Diagnosis of RHD in the Setting of a Documented Episode of ARF

In individuals with a documented history of ARF, once acute inflammation subsides, the persistence of pathologic regurgitation of the mitral and/or AVs on echocardiography is sufficient to confirm chronic RHD. The echocardiographic criteria to diagnose pathologic mitral and aortic regurgitation (AR) are detailed in Box 55.1 . In circumstances where echocardiography is not available, the persistence of a mitral and/or aortic regurgitant murmur is sufficient, although auscultation has a low positive predictive value and hence low diagnostic utility in detecting mild regurgitation.

Diagnosis of RHD Without a Previous History of ARF

The majority of patients with RHD worldwide fit into the category of having RHD with no prior history of ARF. The reason for cardiology referral or assessment may include evaluation of cardiac murmur, symptomatic status, complications of RHD, or abnormality detected on echocardiographic screening.

The 2012 World Heart Federation echocardiographic criteria were established to facilitate early diagnosis of RHD in individuals without a previous history of ARF. Box 55.1 details the minimum diagnostic criteria. In this setting, pathologic regurgitation is insufficient to diagnose RHD. Both morphologic features of RHD and pathologic regurgitation must be present or, alternatively, there must be multivalve disease of both the MVs and AVs.

If echocardiography is not available, then the diagnosis relies on auscultatory findings of valvar dysfunction. Naturally auscultation alone does not determine the etiology of disease. In this setting, the pretest probability of RHD will determine diagnostic and management strategies.

Mitral Regurgitation

In the setting of MR, symptoms occur as increasing left atrial pressure causes pulmonary venous hypertension with symptoms of breathlessness. In the setting of chronic severe MV disease, symptoms may be very gradual and very subtle, such as being unable to complete a full game of football—thus shortness of breath during peak physical activity. This may progress to shortness of breath at rest, followed in time by clinical decompensation and death. More rapid progression of symptoms can also occur in the setting of acute-on-chronic MV disease.

The clinical signs of MR include a pansystolic murmur heard best at the apex with radiation to the axilla, as the direction of regurgitant jet is usually posterolateral. Less commonly the murmur radiates medially if the regurgitant jet is directed that way. Patients with moderate or more severe MR will have lateral displacement of the apex beat, and there may be an associated diastolic murmur related to increased transmitral flow.

If MR is severe, ECG and chest x-radiograph (CXR) will demonstrate left ventricular (LV) dilatation/hypertrophy as well as pulmonary congestion.

Mitral Stenosis

In the setting of MV stenosis, progressive obstruction to LV inflow develops, leading to a diastolic gradient between the left atrium and ventricle. This pressure gradient is increased in settings of increased flow and faster heart rates, for example during exercise, pregnancy, or in the presence of atrial fibrillation with rapid ventricular rates. Patients usually do not develop symptoms until the MV orifice decreases to less than 2 cm ² . The initial symptom is exertional dyspnea with symptoms of orthopnea and paroxysmal dyspnea as the MV orifice decreases to less than 1.0 to 1.5 cm ² . Symptoms of cough, hemoptysis, chest pain, palpitations, hoarse voice due to compression of the left recurrent laryngeal nerve and left atrial dilatation are signs of very advanced disease.

The characteristic clinical finding of mild to moderate MS is a low-pitched, diastolic rumble or heart murmur heard best at the apex with the patient in a left lateral position. The murmur is accentuated by increasing heart rate with mild exercise. As disease progresses in severity, the pulses become small in volume and a parasternal heave and loud P2 develop due to pulmonary hypertension. Unless the patient is in atrial fibrillation (AF), the duration of the murmur increases and a presystolic accentuation develops. Less commonly, patients may present with or have signs of systemic embolism from the left atrium, although this is likely related more to the development of AF rather than the severity of the MS in itself.

ECG is useful to confirm sinus rhythm or AF. Left atrial enlargement and right ventricular hypertrophy is a marker of severe disease. CXR may show left atrial enlargement and upper lobe diversion of blood flow. Calcification of the MV apparatus may be visible, as well as pulmonary congestion if in heart failure.

