Approach Considerations
The incidence of rheumatic heart disease, the facilities available for identifying and treating the illness, and physician training and experience with this disorder all vary widely with geographic location. Furthermore, scientific understanding of rheumatic heart disease remains incomplete. For these reasons, recommending a fixed set of guidelines that apply to all situations with respect to the diagnostic approach for rheumatic heart disease is difficult.
Laboratory Studies
Testing indicated in patients with acute rheumatic fever is outlined in this section.
Throat culture
Appropriate technique for throat culture collection includes vigorous swabbing of both tonsils and the posterior orpharynx. The sample is grown on sheep blood agar to demonstrate the presence of beta-hemolytic streptococci infection. Colonies that grow on this agar can then be tested with latex agglutination, fluorescent antibody assay, coagglutination, or precipitation techniques to demonstrate group A beta hemolytic streptococci (GABHS) infection.
Note: Throat culture findings for GABHS are usually negative by the time symptoms of rheumatic fever or rheumatic heart disease appear.
Attempt to isolate the organism before the initiation of antibiotic therapy to help confirm a diagnosis of streptococcal pharyngitis and to allow typing of the organism if it is isolated successfully.
Rapid antigen detection test (RADT)
RADT allows for rapid detection of group A streptococcal (GAS) antigen as well as for rapid diagnosis of streptococcal pharyngitis and the initiation of antibiotic therapy while the patient is still in the physician's office.
Because RADT has a specificity of greater than 95% but a sensitivity of only 60-90%, a throat culture should be obtained in conjunction with this test.
Anti-streptococcal antibodies
The clinical features of rheumatic fever begin at the time antistreptococcal antibody levels are at their peak. Thus, antistreptococcal antibody testing is useful for confirming previous GAS infection. The elevated level of antistreptococcal antibodies is useful, particularly in patients that present with chorea as the only diagnostic criterion.
Sensitivity for recent infections can be improved by testing for several antibodies. Antibody titers should be checked at 2-week intervals to detect a rising titer.
The most common extracellular anti-streptococcal antibodies tested include antistreptolysin O (ASO), anti-deoxyribonuclease (DNAse) B, anti-hyaluronidase, anti-streptokinase, anti-streptococcal esterase, and anti-nicotinamide adenine dinucleotide (anti-NAD). Antibody tests for cellular components of GAS antigens include anti-streptococcal polysaccharide, anti-teichoic acid antibody, and anti–M protein antibody.
In general, the ratio of antibodies to extracellular streptococcal antigens rises during the first month after infection and then plateaus for 3-6 months before returning to normal levels after 6-12 months. When the ASO titer peaks (2-3 weeks after the onset of rheumatic fever), the sensitivity of this test is 80%-85%.
The anti-DNAse B has a slightly higher sensitivity (90%) for detecting rheumatic fever or acute glomerulonephritis than ASO titers. Anti-hyaluronidase results are frequently abnormal in rheumatic fever patients with a normal level of ASO titer and may rise earlier and persist longer than elevated ASO titers during rheumatic fever.
Acute phase reactants
C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are elevated in rheumatic fever due to the inflammatory nature of the disease. Both tests have a high sensitivity but low specificity for rheumatic fever. They may be used to monitor the resolution of inflammation, detect relapse when weaning from aspirin, or identify the recurrence of disease.
Specifically, elevated mean plasma high-sensitive CRP has been shown to have an association with rheumatic heart disease. [32]
Heart-reactive antibodies
Tropomyosin levels are elevated in acute rheumatic fever.
Rapid detection test for D8/17
This immunofluorescence technique for identifying the B-cell marker D8/17 is positive in 90% of patients with rheumatic fever. It may be useful for identifying patients who are at risk for developing rheumatic fever.
Ongoing investigations
Current research is being pursued to evaluate for new diagnostic and prognostic markers in rheumatic heart disease. In subjects with rheumatic heart disease requiring percutaneous balloon mitral valvotomy, N-terminal (NT)-pro b-type natriuretic peptide (BNP) (NT-proBNP) levels correlated with improvements in left atrial function seen after the procedure. [33] Another marker that has demonstrated elevation in rheumatic heart disease is procollagen type 1 C-peptide and interleukin (IL)-6 concentration. [34]
Lower vitamin D levels, specifically 25-hydroxyvitamin D, have been shown to correlate with more severely damaged and calcified valves in rheumatic heart disease. It has been hypothesized that the role of vitamin D as an immunomodulator may have an impact on the severity of autoimmune valve damage in rheumatic heart disease. [35]
Electrocardiography
On electrocardiography (ECG), sinus tachycardia most frequently accompanies acute rheumatic heart disease. Alternatively, some children develop sinus bradycardia from increased vagal tone. However, no correlation between bradycardia and the severity of the carditis is noted.
