Rheumatic heart disease

Article written and reviewed by Dr Luca Moretti

Rheumatic heart disease is the chronic valvular outcome of one or more episodes of acute rheumatic fever, an immune-mediated inflammatory response that follows infection with Streptococcus pyogenes, group A beta-hemolytic streptococcus. This continuum should not be confused with a persistent infection of the heart: the microorganism triggers immunity in the oropharynx and, perhaps in some epidemiologic settings, in the skin; cardiac injury instead results from host cross-reactivity. Valvulitis, fibrous repair and recurrences progressively transform leaflets, commissures and chordae, producing regurgitation, stenosis or both dysfunctions.

The disease remains a global problem despite being largely preventable. The greatest burden falls on children, adolescents and young adults in low- and middle-income countries and on marginalized communities, including some Indigenous populations in high-income countries. Overcrowding, poverty, inconsistent access to streptococcal diagnosis, difficulties with prophylaxis and delayed valve intervention explain much of this distribution. It is therefore incorrect to attribute risk to a presumed “racial” predisposition independent of the social context, while recognizing that individual susceptibility and immune response modulate outcome.

The clinical pathway requires three distinct diagnostic frameworks. The Jones criteria estimate the probability of acute rheumatic fever; the 2023 WHF echocardiographic criteria identify minimum findings compatible with rheumatic heart disease during screening and expert confirmation; valvular guidelines then quantify hemodynamic severity and guide intervention. Conflating these levels creates errors: an adult with scarred mitral stenosis does not need to “meet Jones criteria,” and a jet that exceeds a WHF threshold does not thereby become clinically severe regurgitation.

The mitral valve is most frequently affected, often initially with regurgitation and, after years, with progressive commissural fusion and stenosis. The aortic valve may also be involved; organic tricuspid disease and, even more so, pulmonary valve disease are less common. The same person may have lesions with different mechanisms and severity, compounded by atrial fibrillation, embolism, pulmonary hypertension, ventricular dysfunction and obstetric risk. Prevention of recurrences and treatment of the valve therefore belong to the same longitudinal strategy, but they follow different indications.

From streptococcal infection to valvular scarring

Streptococcus pyogenes primarily colonizes and infects the pharynx and skin. The classic causal relationship with rheumatic fever is pharyngitis; the 2024 WHO guideline recognizes that superficial skin or soft-tissue infections might contribute, especially in high-incidence populations, but the evidence does not allow the two portals of entry to be definitively considered equivalent. The latency, typically one to five weeks between infection and the inflammatory syndrome, and the usual absence of the bacterium from cardiac tissues support the post-infectious, rather than septic, nature of the disease.

The pathogenic model includes molecular mimicry, endothelial activation and loss of tolerance. Antibodies and lymphocytes induced by streptococcal antigens may recognize cardiac structures, including contractile proteins and components of the valvular matrix. Activated valvular endothelium facilitates T- and B-cell infiltration; cytokines, complement and neovascularization amplify inflammation. No single epitope, however, explains every case: bacterial strain, reinfections, host genetics and environment interact, and several steps remain incompletely defined.

During acute carditis, the mitral valve may show leaflet edema, annular dilatation, chordal elongation or rupture and prolapse, with regurgitation rather than stenosis. The aortic valve may also become regurgitant. Myocardium and pericardium may participate in pancarditis, but the permanent consequence is predominantly valvular. So-called subclinical carditis, in which Doppler demonstrates pathologic regurgitation without an audible murmur, is diagnostically relevant in acute rheumatic fever and should not be confused with an incidental physiologic finding.

Healing does not always restore normal anatomy. Organization of inflammation, collagen deposition and repeated cycles of injury cause thickening of the free margins, commissural fusion, and shortening and fusion of the chordae. In the mitral valve, the orifice progressively assumes a funnel-shaped geometry; mobility may remain at the base but is lost at the tips. Calcification of the leaflets and subvalvular apparatus is added with age, disease duration and recurrences, making commissurotomy and repair less favorable.

