Management of Cardioembolic syndrome

1. CARDIOEMBOLIC STROKE;
THE BURDEN AND IMPACT OF
RHEUMATIC VALVULAR HEART
DISEASE
DEPARTMENT OF MEDICINE
LAUTECH TEACHING HOSPITAL
DR SOPE TOPE ORUGUN

2. Outline
 Stroke
 Introduction
 Epidemiology
 Types of stroke
 Cardioembolic stroke
 Rheumatic fever
 Pathophysiology
 Rheumatic Valvular heart disease

3. Outline
 Clinical presentation
 Complications
 Differential diagnosis
 Management
 Conclusion
 References

4. Introduction
 Stroke is defined as sudden onset
of focal or global neurological
deficit lasting more than 24hours
with no other apparent cause
apart from a vascular one.

5. Epidemiology
 Stroke is the leading cause of adult disability
 The 2nd leading cause of death; 6.5million in 2013
 Up to 1million persons worldwide have an episode per year
 750,000 incident cases in the US yearly, likely more in developing
countries
 30% stroke affected workers proceed to lose their jobs because
of disabilities.

6. Epidemiology
 The risk of stroke doubles with each decade after 55yrs
 Blacks & Hispanics are twice at risk as whites
 Men stand 40% higher chance of stroke than women worldwide
 Hypertension increases risk 4folds
 Smoking doubles the risk
 On the average, someone in the US has stroke every 40secs and,
someone dies from stroke every 4mins

7. Epidemiology
KW Wahab reported 1.14/1000 cases incident rate in
hospital admission at UITH, Ilorin in 2008
Also, a 30day case fatality may be upto 40%.
Corroborated in 2015 by MA komolafe et al
Men are almost twice as affected as women before age
65, thereafter women predominate in NIgeria

8. Statistics
Type of stroke Percentage
Atherothrombotic 44%
Ischemic
84%
Cardioembolic 21%
Small vessel disease 19%
Intrcerebral
haemorrhage
10% Haemorrhagic
16%
Subarachnoid 6%
100%

9. Cardioembolic stroke
 Embolism is the primary mechanism of stroke due to
heart diseases.
 Thrombi form in the cardiac chambers and detach, and
get dislodged downstream.
 If the thrombus lyses quickly, Transient Ischemic Attack
may occur.
 Longer staying thrombus causes stroke
 Embolic stroke tends to be sudden in onset with
maximal neurologic deficit all at once

10. Cardioembolic stroke
 Middle cerebral Artery(MCA) and Posterior Cerebral
artery(PCA) are more affected then anterior cerebral
artery
 MCA infarcts are usually extensive,
 Branches 3-4mm wide, if occluded lead to cortical and
white matter infarcts
 Location and extent of infarct depends on collateral
circulation

11. Cardioembolic Stroke
 Mechnism of Cardioembolic stroke can be subsclassified:
a. Mural Emboli
b. Valvular heart disease
c. Arrhythmia
d. Paradoxical emboli
e. Septic Emboli

12. Cardioembolic Stroke
 Causes:
 Non rheumatic nonvalvular atrial fibrillation is
commonest cause worldwide
 Myocardial infarction(MI)
 Prosthetic valves
 Rheumatic valvular heart disease
 Ischaemic Cardiomyopathy

13. Cardioembolic Stroke
 Presumed mechanism in Atrial fibrillation are:
 Thrombus formation in fibrillating atrium
 Atrial appendage detachment embolization
 Average risk of stroke is 5%
 CHADSVasc Score

14. Cardioembolic stroke
 RVHD causes stroke when there is either prominent
mitral stenosis or atrial fibrillation
 MI especially if transmural and anteroapical
predisposes to thrombus formation
 Prophylactic anticoagulation has shown benefit in
stroke prevention.

15. Cardioembolic stroke
 Paradoxical emboli
 Arterial presence of a venous thrombus
 Due to any of these:
 patent foramen ovale
 ASD
 Pulmonary AV malformations

16. Circle of Willis

17.  The link between Cardioembolic stroke and RHD is
important in this presentation, though being relatively
not as common as other causes, it may contribute to
early onset incapacitation of patients and increase
both morbidity and mortality.

