Acute Rheumatic fever and Rheumatic Heart disease: overview of pathophysiology, clinical manifestations, diagnosis and management

1. Acute Rheumatic Fever and
Rheumatic Heart Disease
Jinja Regional Referral Children hospital / Nalufenya
Continue Medical Education (CME)
Prepared by
Dr Gabriel K. Shamavu, Paediatrics Resident at KIU
Dr Nambaziira Hajarah, Intern at JRRH
Dr Naigaga Josephine, Intern at JRRH
Robinah, Medical Student (BMS) at KIU

2. Case presentation
• Demographics
Name: NB
Age: 8 years
Sex: Female
Level of Education: Primary 2
Religion: Anglican
Tribe: Samya
Address: Bugiri district
Next of kin: MD, the father

3. Case presentation
Referral from First line Medical center for ASOT titers, ECG, ECHO
and pediatric cardiologist review.
Presenting complain
Palpitations for 1 month.

4. Case presentation
• History of the presenting complaint
NB is an 8 year old female, Ugandan by nationality, coming from a household with 8 family members and with
a history of recurrent Upper Respiratory Tract Infections mainly experienced as sore throats, with the most
previous one being 2 months ago, came in as a referral from First Line Medical Center for ASOT titers, ECG ,
ECHO and Pediatric cardiologist review. From the referring center, she was managed for Acute Rheumatic
Fever and Severe malaria with hyperparasitemia on IV Ampiclox and IV Artesunate having presented with a 5
days history of migratory joint pains, high grade fevers and had (+++) on Blood Smear for malaria.
While here, she in addition to the above reported a 1 month history of palpitations associated with easy
fatigability but no history of difficulty in breathing, blue episodes, orthopnea or PND.
Had not yet started oral antimalarial treatment.

5. Case presentation
Review of systems
RESPIRATORY and ENT:
• No history of cough, hemoptysis, chest pain or difficulty in breathing
• Reported no history of ear pains or discharge
GUS
• Reported normal micturition habits
GIT
• Had a reduced appetite, no dysphagia, no vomiting, no history of abdominal pains or
abdominal distension, no diarrhea or constipation
CNS
• No history of headache, convulsions or loss of consciousness, no visual or hearing
problems
Skin
• No history of skin rash

6. Case presentation
• Past medical history
This is the second admission to a health care facility, having been previously admitted and managed for severe malaria. Reported no
known Chronic illnesses. No history of food or drug allergies.
• Past Surgical history
Has previously received blood transfusion due to severe malaria anemia, no history of any major surgeries done or involvement in
major trauma
• Developmental history
She is reported to have attained all developmental milestones on time
• Vaccination history
Reported to have been fully vaccinated for age.

7. Case presentation
On examination
• Vital signs
PR: 120beats/min, RR: 30cycles/min, Axillary temperature: 37.3degrees Celsius, SPO2; 96-98% on room air
• General exam: She was a child of school going age, in a fair general condition, not in obvious respiratory
distress, afebrile on touch.
Had no pallor, no jaundice, no dehydration and no edema
• CVS: Had warm peripheries, cap refill time was 2 seconds, tachycardic with a pulse rate 120 beats/min,
regular, full volume, no radio-radial delay or radial femoral delays. No distended neck veins. She had a
hyperactive precordium, apex beat 6th intercostal space MCL-AAL, heave in the mitral and tricuspid areas,
Heart Sounds 1 and 2 heard with a pan systolic murmur, grade 4, blowing in character best heard in the mitral
area and radiating to the axilla. Lung bases were clear

8. Case presentation
On examination
• Respiratory
Was not in obvious respiratory distress, equal air entry bilaterally, breath sounds were vesicular in all lung fields.
No added sounds
• Per abdomen
• It was of normal fullness, moving with respiration, soft, non tender with no palpable organomegalies. Bowel
sounds were present.
• CNS
Was awake and alert, GCS 15/15. Pupils equal and reactive to light. Had normal tone, power and reflexes in all
limbs.

9. Case presentation
Impression
8 year old female with,
• Rheumatic heart disease with Mitral regurgitation
• Congenital heart disease
• Heart failure with preserved ejection fraction (AHA class C. NYHA class II)
• Resolving Malaria
Differential diagnosis
• Infective endocarditis
• Juvenile idiopathic arthritis

10. Case presentation
Investigations done and results
• mRDT: Positive
• BS for malaria.. (+++) and repeat BS for malaria (+)
• Complete blood count. Hb: 10.3g/dl, WBC count: 15*10^3/ microliter
Neutrophils: 7*10^9/ microliter, platelets: 300*10^3/microliter
• Chest X-ray:
• Cardiomegaly
• Echocardiography
• Severe Aortic regurgitation, Severe Mitral regurgitation, moderate tricuspid
regurgitation and moderate pulmonary artery hypertension.

11. Case presentation
Treatment
• IV Lasix, 20mg once a day for 5 days
• IV Ceftriaxone 1g once a day for 1 week
• IM Benzathine Penicillin, 0.6 MU once every month
• Tabs D-Artep 1.5 tablets once a day for 3 days.
• Tabs Losartan 12.5mg once a day for 1 month
• Tabs Spironolactone 6.25mg 12 hourly for 1 month
• Tabs Ibuprofen 100mg 8hourly for 5 days.
Definitive management
• Double Valve replacement.