The course is not necessarily linear. A first overt episode may leave modest regurgitation that subsequently regresses, whereas later recurrences accelerate scarring. Other patients reach adulthood with valvular disease but no recognized history of rheumatic fever: the initial episode may have been mild, subclinical, diagnosed as another illness or forgotten. The absence of a history of migratory arthritis or carditis therefore does not exclude a rheumatic etiology when morphology and context are convincing.

The most characteristic chronic phenotype is mitral stenosis with commissural fusion and subvalvular involvement. Many people, however, have both restricted opening and loss of coaptation: mixed mitral valve disease must be interpreted as an integrated hemodynamic burden rather than by mechanically adding two severity labels. Pure mitral regurgitation is relatively more common in younger patients and early disease, but it may persist or become severe.

Aortic involvement is usually associated with mitral disease and manifests mainly as regurgitation, sometimes with a late stenotic component. An isolated aortic lesion requires a rigorous differential diagnosis with bicuspid aortic valve, degeneration and endocarditis. The tricuspid valve may be organically thickened and retracted in extensive disease, but right-sided regurgitation is more often secondary to pulmonary hypertension, annular dilatation and right ventricular remodeling. Rheumatic pulmonary valve disease is exceptional.

This distribution makes multiple valve disease common. Mitral stenosis may reduce cardiac output and mask the gradient of aortic stenosis; concomitant regurgitation may instead increase flow through a stenotic orifice. Pulmonary hypertension may reflect left atrial pressure, pulmonary vascular disease and right-sided lesions. For this reason, a common etiology does not make the valves hemodynamically interchangeable: each lesion must be described and then interpreted within the overall system.

Chronic progression enlarges the left atrium and promotes atrial fibrillation, stasis, thrombus and embolism. Elevated pulmonary venous pressures cause dyspnea, edema, hemoptysis and, over time, vascular remodeling; pulmonary hypertension and tricuspid regurgitation worsen systemic congestion. Heart failure, stroke, endocarditis and pregnancy complications account for much of the morbidity in young adults. International registries also show that prognosis and access to prophylaxis, anticoagulation and interventions remain profoundly unequal.

Acute rheumatic fever and the Jones criteria

Acute rheumatic fever is a probabilistic clinical diagnosis: there is no single pathognomonic test. It is suspected mainly in children and adolescents with articular, cardiac, neurologic or cutaneous manifestations after possible streptococcal infection, although recurrences may occur later. Assessment includes epidemiologic history, physical examination, ECG, inflammatory markers, evidence of streptococcal infection and Doppler echocardiography. Alternative infectious, autoimmune, hematologic and neurologic diagnoses must be excluded according to the phenotype.

The revised Jones criteria distinguish low-risk populations from moderate- or high-risk populations because the same manifestation has a different pretest probability. A population is considered low risk when the annual incidence of rheumatic fever is no more than 2 per 100,000 school-age children or the prevalence of rheumatic heart disease, at all ages, is no more than 1 per 1,000. The classification refers to the source population, not to a subjective perception of risk in the individual patient.

For a first episode, the required combination is two major criteria or one major and two minor criteria, together with evidence of preceding group A streptococcal infection. For a recurrence in a person with previously documented rheumatic fever or rheumatic heart disease, two major manifestations, or one major and two minor manifestations, or three minor manifestations are accepted, always after excluding alternative explanations. Sydenham chorea and indolent carditis are classic situations in which evidence of streptococcal infection may no longer be demonstrable because of the long latency.

The major criteria include clinical or subclinical carditis, chorea, erythema marginatum and subcutaneous nodules. In low-risk populations, the major joint manifestation is polyarthritis; in moderate- to high-risk populations, monoarthritis or polyarthritis and also polyarthralgia may qualify after other causes have been excluded. The greater sensitivity in endemic settings reflects different epidemiology and does not make every joint pain evidence of rheumatic fever.

Minor criteria include fever, arthralgia not already counted as a major manifestation, elevated inflammatory markers and age-adjusted PR prolongation. In low-risk populations the thresholds are a temperature of at least 38.5 °C and an erythrocyte sedimentation rate of at least 60 mm/h, with C-reactive protein of at least 3 mg/dL; in moderate- to high-risk populations they are 38.0 °C, ESR of at least 30 mm/h and CRP of at least 3 mg/dL, respectively. PR prolongation is not counted as a minor criterion if carditis is already a major criterion.

