A 68-year-old male with a history of dilated cardiomyopathy and pacemaker implantation 2 years prior was hospitalized with repeated chills, fever and weakness for 20 days. After examination in the local hospital, the WBC count (10.38x109/L) and CRP level (75 mg/L) were both increased. Moxifloxacin, meropenem and vancomycin were used for anti-infection treatment, but they were ineffective. The patient was transferred to the provincial hospital, indicating that the WBC count (11.5x109/L) and CRP level (173 mg/L) were further increased, but procalcitonin did not increase (0.08 ng/mL). To identify the pathogens causing infection, the patient came to our hospital for treatment. However, the patient's condition further deteriorated, and the inflammatory markers continued to rise (18.26x109/L WBCs and 15.95x109/L neutrophils), with negative results for hepatitis B virus, hepatitis C virus, human immunodeficiency virus, and Treponema pallidum as well as culture of blood, sputum and urine. Acid-fast staining of sputum was also negative, indicating that pulmonary tuberculosis was preliminarily excluded. The erythrocyte sedimentation rate (32 mm/h) and procalcitonin (0.08 ng/mL) of the patient were negative. Serum 1,3-beta-D-glucan (G) assay, galactomannan antigen (GM) assay and filamentous fungus examination of bronchoalveolar lavage fluid (BALF) were performed. The G assay showed that serum 1,3-beta-D-glucan was 243.63 pg/mL (normal reference interval was 0-60 pg/mL), and the GM assay showed that galactomannan was 1.13 mug/L (normal reference interval was 0-0.5 mug/L), while BALF culture was negative. Echocardiography showed a 38.6x26.2x30.0 mm vegetation (white arrow) adhered to the right cardiac pacemaker and tiny mitral subvalvular vegetations, which aroused our concern (Figure 1). CT angiography showed pulmonary embolism, and laboratory examination showed coagulation dysfunction with abnormal elevation of prothrombin time (30.8 s), fibrinogen (4.33 g/L), D-dimer (3860 mug/L), and fibrin degradation product (13,000 mug/L). Doctors considered that pulmonary embolism was probably caused by the shedding of vegetation, so they performed pulmonary artery thrombectomy, removal of the cardiac pacemaker and implantation of a temporary pacemaker. Then, pathological examination and pathogenic examination of the cardiac tissues, cardiac pacemaker and vegetation were performed. According to the ultrasonic morphological characteristics of this vegetation accompanied by some tiny flocculent floaters and positive serological results, we suspected that it might be caused by filamentous fungal infection. Therefore, a resident physician used caspofungin as an empirical antifungal treatment, administering 70 mg on the first day and 50 mg once a day thereafter. Histopathological digital slices of the vegetations demonstrated multiple fibrinoid and hemorrhagic necrosis with extensive inflammatory infiltration, accompanied by hyaline sporophores and filamentous hyphae, 2-7 mum in diameter, dark in HE staining (Figure 2). Antler-like filamentous hyphae were stained by Gram staining of the vegetations (Figure 3A). Septate hyphae with branches at acute angles were shown in bright blue by fluorescence staining (Figure 3B). The colony cultured from vegetations was grayish-green and velutinous (Figure 3C). Lactophenol cotton blue staining showed that the top of the smooth conidia stalk expanded to form an inverted flask-shaped top cyst with a single-layer sterigma, and unstained conidia were spherical, forming a blue chrysanthemum (Figure 3D). A phylogram was constructed utilizing the ITS sequence of the isolated strain Aspergillus fumigatus ZJPPH1 along with 18 available sequences with the highest homology retrieved from GenBank by MEGA11 (Figure 3E). After confirming that the infection factor was Aspergillus fumigatus, we changed caspofungin to 0.2 g of voriconazole every 12 hours for anti-Aspergillus fumigatus infection treatment. However, on the second day, the patient had severe liver and kidney dysfunction with abnormal decreases in serum albumin (55.2 g/L), albumin (32.4 g/L), and cholinesterase (3824 U/L) and abnormal increases in glutamic pyruvic transaminase (3214 U/L), glutamic oxaloacetic transaminase (2199 U/L), glutamyl transpeptidase (214 U/L), lactate dehydrogenase (1259 U/L), total bilirubin (83.7 mumol/L), direct bilirubin (42.2 mumol/L), total bilirubin (41.5 mumol/L), creatinine (185.2 mumol/L) and urea (17.21 mmol/L). The liver and kidney function indices of the patient were normal and stable during treatment with caspofungin, so we reused caspofungin as the antifungal drug at 50 mg once a day and continued to use caspofungin for 42 consecutive days of continuous antifungal treatment. We performed a series of surgical interventions on the patient (we described the operation process in detail in the Supplementary Materials). G and GM assays were performed again, and the results showed that serum 1.3-beta-D-glucan (14.87 pg/mL) and galactomannan (0.79 mug/L) decreased significantly compared with the previous levels, which suggested that the anti-Aspergillus treatment was effective. The patient improved; his inflammatory markers, including WBCs (7.54x109 /L) and CRP (9.3 mg/L), returned to normal, and he was discharged. One year later, the patient had recovered well, with normal routine blood and inflammatory indicators. He underwent permanent pacemaker implantation and was discharged from the hospital. According to our latest follow-up, he had recovered well.