12. Acute Rheumatic Fever
Jinja Regional Referral Children hospital / Nalufenya
Continue Medical Education (CME)
Prepared by
Dr Gabriel K. Shamavu, Paediatrics Resident at KIU

13. Case presentation
• Management and follow up plan
Outline
• Introduction
• Pathophysiology
• Clinical manifestations and
Diagnosis
• Treatment and Follow up

14. Introduction
• The potential complications of group A (GAS) pharyngeal infection include both
suppurative (eg, peritonsillar abscess, otitis media, sinusitis) and inflammatory,
nonsuppurative conditions.
• Acute rheumatic fever (ARF) is one of the nonsuppurative complications (others
include scarlet fever and acute glomerulonephritis [AGN]).

15. Definition of ARF
• ARF is a nonsuppurative sequela that occurs two to four weeks following group A
beta hemolytic Streptococcus Streptococcus (GAS) pharyngitis
• Characterized by an exudative and proliferative inflammatory lesion of the
connective tissue, especially that of the heart, joints, blood vessels and
subcutaneous tissue
• May consist of arthritis, carditis, chorea, erythema marginatum, and
subcutaneous nodules.

16. Complications of GAS infection
Non-Suppurative Suppurative
• Acute rhematic fever (ARF)
• Post streptococcal reactive arthritis (PSRA)
• Scalet fever
• Streptococcal toxic shock syndrome
• Acute glomerulonephritis
• Pediatric autoimmune neuropsychiatric
disorders associated with Streptococcus
pyogenes (PANDAS)
• Tonsilopharyngeal cellulitis or abscess
• Otitis media
• Sinusitis
• Pneumonia
• Skin and soft tissue infections:
impetigo,pyoderma, cellulitis, vaginitis,
Necrotizing fasciitis, …
• Osteomyelitis

17. Epidemiology of ARF
• Rheumatic fever and rheumatic heart disease are diseases of poverty and economic
disadvantage.
• In developing areas of the world, severe disease caused by group A Streptococcus
(GAS; eg, ARF, rheumatic heart disease, glomerulonephritis, and invasive
infections) is estimated to affect over 33 million people and is the leading cause of
cardiovascular death during the first five decades of life.
• ARF can occur at any age, although most cases occur in children 5 to 15 years of
age.

18. Epidemiology of ARF
• Worldwide, based upon conservative estimates, there are approximately 470,000 new cases of ARF and
275,000 deaths attributable to rheumatic heart disease each year
• Most cases occur in low- and middle-income countries and among Indigenous groups. Regions with the
highest rates are likely to have the least accurate data with substantial underreporting.
• The mean incidence of ARF is 19 per 100,000 school-aged children worldwide, but it is lower (≤2 cases per
100,000 school-aged children) in the United States and other developed countries.
• In many low- and middle-income countries and in certain Indigenous populations, such as those in Australia
and New Zealand, the incidence of ARF is substantially higher, with some of the highest rates reported in
Indigenous Australians at 153 to 380 cases per 100,000 children aged 5 to 14 years

19. Pathogenesis of ARF
Cytotoxicity theory
• Suggests that a GAS toxin is involved in the pathogenesis of acute rheumatic fever and rheumatic
heart disease.
• GAS produces a number of enzymes that are cytotoxic for mammalian cardiac cells, such as
streptolysin O, which has a direct cytotoxic effect on mammalian cells in tissue culture. Most
proponents of the cytotoxicity theory have focused on this enzyme.
• However, a major problem with the cytotoxicity hypothesis is its inability to explain the substantial
latent perid (usually 10-21 days) between GAS pharyngitis and onset of acute RF

20. Pathogenesis of ARF
Immune-mediated pathogenesis
• The antigenicity of several GAS cellular and extracellular epitopes and their immunologic cross-
reactivity with cardiac antigenic epitopes also lends support to the hypothesis of molecular
mimicry. Common epitopes are shared between certain GAS components (e.g., M protein, cell
membrane, group A cell wall carbohydrate, capsular hyaluronate) and specific mammalian tissues
(e.g., heart valve, sarcolemma, brain, joint).
• For example, certain rheumatogenic M proteins (M1, M5, M6, and M19) share epitopes with
human myocardial proteins such as tropomyosin and myosin

21. The major clinical manifestations of ARF are
• Carditis and arthritis,
• followed in descending frequency by chorea, subcutaneous nodules, and
erhythema marginatum (uncommon but specific of ARF).
Clinical manifestations and diagnosis of ARF

22. There are two primary forms of presentation for ARF:
Acute febrile illness Neurologic/behavioral disorder
Most common form (approximately 70 to 75 %)
+ joint manifestations and often carditis.
The less common
with Sydenham chorea.
Joint manifestations are usually absent, and
carditis, when present, is often subclinical.
Clinical manifestations and diagnosis of ARF

23. Acute febrile illness (70 to 75%) Neurologic illness (25 to 30%)
•Onset two to four weeks after GAS infection
•Fever is common
•Acute joint symptoms and signs
•Carditis
• Clinical and subclinical
•Skin manifestations and subcutaneous nodules (both
are rare)
•Raised inflammatory markers
•Evidence of preceding GAS infection (elevated ASO
and anti-DNase B titers)
•Dramatic symptomatic response to aspirin and
NSAIDS
•Duration usually <6 weeks
•Followed by RHD in approximately 75%
•Later onset
• Two to six months after GAS infection
•No fever
•Joint manifestations are not a feature
•Behavioral disorder and distinctive chorea
•Carditis >30%
• Often subclinical
•Often normal inflammatory markers
•ASO often unhelpful, anti-DNase B may be raised
•Followed by RHD in approximately 50%
Febrile illness versus Neurologic illness in ARF
Clinical manifestations and diagnosis of ARF

