When echocardiography fails: Fatal Staphylococcus aureus endocarditis of a right ventricle-pulmonary artery conduit in an adult with DiGeorge syndrome (Lessons from a delayed PET/CT diagnosis)

Abstract

Background

22q11.2 Deletion Syndrome (DiGeorge Syndrome) confers a high risk for infective endocarditis (IE) due to coexisting conotruncal heart defects, prosthetic material, and immune deficiency. Diagnosing IE on a right ventricle-to-pulmonary artery (RV-PA) conduit can be challenging.

Case summary

A 31-year-old female with 22q11.2 deletion syndrome and repaired pulmonary atresia with a ventricular septal defect (RV-PA conduit) presented with febrile syndrome two months after pacemaker implantation. Initial transesophageal echocardiography (TEE) was negative. She was treated for a pacemaker lead infection with lead extraction and antibiotics, with initial improvement. She relapsed shortly after completion of therapy.

The second TEE was not diagnostic. A definitive diagnosis was only achieved by 18F-FDG PET/CT, which demonstrated intense uptake at the conduit and a septic embolism in the fourth dorsal vertebra. Despite emergency surgery, the conduit was found to be destroyed by a fistulizing pseudoaneurysm, and the patient died due to uncontrollable hemorrhage.

Conclusion

This fatal case highlights the critical limitations of echocardiography in diagnosing prosthetic conduit endocarditis. 18F-FDG PET/CT was the pivotal diagnostic modality, confirming the infection after all other methods failed. This underscores the necessity of integrating advanced molecular imaging early in the diagnostic algorithm for such high-risk patients to enable timely intervention and prevent catastrophic outcomes.

Introduction

DiGeorge syndrome, resulting from a 22q11.2 microdeletion, has an incidence of approximately 1 in 4000 live births [1]. Pulmonary atresia with ventricular septal defect (PA-VSD) occurs in 10–26% of children with del22q11 [2], [5]. Surgical repair of PA-VSD often requires the use of a valved conduit, which introduces a lifelong risk of infective endocarditis (IE) [6]. While IE is a known complication of prosthetic material, its clinical course in immunocompromised hosts with complex congenital heart disease can be exceptionally virulent and fatal. We present a case of fatal IE of prosthetic material in an adult with DiGeorge syndrome following pacemaker implantation.

Case presentation

A 31-years-old female with a confirmed 22q11.2 deletion and repaired PA-VSD presented to the emergency department with a 07-day history of high-grade fever (40.1°C). Her surgical history was significant for complete repair at 2 years of age, which involved patch closure of the ventricular septal defect and placement of a 14 mm non-valved Hemashield conduit for right ventricle-to-pulmonary artery continuity. Thirteen years later, the patient underwent replacement of the conduit due to severe pulmonary regurgitation and right ventricular dilation with a valved Medtronic Hancock conduit (size 20). Two months before her admission, a dual-chamber pacemaker was implanted for sinus node dysfunction.

On admission, the patient was critically ill. Vital signs included a temperature of 39.8°C, heart rate of 130 bpm, respiratory rate of 25 breaths/min, and low blood pressure of 90/45 mmHg. Cardiovascular examination revealed a palpable thrill, a loud mechanical conduit sound, and a new, harsh systolic murmur, grade 4/6, at the left upper sternal border. There were no peripheral stigmata of infective endocarditis (IE).

Laboratory findings revealed a white blood cell count of 25,000/µL with 90% neutrophils. C-reactive protein was elevated at 245 mg/L. Chest radiography showed cardiomegaly with the RV-PA conduit in place (Fig. 1). Transthoracic echocardiography showed severe pulmonary regurgitation with paradoxical septal motion. The right ventricle was dilated with systolic dysfunction (TAPSE of 6 mm/s) (Fig. 2). Transesophageal echocardiography (TEE) did not identify vegetations, a paravalvular abscess, or lead-associated vegetations. Three separate sets of blood cultures drawn on admission were positive for methicillin-sensitive Staphylococcus aureus (MSSA). The pacemaker leads were removed, and empirical antibiotic therapy was initiated, resulting in apyrexia within 48 h and improvement in inflammatory markers. A six-week course of intravenous flucloxacillin was administered with good clinical response, and she was discharged home.

Fig. 1.

Chest radiography showed cardiomegaly with the RV-PA conduit in place.

Fig. 2.

Transthoracic echocardiography showed severe pulmonary regurgitation with paradoxical septal motin. The right ventricle was dilated with systolic dysfunction.

