Scratches of danger: from Bartonella to heart failure in a young patient—a case report

Abstract

Background

Infective endocarditis (IE) is an uncommon but potentially fatal disease, with an incidence of 13.8 per 100 000 and persistent high mortality (15–30%). In 10–20% of cases, cultures remain negative and additional serological testing for infectious and non-bacterial endocarditis is required.

Case summary

We report a case of a 25-year-old North African man with a history of lupus nephritis presenting with progressive dyspnoea, retrosternal pain, and fever. Transthoracic echocardiography showed extensive calcifications on the aortic valve with severe aortic regurgitation. Prior echocardiograms had already documented a large aortic valve calcification, which was not considered suspicious for IE on previous FDG-positron emission tomography scan. However, a transoesophageal echocardiogram at admission revealed a functional bicuspid aortic valve with a large vegetation and severe left ventricular dysfunction. The patient rapidly deteriorated into beginning cardiogenic shock, necessitating emergency mechanical aortic valve replacement. Blood cultures remained negative, but serology testing revealed elevated Bartonella henselae IgG (≥1:1280) with positive polymerase chain reaction for Bartonella species on the resected valve. B. henselae, known as the causative pathogen of ‘cat-scratch disease’, was identified as the aetiological pathogen of blood culture–negative IE (BCNIE). The patient was successfully treated with doxycycline and gentamicin, in combination with guideline-directed medical therapy for heart failure and cardiac resynchronization therapy.

Discussion

This case illustrates the diagnostic challenges of BCNIE. Serologic and molecular testing should be pursued when cultures remain negative. Multi-disciplinary management, early surgical intervention, appropriate antibiotic treatment, and optimized heart failure therapy in IE presenting with acute heart failure can improve patient outcomes.

Learning points.

• Bartonella henselae should be considered in blood culture–negative infective endocarditis, particularly in younger patients with zoonotic or endemic exposure, and confirmed with serology or polymerase chain reaction.

• Multi-disciplinary management, early surgery, targeted antibiotics, and optimized heart failure therapy are essential for favourable outcomes in infective endocarditis presenting with acute heart failure.

Introduction

Infective endocarditis (IE) is an uncommon disease with an estimated incidence of 13.8 cases per 100 000 in 2019, and carries high mortality (15–30%), without any substantial change in the past 25 years. In 10–20% of cases, cultures remain negative and extensive molecular sequencing, prolonged incubation of blood cultures, and serological testing are required. Poor outcomes are associated with age, frailty, prosthetic valve IE, Staphylococcus aureus infection, and complications such as septic emboli, peri-annular abscess, heart failure, severe left-sided valve regurgitation, or cardiogenic shock. A rapid identification of the causative pathogen with appropriate antibiotic therapy and early surgical removal of infected tissue may improve survival, especially in high-risk patients with uncontrolled infection or heart failure.^1,2

Case presentation

A 25-year-old man of North African origin presented to the emergency department (ED) with months of progressive retrosternal pain and exertional dyspnoea. One year prior, he was hospitalized for acute renal failure with positive anti-cardiolipins, increased inflammatory markers, and biopsy-proven immune complex glomerulonephritis. Transthoracic echocardiogram (TTE) and transoesophageal echocardiogram (TOE) showed a functionally bicuspid aortic valve with a calcified mass between the right and non-coronary cusp, but no regurgitation or stenosis. Blood cultures remained negative, and FDG-positron emission tomography scan showed no infectious focus. A tentative diagnosis of focal lupus endocarditis was made, and treatment with prednisolone, mycophenolate mofetil, hydroxychloroquine, and prophylactic sulfamethoxazole/trimethoprim was started.

At the time of arrival in the ED, the patient appeared uncomfortable, with a heart rate of 123 b.p.m., blood pressure of 138/54 mmHg, respiratory rate of 30/min with oxygen saturation of 98%, and fever (38.8°C). Physical examination revealed sinus tachycardia and a diastolic murmur at the left parasternal border. The electrocardiogram showed a new left bundle branch block, with T-wave inversions in I and V6. Lab results showed an elevated troponin T level of 131 ng/mL (normal value: 0–14 ng/L) with limited inflammatory markers [white blood cell count of 10.8 × 10⁹/L (normal value: 4.0–11.0 × 10⁹/L) and C-reactive protein of 16.8 mg/L (normal value: 0–10 mg/L)]. The patient’s maintenance medication consisted of bisoprolol 5 mg, sulfamethoxazole 800 mg/trimethoprim 160 mg (3 times/week), pantoprazole 20 mg OD, hydroxychloroquine sulfate 200 mg OD, and mycophenolate mofetil 1500 mg BID.

