Isolated Native Pulmonary Valve Endocarditis

Abstract

Background

Isolated native pulmonic valve endocarditis is a rare presentation of infective endocarditis.

Case Summary

A female patient with a history of stage IV breast cancer requiring anterior chest wall radiation and chemotherapy presented with a 3-month course of constitutional symptoms and was found to have isolated pulmonary valve endocarditis that was medically managed with antibiotics and outpatient follow-up.

Discussion

Isolated native pulmonic valve endocarditis is a rare diagnosis, and pulmonic valve endocarditis can be difficult to appreciate or missed on an echocardiogram. Valvular degeneration can begin with as little as 25 Gy of radiation.

Take-Home Message

Valvular degeneration from chest wall radiation is a rare risk factor in developing infective endocarditis, and careful attention must be paid to the pulmonic valve if endocarditis is being considered.

Graphical Abstract

History of Presentation

A 61-year-old woman with stage IV breast cancer, complicated by a left anterior mediastinal mass and boney metastases, presented to the emergency department with a 3-month history of chills and night sweats. She reported pelvic pain and heavy vaginal bleeding but denied any dental caries, skin wounds, chest pain, shortness of breath, palpitations, nausea, vomiting, diarrhea, abdominal pain, and urinary symptoms. She had no known cardiac history, recent indwelling central access, intravenous drug use, recent illness, sick contacts, or travel history.

On arrival, her vital signs were normal. She was afebrile, her blood pressure was 121/74 mm Hg, her heart rate was 85 beats/min, and she was breathing at a rate of 20 breaths/min, saturating 97% on room air. Her examination was remarkable for poor oral dentition and a 2/4 diastolic murmur best heard at the left upper sternal border. Her lungs were clear to auscultation, and there was no peripheral edema. She had postsurgical changes from a left breast mastectomy and a chronic 5-cm area of hyperpigmentation of her anterior chest wall with overlying induration from prior radiation. She had no evidence of nonsplinter hemorrhages, Osler nodes, or Janeway lesions.

Past Medical History

The patient was initially diagnosed with left-sided stage IIA breast cancer (ypT1cN1) in 2006. She initially underwent neoadjuvant chemotherapy, followed by wide local excision with axillary lymph node dissection and radiation therapy, with a total dose of 80.6 Gy to the left chest wall and supraclavicular region in 2006. After 5 years of maintenance tamoxifen, she had a left anterior mediastinal mass recurrence (2011). She subsequently underwent multiple lines of chemotherapy and hormonal therapy, including 3 months of Taxol (Paclitaxel), requiring a peripherally inserted central venous catheter placed and removed in 2012. Despite treatment, she had a progression of disease, and in 2012, she received additional radiation to her chest wall mass, with a total dose of 52 Gy. In 2015, she received intensity-modulated radiation therapy for metastatic lesions to her sternum and mediastinum. Her course was further complicated by metastatic lesions to her left lesser trochanter, and in 2017, she underwent radiation therapy of her hip with a total dose of 44 Gy. At the time of this presentation in 2021, she was on palbociclib (started 2017) and anastrozole (started 2019).

Differential Diagnosis

The differential diagnoses included endocarditis, pulmonary embolism, pneumonia, bacteremia, heart failure, tuberculosis, and progression of metastatic breast cancer.

