Acute Rheumatic Fever

ELA-BELA
 Acute rheumatic fever (ARF) is a multisystem disease resulting from an
autoimmune reaction to infection with group A streptococcus.

 Although many parts of the body may be affected, almost all of the
manifestations resolve completely.

 The exception is Cardiac Valvular Damage [Rheumatic Heart Disease (RHD)],

which may persist after the other features have disappeared.
Rheumatic fever (RF) is an autoimmune disorder that remains
incompletely characterized with regard to its basic elements—
cause, pathophysiology, diagnosis, and treatment—despite
evidence of its existence dating to at least the 1600s.

The classic understanding that the disease is a post–suppurative

streptococcal pharyngitis cascade, leading variably to arthritis,
chorea, dermal manifestations, and, most important, carditis, has
largely withstood challenge.
Immunologic studies have confirmed the presence of epitopes on
the bacterial surface that mimic cardiac myosin as well as antigens
found in valve, skin, joint, and brain tissue that account for the
immunologic cross-reactive attack characteristic of RF.

No single diagnostic tool or laboratory test exists for RF.

Hence, the diagnosis depends on a composite of clinical criteria.

The sequelae of only one manifestation, carditis, account for most
of the morbidity and essentially all of the mortality associated with
RF.

As a cause of heart disease in adults, RF has declined dramatically

in industrialized nations but remains a major source of morbidity
and mortality in developing countries and in some selected
aboriginal populations in wealthy nations.
The primary consequences of RF, rheumatic mitral and aortic
valve disease in adults, are also declining worldwide but remain a
major burden on the limited health care resources of the countries
where the disease is most prevalent.

The diagnostic and treatment algorithms for RF are still largely

based on descriptive series and expert opinion panels.

Because failure to diagnose RF and to institute secondary

prophylaxis results in RHD, increasing attention is being focused
on improving sensitivity of diagnosis in areas where the disease is
endemic.
Global Considerations
 ARF and RHD are diseases of poverty.

 They were common in all countries until the early twentieth century, when their
incidence began to decline in industrialized nations.

 This decline was largely attributable to improved living conditions—particularly

less crowded housing and better hygiene—which resulted in reduced transmission
of group A streptococci.

 The introduction of antibiotics and improved systems of medical care had a

supplemental effect.

 Recurrent outbreaks of ARF began in the 1980s in the Rocky Mountain states of
the United States, where elevated rates persist.
 The virtual disappearance of ARF and reduction in the incidence of RHD in
industrialized countries during the twentieth century unfortunately was not
replicated in developing countries, where these diseases continue unabated.

 RHD is the most common cause of heart disease in children in developing

countries and is a major cause of mortality and morbidity in adults as well.

 It has been estimated that between 15 and 19 million people worldwide are
affected by RHD, with approximately one-quarter of a million deaths occurring
each year.

 Some 95% of ARF cases and RHD deaths now occur in developing countries.
 Although ARF and RHD are relatively common in all developing countries, they
occur at particularly elevated rates in certain regions.

 These "hot spots" are sub-Saharan Africa, Pacific nations, Australasia, and the
Indian subcontinent (Fig. 322-1).

 Unfortunately, most developing countries do not currently have coordinated,

register-based RHD control programs, which are proven to be cost-effective in
reducing the burden of RHD.

 Enhancing awareness of RHD and mobilizing resources for its control in

developing countries is an issue requiring international attention.
Prevalence of rheumatic heart disease in children aged 5–14 years. Circles within Australia and
New Zealand represent indigenous populations, and also Pacific Islanders in New Zealand.
Epidemiology
 ARF is mainly a disease of children aged. 5–14 years

 Initial episodes become less common in older adolescents and young adults and
are rare in persons aged >30 years.

 By contrast, recurrent episodes of ARF remain relatively common in

adolescents and young adults.

 This pattern contrasts with the prevalence of RHD, which peaks b/n 25-40
years.

 There is no clear gender association for ARF, but RHD more commonly affects
females, sometimes up to twice as frequently as males.
Streptococcus pyogenes is responsible for diseases ranging from
pharyngitis to AGN, necrotizing fasciitis, and toxic shock
syndrome.

Suppurative pharyngitis is the only clearly established prequel to

RF.

Given a causal association between group A beta-hemolytic

streptococci (GABHS) and RF, their epidemiology is also linked.

