Syphilitic Mitral Valve Endocarditis

Abstract

Background

Syphilis, caused by the bacterium Treponema pallidum, affects over 5 million people annually. Although rates have been declining, recent increases have been seen in men who have sex with men and in younger age groups.

Case Summary

A 38-year-old man with polysubstance abuse presented with chest pain, dyspnea, and orthopnea after a viral prodrome. Laboratory tests showed elevated levels of troponin and B-type natriuretic peptide. Coronary angiogram was normal, and right heart catheterization indicated elevated filling pressures. An echocardiogram showed severe mitral and tricuspid regurgitation, along with a 1.5 × 1.0 cm vegetation on the mitral valve. Syphilis serologies were positive, and polymerase chain reaction analysis of valve tissue confirmed the presence of T pallidum.

Discussion

Untreated syphilis can progress to tertiary syphilis, causing syphilitic aortitis. Mitral valve endocarditis is rare. This case emphasizes the importance of considering syphilis in cases of culture-negative endocarditis.

Take-Home Message

Consider T pallidum infection in cases of culture-negative endocarditis.

Graphical Abstract

History of Present Illness

A 38-year-old community-dwelling man with a history of polysubstance abuse (primarily methamphetamine and cannabis) for several years and poor dental hygiene, as evidenced by cracked teeth and dental caries, presented to the emergency department with pleuritic chest pain and exertional shortness of breath (NYHA functional class II symptoms). Two weeks before presentation, he had experienced productive cough, fever, chills, and body aches, leading to a diagnosis of multifocal pneumonia at another hospital. He was treated with a 7-day course of doxycycline and azithromycin, which he completed 1 week before this presentation. Despite his completing the course of antibiotics, his symptoms worsened, with progressive dyspnea, orthopnea, pleuritic chest pain radiating to the left arm, and bilateral lower extremity edema.

Take-Home Message

• •In cases of culture-negative endocarditis with suggestive clinical and imaging findings, clinicians should consider less common pathogens such as T pallidum.

A more detailed history was obtained to further elucidate potential risk factors. The patient initially denied intravenous drug use, recent travel, sick contacts, or any history of sexually transmitted infections. He stated he had never been evaluated by a physician for sexually transmitted infections, including syphilis or HIV. On further questioning, he admitted to being sexually active with multiple female partners in the past year and reported inconsistent condom use. He denied any history of prior syphilis testing or diagnosis. The patient's social history included current smoking (1 pack/d for 20 years) and occasional alcohol use. He reported polysubstance abuse (methamphetamine and cannabis) but denied intravenous drug use. His employment status was unknown, and he identified as heterosexual and single.

Physical Examination

On initial evaluation, the patient was afebrile but appeared acutely ill. His blood pressure was 104/74 mm Hg, he was tachycardic, with a heart rate between 109 and 122 beats/min, and he was tachypneic, with respiratory rate between 16 and 27 breaths/min and oxygen saturation of 91% on room air, improving to 98% with 2 L/min nasal cannula. Further examination revealed him to be alert and oriented, although he appeared ill and was dyspneic. The oral examination revealed dental caries involving the first left molar. He exhibited scleral icterus. The neck examination revealed jugular venous distension extending to the angle of the jaw. Cardiovascular auscultation revealed a pronounced gallop at the apex, along with a new 3/6 pansystolic murmur loudest at the apex and radiating to the axilla. Lung auscultation revealed diminished breath sounds in the lower right posterior lung field. He did not have organomegaly, abdominal tenderness, joint swelling or tenderness, petechiae, or any skin rashes. The palpation of the liver was unremarkable, and no hepatomegaly was appreciated.

Investigations

Differential diagnosis

The differential diagnoses included infective endocarditis, acute congestive heart failure exacerbation, pneumonia, and pulmonary embolism (Table 1).

Table 1.

Summary of Key Laboratory Investigations

	Result	Reference Range
White blood cell count	11.5 × 103/L	4.0-11.0 × 103/L
Hemoglobin	10.5 g/dL	13.5-17.5 g/dL
Platelet count	210 × 109/L	150-400 × 109/L
High-sensitivity troponin	67 ng/L	<0.4 ng/L
BNP	1,739	0-15 pg/mL
ALT	1,073 U/L	7-55 U/L
AST	504 U/L	8-48 U/L
Total bilirubin
Serum creatinine	1.4 mg/dL	0.6-1.3 mg/dL
Blood cultures	Multiple sets negative	NA
Rapid plasma reagin	Reactive	Nonreactive
HIV 1/2	Nonreactive	Nonreactive
Hepatitis C antibody	Nonreactive	Nonreactive
Hepatitis B surface antigen	Nonreactive	Nonreactive
Hepatitis B core antibody	Nonreactive	Nonreactive
Cocaine	Positive	Negative

ALT = alanine aminotransferase; AST = aspartate aminotransferase; BNP = B-type natriuretic peptide; NA = not applicable.

