This document discusses prevalence and incidence of acute rheumatic fever (ARF) and rheumatic heart disease (RHD) in India. It covers the molecular mimicry theory of how group A streptococcal pharyngitis can trigger an autoimmune response attacking the heart and other tissues. Host genetic factors play a role in susceptibility. Clinical manifestations of ARF include arthritis, carditis, chorea, and subcutaneous nodules. Echocardiography is important for diagnosing carditis. RHD remains a major cause of cardiovascular disease in India. Prevention requires prompt treatment of streptococcal infections.

1. Prevalence & incidence of ARFPrevalence & incidence of ARF
& chronic RHD in india& chronic RHD in india
DrVirbhan Balai

2. Acute Rheumatic FeverAcute Rheumatic Fever
An entirely preventable disease

3. The theory of molecular mimicryThe theory of molecular mimicry
GAS pharyngitis triggers an autoimmune
response to epitopes in the organism that
cross-react with similar epitopes in the
heart, brain, joints, and skin, and repeated
episodes of rheumatic fever lead to RHD
Cunningham MW: Streptococcus and rheumatic fever. Curr Opin
Rheumatol 24:408, 2012.

4. French physician Ernst-Charles Lasègue - 1884French physician Ernst-Charles Lasègue - 1884
“Pathologists have long known that rheumatic fever
licks at the joints, but bites at the heart.”

5. EpidemiologyEpidemiology TriadTriad
1. Agent: virulence
2. Host: Genetic susceptibility[3-5%]
3. Environment: Challenged socioeconomic

6. Hot spot
 Kyrgyzstan
Highest incidence of RF/RHD
 543/100,000 population per year

7. (Modified from Parry E, Godfrey R, Mabey D, Gill G [eds]: Principles(Modified from Parry E, Godfrey R, Mabey D, Gill G [eds]: Principles
of Medicine in Africa. 3rd ed. Cambridge, Cambridge University Press,of Medicine in Africa. 3rd ed. Cambridge, Cambridge University Press,
2004, p 861.)2004, p 861.)
 4 patterns RF in 150 years.
◦
A- Preantibiotic fall in the incidence of
ARF of industrialized countries
◦ B-Persistent high incidence RF
[Africa and south Asia].
◦ C-Postantibiotic fall in the incidence of
rheumatic fever in countries that
instituted comprehensive programs for
primary and secondary prevention of
rheumatic fever, such as Cuba, Costa
Rica, Martinique, and Guadeloupe.
◦ D-Fall and rise in the incidence of
rheumatic fever in the formerly Soviet
Republics of Central Asia.

8. AgentAgent
Group A beta-haemolytic streptococcus
A poisonous “GAS”

9. PathogenesisPathogenesis

10. 2 Hit hypothesis2 Hit hypothesis
Hit -1:cross reaction Hit-2:T lymphocyte invasion
Epitopes on the cell wall of
Streptococcus forms cross
reacting antibodies to host
antigens
The antigen and antibody
complex at the target site
invites T lymphocytes to
come out of vessel and
stimulates local epitheloid
cell to become Anitkoff’s
cell around the central
Fibrinoid degeneration
forming together called
“Aschoff- Geipel bodies”

11. Targets of molecular mimicryTargets of molecular mimicry
Intracellular Extracellular
Cardiac myosin
Brain tubulin
Laminin on the endothelial
surface of the valve
Lysoganglioside and
dopamine receptors in the
brain

12. Susceptibility of hostSusceptibility of host
 3-6% without primary Rx
 X5 time if family Hx positive
 Poor fellow
 No hygiene
 Lives in tight pack
 X6 time in monozygotic
 X3 times in children if one
parent +
 The heritability of rheumatic
fever is 60%
Family history is must in Rheumatic heart disease

13. PhotomicrographPhotomicrograph
 Aschoff nodule of acute
rheumatic fever. The nodule is
composed of Anitschkow cells;
these have clear nuclei with a
central bar of chromatin, said to
resemble a caterpillar. There is a
central area of fibrin. This central
necrosis is further surrounded by
a mononuclear cell infiltrate.
Myocardial fibres adjacent to the
Aschoff body are undergoing
Fibrinoid necrosis. (Sebire NJ,
Ashworth M, Malone M, Jacques TS
[eds]: Diagnostic Pediatric Surgical
Pathology. Churchill Livingstone,
United Kingdom, 2010.)

