Infective endocarditis

1. Endocarditis:
Evaluation and
Management
Rekha Mankad, MD, FACC
Assistant Professor of Medicine
Mayo Clinic College of Medicine
Director, Women’s Heart Clinic
Mayo Clinic, Rochester, MN
mankad.rekha@mayo.edu
@RMankadMD

2. Disclosure Information
Relevant Financial Relationship(s)
None
Off Label Usage
None

3. “The different modes of
onset, and the
extraordinary diversity of
symptoms which may arise,
render it very difficult to
present a satisfactory
clinical picture”
- Sir William Osler, 1885
Infective Endocarditis

4. What is the annual incidence of IE in
contemporary Western cohorts?
1. 5-7/100,000 person years
2. 50-70/100,000 person years
3. 5-7/1000 person years
4. 5-7/10,000 person years
4

5. Epidemiology
• Infective endocarditis (IE) is uncommon
– Annual incidence of 5-7/100,000 person years
• Associated with significant morbidity and mortality
– 3rd most life threatening infection after sepsis/ pneumonia &
intra-abdominal abscess
• Male: Female approximately 2:1
• Age of onset > 60 yo (men 6-7 years older than women)
• Uncommon in children (when occurs typically due to
congenital heart disease)
• Mitral valve > aortic valve >> tricuspid valve
5

6. Major Criteria Minor Criteria
Positive blood culture for IE with
typical organism
Predisposition: predisposing heart condition or
IVDU
Persistently positive blood cultures for
any organism
Fever ≥ 380C
Single positive blood culture for
C.burnetti
Vascular phenomena: arterial embolism, septic
pulmonary infarcts, mycotic aneurysm, ICH,
Janeway lesions
Echocardiogram positive for IE Microbiologic evidence that does not meet major
criteria
Positive blood culture not meeting major criteria
Immunologic phenomena 6
Diagnosis of Infective Endocarditis

7. Positive Echocardiogram
Oscillating intracardiac massor
Abscess or
New partial dehiscence of prosthetic
valve or
New Valvular Regurgitation
Diagnosis of Endocarditis
Duke Criteria
Durak et al. Am J Med 1994;96:200.

8. Diagnosis
Diagnostic Clinical Criteria
8
DEFINITE
2 major criteria
1 major & 3 minor criteria
5 minor criteria
POSSIBLE 1 Major AND 1 minor criteria or 3 minor criteria
REJECTED
Firm alternative diagnosis
Resolution of syndrome ≤ 4 days
No pathologic evidence of IE after ABx for ≤ 4 days

9. Osler’s Nodes: 7-10% of cases

10. Janeway Lesion:10% of IE Cases

11. Echo features of a Vegetation
• Echogenic mobile mass
• Location: atrial side for MV,
ventricular side for AV
• Shaggy, irregular, amorphous
• Intermediate echogenicity: like
the myocardium
• Motion independent of valve
(oscillating)
• Associated tissue deformity,
destruction

12. Risk Factors for Infective Endocarditis
74.6
19.4
13.4
6.7
4.2
1
0 50 100
Adjusted
Odds
Ratio
Dental Treatment
Heart Murmur
Congenital Heart
Disease
Rheumatic Fever
Mitral Valve
Prolapse
Cardiac Valve
Surgery
Adapted from Strom BL et al., Ann Intern Med 1998;129:761-9

13. Endocarditis Prevention
13
Who needs
prophylaxis?
Prior IE
Prosthetic valves
Congenital Heart
Disease
Valvulopathy
after cardiac
transplantation
Unrepaired cyanotic
congenital heart
disease
Completely repaired
CHD with prosthetic
materials placed within
6 months
CHD repair with
residual defects next to
prosthetic materials
Includes TAVR valves
and patients with
prosthetic material
used in valve repair

14. Case
27 year old pregnant woman with cough
• 17 weeks pregnant
• 1-2 weeks of productive cough
–Scant hemoptysis
• ROS: Subjective fevers, dizziness
Courtesy of Dr. Anavekar

15. Case
27 year old pregnant woman with cough
• Vital Signs
• BP 103/67 mmHg, HR 130 bpm, RR 24, Temp 38.90C
• HEENT: JVP mildly elevated
• Resp: Good air intensity bilaterally, scattered areas of
wheeze and crackles
• CV: Tachycardic, regular rhythm, II / VI holosystolic
murmur
• Ext: 1+ pitting edema