24. Arthritis
• Migratory Polyarthritis
• in approximately 75% of patients with acute rheumatic fever and typically involves larger joints, particularly
the knees, ankles, wrists, and elbows.
• Involvement of the spine, small joints of the hands and feet, or hips is uncommon.
• Rheumatic joints are classically hot, red, swollen, and exquisitely tender, with even the friction of bedclothes
being uncomfortable
• The pain can precede and can appear to be disproportionate to the objective findings. The joint involvement
is characteristically migratory in nature; that is, a severely inflamed joint can become normal within 1-3 days
without treatment, even as 1 or more other large joints become involved. Severe arthritis can persist for
several weeks in untreated patients.
Clinical manifestations and diagnosis of ARF

25. Arthritis
• Monoarticular arthritis is unusual unless anti-inflammatory therapy is initiated prematurely, aborting the
progression of the migratory polyarthritis.
• Rheumatic arthritis is almost never deforming. Synovial fluid in acute RF usually has 10,000-100,000
white blood cells/µL with a predominance of neutrophils, protein level of approximately 4 g/dL, normal
glucose level, and forms a good mucin clot. Frequently, arthritis is the earliest manifestation of acute RF
and may correlate temporally with peak antistreptococcal antibody titers.
• There is often an inverse relationship between the severity of arthritis and the severity of cardiac
involvement.
Clinical manifestations and diagnosis of ARF

26. Carditis (acute Rheumatic carditis, ARC)
Clinical manifestations and diagnosis of ARF
• A major change in the 2015 revision of the Jones Criteria is the acceptance of
subclinical carditis (defined as without a murmur of valvulitis but with
echocardiographic evidence of valvulitis) or clinical carditis (with a valvulitis
murmur) as fulfilling the major criterion of carditis in all populations.
• The carditis associated with ARF is classically considered to be a pancarditis that
can involve the pericardium, epicardium, myocardium, and endocardium

27. Carditis (acute Rheumatic carditis, ARC)
Clinical manifestations and diagnosis of ARF
• The presence of valvulitis is established by auscultatory findings together with echocardiographic evidence of
mitral or aortic regurgitation.
• The Carey Coombs murmur, a short mid-diastolic murmur heard loudest at the apex, is an indicator of
moderate-severe mitral regurgitation as a result of increased blood flow across the mitral valve during left
ventricular filling. Subclinical carditis can be diagnosed by echocardiography/Doppler studies that reveal
mitral or aortic regurgitation in the absence of ausculatory findings (either because the clinical exam findings
are absent or are not recognized).
• Damage to cardiac valves may be progressive and chronic Rheumatic Heart Disease (RHD), and may
resulting in cardiac decompensation.

28. Chorea (Sydenham chorea)
• occurs in approximately 10–15% of patients with acute RF and usually presents as an isolated,
frequently subtle, movement disorder.
• Emotional lability, incoordination, poor school performance, uncontrollable movements, and facial
grimacing are characteristic, all exacerbated by stress and disappearing with sleep.
• Chorea occasionally is unilateral (hemichorea). The latent period from acute GAS infection to
chorea is usually substantially longer than for arthritis or carditis and can be months.
Clinical manifestations and diagnosis of ARF

29. Onset can be insidious, with symptoms being present for several months before
recognition. Clinical maneuvers to elicit features of chorea include
• Demonstration of milkmaid’s grip (irregular contractions and relaxations of the
muscles of the fingers while squeezing the examiner's fingers)
• Spooning and pronation of the hands when the patient's arms are extended
• Wormian darting movements of the tongue on protrusion, and
• examination of handwriting to evaluate fine motor movements
Clinical manifestations and diagnosis of ARF
Chorea (Sydenham chorea)

30. Erythema Marginatum
• Rare (approximately 1% of patients with acute RF) but
characteristic rash of acute RF.
• It consists of erythematous, serpiginous, macular lesions with
pale centers that are not pruritic
• It occurs primarily on the trunk and extremities, but not on the
face, and it can be accentuated by warming the skin.
Clinical manifestations and diagnosis of ARF

31. Subcutaneous Nodules
• rare (≤1% of patients with acute RF)
• consist of firm nodules approximately 0.5-1 cm in diameter along the extensor
surfaces of tendons near bony prominences.
• There is a correlation between the presence of these nodules and significant
rheumatic heart disease.
Clinical manifestations and diagnosis of ARF

32. Diagnosis of ARF
Gewitz et al Revised Jones Criteria for Acute Rheumatic Fever,
2015
• The Jones criteria, used for guidance in the diagnosis of ARF since 1944, were last modified by the
American Heart Association (AHA) in 1992.
• They were reconfirmed in principle at an AHA-sponsored workshop in 20003 and historically have
represented the clinical standard to establish the diagnosis of ARF.
• In 2015 the American Heart Association (AHA) published the Revision of the Jones Criteria for the
Diagnosis of Acute Rheumatic Fever in the Era of Doppler Echocardiography A Scientific
Statement From the American Heart Association

33. Diagnosis of aARF, modified Jones criteria, 2015*
Gewitz et al Revised Jones Criteria for Acute Rheumatic Fever,
2015
Circulation. 2015 | Volume 131, Issue 20: 1737–1738, originally publishedMay 19, 2015,
https://doi.org/10.1161/CIR.0000000000000176

34. What is new in the 2015 Revised Jones Criteria?
Gewitz et al Revised Jones Criteria for Acute Rheumatic Fever,
2015
Considering Epidemiologic implications; notion of LOW and HIGH-RISK individuals
The global distribution of ARF and RHD is heterogeneous. certain geographic regions and specific ethnic and socioeconomic
groups experience very high rates of ARF, whereas the disease has virtually disappeared in other regions.
 It is reasonable to consider individuals at low risk of ARF if they come from a setting or population with
known low rates of ARF and RHD
 Where reliable epidemiological data are available, it is reasonable that low risk is defined as an ARF
incidence <2 per 100,000 school-aged children (5-14 years old) per year, or an all-age prevalence of RHD of
≤1 per 1,000 population per year
 Children not clearly from a low-risk population are at moderate to high risk depending on their reference
population

