A 29-Year-Old Man with Uncorrected Congenital Patent Ductus Arteriosus Presenting with Heart Failure and Pulmonary Artery Vegetations Removed During Surgery: A Case Report

Introduction

Infective endocarditis (IE), characterized by inflammation of the endocardial surface due to infection, imposes a significant healthcare burden. In 2019, the global incidence of IE reached 1 090 530 cases, a marked increase from 478 000 cases in 1990 [1,2]. IE carries a high mortality risk, with about 25% of patients dying from the disease [2]. Congenital heart disease (CHD) is an independent risk factor for IE, with 11.7% of IE patients having a history of CHD [3,4]. In these patients, the aortic valve is the most commonly affected (65.6%), followed by the mitral (20.6%), pulmonary (12.8%), and tricuspid valves (8.1%) [4]. However, complications of IE in the pulmonary artery are rarely documented [5–8].

Patent ductus arteriosus (PDA) is the most prevalent congenital heart defect (CHD) in preterm infants, occurring in approximately 1 in 2000 live births and accounting for 5–10% of all cases of congenital heart disease [9]. A variety of diagnostic modalities can be employed to identify PDA, including echocardiography, cardiac computed tomography (CT), cardiac magnetic resonance (CMR) imaging, and cardiac catheterization [10]. PDA is associated with several complications, including heart failure, pulmonary hypertension, aneurysm formation, and, rarely, infective endocarditis (IE) [11]. The current guidelines provide clear indications for PDA closure in adults, which are based on left ventricular (LV) volume overload and a pulmonary vascular resistance (PVR) of less than 3 Wood units [11]. Furthermore, surgical intervention is recommended for patients with PDA and right-sided infective endocarditis if the vegetation is ≥20 mm in size [1]. However, the guidelines do not specifically address the size criteria for vegetation in the pulmonary artery. Moreover, several case reports have highlighted the unpredictable nature of vegetation resolution with antibiotic therapy alone in patients with PDA and IE, suggesting that unresolved vegetations can increase the risk of septic pulmonary embolism [7,8,12–15]. Given the ambiguity surrounding the indication and timing of surgical intervention, this report describes the case of a 29-year-old man with uncorrected congenital PDA presenting with heart failure and pulmonary artery vegetations removed during PDA surgical ligation.

Case Report

A 29-year-old man presented to the Emergency Department with a 3-day history of dyspnea and orthopnea. He had been experiencing exertional dyspnea and ankle edema for 2 months. He had a history of undocumented congenital heart disease since birth, but declined surgical intervention and was subsequently lost to follow-up. He was afebrile, with vital signs showing normal blood pressure (130/80 mmHg), tachycardia (heart rate: 108 bpm), tachypnea, and decreased peripheral oxygen saturation (SpO2: 90%). Physical examinations revealed congestion signs, including an S3 heart sound, laterally displaced apical impulse, rales, elevated jugular venous pressure (JVP), positive hepatojugular reflux, hepatomegaly, and ankle edema. Additionally, a grade 3/6 continuous machinery murmur was heard in the left subclavicular region (Gibson’s murmur). There were no Roth spots, Janeway lesions, or Osler nodes.

An electrocardiogram indicated sinus tachycardia, left atrial enlargement, and left ventricular hypertrophy. Laboratory tests revealed leukocytosis (19 260/μL, NR 4400–11 300/μL), elevated C-reactive protein levels (7.67 mg/dL, NR <0.3 mg/dL), and normal procalcitonin levels (0.22 ng/mL, NR <0.5 ng/mL). A chest radiograph showed cardiomegaly, alveolar edema, and bilateral pleural effusion. Echocardiography revealed a patent ductus arteriosus (PDA) with continuous flow (diameter 6–7 mm) and peak pressure gradient of 78 mmHg, accompanied by multiple vegetations in the main and right pulmonary arteries, with no vegetation visible in the pulmonary valve. It also showed all heart chambers were dilated, eccentric left ventricular (LV) hypertrophy, left atrium volume index (LAVI) of 80.6 mL/m2, right atrium area of 21 cm2, left ventricular end-diastolic diameter (LVEDD) of 75 mm, right ventricular basal diameter of 46 mm, reduced LV systolic function with LV ejection fraction of 43%, peak valvular abnormalities (moderate aortic regurgitation, mild functional pulmonary regurgitation, moderate functional mitral regurgitation, moderate functional tricuspid regurgitation), a high probability of pulmonary hypertension, and estimated pulmonary vascular resistance (ePVR) of 2.82 Woods unit. The echocardiography results are depicted in Figures 1 and 2.

