Rheumatic fever, Rheumatic heart

disease, Infective endocarditis

Dr Uwanuruochi Kelechukwu
 Rheumatic fever
•Rheumatic fever is an immunologically
mediated (Autoimmune) inflammatory disorder, which
occurs as a sequel to pharyngeal infection by group A
beta hemolytic Strep pyogenes.
• Multisystem disease affecting the heart, joints,
brain, cutaneous and subcutaneous tissues
• Major public health problem in heavily
populated underdeveloped and developing
countries
• Preventable disease
 Rheumatic fever-pathogenesis

•Group A streptococcal(GAS) pharyngeal infection

•Body produce antibodies against streptococci ->
•These antibodies cross react with human tissues
because of the antigenic similarity between
streptococcal components and human connective
tissues (molecular mimicry)
[there are certain amino acid sequences in GAS and human
tissue that are similar]->
•Immunologically mediated inflammation & damage
(autoimmune) to human tissues which have antigenic
similarity with streptococcal components- like heart,
joint, brain connective tissues
Streptococcal cell wall
Streptococcal cell wall
 Some enzymes and hemolysins produced by
Streptococci
• Streptokinase (fibrinolysin)
• Can lyse blood clots and may be responsible for the rapid spread of the
organism.
• Used (IV injection) for treatment of pulmonary emboli, coronary artery
thrombosis and venous thrombosis.
• Streptodornase (DNases A to D)
• Decreases viscosity of DNA suspension. A mixture of this and
streptokinase is used in enzymatic debridement-liquifies exudates and
facilitates removal of pus and necrotic tissue.
• Streptolysin O:
• Causes hemolysis deep in blood agar plates.
• ASO (antistreptolysin O) titer >160-200 units suggests recent infection or
exaggerated immune response to an earlier respiratory infection.
• Similarity btw hyaluronic acid in GAS capsule and in the
connective tissue of the joints, Ab produced against GAS
capsule attack the joints and causes arthritis.
• M-protein in GAS cell wall and the myocardium are
similar, thus Ab produced against GAS cell wall attack
heart
 Diagnosis

• Jones criteria for initial attack of rheumatic fever

• Evidence of preceding streptococcal infection +
• 2 major manifestations
or
one major manifestation and 2 minor
manifestations
• Indicates a high probability of acute rheumatic
fever
• Jones criteria 1944 and updated in 1992
Supporting evidence for antecedent
Group A streptococcal infection
• Positive throat culture(in 25% of patients)
• Rapid streptococcal antigen test
• Elevated or rising streptococcal antibody titre
antispreptolysin O and S, antistreptokinase,
anti-streptohyaluronidase and anti DNAase
• These antibodies ( ASO >300 in children >200
in adults) suggest previous infection
 Jones criteria for initial attack of
rheumatic fever
• Major • Minor manifestations
manifestations Clinical findings-
• Carditis • Arthralgia
• Polyarthritis • Fever
• Chorea Laboratory findings-
• Subcutaneous • Elevated acute phase
nodules reactants
• Erythema • raised ESR
marginatum • raised CRP
• Prolonged P-R interval
 Rheumatic fever-epidemiology
• Incidence –
• 3% in epidemics of exudative streptococcal pharyngitis
in closed community(school,army)
• 0.3% in civilian population with sporadic streptococcal
throat infection
• 50% if there is a past history of rheumatic fever(thus
secondary prophylaxis is important)
• First attack between 5-15 years(a childhood disease)
• Associated with poor socioeconomic conditions and
overcrowding
 CARDITIS (pancarditis)
Clinical evidence –
• Murmur(mitral or aortic regurgitation-endocardium
involved) [stenotic murmur is not found in acute R.F. as it
needs long time to develop]
• Heart failure
• Cardiac enlargement(myocardium involvement)
• Pericardial rub or effusion(pericardium involvement)
Investigations for evidence of carditis
• Chest x-ray – cardiomegaly, pulmonary venous congestion
• ECG- heart block, T wave changes, low voltage QRS
• Echocardiogram – cardiac dilatation, valve involvement,
pericardial effusion
• Arthritis
• Polyarthritis, fleeting, migratory, large joints,
no residual deformity, rapid response to
aspirin
• Chorea
• Spasmodic, unintentional, jerky choreiform
movements, speech affected, fidgety, late
manifestation(thus no ESR or ASO titre
elevation)
 .
• Subcutaneous nodule
• Painless, hard nodules beneath skin, over
bony prominence, tendons and joints
• Erythema marginatum(rash)
• Erythematous, ring or crescent shaped,
transient patches over trunk and limbs
 Treatment