First-degree atrioventricular (AV) block (prolongation of the PR interval) is observed in some patients with rheumatic heart disease. This abnormality may be related to localized myocardial inflammation involving the AV node or to vasculitis involving the AV nodal artery. First-degree AV block is a nonspecific finding and should not be used as a criterion for the diagnosis of rheumatic heart disease. Its presence does not correlate with the development of chronic rheumatic heart disease.
Second-degree (intermittent) and third-degree (complete) AV block with progression to ventricular standstill have been described. Heart block in the setting of rheumatic fever, however, typically resolves with the rest of the disease process.
When acute rheumatic fever is associated with pericarditis, ST-segment elevation may be present and is most marked in leads II, III, aVF, and V4 -V6.
Patients with rheumatic heart disease also may develop atrial flutter, multifocal atrial tachycardia, or atrial fibrillation from chronic mitral valve disease and atrial dilatation. Left atrial enlargement may be seen in patients with mitral stenosis. Left ventricular hypertrophy may be observed in patients with significant mitral insufficiency or aortic insufficiency.
Imaging Studies
Chest radiography
Cardiomegaly, pulmonary congestion, and other findings consistent with heart failure may be seen on chest radiography in patients with rheumatic heart disease.
When the patient has fever and respiratory distress, chest radiography helps to differentiate heart failure from rheumatic pneumonia.
Doppler echocardiography
The World Heart Federation has published guidelines for identifying individuals with rheumatic heart disease who don't have a clear history of acute rheumatic fever. Based on two-dimensional (2D) imaging and pulsed and color Doppler interrogation, patients are divided into the following three categories:
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Definite rheumatic heart disease
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Borderline rheumatic heart disease
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Normal
For pediatric patients (defined as age < 20 years), definite echocardiographic features include pathologic mitral regurgitation (MR) and at least two morphologic features of: rheumatic heart disease of the mitral valve, a mitral stenosis mean gradient of more than 4 mmHg, pathologic aortic regurgitation, and at least two morphologic features of rheumatic heart disease of the aortic valve, or borderline disease of both the aortic valve and mitral valve. [36]
The revised American Heart Association criteria align more closely with the World Heart Federation guidelines above. In the most recent version of the revised Jones criteria, morphologic and Doppler findings on echocardiography may supersede ausculatory findings for carditis. Studies in Cambodia and Mozambique demonstrated a 10-fold increase in the prevalence of rheumatic heart disease when echocardiography was used for clinical screening compared with strictly clinical findings. [37]
Acute morphologic changes in the mitral valve may include annular dilatation, chordal elongation, chordal rupture resulting in flail leaflet with severe mitral regurgitation, or prolapse/beading/nodularity of the leaflet tips. Doppler findings should demonstrate regurgitation in at least two views, with a pansystolic jet in at least one view. Chronic changes in the mitral valve show leaflet thickening and calcification, with restricted motion. There may also be evidence of chordal thickening and fusion. Changes in the aortic valve may include prolapse, coaptation defect, and thickening of the leaflets with restricted motion. Doppler findings should demonstrate regurgitation in at least two views, with a pansystolic jet in at least one view. [29]
Acute rheumatic heart disease
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Doppler echocardiography identifies and quantitates valve insufficiency and ventricular dysfunction.
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During acute rheumatic fever, the left ventricle is frequently dilated in association with a normal or increased fractional shortening. Thus, some cardiologists believe that valve insufficiency (from endocarditis), rather than myocardial dysfunction (from myocarditis), is the dominant cause of heart failure in acute rheumatic fever.
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With mild carditis, Doppler evidence of mitral regurgitation may be present during the acute phase of disease but resolves in weeks to months. In contrast, patients with moderate-to-severe carditis have persistent mitral and/or aortic regurgitation. The most important echocardiographic features of mitral regurgitation from acute rheumatic valvulitis are annular dilatation, elongation of the chordae to the anterior leaflet, and a posterolaterally directed mitral regurgitation jet.