Whereas most pharyngitis (80%) is viral in etiology, GABHS is

isolated in up to 75% of cases from children with symptoms of
severe bacterial pharyngitis.
Antistreptolysin O titers more than 200 Todd units are found in up
to 50% of asymptomatic children 6 to 15 years old, the prime age
group for RF.

This reflects the frequent occurrence of pharyngitis in this age

group (estimated to be once yearly), approximately 15% to 20% of
which is caused by GABHS.

Recurrence is most common in adolescents and young adults and

is uncommon beyond the age of 34 years.
Data from the early antibiotic era suggest that 0.3% to 3% of those
with untreated GABHS pharyngitis develop RF.

Although there is no clear gender predisposition, postpubertal

chorea and the development of mitral stenosis are more common
in females.

GABHS is present in 10 - 30% of asymptomatic individuals in the

prime RF age groups in the US, but it is higher in many countries.
A history of pharyngitis has been reported in approximately two
thirds of RF cases.

Carriers (patients with positive throat cultures without clinical

history or rise in antibody titers) do not appear predisposed to RF.

The possibility that RF may follow nonpharyngeal streptococcal

infection, in particular pyoderma, continues to be explored.
Pathogenesis
Organism Factors
 Based on currently available evidence, ARF is exclusively caused
by infection of the upper respiratory tract with group A
streptococci.

 Although classically, certain M-serotypes (particularly types 1, 3, 5, 6, 14,

18, 19, 24, 27, and 29) were associated with ARF, in high-incidence
regions, it is now thought that any strain of group A streptococcus has the
potential to cause ARF.

 Potential role of skin infection and of groups C and G streptococci

are currently being investigated.
Host Factors
 Approximately 3–6% of any population may be susceptible to ARF, and this
proportion does not vary dramatically between populations.

 Findings of familial clustering of cases and concordance in monozygotic

twins—particularly for chorea—confirm that susceptibility to ARF is an
inherited characteristic.

 Particular human leukocyte antigen (HLA) class II alleles appear to be

strongly associated with susceptibility.
 Associations have also been described with high levels of circulating mannose-
binding lectin and polymorphisms of tumor necrosis factor-α1 gene and Ig
genes.

 High-level expression of a particular alloantigen present on B cells, D8-17, has

been found in patients with a history of ARF in many populations, with
intermediate-level expression in first-degree family members, suggesting that
this may be a marker of inherited susceptibility.
The Immune Response
 When a susceptible host encounters a group A streptococcus, an
autoimmune reaction results, which leads to damage to human
tissues as a result of cross-reactivity between epitopes on the
organism and the host (Fig. 322-2).

 Cross-reactive epitopes are present in the streptococcal M protein

and the N-acetylglucosamine of group A streptococcal
carbohydrate and are immunologically similar to molecules in
human myosin, tropomyosin, keratin, actin, laminin, vimentin, and
N-acetylglucosamine.
It is currently thought that the initial damage is due to cross-
reactive antibodies attaching at the cardiac valve endothelium,
allowing the entry of primed CD4+ T cells, leading to subsequent
T cell-mediated inflammation.
Pathogenetic pathway for acute rheumatic fever and rheumatic heart disease.
Pathology
 In patients dying of rheumatic carditis, autopsy examination has
demonstrated verrucous vegetations on the valve leaflets, along
with extensive inflammation and edema.

 In the exudative phase, during the first few weeks after the onset
of RF, fibrinoid degeneration of collagen is noted.
Inflammation is seen in left ventricular (LV) endocardium, with
lymphocytic, macrophage, and, in a minority of cases, plasma cell,
polymorphonuclear leukocyte, eosinophil, and mast cell
infiltration.

In the proliferative phase, 1 to 6 months after the onset of RF,

Aschoff Bodies, granulomatous lesions pathognomonic for
rheumatic carditis, are seen and can be found in valve tissue as
well as in endocardium, myocardium, and pericardium.
Although Aschoff bodies can be demonstrated as early as the
second week of onset of RF, they may be present chronically
without evidence of carditis.

Rheumatic arthritis is manifested by edema, lymphocytic and

polymorphonuclear infiltration, and fibrinoid lesions that resolve.

In patients with chorea, inflammatory changes have been noted in

the cerebral cortex, cerebellum, and basal ganglia.
Clinical Features
 There is a latent period of 3 weeks (1–5 weeks) between the precipitating group
A streptococcal infection and the appearance of the clinical features of ARF.