14. Potential barrier to Rx RF/RHDPotential barrier to Rx RF/RHD
Streptococcal
pharyngitis- 2 to 3
Wk-no lab test +
except throat culture
Rheumatic fever
◦ 30% -asymptomatic
GAS pharyngitis
◦ 50% -asymptomatic
GAS pharyngitis in
epidemic time
◦ Age :4-15 yrs
◦ Juvenile(3-5 yrs) -India
Think of vaccine

15. ArthritisArthritis
Almost 100%
Severe in young adults than in teenagers
(82%) and children (66%)
Migratory
A few days to a week
2/3rd
-polyarthritis
resolves completely
If joint swelling persists after 4 weeks, it
is necessary to consider other conditions

16. Poststreptococcal reactive arthritisPoststreptococcal reactive arthritis
Not typical of rheumatic fever
Recent streptococcal infection
shorter latent period
 responds less well to NSAID
renal manifestations
No carditis
Rx 2ndary prophylaxis with pencillin

17. CarditisCarditis
 most serious
 CRHD
 Accidental detection with chorea
 The incidence of carditis during the initial attack of RF
◦ 40%-No echo
◦ 91%-with echo
 Varies with the age
◦ 90% to 92% of children <3 years
◦ 50% of children 3 to 6 years of age
◦ 32% of teenagers aged 14 to 17 years
◦ 15% of adults
 Myocarditis in the absence of valvulitis is unlikely to be
rheumatic in origin

18. ContdContd
CHF - 5% to 10% during initial attack
and increases with repeated carditis
Transient apical mid-diastolic murmur
(Carey-Coombs) may occur in
association with the murmur of mitral
regurgitation

19. WHF:Minimum Echocardiographic Criteria for theWHF:Minimum Echocardiographic Criteria for the
Diagnosis of Pathologic Valvular RegurgitationDiagnosis of Pathologic Valvular Regurgitation
Secondary to Rheumatic CarditisSecondary to Rheumatic Carditis
PATHOLOGIC MITRAL
REGURGITATION (ALL FOUR
DOPPLER CRITERIA MUST BE MET)
PATHOLOGIC AORTIC
REGURGITATION (ALL FOUR
DOPPLER CRITERIA MUST BE MET)
1. Seen on 2 views
1. Seen on 2 views
2. On at least 1 view jet length is ≥2 cm*
2. On at least 1 view jet length is ≥1 cm*
3. Peak velocity ≥3 meters/sec
3. Peak velocity ≥3 meters/sec
4. Pansystolic jet in at least 1 envelope
4. Pandiastolic jet in at least 1 envelope

20. Sydenham ChoreaSydenham Chorea
 may be the only initial manifestation
F>M
after puberty-more
6 to 8 weeks from pharyngitis
Chorea-involuntary, purposeless, jerky
movements of the hands, arms,
shoulders, feet, legs, face, and trunk along
with hypotonia and weakness,interfere
voluntary activity and disappear during
sleep

21. Hemichorea- completely unilateral
 jack-in-the-box tongue
 “the milking sign”
 Emotional lability
last for a week to 2 years but generally
persists for 8 to 15 weeks
Serological markers may be normal
because of long latency

22. PANDASPANDAS
subgroup of children with tic or
obsessive-compulsive disorders that are
triggered by GAS infection with no
associated cardiac valve damage
 if ever, make a diagnosis of PANDAS
and should rather err on the side of
diagnosis of rheumatic fever and
implement secondary prophylaxis

23. Subcutaneous NodulesSubcutaneous Nodules
Detected over the occiput, elbows,
knees, ankles, and Achilles tendons
Over olecranon
Firm, painless, and freely movable over
the subcutaneous tissue. The nodules
vary in size from 0.5 to 2 cm
1.5%
In crops-carditis

24. Erythema MarginatumErythema Marginatum
less common
upper part of the arms or trunk but not
on the face
not pathognomonic
The rash
Evanescent, pink, and nonpruritic. It extends centrifugally
whereas the skin at the center returns to normal—hence the
name “erythema marginatum.” It has an irregular serpiginous
border. The rash may also become more prominent after a
hot shower. Erythema marginatum generally occurs only in
patients with carditis and may develop early or later in the
course of the disease.

25. 1970-19901970-1990

26. 1991-2011

27. In India, rheumatic fever is endemic
and remains one of the major causes
of cardiovascular disease,
accounting for nearly 25-45% of the
acquired heart disease. ROUTRAY SN2003
PRIMARY ATTACK RATE OF RF
FOLLOWING STREPTOCOCCAL
PHARYNGITIS
◦ EPIDEMICS: 3%
◦ SPORADIC:0.3%

29. RF is a delayed autoimmune response to Group A streptococcal pharyngitis, and
the clinical manifestation of the response and its severity in an individual is
determined by host genetic susceptibility, the virulence of the infecting organism,
and a conducive environment

30. AGENTAGENT
 Beta-haemolytic streptococci
can be divided into a
number of serological groups
on the basis of their cell-wall
polysaccharide antigen
 Serological group A
(streptococcus pyogenes) can
be further subdivided into
more than 130 distinct M
types.
 The available evidence does
not link streptococci in Non-
group A types with the
pathogenesis of rf and rhd

31.  Group A streptococci are the most common
bacterial cause of pharyngitis, with a peak
incidence in children 5–15 years of age.
 15–20% of sore throats are caused by group A
streptococci.
 A patient with a true infection is at risk of
developing RF and of spreading the organism
to close contacts, while this is not thought to
be the case with carriers
 Positive throat culture rate for Gr A
streptococci are around 13.5% in Northern
India in sore throat cases.