18. Rheumatic heart disease
(RHD)
 Rheumatic heart disease is a chronic autoimmune
inflammation of the heart structures especially the valves ,
following group A streptococcal infection which leads to
fibrosis and stenosis of the valves +/- regurgitations.
 It is a chronic sequelae of Acute rheumatic fever

19. RHD
 Rheumatic fever(RF) is an inflammatory disease that occurs as a
delayed non suppurative sequelae of upper respiratory tract infection
with group A streptococci.
 In its classic form, the disorder is acute, febrile and largely self
limiting.
 Damage to heart valves may however be chronic, progressive and
cause cardiac disability or death years down the line.

20. RHD
 One of the major causes of cardioembolic stroke is
Rheumatic heart disease (RHD)
 20% of stroke is due to cardioembolic origin, valvular
pathology contribute importantly to this, predisposing
to clot formation
 RHD accounts for a small percentage of this

21. Rheumatic Heart Disease
 Rheumatic heart disease is a chronic complication of
Rheumatic fever.
 In the acute phase, there is inflammation of all layers
of the heart; pancarditis.
 However there is a residual chronic sequelae of
valvular and endocardial fibrosis and stenosis.
 Regurgitation may be present

22. Epidemiology
 30 million cases worldwide in 2015
 2.4million are children
 Highest incidence of Rheumatic fever is between age
5-25.
 Commoner in developing countries & marginalized
communities of developed countries.
 Varies from 15.2 cases/100000 in Fiji to 1 case/100000
in USA
 Rheumatic fever was the commnest indication for
valvular replacement before advent of adequate
prophylactic method

23. Epidemiology
 Estimated 11.5 million disability adjusted life years lost
 305,000 deaths are due to RHD/ year
 Africa, SEA, Pacific Islanders account for 84% of
prevalence.
 Females are twice as affected as males
 Females account for 2/3 of hospitalized cases in 12
countries including India, Yemen, Africa

24. Epidemiology
 In 2010, economic loss due to RHD is
 $2200 billion (discounted)
 $5400 billion (undiscounted)
 Although, Africa has 10% of world population, it has
up to 50% of world RHD cases.

25. Pathogenesis of RF
 Organism factor
 Host factor
 Immune response

26. Pathogenesis
 A. ORGANISM FACTOR
 The development of RF, and RHD, requires an antecedent history
of infection of Group A Beta hemolytic streptococci ( GABHS)
 Noteworthy is the fact that Cutaneous streptococcal infection
causing post streptococcal GN which was initially not thought to
cause RVHD, actually do – In aborigines in native Australasia

27. Pathogenesis
 GABHS
 Group A streptococci are pure human pathogens
a) Natural streptococcal infection in animals is rare
b) Lab animals are not models for human streptococcal infection e.g
scarlet fever, erysipelas,
c) A much higher dose of inoculum is needed to cause animal
infections
 All group A streptococcal infection have highest incidence in
children lower than 10yrs

28. RF
 Streptococcal Toxins
a) Capsule
b) Cell wall
c) M proteins
d) Streptolysin O
e) Streptolysin S
f) DNAse A-D
g) Pyrogenic exotoxins
h) Nicotine Adenine Dinucleotidase

29. Rheumatic fever
 Suppurative
1. Pharyngitis
2. Scarlet fever
3. Erysipelas
4. Streptococcal pyoderma
5. Cellulitis
6. Lymphangiitis
7. Necrotizing fasciitis
8. Myositis
9. Pneumonia
10. Toxic shock syndrome

30. RHD
 Non suppurative
 Rheumatic fever
 Post streptococcal GN

31. Pathogenesis
 B. HOST FACTORS
 About 3% of population is susceptible to RF
 Concordance among mono zygote twin shows
inherited susceptibility
 HLA 2 is associated with susceptibility
 Associations with mannose binding lectine &
polymorphism of TGF Beta 1 & Ig genes


32. Pathogenesis
 C. IMMUNE RESPONSE
 The basis is an autoimmune reaction in susceptible
hosts
 Damage result from cross reaction between epitopes
of bost and organism
 M proteins & Streptococcal N Acetyl glucosamine are
immunologically similar to molecules in human
 myosin, tropomysin, keratin, actin, laminin, vimentin &
N acetyl glucosamine.