• Bed rest 2-6 weeks(till inflammation subsided)

• Supportive therapy- treatment of heart failure
• Anti-streptococcal therapy-
i.m. Benzathine penicillin 1.2 million units once
or i.m Procaine penicillin 600000
units dly x10days or Tab
Phenoxymethyl pen/Pen V 250mg qds x10 days.
If allergic to penicillin erythromycin 500 mg tds
x10 days (antibiotic is given even if throat culture is
negative)
• Anti-inflammatory agents-
Aspirin 1 g qds for arthritis and in the absence of carditis-
Continue till ESR is normal, then taper off over for 4-6
weeks
• Corticosteroids in presence of carditis – 60-120 mg/day
(spread qds), until ESR normal, taper off over 2 weeks.
Secondary prevention – prevention of
recurrent attacks
• Benzathine penicillin G 1.2 million units IM
every 3 weeks
• Or Penicillin V 250 mg twice daily orally
• Or Sulfadiazine 1 g daily orally
• If allergic to both – Erythromycin 250 mg
twice daily orally
 Duration of secondary rheumatic
fever prophylaxis
• Rheumatic fever + carditis + persistent valve
disease- 10 years since last episode or until 40
years of age, sometimes life long
• Rheumatic fever + carditis + no valvar disease –
10 years or well into adulthood whichever is
longer
• Rheumatic fever without carditis- 5 years or until
21 years whichever is longer
• (Continous prophylaxis is important since patient
may have asymptomatic GAS infection)
 Prognosis
• Prognosis is good if recurrence is prevented by
continuous antibiotic prophylaxis- particularly if
no carditis in the initial attack
• If carditis, half of them can develop chronic
rheumatic heart disease.
• For development of RHD, it takes 10-20 years.
• Mitral valve is most commonly affected, followed
by aortic and tricuspid valves
• The patients need long term follow up
 Case history
• A 13 year old girl was brought with complaints of
abnormal jerky movements of the limbs of 4 days
duration. She denied any history of fever or joint pains
and swelling. She had a history of frequent sore throats
in the past. On examination she had normal findings in
cardiovascular system.
 Case history
• A 14 year old boy was brought with complaints of fever
and breathlessness of 6 days duration. He gave a history
of joint pains involving both knees one week before the
onset of the illness. On questioning he gave a history of
sore throat 4 weeks ago for which he had taken some
medication. On examination he had no signs of
inflammation in the jointsAuscultation of the heart
revealed pan systolic murmur at the apexand early
diastolic murmur along the left sternal borderJVP was
elevatedand he had tachypnea
 Case history

• A 12 year old girl was brought with complaints of

fever and joint pains of 5 days duration. She had
pain and swelling of left knee and this subsided
and she developed pain and swelling of right
ankle and elbow. She had a history of sore throat
3 weeks ago and it subsided without treatment.
On examination she had signs of inflammation in
the above joints. Heart was normal on
examination.
 Infective endocarditis (IE)
• Defination
• Infective endocarditis (IE) is defined as an
infection of the endocardial surface of the
heart, primarily of 1 or more heart valves, the
mural endocardium, or a septal defect.
 RISK FACTORS
• Valvular heart disease – MR with degenerative MVP,
followed by AR.
• Congenital heart disease – most common is VSD.
• Prosthetic valves, Cardiovascular implantable electronic
devices -CIED(pacemakers)
• Chronic rheumatic heart disease
• IV drug use
• Chronic IV access, Hisory of invasive dental procedures.
• Diabetes, alcoholism, Chronic liver disease, HIV/AIDS
• Malignancy, renal failure on hemodialysis.
• Poor oral hygiene
 CLASSIFICATION
According to temporal evolution of disease,
a) Acute
b) Subacute
According to location of infection
a) Native valve endocarditis
b) Prosthetic valve endocarditis
c) Device related endocarditis
d) Right sided endocarditis
Acute Endocarditis –
• Develops over a period of days, rapidly damages cardiac structures and
seeds extracardiac sites.
• Presents as high grade fever, fatigue and tachycardia.
• Usually caused by S. aureus, Beta hemolytic streptococci and
Pneumococci .

