Rheumatic Heart Disease

DR. SRI HASTUTI SPJP.FIHA

RSUD.DR.M.YUNUS BENGKULU
APRIL 2020
 INTRODUCTION
• RHD continues unabated in poor countries and among vulnerable groups in
wealthy ones .
• A 2007 report on RHD among school children in Cambodia and Mozambique
spawned a whole literature on echocardiography and RHD .
• The recent REMEDY study (Global Rheumatic Heart Disease Registry)
documented high rates of disability and premature death across African and
Asian countries .
• In 2015, a civil society movement, RHD Action, was launched to raise awareness
and support countries looking to address RHD .
• In May 2018, the World Health Assembly adopted a resolution to reinvigorate
global and national RF/RHD prevention and control efforts .
Watkins, DA,MD, Beaton AZ, MD et all Journal of the american
college of cardiology vol 72 No. 12,2018
Epidemiology
The Global Burden of Disease 2015
study identified prevalence data from
59 countries .
Using epidemiological modeling
techniques, this study estimated about
33 million individuals (0.4% of the
global population) currently live with
RHD.
The disease is most common in sub-
Saharan Africa, South Asia, and
Oceania

Watkins, DA,MD, Beaton AZ, MD et all Journal of the

american college of cardiology vol 72 No. 12,2018
• The highest incidence is observed in children aged 5-15 years and in
underdeveloped or developing countries where antibiotics are not
routinely dispensed for pharyngitis and where compliance is low. 
 Rheumatic Fever
• Rheumatic fever is an inflammatory disease that can involve the
heart,joint, skin and brain.
• Develop 2-4 weeks after streptococcal throat infection.
• The symtomps are fever, multiple painful joints, involuntary muscle
movements, erytema marginatum.
 Diagnosis

• Modified Jones criteria were first published in 1944 by T. Duckett

Jones, MD. They have been periodically revised by the American
Heart Association in collaboration with other groups.
• According to revised Jones criteria, the diagnosis of rheumatic fever
can be made when two of the major criteria, or one major criteria
plus two minor criteria, are present along with evidence of
streptococcal infection: elevated or rising antistreptolysin O titre or
DNAase.Exceptions are chorea and indolent carditis, each of which by
itself can indicate rheumatic fever.
https://www.textbookofcardiology.o
rg/wiki/Rheumatic_Heart_Disease
MAJOR CRITERIA
• Polyarthritis: A temporary migrating inflammation of the large joints, usually starting in the legs
and migrating upwards.
• Carditis: Inflammation of the heart muscle (myocarditis) which can manifest as congestive heart
failure with shortness of breath, pericarditis with a rub, or a new heart murmur.
• Subcutaneous nodules: Painless, firm collections of collagen fibers over bones or tendons. They
commonly appear on the back of the wrist, the outside elbow, and the front of the knees.
• Erythema marginatum: A long-lasting reddish rash that begins on the trunk or arms as macules,
which spread outward and clear in the middle to form rings, which continue to spread and
coalesce with other rings, ultimately taking on a snake-like appearance. This rash typically spares
the face and is made worse with heat.
• Sydenham's chorea (St. Vitus' dance): A characteristic series of rapid movements without
purpose of the face and arms. This can occur very late in the disease for at least three months
from onset of infection.
MINOR CRITERIA

• Fever of 38.2–38.9 °C (101–102 °F)

• Arthralgia: Joint pain without swelling (Cannot be included if polyarthritis is
present as a major symptom)
• Raised erythrocyte sedimentation rate or C reactive protein
• Leukocytosis
• ECG showing features of heart block, such as a prolonged PR interval
(Cannot be included if carditis is present as a major symptom)
• Previous episode of rheumatic fever or inactive heart disease
• In the revised 2015 Jones criteria (Table II) [4], a low, medium and high-risk
population was identified. A low risk population is one in which cases of
acute RF occur in ≤ 2/100 000 school-age children or rheumatic heart
disease is diagnosed in ≤ 1/1000 patients at any age during one year
• The diagnosis of RF in the whole population with evidence of antecedent
group A β-hemolytic streptococcal infection requires a confirmation of two
major criteria or one major and two minor criteria – the first episode of
the disease.
• The diagnosis of subsequent episodes of the disease requires a
confirmation of two major criteria or one major and two minor criteria or
three minor criteria
Modified Jones criteria 2015
 Etiology and Phatophysiology
• Rheumatic heart disease is cardiac inflammation and scarring
triggered by an autoimmune reaction to infection with 
group A streptococci.
• In the acute stage, this condition consists of pancarditis, involving
inflammation of the myocardium, endocardium, and epicardium.
• Chronic disease is manifested by valvular fibrosis, resulting in stenosis
and/or insufficiency.