16. Case
• Labs: Blood cultures growing S. aureus
–3 of 3 bottles in 8 hours
–Blood work: Hgb 8.0, WBC 17.8, Plt
26K, Sodium 120, Creatinine 0.6

18. What is the most appropriate next
diagnostic step?
1. Cardiac CT
2. Cardiac MRI
3. Transthoracic echocardiogram
4. Transesophageal echocardiogram
5. PET/CT

19. ©2016 MFMER
Imaging in Infective Endocarditis
Imaging
Non cardiac
CT
MRI
Cardiac
Chest x-ray
ECG
Echo
Cardiac CT
PET-CT
?Cardiac MRI?
TTE
TEE
Goal
• Assess cardiac
structure and function
• Assess peri-annular anatomy
• Assess conduction system function
• Coronary anatomy
Assess for
• Mycotic aneurysm
• Stroke
• Intra-abdominal pathology
Goal
Courtesy of Dr. N. Anavekar

20. Echocardiography: Sensitivity
• TTE: 54-83%
–30% for prosthetic valves
• TEE: 95-100%
–77-90% for prosthetic valves
• Specificity: good for both (92-100%)
- Mugge et al, J Am Coll Cardiol 1989
- Aragram et al, in Weyman’s Principles and Practice of Echocardiagraphy, 2nd edition
- Shively et al, J Am Coll Cardiol 1991

21. Sources of Error in Echo Interpretation
• Poor image quality
• Valvular degeneration, calcification,
sclerosis
• Other masses
–Papillomas
–Thrombi
–Myxomatous degeneration
–Healed (old) vegetations
• Small size
• Overzealous interpretation

22. Transthoracic Echocardiography

24. S. aureus Bacteremia
• Must exclude IE via TEE
– Highest sensitivity on days 5-7
• If no other metastatic foci the antibiotic course will be
14 days
• TEE should be repeated at the end of the 2 week
course prior to completing antibiotics
– 10-15% of will have developed IE
Sochowski RA, et al. J Am Coll Cardiol. 1993.

25. Staphylococcus aureus
Bacteremia
• 103 pts Staphylococcus aureus Bacteremia
• All patients had fever and > 1 + blood culture
• DUKE Criteria used for diagnosis
• Death due to sepsis:
15%* with I.E. (*p<0.01)
3% without I.E.
Fowler et al. J Am Coll Cardiol 1997;30:1072

27. Right-sided Infective Endocarditis
• Associated with IV drug abuse or Indwelling
catheters/devices
• Septic pulmonary emboli
– Often multifocal and cavitating
• Right heart failure
– Dyspnea on exertion
– JVD + Lower extremity edema
• Perivalvular extension of infection
– Increased mortality (23%)
– Increased embolic risk (64%)
Omari B, et al. Chest. 1989.
Daniel WG, et al. N Engl J Med. 1991.

28. Case continued
• Hospital day 14 – clinical deterioration
–Low grade fevers
–Rising leukocytosis
–TEE performed
• To assess for progression of cardiac disease

32. IE in Pregnancy - Outcomes
• Maternal morbidity/mortality
– Mortality: 11.5%
• Left-sided > Right-sided
– Septic pulmonary emboli ~20-25%
– CNS emboli ~10-15%
• Fetal Outcomes
– Delivery and survival to discharge 80%
– Intrauterine demise 10-15%
Kebed K, et al. Mayo Clin Proc. 2014.

33. Case
• 55 year old female with fever, chills
• Staph aureus bacteremia
• Systolic murmur
• Started on antibiotics, but within 24 hours had
transient left arm weakness
–No CVA on CT
–No residual neurologic symptoms (left arm
weakness resolved)
• TEE performed

34. Transesophageal
Echocardiogram
2D TEE 3D TEE
(View from Left Atrium)
LA
LV

35. What do you recommend?
1. Immediate mitral valve surgery
2. Continue antibiotics and close observation
3. Anticoagulation
Can Echo help decide based on
size and mobility?