33. RHEUMATOGENIC STRAINSRHEUMATOGENIC STRAINS
 Very rich in M-
protein
 Heavily
encapsulated
 produce striking
"mucoid" colonies on
blood agar plates
 Tropic primarily for
the throat
 M 1, 3, 5, 6, 18, 19
and 24
 The site of infection
must be pharyngeal
 GAS virulence
◦ (Extractable and
heterotypic antigen,
the M protein)
◦ Capsule of hyaluronic
acid("mucoid"
appearance of GAS
colonies)
◦ M protein and
capsule, are primarily
responsible for the
striking resistance of
virulent strains of
GAS to phagocytosis

34. M protein and antigensM protein and antigens

35. M proteinM protein
 The streptococcal M-
protein extends from
the surface of the
streptococcal cell as
an alpha–helical coiled
dimer,
 Shares structural
homology with cardiac
myosin and other
alpha-helical coiled
molecules, such as
Tropomyosin, keratin
and laminin(lines
valve structure and is
a target for poly
reactive antibody)

36.  Nonsuppurative sequel, such as RF and RHD,
are seen only after group A streptococcal
infection of the upper respiratory tract.
Bramhanathan et al 2006
 Exception: skin infection leading to RF
described in some aborginal tribes of australia
 Chronic streptococcal “carrier” states do not
trigger the development of RF.
 The role of group A streptococcus infection is
complex and repeated infection is necessary
to prime the immune response, quantitatively
and qualitatively ,before the first episode of
ARF occurs

37. HOST FACTORS
 An inherited susceptibility to ARF and RHD is
supported by twin studies that have found a
significantly increased concordance in
monozygotic twins compared with dizygotic
twins.
 2 % OF ARF INFECTIONS HAVE BEEN
FOUND TO BE FAMILIAL
Padmavathi 1962
GAS pharyngitis is primarily a disease of
children 5 to 15 years of age

38. HOST FACTORSHOST FACTORS
 ARF is a rare disease in the very young;
 Only 5% of first episodes arise in children
younger than age 5 years and the disease is
almost unheard of in those younger than 2
years.

39. HOST FACTORSHOST FACTORS
 First episodes of ARF
are most common just
before adolescence,
wane by the end of the
second decade, and
are rare in adults
older than age 35
years.
 Recurrent episodes
are especially frequent
in adolescence and
early adulthood, and
occasional cases are
seen in people older
than age 45 years

40. HOST FACTORSHOST FACTORS
 In many populations, ARF and RHD are more
common in females than males
◦ ?Innate susceptibility,
◦ ? Increased exposure to group a
streptococcus because of greater
involvement of women in child rearing,
◦ ?Or reduced access to preventive medical
care for girls and women.
 In populations exposed to rheumatogenic
group A streptococci, the lifetime cumulative
incidence of ARF is 3% to 6%.

41. HOST FACTORSHOST FACTORS

42. ENVIRONMENT FACTORSENVIRONMENT FACTORS

44. Direct and indirect results of environmental and health-
system determinants on
rheumatic fever and rheumatic heart disease

45. PATHOGENETIC PATHWAY FOR ARF AND RHD

49.  Myosin is not present in cardiac valves, so how can an immune response against
myosin induce valvulitis?
 The initial damage to the valve might be due to the presence of laminin, another
alpha-helical coiled-coil molecule present in the valvular basement membrane
and around endothelium, and which is recognised by T cells
 There is also evidence that antibodies to cardiac valve tissues cross-react with N-
acetyl glucosamine in group A carbohydrate.
 An exaggerated antibody response to group A carbohydrate was noted in
patients with ARF, and titres remained raised in individuals with residual mitral
valve disease, providing further support for the notion that these antibodies
cause valve damage
THE IMMUNE RESPONSE

50.  Immune complexes may produce
nondestructive synovitis of the joints in
patients with ARF and nondestructive
reactions in the basal ganglia observed in
Sydenham's chorea, whereas cell mediated
autoimmune cytotoxic reactions may destroy
heart valves.

51.  Are spheroidal or fusiform
distinct tiny structures or
granulomas, 1-2 mm in
size, occurring in the
interstitium of the heart in
RF.
 Especially found in the
vicinity of small blood
vessels in the myocardium
and endocardium and
occasionally in the
pericardium.
 Lesions similar to the
aschoff nodules may be
found in the extracardiac
tissues .

53. CLINICAL FEATURES AND DIAGNOSIS OF
STREPTOCOCCAL SORE THROAT
CLINICAL ASPECTS
AROUND 20% OF
SORETHROAT
CASES

54. JONES CRITERIA AND ITSJONES CRITERIA AND ITS
EVOLUTIONEVOLUTION

55. Every revision increased the specificity but decreased the
sensitivity of the criteria,

56. 2002–2003 WHO criteria for the diagnosis of
rheumatic fever and rheumatic heart disease
(based on the revised Jones criteria)
These revised WHO criteria facilitate the
diagnosis of:
— A primary episode of RF
— Recurrent attacks of RF in patients without
RHD
— Recurrent attacks of RF in patients with RHD
— Rheumatic chorea
— Insidious onset rheumatic carditis
— Chronic RHD.