The rules prevent double counting: arthritis and arthralgia cannot be added as independent manifestations in the same episode, and the same applies to elements that represent a single process. ESR and CRP values are affected by timing and treatment; a normal ECG does not exclude carditis. Erythema marginatum and nodules are rare and require experience. Chorea may be unilateral, associated with emotional lability and hypotonia, and may occur months after infection when inflammatory markers are normal.

Evidence of preceding infection may come from a positive throat culture or rapid antigen test, or from an elevated or rising antistreptolysin O or anti-DNase B titer interpreted against local reference ranges. A single elevated titer demonstrates exposure, not definite causality, and may remain high after a remote infection. Antibiotics already taken reduce the sensitivity of throat tests; conversely, asymptomatic carriers may have a positive test for reasons unrelated to the current syndrome.

Echocardiography should be performed whenever rheumatic fever is suspected, even in the absence of a murmur. Subclinical carditis is a major criterion when Doppler demonstrates pathologic mitral or aortic regurgitation according to features of length, velocity, duration and visualization; a small physiologic jet is not sufficient. The published correction to the 2023 WHF guidelines specifies that, in diagnosing carditis in the index case, pathologic mitral and/or aortic regurgitation is that defined in Box 5 of the document.

The Jones criteria should be interpreted as a probabilistic tool rather than an automatic algorithm. Sepsis, endocarditis, septic arthritis, leukemia, lupus or Kawasaki disease can produce superficially similar combinations, and chorea also requires a drug-related, autoimmune and neurologic differential diagnosis. In high-incidence areas, pre-existing heart disease may also make it difficult to distinguish new carditis from a chronic lesion. Clinical experience, echocardiographic quality and follow-up therefore remain indispensable even when the numerical combination of criteria is met.

Treatment of the acute episode includes eradication of streptococcus, relief of arthritis, management of heart failure or arrhythmias, and immediate initiation of secondary prophylaxis. Salicylates and other anti-inflammatory drugs improve fever and joint manifestations; corticosteroids are sometimes used for severe carditis according to specialist protocols. WHO, however, makes no recommendation for or against aspirin, NSAIDs, immunoglobulins or steroids as a strategy capable of preventing progression to chronic heart disease: symptomatic benefit is not equivalent to evidence of valvular protection.

Chronic echocardiography and 2023 WHF criteria

In chronic rheumatic heart disease, transthoracic echocardiography with Doppler identifies the probable etiology, mechanism, combination of lesions and chamber consequences. Diagnosis does not depend on a single finding: leaflet thickening, restriction, excessive motion, commissural fusion and chordal abnormalities are correlated with regurgitation or stenosis and with age and alternative diagnoses. A thickened mitral leaflet in an older adult is not automatically rheumatic, just as functional regurgitation does not become rheumatic because of geographic origin.

The 2023 WHF guidelines separate a sensitive protocol intended for echocardiographic screening from more specific criteria for expert confirmation. This structure allows large-scale programs using portable equipment and trained personnel, but requires a positive finding to be confirmed before definitively labeling the person or initiating a long-term care pathway. WHF stages A-D describe the continuum of rheumatic disease and do not correspond to heart failure stages.

During screening, mitral regurgitation is considered suspicious if the jet measures at least 1.5 cm in individuals weighing less than 30 kg or at least 2.0 cm in those weighing 30 kg or more, is visible in at least one view and persists for at least two frames. Any aortic regurgitation visible in at least one view and two frames meets the screening signal. Mitral stenosis is suspected when there is restricted motion and reduced opening. These thresholds prioritize sensitivity and are not criteria of clinical severity.

In expert assessment, pathologic mitral regurgitation must be seen in at least two views, meet the weight-based jet-length threshold, reach a peak velocity of at least 3 m/s and be pansystolic in at least one complete envelope. For aortic regurgitation, visualization in at least two views, a jet length of at least 1 cm, an early diastolic velocity of at least 3 m/s and a pandiastolic signal are required. Mitral stenosis is confirmed by restrictive morphology and a mean gradient of at least 4 mmHg, taking heart rate and flow into account.

