Infective Endocarditis

Definition

• Conditions in which structures of the heart, most frequently the valves, harbor an infective process.

• This might lead to:– Valvar dysfunction– Localized or generalized sepsis– Sites for embolism

• The term “Infective Endocarditis” includes:– Acute, subacute, and chronic – Bacterial, viral, rickettsial, or fungal– Native or prosthetic

Definition

• Endocarditis:– Exudative and proliferative inflammatory

alterations of the endocardium– Characterized by vegetations on the endocardial

surface or within the endocardium– May occur as the primary disorder (infective

endocarditis) or as a secondary complication of another disease (SLE, Rheumatic Heart Disease)

Definition

• Infective Endocarditis:– Invasion and multiplication of micro-organisms on

the endocardial surface, within the endocardium, within the myocardium, or on prosthetic materials within and around cardiac structures

– Most frequently involves the valvar structures and it may lead to destruction of these structures, localized or genertalized sepsis, or sites of embolism

Pathogenesis

• The most common site of involvement is on the line of closure of the valves– Atrial side of the atrio-ventricular valves– Ventricular side of the semilunar valves

• Maturation of the vegetation:– Bacterial attachment– Bacterial proliferation + fibrin deposition

• The bacteria remain below the surface of the vegetation and this protects them from:– Phagocytes– High antibiotic concentrations

Pathogenesis

• Altered Endocardial Surface to allow deposition of bacteria and fibrin:– Rheumatic Valvulitis– Annular or Valvar Calcification– Catheter Trauma

• Haemodynamic Factors:– Jet effect of blood flow through

• PDA • Restrictive VSD• Mitral Valve Prolapse• BAV

• Bacteraemia : 60-80% of normal individuals

Pathogenesis

• Compromised or Altered Immune System– Histopathologic analysis of kidney tissue of the patients

with IE:• Diffuse proliferative glumerolonephritis• Evidence of deposition of IgG and IgM• Circulating immune complexes (CICs) may be found in the:

– Glomerular basement membrane – Retina– Peripheral lesions (Janeway lesions and Roth Spots)

• CIC Levels correlate with the duration of the illness• Drop in CIC levels correlate with the success of the treatment

– Various manifestations of complement activation

Pathogenesis

• 25% of IE happen in normal valves– Organisms involved are those with increased adhesions molecules:

• Staphylococcus• Streptococcus Viridans• Enterococcus

– Common Risk Factors:• Overwhelming Sepsis• Resuscitation from Shock• Use of Long-Term IDCs• IVDU• Fungemia associated with prolonged ABx use

• Only 5% of patients with IDC sepsis have endocarditis and it is usually due to Staphylococcal Organisms.

Pathogenesis

• Iathrogenic IE:– Those undergoing chronic hemodialysis– Frequent Staphylococcal bacteremia– Sclerotic Aortic/Mitral Valves

Rodbard Hypothesis for Pathogenesis

• High velocity jets of blood from a high-pressure source form at an orifice and enter a low-pressure sink

• Venturi currents deposit bacteria immediately beyond the orifice to form vena contracta and result in mechanical erosion and deposition of platelets and thrombin

Pathogenesis

• The same mechanism exists – Against the stenotic valves– Opposite to a PDA in

pulmonary artery– Left atrial side of the

regurgitant mitral valve.

• Most IE lesions of aortic valve happen on the ventricular side which suggest the a role for valvar regurgitation and also the venturi effect

Morphology

• Vegetations and eorsive cavities are on the: – Ventricular aspect of the aortic valve cusps– Base of the atrial side of the mitral valve leaflets

• Often causing separation or discontinuity at the– Ventriculoarterial junction– Atrioventricular junction

– Drop Lesions from the aortic valve vegetations occur on the anterior leaflet of the mitral valve and the tensor apparatus.

– Discrete perforations also occur by isolated vegetations.

Aortic valve with vegetation on non-coronary cusp and partial destruction of left coronary cusp.

Aortic valve with vegetation between non-coronary and right coronary cusps extending as an anular abscess

Leaflet vegetation and ring abscess of posterior medial aspect of mitral valve

Mitral valve with drop lesion of anterior leaflet

Morphology• NVE:

– Non-IV-Drug-Related:• Left Sided

– IV-Drug-Related:• Tricuspid Valve 50%• Aortic and Mitral 50%

• Perianular Abscess (Pseudoaneurysm):– More common with aortic valve endocarditis than it is with mitral– It is present in 1/3 of cases studied with TOE– Predominant organism is : S. aureus– Clinical features:

• Presence of pericarditis• Rapid progression of the disease• High degree of AV Block

Morphology

• PVE:– All or most of the vegetations are on the ventricular

aspect– Only a small area of sewing ring detachment might be

apparent and it might appear sterile – A thorough search at operation must be made beneath

the valve to identify the bulk of the pathologic process– There may be important detachment without

vegetation. This might be in the absence of an abscess or even positive blood culture.

