1. Rheumatic heart disease remains a major public health problem, affecting over 30 million people worldwide. It is most prevalent in low and middle income countries. 2. Echocardiography plays a key role in the diagnosis and screening of rheumatic heart disease. It can detect subclinical disease and assess disease progression over time. 3. Secondary prophylaxis with benzathine penicillin injections every 3-4 weeks is effective at preventing recurrent rheumatic fever and progression of rheumatic heart disease. However, ensuring consistent access to prophylaxis remains a challenge, especially in low resource settings.

1. Recent literature in
Rheumatic Heart Disease

2. Index
Recent Data In:
1. Epidemiology And Natural History Of RHD
2. Pathogenesis
3. RHD Diagnosis
4. Echocardiography Screening
5. RHD Management
6. Outcomes

3. Source:
1. Contemporary Diagnosis and Management of Rheumatic Heart Disease: Implications for Closing Gap: A Scientific
Statement From American Heart Association;R Krishna Kumar et al
2. Rheumatic heart disease and COVID-19, Andrea Beaton, Liesl Zühlke, Jeremiah Mwangi, Kathryn A Taubert:
European Heart Journal 2020 November 7, 41 (42): 4085-4086
3. Review Article Current status of rheumatic heart disease in India: PC Negi , Sachin Sondhi, Sanjeev Asotra , Kunal
Mahajan , Ayushi Mehta
4. Rheumatic Heart Disease Worldwide JACC Scientific Expert Panel David A Watkins, MD, MPH,a,b,c Andrea Z Beaton,
MD,d Jonathan R Carapetis, MBBS, PHD,e,f Ganesan Karthikeyan, MD, DM,g Bongani M Mayosi, MBCHB, DPHIL, b,h
Rosemary Wyber, MBCHB, MPH,e,i Magdi H Yacoub, MD,j Liesl J Zühlke, MBCHB, MPH, PHDb
5. Alternative Hypothesis to Explain Disease Progression in Rheumatic Heart Disease Circulation 2020;142:2091–2094
6. Global Rheumatic Heart Disease Registry (REMEDY study)
7. Ficolin-3 in rheumatic fever and rheumatic heart disease
Sandra Jeremias Catarino, Fabiana Antunes Andrade, Lorena Bavia, Luiza Guilherme, Iara Jose Messias-Reason
Immunology Letters 2020 November 21, 229: 27-31
8. Ahmed A Elhewala, Mohammed Sanad, Alshimaa M Soliman, May M Sami, Alshymaa A Ahmed
Biomedical Reports 2021, 14 (1): 4
9. Hunter LD, Monaghan M, Lloyd G, et al Interscallop separations of posterior mitral valve leaflet: a solution to
‘borderline RHD’ conundrum? Open Heart 2020;7:e001452 doi:101136/ openhrt-2020-001452
10. GOAL [Gwoko Adunu pa Lutino] trial

4. EPIDEMIOLOGY
• The prevalence ranged from 0.34 cases per 1000 population in non
endemic countries to >10 cases per 1000 in endemic countries
• The highest prevalence, disability, and mortality seen in  Oceania, South
Asia, and sub-Saharan Africa
• Total number of RHD cases globally in 2017  38-40 million
• RHD remains endemic- as defined by RHD related Mortality exceeding
0.15 deaths / 100 000 population among children 5-9 years of age

5. INCIDENCE AND GLOBAL BURDEN RELATED TO RHD

8. Current Indian Scenario
• Estimated average prevalence of RF/RHD is 0.5/1000 children in age
group of 5–15 years
• 3.6 million patients of RHD estimated from 2011 census
• 44,000 new patients every year
• Mortality is 1.5%–3.3% per year
• Underestimation of disease as no data are available from large
populous, like underdeveloped states such Bihar, Jharkhand etc
Review Article(2019) Current status of rheumatic heart disease in India: PC Negi , Sachin Sondhi, Sanjeev
Asotra , Kunal Mahajan , Ayushi Mehta

9. NATURAL HISTORY
• Chronic RHD occurs only as a sequel to ARF, majority(50-70%) lack a
history of past ARF
• Transition from carditis to RHD evolve over years after ≥1 episodes of ARF
• ARF recurrence (incidence, 3.7 per 100 person-years) and progression to
RHD was highest (incidence, 35.9 per 100 person-years) in first year
• Those with severe disease at presentation had rapid disease progression
• Cannon et al-Northern Territory(Australia) data-RHD between ages of 5 to
24 years
• Of 16.2% of patients with severe RHD at diagnosis, 50% had proceeded to valve
surgery by 2 years
• Patients with mild RHD at diagnosis - 64% continuing to have mild RHD even after 10
years, only 11.4% progressed to severe RHD