Investigations

Laboratory data on presentation were notable for a leukopenia to 4.3 × 10³/μL, with neutrophil predominance of 81% and an absolute lymphocyte manual count of 0.3 × 10³/μL. She had a macrocytic anemia with a hemoglobin level of 8.7 g/dL. Her basic metabolic panel was otherwise unremarkable with a creatinine level of 0.60 mg/dL. On hospital day 1, blood cultures grew gram-positive cocci in 4/4 bottles, later speciating to Streptococcus cristatus (a member of the Streptococcus viridans family). She was initiated on ceftriaxone and vancomycin. A transthoracic echocardiogram (TTE) demonstrated a normal left ventricular ejection fraction (65%-70%), and all her valves appeared structurally normal with moderate tricuspid valve regurgitation. The pulmonic valve was poorly visualized but demonstrated a normal Doppler profile with a peak velocity of 1.8 m/s. Right ventricular size and function were both preserved and normal. The tricuspid valve appeared structurally normal. A transesophageal echocardiogram (TEE) was recommended given heightened concern for endocarditis because of her murmur, moderate tricuspid regurgitation, and type of bacterial species. Given the concern for endocarditis, a TEE was assessed. It demonstrated a small, 7-mm, mobile vegetation on the anterior cusp of the pulmonary valve with moderate-to-severe regurgitation concerning for endocarditis (Figure 1, Figure 2, Figure 3). All other valves were without evidence of vegetation. Computed tomography thorax with contrast demonstrated an acute pulmonary embolism within her right interlobar pulmonary artery; postsurgical and radiation changes of the left lung apex, chest wall, and sternum; and interval increase in mediastinal lymphadenopathy.

Visual Summary.

Timeline of Patient's Diagnosis, Chemotherapy/Radiation Treatment, and Hospital Presentation

PICC = peripheral inserted central catheter.

Figure 1.

Midesophageal View at 130° With X-Plane During a Transesophageal Echocardiogram Demonstrating the Pulmonic Valve Endocarditis

The figure on the right is a 90° view of the figure on the left. The arrows point to the pulmonary valve lesion concerning for endocarditis.

Figure 2.

Close-Up View of a Midesophageal View at 130° With X-Plane During a Transesophageal Echocardiogram Demonstrating the Pulmonic Valve Endocarditis

The arrows point to the pulmonary valve lesion concerning for endocarditis.

Figure 3.

Midesophageal View of a Transesophageal Echocardiogram at 75° Demonstrating Pulmonic Regurgitation

Management (Medical/Interventions)

The patient was continued on a 6-week course of antibiotics. She was not referred to cardiothoracic surgery for any surgical intervention because she demonstrated no signs of heart failure and no complications of endocarditis (ie, abscess and cardioembolic phenomenon), and the speciated organism was not resistant. Repeat TTE 6 months later remained largely unchanged with evidence of severe pulmonary regurgitation given cusp perforation, flow reversal in the main pulmonary artery, and moderate tricuspid regurgitation with preserved right ventricle function and size. No new vegetation has been identified on the surface echo. She has continued to follow up in the cardiology clinic without any evidence of heart failure and remains euvolemic and asymptomatic.

Discussion

Isolated native pulmonary endocarditis in structurally normal hearts is very rare. Diagnosing isolated native pulmonic valve endocarditis (IPVE) presents significant challenges, given that most patients lack signs of valvular disease. Infrequently, IPVE can manifest with clinical sequelae from pulmonic regurgitation with right-sided heart failure symptoms. More commonly, patients with IPVE present with nonspecific symptoms such as persistent fever and pulmonary symptoms, including dyspnea, cough, and a low-pitched diastolic murmur. An added difficulty in this diagnosis is the lack of sensitivity of echocardiogram. TTE has an estimated sensitivity of 30% to 63% and specificity of 91% to 100%, given technical challenges to capture regurgitant flow, which can be attributed to limited or poor acoustic windows. Pulmonary regurgitation can be overlooked on echocardiography as the regurgitant diastolic flow can be laminar and low velocity. Identifying pulmonic regurgitation requires careful attention to the images obtained and performing dedicated transthoracic views when uncertain. Guideline-based pulmonic regurgitation quantification, most importantly, includes looking for main or branch pulmonary artery diastolic flow reversal with appropriately targeted color Doppler acquisition. Additional important parameters are identifying signs of right ventricular volume overload (dilation, septal flattening), measuring a pulmonic regurgitation index, and pressure half-time. In our patient, pulmonic valve vegetation and regurgitation were missed on the initial TTE, common with acquired pulmonic valve disease. There are very few validated studies assessing pulmonic regurgitation. Pulmonic regurgitation is best evaluated by TTE using color Doppler imaging in the parasternal short-axis view, which allows visualization of the pulmonary valve and the diameter of the regurgitant jet. The vena contracta width measurement is a different, possibly more accurate method, currently limited by validation studies.¹ In this method, the regurgitation jet is measured at the narrowest part of the jet, just distal to the regurgitant orifice. In contrast, TEE has an estimated sensitivity of 87% to 100% and a specificity of 91% to 100%, despite challenges with visualizing this more anterior valve.^2,3