35. What is new in the Revised Jones Criteria?
Gewitz et al Revised Jones Criteria for Acute Rheumatic Fever,
2015
Carditis as major criteria can be “Clinical and/or “subclinically” diagnosed, in an era of widely
available echocardiography:
 Echocardiography with Doppler should be performed in all cases of confirmed and suspected ARF
 It is reasonable to consider performing serial echocardiography/Doppler studies in any patient with
diagnosed or suspected ARF, even if documented carditis is not present on diagnosis
 Echocardiography/Doppler testing should be performed to assess whether carditis is present in the absence
of auscultatory findings, particularly in moderate- to high-risk populations and when ARF is considered
likely
 Echocardiography/Doppler findings not consistent with carditis should exclude that diagnosis in patients
with a heart murmur otherwise thought to indicate rheumatic carditis

36. What is new in the Revised Jones Criteria?
Carditis as major criteria can be “Clinical and/or subclinically” diagnosed, in an era of widely
available echocardiography:
Numerous studies over the past 20 years have addressed the role of echocardiography (compared with purely
clinical assessment) in the diagnosis of ARF. More than 25 studies have reported echocardiography/Doppler
evidence of mitral or aortic valve regurgitation in patients with ARF despite the absence of classic auscultatory
findings.
Specific criteria exist for Doppler findings in subclinical rheumatic valvulitis:
Mitral regurgitation Aortic regurgitation
All four following criteria
• Seen in ≥2 views
• Jet length ≥2 cm
• Peak velocity >3 m/s
• Pansystolic
All four following criteria
• Seen in ≥2 views
• Jet length ≥1 cm
• Peak velocity >3 m/s
• Pandiastolic

37. Investigations for ARF
Evidence of preceding GAS infection
The evidence of prior GAS infection may be sought in one of the following ways:
• Positive throat culture for group A beta-hemolytic streptococci
• Positive rapid streptococcal antigen test
• Elevated or rising antistreptococcal antibody titer – Either antistreptolysin O (ASO) or
antideoxyribonuclease B (ADB)

38. Investigations for ARF
Laboratory studies obtained during the initial evaluation include
• Measurement of CRP or ESR to seek evidence of systemic inflammation
• Complete blood count with differential to look for anemia and leukocytosis
Electrocardiogram and echocardiogram are performed as part of the initial
screening

39. Differential diagnosis of ARF
Differentials
Rheumatic Arthritis Septic arthritis (including gonococcal)
Connective tissue and other autoimmune diseases such as juvenile idiopathic arthritis
Viral arthropathy
Reactive arthropathy
Lyme disease
Sickle cell anemia
Infective endocarditis
Leukemia or lymphoma
Gout and pseudo gout
Poststreptococcal reactive arthritis
Henoch-Schonlein purpura
Acute Rheumatic Carditis Physiological mitral regurgitation
Mitral valve prolapse
Myxomatous mitral valve
Fibroelastoma
Congenital mitral valve disease
Congenital aortic valve disease
Infective endocarditis
Cardiomyopathy
Myocarditis, viral or idiopathic
Kawasaki disease

40. Differential diagnosis of ARF
Differentials
Chorea Drug intoxication
Wilson disease
Tic disorder
Choreoathetoid cerebral palsy
Encephalitis
Familial chorea (including Huntington disease)
Intracranial tumor
Lyme disease
Metabolic (eg, Lesch-Nyhan, hyperalaninemia, ataxia
telangiectasia)
Antiphospholipid antibody syndrome
Autoimmune: Systemic lupus erythematosus, systemic vasculitis
Sarcoidosis
Hyperthyroidism

41. Treatment of ARF
Treatment of ARF consists of anti-inflammatory therapy, antibiotic therapy, and heart
failure management
Goals of treatment — The four major goals of treatment are:
• Symptomatic relief of acute disease manifestations (eg, arthritis): corticosteroids
• Eradication of group A beta-hemolytic Streptococcus (GAS): antimicrobial
• Prophylaxis against future GAS infection to prevent progression of cardiac disease
• Provision of education for the patient and patient’s caregivers
There is no therapy that slows progression of valvular damage in the setting of ARF.

42. Treatment of ARF
Drug Dosing in adults
Penicillins
(preferred)
Penicillin V  500 mg orally two to three times daily for 10 days
Amoxicillin*  500 mg orally twice daily for 10 days
Penicillin G
benzathine*
(Bicillin L-A)
 1.2 million units IM as a single dose
Cephalosporins
(potential alternatives for mild reactions to
penicillinΔ)
Cephalexin*
(first generation)
 500 mg orally twice daily for 10 days
Cefuroxime*
(second generation)
 250 mg orally twice daily for 10 days
Cefpodoxime*
(third generation)
 100 mg orally twice daily for 5 to 10 days
Cefdinir*
(third generation)
 300 mg orally twice daily for 5 to 10 days or 600 mg orally
once daily for 10 days
Macrolides
(alternatives)
Azithromycin  500 mg orally on day 1 followed by 250 mg orally on days 2
through 5
Clarithromycin*  250 mg orally twice daily for 10 days
Lincosamides
(alternative when macrolide resistance is a concern
and penicillins and cephalosporins cannot be used)
Clindamycin  300 mg orally three times daily for 10 days
Treatment of pharyngitis due to group A Streptococcus in adults

43. Rheumatic Heart Disease

44. Introduction to RHD
• Rheumatic heart disease (RHD) remains a major cause of
cardiovascular disease in wideworld.
• While RHD occurs only as a sequela of acute rheumatic fever (ARF),
the majority of patients with RHD lack a history of past ARF,
suggesting that the diagnosis of ARF is frequently missed.