 The exceptions are chorea and indolent carditis, which may follow prolonged
latent periods lasting up to 6 months.

 Although many patients report a prior sore throat, the preceding group A
streptococcal infection is commonly subclinical;

 In these cases it can only be confirmed using streptococcal antibody testing.

 The most common clinical presentation of ARF is polyarthritis and fever.

 Polyarthritis is present in 60–75% of cases and carditis in 50–60%.

 The prevalence of chorea in ARF varies substantially between populations,

ranging from <2% to 30%.

 Erythema marginatum and Subcutaneous Nodules are now rare, being found
in <5% of cases.
Heart Involvement (Carditis)
 Up to 60% of patients with ARF progress to RHD.

 The endocardium, pericardium, or myocardium may be affected.

 Valvular damage is the hallmark of rheumatic carditis.

 The mitral valve is almost always affected, sometimes together with the aortic valve;
isolated aortic valve involvement is rare.

 Early valvular damage leads to regurgitation.

 Over ensuing years, usually as a result of recurrent episodes, leaflet thickening,
scarring, calcification, and valvular stenosis may develop (Fig. 322-3).

 Therefore the characteristic manifestation of carditis in previously unaffected

individuals is mitral regurgitation, sometimes accompanied by aortic
regurgitation.

 Myocardial inflammation may affect electrical conduction pathways, leading

to P-R interval prolongation (first-degree AV block or rarely higher-level
block) and softening of the first heart sound.
 Transthoracic echocardiographic
image from a 5-year old boy with
chronic rheumatic heart disease.

This diastolic image demonstrates leaflet thickening, restriction of the anterior mitral valve leaflet
tip, and doming of the body of the leaflet toward the interventricular septum. This appearance
(marked by the arrowhead) is commonly described as a "hockey stick" or an "elbow" deformity.
 Transthoracic echocardiographic images of a 9-year-old girl with first episode
of acute rheumatic fever.

 Images demonstrate the typical echocardiographic findings of acute rheumatic

carditis. The valve leaflets are relatively thin and highly mobile. The failure of
coaptation of the mitral valve leaflets is the result of chordal elongation and
annular dilatation. The mitral valve regurgitation is moderate with a typical
postero-laterally directed regurgitant jet of rheumatic carditis. A. Acute
rheumatic carditis (apical 4-chamber view echocardiogram).
 Transthoracic echocardiographic images are from a 5-year-old boy with
chronic rheumatic heart disease with severe mitral valve regurgitation and
moderate mitral valve stenosis.

 Images demonstrate the typical echocardiographic findings in advanced

chronic rheumatic heart disease. Both the anterior and posterior mitral valve
leaflets are markedly thickened. During diastole, the motion of the anterior
mitral valve leaflet tip is restricted with doming of the body of the leaflet
towards the interventricular septum. This appearance is commonly described as
a "hockey stick" or an "elbow" deformity. A. Chronic rheumatic heart disease
(parasternal long-axis view).
Joint Involvement (Arthritis)
 To qualify as a major manifestation, joint involvement in ARF
must be arthritic, i.e., objective evidence of inflammation, with
hot, swollen, red and/or tender joints, and involvement of more
than one joint (i.e., polyarthritis).
 The typical arthritis is migratory, moving from one joint to
another over a period of hours.

 ARF almost always affects the large joints—most commonly the

knees, ankles, hips, and elbows—and is asymmetric.

 The pain is severe and usually disabling until anti-inflammatory

medication is commenced.
 Less severe joint involvement is also relatively common but qualifies only as a
minor manifestation.

 Arthralgia without objective joint inflammation usually affects large joints in

the same migratory pattern as polyarthritis.

 In some populations, aseptic monoarthritis may be a presenting feature of ARF.

 This may occur because of early commencement of anti-inflammatory

medication before the typical migratory pattern is established.
 The joint manifestations of ARF are highly responsive to salicylates and other
nonsteroidal anti-inflammatory drugs (NSAIDs).

 Indeed, joint involvement that persists >1 or 2 days after starting salicylates is
unlikely to be due to ARF.

 Conversely, if salicylates are commenced early in the illness, before fever and
migratory polyarthritis have become manifest, it may be difficult to make a
diagnosis of ARF.

