Persistent Left Superior Vena Cava in the Setting of Granulicatella adiacens Bactermia and Crescentic Glomerulonephritis

Abstract

Persistent left superior vena cava is a rare congenital condition, that is, commonly found to be asymptomatic in affected patients. Such pathology can lead to dilatation of the coronary arteries, creating a favorable environment for bacterial growth. We present a case of Granulicatella adiacens bacteremia ultimately leading to renal failure in the setting of an IgA-dominant infection-associated glomerulonephritis. Our case highlights the importance of multimodal imaging for the diagnosis of this unusual vascular anomaly, as well as the management of this atypical etiology of high-grade bacteremia.

Introduction

Congenital vascular abnormalities represent a variety of pathologies, ranging from benign to life-threatening conditions. ¹ Currently, the International Society for the Study of Vascular Anomalies exists primarily for the classification of vascular anomalies. ¹ Early identification and detection are essential for proper management of these rare abnormalities. Embryogenesis for the development of the venous system includes the development of the vitelline veins, umbilical veins, and cardinal veins (CV). ² During typical angiogenesis, the caudal right superior CV will combine with the common CV and form a right superior vena cava. ² However, if embryogenesis does not occur correctly, this may lead to rare vascular abnormalities, including a persistent left superior vena cava (PLSVC). ² Several theories exist for the development of this rare vascular abnormality, including the “low atrial left atrial pressure theory.” ² This theory suggests reduced left atrial pressure may impair regression of the left and superior CV, leading to a PLSVC. ² A relatively rare vascular abnormality that affects ~0.3% of the general population, many cases remain undetected, as most patients are asymptomatic, and the anomaly is often detected incidentally.^2,3 Cases have identified PLSVC with dilatation of the coronary sinuses secondary to direct drainage to the right atrium through the coronary sinus. ⁴ Dilatation of the coronary sinus likely predisposes blood vessels as seeding grounds for bacteria in the setting of high-grade bacteremia.

Bacteremia remains a major cause of morbidity and mortality worldwide, with an especially high mortality rate of 37%. ⁵ Older individuals, especially those with multiple medical comorbidities, are at increased risk for the development of bacteremia. ⁵ Granulicatella adiacens, also known as nutritionally variant streptococci, is a Gram-positive bacterium characterized by its complex growth patterns. ⁶ First described in 1960, G. adiacens accounts for 2.3% streptococcus bacteremia. ⁶ Cincotta et al explored typical cases of G. adiacens, finding infected mitral valves, aortic valves, and tricuspid valves to be the most common infectious etiology. ⁷ One case described an infected abdominal aortic graft as a source of bacteremia. ⁷ Here, we present a case of high-grade bacteremia secondary to G. adiacens leading to acute renal failure in the setting of biopsy-proven crescentic glomerulonephritis.