Chronic rheumatic heart disease
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Echocardiography may be used to track the progression of valve stenosis and may help to determine the time for surgical intervention.
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The leaflets of affected valves become diffusely thickened, with fusion of the commissures and chordae tendineae.
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Increased echodensity of the mitral valve may signify calcification.
Simplified echocardiographic screening with handheld echocardiography
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A 2019 study suggests that simplified echocardiographic screening criteria are highly accurate in the recognition and risk stratification of rheumatic heart disease. [38]
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An investigation of handheld echocardiography as a screening tool in Ugandan children found it to be 90% sensitive and 92% specific for identifying rheumatic heart disease. [39]
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A study by Godown et al that assessed the value of handheld echocardiography over auscultation to identify rheumatic heart disease demonstrated that auscultation alone was a poor screening test for rheumatic heart disease and that handheld echocardiography significantly improved detection of rheumatic heart disease. [40] This study also showed that handheld echocardiography was a cost-effective screening strategy for rheumatic heart disease in resource-limited settings.
The image below depicts the typical systolic mitral insufficiency jet observed with rheumatic heart disease.
Pediatric rheumatic heart disease. This parasternal long-axis echocardiographic view demonstrates the typical systolic mitral insufficiency jet observed with rheumatic heart disease (blue jet extending from the left ventricle [LV] into the left atrium [LA]). The jet is typically directed to the lateral and posterior wall. Ao = aorta; RV = right ventricle.
The image below depicts the typical diastolic aortic insufficiency jet observed with rheumatic heart disease.
Pediatric rheumatic heart disease. This parasternal long-axis echocardiographic view demonstrates the typical systolic mitral insufficiency jet observed with rheumatic heart disease (blue jet extending from the left ventricle [LV] into the left atrium [LA]). The jet is typically directed to the lateral and posterior wall. Ao = aorta; RV = right ventricle.
Cardiac magnetic resonance imaging (CMR)
The use of CMR in rheumatic heart disease is still being investigated
Studies have demonstrated that CMR may be superior to echocardiography in obtaining information about myocardial fibrosis. Other advantages of CMR include that this imaging modality is not operator dependent nor dependent on acoustic windows. One of the major drawbacks to CMR however, is that this type of study is often not available in endemic areas. Other limitations include the inability to perform this testing on anyone with metallic implants of any nature. [41]
Histologic Findings
Pathologic examination of the insufficient valves in patients with rheumatic heart disease may reveal verrucous lesions at the line of closure.
Aschoff bodies (perivascular foci of eosinophilic collagen surrounded by lymphocytes, plasma cells, and macrophages) are found in the pericardium, perivascular regions of the myocardium, and endocardium. The Aschoff bodies assume a granulomatous appearance with a central fibrinoid focus and are eventually replaced by nodules of scar tissue. Anitschkow cells are plump macrophages within Aschoff bodies.
In the pericardium, fibrinous and serofibrinous exudates may produce an appearance of "bread and butter" pericarditis.
Procedures
Cardiac catheterization
Cardiac catheterization is not indicated in acute rheumatic heart disease. However, with chronic disease, heart catheterization has been performed to evaluate mitral and aortic valve disease. This procedure is also performed in preparation for balloon valvuloplasty of the stenotic mitral valves if indicated.
Postcatheterization precautions include hemorrhage, pain, nausea, vomiting, and arterial or venous obstruction from thrombosis or spasm. Complications may include mitral insufficiency after balloon dilation of the mitral valve, tachyarrhythmias, bradyarrhythmias, and vascular occlusion.
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Pediatric rheumatic heart disease. This parasternal long-axis echocardiographic view demonstrates the typical systolic mitral insufficiency jet observed with rheumatic heart disease (blue jet extending from the left ventricle [LV] into the left atrium [LA]). The jet is typically directed to the lateral and posterior wall. Ao = aorta; RV = right ventricle.
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Pediatric rheumatic heart disease. This parasternal long-axis echocardiographic view demonstrates the typical diastolic aortic insufficiency jet observed with rheumatic heart disease (red jet extending from the aorta [Ao] into the left ventricle [LV]). LA = left atrium; RV = right ventricle.