 For this reason, salicylates and other NSAIDs should be withheld—and pain
managed with acetaminophen or codeine—until the diagnosis is confirmed.
Chorea
 Sydenham's chorea commonly occurs in the absence of other manifestations,
follows a prolonged latent period after group A streptococcal infection, and
is found mainly in females.

 The choreiform movements affect particularly the head (causing

characteristic darting movements of the tongue) and the upper limbs.

 They may be generalized or restricted to one side of the body (hemi-chorea).

 The chorea varies in severity.

 In mild cases it may be evident only on careful examination, while in the most
severe cases the affected individuals are unable to perform activities of daily
living and are at risk of injuring themselves.

 Chorea eventually resolves completely, usually within 6 weeks.

Skin Manifestations
 The classic rash of ARF is Erythema Marginatum

 Which begins as pink macules that clear centrally, leaving a serpiginous, spreading
edge.

 The rash is evanescent, appearing and disappearing before the examiner's

eyes.

 It occurs usually on the trunk, sometimes on the limbs, but almost never on the
face.
 Subcutaneous Nodules occur as painless, small (0.5–2 cm), mobile lumps
beneath the skin overlying bony prominences, particularly of the hands, feet,
elbows, occiput, and occasionally the vertebrae.

 They are a delayed manifestation, appearing 2–3 weeks after the onset of
disease, last for just a few days up to 3 weeks, and are commonly associated
with carditis.
Other Features
 Fever occurs in most cases of ARF, although rarely in cases of pure chorea.

 Although high-grade fever (39°C) is the rule, lower grade temperature

elevations are not uncommon.

 Elevated acute-phase reactants are also present in most cases.

 C-reactive protein (CRP) and ESR are often dramatically elevated.

 Occasionally the peripheral leukocyte count is mildly elevated.

Evidence of a Preceding Group
A Streptococcal Infection
 With the exception of chorea and low-grade carditis, both of which may become
manifest many months later, evidence of a preceding group A streptococcal
infection is essential in making the diagnosis of ARF.

 As most cases do not have a positive throat swab culture or rapid antigen test,
serologic evidence is usually needed.

 The most common serologic tests are the anti-streptolysin O (ASO) and anti-
DNase B (ADB) titers.

 Where possible, age-specific reference ranges should be determined in a local

population of healthy people without a recent group A streptococcal infection.
 Other Post-Streptococcal
Syndromes that May Be Confused
with RF
 Post-streptococcal reactive arthritis (PSRA) is differentiated from ARF on the
basis of:

(1) Small-joint involvement that is often symmetric;

(2) A short latent period following streptococcal infection (usually <1 week);

(3) Occasional causation by nongroup A -hemolytic streptococcal infection;

(4) Slower responsiveness to salicylates; and

(5) The absence of other features of ARF, particularly carditis.

 Pediatric autoimmune neuropsychiatric disorders associated with streptococcal
infection (PANDAS) is a term that links a range of tic disorders and obsessive-
compulsive symptoms with group A streptococcal infections.

 People with PANDAS are said not to be at risk of carditis, unlike patients with
Sydenham's chorea.

 The diagnoses of PANDAS and PSRA should rarely be made in populations with
a high incidence of ARF.
Confirming the Diagnosis
 Because there is no definitive test, the diagnosis of ARF relies on the presence
of a combination of typical clinical features together with evidence of the
precipitating group A streptococcal infection, and the exclusion of other
diagnoses.

 This uncertainty led Dr. T. Duckett Jones in 1944 to develop a set of criteria
(subsequently known as the Jones criteria) to aid in the diagnosis.

 An expert panel convened by the World Health Organization (WHO) clarified

the use of the Jones criteria in ARF recurrences (Table 322-1).
 Because each revision of the Jones criteria since 1944 has reduced sensitivity
and increased specificity, in response to the decline in incidence of ARF in high-
income countries, there is now concern that they may be too insensitive for
countries where ARF incidence remains high.

 As a result, some countries (e.g., Australia and New Zealand) have developed
their own, more sensitive, diagnostic criteria for ARF in their populations (links
available at the RHDnet websitewww.worldheart.org/rhd).
a
Patients may present with polyarthritis (or with only polyarthralgia or monoarthritis) and with
several (three or more) other minor manifestations, together with evidence of recent group A
streptococcal infection.

Some of these cases may later turn out to be rheumatic fever.