10. ALTERNATIVE HYPOTHESIS FOR EXPLANATION
OF DISEASE PROGRESSION
• Pro inflammatory cytokines priming gene expression in all 4 cardiac valves
+ hemodynamic stress to valve
• The TGF-β1 pathway has been successfully modulated with angiotensin
receptor blockers to reduce mitral valve fibrosis after myocardial infarction
• Successfully delaying disease initiation in patients with ARF and disease
progression in patients with subclinical or mild disease using a safe, orally
administered drug(ACE inhibitor) represents a major advance for RHD
control globally
• Alternative Hyposis to Explain Disease Progression in Rheumatic Heart Disease Circulation
2020;142:2091–2094

12. RHEUMATIC HEART DISEASE AND COVID-19
• The direct and indirect risk of COVID-19 infection to people living with RHD
1. Direct risk : World Heart Federation lists RHD as a risk factor for severe
COVID 19 disease Magnitude is unknown
2. Indirect risk : a known increased risk of progression and adverse
outcomes in RHD patients due to disruption of regular & timely care
Mainly being secondary prophylaxis
- Oral Penicillin is far superior than no prophylaxis- but should switch to IM
as soon as it can
- Provisions for secondary prophylaxis should be taken care under essential
services
- Patients should continue taking their medicines
Rheumatic heart disease and COVID-19
Andrea Beaton, Liesl Zühlke, Jeremiah Mwangi, Kathryn A Taubert
European Heart Journal 2020 November 7, 41 (42): 4085-4086

13. Ahmed A Elhewala, Mohammed Sanad, Alshimaa M Soliman, May M Sami, Alshymaa A Ahmed
Biomedical Reports 2021, 14 (1): 4
• MMP-9- an independent sensitive marker with which to detect
• HF in children with RHD
• Predict prognoses of patients as it correlates with severity of HF
• MMP-9 in detection of
• 'silent' RHD in school aged children and
• asymptomatic HF in children with known RHD especially in rural areas
• MMP-9 detected HF with a sensitivity 95%, specificity 75%, positive
predictive value 70%, negative predictive value 95%
MARKERS THAT EXPLAIN DISEASE PROGRESSION

14. MARKERS THAT EXPLAIN DISEASE PROGRESSION
Ficolin-3 in rheumatic fever and rheumatic heart disease
Sandra Jeremias Catarino, Fabiana Antunes Andrade, Lorena Bavia, Luiza Guilherme, Iara
Jose Messias-Reason Immunology Letters 2020 November 21, 229: 27-31
• Role of complement pathway: Low ficolin-3 levels might be associated
with RF and even more so with RHD, being a potential marker of
disease progression

15. DIAGNOSIS – General Features
• Acute rheumatic valvulitis manifests as valvular regurgitation
• Chronic inflammation leads to valve stenosis from commissural fusion with or
without associated regurgitation
• Typically affects left-sided valves, with greater affinity for mitral valve
• Isolated aortic disease occurs in 2% of cases
• Right sided valve disease is not infrequent, typically affects tricuspid valve
(primary valvulitis or result of hemodynamic consequences of left-sided valve
disease), and rarely affects pulmonic valve

17. Burden and progression of RHD- Tip of
ICEBERG and Role of Echo

18. Role of Echocardiography in ARF/ RHD –
1) Assessment of
a)The mechanism and severity of valvular regurgitation and/or stenosis
b) leaflet and chordal morphology
c)Annular size, chamber sizes and function, pericardial effusion, and PAP Pressure
2) Serial assessment of disease progression
3) Earlier detection of subclinical carditis
4) Helps avoidance of over diagnosis of RF

19. Criteria for pathologic regurgitation (acute rheumatic
carditis as well as for RHD) (all four):
Pathological Mitral Regurgitation
1. Seen in 2 views
2. In at least 1 view, jet length ≥2
cm
3. Velocity ≥3 m/s for 1 complete
envelope
4. Pan-systolic jet in at least 1
envelope

20. Pathological Aortic Regurgitation
1. Seen In 2 views
2. In at least 1 view, jet length ≥1
cm
3. Velocity ≥3 m/s in early diastole
4. Pan-diastolic jet in at least 1
envelope
Criteria for pathologic regurgitation (acute rheumatic carditis as well
as for RHD) (all four):