Imaging

Findings on diagnostic imaging were as follows:

• •Computed tomography angiography of the chest was negative for pulmonary embolism, and it showed multifocal pulmonary consolidations suggestive of septic emboli, trace bilateral pleural effusions, and cardiomegaly. The size of the thoracic aorta was normal, and there were no signs of aortitis.
• •Two-dimensional echocardiography demonstrated a left ventricular ejection fraction of 70%, grade 2 diastolic dysfunction, severe mitral and tricuspid regurgitation, and mild aortic regurgitation. Aortic root, thickness, and diameter were within normal limits (Figure 1).
• •Right heart catheterization indicated severe combined pre- and postcapillary pulmonary hypertension, evidenced by significantly elevated V-wave in the pulmonary capillary wedge pressure tracing, suggestive of mitral regurgitation. The hemodynamic measurements were as follows: right atrial pressures of 10/10/7 mm Hg, right ventricular pressures of 41/2 mm Hg, pulmonary artery pressures of 61/36 mm Hg (mean: 47 mm Hg), pulmonary capillary wedge pressure of 32/31/25 mm Hg, pulmonary vascular resistance of 7 WU, and cardiac output/cardiac index of 3.3/1.8 L/min/m² by Fick method.
• •Left heart catheterization and coronary angiogram revealed no evidence of coronary artery disease.
• •Transesophageal echocardiography (Figure 2, Videos 1 and 2) performed 1 week after hospitalization for the evaluation of valvular regurgitation confirmed severe mitral regurgitation, with vegetation measuring 1.5 × 1.0 cm on the atrial aspect of anterior mitral valve leaflet, restricted mobility of the posterior leaflet, severe left atrial enlargement, and a right-to-left atrial shunt.

Figure 1.

Computed Tomography Angiogram Cross-Sectional View of the Chest Showing Multiple Pulmonary Nodules With Trace Bilateral Effusion

Figure 2.

Multiplanar Reconstruction of 2- and 3-Dimensional Transesophageal Echocardiograms With 1.5 × 1.0 cm Vegetation on the Atrial Aspect of the Anterior Leaflet

Management (Medical/Interventions)

Management of syphilitic mitral valve endocarditis requires a collaborative, multidisciplinary approach involving infectious disease specialists, cardiologists, and cardiothoracic surgeons. The clinical course in this case was managed through a series of carefully coordinated interventions.

Given the serologic confirmation of syphilis, the patient was initiated on a course of high-dose intravenous penicillin G. Although the optimal treatment for cardiovascular syphilis typically involves prolonged antibiotic therapy, the presence of severe valvular pathology necessitated surgical intervention. In addition to antibiotic therapy, supportive care with anti-inflammatory and symptomatic medications was provided.

Given the hemodynamic compromise caused by severe mitral regurgitation, the patient underwent surgical repair of the mitral valve. Intraoperative findings confirmed the destruction of the leaflet architecture with friable vegetations, consistent with an active infectious process. The surgical team performed a meticulous debridement of infected tissue and reconstructed the valve using autologous pericardial patch material. In some series of syphilitic cardiac disease, isolated mitral involvement is exceedingly rare; hence, the surgical approach was tailored to preserve as much native valve tissue as possible.

Outcome/Follow-Up

The immediate surgical outcome was uncomplicated. Postoperatively, the patient demonstrated good recovery, with normalization of hemodynamic parameters and progressive improvement in his functional status. He was successfully weaned from inotropic support in the intensive care unit and was transferred to the cardiac telemetry unit after stabilization.

The patient was ultimately discharged with referral to a cardiac rehabilitation program to continue his recovery. Unfortunately, attempts to schedule follow-up evaluations after discharge were unsuccessful, and the patient was subsequently lost to follow-up. This loss underscores the challenges of ensuring long-term compliance in patients with complex medical and social histories.

Although the hospital course was marked by a resolution of the acute infectious process and successful repair of the mitral valve, the lack of continued follow-up raises concerns regarding potential residual or recurrent complications. Regular monitoring for arrhythmias, residual valve dysfunction, and the gradual progression of cardiovascular syphilitic lesions is critical in patients with tertiary syphilis. This case illustrates an important lesson for clinicians: The need for structured follow-up protocols, especially in patients with high-risk lifestyles and social barriers.