Aortic Regurgitation

Patients with chronic stable moderate or severe regurgitation often remain asymptomatic for years. Eventually dyspnea on exertion, orthopnea, and even paroxysmal nocturnal dyspnea and edema develop. Angina can occur, even if the patient has normal coronary arteries, as the result of reduced coronary perfusion due to low diastolic blood pressure.

The clinical signs of mild AR are normal pulses and an early diastolic, blowing decrescendo diastolic murmur best heard at the lower left sternal edge at the end of expiration with the patient sitting upright and leaning forward. In general, more severe disease is associated with a shorter murmur. A widened pulse pressure indicates moderate to severe AR. Collapsing pulses indicate severe AR. In torrential AR, the murmur is heard with the patient lying flat and is associated with what is described as a “water-hammer pulse.” The Korotkoff sounds are heard almost down to the pressure of zero. The apical impulse is hyperdynamic and displaced due to LV enlargement. The presence of a systolic flow murmur across the AV reflects increased stroke volume.

If AR is severe, the ECG will show increased LV voltages and the CXR will demonstrate left ventricle enlargement.

Aortic Stenosis

Mild to moderate aortic stenosis is often asymptomatic and is associated with an ejection systolic murmur at the right upper sternal edge.

With severe aortic stenosis, a classic triad of symptoms may develop: dyspnea on exertion, angina, and syncope. On auscultation, a loud, low-pitched midsystolic ejection murmur in the aortic area will be noted, radiating to the neck and often associated with a thrill over the aortic area and at the suprasternal notch.

In the setting of severe aortic stenosis, an ECG will show LV hypertrophy. The CXR often remains normal in isolated aortic stenosis.

Tricuspid Regurgitation

Symptoms of tricuspid regurgitation are often more related to the severity of coexisting MV disease. Specific features due to tricuspid regurgitation include abdominal discomfort due to hepatomegaly, ascites, weight loss, and jaundice. If tricuspid regurgitation is severe on clinical assessment, jugular venous pressure will be elevated. A pansystolic, low-pitched cardiac murmur will be heard, loudest at the left lower sternal edge, that increases in intensity with inspiration. If tricuspid regurgitation is secondary to pulmonary hypertension, the murmur tends to be higher-pitched with a loud second heart sound.

Mitral Valve Disease

Chronic MV disease is the most common manifestation of RHD. The natural history of rheumatic MV disease has been described as a pendulum swinging from regurgitation to complete resolution without evidence of heart disease in some cases but progression to mixed MR/MS or pure valvar stenosis in others.

In children, isolated pure MR is the most common form of chronic RHD. Early in the disease process the leaflets remain relatively thin, chordae elongate, and the annulus dilates, leading to valvar regurgitation. With time, scarring and fibrosis of the leaflet apparatus result in rigidity and restricted movement of the leaflets. The appearance of the anterior MV leaflet is often described as a “dog leg” or “hockey stick” deformity ( Figs. 55.4 and 55.5 ). With time the leaflets thicken, retract, and calcify. There is also commissural fusion as well as chordal shortening, thickening, and fusion leading to MS ( Figs. 55.6 and 55.7 ). Progressive calcification of the MV apparatus may develop. This process often takes many decades ; however, in some regions of the world where ARF remains hyperendemic, progression to severe MS can be very rapid and affect children as young as 5 to 10 years of age. This is often referred to as juvenile or malignant MS.

Schematic images of the mitral valve. (A) Systolic frame in a normal patient showing a competent mitral valve in the closed position. Note the extent of coaptation of the two leaflets. (B) Diastolic frame showing a wide open mitral valve. (C) Systolic frame in regurgitant heart disease. The anterior mitral valve leaflet (AMVL) is shortened and thickened as a result of fibrosis. The posterior mitral valve leaflet (PMVL) is relatively fixed. The tip of the AMVL faces the left atrium. The leaflets do not coapt. (D) Diastolic frame showing restriction of the mitral valve orifice because of restricted mobility of both AMVL and PMVL. Note the “dog leg” deformity of the AMVL.