Fifteen days after discharge, the patient was re-admitted for high-grade fever and respiratory symptoms. She was stable and laboratory studies showed a white blood cell count of 14,000/µL with 90% neutrophils and a C-reactive protein of 170 mg/L. A repeat of three separate sets of blood cultures drawn on admission were positive for the same bacteria sensible to Penicillin M. Transthoracic echocardiography and TEE demonstrated findings similar to the previous study. An 18F-FDG PET/CT revealed increased FDG uptake of the conduit and at the fourth dorsal vertebra suggesting associated spondylodiscitis (Fig. 3). A diagnosis of definite prosthetic conduct endocarditis was made according to the Modified Duke Criteria. Intravenous flucloxacillin was readministered with apyrexia in 72 h.

Fig. 3.

18F-FDG PET/CT revealed increased FDG uptake of the conduit and at the fourth dorsal vertebra suggesting associated spondylodiscitis.

05 days later, the patient's clinical condition acutely deteriorated with the onset of massive hemoptysis, which the chest radiography and thoracic angioscanner confirmed was due to a fistulating pseudoaneurysm of the pulmonary conduit, with active contrast extravasation into the adjacent bronchial tree (Fig. 4). Given the clinical deterioration and high risk of embolization or conduit rupture, the patient was taken for emergency surgery. Intraoperatively, the conduit was found to be extensively destroyed by the infective process. The vegetations had eroded through the conduit wall, and upon explantation, a large aneurysm of the pulmonary artery with a significant tissue defect was encountered. Attempts to control hemorrhage and implant a new pulmonary homograft were unsuccessful due to the poor tissue integrity.

Fig. 4.

Thoracic X ray (A) and angioscanner (B) confirmed fistulating pseudoaneurysm of the pulmonary conduit, with active contrast extravasation into the adjacent bronchial tree.

Postoperatively, the patient developed progressive multiorgan failure, including anuric renal failure and disseminated intravascular coagulation. The patient died despite maximal medical and surgical intervention.

Discussion

The management of infective endocarditis (IE) in adults with congenital heart disease (ACHD) remains particularly challenging, especially when multiple predisposing factors converge. This case illustrates a true “perfect storm”: a patient with 22q11.2 deletion syndrome (22q11.2DS), complex conotruncal anatomy requiring prosthetic reconstruction, longstanding endovascular hardware, and recent device implantation, who developed a rapidly destructive methicillin-sensitive Staphylococcus aureus (MSSA) infection with fatal consequences.

Our patient’s underlying 22q11.2DS was central to her vulnerability. This syndrome is strongly associated with severe conotruncal anomalies, particularly pulmonary atresia with ventricular septal defect (PA-VSD), which often necessitates the surgical creation of right ventricle–to–pulmonary artery (RV–PA) continuity using a prosthetic conduit [1]. Such conduits constitute permanent non-endothelialized surfaces and therefore lifelong substrates for infection. The risk is further amplified by the T-cell lymphopenia characteristic of 22q11.2DS, which results in a state of relative immunodeficiency [2]. In this context, even a routine procedure such as pacemaker implantation can serve as a portal of entry for invasive pathogens. The fulminant course of MSSA infection in our patient—marked by rapid conduit destruction, pseudoaneurysm formation, and metastatic spread—likely reflects both the intrinsic virulence of S. aureus and an impaired host immune response [3]. These factors underscore the need for meticulous antibiotic prophylaxis, strict aseptic technique, and heightened post-procedural surveillance in this population.

Despite high clinical suspicion during both admissions, transesophageal echocardiography (TEE) failed to demonstrate vegetations. This limitation is well recognized in prosthetic valve and conduit endocarditis. Acoustic shadowing and reverberation artifacts caused by prosthetic material can obscure vegetations, particularly on the pulmonary side of an RV–PA conduit [4]. In such patients, reliance on echocardiography alone may delay diagnosis and treatment.

Importantly, recent updates in diagnostic criteria reinforce the role of advanced imaging in this setting. The 2023 European guidelines from the European Society of Cardiology (ESC) incorporated abnormal uptake on 18F-FDG PET/CT and paravalvular lesions detected by cardiac CT as major criteria for prosthetic valve endocarditis [5]. In parallel, the 2023 Duke–ISCVID criteria—an updated revision of the modified Duke Criteria—also added both PET/CT and cardiac CT findings as major imaging criteria in prosthetic IE [6]. Thus, our case aligns with contemporary recommendations from both frameworks: in patients with suspected prosthetic IE and negative TTE/TEE, advanced imaging is no longer adjunctive but integral to diagnosis.