61. DEFINITIONS
Recurrence: A new episode of rheumatic fever following another
GABHS infection; occurring after 8 week following stopping
treatment
Rebound: Manifestations of rheumatic fever occurring within 4-6 wk
of stopping treatment or while tapering drugs.
Relapse: Worsening of rheumatic fever while under treatment and
often with carditis.
Sub clinical carditis: When clinical examination is normal but
echocardiogram is abnormal. Around 30 percent of patients
having chorea present as subclinical carditis.
Indolent carditis: It is a common entity in our country. Patient
presents with persistent features of CHF, murmur and
cardiomegaly.

62. JONES CRITERIAJONES CRITERIA
INDIAN CONTEXTINDIAN CONTEXT
ROY PADMAVATHI
66% 55%

64.  75%subside within 6 weeks
 90% subside within 12 weeks
 <5% active after 6 months
 MORTALITY FROM ARF
◦ GROVER: 7%
◦ SHARMA:1.2%
PROGRESSION TO RHD:
India 5-20yrs
West 15-40yrs.

65. CARDITIS
 Most important manifestation
 Most often causes no symptoms of its own
and is most often diagnosed in the course of
examination of a patient with arthritis or
chorea.
 In 93% carditis develops with in 3 months
 Rare to hear murmur after 6 months after the
onset of ARF

66. CARDITIS
1. SLEEPING HR >
100
2. NEW ONSET
MURMURS
3. CHF
4. CARDIOMEGALY
5. PERICARDIAL
RUB
6. S3
Incidence
◦ 33 to 55%( India)
◦ 40-50% west)
Murmurs manifest
in 85%by 2nd
or 3
rd week.
In an RHD patient
CCF should be
suspected as a
reccurence of
carditis

67. MyocarditisMyocarditis
Due to an acute hemodynamic overload on the
left ventricle from acute/ subacute mitral
and/or aortic regurgitation.
Myocarditis (alone) in the absence of
valvulitis is unlikely to be of rheumatic
origin. It should always be associated
with an apical systolic or basal diastolic
murmur.

68. PERICARDITISPERICARDITIS
 Rheumatic pericarditis is relatively less common
clinically and is present in up to 15% patients.
 Since pericarditis neither results in tamponade nor
constriction and clears up without leaving a residue, its
limited clinical significance lies in the fact that it
provides clear cut evidence for the presence of active
carditis as well as active RF.
 Pericarditis does not occur in the absence of clinical
findings indicative of valvulitis.
 Simultaneous demonstration of valvular involvement
generally considered essential.

69. CONGESTIVE HEART FAILURE
Least common but most serious
manifestation.
Occurs in5 to 10% of first attacks
of carditis.
More common in children <6yrs of
age.

70. Malignant rheumatic feverMalignant rheumatic fever
Severe disease with multi valvular
lesions, gross cardiac enlargement, and
congestive failure can occur in young
patients, and such children show more
symptoms of congestive failure than of
rheumatic disease.
This severe disease may be due in large
measure to a lack of rest during the
initial carditis

71. The wide difference in the reported prevalence of carditis
in the first attack could thus be related to clinically
undiagnosed carditis in the first attack which becomes
apparent after recurrences of acute RF

72. Arthritis and arthralgiaArthritis and arthralgia
 Most common and least specific
 75% of pts with 1st attack of ARF.
 Occurs early in the course of the disease, as
the presenting complaint
 Incidence increases with age.(Often the only
major manifestation in adolescents, as well as
in adults, where carditis and chorea become
less common in older age groups.)

73.  Inflamed joints are characteristically warm,
red and swollen, and an aspirated sample of
synovial fluid may reveal a high average
leukocyte count
 Important to differentiate from arthalgia( less
specific)
 Usually large joint
 Almost any joint can be affected

74. Tenderness in rheumatic arthritis may
be out of proportion to the objective
findings and severe enough to result in
excruciating pain on touch.
“MIGRATORY” reflects the sequential
involvement of joints, with each
completing a cycle of inflammation and
resolution, so that some joint
inflammation may be resolving while
others are beginning.

75.  If untreated as many as 16 joints can be involved and
atleast 6 in half of the patients
 Resolves spontneously with in 3 weeks without
sequelae( except jaccoud’s)
 Inverse relation with carditis
Feinstein AR, Sterno EK, Spagnuolo M. The prognosis of acuterheumatic fever.
Am Heart J 1964; 68: 817–834
severity Total no number % carditis
1 Red hot/
swollen
179 47 26
2 tender 30 12 40
3 Joint pains 25 24 96
4 No joint
symptoms
29 29 100

76. JOCCOUD CHRONIC POSTRHEUMATIC
ARTHRITIS
Periarticular fibrosis of the
metacarpophalangeal joints.
It usually occurs in patients with
severe RHD,but is not associated with
evidence of RF

77. POST STREPTOCOCCAL REACTIVE
ARTHRITIS (PSRA)
• Does not fulfill jones criteria
• Latent period is shorter (1 week).
• Arthritis is additive rather than migratory
• Poor response to salicylates
• Arthiritis persists for a mean period of two
months.
• Evidence of recent GABS infection is
Mandatory
• 6% develop mitral heart disease.
Not associated with other major
manifestations of RF