Echocardiographic equivalents of Fig. 55-4. Echocardiograms from a normal patient during systole (A) and diastole (B). (C–D) Echocardiograms obtained from a patient with rheumatic heart disease and mitral valve disease. (C) Systolic frame demonstrating thickening of the anterior mitral valve leaflet (AMVL) tip and a fixed posterior mitral valve leaflet (PMVL). The tip of the AMVL does not coapt with the PMVL, resulting in a visible gap. The mitral regurgitation occurs through this gap and is directed toward the posterior and lateral wall of the left atrium.

(A) Left atrium opened to show the thickened mitral valve with a characteristic “fish mouth” opening. The asterisk indicates the mural (posterior) leaflet. (B) Opened mitral valve with chronic rheumatic lesions characterized by short and thick cords and fusion of the ends of the zone of apposition.

(From Grinberg M, Sampaio RO, editors. Doença Valvar. São Paulo, Brazil: Editora Manole, 2006.)

Morphologic features of a surgically excised stenotic rheumatic mitral valve. (A) Atrial aspect, revealing the stenotic orifice and thickened leaflets. (B) Ventricular aspect, with fused tendinous cords and obliteration of intercordal spaces.

In the setting of RHD, the entire MV apparatus must be interrogated carefully to clarify the mechanism and nature of valvar dysfunction. The international standard to describe the segments of anterior (A) and posterior (P) MV leaflets divides these into a total of six scallops: A1, A2, A3, and P1, P2, P3 ( Fig. 55.8 ). On the anterior MV leaflet, A1 is the most anterior scallop and A3 is the closest to the AV. Each segment must be carefully inspected, as the disease process may involve different segments in different ways, with some areas having restricted and others excessive leaflet motion based on the complex interplay of the chordal apparatus, leaflets, and annulus. The key elements of echocardiographic evaluation of the MV apparatus in RHD are listed in Box 55.2 .

Anatomy of the mitral valve—left atrial or surgeon’s perspective.

The most commonly used functional classification of rheumatic MV disease is the Carpentier classification. This classification is aimed at optimizing surgical repair strategies for mitral insufficiency and is detailed in Box 55.3 .

Aortic Valve Disease

The early disease process is characterized by AR, which can be eccentric, with leaflet prolapse resulting in a loss of the height of the cusp tissue and commissures ( Fig. 55.9A–B ). With time the leaflets thicken, retract, and their edges roll, giving rise to a mixed hemodynamic effect (stenosis and regurgitation, Fig. 55.9C ). Over the course of decades, calcification of leaflets occurs progressively and the pendulum swings toward a predominantly stenotic hemodynamic effect. This is extremely rare in children and adolescents. The key elements of AV assessment by echocardiography are listed in Box 55.4 .

Rheumatic heart disease of the aortic valve. (A) Transesophageal echocardiogram (TEE) in a patient with mixed aortic and mitral valve disease. View was obtained at 115 degrees and shows prolapse of the right coronary commissure. There is thickening of the valve leaflet edge. (B) TEE obtained at 56 degrees showing a short-axis view of the aortic valve. The right coronary cusp has prolapsed, resulting in a central area of noncoaptation that results in aortic regurgitation. (C) Parasternal long-axis view showing markedly thickened aortic valve involving both right and left coronary cusps.

Tricuspid Valve Disease

Tricuspid regurgitation in the setting of RHD is most commonly functional and is the result of advanced left-sided pathology and pulmonary hypertension. Organic tricuspid valve disease that results from direct rheumatic inflammation is less common; it almost always coexists with mitral and/or AV involvement and is considered to be a marker of severity of RHD. Like the MR, tricuspid valve regurgitation may also progress to stenosis with leaflet thickening, chordal shortening, and commissural fusion.

Pulmonary Valve Disease

Pulmonary valve involvement in RHD is exceptional but has been described.