It is prudent to consider them as cases of "probable rheumatic fever" (once other diagnoses are
excluded) and advise regular secondary prophylaxis.

Such patients require close follow-up and regular examination of the heart.

This cautious approach is particularly suitable for patients in vulnerable age groups in high incidence
b
Infective endocarditis should be excluded.

c
Some patients with recurrent attacks may not fulfill these criteria.

d
Congenital heart disease should be excluded.

e
1992 Revised Jones criteria do not include elevated leukocyte count as a laboratory minor
manifestation (but do include elevated C-reactive protein), and do not include recent scarlet fever as
supporting evidence of a recent streptococcal infection.
Algorithm for diagnosis of acute
rheumatic fever, incorporating the
1992 revision of the Jones criteria
and the World Health
Organization (WHO) expert
consultation report (2002-2003).
The WHO modifications
incorporated in the flow chart are
more sensitive and less specific
than those incorporated in the
American Heart Association
criteria. GABHS = group A beta-
hemolytic streptococci; RF =
rheumatic fever; RHD =
rheumatic heart disease.
Treatment
Algorithm for management
of rheumatic fever and its
primary manifestations.
*Salicylates are also
indicated for fever and
arthralgia, but there is no
evidence of effectiveness
for carditis or chorea.
PSRA = poststreptococcal
reactive arthritis; RF =
rheumatic fever.
 Patients with possible ARF should be followed closely to ensure that the
diagnosis is confirmed, treatment of heart failure and other symptoms is
undertaken, and preventive measures including commencement of secondary
prophylaxis, inclusion on an ARF registry, and health education are
commenced.

 Echocardiography should be performed on all possible cases to aid in making

the diagnosis and to determine the severity at baseline of any carditis.

 Other tests that should be performed are listed in Table 322-2.

 There is no treatment for ARF that has been proven to alter the likelihood of
developing, or the severity of, RHD.

 With the exception of treatment of heart failure, which may be life-saving in

cases of severe carditis, the treatment of ARF is symptomatic.
Antibiotics
 All patients with ARF should receive antibiotics sufficient to treat
the precipitating group A streptococcal infection (Chap. 136).

 Penicillin is the drug of choice and can be given orally [as

phenoxymethyl penicillin, 500 mg (250 mg for children < 27 kg)
PO twice daily, or amoxicillin 50 mg/kg (max 1 g) daily, for 10
days] or as a single dose of 1.2 million units (600,000 units for
children < 27 kg) IM benzathine penicillin G.
Salicylates and NSAIDs
 These may be used for the treatment of arthritis, arthralgia, and
fever, once the diagnosis is confirmed.

 They are of no proven value in the treatment of carditis or chorea.

 Aspirin is the drug of choice.

 An initial dose of 80–100 mg/kg per day in children (4–8 g/d in adults) in 4–5
divided doses is often needed for the first few days up to 2 weeks.

 A lower dose should be used if symptoms of salicylate toxicity emerge, such as

nausea, vomiting, or tinnitus.
 When the acute symptoms are substantially resolved, the dose can be reduced to
60–70 mg/kg per day for a further 2–4 weeks.

 Fever, joint manifestations, and elevated acute-phase reactants sometimes recur

up to 3 weeks after the medication is discontinued.

 This does not indicate a recurrence and can be managed by recommencing

salicylates for a brief period.

 Although less well studied, naproxen at a dose of 10–20 mg/kg per day has been
reported to lead to good symptomatic response.
Glucocorticoids
 The use of glucocorticoids in ARF remains controversial.

 Two meta-analyses have failed to demonstrate a benefit of

glucocorticoids compared to placebo or salicylates in improving
the short- or longer term outcome of carditis.
 However, the studies included in these meta-analyses all took place >40 years
ago and did not use medications in common usage today.

 Many clinicians treat cases of severe carditis (causing heart failure) with
glucocorticoids in the belief that they may reduce the acute inflammation and
result in more rapid resolution of failure.
 However, the potential benefits of this treatment should be balanced against the
possible adverse effects, including gastrointestinal bleeding and fluid retention.

 If used, prednisone or prednisolone are recommended at doses of 1–2 mg/kg per

day (maximum, 80 mg).

 Glucocorticoids are often only required for a few days or up to a maximum of 3

weeks.
Management of Heart Failure

See Chap. 234.