45. Definition of RHD
RHD is defined as permanent heart valve damage subsequent to ARF.
Note: RHD is different to Rheumatic carditis
• Acute rheumatic carditis includes a spectrum of lesions ranging from
pericarditis, myocarditis, and valvulitis during acute rheumatic fever (ARF);
• There is a transition from rheumatic carditis to RHD with chronic valvular
lesions that evolve over years following one or more episodes of ARF.

46. Pathophysiology of RHD
• The valvular lesions begin as small verrucae composed of fibrin and blood cells along the borders of 1 or
more of the heart valves.
• As the inflammation subsides, the verrucae tend to disappear and leave scar tissue.
• A single episode of acute rheumatic carditis often results in complete healing of the valvular lesions, while
repeated episodes, especially involving previously affected valves, result in chronic RHD
• With repeated attacks of ARF, new verrucae form near the previous ones, and the mural endocardium and
chordae tendineae become involved.
• The mitral valve is affected most often, followed in frequency by the aortic valve.
• Isolated aortic valve disease is rare and generally seen with concomitant mitral valve involvement.

47. Patterns of valvular disease in RHD
Rheumatic Mitral valve disease
• Mitral stenosis
• Mitral regurgitation OR insufficiency
• Mixed mitral stenosis/regurgitation
Rheumatic Aortic valve disease
• Aortic stenosis
• Aortic regurgitation
• Tricuspid valve disease
• Pulmonary valve disease

48. Patterns of valvular disease in RHD
• Among patients with acute rheumatic carditis (ARC), the intensity and time course of the
inflammatory process may impact the course of mitral valve disease.
• Severe inflammation of the chordal structures and mitral valve leaflets can lead to isolated MR,
seen predominantly in children and young adults.
• Moderate chordal and leaflet inflammation, which may be exacerbated by repeated ARC, may
lead to mixed MR and mitral stenosis (MR+MS).
• Chronic chordal and leaflet inflammation may be exacerbated by repeated acute rheumatic
carditis, which may lead to mitral stenosis (MS) See algorithm on next slide
Rheumatic Mitral valve disease

49. Patterns of valvular disease in RHD
Pathogenesis
Rheumatic Mitral valve disease
ARC: acute rheumatic carditis;
MV: mitral valve
MS: mitral stenosis
MR: mitral regurgitation.

50. Patterns of valvular disease in RHD
Mitral regurgitation
• RHD related mitral valve structural changes include some loss of valvular substance and/or changes
to the subvalvular apparatus (elongation of the chordae)
• During ARF with severe cardiac involvement, heart failure is caused by a combination of mitral
insufficiency coupled with a pancarditis , involving the pericardium and myocardium in addition to
the endocardium/valve.
• Because of the increased volume load from the mitral insufficiency and the inflammatory process, the
left ventricle dilates. The left atrium also enlarges to accommodate the regurgitant volume. Increased
left atrial pressure results in pulmonary congestion and symptoms of left-sided heart failure.

51. Patterns of valvular disease in RHD
Mitral regurgitation
RHD related mitral valve structural changes include
loss of valvular substance and/or changes to the subvalvular
apparatus (elongation of the chordae)
The mitral valve becomes no longer
able to close properly during the
systole (insufficiency)
Mitral regurgitation
Increased Left Atrial pressure
Pulmonary congestion
Left-sided Heart failure
Chronic
MR+MS
MR+MS
Other complications :
the onset of atrial fibrillation (AF) or other
arrhythmias, or infective endocarditis.
rheumatic process, recurrent episodes of ARF

52. Patterns of valvular disease in RHD
Mitral regurgitation
Chest x ray
This plain chest radiograph from a female with known mitral
regurgitation demonstrates cardiomegaly with left atrial
(arrow) and left ventricular enlargement (arrowhead), as well
as mild pulmonary venous redistribution, all features
characteristic of mitral regurgitation.

53. Patterns of valvular disease in RHD
Mitral regurgitation
Mild MR Severe MR
Clinical
manifestation
signs of heart failure are not present,
the precordium is quiet, and
auscultation reveals a high-pitched
holosystolic murmur at the apex that
radiates to the axilla
• Enlarged heart with heaving apical left ventricular (LV)
impulse and often an apical systolic thrill
• Accentuated S2 if pulmonary hypertension is present
• A third heart sound or gallop is generally prominent
• Severe signs of Heart failure
ECG Normal • Prominent, longer duration and often bifid P waves, signs
of LV hypertrophy, and associated right ventricular (RV)
hypertrophy if pulmonary hypertension is present.
Chest X Ray Normal • Prominence of the left atrium and ventricle
• Congestion of the perihilar
vessels, a sign of pulmonary venous hypertension

54. Patterns of valvular disease in RHD
Mitral regurgitation
Apical four chamber view
with color flow Doppler
shows severe mitral
regurgitation during systole
associated with marked
enlargement of the left
ventricle and left atrium.
Echocardiography apical four chamber view of mitral regurgitation
Chronic mitral insufficiency (regurgitation) from RHD is characterized on echocardiography by leaflet and
chordal thickening, chordal fusion, and restricted leaflet motion. These changes often lead to stenosis