Grading of Valvar Severity

Significant limitations exist with regard to grading the severity of rheumatic valvar dysfunction by echocardiography. This relates to the fact that multivalve disease is common and often manifests as mixed valve disease—concomitant stenosis and regurgitation. Even in the setting of pure MR, evaluation can be challenging, as the regurgitant jet is typically very eccentric and wall hugging, and multiple jets are common. AR often arises as a result of leaflet prolapse, resulting in eccentric regurgitant jets. The American Society of Echocardiography recommendations for evaluating the severity of native aortic and mitral valvar regurgitation with two-dimensional (2D) and Doppler echocardiography are detailed in Chapters 34 and 44 . These guidelines, however, do not detail how to differentiate trivial or physiologic regurgitation from mild/pathologic regurgitation, since these findings in degenerative or congenital heart disease have no clinical significance. However, in the setting of RHD, the prescription of long-term secondary prophylaxis in the form of three to four weekly intramuscular injections of benzathine penicillin may depend on whether the regurgitation is trivial or mild. For this reason, the 2012 World Heart Federation echocardiographic diagnostic criteria were established with an aim to clearly define how to differentiate physiologic from mild pathologic regurgitation (see Box 55.1 ).

Monitor Progression/Resolution

Serial echocardiography allows for the monitoring of disease progression or resolution. In addition to assessing valvar morphology and grading the severity of valvar dysfunction, serial measurements of left atrial size, LV size, and LV volume using 2D (M-mode, area/length, and Simpson biplane methods) or newer three-dimensional (3D) modalities allow for optimizing medical management and the timing of surgery. Serial assessment of ventricular function and estimation of pulmonary artery pressure are required.

It is important to note that in the setting of significant mitral and/or AR, fractional shortening or ejection fraction are poor surrogates for cardiac contractility due to the altered loading conditions; therefore they may underestimate cardiac impairment. Load-independent measures, such as stress velocity index, may correlate more closely with the state of cardiac contractility in these circumstances.

Guide to the Nature of Cardiosurgical Intervention

Echocardiographic parameters guide the timing of surgery in acute and chronic RHD. Two-dimensional and 3D imaging can accurately identify the mechanism of valvar dysfunction; evaluate the patient’s suitability for percutaneous intervention; and guide surgical mitral, aortic, and tricuspid valve repair strategies ( Fig. 55.10 ).

Three-dimensional echocardiographic image of rheumatic heart disease of the mitral valve.

Atrial Fibrillation

AF is a relatively rare complication of RHD in the pediatric population; it is most commonly seen in the setting of MS. Age and left atrial dimension are the most important risk factors for the development of AF in the setting of MS. Other risk factors include left atrial strain as well as elevated right atrial pressure and ejection fraction. Initially AF may be paroxysmal, but as MS and left atrial dilatation progresses, it eventually becomes chronic. AF has very serious complications, including systemic embolism or stroke. The risk of AF and its complications persists even after the specific structural disease has been treated with use of either percutaneous or surgical techniques. Even episodes of transient AF shorter than 30 seconds detected by Holter monitoring predict the primary composite end point of stroke, transient ischemic attack, or non–central nervous system systemic embolization.

Stroke

In pediatric populations, the incidence of cerebrovascular accidents in the setting of RHD is not well defined. It may be ischemic or hemorrhagic in nature and can be associated with the specific native valvar abnormality, such as MS, mechanical/bioprosthetic valve replacements, and/or atrial arrhythmias such as AF/flutter. However, factors other than AF—including regional (left atrial) hypercoagulability, increased prothrombotic biomarkers, and reduced fibrinolytic activity—may contribute to stroke. Mechanical valve replacements in the pediatric population pose an extreme risk of cerebrovascular events. This is especially so in resource-poor settings, where the majority of RHD patients reside.

Heart Failure

Advanced valvar dysfunction eventually leads to congestive cardiac failure. An Australian study showed that 27% of patients developed heart failure within 5 years from the time of diagnosis of RHD. Those who develop heart failure require surgical or percutaneous intervention or they will succumb. In South Africa the 60-day mortality after admission with acute heart failure due to RHD was 25% and 180-day mortality was 35%.

Infective Endocarditis

RHD is a risk factor for infective endocarditis, which can be minimized by exercising meticulous dental hygiene. It is unclear whether RHD, compared with other valve diseases, poses an incrementally increased risk due to rheumatic valve pathology itself or to confounding factors (such as poor dentition, low level of education, and other social determinates of health) common in patients with this disease. With RHD, the need for infective endocarditis prophylaxis before dental and surgical procedures is controversial; it is recommended by the Australian and New Zealand authorities but not by the American College of Cardiology (ACC) and the American Heart Association (AHA) 2017 guidelines.