Bedside TTE (Figure 1A) revealed a large, mobile vegetation on the bicuspid aortic valve, resulting in severe aortic regurgitation, along with a hypertrophic and dilated left ventricle with moderately reduced systolic function (ejection fraction (EF) 45%), apico-septal hypokinesia and a limited pericardial effusion. Diastolic blood pressure progressively dropped. Urgent computed tomography (CT) excluded aortic dissection. Transoesophageal echocardiogram confirmed further deterioration of left ventricular ejection fraction to 10–15%, severe regurgitation due to a ruptured left coronary cusp (LCC), and a large mobile vegetation protruding into the left ventricle (Figure 1B and D).

Figure 1.

(A) Transthoracic echocardiogram showing hypertrophic, dilated left ventricle with calcified aortic valve with a large mobile vegetation protruding into the left ventricle (arrow). (B and C) Transoesophageal echocardiogram showing diffuse hypokinetic dilated left ventricle with a large mobile vegetation (red arrow) with rupture of the left coronary cusp (green asterisk). (D) Transoesophageal echocardiogram showing a large aortic regurgitant jet due to a ruptured left coronary cusp. (E) Cardiac surgery view of complete destruction of the aortic valve, as well as multiple calcifications on all leaflets.

Seen the rapid deterioration to beginning cardiogenic shock (Society for Cardiovascular Angiography and Interventions [SCAI] Shock Stage B), urgent mechanical aortic valve replacement surgery was performed. Surgery revealed complete destruction of the valve, detachment of the LCC, as well as multiple calcifications on all leaflets (Figure 1E). Based on the clinical presentation and severe aortic insufficiency due to valve destruction, IE was suspected. However, due to the patient's history of lupus nephritis, the initial differential diagnosis included Libman–Sacks endocarditis, systemic lupus erythematosus valvulitis, and blood–culture negative IE (BCNIE). Empiric antibiotic therapy with flucloxacillin, benzylpenicillin, and gentamicin was started. Blood cultures and valve tissue cultures remained negative. Extensive serology and polymerase chain reaction (PCR) testing confirmed Bartonella henselae (IgG ≥1:1280; PCR positive on valve tissue). The patient’s history revealed close exposure to his cat, suggesting a potential source of zoonotic transmission. Antibiotics were switched to gentamicin/doxycycline, resulting in a C-Reactive Protein (CRP) reduction to 2.2 mg/L (normal value: 0–10 mg/L) at discharge. According to this result, the patient was diagnosed with BCNIE caused by B. henselae.

The post-operative course in the intensive care unit was complicated by a pericardial tamponade secondary to post-operative haematoma, requiring drainage. LV function remained poor (EF <35%), despite introduction of medical heart failure therapy (sacubitril/valsartan, spironolactone, bisoprolol, and empagliflozin). After multi-disciplinary discussion, Cardiac Resynchronization Therapy Defibrillator (CRT-D) implantation was performed. A follow-up TTE at Day 35 showed a correct function of the mechanical aortic valve without new vegetations. At discharge, biochemical resolution of inflammation as well as resolution of pericardial fluid was obtained. At 3 months, EF improved to 40% after CRT optimization, uptitration of medical therapy for heart failure, and cardiac rehabilitation.

Discussion

Blood cultures and echocardiography remain the gold standard for diagnosing IE. The 2023 Duke-ISCVID IE criteria include positive culture and suggestive echo findings (vegetation or abscess).³ However, in 10–20% of cases, cultures remain negative.^2,4,5 FDG-PET/CT is useful in prosthetic valve IE but has limited sensitivity for native valve endocarditis (NVE) (pooled sensitivity 36% and specificity 99%).⁶

