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 [email protected] @RMankadMD Disclosure Information

Relevant Financial Relationship(s) None

Off Label Usage None Infective Endocarditis

“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 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 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 Diagnosis of Infective Endocarditis

Major Criteria Minor Criteria

Positive blood culture for IE with Predisposition: predisposing heart condition or typical organism IVDU

Persistently positive blood cultures for Fever ≥ 380C any organism

Single positive blood culture for Vascular phenomena: arterial embolism, septic C.burnetti 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 Endocarditis Duke Criteria

Positive Echocardiogram Oscillating intracardiac massor Abscess or New partial dehiscence of prosthetic valve or New Valvular Regurgitation

Durak et al. Am J Med 1994;96:200. Diagnosis Diagnostic Clinical Criteria

2 major criteria

DEFINITE 1 major & 3 minor criteria

5 minor criteria

POSSIBLE 1 Major AND 1 minor criteria or 3 minor criteria

Firm alternative diagnosis

REJECTED Resolution of syndrome ≤ 4 days

No pathologic evidence of IE after ABx for ≤ 4 days

8 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

Dental Treatment 1 4.2 Heart Murmur

Adjusted 6.7 Congenital Heart Odds Disease Ratio 13.4 Rheumatic Fever 19.4 74.6 Mitral Valve Prolapse Cardiac Valve 0 50 100 Surgery

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

Prior IE Includes TAVR valves and patients with prosthetic material used in valve repair

Prosthetic valves Completely repaired CHD with prosthetic materials placed within Who needs 6 months prophylaxis?

Congenital Heart Unrepaired cyanotic Disease congenital heart disease

Valvulopathy CHD repair with after cardiac residual defects next to transplantation prosthetic materials 13 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 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 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

What is the most appropriate next diagnostic step?

1. Cardiac CT

2. Cardiac MRI

3. Transthoracic echocardiogram

4. Transesophageal echocardiogram

5. PET/CT Imaging in Infective Endocarditis

Chest x-ray

• Assess cardiac ECG structure and function • Assess peri-annular anatomy Cardiac Echo • Assess conduction system function • Coronary anatomy TTE Goal Cardiac CT TEE

PET-CT

Imaging ?Cardiac MRI?

Assess for CT • Mycotic aneurysm Non cardiac Goal • Stroke MRI • Intra-abdominal pathology

Courtesy of Dr. N. Anavekar

• 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 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

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) 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? Vegetation Size and Risk of Embolism 100 90 80 70 60 50 40 30 20 10 Cumulative Probability (%) 0 0 2 4 6 8 1012141618202224

Vegetation Size (mm)

Sanfilippo JACC 18:1191(1991) TEE in Infective Endocarditis Incidence of Embolism

Veg <10mm 80 Veg >10mm p <0.001 p = ns 60 67 p = ns 52 40 38 35 20 16 4 0

Incidence of Embolism Incidence ofEmbolism (%) Aortic valve Mitral Valve Prosth valve n = 45 n = 31 n = 25

Mugge JACC 14:631(1989)

Importance of Vegetation Size and Mobility 90 90 80 n = 178 80 70 70 60 60 50 50 40 40 30 30 20 20 Embolic events (%)events Embolic 10 10 0 0 Absent <10 10-15 >15 Absent Low Mod Severe Vegetation size (mm) Vegetation mobility

De Salvo G et al. J Am Coll Cardiol 2001;37: 1077-1079. 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 Embolism in Infective Endocarditis Vegetation Size by TEE and Impact of Therapy

Relation of Embolic events embolism to vegetation size Total On therapy 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) Vilacosta et al: Positive 33% 13% JACC, 2002 (>10 mm) (211 pt)

CP1189948-74 One Year Survival According to Vegetation Length

n = 384

Thuny F et al. Circulation 2005; 112:69-75 Predictors of 1-Year Mortality (Cox Multivariable Analysis) Adjusted RR 95% CI P Age 1.021.01–1.040.007 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 1.19–3.240.001 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) Mortality Composite End-Point

8 vs 0 embolic events

N Engl J Med 2012;366:2466-73 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 2014 AHA/ACC Valve Guidelines, Circulation 2014 • 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) 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

100 TTE TEE 80

60 % 40

0 Daniel, Karalis, Blumberg, n=46 n=24 n=24 NEJM 1991; Circulation 1992; Chest 1995; 324:795-800 86: 353-62 107:898-903 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

Normally Functioning AVR

LV 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 operatingWhen room 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 Staph aureus bacteremia Transthoracic Echo + Vegetation - Vegetation

No Complications Any Clinical Instability + Clinical Suspicion

Antibiotics + TEE Observation + Vegetation - Vegetation

Abscess/Perforation No Complications Probably NOT ? Large Vegetation Endocarditis Antibiotics + Antibiotics + Surgery Observation Thank You! [email protected] @RMankadMD