A positive WHF cutoff identifies a phenotype compatible with rheumatic heart disease, but by itself does not establish clinical severity or the indication for intervention. Jet length varies with gain, Nyquist limit, pressure and geometry, whereas the transmitral gradient increases with tachycardia, anemia, pregnancy and concomitant regurgitation. Hemodynamic severity therefore requires a multiparametric protocol dedicated to the individual valve, separating screening from therapeutic decision-making.

Classic rheumatic mitral morphology combines thickening of the leaflet margins, doming of the anterior leaflet, restriction of the posterior leaflet, commissural fusion and chordal shortening. 3D and transesophageal echocardiography show commissural distribution, the orifice and the subvalvular apparatus; 3D planimetry reduces obliquity error. Before commissurotomy, left atrial thrombus must also be excluded and regurgitation accurately quantified, because regurgitation greater than mild is a contraindication to the percutaneous procedure.

When regurgitation predominates, the mechanism may include anterior leaflet prolapse due to chordal elongation, posterior leaflet restriction and a coaptation defect. Vena contracta, pulmonary venous flow, PISA when applicable, ventricular volumes and pulmonary pressure are integrated. Atrial dilatation may be disproportionate after years of atrial fibrillation. An eccentric wall-hugging jet may appear small on color Doppler and requires particular caution.

The study cannot stop at the mitral valve and must include all valves. Thickened and retracted aortic cusps may cause regurgitation, and any stenotic component must be distinguished from degenerative calcification; at the tricuspid valve, by contrast, it is essential to determine whether the lesion is organic or secondary because this changes the strategy and expected durability of repair. The size and function of both ventricles, left atrial volume, estimated pulmonary pressure and the vena cava complete the profile of cardiac damage.

Transesophageal echocardiography, CT and magnetic resonance imaging answer selected questions. Transesophageal imaging is central for thrombus, commissures, regurgitation and procedural planning; CT can define calcification and anatomy when an intervention is complex. Magnetic resonance imaging quantifies discordant volumes and regurgitation but resolves thin commissures less well. Catheterization is reserved for clinical-echocardiographic discrepancies, uncertain pulmonary pressure or coronary and preoperative assessment according to age and risk.

Population screening is not the same as a diagnostic echocardiogram requested because of symptoms or a murmur. WHO recommends echocardiographic screening in children and adolescents aged 5-19 years in settings with moderate or high prevalence and allows handheld ultrasound when standard echocardiography is unavailable; however, the program must ensure confirmation, registration, prophylaxis and follow-up. Detecting a lesion without being able to provide continuity of care reduces its public-health value and may produce stigma or loss to follow-up.

Primary prevention, secondary prophylaxis and follow-up

Primordial prevention acts on determinants of transmission and access: non-overcrowded housing, water and hygiene, culturally safe health education, accessible primary care and continuous availability of testing and penicillin. It is not an alternative to clinical therapy, but it determines its effectiveness. Programs that blame a person for a missed dose without addressing distance, costs, pain, discrimination and intermittent supplies cannot achieve reliable prophylaxis.

Primary prevention promptly treats group A streptococcal pharyngitis before it triggers rheumatic fever. The 2024 WHO guideline does not currently recommend a specific clinical prediction rule as a substitute for microbiologic diagnosis. A positive rapid test or culture guides antibiotic treatment; if testing is unavailable, clinically suspected pharyngitis in children and adolescents from moderate- to high-risk populations may be treated according to a local pathway. Penicillin remains the first choice in the absence of a relevant allergy.

Treatment of streptococcal infection should use doses and durations validated for the specific agent, age, weight and local guideline. The choice between intramuscular and oral penicillin also depends on adherence, availability and preferences, whereas an immediate allergy requires an appropriate alternative and attention to macrolide resistance. Viral sore throat does not benefit from antibiotics: pathway quality therefore depends on early access, testing when available and stewardship, not on indiscriminate expansion of prescribing.

