1. Acquired Heart Disease
Mohammed Alghamdi, MD, FRCPC (peds), FRCPC (card), FAAP, FACC
Assistant Professor and Consultant
Pediatric Cardiology, Cardiac Science
King Fahad Cardiac Centre
King Saud University

2. Acquired Heart Disease
Rheumatic Fever
Kawasaki Disease
Infective Endocarditis
Pericarditis
Myocarditis
Cardiomyopathy
Cardiac Arrhythmias: Any case scenario of heart failure and a heart rate more than 200 is arrhythmia until proven other wise. The commonest arrhythmia in children is SVT.

3. Rheumatic Fever
RF: most common cause of acquired heart disease in developing countries.
150 in 100,000 in developing countries (more common in developing)
1 in 100,000 in developed countries.
Rheumatic heart disease (RHD) inflammatory changes to cardiac valves and myocardium.
RF is the commonest acquired heart disease in developing countries while Kawasaki is the commonest in developed countries.

4. Rheumatic Fever
Precipitated by Group A Streptococcal (GAS) pharyngitis (not other types of GAS infections)
Acquiring the disease depends on the host susceptibility which depends on genetic, environmental, socioeconomic and immunological status.
2-4 weeks after untreated GAS Pharyngitis
T-cell and B-cell lymphocytes produce antibodies against some Streptococcal antigens that cross-react with antigens on myocytes or cardiac valve tissue.
RF no heart sequale unlike RHD. RHD will lead to rheumatic fever which will lead to well established disease.

5. It is not due to the infection itself rather due to cross-reactivity between myocytes and bacterial antigens.
Not from one infection but clinical + sub-clinical infection leading to acute rheumatic fever, and if it is not recognized rheumatic heart disease.

6. Rheumatic Fever Jones criteria (1992) Major Manifestations
Minor Manifestations
Carditis
Arthralgia
Polyarthritis
Fever
Chorea
Raised ERS or CRP
Erythema marginatum
Prolonged PR interval on ECG
Subcutaneous nodules
ASO > 480 IU/ml / Anti Dnase > 680 IU/ml
ASO titer may be normal initially
need to reapeat in ? Wks if high suspecion of ARF
CRP level of ≥30mg/L
ESR of ≥50mm/h
ESR in ARF is typically >80mm/hr, usually remains elevated for >4 weeks, and may remain elevated for 3-6 months despite a much shorter duration of symptoms
CRP concentration rises more rapidly than the ESR and also falls more rapidly with resolution of the attack
Evidence of antecedent GAS infection
1. Positive throat culture or rapid antigen test for GAS
2. Raised or rising streptococcal antibody titre

7. Rheumatic Fever Jones criteria (1992)
Two majors or one major and two minors plus evidence of antecedent GAS infection. ASO titer may be –ve; repeat in 2-4 weeks if there is a high index of suspicion.
Exceptions:
Chorea & indolent carditis do NOT require evidence of antecedent GAS infection
Recurrent episode requires :
Only one major OR
Several minor manifestations
Plus evidence GAS infection

8. Rheumatic Fever Arthritis:
Most common ARF presentation (75% of first attacks)
Migratory, Asymmetrical, Polyarthritis, of large joints
Typically: extremely painful
Highly responsive to salicylate and NSAID therapy
Within 3 days
Monoarthritis if history of early use of NSAID
Premature abortion the polyarthritis manifestation.
You can’t give aspirin if patient has already started on NSAID
swelling of the joint
two or more of the following:
limitation of movement
hotness of the joint
pain and/or tenderness.(Typically: extremely painful)

9. Rheumatic Fever Cardiatis: Valvulitis:
Isolated MV is the commonest followed by MV plus AV then AV, and rarely affects the right side.
Early disease leads to valvular regurgitation,
Prolonged or recurrent attacks lead stenosis
Pericarditis and myocarditis may occur
RHD is less rare in children less than 5 ears because it requires recurrent infection.
Congestive heart failure in ARF results from valvular dysfunction secondary to valvulitis and is not due to primary
Myocarditis
The rheumatic aetiology can usually be confirmed by a typical appearance on echocardiography
In New Zealand, echocardiographic evidence of subclinical carditis can also be accepted as a major
Manifestation

10. Rheumatic Fever Sydenham’s chorea
Jerky, uncoordinated movements esp. of hands, feet, tongue and face.
Disappear during sleep
More common in adolescence female
Occur after a prolonged latent period following GAS
6 wks - 3 yrs following GAS infection
Strong association with carditis
In sydenham chorea, it’s RHD until proven otherwise. Because it can happen 3 years post-GAS where it’s hard to find any evidence of strep infection. Therefore, anyone with chorea should do echo.
Usually seen in people who have beautiful handwriting and suddenly drops.