Loci of Infective Endocarditis Lesions

Clinical Features

• IE is present when– Positive blood cultures associated with:

• New or changing murmurs• Embolic phenomena

– New or changing murmurs in a patient with congenital cardiac anomaly or prior valve damage associated with:• Embolic phenomena• Sustained fever, anemia, and splenomegaly

– Some authorities also accept the presence of progressive heart failure in the presence of positive blood cultures.

Duke’s Criteria - Major

• Positive blood culture– Typical MOs for IE from 2 separate blood cultures in

the absence of a primary focus:• Strep Viridans, Strep Bovis, HACEK (Haemophilus,

Actinobacillus, Cardiobacterium, Eikenella, and Kingella), Community-acquired staph aureus, or Enterococci

– Persistently positive blood cultures, defined as recovery of a microorganism consistent with IE from:• Blood cultures drawn more than 12 hours apart• All of three or majority of 4 or more separate blood

cultures with first and last drawn at least 1 hour apart

Duke’s Criteria - Major

• Evidence of Endocardial Involvement:– Positive echocardiogram for infective endocarditis:

• Oscillating intra-cardiac mass in absence of an alternative anatomic explanation:– On valve or supporting structures – In path of regurgitant jets – On implanted material

• Abscess• New partial dehiscence of prosthetic valve • New valvar regurgitation (increase or change in

preexisting murmur not sufficient for diagnosis)

Duke’s Criteria - Minor

• Predisposition:– Predisposing heart

condition or IV drug use– Fever ≥38°C

• Vascular Phenomena:– Major arterial emboli– Septic pulmonary infarcts– Mycotic aneurysm– Intracranial hemorrhage– Conjunctival hemorrhages– Janeway lesions

Duke’s Criteria - Minor

• Immunologic Phenomena:– Glomerulonephritis – Osler nodes – Roth spots – Rheumatoid factor

Duke’s Criteria - Minor

• Microbiological Evidence:– Positive blood cultures but not meeting the major

criterion– Serologic evidence of active infection with a MO

consistent with IE• Echocardiogram:– Consistent with infective endocarditis but not

meeting major criterion

Clinical Feature• Fever:

– The most common clinical manifestation– 95-100% present– Low-grade– Spiking– Following the peak of bacteremia by 2 hours– Those at risk of IE who develop fever for more than 48 hours should have 2 or more sets

of blood cultures drawn from different sites• Positive blood cultures:

– 95% of cases even when those with right-sided IE, fungal IE, IE in addicts, IE caused by fastidious organisms are included.

• Culture negative IE: 10% – Mostly in those with PVE– Intracellular or fastidious organisms– Previous antibiotic therapy– A history of AB therapy and serologic evidence of mycoplasma, or chlamydia – Other causes:

• Aspergillus, Q-fever, Bartonella

Clinical Feature• Heart Murmur:

– 85-95%– 10% lack murmur– Aortic root and valve:

• Short Diastolic Murmur• Early systolic or midsystolic murmurs also can be present

– Mitral valve:• Like other MR, systolic murmurs and in the case of anterior leaflet drop lesions there is a

distinct radiation to the back.• Diastolic murmurs like MS: obstruction with large vegetation.

• Anemia– Multifactorial causes: Marrow suppression as a result of the chronic disease

• Arthralgia / Arthritis : rarely seen today as a result of earlier diagnosis of the condition

• Myalgia: common– Associated with bacteremia – Occasionally may result from myocardial microabscesses which generally happen in

staph bacteremia

Clinical Feature• Embolic Phenomenon:

– 10-15% presenting manifestation– 50% of patients with IE have embolic phenomenon:

• Diagnosed on either clinical examination or by an imaging modality• Evenly distributed between cerebral and peripheral sites• Classic ones are now rarely seen in surgical practice:

– Osler Nodes– Janeway Lesions : Staph almost always is the organism– Roth Spots– Petechiae– Clubbing

• Neurologic Abnormalities: 25-30% of patients at initial presentation:– TIA/Stroke/Loss of Vision/Seizures/Headache/Backache/Acute