Case Presentation

The patient is a 55-year-old male with past medical history of hypertension, hyperlipidemia, gastroesophageal reflux disease, obstructive sleep apnea, morbid obesity, tobacco use disorder in remission, chronic obstructive pulmonary disease, chronic diastolic heart failure with preserved ejection fraction (69.7%), mild tricuspid regurgitation, mild mitral regurgitation, and metabolic dysfunction-associated steatohepatitis who initially presented to an outside facility’s emergency department for acute hypoxemic respiratory failure secondary to volume overload in the setting of acute renal failure, as well as back pain. At admission, examination revealed a bilateral rash on the anterior calves, characterized as a violaceous, palpable purpuric rash that was nonitching and painful. The patient also endorsed reduced urine output. At presentation, blood urea nitrogen was elevated to 90 mg/dL (6-20 mg/dL), creatinine of 6.46 mg/dL (0.7-1.3 mg/dL), bicarbonate of 19 mmol/L (22-29 mmol/L), C-reactive protein of 82.9 mg/L (<3 mg/L), and brain natriuretic peptide of 1728 pg/mL (<100 pg/mL). The patient was hypotensive and found to be in atrial fibrillation with rapid ventricular response. Initial chest x-ray revealed mild cardiomegaly, pulmonary edema, and a trace right pleural effusion. Blood cultures were also obtained, and the patient was started on vancomycin. The patient was started on a diltiazem drip and titrated to 15 mg/hour and transferred to our academic medical center’s medical ICU (MICU) for further management of care. Blood cultures from the outside hospital were positive in 1/2 bottles obtained from the patient’s left peripheral intravenous (IV) and positive in 2/2 bottles from the patient’s right peripheral IV, with Gram-positive cocci in pairs and chains speciated as G. adiacens. On presentation to the MICU, the patient was continued on vancomycin, and blood cultures were re-drawn. Due to an increased oxygen requirement, the patient was initiated on bi-level positive pressure ventilation and treated for an exacerbation of chronic obstructive pulmonary disease (COPD) and treated with a course of 500 mg azithromycin as well as a 5-day course of 40 mg Prednisone. The patient was ultimately transferred from the MICU to the floor for further management. Further laboratory workup revealed C3 decreased to 68 mg/dL (81-157 mg/dL), C4 decreased to 11 mg/dL (12-39 mg/dL), rheumatoid factor increased to 89 IU/mL (0-30 IU/mL), cytoplasmic antineutrophil cytoplasmic antibody elevated to 1:20, and proteinase IgG antibodies were positive with a titer of 6.1 AAU/mL (<1.0 AAU/mL). A renal biopsy was performed due to the progression of the patient’s acute renal failure, and the patient also underwent a skin biopsy, which was remarkable for a leukocytoclastic vasculitis. Blood cultures obtained at admission to our facility from the patient’s right peripheral IV site were positive for Gram-positive cocci in pairs and chains in 1/2 bottles (aerobic bottle), whereas cultures from the patient’s left peripheral IV site were positive in both bottles (aerobic and anaerobic bottle) for Gram-positive cocci in pairs and chains, and the patient was initiated on vancomycin due to continued bacteremia despite broad spectrum antibiotics at the outside hospital. A transthoracic echocardiogram (TTE) was obtained and was unrevealing for a vegetation or infectious source. An orthopantogram was obtained due to poor dentition and was unremarkable. A lumbar spine X-ray was also obtained due to endorsements of back pain upon admission and was also unrevealing. The patient denied a history of IV drug use, as well as external hardware implantation from prior surgeries. A transesophageal echocardiogram was obtained and was concerning for a contained left atrial free rupture with evidence of a PLSVC and dilated coronary sinus (Figure 1). Agitated saline was not performed in our case as we had a lower suspicion for a stroke and a congenital cardiac pathology such as a patent foramen ovale (PFO) contributing to a thromboembolic event. Cardiac surgery was consulted and recommended a computed tomography angiography (CTA) heart morphology for further characterization of the suspected contained perforation (Figure 2). After a further review of the patient’s CTA heart morphology, there was no evidence of an atrial wall perforation or contained rupture, but rather a PLSVC draining into a dilated coronary sinus not requiring surgical intervention. The patient’s unusual anatomy and dilated coronary sinus created a seeding ground for bacteria and was the etiology of the patient’s bacteremia. His repeat blood cultures remained negative, and he was continued on vancomycin for a total of 6 weeks. The patient’s renal function continued to decline during his hospitalization, and he ultimately required intermittent hemodialysis. Vancomycin therapy was continued in the setting of the patient’s declining renal function, as we hypothesized his renal failure was secondary to an infection-related glomerulonephritis and would recover with treatment of his underlying infection. The patient underwent a renal biopsy and was found to have IgA crescentic glomerulonephritis with C3 codominant immune deposits, consistent with an IgA-dominant infection-associated glomerulonephritis (Figure 3). The source of the patient’s vasculitis was thought to be secondary to his concurrent infection. Due to his bacteremia, immunosuppressive therapy was deferred. The patient was ultimately discharged and scheduled to receive dialysis 3 times weekly as an outpatient, as well as continuation of antimicrobial therapy for a total of 6 weeks.

Figure 1.

TEE with evidence of a perforation of the left atrial free wall between the mitral annulus and the left atrial appendage with what appears consistent with a contained rupture (red arrow). Evidence of a PLSVC with dilated coronary sinus without visible valvular vegetation. The mitral valve can be observed to the left of the contained rupture, whereas the left atrial appendage can be observed on the right. PLSVC, persistent left superior vena cava; TEE, transesophageal echocardiogram.

Figure 2.

CTA heart morphology illustrating a PLSVC (red arrow, red dot) draining to a coronary sinus with evidence of dilation (blue dot). There was noted to be an absent right-sided superior vena cava (SVC) as well as a communication of 1.1 cm between the coronary sinus and the left lateral atrial wall. CTA, computed tomography angiography; PLSVC, persistent left superior vena cava.

Figure 3.

Kidney biopsy demonstrating an IgA dominant-infection associated glomerulonephritis. (A) Low-power image demonstrating moderate interstitial fibrosis and tubular atrophy, Masson-Trichrome, 20×. (B) Acute tubular injury with a red blood cell cast, hematoxylin and eosin, 400×. (C) Glomerulus with mesangial matrix expansion and mesangial hypercellularity, periodic acid Schiff, 400×. (D) SMMT stain showing a cellular crescent, 400×. (E, F) Direct immunofluorescence for IgA and C3 demonstrating positive granular mesangial and segmental capillary loop staining, 400×. SMMT, silver methenamine Masson trichrome.

