Pathophysiological Progression of Rheumatic Heart Disease

Initial Infection and Immune Response

Rheumatic fever begins with a GAS throat infection that triggers an abnormal autoimmune response in genetically susceptible individuals 1
The immune response is directed against the M-protein serotypes of the GAS organism, which share structural similarities with human cardiac tissues 2, 3
After recovery from the initial episode of rheumatic fever, 60-65% of patients develop valvular heart disease 1

The autoimmune reaction begins in the periphery following a symptom-free interval of 14-21 days after the GAS pharyngitis 4

Carditis is a major manifestation of acute rheumatic fever according to the revised Jones criteria 5
Carditis can be clinical or subclinical 5
Valvulitis primarily affects the mitral valve, with the anterior leaflet tip showing abnormal coaptation and regurgitation typically directed posterolaterally 5
Aortic valve involvement is less common and rarely occurs in isolation 5

Recurrent GAS infections lead to repeated episodes of acute rheumatic fever, which progressively damage the heart valves 1, 6

Rheumatic mitral stenosis results from fusion of the commissures with scarring and eventual calcification of the cusps 3
Rheumatic aortic stenosis is less common and is invariably accompanied by mitral valve disease 3
As the disease progresses, valvular fibrosis and calcification lead to permanent structural changes 1
The chronic phase is characterized by progressive valvular stenosis and/or regurgitation 1
Long-term complications include atrial fibrillation, heart failure, stroke, infective endocarditis, and pregnancy-related complications 1

Recurrent GAS infections accelerate the progression of valvular damage 6
Secondary prophylaxis with continuous antimicrobial therapy is critical to prevent recurrent episodes of rheumatic fever and further valvular damage 4, 7
The duration of prophylaxis depends on whether carditis was present and if residual heart disease persists 7, 8

Early recognition and treatment of GAS pharyngitis is essential for primary prevention of rheumatic fever 2, 4
Secondary prophylaxis with penicillin is crucial to prevent recurrent episodes of rheumatic fever and further valvular damage 4, 7, 8
Patients with rheumatic heart disease require regular clinical follow-up to monitor disease progression 9
The rate of progression of valvular stenosis appears to be more rapid in patients with degenerative calcific disease than in those with congenital or rheumatic disease 9

In susceptible individuals, untreated group A streptococcal pharyngitis can precipitate acute rheumatic fever, establishing the initial autoimmune cascade【10】.
Historical epidemic data indicate that up to 3 % of untreated streptococcal throat infections progressed to rheumatic fever, although contemporary endemic rates are lower【10】.

Specific HLA class I and II antigens—including HLA‑B17, HLA‑B18, HLA‑B35, and HLA‑DR2—have been linked to increased susceptibility to rheumatic heart disease, with variability observed across different populations【11】.

Because the disease is driven by an autoimmune response, a streptococcal infection does not need to be clinically apparent to trigger a recurrent rheumatic fever episode, and recurrence can occur even when the acute infection is adequately treated【12】.
Effective secondary prevention therefore requires long‑term antimicrobial prophylaxis rather than reliance solely on the recognition and treatment of acute streptococcal pharyngitis episodes【12】.

In the absence of appropriate prophylaxis, rheumatic heart disease leads to premature cardiovascular mortality, with reported mean age at death of under 25 years in several cohort studies【13】.