21. MORPHOLOGIC CRITERIA MITRAL VALVE
A Acute Rheumatic carditis
• Annular dilatation
• AML prolapse
• Beading & focal
thickening of leaflet
(verrucous vegetation)
• Elongated chordae
• Chordal rupture ( may
result in flail leaflet
B Chronic RHD
1. AMVL thickening
≥3 mm (age ≤20 yrs)
≥4 mm (age 21 to 40 yrs)
≥5 mm (age >40 yrs)
2. Chordal thickening
3. Restricted leaflet motion
4. Excessive leaflet tip
motion during systole

22. MV in systole a normal MV b RHD with excessive leaflet tip motion, which results in abnormal coaptation and
regurgitation, but usually does not meet echocardiographic definition of ‘MV prolapse’ c Echocardiographic
MV prolapse, defined by >2 mm billowing of leaflet tissue into left atrium In MV prolapse (c), coaptation of
leaflets often remains normal, as free edges of leaflet stay in apposition below plane of MV annulus
MV in diastole a normal MV b rheumatic MV with thickened and restricted
anterior &posterior leaflets

23. MORPHOLOGIC CRITERIA AORTIC VALVE
1. Irregular or focal thickening
2. Coaptation defect
3. Restricted leaflet motion
4. Prolapse

24. Definite RHD (A, B, C, D) Age ≤20 yrs Definite RHD (A, B, C, D) Age >20 yrs
A Pathological MR and at least 2 morphological
features of RHD of MV
A Pathological MR and at least 2 morphological
features of RHD of MV
B MS mean gradient ≥4 mm Hg B MS with mean gradient ≥4 mm Hg
C Pathological AR and at least 2 morphological
features of RHD of AV
C Pathological AR and at least 2 morphological
features of RHD of AV in those age <35 yrs
D Borderline disease of both AV and MV D Pathological AR and at least 2 morphological
features of RHD of MV
Borderline RHD (A, B, C)
A At least 2 morphological features of RHD of
MV without pathological MR or MS
B Pathological MR C Pathological AR
Borderline Not Applicable to Those Age >20 yrs
World Heart Federation Criteria for Diagnosis of RHD

25. Hunter LD, Monaghan M, Lloyd G, et al Interscallop separations of posterior mitral valve leaflet: a
solution to ‘borderline RHD’ conundrum? Open Heart 2020;7:e001452 doi:101136/ openhrt-2020-
001452
Is it really a Borderline RHD?
• Currently screened cases with isolated mild, ‘pathological’ MR are classified as
borderline RHD This subcategory contributes to majority of WHF-screen
positive disease around world
• Small slits in posterior mitral valve leaflet, interscallop separations, are
frequently underlying cause of mild pathological MR These cases are devoid of
any morphological features of RHD and should not be considered as such
• Mechanistic approach to MR in RHD screening should replace current Doppler
based criteria for evaluation of MR Will enable disease control programes to
reduce amount of screen positive cases misclassified as RHD significantly

26. ROLE OF ACTIVE CASE DETECTION AND SCREENING
• Target populations - school-aged children and pregnant women
• Incidence of primary episodes of ARF is highest in 5 to 15 year old and incidence of
recurrent episodes of ARF is highest within 5 years of original presentation
• Previously undetected latent RHD poses a special risk during pregnancy; if severe, it
could compromise life of mor and baby
• The key focus
(1) establish disease burden
(2) use prevalence data for regional and global advocacy (led to development of local
RHD registries and secure supplies of benzathine penicillin)
(3) ascertain short- and medium-term outcomes of echocardiographically detected
latent RHD

27. Latent RHD
All cases of RHD diagnosed through echocardiographic screening, to
include previously unrecognized clinical RHD and subclinical RHD
Clinical RHD
All cases of RHD that have clinical signs or symptoms including
pathological heart murmur diagnosed through echocardiographic
screening or clinical evaluation Clinical RHD is typically more advanced
than subclinical RHD
Subclinical RHD
All cases of RHD that do not have clinical signs or symptoms including
heart murmur Subclinical RHD is only diagnosed by echocardiography

28. Call for simplified protocols
• 2012 WHF criteria were intended for RHD diagnosis by experts
• In a screening environment, criteria have proved less practical, with
• its rapid pace,
• providers with varying experience, and
• suboptimal conditions
• Some portable devices lack spectral Doppler, which is required for
diagnosis of RHD according to WHF criteria
• Re-evaluate components of WHF criteria toward simplification of
diagnosis & Standardize simplified protocols for screening