Patients with IPVE usually have underlying risks for right-sided endocarditis such as indwelling cardiac lines and/or intravenous drug use. Although our patient lacked traditional risk factors, her oncologic history likely put her at heightened risk for this phenomenon. Specifically, radiation therapy is known to cause degenerative valvular heart disease, with higher radiation doses increasing the likelihood of radiation heart disease. Throughout her current cancer treatment, she had received 2 separate rounds of radiation treatment, both with a focus on the left anterior mediastinal chest wall mass, with a total dose of 132.6 Gy. There is a direct dose-dependent relationship between cardiotoxicity and the amount of anterior chest wall radiation. Valvular pathologies are the most common cardiac complication affecting 21% to 41% of patients who undergo radiation.⁴ Asymptomatic valvular disease can occur with as little as 25 Gy.^5,6 Although left-sided valvular pathologies are more common, the location and dosage of our patient's radiation likely increased her risk for right-sided valvular involvement.⁷ We hypothesize that she had underlying radiation-induced PV degeneration, which allowed endocarditis to take hold. In addition, our patient had a remote history of a peripheral inserted central catheter, a known source of right-sided infective endocarditis. Given that the peripheral inserted central catheter was removed 10 years before the presentation, we do not suspect that this was the driving risk factor.

Her history of chemotherapy and immunocompromised state also heightened her risk of endocarditis. On presentation, she was taking palbociclib and anastrozole. Palbociclib has been described to cause severe lymphopenia and severe cellular immunodeficiency, whereas anastrozole has not been described to have significant direct immunosuppressive effects.⁸ S. cristatus (a member of the Streptococcus viridans family) is an infrequently reported cause of infective endocarditis,⁹ but this more indolent organism likely was able to be pathogenic given her immunocompromised state.

Specific guidelines for managing and treating acquired pulmonic valve endocarditis are limited. Because pulmonic valve endocarditis tends to be secondary to congenital abnormalities, management tends to be extrapolated from current adult congenital heart disease guidelines and is dependent on right ventricular dilation, dysfunction, and symptoms. Current guidelines suggest the use of serial cardiac magnetic resonance for quantitative assessment of the right ventricular size and function. Current guidelines for adult patients with congenital heart disease are limited to pulmonic regurgitation secondary to previous interventions of pulmonic stenosis. There is a Class I recommendation for the treatment of moderate-to-severe pulmonic regurgitation causing right ventricular dilation or dysfunction.¹⁰ Like our patient, surgery is not recommended in well-compensated patients without evidence of right ventricular dysfunction.

Follow-Up

The patient was seen in the cardiology clinic after completing her 6-week antibiotic course and felt significantly better. She continues to undergo treatment for her breast cancer with oncology and has been stable from a cardiology perspective. Although she remains asymptomatic from her pulmonic regurgitation, additional work-up with cardiac magnetic resonance has been ordered to further assess the right ventricle and pulmonic regurgitation.

Conclusions

IPVE is a rare form of endocarditis. It should be considered in individuals with a significant amount of chest wall radiation or who are immunocompromised, even if they lack other typical risk factors.

Take-Home Messages

• •Isolated pulmonary valve endocarditis is a rare condition and can be easily missed on a transthoracic echocardiogram if careful consideration is not given.
• •It is important to highlight complications of chest wall radiation and chemotherapy given the increasing survival rate in patients with cancer.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.