Subacute Endocarditis –
• Develops over week to months.
• Indolent course
• Damages cardiac structures slowly. Rarely metastasizes.
• Presents with vague constitutional symptoms.
• Usually caused by Viridans streptococci, Enterococci, Coagulase negative
Staph and the HACEK (Haemophilus, Aggregatibacter (previously
Actinobacillus), Cardiobacterium, Eikenella, Kingella)group.
 Native valve endocarditis (NVE) –
• Acute NVE frequently involves normal valves.
Virulent organisms such as S aureus and group B
streptococci, are typically the causative agents of
this type of endocarditis.
• Subacute NVE typically affects only abnormal
valves. Alpha-hemolytic streptococci or
enterococci are usual causative
• Health care associated NVE usually caused by S.
aureus, Coagulase negative Staph. and
Enterococci
Etiology
 Prosthetic Valve Endocarditis (PVE) –
• Between 16 to 30 % of all cases of
endocarditis occur in prosthetic valves.
• Risk of infection highest in first 6 to 12 months
of valve replacement.
• Early PVE if occurring within 1 year and late
PVE if occurring 1 year.
• Early PVE caused by S. aureus and Coagulase
negative Staph.
• Late PVE caused by same organisms as NVE.
 Device – related Endocarditis
• IE related to Cardiovascular Implantable
Electronic Devices involves the device or the
endothelium point of device contact.
• Mostly caused by S. aureus and CoNS.
• Risk factors are Renal failure, DM, hematoma
at the site of implantation
 Right – sided Endocarditis
• Mostly associated with IV drug use.
• S. aureus is the most common causative
organism.
• Tricuspid valve is most commonly affected.
• Pulmonary valve may also be involved
 ORGANISMS causing IE
• Over 3/4 cases - Streptococci or Staphylococci
• S. aureus-most common cause of Acute BE
(Cause 31% of cases)
highly virulent and invasive organism -
Acute presentation. –skin infections, abscesses or
vascular access sites (e.g. intravenous and central
lines) Often acquired ff procedures that break
skin integrity. Cause both NVE and PVE.
• Coagulase negative staphylococci – Mostly in
prosthetic valve. Subacute presentation
 ORGANISMS causing IE
• •Streptococci -Cause most cases of SABE, –Commensal in
Upper respiratory tract –chewing or teeth-brushing, or
dental treatment,
• –viridans group (Strep. mitis, Strep. sanguis) and Strep.
pneumoniae and Strep. pyogenes
• Streptococcus viridans – second most common. Include S
oralis, S sanguis, etc. Mainly inhabit oral cavity, enter
bloodstream following dental surgical procedures. Cause
native valve infection in RHD pts
• Beta Hemolytic Streptococci – Acute presentation.
Frequent complications.
• Streptococcus gallolyticus - <10% cases of IE
• Strep bovis
 ORGANISMS causing IE
• Enterococcus –third most common. Follows CV
catheter use. Multi drug resistance.
• Aerobic gram –ve bacilli – E. coli, Klebsiella,
Enterobacter, Pseudomonas
• Atypical organisms – Coxiella, Bartonella, Brucella,
T.whipelli, Legionella
• HACEK group – rare causes. Live on dental gums.
Subacute presentation. Large vegetation.
• Fungi – Candida albicans is most common organism.
Associated with IV drug use, prosthetic valves and
immunocompromised patients. -follows IV drug use
and in prosthetic valve. Often fatal. Surgery needed.
 PATHOGENESIS
• When the infection is established, vegetations composed of
organisms, fibrin and platelets grow and may become large
enough to cause obstruction or embolism
• Typically occurs at sites of preexisting endocardial damage
(As damaged endocardial sites - attract deposits of platelets
and fibrin – colonization by blood borne organism
• May occur in normal heart as well
• –particularly caused by virulent or aggressive organisms
(e.g. Staphylococcus aureus)
• –Areas receiving high pressure jet of blood- more prone to
injury
• Avascular valve tissue - protect proliferating organisms
from host defense mechanism
 PATHOGENESIS
• Organisms enter bloodstream from skin, mucosal
surfaces or focal sites of infection.
• Organisms express surface adhesins that mediate
adherence to damaged endothelium. Non-bacterial
thrombotic endocarditis