33. Pathogenesis
 Cross reacting antibodies attach at the cardiac valve
endothelium.
 This allows entry of primed CD4+ lymphocytes.
 This leads to T Cell Mediated inflammation

34. Pathophysiology
 Rheumatic fever , non suppurative complication of pharyngitis
caused by GABHS
 Rheumatic heart disease is a Chronic sequelae
 It usually occurs after repeated bouts of acute illness
 The risk of developing ARF after an acute episode of GABHS
infection is said to be 0.3 – 3%
 However, 60% of those with ARF develop RHD

35. Pathophysiology
 ARF is a multisystemic disease.
 Affects the Skin, joints, CNS,
 Usually Acute rheumatic fever starts 1-3wks after
pharyngitis.
 It has an average period of 20-40years before
development of Chronic Cardiac complications.
 A history of Rheumatic Fever is positive in 60% of pure
mitral stenosis

36. Pathophysiology
 It is an interplay of several factors.
 Cellular immunity {Thelper 1 cells}
 Humoral mediated immunity
 Molecular mimicry
 Genetic predisposition - HLA DR (familial studies)
 The inflammation generated persists beyond the acute infection and
lead to the picture seen in ARF

37. Pathophysiology
Direct toxic effect theory
The antigen/ antibody complex formed after infection
with GABHS are in excess of what is needed and are thus
deposited on tissues in the body causing a direct toxic
effect in the valves and Glomeruli especially.

38. Pathophysiology
 TCell responsive to Streptococcal M protein invade the
valve through the valvular endothelium
 Antistreptococcal Carbohydrate stimulates T cell to
release TNF & Interleukins
 Thelper 17 associated cytokines are increased in RHD

39. Pathophysiology
 Streptococcal antigens display molecular mimicry
recognized by the human immune system.
 M protein of GABHS mimics Cardiac Myosin & Valvular
Endothelium

40. Pathophysiology
 The mitral valve is most affected, then- aortic, tricuspid &
Pulmonary
 Mitral valve(MV) regurgitation is usually accompanied
with 1 or more other valves
 It is said that in almost all acquired cases of MV stenosis,
RHD is the cause
 It is on the downward trend in developed countries

41. Pathophysiology
Cell wall components - peptidoglycan, lipotechoic
backbone interact with host immunity.
M proteins A-D
Inhibit phagocytosis by leucocytes
B& C region camouflage the bacteria against
opsonization

42. Pathophysiology
Streptolysin O
A thiol activated cytolysin inhibited by Antibodies &
Cholesterol.
Capsule
Binds epithelial CD 44 and acts as antiphagocytic.

43. Figure 1

44. Clinical presentation
 History of
 Recurrent throat infection, usually untreated
 High Fever. Usually >39oC
 Malaise
 Chest or abdominal pain

45. Clinical presentation
 Examination:
 Fever
 Pedal edema
 Pulmonary Congestion
 Tachycardia
 Cardiac murmurs
 S3
 Loud pulmonary component of 2nd heart sound
 Paresis or paralysis

46. Revised Jones criteria
 Major Criteria
 Migratory polyarthritis 70%
 Carditis 50- 60%
 Syndeham Chorea < 15%
 Subcutaneous Nodules rare in adults
 Erythema Marginatum

47. Revised Jones Criteria
 Minor Criteria
Clinical
 Fever >38.5
 Polyarthralgia(not considered if polyarthritis is a major
criterion)
Laboratory
 Elevated ESR or WBCC
 ECG: prolonged PR interval

48. Revised Jones Criteria
 Supporting evidence of past GABHS infection
 A positive throat culture
 Rapid antigen testfor group A
 Recent scarlet fever

49. Diagnostic criteria
 1 major and 2 minor with evidence of GABSH
 2 major criteria
 2 minor criteria + previous throat infection with
GABHS
 Patients presenting for the 1st time with Pure mitral
valve stenosis or mixed mitral valve disease and or
aortic disease.
 They donot require any other criteria for diagnosis of
RHD

