Chronic Q fever infective endocarditis: a case report

Abstract Q fever is an epidemic disease caused by the Coxiella burnetii infection. It can manifest clinically as an acute or chronic disease, with chronic infections being more common. Q fever endocarditis is the most common manifestation of chronic infection and usually occurs in patients with previous valvular heart disease like in our present study, a case of Q fever endocarditis that occurred in background of tetralogy of Fallot surgical repair. However, Q fever endocarditis is difficult to diagnose clinically and may lead to very serious or even life-threatening outcomes if not diagnosed promptly. In the present study, accurate diagnosis and treatment were achieved by 18F-FDG PET/CT combined with detection of the Q fever serological antibodies.


Case presentation
We present a case of thirty-four-years-old male with a background of tetralogy of Fallot (TOF) surgicaly repaired in 1995, followed with surgical pulmonary valve replacement (Perimount 25) in 2012 for severe pulmonary regurgitation.
On October 30, 2018, he was admitted with bioprosthetic infective endocarditis (IE) (þve blood culture þ echo showed large vegetation on pulmonary bioprosthesis þ CT chest: showed multiple septic emboli and mycotic aneurysm of right lower lobe pulmonary artery) which was treated medically.After recovery from IE, echocardiography showed no vegetation on the pulmonary valve but because of severe regurgitation, the patient underwent a successful percutaneous pulmonary valve implantation (PPVI) with 29-mm Edward SAPIEN Valve.
Echocardiography after PPVI showed the stent of PPVI in situ, mild paravalvular leak, and PG 24 mmHg.

Investigations
The patient was lost for follow-up for 2 years after PPVI and admitted having been living in an area where he was taking care of cattle.When he presented for the OPD follow-up after 2 years, he has mild shortness of breath on exertion but denied any fever or other cardiac symptoms.
Investigations revealed high erythrocyte sedimentation rate (ESR92), and blood cultures were negative.
Transesophageal echocardiography showed Edward SAPIEN in 25-mm Perimount valve in pulmonary position with 2 mobile masses attached to valve probably vegetations, severe pulmonary valve regurgitation and pulmonary stenosis with a gradient of 40-50 mmHg along with mild-to-moderate tricuspid regurgitation (TR) with right ventricular systolic pressure (RVSP) of 60 mmHg.
Cardiac MRI was done and showed severe valvular and para valvular pulmonary regurgitation (PR) with right venticular end diastolic volume (RV EDV) of 174 ml.
The plan was for surgical pulmonary valve replacement after complete clearance from infection.Three sets of blood culture from 3 different sites were negative.Brucella antibodies and PCR were negative.
Q fever (Coxiella burnetii) showed phase I and phase II IgG at high levels with IGM compatible with a chronic infection.

Differential diagnosis
The patient had 1 major criteria (findings in echocardiography) and only 1 minor diagnostic criteria (predisposing heart condition of prior prosthetic valve implantation) from the modified Duke criteria for IE, thus confirming a diagnosis of possible IE of the pulmonary valve prosthesis.
Because of the high likelihood of IE, 18F-FDG PET/CT was performed for further confirmation.
The patient was put on special preparation for cardiac PET procedures that include cardiac diet (high fat, very low/zero carbohydrates) for 72 h prior to performing the PET/CT scan and 6 h fast before the injection of 18F-FDG.He was then injected with a dose of 0.15 mCi/kg 18F-FDG and the PET/ CT scan was performed from skull base to midthigh after approximately 60 min uptake period.
The ULTRA HD-PET (Tru þ TOF) reconstruction method was used with scatter correction (RELATIVE) and GAUSSIAN filter.
The PET/CT scan showed focal increased FDG activity in the lateral and posterior aspects of the prosthetic pulmonary valve, SUV max up to 5 (Figures 1and 2).No other areas of abnormal FDG uptake were noted in the heart.Similar findings were noted in the non-attenuated (uncorrected) PET scan (Figure 3).