55. Patterns of valvular disease in RHD
Mitral stenosis
• Nearly all cases of MS are caused by RHD
• Mitral stenosis of rheumatic origin results from fibrosis of the mitral ring, commissural
adhesions, and contracture of the valve leaflets, chordae, and papillary muscles over time
• MS causes an obstruction to blood flow from the left atrium to left ventricle. As a result,
there is an increase in pressure within the left atrium, pulmonary vasculature, and right
side of the heart, while the left ventricle is unaffected in isolated MS.
• This is a chronic process and often takes ≥10 yr for the lesion to become fully established,
although the process may occasionally be accelerated

56. Patterns of valvular disease in RHD
Mitral stenosis
Clinical manifestations
• Related to the severity of the valvular stenosis, as it impacts the left atrial pressure,
pulmonary pressures, pulmonary vascular resistance, and cardiac output.
• MS usually presents with exertional dyspnea and/or decreased exercise tolerance
• Less common clinical presentations include hemoptysis, chest pain (often due to
pulmonary hypertension), fatigue, ascites and lower extremity edema associated with right
heart failure…

57. Patterns of valvular disease in RHD
Mitral stenosis
Mild MS Severe MS
Clinical
manifestation
• Asymptomatic
• Exercise
intolerance and
dyspnea
• Normal heart
size
• Dyspnea
• Hemoptysis
• Atrial fibrillation and other atrial arrhythmias
• Thromboembolism
• Chest pain
• Right-sided heart failure
• Moderate cardiomegaly
• loud S1, an opening snap of the mitral valve, and a long, low-pitched,
rumbling mitral diastolic murmur with presystolic accentuation at the apex
ECG Normal • prominent and notched P waves and varying degrees of RV hypertrophy
become evident.
• Atrial arrhythmias are common late manifestations.
Chest X Ray Normal • redistribution of pulmonary blood flow so that the apices of the lung have
greater perfusion (the reverse of normal)

58. Patterns of valvular disease in RHD
Echocardiogram
• Echocardiography demonstrates thickening of the mitral valve and chordal apparatus, as well as
restricted motion of the valve.
• The typical “elbow” or “dog leg” appearance of the anterior leaflet of the mitral valve can aid in the
distinction of a rheumatic valve from the various forms of congenital mitral stenosis
• Left atrial dilation is common; color Doppler flow across the mitral valve shows a narrow jet with flow
acceleration, and variable degrees of tricuspid insufficiency can be seen from left atrial hypertension
Mitral stenosis

59. Patterns of valvular disease in RHD
Apical long axis view from a 2-D
echocardiogram shows:
• Thickened mitral valve leaflets which
have marked limitation of mobility
• and show doming, with failure to open
normally during diastole.
Play the video
Mitral stenosis

60. Patterns of valvular disease in RHD
Four chamber echocardiogram shows thickened mitral valve with
reduced motion and doming during diastole. Right and left atrial
enlargement are also present.
Mitral stenosis
Play the video

61. Patterns of valvular disease in RHD
A real-time, three-dimensional TEE image in a long-axis orientation shows the thickened mitral leaflet with commissural fusion and
diastolic doming, typical for rheumatic mitral valve disease.
LA: left atrium; Ao: aorta; LV: left ventricle; TEE: transesophageal echocardiogram.
Play the video
Mitral stenosis

62. Patterns of valvular disease in RHD
On transesophageal echocardiogram (TEE) imaging, a full volume acquisition of the mitral valve in a patient with rheumatic mitral stenosis
shows the typical commissural fusion with a small oval central orifice in diastole. Images are shown from the perspective of the left atrial side
of the valve and from the left ventricular side of the valve.
Play the video
Mitral stenosis

63. Patterns of valvular disease in RHD
Aortic regurgitation / insufficiency
• In acute rheumatic aortic insufficiency, poor coaptation of the leaflets or leaflet prolapse is seen.
Chronic rheumatic aortic insufficiency leads to sclerosis of the valve and results in distortion and
retraction of the cusps.
• In both settings, regurgitation of blood leads to LV volume overload with dilation and
hypertrophy of the left ventricle, as it attempts to compensate for the excessive volume load.
Combined mitral and aortic insufficiency in the acute phase of ARF is much more common than
aortic involvement alone.

64. Patterns of valvular disease in RHD
Aortic regurgitation / insufficiency
Symptoms are unusual except in severe aortic insufficiency, or in the presence of significant concomitant
mitral valve involvement or myocardial dysfunction:
• Dyspnea on exertion can progress to orthopnea and pulmonary edema; angina
• Nocturnal attacks with sweating, tachycardia, chest pain, and hypertension may occur

65. Patterns of valvular disease in RHD
Aortic regurgitation / insufficiency
Peripheral signs

66. Patterns of valvular disease in RHD
Aortic regurgitation / insufficiency
• Corrigan’s pulse or water-hammer sign (collapsing pulse)
• De Musset’s sign: Bobbing of the head with each heartbeat (like a bird walking)
• Muller’s sign: Visible pulsations of the uvula
• Quincke’s sign: Capillary pulsations seen on light compression of the nail bed
• Traube’s sign: Systolic and diastolic sounds heard over the femoral artery (“pistol shots”)
• Duroziez’s sign: Gradual pressure over the femoral artery leads to a systolic and diastolic bruit
• Hill’s sign: Popliteal systolic blood pressure exceeding brachial systolic blood pressure by ≥ 60 mmHg (most sensitive
sign for aortic regurgitation)
• Shelly’s sign: Pulsation of the cervix
• Rosenbach’s sign: Hepatic pulsations
• Becker’s sign: Visible pulsation of the retinal arterioles
• Gerhardt’s sign (aka Sailer’s sign): Pulsation of the spleen in the presence of splenomegaly
• Mayne’s sign: A decrease in diastolic blood pressure of 15 mmHg when the arm is held above the head (very non-specific)
• Landolfi’s sign: Systolic contraction and diastolic dilation of the pupil
Peripheral signs of severe Aortic Regurgitation