36. Cumulative
Probability
(%)
Vegetation Size (mm)
Sanfilippo JACC 18:1191(1991)
0
10
20
30
40
50
60
70
80
90
100
0 2 4 6 8 10 12 14 16 18 20 22 24
Vegetation Size and Risk
of Embolism

37. TEE in Infective Endocarditis
Incidence of Embolism
0
20
40
60
80
Aortic valve Mitral Valve Prosth valve
Incidence
of
Embolism
(%)
Veg <10mm
Veg >10mm
n = 45 n = 31 n = 25
16
35
67
4
38
52
p = ns
p <0.001
p = ns
Mugge JACC 14:631(1989)

39. 0
10
20
30
40
50
60
70
80
90
Absent <10 10-15 >15
Vegetation size (mm)
Embolic
events
(%)
0
10
20
30
40
50
60
70
80
90
Absent Low Mod Severe
Vegetation mobility
Importance of Vegetation
Size and Mobility
De Salvo G et al. J Am Coll Cardiol 2001;37: 1077-1079.
n = 178

40. Vegetation Size
• 145 patients with endocarditis
• Aortic: 62 (43%) Mitral valve 83 (57%)
• Strokes occurred more often in mitral valve
endocarditis: 33% vs. 11% with aortic
• Independent Predictor of stroke:
• Mitral Valve Vegetation Length > 7 mm
Cabell et al. Am Heart J. 2001;142:75-80

41. Relation of
embolism to
vegetation size
Relation of
embolism to
vegetation size
Embolic events
Embolic events
Di Salvo et al: Positive 37% 9%
JACC, 2001 (>10 mm)
(178 pt)
Di Salvo et al: Positive 37% 9%
JACC, 2001 (>10 mm)
(178 pt)
Cabell et al: Positive 23% 11%
AHJ, 2001 (>7 mm)
(145 pt)
Cabell et al: Positive 23% 11%
AHJ, 2001 (>7 mm)
(145 pt)
Vilacosta et al: Positive 33% 13%
JACC, 2002 (>10 mm)
(211 pt)
Vilacosta et al: Positive 33% 13%
JACC, 2002 (>10 mm)
(211 pt)
Embolism in Infective Endocarditis
Vegetation Size by TEE and Impact of Therapy
Embolism in Infective Endocarditis
Vegetation Size by TEE and Impact of Therapy
On therapy
On therapy
Total
Total
CP1189948-74

42. One Year Survival According to
Vegetation Length
Thuny F et al. Circulation 2005; 112:69-75
n = 384

43. Predictors of 1-Year Mortality
(Cox Multivariable Analysis)
Adjusted RR 95% CI P
Age 1.02 1.01–1.04 0.007
Female sex 1.6 1.01–2.58 0.048
Comorbidity index >2 1.6 0.92–2.64 0.1
Serum creatinine >2 mg/L 1.9 1.16–3.23 0.01
Prosthetic valve 1.6 0.99–2.68 0.053
S aureus IE 2 1.19–3.24 0.001
Moderate or severe CHF 1.6 1.02–1.54 0.04
Vegetation length >15 mm 1.8 1.10–2.82 0.02
Thuny F et al. Circulation 2005; 112:69-75

44. N Engl J Med 2012;366:2466-73

45. Early Surgery for Infective Endocarditis
with Large Vegetations (> 10 mm)
N Engl J Med 2012;366:2466-73
Mortality Composite End-Point
8 vs 0 embolic events

46. Risk of Embolism
• Consider early surgical treatment for:
• Larger vegetations
• Highly mobile vegetations
• Mitral valve location
• Controversial
• Risk diminishes significantly over time with
antibiotics

47. Indications for Intervention in Infective Endocarditis
• Class IIA: Early surgery (during initial hospitalization
before completion of a full therapeutic course of
antibiotics) is reasonable in patients with IE who
present with recurrent emboli and persistent
vegetations despite appropriate antibiotic therapy.
(Level of Evidence: B)
• Class IIb: Early surgery (during initial hospitalization
before completion of a full therapeutic course of
antibiotics) may be considered in patients with native
valve endocarditis who exhibit mobile vegetations
greater than 10 mm in length (with or without clinical
evidence of embolic phenomenon). (Level of
Evidence: B)
2014 AHA/ACC Valve Guidelines, Circulation 2014