• Adhesins are – Fibronectin binding proteins, clumping
factor in S. aureus, Fibrinogen binding surface proteins
(Fss2), Collagen binding protein in Enterococcus,
Glucans or FimA on streptococci.
• Prototypic lesion is the Vegetation which is a mass of
platelet, fibrin, microcolonies of organism and scant
inflammatory cells.
PATHOGENESIS OF INFECTIVE
ENDOCARDITIS
• Underlying valvular or non valvular structural
abnormality
• Blood flow turbulence and endothelial damage
• Fibrin deposition and thrombus formation (Non-
bacterial thrombotic endocarditis)
• Bacterial growth in thrombus and formation of dense
microcolonies
• Microorganisms induce further platelet deposition by
eliciting tissue factor
• Fibrin deposition, platelet aggregation and
microorganism proliferation together form infected
vegetation
 CLINICAL MANIFESTATIONS
• SYMPTOMS
• Fever – most common symptom but maybe absent in up to
20% cases.
• Constitutional symptoms like chills, night sweats,
headache,
• malaise, nausea, myalgia, arthralgia.
• Dyspnea if present is indicative of a severe hemodynamic
lesion probably a left sided valvular regurgitation.
• Orthopnea/ PND indicate onset of heart failure.
• Pleuritic chest pain may occur due to septic embolization
and infarction complicating tricuspid valve IE.
 CLINICAL MANIFESTATIONS
• SIGNS
• Murmurs – Occur in less than half of the
patients. New or worsened regurgitant
murmur occurs.
• Splenomegaly
• Clubbing may be seen
• Peripheral manifestations like Osler ’s node,
subungal hemorrhages, Janeway lesions,
Roth’s spot.
Roth spots
Janeway lesions
 Diagnosis: MODIFIED DUKE CRITERIA
• A highly sensitive and specific diagnostic criteria known as
the Modified Duke Criteria is
• based on clinical, laboratory and echocardioagraphic
findings commonly encountered in patients of IE.
• Definite Endocarditis –
2 major criterion or 1 major + 3 minor criterion or 5 minor
criterion
• Possible IE –
1 major + 1 minor or 3 minor criteria
• Diagnosis of IE rejected if, Alternative diagnosis established,
If symptoms resolve with <4 days of antimicrobial therapy
or If surgery or autopsy reveals no histologic evidence of IE
after <4days of antimicrobial therapy
 MAJOR CRITERIA
1. Blood culture positive
• a. Typical organism (Betα hemolytic streptococcus, Streptococcus bovis ,
HACEK organisms, or community acquired Staphylococcus aureus or
enterococcus without a primary focus) from 2 separate blood cultures Or
• b. Persistent bacteremia with any organism (two positive cultures >12 hr
apart or three positive cultures or a majority of ≥4 cultures positive >1 hr
apart) Or
• c. single positive blood culture for Coxiella burnetii or antiphase 1 IgG
antibody titer >1 : 800
2. Evidence of endocardial involvement on echocardiography.
• Mobile mass attached to valve or valve apparatus, in the path of
regurgitant jets, or on implanted material in the absence of an alternative
anatomic explanation, or
• Abscess, or new partial dehiscence of prosthetic valve or
• New valvular regurgitation
 MINOR CRITERIA
• 1. Predisposing condition: IV drug use or predisposing
cardiac condition
• 2. Fever ≥38° C
• 3. Microbiologic evidence: positive blood cultures not
meeting major criteria or serologic evidence of active
infection consistent with endocarditis
• 4. Immunologic phenomena: glomerulonephritis, Osler
nodes, Roth spots, rheumatoid factor
• 5. Vascular phenomena: arterial embolism, septic
pulmonary emboli, conjunctival hemorrhages,
intracranial hemorrhage, mycotic aneurysm, Janeway
lesions
 Investigations
• Serologic tests for Brucella, Bartonella,
Legionella,
• C.burnetti, C.psittaci.
• PCR tests.
• CBC – Anemia, Leukocytosis
• Microscopic hematuria
• Elevated ESR and CRP
• Circulating Immune complexes
• Decreased complement
 BLOOD CULTURE
• Three 2-bottle blood culture sets , separated
from one another by at least 2 h should be
obtained from different venipuncture sites over
24 h.
• If culture remain negative two or three additional
blood culture sets should be obtained.
• Empirical antimicrobial therapy should be
withheld in suspects of subacute endocarditis till
cultures are obtained.
 ECHOCARDIOGRAPHY