78. Migratory arthritisMigratory arthritis
 RF ,
Gonococcemia
Meningococcemia
Viral arthritis
Systemic lupus erythematosus
Acute leukemia
Whipple's disease

79. SYDENHAM’S CHOREA
Occurs primarily in children
Rare after the age of 20
Occurs primarily in females
Less commonin postpubertal males.
Prevalence of chorea in RF patients
varied from 5–36%

80. CHOREA
Concomitant subclinical carditis
detected by echocardiography appears
to be as high as 70%
Chorea is a uniquely delayed
manifestation of RF, with a wide range
in reported incidence between 5% and
35%, latency of 1 to 7 months, and
choreiform manifestations that may
last for months and occasionally years

81. CHOREA
There is a substantial risk of
subsequent RHD in these patients.
Neurologic deficits typically resolve
within 2 years, but residual psychiatric
disturbances occur in a small but
significant number of patients in the
subsequent decades

82. CHOREA
A syndrome of pediatric autoimmune
neuropsychiatric disorders associated
with streptococcal infections (PANDAS),
in a fashion similar to
poststreptococcal reactive arthritis, has
a temporal relationship to GABHS
infection but is not associated with
other features of RF

83. Sub cutaneous nodulesSub cutaneous nodules
 Firm round painless.
 0.5 to 2cms
 Overlying skin freely mobile
 Occurs in crops
 Located over bony prominences
 Lasting for 1 to 2 weeks
 Incidence:
 sanyal et al India: 2.3%combined with
erythema marginatum
 Subcutaneous nodules are almost always
associated with cardiac involvement and are
found more commonly in patients with
severe carditis

84. Subcutaneous nodulesSubcutaneous nodules
They may also be found over the scalp,
especially theocciput, and the spinous
processes of the vertebrae.
The number of nodules varies from one
to a few dozen, but usually three or four.
They persist from days to 1–2 weeks to,
rarely, more than a month

85. Erythema marginatumErythema marginatum
 Erythema marginatum occurs in up
to 15% of RF patients
 In view of the evanescent nature
may be easily missed.
 Appear first as a bright pink
macule or papule that spreads
outward in a circular or
seripiginous pattern.
 The lesions are multiple, appearing
on the trunk or proximal
extremities, rarely on the distal
extremities, and never on the face.
 They are nonpruritic and
nonpainful, blanch under pressure

86. Erythema marginatum usually
occurs early in the course of a
rheumatic attack.
It may, however, persist or recur for
months or even years, continuing
after other manifestations of the
disease have subsided, and it is not
influenced by anti-inflammatory
therapy.
Nodules and erythema marginatum
tend to occur together

87.  The latent period between streptococcal infection and
onset of RF is shortest in arthritis and erythema
marginatum and longest in chorea with carditis and
subcutaneous nodules in between.
 Atleast 1/3 rd of cases of acute rheumatic fever may
present with inapparent streptococcal infections
 Arthralgia and fever are termed “minor”
clinical manifestations of RF in the jones
diagnostic criteria, because they lack
diagnostic specificity

88. Elevated or rising streptococcal
antibody titers.
It is recommended that acute serum be collected at the onset of illness, and that
the antibody titer be compared to a convalescent serum collected 2-4 weeks
later, to detect a rise in titer

90. 1. The mitral valve is most often involved
2. Mitral regurgitation is the most common finding on color flow imaging.
3. Mitral regurgitation in rheumatic carditis is related to ventricular dilatation
and/or restriction of leaflet mobility.
4. Rheumatic carditis does not result in congestive heart failure in the absence of
hemodynamically significant valve lesions.
5. In a quarter of patients with rheumatic carditis, valve nodules were present
that may represent echocardiographic equivalents of rheumatic verrucae

91. THE ECHOCARDIOGRAPHIC CRITERIA
HAD SENSITIVITY OF 81% AND
SPECIFICITY OF 93%.
 THE EFFICACY OF ECHOCARDIOGRAPHIC CRITERIONS FOR THE DIAGNOSIS OF
CARDITIS IN ACUTE RHEUMATIC FEVER .B. VIJAYALAKSHMIA1 C1, RAJAN O.
VISHNUPRABHUA1, NARASIMHAN CHITRAA1,

92. Echocardiographic evidence ofEchocardiographic evidence of
definite RHDdefinite RHD
 ANY OF:
a) A mitral regurgitant jet at least 2 cm from the coaptation point of the
valve leaflets, seen in two planes and persisting throughout systole plus
thickened mitral valve leaflets and/or elbow or dog leg deformity of the
anterior mitral valve leaflet.
b) An aortic regurgitant jet at least 1 cm from the coaptation point of the
valve leaflets, seen in two planes plus thickened mitral valve leaflets and/or
elbow or dog leg deformity of the anterior mitral valve leaflet.
c) Any significant mitral stenosis (defined as flow acceleration across the
mitral valve with a mean pressure gradient greater than 4mmHg

93.  Echocardiographic demonstration of valvular
regurgitation is not a prerequisite for the diagnosis of
rheumatic carditis and should not be considered a
limitation where the facilities are not available.
 Currently, data do not allow subclinical valvular
regurgitation detected by echocardiography to be
included in the Jones criteria, as evidenceof a major
manifestation of carditis.