Additionally, cardiac computed tomography (CT) confirmed a large PDA with tubular morphology and no constriction (Type C), measuring 8.1–8.9 mm in diameter. The CT also identified multiple hypoattenuating masses in the main pulmonary artery, indicative of several vegetations. The CT images are depicted in Figures 3 and 4.

Initial decongestion was achieved using intravenous furosemide (40 mg twice daily) until the patient became euvolemic on day 3 of hospitalization. Blood samples were taken for culture prior to commencing antibiotic treatment. Empirical antibiotics, ampicillin-sulbactam (3 g IV 4 times daily) and gentamicin (150 mg IV once daily), were initiated while awaiting blood culture results. Leukocyte and CRP levels significantly decreased to 8870/μL and 4.12 mg/dL, respectively, after 2 days of antibiotic administration. On day 3, he underwent open surgical evacuation of the pulmonary artery vegetations and PDA ligation. The intraoperative findings of multiple vegetations in the pulmonary artery are depicted in Figure 5.

Echocardiography revealed no residual leakage and no apparent vegetations in the pulmonary artery after surgery. Blood and vegetation cultures were negative for bacterial infection. Histopathological analysis of the vegetation revealed the presence of platelets, fibrin, erythrocytes, and inflammatory cells. Hence, he was diagnosed with possible IE, and antibiotics were continued until 13 days after surgery, along with medical care of innate oro-dental infections associated with the IE. To manage heart failure associated with PDA, we administered ramipril 5 mg orally once daily, bisoprolol 2.5 mg orally once daily, and spironolactone 25 mg orally once daily. He developed catheter-associated urinary tract infections (CAUTI) on day 4 after surgery and was safely discharged on day 10 with amoxicillin/clavulanic acid to treat the CAUTI.

Four months after discharge, he was asymptomatic and hemodynamically stable. The echocardiography revealed no residual PDA and no vegetation visible in the pulmonary artery, with a significant improvement of LVEF to 50% and a substantial reduction of LAVI, RA area, LVEDD, and RV basal diameter to 26 mL/m2, 14 cm2, 59 mm, and 42 mm, respectively.

Discussion

This case report highlights a rare presentation of PDA complicated by IE and multiple vegetations in the pulmonary artery, which was successfully managed with open surgical evacuation, PDA ligation, and antibiotics. Our case report also shows the importance of aggressive surgical intervention for the removal of pulmonary artery vegetations, irrespective of their size, in reducing the risk of acute pulmonary embolism. The patient was diagnosed with possible IE based on the modified Duke criteria, fulfilling 1 major criterion (multiple vegetations in the pulmonary artery) and 1 minor criterion (predisposing heart condition: PDA) [1]. The left-to-right shunt caused by the PDA increases blood flow via the pulmonary artery, exacerbating pathological pulmonary vascular shear stress and endothelial breakdown, which promotes vegetation development during bacteremia. Endothelial disruption promotes fibrin deposition and aggregation, resulting in formation of vegetations and development of infective endocarditis [16].

Three critical points emerge from this case report: (1) the importance of screening symptomatic CHD patients for IE and its complications to avoid missed diagnoses and poor outcomes; (2) the benefit of aggressive intervention in IE patients with PDA and multiple vegetations in the pulmonary artery to prevent septic pulmonary embolism; and (3) the necessity of identifying the etiology of IE to guide suitable therapeutic measures.