50. Differential diagnosis of RHD
 Gonococcal arthritis
 Juvenile idiopathic Arthritis
 Lyme’s disease
 Mixed connective tissue disorder
 SLE
 Reactive Arthritis
 Rheumatoid arthritis
 Septic Arthritis

51. Complications
 Cardiac involvements are most serious in ARF
 60% of patients develop carditis in ARF
 Add to prevalence rate of RHD of 15million world
wide
 RHD predisposes to further cardiac damage with
subsequent bouts of infection
 There is need for Secondary prophylaxis

52. Complications
 Cardioembolic Stroke
 Infective Endocarditis
 Acute Pulmonary Edema
 Cardiac failure
 Death 1.5% of all patients annually
 Increased Perinatal mortality
 Cole & Adeleye et al 1982 revealed most of these
complications especially in Pregnancy women are due to
poor socioeconomic & healthcare facilities

53. Investigations
 No single Laboratory result can diagnose RHD without
positive history
 ESR or CRP are elevated, at times markedly
 They useful in monitoring disease but sensitivity is poor
 Throat culture – it is criterion standard for diagnosis of GABHS
 Note that rapid antigen detection are not sensitive, but
specific

54. Investigations
 ASO – elevated ASO shows previous or ingoing infection,
higher post pharyngitis than after skin infection
 Blood culture may help rule out infective endocarditis,
bacteremia and disseminated gonococcal infection

55. Imaging studies
 Echocardiography:
a) Valvular stenosis commonly Mitral()
b) Thickening of the valves
c) Calcification of valves and subvalvular apparatus
d) Regurgitations
e) Involvement if aortic valve may accompany but rarely
presents alone

56. Echocardiography

57. Echocardiography

58. Echocardiography
 video

59. Echocardiographic criteria

60. ECG
 ECG
 May show prolonged PR interval
 AV block
 Repeat in 2 weeks and 2 months if prolonged PR
interval


61. Gross findings
 Acute phase;
a) Small verrucuous endocarditis
b) Small uniformly sized thrombi with no vlave destruction
 Chronic state:
a) Commisural fusion
b) Valve thickening
c) Shortened, fused subvalvular chorda – ‘fish mouth deformity’
d) Affectation of Mitral and aortic valves mostly

63. Gross findings
 Post rheumatic valve disease is generally diagnosed at surgery
 Aortic stenosis is usually caused by degenerative calcific disease
50% of which is due to bicuspid aortic valve
 Nodular calcific stenosis with calcific deposit in sinus of vasalva
sparing the free edges
 Post rheumatic stenosis involves the edges, commisures and leaflets

64. Gross findings
 Post rheumatic Mitral insufficiency
 Closely related to mitral prolapse but differentiated by
 Has Chordal fusion, thickening and shortening

65. Immunochemistry
 Presence of CD 4 and CD 8 in T cell subsets in Acute rheumatic
fever valves
 Major histocompatibility complex 2 (MHC-2) antigens are
expressed in blood vessel endothelial cells and fibroblasts

66. Other investigations
 Blood culture: if febrile
 Serology
 CXR

67. Microscopy
 Vegetations in ARF shows surface thrombi, lack of
underlying valve destruction and mild edema,
 Chronic RVHD shows neovascularization, chronic
inflammation and calcification. Her calcium is deposited in
the leaflet itself as opposed to annular calcification

68. Microscopy
 Aschoff nodules are considered pathognomonic of
post rheumatic heart disease.
 Interstitial fibroinflammatory lesions with
macrophages, and collagen necrosis

69. Management
 Primary prevention
 Secondary prevention
 Tertiary Prevention

70. Primary prevention

71. Management
 1° prevention involves removal of of all factors that predispose to
streptococcal infection
 Personal hygiene
 Environmental Sanitation
 Prevention of overcrowding
 Governmental policies that favour reduction in the incidence of
RVHD
 These are very difficult in developing countries where RF is common.