94. CARDIAC ENZYMES
Markers of myocardial damage in the form
of troponin I, myoglobin and CPK-MB were
evaluated in patients with acute rheumatic
carditis with and without cardiomegaly or
congestive cardiac failure. The markers of
myocardial damage remained normal inspite
of clinically active carditis.
 Gupta M, Kaplan EL,. Serum cardiac troponin I in acute rheumatic
fever. Am J Cardiol 2002

96. NATURAL HISTORY OF MSNATURAL HISTORY OF MS
 In India, critical MS may be found in children
as young as 6 to 12 years old. ( UP TO 20%)
 In the asymptomatic or minimally
symptomatic patient, survival is greater than
80% at 10 years,
 with 60% of patients having no progression of
symptoms.
 once significant limiting symptoms occur,
there is a dismal 0% to 15% 10-year survival
rate
 Once there is severe pulmonary hypertension,
mean survival drops to less than 3 years.

97. 30 to 40% of patients with MS
develop atrial fibrillation (AF).
 Atrial fibrillation occurs more
commonly in older patients and is
associated with a poorer
prognosis, with a 10-year survival
rate of 25% compared with 46% in
patients who remain in sinus
rhythm.

98. The mortality of untreated patients with
MS is due to
1.Progressive pulmonary and systemic
congestion in 60% to 70%,
2.Systemic embolism in 20% to 30%,
3.Pulmonary embolism in 10%,
4.Infection in 1% to 5%.
Serial hemodynamic and Doppler-
echocardiographic studies have reported
annual loss of MV area ranging from 0.09
to 0.32 cm2.

99. Mitral regurgitation can be alone
or with other lesions
As high as 70% of MR in initial
attack can disappear over a period
of time.
If AS is present with MV
involvement it is likely to be
rheumatic

100. AORTIC REGURGITATIONAORTIC REGURGITATION
Asymptomatic patients with normal LV
systolic function
◦ Progression to symptoms &/or LV dysfn: 6%
◦ Progression to asymptomatic LV dysfunction
< than 3.5% per year
Asymptomatic patients with LV
dysfunction
◦ Progression to symptoms: more than 25% per
year

101. ARF AND RHD INDIAN SCENARIO
1. SCHOOL HEALTH SURVEYS
2. HOSPITAL SURVEYS
3. POPULATION DATA
4. AUTOPSY SERIES

102. 1970-19901970-1990

103. 1991-2011

106. ICMR SCHOOL SURVEYSICMR SCHOOL SURVEYS

108. HOSPITAL BASED SURVEYS
AUTHOR YEAR REGION TOTAL CARDIAC
CASES
% RF/RHD
KUTUMBAIAH 1932-38 VIZAG 1155 39.5
RAMAN 1935-41 VIZAG 2076 35.6
SANJEEV 1941 MADRAS 616 46.8
VAKIL 1941-45 BOMBAY 1860 24.7
PADMAVATHI 1951-55 DELHI 2360 39.1
BENARJEE 1936-43 CALCUTTA 717 44.6
VAKIL 1946-55 BOMBAY 6825 29.7
MALHOTRA, GUPTA 1949-59 PUNJAB 5378 27.6
SEPAHA ET AL 1952-62 INDORE 61.38 13.5
JOSHI ETAL 1957-62 GUJARAT 1216 35.6
BHARGAVA 1945-1964 RAJASTHAN 3722 33.39
AGARWAL 1966-73 ALLAHABAD 2843 40.6
K S MATHUR 1947-61 AGRA 3309 35.1

109. Manifestations of RFManifestations of RF
AUTHOR YEAR CARDITIS% ARTHRITIS
%
ARTHRALGI
A%
CHOREA% SC
NODULES%
ERYTHEMA
MARG%
ROY 1960 46 32 94 4 3 0
PADMAVATHI 1962 30.9 60.1 8.3 1.5 0
MAHAJAN 1972 77.1 33.9 45.7 77 18 0.3
SANYAL ET
AL
1974 33.3 66.6 20 1.9 1.9
ARORA 42 30 42 2.6 6 0.2
GROVER 1ST 1988-1991 37.5 75 8.3 4 2
RECCURENCE 41 50 8.3 4 2

110. PERCENTAGE INCIDENCE OF VALVULAR
INVOLVEMENT IN VARIOUS AUTOPSY REPORTS
AUTHOR
&YEAR
MITRAL AORTIC MITRAL&A
ORTIC
MITRAL,AORT
IC&TRICUSPI
D
MITRAL&TRICU
SPID
TOTAL
CASES
REDDY 1968 67.5 2.5 17.5 10 2.5 40
ROY AND
TANDON
1972
22.9 3 31.8 25.1 16.6 66
KINARE
1972
35.3 1.8 32.6 22.6 8 150
B N DATTA 37.3 1.5 27 22.6 11 252