Treatment
The patient was started on Q fever IE treatment: doxycycline 100 mg twice daily (bid) and hydroxychloroquine 200 mg three times a day.He subsequently underwent redo Pulmonary valve replacement (27-mm Avalus Bioprosthetic valve).
The excised pulmonary valve tissue microscopic examination revealed bacterial and fibrin colonies with extensive calcification are shown in (Figures 4 and 5).Zones of fibrous tissue (Figure 6) were found, which is suggestive of vegetations.Special statins were negative for microorganisms.
Q fever PCR came as positive.

Outcome and follow-up
On further follow-up, the patient is asymptomatic and inflammatory markers are back to normal.Postsurgical Echocardiography revealed no more vegetations or intracardiac masses.The bioprosthetic valve seen in place with a presurre gradient (PG) of 17 mmHg.There was trace valvular leak and no paravalvular leak.

Discussion
IE is a life-threatening disease with substantial morbidity and mortality.The incidence of the disease is increasing worldwide, likely due to an expanding option for cardiac valve repair and/or replacement and increasing use of cardiacimplanted devices. 1-3IE is a difficult-to-diagnose condition because of its highly variable clinical presentation.The diagnosis of this disease is  based on the Duke criteria introduced in 1994 and modified in 2000, 4 but their specificity and sensitivity are limited in cases of prosthetic valve endocarditis (PVE) and cardiac device-related infective endocarditis; hence, they should support rather than replace clinical judgement. 5,6n the case of PVE, FDG PET/CT has both high sensitivity and specificity for intracardiac infection.Laurens al. reported that FDG PET/CT had a sensitivity/specificity/positive predictive value/negative predictive value for PVE of 91%/95%/ 95%/91%, respectively. 7The most recent meta-analysis of this indication found similar data for PVE, but with low sensitivity (36%) and high specificity (99%) in native valve endocarditis. 8,9lood culture-negative IE is a potentially severe disease that can be associated with infectious agents such as Bartonella spp., C burnetii, Tropheryma whipplei, and some fungi.The disease that is caused by C burnetii is Q fever.Q fever is a zoonotic disease which can either present in an acute or chronic form.Chronic Q fever mainly affects the heart where the disease manifests as endocarditis in 60%-80% of all cases of chronic Q fever worldwide. 10he diagnosis of Q fever endocarditis remains challenging.In a recent series, only 18% of cases showed the typical histological features of endocarditis, specifically, vegetations, inflammatory infiltrates and significant tissue destruction. 11ore commonly, only extensive fibrosis and calcification were evident, which were difficult to discern from degenerative changes.C burnetii itself is not visible within macrophages on routine haematoxylin and eosin staining, and even special staining is unlikely to reveal the organism.Immunohistochemistry and polymerase chain reaction are more successful in demonstrating the presence of the organism; however, polymerase chain reaction has a sensitivity of only 75%. 11he optimum treatment of Q fever endocarditis includes doxycycline (100 mg/bid) and hydroxychloroquine (200 mg/ bid) for the duration of 24 months.Furthermore, it is recommended to establish a goal of therapy of phase IgG titres less than 1:800 by maintaining doxycycline serum concentration 5 g/ml. 12Surgical replacement of the injured valve is often necessary for patients with Q fever endocarditis due to hemodynamic reasons.

Learning points
� IE is a life-threatening disease with significant morbidity and mortality.� Physicians should maintain a high index of suspicion of Q fever IE, especially among patients with pre-existing structural heart disease and associated risk factors.� 18F FDG PET/CT plays an important role in confirming the diagnosis leading to well informed management plan.� The diagnosis of IE due to chronic Q fever infection remains challenging, due to its highly variable clinical presentation.FDG PET/CT scan aids the diagnosis in    patients with high clinical suspicion but inconclusive investigations.

Figure 1 .
Figure 1.MIP image from 18FDG PET/CT scan showing intense focal uptake in the prosthetic valve (black arrow) in keeping with infective endocarditis.

Figure 2 .
Figure 2. Axial (A) and coronal (C) PET images show two intense foci of increased FDG uptake seen to correspond to the prosthetic valve on the fused images (B and D).