Bed Rest
 Traditional recommendations for long-term bed rest, once the
cornerstone of management, are no longer widely practiced.

 Instead, bed rest should be prescribed as needed while arthritis

and arthralgia are present, and for patients with heart failure.

 Once symptoms are well controlled, gradual mobilization can

commence as tolerated.
Chorea
 Medications to control the abnormal movements do not alter the
duration or outcome of chorea.

 Milder cases can usually be managed by providing a calm

environment.

 In patients with severe chorea, carbamazepine or sodium

valproate are preferred to haloperidol.
 A response may not be seen for 1–2 weeks, and a successful response may only
be to reduce rather than resolve the abnormal movements.

 Medication should be continued for 1–2 weeks after symptoms subside.

Intravenous Immunoglobulin (Ivig)

 Small studies have suggested that IVIg may lead to more rapid
resolution of chorea but has shown no benefit on the short- or
long-term outcome of carditis in ARF without chorea.

 In the absence of better data, IVIg is not recommended except in

cases of severe chorea refractory to other treatments.
Prognosis
 Untreated, ARF lasts on average 12 weeks.

 With treatment, patients are usually discharged from hospital

within 1–2 weeks.

 Inflammatory markers should be monitored every 1–2 weeks until

they have normalized (usually within 4–6 weeks), and an
echocardiogram should be performed after 1 month to determine
if there has been progression of carditis.
 Cases with more severe carditis need close clinical and echocardiographic
monitoring in the longer term.

 Once the acute episode has resolved, the priority in management is to ensure
long-term clinical follow-up and adherence to a regimen of secondary
prophylaxis.

 Patients should be entered onto the local ARF registry (if present) and contact
made with primary care practitioners to ensure a plan for follow-up and
administration of secondary prophylaxis before the patient is discharged.
 Patients and their families should also be educated about their disease,
emphasizing the importance of adherence to secondary prophylaxis.

 If carditis is present, they should also be informed of the need for antibiotic
prophylaxis against endocarditis for dental and surgical procedures.
Prevention
Primary Prevention
 Ideally, primary prevention would entail elimination of the major
risk factors for streptococcal infection, particularly overcrowded
housing.

 This is difficult to achieve in most places where ARF is common.

 Therefore, the mainstay of primary prevention for ARF remains

primary prophylaxis (i.e., the timely and complete treatment of
group A streptococcal sore throat with antibiotics).
 If commenced within 9 days of sore throat onset, a course of penicillin (as
outlined above for treatment of ARF) will prevent almost all cases of ARF that
would otherwise have developed.

 This important strategy relies on individuals presenting for medical care when
they have a sore throat, the availability of trained health and microbiology staff
along with the materials and infrastructure to take throat swabs, and a reliable
supply of penicillin.

 Unfortunately, many of these elements are not available in developing

countries.
Secondary Prevention
 The mainstay of controlling ARF and RHD is secondary
prevention.

 Because patients with ARF are at dramatically higher risk than

the general population of developing a further episode of ARF
after a group A streptococcal infection, they should receive long-
term penicillin prophylaxis to prevent recurrences.

 The best antibiotic for secondary prophylaxis is benzathine

penicillin G (1.2 million units, or 600,000 units if <27 kg)
 It can be given every 3 weeks, or even every 2 weeks, to persons considered to
be at particularly high risk, although in settings where good compliance with 4-
weekly dosing can be achieved, more frequent dosing is rarely needed.

 Oral penicillin V (250 mg) can be given twice-daily instead but is somewhat
less effective than benzathine penicillin G.

 Penicillin allergic patients can receive erythromycin (250 mg) twice daily.
 The duration of secondary prophylaxis is determined by many factors, in
particular

1. The duration since the last episode of ARF (recurrences become less likely with
increasing time),

2. Age (recurrences are less likely with increasing age), and

3. The severity of RHD (if severe, it may be prudent to avoid even a very small
risk of recurrence because of the potentially serious consequences)

(Table 322-3).
 Secondary prophylaxis is best delivered as part of a coordinated RHD control
program, based around a registry of patients.

 Registries improve the ability to follow patients and identify those who default
from prophylaxis and institute strategies to improve adherence.
*
These are only recommendations and must be modified by individual circumstances as warranted.

Note that other organizations have slightly different recommendations (see www.worldheart.org/rhd for
links).
TH
E
EN
D