29. MEDICAL MANAGEMENT OF HEART FAILURE
• MR - diuretic agents and afterload reduction. Digoxin and β-blockade may be considered
• A Turkish study reported that addition of ACE inhibitor lowered LV EDV and atrial natriuretic
peptide levels after 20 days of treatment
• Both enalapril and nicorandil resulted in decreased LV ESV and increased ejection fraction in 87
patients with RHD with severe MR over 6 months; nicorandil had a greater effect
• MS -
• Loop diuretic agents are useful in acute pulmonary edema and for long-term
• Diuretic agents such as aldosterone blockers (spironolactone and eplerenone) and thiazide diuretic
drugs (metolazone and chlorthalidone) are also used
• β-Blockers allowing for greater diastolic filling into left ventricle, and reduce left atrial pressure
and provide symptom relief

30. • AR –
• Treatment with ACE inhibitor , ARB and β-blockers has been shown to
be beneficial in large population cohort particularly those with left
ventricular dysfunction
• Multivalve disease with MR and AR - afterload reduction, diuretic
agents, and possibly β-blockade
• Mixed mitral valve disease - diuretic agents may be only medical
rapy available

31. SECONDARY PROPHYLAXIS
• Individuals who have had one episode of ARF are at higher risk for
recurrent ARF
• ARF becomes less common after 25 years of age and is rare in >30 years
• BPG is most effective and is superior to oral penicillin prophylaxis in
preventing GAS pharyngitis and recurrent ARF
• Every 4-week dosing of BPG is used in most settings
• There are limited data that more frequent dosing, every 2 or 3 weeks, may
provide superior protection and more stable penicillin levels

32. • AHA recommend IM BPG as preferred agent for secondary
prophylaxis, with an every-4-week schedule for most individuals,
although an every-3-week schedule can be considered for those at
high risk or those who experience recurrent ARF despite high
adherence to a 4-week schedule
• The pain of BPG injection can be reduced significantly when
reconstituted with 1% lidocaine
• Pain relief may be achieved with vibratory device

33. Guideline Secondary Prophylaxis Duration
Australian (2020) Possible ARF: 1 year
Probable or definite ARF without carditis: minimum of 5 y or until age 21 y (whichever is longer)
Borderline RHD: not usually recommended but can be considered for 1–3 y based on risk factors
Mild RHD: If documented history of ARF, n a minimum of 10 y after most recent episode of ARF or until
age 21 y (whichever is longer)
If no documented history of ARF and aged <35y, n a minimum of 5 y after diagnosis of RHD or until age
21 y (whichever is longer)
Moderate RHD: If documented history of ARF, n a minimum of 10 y after most recent episode of ARF
or until age 35 y (whichever is longer)
If no documented history of ARF and aged <35y, n a minimum of 5 y after diagnosis of RHD or until age
35 y (whichever is longer)
Severe RHD: If documented history of ARF, n a minimum of 10 y after most recent episode of ARF or
until age 40 y (whichever is longer) If no documented history of ARF, n a minimum of 5 y after diagnosis
of RHD or until age 40 y (whichever is longer)

34. • Current recommendations for duration of secondary prophylaxis is
based mainly on expert opinion
• The most significant considerations regarding duration of secondary
prophylaxis are
• characteristics of initial ARF presentation (age, time since last ARF, rheumatic
carditis at presentation) and
• presence and severity of chronic RHD
• Before stopping prophylaxis
• an individual’s risk of GAS exposure like high-risk status (teachers, parents,
healthcare providers, etc) and
• high-risk GAS transmission environments (poor housing conditions,
overcrowding, etc), should be considered

35. • High BPG adherence reduces ARF risk and improves outcomes
• RHD register (from Australian Northern Territory) showed risk of
recurrent ARF decreased once a person had received at least 40% of
BPG doses, after which there was a further 17% decreased risk for
every 10% increase in adherence
• The majority of patients do not have a documented history of ARF-
current guidelines on duration of secondary prophylaxis may not
directly apply

36. GOAL [Gwoko Adunu pa Lutino] trial
• To determine absolute benefit of secondary prophylaxis in setting
of subclinical mild RHD
• Children with borderline and mild definite RHD are randomized to
receive monthly BPG or no BPG (458 in each group)
• Primary outcome - echocardiographic regression at 24 months
from time of enrollment
• The study will also track adverse reactions to BPG
• The results of this trial will hopefully provide most definitive data
to date to inform recommendations for follow-up and whether or
not BPG prophylaxis in indicated in patients with borderline and
mild definite RHD