Discussion

PLSCV remains a rare congenital vascular anomaly, occurring in ~0.3% of individuals. ² Although typically asymptomatic, this pathology may lead to dilated coronary sinus and ultimately create a seeding environment for bacteria, such as in high-grade bacteremia, as seen in our case.^4,8 In more severe cases, PLSVC may lead to stroke secondary to thromboembolism formation in the setting of right-to-left shunting. ⁹ As patients are typically symptomatic, diagnosis requires imaging evidence of PLSVC. Detection of PLSVC by TTE relies on proper administration of agitated saline by the operator, as introduction of agitated saline to the right upper extremity venous system will likely fail to detect a PLSVC. ⁹ Our case demonstrated this, as the initial TTE was unable to identify the PLSVC. Azizova et al further expanded on the directionality of saline administration in a case of PLSVC, ultimately diagnosing a PLSVC after the introduction of agitated saline to the left cubital vein. Azizova et al explored the limitations of echocardiography for the diagnosis of PLSVC, finding the diagnosis to be operator-dependent, acoustic window-dependent, and often limited by spatial resolution. ² Coronary CT provides superior spatial resolution, and unlike echocardiography, is independent of the directionality of contrast injection, as shown in Figure 2. ² We suspect that this vascular anomaly led to dilation of the coronary sinus, ultimately creating a seeding environment for bacteria, and was the source of the patient’s bacteremia.

G. adiacens is an unusual cause for bacteremia, accounting for only 2.3% of bacteremia secondary to streptococci. ⁶ On admission, our patient was initially found to be bacteremic secondary to G. adiacens; however, blood cultures to date have shown no growth with the continuation of vancomycin. Because of the patient’s underlying congenital heart pathology and high concern for endocarditis, we decided to treat the patient’s bacteremia according to the American Heart Association guidelines for endocarditis due to G. adiacens. ¹⁰ According to the guidelines, penicillin G is preferred in combination with gentamycin or vancomycin alone. Alternatively, ceftriaxone in combination with gentamycin is an alternative regimen. ¹⁰ Due to the patient’s acute renal failure, gentamycin combination therapy was deferred for vancomycin therapy alone. Although typically observed in normal oral flora, immunocompromised hosts have been implicated in infection, including osteomyelitis, meningitis, and infective endocarditis. ¹¹ When infection is found, early diagnosis and treatment are essential, as multiple cases of mortality and morbidity have been reported. ¹¹ Our case highlights the importance of vigilance for this uncommon bacterium, even in an immunocompetent host without risk factors for intravascular infection.

Prior to admission, our patient endorsed notably dark urine and a lower extremity rash prior to presentation. During his admission, he had notably decreased urine output with a significant uptrend in his creatinine, with renal biopsy ultimately positive for IgA crescentic glomerulonephritis with C3 codominant immune deposits (Figure 3). Crescentic glomerulonephritis is a common cause of rapidly progressive renal failure, which was consistent with our patient’s clinical course. ¹² Histologically, crescentic IgA nephropathy is defined as more than 50% of crescentic glomeruli, as well as polyclonal IgA and C3, all of which were consistent with our case.^12,13 Classically, IgA infection-related glomerulonephritis occurs in the setting of Staphylococcus infection. ¹³ Our case highlights the unusual manifestation of this renal pathology in this setting of G. adiacens. Differentiating between an IgA infection-related glomerulonephritis and a noninfectious glomerulonephritis may be difficult based on pathology findings alone. More pronounced staining of C3 compared to IgA may be visible on biopsy in an IgA infection-related glomerulonephritis; however, this finding was not apparent in our case.^13,14 Additionally, findings of glomerular crescent formation are more common in an IgA infection-related glomerulonephritis, as observed in our case (Figure 3D). ¹⁵ In both cases, mesangial matrix expansion and interstitial fibrosis are visible. ¹⁶ Because of this overlap, biopsy findings, along with the clinical presentation, must be taken into consideration when differentiating between IgA infection-related glomerulonephritis and a noninfectious etiology. ¹⁴ In the setting of an IgA glomerulonephritis secondary to an active infection, differences exist regarding immunosuppressive treatment in the setting of an ongoing infection. Kitamura et al performed a retrospective cohort study, analyzing renal biopsies performed between 2010 and 2021 and outcome differences in those who received immunosuppression and those who did not. Progression to renal loss was significantly higher in those not receiving immunosuppression, suggesting even in the setting of an active infection, immunosuppression should be cautiously considered.

Conclusion

PLSVC remains a rare congenital abnormality, presenting in 0.3% of individuals. ² Although typically asymptomatic, this vascular abnormality can lead to coronary artery dilatation and should be considered in patients with bacteremia of an unknown source. Our patient was found to be bacteremic secondary to G. adiacens with a response to vancomycin therapy. IgA-dominant infection-associated glomerulonephritis should be considered an etiology of renal failure in an individual with high-grade bacteremia and persistent renal decline. Our case highlights multiple atypical pathologies and the importance of multimodal imaging in the diagnosis and treatment.