Allen Patrick Burke, MD; Chief Editor: Allen Patrick

Burke, MD  more;The Heart orang Medscape; oct
2015
 Etiology and Pathophysioloy

• Rheumatic fever results from humoral and cellular-mediated immune responses

occurring 1-3 weeks after the onset of streptococcal pharyngitis.
• Streptococcal proteins display molecular mimicry recognized by the immune
system, especially bacterial M-proteins and human cardiac antigens such as
myosin  and valvular endothelium.
• Antimyosin antibody recognizes laminin, an extracellular matrix alpha-helix coiled
protein, which is part of the valve basement membrane structure.
•  caused by antibody cross-reactivity is Type II hypersensitivity
reaction and is termed molecular mimicry.
• During a Streptococcus infection, mature antigen presenting cells
such as B cells present the bacterial antigen to CD4-T cells which
differentiate into helper T2 cells. Helper T2 cells subsequently activate
the B cells to become plasma cells and induce the production of
antibodies against the cell wall of Streptococcus.
• However the antibodies may also react against the myocardium and
joints, producing the symptoms of rheumatic fever.
• T-cells that are responsive to the streptococcal M-protein infiltrate the valve
through the valvular endothelium, activated by the binding of antistreptococcal
carbohydrates with release or tumor necrosis factor (TNF) and interleukins. 
• The increased expression of Th17 cell-associated cytokines might play an
important role in the pathogenesis and development of rheumatic heart disease.
• The acute involvement of the heart in rheumatic fever gives rise to pancarditis,
with inflammation of the myocardium, pericardium, and endocardium.
• Carditis occurs in approximately 40-50% of patients on the first attack; however,
the severity of acute carditis has been questioned.  
• Pericarditis occurs in 5-10% of patients with rheumatic fever; isolated myocarditis
is rare.
• The valves most affected by rheumatic fever, in order, are the mitral, aortic,
tricuspid, and pulmonary valves.
• In most cases, the mitral valve is involved with 1 or more of the other 3.
• In acute disease, small thrombi form along the lines of valve closure.
• In chronic disease, there is thickening and fibrosis of the valve resulting in
stenosis, or less commonly, regurgitation.
• The antibodies which the immune system generates against the M protein
may cross react with cardiac myofiber protein myosin, heart muscle
glycogen and smooth muscle cells of arteries, inducing cytokine release and
tissue destruction
• This inflammation occurs through direct attachment of complement and Fc
receptor-mediated recruitment of neutrophils and macrophages.
• Characteristic Aschoff bodies, composed of swollen eosinophilic collagen
surrounded by lymphocytes and macrophages can be seen on light
microscopy. The larger macrophages may become Anitschkow cells or
Aschoff giant cells.
• Acute rheumatic valvular lesions may also involve a cell-mediated immunity
reaction as these lesions predominantly contain T-helper cells and
macrophages
• In acute rheumatic fever, these lesions can be found in any layer of
the heart and is hence called pancarditis.
• The inflammation may cause a serofibrinous pericardial exudate
described as "bread-and-butter" pericarditis, which usually resolves
without sequelae.
• Involvement of the endocardium typically results in fibrinoid necrosis
and verrucae formation along the lines of closure of the left-sided
heart valves.
• Warty projections arise from the deposition, while subendocardial
lesions may induce irregular thickenings called MacCallum plaques.
 Molecular and genetic factor
• Human leukocyte antigen (HLA) class II allele DR7 (HLA-DR7) is most often associated with RHD, and its
combination with certain DQ alleles is seemingly associated with the development of valvular lesions.
• The mechanism by which MHC class II molecules increase a host's susceptibility to autoimmune
reactions in RHD is unknown, but it is likely related to the role HLA molecules play in presenting antigens
to T cell receptors, thus triggering an immune response.
• Also found on human chromosome 6 is the cytokine TNF-α which is also associated with RHD.
• High expression levels of TNF-α may exacerbate valvular tissue inflammation, contributing to RHD
pathogenesis.
• Mannose-binding lectin (MBL) is an inflammatory protein involved in pathogen recognition. Different
variants of MBL2 gene regions are associated in RHD.
• RHD-induced mitral valve stenosis has been associated with MBL2 alleles encoding for high production
of MBL. Aortic valve regurgitation in RHD patients has been associated with different MBL2 alleles that
encode for low production of MBL.
• Other genes are also being investigated to better understand the complexity of autoimmune reactions
that occur in RHD.
World Heart Federation Criteria for Diagnosis of RHD

