Timing of Timing of Surgery in Surgery in

EndocarditisEndocarditisJimmy Klemis, MDJimmy Klemis, MD

CT Surgery ConferenceCT Surgery Conference

EndocarditisEndocarditis Potentially lethal disease with varying Potentially lethal disease with varying

etiologic agents and different clinical etiologic agents and different clinical situations (NVE vs PVE, etc)situations (NVE vs PVE, etc)

No “cookbook” approach to proper No “cookbook” approach to proper therapy, esp when considering surgerytherapy, esp when considering surgery

In select patients, combined medical and In select patients, combined medical and surgical Rx offers substantial benefit surgical Rx offers substantial benefit compared with medical Rx alonecompared with medical Rx alone

However, surgery carries risk and decision However, surgery carries risk and decision on whether or not to operate must be on whether or not to operate must be carefully thought out with good carefully thought out with good communication between surgical and communication between surgical and medical teamsmedical teams

EndocarditisEndocarditis

In pre-Abx era, largely fatal diseaseIn pre-Abx era, largely fatal disease 1885 – Sir William Osler in Gulstonian 1885 – Sir William Osler in Gulstonian

lectures referred to IE as the “malignant lectures referred to IE as the “malignant endocarditis”, 30 years later he expressed endocarditis”, 30 years later he expressed pessimism about ever finding a “cure” for IEpessimism about ever finding a “cure” for IE

1940’s – PCN revived hope for a cure of IE, 1940’s – PCN revived hope for a cure of IE, however morbidity and mortality only however morbidity and mortality only partially alteredpartially altered

resistant organisms and shifting etiology resistant organisms and shifting etiology (IVDA) (IVDA)

Chamoun. Am J Med Sci. Oct 2000; 320 (4)

Endocarditis – surgical Endocarditis – surgical RxRx

1961 – Kay et al first to report surgical 1961 – Kay et al first to report surgical cure of pt with medically resistant IE cure of pt with medically resistant IE (fungal TV)(fungal TV)

1965 Wallace, et al – first report of 1965 Wallace, et al – first report of successful valve replacement in active successful valve replacement in active endocarditisendocarditis

early success in many studies of early success in many studies of selected patients led to “paradigm shift” selected patients led to “paradigm shift” in management of complicated in management of complicated endocarditisendocarditis

Indications for SurgeryIndications for Surgery

Hemodynamic compromise/ Heart Hemodynamic compromise/ Heart failurefailure

Persistent sepsisPersistent sepsis Peripheral embolizationPeripheral embolization Extravalvular extension of infxnExtravalvular extension of infxn

Heart FailureHeart Failure

Mills, et al. UCSF 1974Mills, et al. UCSF 19741

79/144 pt developed CHF within 6mos 79/144 pt developed CHF within 6mos of admitof admit

60% moderate-severe60% moderate-severe MR – 50% developed CHF, 1/2 severeMR – 50% developed CHF, 1/2 severe AR – 80% CHF, 2/3 severeAR – 80% CHF, 2/3 severe

6 month survival with severe CHF/AR6 month survival with severe CHF/AR medical 7 % med/surgical 64%medical 7 % med/surgical 64%

1Mills J, et al. Chest 66:151-157, 1974

CHFCHF

Lewis, et al. Johannesburg, South Africa, Lewis, et al. Johannesburg, South Africa, 1975-801975-801

early valve replacement in 95 early valve replacement in 95 hemodynamically unstable pt – 64% emergent hemodynamically unstable pt – 64% emergent 88% 48hrs88% 48hrs

MortalityMortality urgent surgery 15% (13/84)urgent surgery 15% (13/84) elective 18% (2/11)elective 18% (2/11) 5 year survival 60%5 year survival 60%

Periprosthetic leaks in 13% (10/80) of Periprosthetic leaks in 13% (10/80) of survivorssurvivors

1Lewis BS, et al. J Thorac Cardiovasc Surg 84:579-84, 1982

CHFCHF

Johannesburg, SA 1982-1988Johannesburg, SA 1982-198811

203pt with active IE and early valve 203pt with active IE and early valve replacementreplacement