Mononeuropathy

Causative Organisms• Strep and Staph : 80% of cases

– S. aureus:• The most common cause of IE amongst hospital-acquired and drug-related • Mitral > Aortic• Higher occurrence of embolism comparing to the other oranisms

– Strep: • 30% of IE cases• Viridans is the most common

• Enterococci: – The third common– 10% of cases– Elderly male – Multiple comorbidities– Less common embolic events– More avidity to Aortic Valve

• Gram-negative bacilli:– 5% of cases

Causative Organisms

• PVE:– 2 months post-op: Staph. Epidermidis– Late onset: as NVE– Enterococcal:• E. Faecalis/ E. Faecium • Associated with manipulation of GI or GU tract • GI or GU tract malignancy

Complications

• Heart Failure• Renal • Embolic Events• Neurologic Manifestations

Heart Failure• The most common• Valvular regurgitation is the cause• NVE occasionally results is MS and/or TS and infrequently AS• Perianular Extension

– Major causes of heart failure in PVE. – 50% of cases with PVE– 10-40% of NVE– More commonly involves the aortic valve– Can lead to:

• Abscess formation / pseudoaneurysm/aortocavitary fistula

• Myocardial abscess:– S. aureus– PVE / Aortic Valve / BAV – Development of conduction abnormalities should prompt further TOE examination– Untreated: fistula formation and intracardiac shunting from myocardial perforation

Renal

• At least in 4 forms:– Pre-renal due to low cardiac output– Microabscess formation secondary to septic

emboli– Golmerular dysfunction as a result of CIC– Renal failure as a result of ABx

Embolic Events• Common:

– NVE : 43%– IV Drug-Associated : 67%– PVE: 25%

Embolic Events• Metastatic infection of viscera is typically caused by Staph.• Multiple Coronary emboli:

– MI– Ventricular Dysfunction– Most common causative organisms:

• S. Aureus• Candida• HACEK (Hemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)

• Neurologic Manifestations:– 50% of embolic complications are associated with neurologic manifestations– 1/4 – 1/3 of patients with NVE or PVE at some time have neurologic

complications of which 90% are related to emboli in the territory of MCA– S. aureus increases the risk– Stroke is the most common neurologic event

Embolic Neurologic Events• Cerebral embolism generally happens before the start of antibiotic therapy and the

risk dramatically falls following the commencement of an effective therapy.– The risk falls from ~ 12% to 4%

• The absolute size of vegetation and failure of decrease in size of the vegetation following ABx is a risk for embolization.

• HACEK Group and fungi create the large vegetation.

Intracerebral Hemorrhage

• The most devastating complication• 5% of IE• 50% mortality• Pathophysiology:– Septic arteritis with erosion of the vessel wall

during uncontrolled infection– Hemorrhage following infarction– Rupture of mycotic aneurysm

Treatment

• Antibiotics:– > 50% of cases can be managed solely with antibiotics– Once antibiotics started blood cultures should be taken every 1-2

days and the length of the treatment should be calculated based on the date the blood cultures have become negative

• Surgery:– It is necessary in 40-45% of patients – Goals:

• Remove infected tissues and drain abscesses• Restore or reconstruct atrioventricular or ventriculo-arterial continuity• Reverse the haemodynamic abnormality• Closing the acquired defect / in children: repair of congenital

malformation

Indications for Surgery

• NVE:– Healed: those hemodynamic indications present for

those without IE and similar valvular lesions– Active:

• Congestive Heart Failure • Perianular Extension• Systemic Embolism• Cerebrovascular Complications• Persistent Sepsis• Difficult Organisms• PVE

Indications for Surgery

• Congestive Heart Failure:– Caused by severe aortic or mitral regurgitation,

more rarely by valve obstruction caused by vegetations.

– Severe acute aortic or mitral regurgitation with echocardiographic signs of elevated left ventricular end-diastolic pressure or significant pulmonary hypertension.

– As a result of prosthetic dehiscence or obstruction.