Although most patients with IE present with fever, some are afebrile, defining euthermic endocarditis [17]. According to an observational study conducted by Abdelgawad et al, fever occurs in only 69.67% of hospitalized IE patients [18]. Euthermic endocarditis is more common in older individuals and has been linked to longer symptom duration and delayed identification of IE [17]. In this case, our patient presented to the Emergency Department with acute decompensated heart failure, no fever, and an unknown history of CHD. The diagnosis of PDA complicated by IE and multiple vegetations in the pulmonary artery was first established during this hospitalization, underscoring that IE with a high risk of pulmonary embolism can occur in symptomatic PDA patients without signs of IE. According to the 2020 ESC guidelines on adult congenital heart disease, echocardiographic examinations should be repeated every 1–3 years in patients with PDA to evaluate heart size, function, estimated pulmonary arterial pressure, and complications such as IE [11]. Thus, an aggressive and comprehensive diagnostic approach is warranted for all patients with CHD.

The 2023 European Society of Cardiology (ESC) guidelines recommend several imaging modalities to evaluate IE complications, including echocardiography, CT, SPECT, and FDG-PET scans [1]. The meta-analysis conducted by Jain et al demonstrated that cardiac CT is advantageous in cases of prosthetic valve involvement and shows a trend toward improved detection of peri-annular complications compared to echocardiography, but echocardiography was superior in detecting vegetation [19]. Thus, cardiac CT is an invaluable adjunct imaging modality for evaluating infective endocarditis (IE) and its complications, as well as in the preoperative assessment for IE surgery. In this case, initial trans-thoracic echocardiography identified the PDA and multiple vegetations in the pulmonary artery. Moreover, cardiac CT confirmed the findings and showed no other IE complications, including abscess, valve perforation, and fistula, indicating isolated IE in the pulmonary artery.

According to the 2023 ESC guidelines on infective endocarditis, open surgical removal of embolic materials is recommended for patients with vegetation sizes of ≥10 mm and ≥20 mm in left-sided and right-sided IE, respectively [1]. However, the guidelines do not specifically address the size criteria for vegetations in the pulmonary artery. Due to the limited number of cases, no observational study has evaluated the benefits and risks of surgical intervention for pulmonary artery vegetation. However, several case reports have documented scenarios similar to ours. For instance, Mahajan et al, in India, reported a case involving a 10-year-old girl with patent ductus arteriosus (PDA) complicated by infective endocarditis (IE) and a solitary vegetation located in the pulmonary artery [8]. She presented with intermittent fever, and blood cultures identified Pseudomonas aeruginosa as the causative pathogen. Unlike our case, surgical intervention was not required, as echocardiographic follow-up revealed complete resolution of the vegetation after 14 days of antibiotic therapy. Similarly, Kanai et al described the disappearance of pulmonary artery vegetations after a 4-week course of antibiotics in a patient with PDA and IE [12]. In contrast, Sabzi et al, in Iran, reported a case involving a 28-year-old woman with PDA complicated by IE and a single, non-mobile vegetation in the pulmonary artery [7]. She exhibited febrile symptoms, and blood cultures confirmed Streptococcus pneumoniae infection. However, despite 4 weeks of antibiotic treatment, the vegetation persisted, necessitating surgical intervention, including PDA ligation and removal of the vegetation. This aligns with findings by Ku et al and Ramiro et al, who also observed a lack of resolution of pulmonary artery vegetations following antibiotic therapy, ultimately requiring surgical removal of the vegetations and PDA ligation [14,15]. Additionally, Cruz-Gonzalez et al reported a case of septic pulmonary embolism occurring after 10 days of antibiotic treatment in a patient with PDA and IE complicated by pulmonary artery vegetations [13]. Collectively, these case reports highlight the unpredictable nature of vegetation resolution with antibiotic therapy alone in patients with PDA and IE. Untreated vegetations can increase the risk of complications such as septic pulmonary embolism, emphasizing the importance of consideration of urgent surgical intervention.