Urgent surgery (<48hrs) in 53%Urgent surgery (<48hrs) in 53% MortalityMortality

Urgent 7%Urgent 7% Overall 4%Overall 4% long term 6% pt followed 38± 22moslong term 6% pt followed 38± 22mos

1Middlemost S, et al. JACC 18:663-667, 1991

CHF – Meta-analysis CHF – Meta-analysis

Mortality

MedicalMed/

Surgical

No CHF 15%15% 11%11%

CHF 60%60% 29%29%

Moon, et al. Prog Cardiovasc Dis. 1997

Persistent SepsisPersistent Sepsis nonsterile Bld Cx 3-5d after dxnonsterile Bld Cx 3-5d after dx lack of improvement sxs after 1wk appropriate Abxlack of improvement sxs after 1wk appropriate Abx usually due to usually due to

Bacterial resistance Bacterial resistance valvular/perivalvular infectionsvalvular/perivalvular infections non cardiac septic foci (splenic, renal, cerebral abcess, non cardiac septic foci (splenic, renal, cerebral abcess,

mycotic aneurysmmycotic aneurysm GNR, staph or fungal infxnGNR, staph or fungal infxn

surgery may eliminate septic focus, but not surgery may eliminate septic focus, but not necessarily improve pt hemodynamic condition necessarily improve pt hemodynamic condition unless significant valvular regurgunless significant valvular regurg

+Bld Cx at surgery predict adverse outcome+Bld Cx at surgery predict adverse outcome

Persistent SepsisPersistent Sepsis

Postive Cx @ time of surgery Postive Cx @ time of surgery predicts poorer outcomepredicts poorer outcome

D`Agostino, et al Ann Thor Surg D`Agostino, et al Ann Thor Surg 19851985 108pt with NVE108pt with NVE 87pt Bld Cx (-) >90% 1 year 87pt Bld Cx (-) >90% 1 year

complication free survival (no complication free survival (no perivalvular leak, IE recurrence)perivalvular leak, IE recurrence)

19 pt Bld Cx (+) <70%19 pt Bld Cx (+) <70%

Persistent SepsisPersistent Sepsis

although ↑ complication if Bld Cx +, although ↑ complication if Bld Cx +, still important to intervene esp in still important to intervene esp in face of further destruction of face of further destruction of valvular/annular tissuevalvular/annular tissue

Boyd, et al. NYU 1977Boyd, et al. NYU 197711

operative mortality risk in uncontrolled operative mortality risk in uncontrolled infxn better when operated earlier infxn better when operated earlier (within 10d of admit) (17%) than when (within 10d of admit) (17%) than when abx continued for 4-6wks (90%)abx continued for 4-6wks (90%)

1Boyd et al. J Thorac Cardiovasc Surg 73:23-30, 1977

Persistent Persistent Sepsis/Surgery riskSepsis/Surgery risk

Risk Mortality

Recurrent IE after

successful medical Rx

10% 10%

PVE after valve

replacement in active IE

10%Approaches

50%

Alsip et al, Am J Med 78:138-148, 1985

Persistent SepsisPersistent Sepsis

may also be from extracardiac may also be from extracardiac source/embolisource/emboli

splenic, renal, cerebral abcessessplenic, renal, cerebral abcesses ? proper Rx – surgery?, incidence of ? proper Rx – surgery?, incidence of

recurrent endocarditis in these recurrent endocarditis in these situations?situations?

Splenic abcessSplenic abcess

Image: Roberts, Cornell Univ Web Site:Vascular infections

Infectious etiologyInfectious etiology

S. aureusS. aureus highly destructivehighly destructive meta-analysis showed higher mortality meta-analysis showed higher mortality

with medical (39/76 with medical (39/76 56%56% ) compared with ) compared with med/surgical Rx (24/77 med/surgical Rx (24/77 31%31% ) p<.03 ) p<.03

not absolute indication but more not absolute indication but more aggressive surgical approach should be aggressive surgical approach should be considered, esp if other factors considered, esp if other factors