Indications for Surgery

• Perianular Extension• Systemic Embolism– Recurrent emboli despite appropriate antibiotic therapy.– Large vegetations (>10 mm) after one or more clinical or

silent embolic events after initiation of antibiotic therapy – Large vegetations and other predictors of a complicated

course– Very large vegetations (>15 mm) without embolic

complications, especially if valve-sparing surgery is likely (remains controversial)

Indications for Surgery

• Cerebrovascular Complications– Silent neurologic complication or TIA and other

surgical indications– Ischemic stroke and other surgical indications

(hemorrhage should have been excluded and the neurologic complications are not severe and there is a chance for recovery)

Indications for Surgery

• Persistent Sepsis:– Fever or positive blood cultures persisting > 5-7

days despite appropriate antibiotic regimen, assuming that vegetations or other cardiac lesions requiring surgery persist and extracardiac sources of sepsis have all been excluded

– Relapsing infective endocarditis, esp. when caused by organisms other than sensitive strep or in patients with prosthetic valves

Indications for Surgery

• Difficult Organisms:– S. aureus involving a prosthetic valve and most cases involving a

native valve – IE caused by other aggressive organisms:

• Brucella• Stpahylococcus Lugdunensis

– IE caused by MRO:• MRSA• VRE

– P. aeruginosa IE– Fungal IE– Q Fever IE at the presence of other indications for intervention

Indications for Surgery

• Prosthetic valve endocarditis:– All cases of early PVE – All cases of PVE and S. aureus– Late PVE

• With heart failure caused by:– Prosthetic dehiscence – Prosthetic obstruction– Other indications of surgery

• With perianular extension (abscess or fistulous tract)• With persistent bacteremia, recurrent emboli, or

relapsing infection while on appropriate antibiotics

Timing of Surgery

• Emergency (within 24 h):– Native (mitral or aortic) or prosthetic valve

endocarditis and severe CHF or Cardiogenic Shock:• Acute valvular regurgitation• Severe prosthetic dysfunction (dehiscence or

obstruction)• Fistula into a cardiac chamber or the pericardial space

Timing of Surgery

• Urgent (within days):– NVE or PVE with:

• Persisting CHF• Signs of poor hemodynamic tolerance• Abscess

– PVE caused by:• Staph• Gram-negative organisms

– Large vegetation (> 10 mm) with:• An embolic event• Other predictors of a complicated course

– Very large vegetations (> 15 mm)– Large abscess and/or perianular involvement with uncontrolled

infection

Timing of Surgery

• Early Elective Surgery (During In-Hospital Stay):– Severe AR or MR with CHF and good response to

antibiotic therapy– PVE with valvular dehiscence or CHF and good

response to medical therapy– Presence of abscess or perianular extension– Persisting infection when extracardiac focus has

been excluded– Fungal or other infections resistant to medical

therapy

Surgical Approach

• Considerations:– Aortic valve IE: • Anterior leaflet of mitral valve and its chordae should

be examined for drop lesions• There might be a need for the left atrium to be entered

to examine the posterior leaflet apparatus

– Mitral valve IE: • Aortic valve involvement is unlikely if:

– Absence of thrill or murmur– Competent aortic valve– No echo evidence of vegetations

Surgical Approach

• Mitral Valve IE:– Posteroinferior portion of the mitral annulus

should be inspected to look for myocardial ring abscess

• Aortic Root Abscess:– Posterior to the membranous portion of IVS– Posterior portion of the septum anterior to the

LMCA

Surgical Approach

• Mitral Valve Endocarditis – Repair:• Healed, Small, or Discrete

Vegetations• Does not involve a major

portion of the tensor apparatus• How:

– Closure of small defects of the anterior or posterior leaflet using autologus or bovine pericardium or direct suturing

– Small vegetations might be stripped off the chordae tendineae

Surgical Approach

• Mitral Valve Endocarditis:– Major destructions:

• Major challenge for repair• Options:

– Replacement for all but small vegetations : there is a risk of PVE in the setting of active infection

– Debridement of infected tissue > Sliding annuloplasty to reconstruct commissural areas

– Partial leaflet resection and/or pericardial patch replacement might be needed

– Suture annuloplasty is preferable to prosthetic ring.

– Biodegradable rings have also been used in active infection setting and has been shown to be safe

Surgical Approach

• Abscesses:– When found: should be completely evacuated and

surrounded tissue debrided:– Atrioventricular/ventriculoarterial discontinuity is

an important issue

Mitral Valve IE with Ring Abscess

Mitral Valve IE with Ring Abscess

Mitral Valve IE with Ring Abscess

Aortic Valve IE with Abscess

Aortic Valve IE with Abscess

Aortic Valve IE with Abscess

Choice of Devices• Aortic Valve:

– Allograft – Other devices also have good outcome– When aortic root replacement is considered, allograft is not superior to

other choices• Tricuspid:

– Repair– Allograft

• Mitral:– Repair– If not possible then Mechanical Valve

• Recurrent Infections:– Cardiac Transplant

Post Operative Considerations

• Vasoplegia• Diuresis and PEEP for Early Extubation• Renal Function• Antibiotics• Persistent Fever and Sepsis Despite

Satisfactory Operation