Watkins, DA,MD, Beaton AZ, MD et all

Journal of the american college of
cardiology vol 72 No. 12,2018
 Treatment
• Rheumatic fever treatment has not changed for many years. It covers:
• • anti-streptococcal treatment (primary and secondary prevention),
• • anti-inflammatory treatment.
Primary prevention
• Primary prevention relies on the proper treatment of streptococcal
pharyngitis, that is, prevention of the first RF episode.
• Phenoxymethylpenicillin orally at the following doses: adults and
children with a body weight > 40 kg – 2–3 MIU/day in 2 divided doses
every 12 hours for 10 days, children with a body weight < 40 kg –
100,000 to 200,000 IU/kg/day in 2 divided doses every 12 hours for
10 days.
• Benzylpenicillin, im at a single dose (only in hospital settings), is
acceptable, for adults and children with a body weight > 40 kg – 1.2
MIU, children with a body weight < 40 kg – 600,000 IU.
• Cefadroxil: adults and children with a body weight >40kg–
1g,childrenwithabodyweight<40kg–30mg/kg, in a single dose for 10
days.
• Cefalexin: adults 500 mg twice per day, children 25– 50 mg/kg/day in
2 doses for 10 days.
• Erythromycin: adults and children with a body weight > 40 kg – 0.2–
0.4 g every 6–8 hours, children with a body weight < 40 kg – 30–50
mg/kg/day in 3–4 doses, for 10 days.
• Clarithromycin: adults and children with a body weight > 40 kg – 250–
500 mg every 12 hours, children with a body weight < 40 kg – 15
mg/kg/day in 2 doses, for 10 days.
• Azithromycin: adults and children with a body weight > 40 kg – 500
mg on the first day, then 250 mg for three consecutive days, children
with a body weight < 40 kg – a single daily dose of 12 mg/kg/day for 5
days or 20 mg/kg/day for 3 days [9].
Secondary prevention

• Secondary prevention is the prevention of subsequent rheumatic fever

relapses through the chronic antistreptococcal treatment:
phenoxymethylpenicillin or benzathine benzylpenicillin or possibly
macrolides.
• The patient has developed carditis and complications in the form of chronic
valvular heart disease.
• Secondary prevention should be administered from 5 to 10 years from the
last RF relapse, or up to 21 years of age (whichever is longer)
• In RF cases with carditis leading to chronic valvular heart disease, the
prevention should be administered for 10 years or until 40 years of age
(whichever is longer) .
• Secondary prevention makes use of benzathine benzylpenicillin,
intramuscularly: in adults and children with a body weight > 20 kg –
1.2 MIU, in children with a body weight < 20 kg – 600,000 IU every 4
weeks .
• Phenoxymethylpenicillin orally at a dose of 2 × 250 mg (i.e. 2 ×
400,000 IU).
Anti inflammation treatment

• In the case of heart involvement, glucocorticosteroids (GCs) are used

prednisone at a dose of 1–2 mg/ kg/day for 2–3 weeks, then the dose
should be reduced gradually. The total duration of GCs treatment is 6
weeks. During the period of prednisone dose reduction, acetyl-
salicylic acid should be initiated – at 60 mg/kg/day .
• The treatment of chorea is based on sedatives, anti- epileptics, in
some cases GCs, infusions of immunoglobulins or plasmapheresis.
THANK YOU