48. Timing of Surgery in
Endocarditis After Embolic CVA
–Embolic stroke-wait 7-21 days
–Hemorrhagic stroke- wait 4 weeks
–If headache, think mycotic aneurysm
(avoid valves that need anticoagulation)
Hoen B and Duval X. N Engl J Med 2013;368:1425-33

49. 2017 Focused Valve Update: IE
• Operation without delay may be considered in
patients with IE and an indication for surgery who
have suffered a stroke, but have no evidence of
intracranial hemorrhage or extensive neurological
damage (Class IIb, LOE B-NR).
• If hemodynamically stable, delaying valve surgery for
≥4 weeks may be considered among patients with IE
and major ischemic stroke or intracranial hemorrhage
(Class IIb, LOE B-NR).

50. Complications of Endocarditis Identified
by Echocardiography
• Abscess
• Aneurysm of intervalvular fibrosa
• Fistula
• Perforation
• Other Mechanical Complications Secondary to
Leaflet Destruction
• Hemodynamic
– Most common cause of death is a regurgitant lesion with
CHF (Lerner et al, N Engl J Med 1966)

51. 47 Year Old Male with Fever and Heart
Block
TEE: Large Aortic Root Abscess

52. Peri-Valvular Infection:
Phlegmon

53. Detection of Abscess by Echo
TTE
TEE
0
20
40
60
80
100
Daniel,
n=46
Karalis,
n=24
Blumberg,
n=24
%
Circulation 1992;
86: 353-62
NEJM 1991;
324:795-800
Chest 1995;
107:898-903

54. Case: When to operate in a
patient with an Abscess?
• 57 year old male s/p Medtronic-Hall AVR
• Normal coronary arteries 3 years prior
• Transferred to Mayo Clinic on a Friday with
endocarditis, abscess, and heart block
• Temporary pacemaker in place (screw in lead)
• Hemodynamically Stable
• Surgery planned for Monday

55. Complete Heart Block – Temporary
Pacemaker (screw in lead)

56. TEE
LA
LV
Normally Functioning AVR

57. Extensive Abscess

58. At 3:00 AM on Saturday: Sudden Chest
Pain

59. Emergency Cath: Severe
Compression of Ramus and LAD

60. • Patient being prepped for emergency
surgery
• Suddenly developed hypotension followed
by ventricular fibrillation
• 45 minutes of resuscitation
– Unsuccesful
• Patient died before he could make it to
operating room
When to operate in a
patient with an abscess?
 Urgently !

61. Case
• 68 yo male presented at an outside hospital
with 4 weeks of chills, night sweats, and
fatigue.
–PMH: s/p TAVR 1 year prior, hepatitis C and
alcoholic cirrhosis
–Blood cultures drawn at the outside hospital
were positive for Gemella haemolysans
Courtesy of Dr. J. Thaden

62. Case

63. Case

64. Case
The structure highlighted by
the arrow is:
A. A paravalvular abscess
B. A pseudoaneurysm
C. The transverse sinus
D. An artifact

65. The Transverse Sinus
Netter’s Cardiology, 2010.

66. Case

67. Case
• Echo-guided pericardiocentesis (575 mL)
• 6 weeks of IV antibiotics
• Plans to undergo liver transplant workup prior to
potential aortic valve replacement
• Repeat TEE at 4 weeks…..

68. Case
Repeat TEE at 4 weeks

69. TAVR-related Endocarditis
• Incidence ~1%
• Median time from implantation
5 months
• Risk Factors:
– Younger age
– Male
– Moderate-Severe AR
• Healthcare associated
organisms common:
enterococcus, staph aureus
Regueiro et al. JAMA 2016

70. Survival in Patients with TAVR
Endocarditis
Regueiro et al. JAMA 2016

71. SUMMARY: ECHO and ENDOCARDITIS
Clinically Suspected Endocarditis
Transthoracic Echo
+ Vegetation - Vegetation
No Complications
Antibiotics +
Observation
Any Clinical Instability + Clinical Suspicion
TEE
+ Vegetation - Vegetation
Probably NOT
Endocarditis
Abscess/Perforation
? Large Vegetation
Antibiotics + Surgery
No Complications
Antibiotics +
Observation
Staph aureus bacteremia

72. Thank You!
mankad.rekha@mayo.edu
@RMankadMD