72. Management
 Mainstay is thus Prophylaxis
 Timely and complete treatment of streptococcal
infection
 Requires:
a) Prompt presentation of patients to health facility
b) Availability of trained medical staff & microbiologist
c) Material for throat sab and culture
d) Reliable supply of penicillin

73. Primary prevention of RF
Penicillins
Penicillin V Children >27kg: 250mg b.d
<27kg: 500mg b.d or tds
oral 10days
Amoxicillin 50mg/kg dly, maximum of n1gm oral 10days
Penicillin G <27kg, 600000IU
>27kg, 1200000
IM once
Individuals with Penicillin allergy
Azithromycin 12mg/kg, max 500mg Oral 5dys
Cephalexin/Cefadroxi
l
Variable oral 10days
Clindamycin 20mg/kg/dy in 3 divided doses,
maximum if 1.8g
Oral 10days
Clarithromycin 15mg/kg/dy divide b.d Oral 10days

74. Secondary
prevention

75. Secondary prevention
 It’s the mainstay of RF and RVHD
 There is an n exponential increase in predilection for ARF in
patients with ARF after episode GABHS infection
 Benzathine penicillin is best antibiotic for prophylaxis
 1.2million units or 600000units in < 27kg 2-4wkly
 Oral penicillin V is less effective, 250mg b.d
 Erythromycin 250mg b.d in penicillin allergy

76. Secondary prevention
 Oral Sulfadiazine
 Children:
 0.5gm daily <27kg
 1gm in >27kg

77. AHA recommendation for
duration of 2o prophylaxis
Category of patients Duration
RF without carditis 5years after last attack or 21years,
whichever is longer
RF with carditis but no residual
valvular disease
10years after last attack or 21 years
whichever is longer
RF with persistent valvular disease,
evident clinically or on Echo
For 10years after last attack or
40years of age, whichever is longer .
Prophylaxis may be life long at times.

78. Tertiary Prevention

79. Management of
Complications
Major complications include
Stroke
Principle of management
1. ABCs of resuscitation
2. Optimize Cerebral Circulation in penumbra
3. Investigation: Cranial CT, ECG, Echo
4. Prevent comorbidities - infection, pneumonia, bedsores

80. Management
4. Monitor the orifices
5. Treat modifiable risk factors
6. Thrombolysis – within 3hours of Ischaemic stroke, IV rtPA 0.9mg/kg, up to
90mg maximum
7. Antiplatelets- Aspirin 300mg
Neuroprotection
8. Physiotherapy
9. Rehabilitation & Social integration

81. Management
 Heart failure
 Principle of management
 Reduce preload
 Reduce afterload
 Increase cardiomyocyte contractility
 Reduce salt and water retention
 Treat other comorbidities
 Interventional techniques eg intraortic balloon, ICD,
cardiac resynchronization.

82. Surgical intervention
 Percutaneous ball Valvuloplasty/ Percutaneous mitral
commisurotomy
 Surgical valvotomy/ valve replacement
 Balloon expandable valve implantation
 Open commisurectomy
 Prosthetic valvular replacement

83. AHA algorithm for Valvular
disease

84. Prognosis
 Runs a variable course especially with valvular lesions
 Reparability of valves is inconsistent
 Subvalvular apparatus repair has better prognosis than
valvular lesions
 The lower the degree of fibrosis of subvalvular
apparatus the btter the prognosis
 Prognosis is worse with pulmonary hypertension

85. Conclusion
 The impact of RVHD is felt by some but is the burden
of all. More effort obviously needs be put in to rid the
health landscape of this menace; this is economically
beneficial and aesthetically a feet at par with
international best practice.

86. THANK YOU FOR YOUR
ATTENTION
GOD BLESS

87. References
 71st WHO General AssemblyWHO provisional item, April 2018
 Pathophysiology of Rheumatic Fever, Allen Burke, April 2016
 Changes in Th17 associated cytokine expression in Rheumatic
heart disease. Cardiovasc Pathology. July 2015, Wen Y, Zeng z
et al
 Komolafe M A, Olaogu M, Adebiyi A M, Obembe A O, Fawale
M B, Adebowale A A. Stroke risk factors among participants of
a world stroke day awareness program in South-Western
Nigeria. Niger J Clin Pract 2015;18:807-9

88. References
 23rd edition, Cecil Medicine, Chapter 312, pages 2178-
2189
 World heart federation guideline on treayment of
valvular heart diseases