According to the European Society of Cardiology (ESC) guidelines on infective endocarditis, surgical vegetation removal should be performed urgently, within 3–5 days, in patients at imminent risk of pulmonary embolization [1]. Furthermore, the ESC guidelines for congenital heart disease recommend PDA closure in patients with left ventricular (LV) volume overload and pulmonary vascular resistance (PVR) below 3 Wood units [11]. Our patient presented with an LVEDD of 75 mm, indicating significant LV volume overload, and an ePVR of 2.82 wood units, confirming acceptable pulmonary vascular resistance. In addition, the presence of highly mobile, multiple vegetations in the pulmonary artery posed a substantial risk of pulmonary embolization. Given these findings, we opted for early open surgery on the third day of hospitalization. The procedure involved evacuation of the vegetations from the pulmonary artery to mitigate the embolic risk and ligation of the PDA to address the LV volume overload. There were no bleeding complications or surgical site infections during hospitalization, and echocardiography showed no residual PDA, and no vegetation visible in the pulmonary artery, accompanied a significant improvement of LVEF and a substantial reduction of heart chambers dimension 4 months after surgery, suggesting that the benefits of early surgical intervention outweigh the risks in patients with IE and multiple thrombi in the pulmonary artery.

Identifying the causative bacteria in IE is crucial not only for selecting the appropriate antibiotic regimen but also for predicting the risk of embolism, perivalvular complications, and long-term mortality. Staphylococcus aureus IE significantly increases the risk of embolism and long-term mortality compared to other bacteria [20]. However, conventional blood culture procedures do not always yield an organism, defined as blood culture-negative infective endocarditis (BCNIE) [21].

A systematic review of 33 214 cases reporting IE microbiology indicated that the BCNIE incidence was approximately 26%, making this condition somewhat prevalent in daily clinical practice [22]. According to ESC guidelines, polymerase chain reaction (PCR) and bacterial serology tests should be performed to identify viral infections and other bacterial infections (eg, Bartonella spp., Coxiella burnetii, Aspergillus spp., Legionella pneumophila, Brucella spp., and Mycoplasma pneumoniae) [1]. However, due to limited facilities, we were unable to perform these tests. Non-infectious causes of endocarditis, particularly nonbacterial thrombotic endocarditis (NBTE), should also be considered in the differential diagnosis of BCNIE in the appropriate clinical setting. Given that our patient’s clinical presentation more strongly suggested an infection, we ruled out this scenario, since NBTE is often linked to hypercoagulable disorders, such as autoimmune diseases or cancer, which can cause sterile thrombi to lodge on heart valves [23].

Since IE-related fastidious microorganisms (requiring prolonged incubation periods) account many BCNIE cases, it is indicated to cover infections caused by S. aureus, enterococci, streptococci from the viridans group, and HACEK (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, and Kingella) organisms with a suitable broad-spectrum treatment regimen comprises vancomycin and ampicillin-sulbactam for a 2-week course [23]. However, in this case, based on the reduced leukocyte and C-reactive protein (CRP) levels after 3 days of antibiotic administration, we continued antibiotic therapy with ampicillin-sulbactam and gentamicin until discharge. The CRP and leukocyte level at discharge was not significantly reduced due to a secondary urinary infection during hospitalization.

The main limitation of this case report was the lack of laboratory facilities. Hence, we could not perform PCR and bacterial serology tests to identify the source of infection.

Conclusions

This case report presents a rare instance of a patient with PDA complicated by IE and multiple, mobile vegetations in the pulmonary artery. It underscores the importance of aggressive treatment with open surgical evacuation of vegetation, regardless of size, and PDA ligation in diminishing the risk of acute pulmonary embolism, improving the LV function and reducing the heart chambers’ dimensions. This management approach was also safe with no significant adverse effects observed after surgery.