37. ENDOCARDITIS
• Uncommon but severe disease still carries high mortality rates (30% at 1 year)
• Guidelines have considerably reduced role of antibiotic prophylaxis before dental
procedures because of lack of scientific evidence of reduction of IE burden when
using prophylaxis
• There is uncertainty whether Western guidelines are valid for LMICs, where
dental hygiene is much poorer
• Poor access to oral health services in low- and lower-middle income settings may
render question of prophylaxis hypothetical

38. PREGNANCY
• Unoperated RHD is most commonly diagnosed in pregnancy when
• increase in cardiac output and
• drop in vascular resistance
- unmask moderate or severe valve lesions
• Stenotic lesions are less well tolerated than regurgitant lesion
• May require interventions (BMV, cardiothoracic surgery, or termination of pregnancy)
• Appropriate preconception counseling, including advice on contraception
• REMEDY study showed that only 5% of women with prosthetic heart valves and 2% with severe MS were on
contraception
• A recent study of 3506 pregnant women in Uganda found that 17% had cardiac disease, 88% of which was RHD
• Additionally, study found that <5% of women were aware of their diagnosis, 50% required intervention or
change in delivery planning, and attributable risk of heart disease on maternal mortality was 11%
• Mechanical valve - anticoagulation throughout pregnancy (warfarin, unfractionated heparin, LMWH)
• In women needing warfarin ≤5 mg/d, medication should be continued until end of pregnancy
Beaton, A, Okello, E, Scheel, A, DeWyer, A, Ssembatya, R, Baaka, O, Namisanvu, H, Njeri, A, Matovu, A, Namagembe, I, et al Impact of heart disease on maternal, fetal and neonatal outcomes in a low-resource
setting Heart 2019;105:755–760 doi: 101136/heartjnl-2018

39. PERCUTANEOUS INTERVENTIONS
• In symptomatic patients with severe isolated rheumatic MS - BMV
• Long-term outcomes are comparable between BMV and open mitral commissurotomy
• 80% of symptomatic patients are candidates for BMV, leaving only 20% to undergo surgery because of
unfavorable anatomy and high Wilkins score
• Balloon dilation is traditionally reserved for pure mitral valve stenosis, selected patients with mild central
MR can also undergo BMV
• BMV - Younger patients
Severe MS manifesting during pregnancy (BMV can be lifesaving)
Restenosis after surgical valvotomy
Restenosis after previous BMV
• With careful case selection- 80% of patients achieve valve areas in excess of 15 cm2
• Complications after BMV occur in 2% to 5% (cardiac tamponade, stroke, and acute MR) A ruptured valve
leaflet requires urgent surgery
• The most significant barrier to widespread application of BMV is prospect of emergency surgery in a small
number of patients

40. • INDICATIONS - Similar to those of non rheumatic pathologies (both for mitral and aortic valves)
• Removal of left atrial appendage in patient with atrial fibrillation
• Repair versus replacement-
Young patients from underprivileged regions of globe, who face significant challenges to be
compliant with anticoagulation therapy
Rheumatic mitral valve repair has evolved significantly New procedures, such as artificial chordal
implantation, have made rheumatic mitral valve repair more standardized and reproducible The majority
of surgeons reported feasibility of repair in 75% to 80% of patients and long-term survival superior to
those after valve replacement
• Note that Durability of repair of rheumatic mitral valve is generally poorer than in nonrheumatic valves
• Lower incidence of complications with aortic prosses and greater difficulty with aortic valve repair
makes aortic valve replacement more acceptable
• The TTK Chitra prostic heart valve is an example of a low-cost solution that was developed in an LMIC
and offers an affordable alternative
SURGERY

41. MORBIDITY AND MORTALITY
• Mortality and Morbidity: Lessons Learned From REMEDY
The Global Rheumatic Heart Disease Registry ( REMEDY study)
-a contemporary cohort of 3343 RHD patients from 14 LMICs, including India
They concluded that Patients with RHD
- Young (median age 28 years)
- Female (66.2%),
- Unemployed (75.3%)
- Majority (63.9%) of patients had moderate to severe multivalvular disease
- Complicated by congestive heart failure (33.4%), pulmonary hypertension
(28.8%), atrial fibrillation (21.8%), stroke (71%), IE (4%), and major bleeding (27%)

43. ENDING RHEUMATIC HEART DISEASE IN AUSTRALIA: THE EVIDENCE FOR A NEW
APPROACH-2020

45. Thank You