Endocarditis: Evaluation and ManagementRekha 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

Disclosure Information

Relevant Financial Relationship(s)None

Off Label UsageNone

“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

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 years4

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

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

Positive EchocardiogramOscillating intracardiac massor Abscess orNew partial dehiscence of prosthetic

valve orNew Valvular Regurgitation

Diagnosis of EndocarditisDuke Criteria

Durak et al. Am J Med 1994;96:200.

DiagnosisDiagnostic 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

Osler’s Nodes: 7-10% of cases

Janeway Lesion:10% of IE Cases

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

Risk Factors for Infective Endocarditis

74.6

19.4

13.4

6.7

4.2

1

0 50 100

AdjustedOddsRatio

Dental Treatment

Heart Murmur

Congenital HeartDisease

Rheumatic Fever

Mitral ValveProlapse

Cardiac ValveSurgery

Adapted from Strom BL et al., Ann Intern Med 1998;129:761-9

Endocarditis Prevention

13

Who needs prophylaxis?

Prior IE

Prosthetic valves

Congenital Heart Disease

Valvulopathyafter 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

Case27 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

Case27 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 holosystolicmurmur

• Ext: 1+ pitting edema

Case

• Labs: Blood cultures growing S. aureus

–3 of 3 bottles in 8 hours

–Blood work: Hgb 8.0, WBC 17.8, Plt26K, Sodium 120, Creatinine 0.6

What is the most appropriate next diagnostic step?

1. Cardiac CT

2. Cardiac MRI

3. Transthoracic echocardiogram

4. Transesophageal echocardiogram

5. PET/CT

©2016 MFMER

Imaging in Infective Endocarditis

Imaging

Non cardiacCT

MRI

Cardiac

Chest x-ray

ECG

Echo

Cardiac CT

PET-CT

?Cardiac MRI?

TTE

TEE

Goal

• Assess cardiacstructure 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

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

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

Transthoracic Echocardiography

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.

Staphylococcus aureusBacteremia

• 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

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.

Case continued

• Hospital day 14 – clinical deterioration

– Low grade fevers

– Rising leukocytosis

– TEE performed

• To assess for progression of cardiac disease

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.

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

Transesophageal Echocardiogram

2D TEE 3D TEE(View from Left Atrium)

LA

LV

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?

Cu

mu

lati

ve P

rob

ab

ility

(%

)

Vegetation Size (mm)

Sanfilippo JACC 18:1191(1991)

0102030405060708090

100

0 2 4 6 8 10 12 14 16 18 20 22 24

Vegetation Size and Risk of Embolism

TEE in Infective Endocarditis

Incidence of Embolism

0

20

40

60

80

Aortic valve Mitral Valve Prosth valveInci

den

ce o

f Em

bol

ism

(%

) Veg <10mm

Veg >10mm

n = 45 n = 31 n = 25

16

35

67

4

38

52p = ns

p <0.001

p = ns

Mugge JACC 14:631(1989)

0

10

20

30

40

50

60

70

80

90

Absent <10 10-15 >15

Vegetation size (mm)

Em

bo

lic

eve

nts

(%

)

0

10

20

30

40

50

60

70

80

90

Absent Low Mod Severe

Vegetation mobility

Importance of VegetationSize and Mobility

De Salvo G et al. J Am Coll Cardiol 2001;37: 1077-1079.

n = 178

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

Relation of embolism to

vegetation size

Relation of embolism to

vegetation size

Embolic eventsEmbolic 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 EndocarditisVegetation Size by TEE and Impact of Therapy

Embolism in Infective EndocarditisVegetation Size by TEE and Impact of Therapy

On therapyOn therapyTotalTotal

CP1189948-74

One Year Survival According to Vegetation Length

Thuny F et al. Circulation 2005; 112:69-75

n = 384

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

N Engl J Med 2012;366:2466-73

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

Risk of Embolism

• Consider early surgical treatment for:

• Larger vegetations

• Highly mobile vegetations

• Mitral valve location

• Controversial

• Risk diminishes significantly over time with antibiotics

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 vegetationsgreater than 10 mm in length (with or without clinical evidence of embolic phenomenon). (Level of Evidence: B)

2014 AHA/ACC Valve Guidelines, Circulation 2014

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

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).

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)

47 Year Old Male with Fever and Heart Block

TEE: Large Aortic Root Abscess

Peri-Valvular Infection: Phlegmon

Detection of Abscess by Echo

TTETEE

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

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

Complete Heart Block – Temporary Pacemaker (screw in lead)

TEE

LA

LV

Normally Functioning AVR

Extensive Abscess

At 3:00 AM on Saturday: Sudden Chest Pain

Emergency Cath: Severe Compression of Ramus and LAD

• 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 roomWhen to operate in a

patient with an abscess? Urgently !

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

Case

Case

Case

The structure highlighted by the arrow is:

A. A paravalvular abscess

B. A pseudoaneurysm

C. The transverse sinus

D. An artifact

The Transverse Sinus

Netter’s Cardiology, 2010.

Case

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…..

Case

Repeat TEE at 4 weeks

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

Survival in Patients with TAVR Endocarditis

Regueiro et al. JAMA 2016

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

Thank You!mankad.rekha@mayo.edu

@RMankadMD