pericardiocentesis was conducted, evacuating 600 mL of serous liquid, returning her to sinus rhythm. The following day, TTE showed a reduction in pericardial effusion size with fibrinous images on the LV, without cardiac compression. A contrast-enhanced body scan revealed a 27-mm pericardial fluid accumulation on the side of the LV, mild enhancement of the adjacent pericardium (Fig. 1B), stable mediastinal adenopathy, and multiple new pulmonary nodules. Pericardial fluid grew Aspergillus fumigatus, leading to voriconazole initiation, later confirmed by positive serology. Golimumab and methotrexate were immediately stopped, and prednisone was gradually weaned and discontinued. Recurrent symptomatic AF occurred, and repeat TTE showed increased accumulation of fibrinous deposits on the heart, in addition to cavitated areas with epicardial infiltrations. Subsequent fluorodeoxyglucose-positron emission tomography showed increased fluorodeoxyglucose uptakes of the following: (i) multiple pulmonary nodules suggestive of infectious or inflammatory lesions; (ii) mediastinal poly-adenopathy secondary to either lymphoproliferative or infectious origin; (iii) the entire pericardium with an oval 30 × 45–mm focal site localized on the anterior wall of the LV; and (iv) multiple-muscle and subcutaneous focal sites (Fig. 1C), consistent with disseminated invasive aspergillosis. Because of hemodynamic consequences with recurring AF despite pericardial drainage, total pericardectomy was planned.

Figure 1

(A) Echocardiographic 2-chamber view of left cavities showing dense tissular/fibrinous accumulation on the left ventricle (LV; red arrow). (B) Computed tomography scan transversal 4-chamber view of the heart showing circumferential pericardial effusion, with a collection on the posterior and lateral side of the LV and heterogenous pericardial thickness at the LV apex (orange arrow). (C, D) Fluorodeoxyglucose-positron emission tomography transversal 4-chamber view of the heart showing (C) increased uptake of the pericardium (green arrow) and (D) increased uptake of loculated area on the LV lateral side (green arrow). (E) Peri-operative photography of the infiltrative process with LV cavitation and abscess (yellow arrows). (F) Pathology analysis with Grocott coloration showing mycelian hyphae with 45°-branching in favor of Aspergillus organism (×400; black arrows).

Surgery occurred through a median sternotomy. The pericardium was markedly thickened. Liquid and tissular collections and enlarged lymph nodes were found around the aorta and superior vena cava. Both ventricles had multiple infiltrated and cavitated areas (Fig. 1D). The pericardium was resected from one phrenic nerve to another. Unfortunately, removing all lesions was impossible, as they had completely infiltrated the myocardium. Following aggressive irrigation, the thorax was closed over 5 chest tubes. Multiple samples were sent for bacterial, fungal, and histopathologic analyses.

Postoperative TTE showed persistent circumferential epicardial tissue without fluid. Her postoperative stay was uneventful. All peri-operative and drainage system samples were positive for Aspergillus fumigatus. Pathology revealed multiple mycelian hyphae with 45° branching in the pericardium (Fig. 1E and F). She was discharged and closely monitored, with regular reviews. One year later, serum galactomannan assay and anti-aspergillus antibodies were both negative, her positron emission tomography scan showed no recurrence of glucose uptake in the mediastinum, her TTE was normal, and the patient was completely asymptomatic.

Discussion

Cardiac aspergillosis has been described with involvement of all 3 layers either isolated or as pancarditis.,,4, 5, 6 Risk factors for invasive aspergillosis include acquired immunodeficiency syndrome (AIDS), diabetes, severe neutropenia, hematologic disease, and immunosuppression, such as Hodgkin disease, requiring bone marrow transplant with chemotherapy, malignant leukemias, and solid organ transplant,,, and long-term steroids and/or immunosuppressive therapies.,,

Our case is interesting, as we report an early diagnosis that enabled early treatments that resulted in favorable postoperative outcomes; this outcome differs from those in previous publications. Other publications have reported either series of autopsies,,, or case reports, of diagnoses established postmortem. Cardiac fungal infections have been well described through a series of 60 autopsies from Atkinson et al. and 51 autopsies from Walsh et al. The latter study carried 13 cases of endocarditis, 34 cases of myocarditis, and 4 cases of pericarditis. These last 4 patients had a history of cytotoxic treatments, steroids, or leukemia, and combined pulmonary and cardiac lesions. The authors felt that the pericardial space was infected by either erosion of pericardial abscesses or direct contact with an infected pleural space.

Le Moing et al. conducted a review of 29 cases of Aspergillus pericarditis. Aspergillus fumigatus was the most common species found (59%). Simultaneous pulmonary or pleural localizations of invasive aspergillosis were present in 86% of the patients, and 34% of these patients did not receive antifungal therapy for invasive aspergillosis. All of them died, and their diagnoses were established at autopsy.

Conclusion

We report the case of an immunocompromised patient with Aspergillus pericarditis in whom imaging revealed cardiac, pulmonary, cutaneous, and subcutaneous invasion. Rapid initiation of antifungal therapy is crucial and must be maintained on a long-term basis. Associated pericardectomy is a key aspect of the treatment of Aspergillus pericarditis.

Aspergillus pericarditis should be contemplated early in immunocompromised patients, especially if they present a pericardial effusion.

Early utilization of multimodal imaging, such as computed tomography, positron emission tomography, and cardiac magnetic resonance, is key to an early diagnosis.

Once a cardiac fungal infection is suspected, antifungal therapy should be started rapidly even if documented infection is not established.

Although we observed that removing all lesions is almost impossible due to a severe infiltrative process, associated pericardectomy should be considered to relieve hemodynamic intolerance and avoid recurring pericarditis.

Long-term antifungal therapy is key to infection control.