The possible role of skin infections has public-health implications, but does not justify a stronger statement than the evidence supports. WHO includes diagnosis and treatment of superficial streptococcal infections within the preventive framework, but does not make a specific antibiotic recommendation solely aimed at preventing rheumatic fever or rheumatic heart disease. Impetigo and other infections should be treated according to their own indications, together with hygiene and transmission-control measures, without promising proven valvular protection.

Secondary prophylaxis is indicated after rheumatic fever or in rheumatic heart disease because preventing new infections reduces immune-mediated recurrences and accumulation of damage. Intramuscular benzathine penicillin G is preferred because of its efficacy and independence from daily adherence; oral penicillin is an alternative when injections are not feasible or acceptable. Correct technique, appropriate needles, analgesia, communication and safe allergy management are part of treatment, not merely organizational details.

The interval and duration are not universal. The type and date of the most recent episode, previous carditis, presence and severity of residual disease, age, streptococcal exposure, occupational or family contact with children, pregnancy, access and regional guidelines are considered. Severe disease or high exposure may require longer protection; after valve surgery, immunologic risk does not automatically disappear because the person may have residual native valves and recurrent rheumatic fever.

Adherence should be measured as the proportion of doses received on schedule and discussed without judgment. Reminders, registries, active recall, decentralized administration, stable staff and family involvement improve continuity. Fear of anaphylaxis should lead neither to inappropriate discontinuation nor to injection without preparation: a careful allergy history, training and availability of emergency treatment make the program safer.

The GOAL trial provided important but circumscribed evidence. In Ugandan children and adolescents aged 5-17 years with latent rheumatic heart disease, benzathine penicillin G every four weeks for two years reduced echocardiographic progression from 8.2% to 0.8%. The result supports prophylaxis after echocardiographic identification in comparable populations; by itself it does not demonstrate identical benefit in every adult, in all WHF categories or in every health system, nor does it justify universal screening without a care pathway.

Follow-up should integrate secondary prophylaxis and valve surveillance into a single pathway. The frequency of visits and echocardiography depends on stage, age, symptoms, rhythm, planned pregnancy and rate of progression; at every visit, functional capacity, adherence, murmur, blood pressure, rhythm and signs of congestion should be reassessed, with ECG and Doppler echocardiography that can be compared over time. Education about pharyngitis, recurrences, heart failure, stroke and the need for urgent care thereby turns follow-up into a tool of active prevention.

Registries are essential to avoid losing patients, who are often young and move between different services. Linking the diagnosis, risk category, dose schedule, echocardiograms, anticoagulation, pregnancy and referral to a valve center provides continuity that a prescription alone cannot guarantee. REMEDY and international cohorts indeed document major gaps in the use of prophylaxis, anticoagulants and interventions, with worse outcomes where access is poorer: improving survival therefore means not only making the correct recommendation, but making it concretely available.

Complications, valvular management and pregnancy

Medical therapy alleviates the hemodynamic consequences but does not reopen fused commissures or reconstruct retracted chordae. Diuretics reduce pulmonary or systemic congestion, and heart rate control, by prolonging diastole, can improve symptoms of mitral stenosis especially during exertion or atrial fibrillation; blood pressure, renal function and cardiac output, however, limit its intensity. The appearance of symptoms, pulmonary hypertension, ventricular dilatation or dysfunction, or new embolic events therefore requires anatomic reassessment rather than simply chronic escalation of medications.

Atrial fibrillation results from left atrial dilatation, fibrosis and pressure and often marks a prognostic change. Heart rate, the possibility of rhythm control, arrhythmia duration, atrial dimensions and the valve lesion are assessed. In atrial fibrillation associated with moderate or severe rheumatic mitral stenosis, guidelines indicate a vitamin K antagonist; the 2025 ESC/EACTS guideline considers this strategy in rheumatic stenosis with a mitral valve area no greater than 2.0 cm². The CHA2DS2-VASc score does not override this specific indication.

INVICTUS compared rivaroxaban with vitamin K antagonists in patients with atrial fibrillation and rheumatic heart disease: the VKA strategy produced fewer cardiovascular events or deaths, without a significant increase in major bleeding. The trial rules out routine substitution with rivaroxaban in this population; it does not prove that every direct oral anticoagulant has the same effect in every valvular disease, nor does it indicate anticoagulation for all people with rheumatic heart disease who remain in sinus rhythm.