11. Rheumatic Fever Erythema marginatum
Rare & difficult to detect esp. in dark-skinned patients
Circular patterns of bright pink macules or papules that blanch under pressure
Trunk and proximal extremities
Almost never on face
Not itchy or painful vs eczema

12. Rheumatic Fever Subcutaneous nodules Rare < 2% of cases,
Highly specific manifestation of ARF but it is not sensitive.
Round, firm, mobile and painless nodules
Appear 1-2 weeks after onset of other symptoms
last 1-2 weeks (rarely > 1 month)
Strongly associated with carditis

13. Rheumatic Fever Treatment:
Antibiotics to eradicate of residual GAS bacteria
Anti-inflammatory agents
High dose aspirin or NSAIDs.
Steroids for severe carditis
CHF therapy as indicated
Primary prevention by preventing the infection from happening, secondary prevention to prevent repeated infection (because RHD does it occur from the first attack it needs several episodes to occur.
Sydenham Chorea:
Haloperidol

14. Secondary Prophylaxis
Rheumatic Fever Secondary prophylaxis
Secondary Prophylaxis
ANTIBIOTIC
DOSE
ROUTE
FREQUENCY
First line
Benzathine penicillin G
(BPG)
1,200,000 U ≥ 20kg
600,000 U < 20kg IM
Q4 wks OR
Q3 wks if confirmed
recurrent ARF despite adherence to
4 wks injection
Second line
Penicillin V
250mg
Oral
BID
Penicillin allergy 0.2% only stop penicillin if patient has anaphylactic shock
Erythromycin
40mg/kg/day (children)
BID –QID
400mg (adults)
First dose of secondary prophylaxis should be delivered in hospital
Second line: Phenoxymethylpenicillin (Penicillin V) (If IM route is not possible or refused)
BID regimens are also likely to result in poorer rates of adherence over long periods of time and less predictable serum penicillin concentrations, when compared to intramuscular BPG
Recent Cochrane meta-analysis
Use of penicillin (compared to no therapy) is beneficial in the prevention of recurrent ARF
IM benzathine penicillin G (BPG) is superior to oral penicillin in the reduction of both recurrent ARF (87–96% reduction) and streptococcal pharyngitis (71-91% reduction) (Level I)
Secondary prophylaxis also reduces the severity of RHD. It is associated with regression of heart disease in approximately 50-70% of those with adequate adherence over a decade (Level III 2) and reduces mortality (Level III 2)
While BPG is usually administered every four weeks (28 days)
Serum penicillin levels may be low or undetectable 28 days following a dose of 1,200,000 U.
Fewer streptococcal infections and ARF recurrences occurred among those receiving three weekly BPG (Level I).
Three-weekly regimen resulted in greater resolution of mitral regurgitation in a long-term randomised study in Taiwan (66%vs 46%)
Prospective data from New Zealand however, showed that recurrences were rare among people who were fully adherent to a four-weekly BPG regimen
four-weekly regime is preferable to a three-weekly regime because of the resource and compliance implications (Grade D).
In New Zealand, three weekly (21-day) BPG is recommended only for those who have confirmed recurrent ARF despite full adherence to four-weekly (28-day) BPG delivery
An alternative strategy is the administration of larger doses of BPG, leading to a higher proportion of people with detectable serum penicillin levels four weeks after injection.
However, until more data are available, this strategy cannot be recommended
The rates of allergic and anaphylactic reactions to monthly BPG are 3.2% and 0.2%
When patients state they are allergic to penicillin or when a non-specific reaction has been reported, they should be investigated for penicillin allergy, preferably in consultation with an allergist.
IM BPG injections in conjunction with anticoagulation therapy:
injections should be continued for those who are anti-coagulated, unless there is evidence of uncontrolled bleeding or INR is outside the defined therapeutic window
the fact that penicillin has failed to eradicate this disease process is irrefutable proof of the need for more laboratory, epidemiological, and clinical research. In another word, some expert suggested it is not because penicillin is not working but because either lack of penicillin or problem with under diagnosis.
Kaplan EL Heart Jan;91(1):3-4