111. Kinare et alKinare et al RHEUMATIC HEART PATHOLOGY
IN THE YOUNG: AUTOPSY SERIES
1. 144 autopsy cases below the age of 18 years were
included.
2. Mitral stenosis was present in 80.23% cases. Pure mitral
valve incompetence was noted in 12.79%.
3. Tricuspid lesions were minor in most of the cases, only in
7.50% had significant stenosis.
4. Multivalvular disease was noted in 75.69%,
5. Pulmonary vasculature was affected in 75% cases.
6. Calcification of valve was uncommon and was present in
6% of mitral valve lesions and 2% of aortic valve lesions
Mitral Aortic Tricuspid Pulmonary
vasculature
100% 63.89% 54.86% 75%

112. IMPORTANT FEATURES OF
B N DATTA AUTOPSY SERIES
Mural thrombi: 13%
Active pericarditis: 30%
Aschoff bodies: 26%
Bacterial endocarditis: 9%
Organic TV disease: 34.2%
When compared to the west:
young age of death and high rate
of TV disease.

115. PADMAVATHIPADMAVATHI

117. Study Patients ARF RECURRENCE
RATE/ PATIENT YEAR
PREVALANCE OF RHD %
UK-US 324 0.026 31.2
Wood 156 0.004 NA
Miller 47 0 NA
Tompkins 115 0.001 26.1
Thomas 73 0.013 42.5
SANYAL 65 0.006 35.4

120. Sujoy roySujoy roy
 Clinical and physiopathological findings in 108 patients
with mitral stenosis who were below the age of 20 years.
 History of at least one attack of rheumatic fever was
obtained in 71 (66%), and of more than one attack in
30(28%) patients.
 Chorea and subcutaneous nodules appeared infrequently
(3%), and erythema marginatum was conspicuously
absent.
 High prevalence of congestive heart-failure (45%)
 Low prevalence of atrial fibrillation (6%)
 The estimated mitral-valve area was less than 1 sq. Cm. In
most of the patients
 Isolated mitral stenosis in patients below the age of 20
with rheumatic heart-disease is common in india.
 Boys are affected oftener than girls

121. Sujoy roySujoy roy
 The frequency of atrial fibrillation was found to
increase with each decade, reaching 40% in patients
over the age of 40.
 Angina(12%) is due to functional impairment of the
coronary flow caused by limitation of the cardiac
output.
 Absence of calcification in the mitral valve and of
thrombi could be due to the youth of the patients.
 Severe pulmonary hypertension with gross pulmonary
vascular obstruction, fairly normal cardiac output

122. MS IN YOUNG( INDIAN( INDIAN
SCENARIO)SCENARIO)
 In developing countries, mitral stenosis is severe
enough to require commissurotomy before the age of
20 or even 15 years.
 In1408 patients with rheumatic heart disease seen at the G B Pant
Hospital, New Delhi, between 1967 and-1973
 713 (51 %) had mitral stenosis
 140 patients below age 20
<10 10-15 15-20
4 (2.8%) 55 (39.4%) 81 (57.8%)

126.  ECHOCARDIOGRAPHY 2010
 High prevalence of rheumatic heart
disease detected by echo in school
children. PANWAR et al
 1059 school children aged 6-15 years
 Careful cardiac auscultation and echo.
 The prevalence of lesions suggestive of
rheumatic heart disease by echo was
51 per 1,000

128. AIIMSAIIMS
2008-20102008-2010
BALLABHGARH
CLINICAL RHD 0.8/1000
SUBCLINICAL RHD 20/1000
Heart
2011;97:201

129. 2012

130. MANAGEMENT ASPECTS
PRIMARY PREVENTION OFPRIMARY PREVENTION OF
ARFARF
Treatment of GAS pharyngitis with a single
intramuscular injection of 1.2 million units of
benzathine penicillin G is the most reliable way
to prevent primary attacks of ARF

134. Secondary prophylaxisSecondary prophylaxis
 Defined as the continuous
administration of specific
antibiotics to patients
with a previous attack of
rheumatic fever, or
documented RHD
 Purpose is to prevent
colonization or infection of
the upper respiratory
tract with group A beta-
hemolytic streptococci
and the development of
recurrent attacks of
rheumatic fever
 After surgery or
intervention secondary
prophylaxis should be
continued
 IMPORTANCE of
secondary prophylaxis
1. Prevents reccurences
2. Reduces new cardiac
damage,
3. Facilitate resolution of
previous damage
4. Reduces mortality due to
RHD.
5. The risk of reccurence is
highest in first year after
an index attack of RF

135. WHO GUIDELINES 2004

136. WHO GUIDELINES 2004

137. Because of the high infection rate
in India, it has been suggested that
penicillin should be given once
every 3 rather than 4 weeks to
maintain adequate blood levels
during reinfection, and this has
certainly resulted in a fall in the
infection rate.
Secondary prophylaxisSecondary prophylaxis

138. RECURRENCE ON PROPHYLAXISRECURRENCE ON PROPHYLAXIS
Sanyal 0.6/100 pt years
Padmavathi 0.1/100 pt years
With out prophylaxis recurrence
rate around 11.6/100 pt years