Administration of antibiotics prior to collecting blood cultures is the predominant cause of BCNIE. Some fastidious micro-organisms (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella [HACEK], nutritionally variant streptococci, Pasteurella spp., mycobacteria, fungi) require prolonged incubation, culturing on specialized media and specific molecular detection. Intracellular pathogens (Bartonella and Coxiella burnetii) require serology or PCR testing of blood or valve tissue [e.g. Tropheryma whipplei, Bartonella spp., and fungi (Candida spp. and Aspergillus spp.)].^1,4,5 Additional serology for zoonotic or endemic pathogens (e.g. C. burnetii, Bartonella spp., Aspergillus spp., Legionella pneumophila, Brucella spp., and Mycoplasma pneumoniae) should be performed if blood cultures remain negative at 48 h.^1,4 If all microbiological assays are negative, non-bacterial endocarditis, including Libman–Sacks or systemic lupus valvulitis, should be considered, with additional testing of rheumatoid factor, anti-nuclear antibodies, and anti-phospholipid syndrome antibodies, including anti-cardiolipin IgG, lupus anticoagulant, and anti-β-2 glycoprotein I antibodies (IgG and IgM) and anti-pork antibodies (in case of a prosthetic porcine valve).^1,4

Bartonella species are small, facultative Gram-negative rods, first identified as IE pathogens in 1993.⁷  Bartonella has now emerged as a significant cause of BCNIE, especially in North and sub-Saharan Africa. The three most prevalent species associated with IE are Bartonella quintana, B. henselae, and Bartonella bacilliformis.^7–9  Bartonella henselae, which causes ‘cat-scratch disease’, spreads to humans through scratches or bites from flea-infected cats.^7,8 Previous case reports indicate that Bartonella endocarditis predominantly affects the aortic valve, with B. henselae responsible for nearly 80% of cases, and is associated with higher rates of valve surgery and mortality compared with endocarditis from other pathogens.^7,10–13

The 2023 ESC guidelines for the management of endocarditis updated the Duke-ISCVID criteria, adding IgG enzyme immunoassay and PCR for B. henselae as major criteria for culture-negative endocarditis.^1,3 Optimal antimicrobial drug therapy for Bartonella endocarditis remains undetermined. Recommended treatment is doxycycline 100 mg/12 h for 4 weeks plus gentamicin 3 mg/24 h IV for 2 weeks, with ≥90% expected success.^1,13

Acute heart failure is the most common complication of NVE and the leading indication for surgery, followed by uncontrolled infection and prevention of embolization. Acute heart failure usually results from severe aortic or mitral regurgitation due to leaflet or chordae rupture, leaflet perforation, fistulae, or valve obstruction by vegetations. In the ESC-EORP EURO-ENDO (European IE) registry, congestive heart failure was observed in 15.9% and cardiogenic shock in 6.2% of patients with NVE. In that registry, both culture-positive and culture-negative IE caused valvular destruction, but heart failure was more frequent and severe in culture-negative cases.¹⁴ Overall operative mortality for valvular IE is 5–15%, with meta-analyses showing improved survival after surgery even at 12 months.¹⁵ The 2023 ESC guidelines recommend managing IE through a multi-disciplinary Endocarditis Team and referring complicated cases to centres with surgical facilities.¹

The present case highlights the challenges of diagnosing BCNIE and importance of identifying the causative pathogen. Retrospectively, early signs of Bartonella endocarditis likely appeared a year before admission, slowly progressing to valvular destruction and acute heart failure. Echocardiographic features suspicious for IE (large vegetations, valve rupture, and severe regurgitation) remain crucial for diagnosis. Multi-disciplinary management guided the timing of surgery, optimized antibiotic therapy, and facilitated guideline-directed medical and device therapy for heart failure, contributing to a favourable outcome in this case.

Lead author biography

I am a final-year cardiology resident with a strong interest in cardiac imaging, particularly transoesophageal echocardiography and echocardiographic cardiopulmonary exercise test (CPET-echo). I am also particularly drawn to the field of heart failure, where I see imaging as a key tool to improve diagnosis and management. I will pursue a fellowship in cardiac imaging and heart failure to further develop my expertise and contribute to patient care and research in these areas.

Author contributions

Laura Braeckeveldt, Imeri Ilire (Writing—original draft [equal]), Prihadi Edgard (Writing—review and editing [supporting]), and Vermeersch Gaëlle (Writing—review and editing [supporting])

Funding

None declared.

Data availability

Echocardiographic images and laboratory results are stored in the hospital’s local clinical information system. These data are not anonymized and remain linked to individual patient profiles; therefore, they cannot be made publicly available. However, they may be shared by the authors upon reasonable request, subject to institutional and ethical restrictions. Materials underlying this case report that are publicly accessible can be found in an online source, which is fully cited in the reference list.