15. Duration of Secondary Prophylaxis
Rheumatic Fever
Duration of Secondary Prophylaxis
CATEGORY
DURATION OF PROPHYLAXIS
ARF with no or mild carditis
Min of 10 years after most recent episode ARF OR until age 21 years (whichever is longer)
ARF with moderate carditis
Min of 10 years after most recent episode ARF OR until age 30 years (whichever is longer)
with ARF with severe carditis
Min of 10 years after most recent episode ARF OR until age 30 years (whichever is longer)
May need life long prophylaxis
Individuals working or living with children or in a living situation where there is overcrowding or close proximity to others (such as boarding schools, barracks, and hostels) have a higher risk of exposure to GAS and subsequent development of ARF. In these cases, consideration should be given to extending the duration of prophylaxis
For those presenting at an older age (over the age of 21 years), with no or mild carditis, it is possible to consider discharge from prophylaxis after 5 years

16. Damage to the heart is permanent whereas the arthritis.

17. Kawasaki Disease
KD: inflammatory disease of unknown etiology causing acute, diffuse vasculitis of medium size blood vessels (mainly coronary arteries).
Most common cause of acquired heart diseases in developed countries.
More common in Japanese population
Higher in males than females
Typical age: 6 months - 5 years

18. Kawasaki Disease Cardiac Involvement: Other medium size arteries
Coronary arteries( late): if left untreated the risk of CAD is 25%, this is reduced to 2% with treatment.
Dilation and aneurysm formation
Thrombus formation
Fibrosis and stenosis
Myocardial infarction.
May cause myocarditis and endocarditis
Other medium size arteries
Axiliary, femoral, iliac, and renal arteries.

19. Kawasaki Disease Fever: at least 5 days duration
At least 4 of the following (to call it complete typical KD).
Conjunctivitis: bilateral, non-purulent
Skin Rash: polymorphous skin rash
Mucous membrane changes: red, dry, and cracked lips, strawberry tongue
Extremities changes: palms/soles erythema, hands/ feet edema, Skin peeling
Cervical lymphadenopathy: unilateral and >1.5 cm in diameter

20. Kawasaki Disease DDX of KD: Scarlet fever EBV infection
Adenovirus infection
Staphylococcal scalded skin syndrome
Drug reactions
Stevens–Johnson syndrome.

21. Kawasaki Disease Atypical (incomplete) KD:
Cases of KD that do not fulfill diagnostic criteria.
More common in infants
Children with
Fever greater than 5 days
Two or three classic symptoms
Supporting laboratory abnormalities or echo evidence of coronary involvements
Should be treated as KD

22. Kawasaki Disease Labs abnormalities in KD: Elevated ESR > 50 (70%)
Elevated C-reactive protein (50%)
CBC:
Neutropenia , leukocytosis (50%)
Nonspecific anemia
Thrombocytosis more than 500,000 is very pathagnomonic.
Marker of KD
Not seen until 2nd week of the disease
Elevated liver transaminases (40%)
Low serum albumin level
Sterile pyuria (33%)
Aseptic meningitis (up to 50%).

23. Kawasaki Disease Treatments: IVIG 2 g/kg
2nd dose if persistent fever within 48 h of the initial dose
High dose of aspirin of 30–100 mg/kg/day.
Once afebrile: aspirin is decreased to 3–5 mg/kg/day
Aspirin acts as an anti-inflammatory agent if give in high doses for long time, analgesic if given in medium doses when needed and antiplatelet if given in small doses for long time.
Echo at base line
Repeat echocardiogram and inflammatory markers at 6–8 weeks
If normal coronary arteries and inflammatory markers : aspirin can be stopped
If coronary artery abnormalities: long-term Rx with aspirin
Other anticoagulants warfrin if giant aneurysm of coronary arteries

24. Infective Endocarditis
infection of the endocardial lining of the heart or cardiac vessels
Rare but with high mortality
Usually affect abnormal cardiac structure
Valvular disease
Septal defects
Presence of foreign material such as mechanical valves and patch material after surgical repair.

25. Infective Endocarditis
Etiology:
Gram- positive bacteria:
> 90 % 0f bacterial case
Streptococci Viridans : most common infectious agent
Staphylococcal species – especially prosthetic valves.
Enterococci : less common pediatric age group.
Gram-negative bacteria:
< 10% of bacterial cases
Example: HACEK group
Haemophilus, Actinobacillus, Cardiobacterium, Eikenella and Kingella
Fungal – uncommon
Neonate, immunocompromised patients, prolonged antibiotic
10% IE case: organisms cannot be identified.