139. EFFECT OF SECONDARY PROPHYLAXIS ONEFFECT OF SECONDARY PROPHYLAXIS ON
RECCURENCE RATESRECCURENCE RATES
CATEGORY BENZATHINE
PENICILLIN
ORAL PENICILLIN SULFONAMIDES
STREPTOCOCCAL
INFECTION
6.3 6.2 16
ARF RECCURENCE 0.45 2.6 3.2

140. VACCINE ??VACCINE ??
ORPHAN STATUS
FOCUS ON STRAINS IN DEVELOPED WORLD
PAUCITY OF CLINICAL TRIALS
COST

144. RHDAustralia (ARF/RHD writing group), National Heart Foundation of Australia and theRHDAustralia (ARF/RHD writing group), National Heart Foundation of Australia and the
Cardiac Society of Australia and New Zealand: Australian Guideline for Prevention, DiagnosisCardiac Society of Australia and New Zealand: Australian Guideline for Prevention, Diagnosis
and Management of Acute Rheumatic Fever and Rheumatic Heart Disease. 2nd ed. Darwin,and Management of Acute Rheumatic Fever and Rheumatic Heart Disease. 2nd ed. Darwin,
Australia, Menzies School of Health Research, 2012Australia, Menzies School of Health Research, 2012
 Recommended for All Cases
White blood cell count
ESR or CRP
Throat swab before giving antibiotics for GAS culture
Blood culture if febrile
Antistreptococcal serology: both antistreptolysin O and anti-DNase B titers (repeated after 10-14 days if the first test is not
confirmatory)
Electrocardiogram
Chest radiograph
Echocardiogram
 Tests for Alternative Diagnoses, Depending on Clinical Features
Repeated blood cultures with temperature spikes if infective endocarditis is suspected
Joint aspiration for possible septic arthritis (microscopy and culture)
Copper, ceruloplasmin, antinuclear antibody, and drug screen for choreiform movements
Serology and autoimmune markers for arboviral, autoimmune, or reactive arthritis
Peripheral blood smear for sickle cell disease

145. Primary prophylaxisPrimary prophylaxis
Antiobiotic Route doses
Benzathine benzylpenicillin
Single IM injection 1.2 million units; 50% if <30 kg
Phenoxymethylpenicillin
(penicillin VK)
PO for 10 days 250-500 mg tid for 10 days
Erythromycin ethylsuccinate
PO for 10 days Varies with the formulation

146. WHO Technical Report Series No. 923. Rheumatic Fever and RheumaticWHO Technical Report Series No. 923. Rheumatic Fever and Rheumatic
Heart Disease: Report of a WHO Expert Panel, Geneva 29 October-1Heart Disease: Report of a WHO Expert Panel, Geneva 29 October-1
November 2001. Geneva, WHO, 2004.November 2001. Geneva, WHO, 2004.
Medication Route Doses
Benzathine
benzylpenicillin
Single intramuscular
injection every 3-4
weeks
For adults and
children ≥30 kg in
weight: 1,200,000
units
For children <30 kg in
weight: 600,000 units
Penicillin V Oral 250 mg twice daily
Sulfonamide (e.g.,
sulfadiazine,
sulfadoxine,
sulfisoxazole)
Oral For adults and
children ≥30 kg in
weight: 1 g daily

147. WHO Technical Report Series No. 923. Rheumatic Fever and RheumaticWHO Technical Report Series No. 923. Rheumatic Fever and Rheumatic
Heart Disease: Report of a WHO Expert Panel, Geneva 29 October-1Heart Disease: Report of a WHO Expert Panel, Geneva 29 October-1
November 2001. Geneva, WHO, 2004.November 2001. Geneva, WHO, 2004.
No carditis: 5 years after the last attack
or until 18 years of age (whichever is
longer)
Mild carditis (mild mitral regurgitation or
healed carditis):10 years after the last
attack or at least until 25 years of age
(whichever is longer)
Severe valvular disease: Life-long
After valve surgery: Life-long

148. IN INDIA
 Endemicity of carditis
 Erythema marginatum almost nonexistent
 Chorea and subcutaneous nodules infrequent
 Polyarthralgia >polyarthritis
 Young >Older
 Short interval - ARF to RHD
 Start at Young
 Rapid progression
 More PAH/CCF
 Rheumatic fever in < 50%
 High incidence of organic tricuspid valve disease

149. FUTURE PERSPECTIVESFUTURE PERSPECTIVES
Overcoming barrier to transmission
◦ Socioeconomic/Political/awareness
Special task force in highly endemicity
Identification of genetic susceptibility(3-5%)
Primary and 2ndary prophylaxis reinforcement
Very long acting penicillin(>3 months)
Vaccine
Understanding molecular genetic

150. Rx for RFRx for RF
PRIMODIAL PRIMARY SECONDARY TERTIARY
AWARENESS
SOCIOECONO
MIC
POLITICAL
Vaccine
Rx pharyngitis Penicillin Surgery/PBMV

151. Socioecomical progress does not mean the extinct of natureSocioecomical progress does not mean the extinct of nature