Discussion

Syphilis, a sexually transmitted infection caused by Treponema pallidum, can silently progress over decades if left untreated.¹ The disease evolves from the primary and secondary stages to a latent phase, then ultimately to tertiary syphilis in approximately one-third of untreated patients. Tertiary syphilis is characterized by systemic complications, notably cardiovascular involvement, which classically manifests as aortitis, aortic root dilation, aneurysms, and aortic regurgitation. These manifestations result from obliterative endarteritis of the vasa vasorum, leading to ischemic injury and weakening of the arterial wall.

Mitral valve involvement is exceptionally rare in syphilitic cardiovascular disease and is not part of the classic spectrum. However, it can occur through similar inflammatory and ischemic mechanisms that compromise valvular architecture. In this patient, the mitral valve was the primary site of endocardial damage, with polymerase chain reaction analysis of the excised valve tissue confirming the presence of T pallidum. The fastidious nature of the organism often leads to culture-negative results, as occurred here, posing significant diagnostic challenges. This case exemplifies how mitral involvement may present atypically, delaying diagnosis and definitive therapy.

The utility of coronary angiography in this patient highlights a critical step in preoperative planning. Although T pallidum primarily affects the aorta, coronary ostia can be involved via extension of syphilitic aortitis, potentially mimicking or precipitating ischemic events. Ruling out obstructive coronary artery disease was essential to avoid complications during surgery and to guide valve intervention.

A review of the literature reveals only a handful of documented cases of mitral valve endocarditis caused by T pallidum. Most reported cases of syphilitic endocarditis involve the aortic valve, with large vegetations and regurgitant lesions. However, case reports such as the one by Brehm et al² suggest that syphilitic mitral valve involvement, although rare, may be under-recognized owing to limited use of advanced diagnostic modalities such as polymerase chain reaction and spirochete-specific immunohistochemistry (Figure 3). These cases frequently share features of culture-negative endocarditis, emphasizing the value of broad infectious serologic screening and tissue-level diagnostics.

Figure 3.

Spirochete Immunohistochemistry of Vegetation Attached on Atrial Aspect of Anterior Mitral Valve Leaflet

Immunohistochemical analysis (polyclonal analyte specific reagent, Leica BOND platform, performed at NeoGenomics California) shows innumerable organisms in the vegetation.

Finally, this case illustrates the essential role of detailed history taking and physical examination. The patient's history of multiple female sexual partners, lack of prior sexually transmitted infection testing, and subtle findings on cardiac auscultation were key clinical clues. The diagnosis hinged on a multidisciplinary approach combining imaging, serology, pathology, and advanced molecular diagnostics.

This case contributes to the limited body of literature on syphilitic mitral valve endocarditis and supports the need to consider T pallidum in patients with culture-negative endocarditis, especially when risk factors for syphilis are present. In such complex cases, timely surgical intervention combined with targeted antimicrobial therapy is critical for a favorable outcome.

Conclusions

This case report underscores the need for a high index of suspicion for less-well-known and yet-to-be-recognized pathogens, such as T pallidum, in patients with infective endocarditis presenting with culture-negative infective endocarditis.² Despite the diagnostic challenges posed by negative blood cultures, multidisciplinary collaboration facilitated accurate diagnosis and timely intervention. This rare instance of syphilitic mitral valve endocarditis not only emphasizes the evolving spectrum of infective endocarditis but also highlights the importance of tailored antimicrobial therapy and surgical management in achieving favorable outcomes.

Visual Summary.

Timeline of Clinical Events

Day	Intervention	Details
Day 1	Admission, initial assessment	Patient presented with chest pain, dyspnea, and new murmur.
Days 2-14	Broad-spectrum antibiotics	Vancomycin and ceftriaxone were administered for 2 wk.
Day 8	Surgical intervention	Bioprosthetic mitral valve replacement and tricuspid valve repair.
Days 15-21	Antibiotic adjustment	Vancomycin continued; ceftriaxone was replaced with piperacillin/tazobactam.
Day 22	Diagnosis of syphilis	Confirmed by PCR.
Days 23-56	IV penicillin	Antibiotic regimen changed to intravenous penicillin at 4 million units every 4 h for 8 wk.
Surgical pathology	Valve tissue analysis	Evidence of chronic inflammation with vegetation comprised of fibrin and acute inflammatory cells. Tissue tested positive for Treponema pallidum via PCR.
Serology testing	Syphilis serologies	Rapid plasma reagin titer of 1:32 and reactive T pallidum IgG and IgM antibodies.

IV = intravenous; PCR = polymerase chain reaction.

Funding Support and Author Disclosures

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

Appendix

Video 1

Transesophageal Echocardiogram Showing Mobile Echo Density (1.5 × 1.0 cm) on the Atrial Aspect of Anterior Mitral Valve Leaflet

Video 2

Transesophageal Echocardiogram Showing a Posteriorly Directed Eccentric Severe Mitral Regurgitation