26. Infective Endocarditis
Clinical Features:
General:
Fever
Nonspecific manifestations
myalgias, arthralgias, headache, and general malaise
Cardiac:
New onset or worsening valvular regurgitation
Congestive heart failure
Heart block

27. Infective Endocarditis
Clinical Features:
Extracardiac - septic embloism: ischemic changes can occur anywhere even in the brain causing stroke.
CNS: infraction, brain abscess
Renal: proteinuria, hematuria, pyuria
PHx - Stigmata of SBE:
Janeway lesions:Non-tender, flat lesions on palms and soles.
Osler’s nodes: Tender, raised nodules on fingers and toes.
Roth’s spots: Exudative lesions of the retina.
Splinter hemorrhages: Non-blanching, linear, under nails.
Splenomegaly

28. Infective Endocarditis
Labs:
Blood cultures are the most important lab test
Three blood cultures collected over a 24-h period from different sites at different times. Because if only one of the cultures is positive it could be contamination.
CBC:
Anemia
Elevated ESR/CRP
Positive rheumatoid factor

29. Infective Endocarditis
Treatment:
Supportive medical therapy
Prolonged antibiotic therapy
Initially empiric broad spectrum Abx which then adjusted according to organism sensitivity. Admit for I.V Abx with a combination of two or three drugs.
4-8 weeks course depending on the type of organism and resistance.
Removal of infected line
Surgical intervention: may be required

30. Infective Endocarditis
SBE prophylaxis:
Only indicated at dental procedures or respiratory procedure (not for gynecological procedures anymore) for high risk patients
No longer recommended for GI or GU procedures
Prophylaxis regimens:
Oral amoxicillin 50 mg/kg (up to 2 g) OR
IV/IM ampicillin 50 mg/kg
Patients allergic to penicillin
Cephalexin 50 mg/kg PO (up to 2 g) OR
Clindamycin 20 mg/kg (up to 600 mg) OR
Azithromycin (or clarithromycin) 15 mg/kg (up to 500 mg)

31. Infective Endocarditis
SBE prophylaxis
Prosthetic cardiac valve
Previous IE
Congenital heart disease
Unrepaired cyanotic CHD, including those with palliative shunts and conduits
Repaired CHD with prosthetic material or device (surgery or cath), during the first 6 months after the procedure
Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device
Cardiac transplantation recipients with cardiac valvulopathy

32. Myocarditis
Inflammatory infiltrate of the myocardium with necrosis/degeneration of the myocytes
Viral infections: most common causes in order:
Coxsackievirus type B
Adenovirus
Parvovirus B19
Others: CMV, EBV, HIV, Hep C
Other infectious causes: bacteria, rickettsiae, protozoa.
Non-infectious causes:
Rheumatologic disease: SLE, rheumatoid arthritis
Drugs and Toxins: chemotherapy

33. Myocarditis Variable initial presentation
Viral prodrome: fever, URTI or GI symptoms precede the S/S of HF by 3 weeks.
Hx: lethargy, poor feeding, irritability, respiratory distress, exercise intolerance
PHx:
Signs of CHF
Tachycardia
Tachypnia (increase work of breathing)
Gallop rhythm and murmur of mitral regurgitation
Hepatomegaly

34. Myocarditis Investigation: CXR: ECG: Echo: Cardiomegaly
Pulmonary congestion
ECG:
Sinus tachycardia
Low voltage QRS
Non-specific T wave changes
Echo:
Dilated LV with reduced systolic function MR
Pericardial effusion

35. Myocarditis Investigation: Treatment: Myocardial biopsy:
Historically used to be the gold standard test
Currently not routinely performed
Invasive
low sensitivity of the procedure (3–63%)
patchy involvement of the myocardium
Treatment:
Cardio-respiratory Support:
Inotropes, Ventilation, ECMO
Anti-CHF therapy
IVIG and Steroid – not supporting evidence for their benefit
Antiviral agents and interferon – need further studies.

36. Cardiomyopathy
Cardiomyopathy: myocardial disease resulting in thickening of myocardial fibers or fibrosis.
Pediatric cardiomyopathy: almost exclusively non- ischemic
Types:
Dilated cardiomyopathy (58%) the commonest, must rule out arrhythmia.
Hypertrophic cardiomyopathy (30%) syncope while exercising might lead to sudden cardiac death in athletics because of ventricular tachycardia progressing to ventricular fibrillation.
Restrictive cardiomyopathy (5%)
Arrhythmogenic Right Ventricular Cardiomyopathy ARVC (5%)