In this patient, 18F-FDG PET/CT was pivotal. Its ability to detect metabolically active inflammatory infiltrates surrounding prosthetic material, as well as distant septic emboli (e.g., vertebral involvement), makes it particularly valuable in prosthetic IE. Meta-analyses have demonstrated a pooled sensitivity of approximately 80–85% and specificity of 75–85% for PET/CT in prosthetic valve endocarditis, with lower sensitivity in native valve IE [7], [8]. These data support its use as a major criterion in contemporary diagnostic algorithms. In our case, PET/CT identified active infection of the RV–PA conduit and extracardiac dissemination, thereby establishing a definitive diagnosis after inconclusive echocardiography.

Given that a central feature of this case is the detection of advanced structural complications, the potential role of cardiac CT also warrants emphasis. Cardiac CT has superior spatial resolution compared with echocardiography and is particularly sensitive for detecting paravalvular complications such as abscesses, pseudoaneurysms, fistulas, and prosthetic dehiscence [9]. In a scenario such as ours—where destructive infection led to a fistulizing pseudoaneurysm and extensive pulmonary artery wall necrosis—earlier cardiac CT may have better delineated the extent of tissue destruction and informed surgical planning. Contemporary ESC and Duke–ISCVID criteria recognize cardiac CT-detected paravalvular lesions as major diagnostic findings, reinforcing its complementary role alongside PET/CT.

The indication for surgery in IE requires balancing operative risk against the consequences of uncontrolled infection. In this case, surgery was clearly indicated due to severe conduit regurgitation causing heart failure, recurrent embolic phenomena, and infection with a highly virulent organism (S. aureus), which is associated with higher rates of heart failure, embolism, and mortality [3], [5]. However, intraoperative findings revealed extensive tissue necrosis and a fistulizing pseudoaneurysm involving the native pulmonary artery, rendering reconstruction technically unfeasible and resulting in uncontrollable hemorrhage.

This outcome raises a critical question: could earlier surgical intervention have altered the trajectory? After the first relapse and confirmation of conduit infection by PET/CT, immediate surgical evaluation—rather than a renewed attempt at medical therapy alone—might have permitted intervention before irreversible structural destruction occurred. In prosthetic IE due to S. aureus, early surgery is frequently advocated given its aggressive course [3], [5]. In patients with 22q11.2DS and relative immunodeficiency, the threshold for surgical referral should arguably be even lower.

Finally, this case highlights the importance of maintaining a high index of suspicion in adults with complex congenital heart disease and longstanding endovascular hardware. In such high-risk patients, negative TTE/TEE should not provide reassurance when clinical suspicion remains strong. Instead, early integration of advanced imaging—PET/CT and cardiac CT—should be pursued proactively in accordance with contemporary ESC and Duke–ISCVID criteria [5], [6]. Delayed escalation of diagnostic evaluation in this vulnerable population may allow destructive infection to progress beyond the point of surgical salvage.

Conclusion

This tragic outcome underscores a critical diagnostic imperative in prosthetic endocarditis: echocardiography has inherent limitations. In this case, it was the 18F-FDG PET/CT scan, and it alone, that provided the definitive diagnosis after repeated echocardiographic failures. This imaging modality proved indispensable, revealing the hidden focus of infection and transforming the management strategy. For high-risk patients with complex anatomy and immunodeficiency, PET/CT must be integrated early into the diagnostic algorithm to bridge the gap between clinical suspicion and actionable findings, thereby guiding timely and potentially life-saving interventions.

CRediT authorship contribution statement

Sara Ahchouch: Formal analysis, Data curation. LAHMOUZ YOUSSEF: Writing – review & editing, Writing – original draft, Methodology, Investigation. Ali Chaib: Visualization, Validation, Supervision. Aatif Benyass: Validation, Supervision, Software. Najat Mouine: Supervision, Data curation. Nora Bennani: Investigation, Data curation. Asmae Benssied: Data curation. Omar Ait Sahel: Formal analysis, Data curation, Conceptualization. Bamous Mehdi: Supervision, Methodology, Investigation. Abderrahim Doudouh: Validation, Supervision, Methodology. Moutakiallah Younes: Supervision.

Consent

Written informed consent was obtained from the patient for publishing this case report and accompanying images.

Ethical approval

This study was conducted in accordance with the principles of the Declaration of Helsinki. As this was a retrospective single case report that did not involve any intervention or identifiable personal information, institutional review board (IRB) approval was not required under the policy of our institution.

Guarantor

None.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of interest statement

None.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.