67. Patterns of valvular disease in RHD
Aortic regurgitation / insufficiency
Echocardiography shows a dilated left ventricle and diastolic mitral valve flutter or oscillations caused by aortic regurgitant flow hitting
the valve leaflets. The aortic valve may demonstrate irregular or focal thickening, decreased systolic excursion, a coaptation defect, and
leaflet prolapse.
Five chamber view from a 2-D
echocardiogram shows a
moderate amount of aortic
regurgitation and left ventricular
enlargement.
Play the video

68. Patterns of valvular disease in RHD
Aortic regurgitation / insufficiency
Chest X Ray and EEG
• Chest radiographs demonstrate enlargement of the left ventricle and aorta
• ECG may be normal, but in advanced cases it reveals signs of LV hypertrophy
with a strain pattern and prominent P waves.

69. Patterns of valvular disease in RHD
Aortic stenosis
• Isolated rheumatic AS is very rarely seen
• AS generally progresses gradually over years with a prolonged asymptomatic
phase, although the clinical course is variable. Mortality dramatically increases
after the development of symptoms.
• Average survival without valve replacement after the onset of angina, syncope, or
HF is only two to three years.

70. Patterns of valvular disease in RHD
Tricuspid valve disease
• Primary tricuspid valve involvement is rare during both the acute and chronic stages of
rheumatic fever.
• Is more common secondary to Right ventricule dilation, resulting from significant left-
sided cardiac lesions.
• The clinical signs of tricuspid insufficiency include prominent pulsations of the jugular
veins, systolic pulsations of the liver, and a blowing holosystolic murmur at the lower left
sternal border that increases in intensity during inspiration

71. Patterns of valvular disease in RHD
Pulmonary Valve Disease
• Pulmonary insufficiency secondary to ARF is rare and usually occurs on a functional
basis secondary to pulmonary hypertension and is a late finding with severe mitral
stenosis.
• The murmur (Graham Steell murmur ) is similar to that of aortic insufficiency, but
peripheral arterial signs (bounding pulses) are absent.
• The correct diagnosis is confirmed by two-dimensional echocardiography and
Doppler studies

72. Primary prevention
• Prevention of the initial development of acute rheumatic fever (ARF) involves prompt diagnosis
and antibiotic treatment of group A streptococcal (GAS) tonsillopharyngitis
• Appropriate antibiotic treatment of streptococcal pharyngitis prevents ARF in most cases.
• However, at least one-third of ARF episodes occur in the setting of subclinical streptococcal
infection.
• In addition, ARF is not preventable in symptomatic patients who do not seek medical care.
Management of RHD

73. How to classify the risk of GAS and guide management
of acute pharyngitis
Estimates probability that pharyngitis is streptococcal, and suggests management course.
Remember : All Pharyngitis is not due to GAS (avoid irrational use of antibiotics)
But don’t miss to treat adequately a real GAS infection

74. Management of RHD
Secondary prevention
• Patients who have had an attack of ARF and develop subsequent GAS pharyngitis are at high risk for a recurrent
attack of ARF. Rheumatic heart disease (RHD) becomes more severe with each recurrent episode.
• Antimicrobial prophylaxis recommend continuous
• Parenteral prophylaxis with penicillin G benzathine is preferred for all patients. Oral agents are used in the case of
shortages of penicillin G benzathine and are also appropriate for patients who are allergic to penicillin.
• During the course of prophylaxis, patients and their household contacts who develop acute episodes of GAS
pharyngitis should be evaluated and treated promptly. Patients with breakthrough GAS pharyngitis on penicillin
should be treated with an alternative agent such as clindamycin.
• Education and counselling of the patient is very important to ensure a good adherence to the prophylactic therapy

75. Management of RHD
Secondary prophylaxis for rheumatic fever - Selection of therapy
Continuous regimen
Adults >27 kg Children ≤27 kg
Penicillin G benzathine
intramuscular (Bicillin LA,
benzathine benzylpenicillin)
1.2 million units every 21 to 28
days*
600,000 units every 21 to 28 days*
Penicillin V oral 250 mg orally twice daily 250 mg orally twice daily
Allergy to penicillin and sulfonamide antimicrobials:
Azithromycin¶ 250 mg orally once daily
5 mg/kg orally once daily (up to
250 mg)
Erythromycin is an acceptable alternative to azithromycin, although the latter has fewer adverse effects and permits once daily dosing. Erythromycin
dosing for adults: 250 mg (base) orally twice daily. Dosing for children: 20 mg/kg/day divided twice daily (maximum 500 mg per day).

76. Management of RHD
Duration of Secondary prophylaxis for rheumatic fever
Category Duration after last attack
Rheumatic fever with carditis and residual heart
disease
(persistent valvular disease*)
10 years or until 40 years of age (whichever is longer)
Sometimes lifelong prophylaxis (refer to UpToDate
topics on treatment and prevention of acute rheumatic
fever and management and prevention of rheumatic
heart disease)
Rheumatic fever with carditis but no residual heart
disease
(no valvular disease*)
10 years or until 21 years of age (whichever is longer)
Rheumatic fever without carditis 5 years or until 21 years of age (whichever is longer)
* Clinical or echocardiographic evidence.