• ECHO confirms and measures vegetation, detects
intracardiac complication and assesses cardiac
function.
TRANSTHORACIC ECHOCARDIOGRAPHY (TTE)
• Non invasive and specific
• can not detect vegetation <2mm in diameter
• Inadequate in emphysema and obese.
• Not optimal for evaluating prosthetic valve or
detecting intracardiac complications.
 ECHOCARDIOGRAPHY
• TRANSESOPHAGEAL ECHOCARDIOGRAPHY (TEE)
• Safe and detects vegetation in >90% with definite
IE.
• Negative TEE does not exclude IE but requires
repetition in 7 – 10 days.
• Optimal for diagnosis of PVE and intracardiac
complications like myocardial abscess, valve
perforation or intracardiac fistulae, and detection
of vegetations in patients with CIED
 Treatment-STAPHYLOCOCCI
MSSA infecting native valves –
• Cefazoline 2 g IV TID for 4 – 6 wks Or
• Vancomycin 15mg/kg IV BD for 4 – 6 wks Or
• Nafcillin, oxacillin or Flucloxacillin 2 g IV 4hrly for 4 – 6 wks
MRSA infecting native valves –
• Vancomycin 15mg/kg IV BD or TID for 4 – 6 wks
MSSA infecting prosthetic valves –
• Nafcillin, oxacillin or Flucloxacillin 2 g IV 4hrly for 6 – 8 wks plus
• Gentamycin 1mg/kg IM or IV TID for 2 wks plus
• Rifampicin 300mg PO TID for 6 – 8 wks
MRSA infecting prosthetic valves –
• Vancomycin 15mg/kg IV BD for 6 – 8 wks plus
• Gentamycin 1mg/kg IM or IV TID for 2 wks plus
• Rifampicin 300mg PO TID for 6 – 8 wks
 STREPTOCOCCI
Penicillin susceptible Streptococci, S. gallolyticus
• Penicillin G 2 – 3 MU IV 4hrly for 4 wks or
• Ceftriaxone 2 g/day as a single dose for 4 wks or
• Vancomycin 15 mg/kg BD for 4 wks Plus
• Gentamycin 3mg/kg IV OD as a single dose for 2 wks
Relatively Penicilllin resistant
• Penicillin G 4 MU IV 4hrly for 4 wks or
• Ceftriaxone 2 g/day as a single dose for 4 wks plus
• Gentamycin 3mg/kg IV OD as a single dose for 2 wks
Moderately Penicillin resistant
• Vancomycin 15 mg/kg BD for 4 wks
• Gentamycin 3mg/kg IV OD as a single dose for 6 wks plus
• Penicillin G 2 – 3 MU IV 4hrly for 6 wks or
• Ceftriaxone 2 g/day as a single dose for 6 wks
ENTEROCOCCI
• Penicillin G 4 – 5 MU IV 4hrly + Gentamycin 1mg/kg IV TID
both for 4 – 6 wks
• Ampicillin 2 g IV 4 hrly + Gentamycin 1mg/kg IV TID both
for 4 – 6 wks
• Vancomycin 15 mg/kg BD + Gentamycin 1mg/kg IV TID both
for 4 – 6 wks
• Ampicillin 2 g IV 4 hrly + Ceftriaxone 2 g IV BD both for 6
wks
HACEK organisms
• Ceftriaxone 2 g/day IV as a single dose for 4 wks
• Ampicillin/sulbactam 3 g IV 6hrly for 4 wks
 SURGERY-Definite Indications for
cardiac surgical interventions
• Moderate to severe CHF due to valve dysfunction
• Partially dehisced unstable prosthetic valve
• Persistent bacteremia despite optimal
antimicrobial therapy
• Lack of effective microbicidal therapy
• S. aureus prosthetic valve endocarditis with
intracardiac complication
• Relapse of prosthetic valve endocarditis
 Surgery considered for improved
outcome
• Perivalvular extension
• Poor responsive S.aureus endocarditis
involving aortic or mitral valve
• Large (>10mm) hypermobile vegetation with
high risk of embolism
• Persistent fever in culture –ve NVE
• Poor responsive endocarditis due to high
antibiotic resistant Enterococci or gram –ve
 Complications of Endocarditis
• Cardiac 33-50%
• Neurologic 25-35%
• Emboli 15-35%
• Metastatic Abscesses <5%
 Complications of Endocarditis
Neurologic Complications
• Acute encephalopathy
• Meningitis
• Embolic stroke
• Cerebral hemorrhage
• Brain abscess
 Complications of Endocarditis
Embolic Phenomena
• Stroke
• Ischemic extremities
• Pulmonary emboli
• Embolic infarction of spinal cord
• Splenic or renal infarction
 Complications of Endocarditis
Metastatic Spread of Infection
• Metastatic abscess – Kidneys, spleen, brain,
soft tissues
• Meningitis and/or encephalitis
• Vertebral osteomyelitis
• Septic arthritis
 Complications of Endocarditis
Local Spread of Infection
• Heart failure – Extensive valvular damage
• Paravalvular abscess (30-40%)
– Most common in aortic valve, IVDA,
and S. aureus
– May extend into adjacent
conduction tissue causing arrythmias
– Higher rates of
embolization and mortality
• Pericarditis
• Fistulous intracardiac connections