In a 26-year-old female with a murmur, which laboratory studies should be ordered in addition to a transthoracic echocardiogram to evaluate for rheumatic heart disease?

Laboratory Evaluation for Suspected Rheumatic Heart Disease

In a 26-year-old female with a murmur concerning for rheumatic heart disease, you should obtain evidence of recent group A streptococcal infection through throat culture or rapid antigen detection test, plus serologic testing with anti-streptolysin O (ASO) and anti-DNase B antibodies, along with acute phase reactants (ESR and CRP). 1

Essential Laboratory Tests

Streptococcal Infection Documentation

The cornerstone of diagnosing acute rheumatic fever (which leads to rheumatic heart disease) requires documented evidence of preceding group A streptococcal infection. 1, 2 This is accomplished through:

• Throat culture or rapid antigen detection test to identify active pharyngeal infection 2
• Anti-streptolysin O (ASO) titer – the most commonly used serologic marker 1, 2
• Anti-DNase B antibody – particularly useful as it remains elevated longer than ASO and can detect both pharyngeal and skin infections 1, 2

A rising titer between acute and convalescent samples provides stronger evidence than a single elevated value, though a single elevated titer combined with clinical findings may be sufficient in the appropriate context. 2

Inflammatory Markers (Minor Criteria)

Elevated acute phase reactants serve as minor criteria in the revised Jones criteria and help support the diagnosis: 1, 2

• Erythrocyte sedimentation rate (ESR) 1, 2
• C-reactive protein (CRP) 1, 2

These markers reflect the inflammatory nature of acute rheumatic fever but are nonspecific and must be interpreted alongside other clinical and laboratory findings. 1

Diagnostic Framework: The Revised Jones Criteria

The 2015 American Heart Association revision of the Jones criteria provides the diagnostic framework. 1 For an initial episode of acute rheumatic fever, you need:

• Evidence of preceding group A streptococcal infection (as outlined above) PLUS 1, 2
• Either 2 major manifestations OR 1 major + 2 minor manifestations 1, 2

Major manifestations include: 1

• Carditis (clinical or subclinical on echocardiography)
• Polyarthritis (or monoarthritis in high-risk populations)
• Chorea
• Erythema marginatum
• Subcutaneous nodules

Minor manifestations include: 1

• Elevated ESR or CRP
• Prolonged PR interval on ECG
• Fever
• Arthralgia (in low-risk populations)

Critical Role of Echocardiography

Echocardiography with Doppler should be performed in all cases of suspected acute rheumatic fever (Class I recommendation). 1 The 2015 guidelines now recognize subclinical carditis detected by echocardiography as a major criterion, even without auscultatory findings. 1

Pathological mitral regurgitation on Doppler requires all 4 criteria: 1

• Seen in at least 2 views
• Jet length ≥2 cm in at least 1 view
• Peak velocity >3 m/s
• Pansystolic jet in at least 1 envelope

Pathological aortic regurgitation requires all 4 criteria: 1

• Seen in at least 2 views
• Jet length ≥1 cm in at least 1 view
• Peak velocity >3 m/s
• Pandiastolic jet in at least 1 envelope

Important Clinical Considerations

Distinguishing Chronic RHD from Acute Presentation

In your 26-year-old patient, you may be encountering chronic rheumatic heart disease rather than acute rheumatic fever. 1 The World Heart Federation criteria distinguish between:

• "Definite RHD" – clear pathological valve changes that warrant secondary prophylaxis 1
• "Borderline RHD" – subtle findings requiring follow-up 1

Chronic mitral valve changes include leaflet thickening, chordal thickening and fusion, restricted leaflet motion, and calcification, whereas acute changes show annular dilation, chordal elongation, and leaflet prolapse. 1

Differential Diagnosis Pitfalls

Do not assume all mitral regurgitation is rheumatic in origin. 2 Other causes to exclude include:

• Infective endocarditis – obtain three separate blood culture sets if fever or systemic symptoms are present 2
• Congenital valve anomalies (bicuspid aortic valve, mitral valve prolapse) 1
• Functional mitral regurgitation from left ventricular dilation 2

Isolated aortic regurgitation is rarely the sole finding in rheumatic carditis, so consider congenital etiologies like bicuspid aortic valve in this scenario. 1

Recurrent Episodes

If your patient has a reliable history of prior acute rheumatic fever or established rheumatic heart disease, the diagnostic threshold is lower for recurrent episodes. 1 In this setting, with documented group A streptococcal infection, 2 major OR 1 major and 2 minor OR 3 minor manifestations may be sufficient for presumptive diagnosis. 1

Management Implications

Once rheumatic heart disease is confirmed, long-term secondary prophylaxis with benzathine penicillin G 1.2 million units intramuscularly every 4 weeks becomes the gold standard, providing approximately 10 times greater protection than oral antibiotics. 3

Duration depends on cardiac involvement: 3

• With carditis but now normal valves: 10 years after last attack or until age 21, whichever is longer
• Without carditis: 5 years after last attack or until age 21, whichever is longer

Serial echocardiographic monitoring is essential as subclinical progression can occur despite normal physical examination. 3