In sinus rhythm, atrial thrombus, previous embolism, dense spontaneous echo contrast and a markedly enlarged atrium may alter the decision according to guidelines and individual assessment. Transesophageal echocardiography is required before commissurotomy and cardioversion when thrombus must be excluded. INR control, interactions, diet, access to laboratory testing and obstetric risk determine the quality and safety of VKA therapy; prescribing it without a monitoring system is not equivalent to protecting against thromboembolism.

Percutaneous mitral commissurotomy is appropriate for clinically significant stenosis, symptoms or high-risk conditions and favorable anatomy, in the absence of left atrial thrombus, regurgitation greater than mild and other contraindications. Commissural fusion must actually be present. Bicommissural calcification, severe subvalvular disease or associated lesions requiring correction favor surgery. Details of thresholds and scores belong to the dedicated assessment of mitral stenosis, not to the etiologic label.

In rheumatic mitral regurgitation, the choice depends on the mechanism and true repairability. In young patients, a durable repair is desirable when tissue quality, the chordal apparatus and center experience make it plausible; diffuse fibrosis, retraction and calcification may instead make replacement more reliable, so there is no rule that repair is always superior. In multivalvular disease, the Heart Team and surgeon must then decide which lesions to correct, avoiding both leaving a major burden untreated and multiplying procedures without benefit.

Timely access is part of prognosis. In the INVICTUS follow-up published in 2024, heart failure and mortality remained high and the availability of valvuloplasty or surgery varied markedly across countries; the observed association between intervention and better survival does not by itself prove causality because patient selection may confound the result. It nevertheless supports early assessment of eligible people before fixed pulmonary hypertension, right ventricular dysfunction, cachexia or organ failure develop.

Pregnancy increases plasma volume, heart rate and cardiac output; stenosis limits the increase in flow and raises the gradient, whereas tachycardia shortens diastole. Stenotic lesions are therefore less well tolerated than regurgitant lesions when ventricular function is preserved. Before conception, echocardiography, functional capacity, rhythm, pulmonary pressure, medications and the need for intervention should be assessed. Significant disease requires a Pregnancy Heart Team, a delivery plan and postpartum surveillance, when rapid volume shifts can precipitate decompensation.

During pregnancy, mitral planimetry is particularly useful because the gradient and pulmonary pressure change with heart rate and cardiac output. Symptoms must be distinguished from normal pregnancy physiology, anemia and other causes. Diuretics and rate-control drugs are used with maternal and fetal objectives in mind; uncontrolled symptomatic severe stenosis may require commissurotomy at an experienced center if anatomy and the absence of regurgitation greater than mild allow it. Surgery with cardiopulmonary bypass carries greater fetal risk and is reserved for extreme situations.

Secondary penicillin prophylaxis continues during pregnancy when indicated. Anticoagulation, however, requires an individualized plan because VKAs, heparins, gestational age, prostheses and rheumatic stenosis carry different risks; substitutions should not be improvised. WHO regards echocardiographic screening of pregnant women in high-prevalence settings only as a conditional recommendation supported by very low-certainty evidence: a program must ensure confirmation and a genuine obstetric-cardiology pathway.

Endocarditis prevention follows contemporary indications based on risk and procedures, not merely the rheumatic etiology. Oral hygiene, access to dental care and recognition of persistent fever are essential; procedural antibiotic prophylaxis is reserved for high-risk categories defined by guidelines, such as some people with prosthetic valves. New regurgitation, a vegetation or embolism in a patient with rheumatic disease should be assessed as possible endocarditis and not automatically attributed to “rheumatic reactivation.”

Rheumatic heart disease ultimately requires continuity throughout the lifespan. Infection prevention, accurate diagnosis of acute fever, prophylaxis against recurrences, standardized echocardiography and access to intervention are different but inseparable links. The best outcome does not come from a single test or drug: it comes from recognizing in time the transition from streptococcal exposure to pathologic immunity and from valvulitis to scarring, without waiting for arrhythmia, embolism, pregnancy or heart failure to reveal already advanced disease.