77. Management of RHD
General management of RHD
• Patients with rheumatic valve disease should undergo periodic clinical and echocardiographic
evaluation with frequency based upon the severity of disease
• As noted above, secondary prevention (Continuous antibiotic prphylaxis) of rheumatic fever is
recommended in patients with history of acute rheumatic fever (ARF) and/or RHD
• Annual influenza vaccination and meticulous dental hygiene with annual check-ups are
recommended for patients with RHD.
• Prophylaxis against infective endocarditis (IE) is recommended for patients with prosthetic heart
valves or a previous history of IE who undergo invasive dental procedures

78. Management of RHD
Management of mitral regurgitation
• Prophylaxis against recurrences
• Afterload-reducing agents— ACE inhibitors and ARBs may reduce the regurgitant volume, attenuate
pathologic compensatory mechanisms, and preserve left ventricular function, but these have not been proven
to alter the natural history of the disease process.
• Diuretics may also provide some symptomatic and clinical benefit in select cases
• Treatment of complications : heart failure , arrhythmias, and infective endocarditis, …
• Surgical treatment (annuloplasty, valve remplacement,…) is indicated for patients who, despite adequate
medical therapy, have persistent heart failure, dyspnea with moderate activity, and progressive cardiomegaly,
often with pulmonary hypertension

79. Management of RHD
Management of mitral stenosis
• Prophylaxis against recurrences
• Pharmacologic therapy (diuretics and β-blockers) can be considered but is generally used only
for symptom control and much less often in children.
• Intervention is indicated in patients with clinical signs and hemodynamic evidence of severe
obstruction, but before the onset of severe manifestations.
• Percutaneous or Surgical valvotomy, or balloon catheter mitral valvuloplasty generally yields
good results; valve replacement is usually not necessary.

80. Management of RHD
Management of aortic regurgitation/ insuffiency
• Treatment consists of ACE inhibitors or ARBs and prophylaxis against ARF recurrence.
• Surgical intervention, which is typically aortic valve replacement, but occasionally can involve
aortic valve repair, should be done well in advance of the onset of heart failure, pulmonary
edema, and angina or when signs of decreasing myocardial performance become evident

81. Management of RHD
Management of aortic stenosis
• Medical management of asymptomatic aortic stenosis includes serial evaluation, treatment of
associated cardiovascular disease, and limitation of physical activity, as appropriate.
• No medical therapies have been proven to delay progression of leaflet disease.
• Symptomatic aortic stenosis is an indication for aortic valve replacement. Surgery or transcatheter
aortic valve implantation in such patients is associated with marked reduction in symptoms and
mortality.
• palliative care is recommended for patients with severe symptomatic aortic stenosis who are not
candidates for surgery or transcatheter aortic valve implantation.

82. Management of RHD
Management of aortic stenosis
• Medical management of asymptomatic aortic stenosis includes serial evaluation, treatment of
associated cardiovascular disease, and limitation of physical activity, as appropriate.
• No medical therapies have been proven to delay progression of leaflet disease.
• Symptomatic aortic stenosis is an indication for aortic valve replacement. Surgery or transcatheter
aortic valve implantation in such patients is associated with marked reduction in symptoms and
mortality.
• palliative care is recommended for patients with severe symptomatic aortic stenosis who are not
candidates for surgery or transcatheter aortic valve implantation.

83. Conclusion and Message to take home
• ARF and RHD are serious conditions that can cause significant damage to the heart and other vital
organs.
• Middle and lower income countries are particularly affected by these conditions, facing challenges
such as limited access to healthcare and poor living conditions
• Despite these challenges, Proper prevention and treatment can help prevent the development and
progression of these conditions
• It’s essential to prioritize resources and efforts towards improving living conditions, providing
appropriate treatment for streptococcal infections to reduce the burden of these debilitating
conditions

84. Society guideline links
International
• World Heart Federation (WHF): Position statement on the prevention and control of rheumatic heart disease (2013)
United States
• American Heart Association (AHA): Scientific statement on the revision of the Jones criteria for the diagnosis of acute rheumatic fever in the era of Doppler
echocardiography (2015)
• AHA: Scientific statement on prevention of rheumatic fever and diagnosis and treatment of acute streptococcal pharyngitis (2009)
• American Academy of Family Physicians (AAFP): Evaluation of poststreptococcal illness (2005)
Europe
• European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS): Guidelines on the management of valvular heart disease (2012)
Australia
• Heart Foundation of New Zealand and the Cardiac Society of Australia and New Zealand (CSANZ): New Zealand guidelines for rheumatic fever – Diagnosis, management
and secondary prevention of acute rheumatic fever and rheumatic heart disease, update (2014)
• Heart Foundation of New Zealand and CSANZ: New Zealand guidelines for rheumatic fever – Group A streptococcal sore throat management guideline, update (2014)
• Heart Foundation of New Zealand and CSANZ: New Zealand guidelines for rheumatic fever – Proposed rheumatic fever primary prevention programme, update (2014)
• Rheumatic Heart Disease (RHD) Australia and National Heart Foundation of Australia and CSANZ: The Australian guideline for prevention, diagnosis and management of
acute rheumatic fever and rheumatic heart disease, 2nd edition (2012)

85. References
• ROBERT M. KLIENGMAN, at al. Nelson textbook of Pediatrics, 21st edition, Elsevier, 2020
• GEWITZ MH, BALTIMORE RS, TANI LY, et al. Revision of the Jones Criteria for the diagnosis
of acute rheumatic fever in the era of Doppler echocardiography: a scientific statement from the
American Heart Association. Circulation 2015; 131:1806.

86. Thank you
for your attention