Gram (-)/serratia/pseudomonas Gram (-)/serratia/pseudomonas

Infectious EtiologyInfectious Etiology Fungal Fungal

most commonmost common: Aspergillus, Candida, : Aspergillus, Candida, Torulopsis glabrataTorulopsis glabrata

risk:risk: prev cardiac surgery, Abx use and prev cardiac surgery, Abx use and hyperalimentation, long therm IV cath, IVDAhyperalimentation, long therm IV cath, IVDA

clinical:clinical: neg Bld Cx/fever, changing murmur, neg Bld Cx/fever, changing murmur, chorioretinitis, and large peripheral embolichorioretinitis, and large peripheral emboli

overall survival with medical Rx 25% c/w overall survival with medical Rx 25% c/w med/surgical rx 58%med/surgical rx 58%

compelling if not absolute indication for compelling if not absolute indication for surgerysurgery

Rubenstein and Lang. Fungal Endocarditis. Eur Heart J 1995

Peripheral EmbolizationPeripheral Embolization

embolic events common 30-40% of IEembolic events common 30-40% of IE brain>limbs, coronary, spleen, kidneybrain>limbs, coronary, spleen, kidney directly responsible for ~25% of fatalitiesdirectly responsible for ~25% of fatalities11

recurrence rate 54% within 30drecurrence rate 54% within 30d incidence falls after initiation of Abx incidence falls after initiation of Abx

therapy ~ 2wkstherapy ~ 2wks riskrisk

size > 10mm (47% vs 19%)size > 10mm (47% vs 19%)22

staph, candida, GNRstaph, candida, GNR mobile, pedunculated, mitral>aorticmobile, pedunculated, mitral>aortic

2Mugge et al. JACC 14:631-638. 19891Acar, et al. Eur Heart J, 16 (supplement B), 94-98. 1995

Moon, et al. Prog Cardiovasc Dis 1997

Vegetation on atrial surface of PMVL

Peripheral EmbolizationPeripheral Embolization Rohmann, et alRohmann, et al11

64% vegetations resolved/decreased64% vegetations resolved/decreased 36% no change/increased36% no change/increased valve replacement 2% vs 45%valve replacement 2% vs 45% perivalvular abcess 2%vs 13%perivalvular abcess 2%vs 13% mortality 0% vs 10%mortality 0% vs 10%

Vuille, et alVuille, et al22

persistent veg in 50% despite clinical healing, no persistent veg in 50% despite clinical healing, no independent association with late complicationsindependent association with late complications

in the absence of valvular dysfxn, persistent in the absence of valvular dysfxn, persistent vegetation on echo shouldn’t be criterion for vegetation on echo shouldn’t be criterion for valve replacement in absence of other valve replacement in absence of other indicationsindications

1Rohmann, et al. J Am Soc Echo 4:465-474, 19912Vuille, et al. Am Heart J 128: 1200-1209. 1994

Peripheral EmbolizationPeripheral Embolization

recurrent emboli are relative recurrent emboli are relative indication for surgery (class IIa) but indication for surgery (class IIa) but should not be considered absolute should not be considered absolute indicationindication

Emboli – Cerebral (Con)Emboli – Cerebral (Con) surgical intervention with cardiopulm bypass surgical intervention with cardiopulm bypass

can cause extension of infarct or hemorrhagic can cause extension of infarct or hemorrhagic transformation of previously bland infarcttransformation of previously bland infarct

Eishi et al – cerebral emboli + surgeryEishi et al – cerebral emboli + surgery

24hrs24hrs 2wks2wks 4wks4wks

Extension or Extension or expansion of expansion of infarctinfarct

50%50% <10%<10% 2%2%

MortalityMortality 67%67% <20%<20% <10%<10%

Eishi, et al. J Thorac Cardiovasc Surg 110:1745-1755, 1995

Eishi,et al. J Thorac Cardiovasc Surg 1995;110:1745-55

Fig. 1. Computed tomographic scans of a patient with right middle cerebral artery infarction resulting from infective endocarditis. This patient underwent a Bentall-type operation for graft infection on the same day, resulting in massive brain swelling, and died 3 days later. Top row, Preoperative computed tomographic scans; bottom row, postoperative scans.

Emboli – Cerebral (Pro)Emboli – Cerebral (Pro) Ting, et al – smaller, bland cerebral infarcts 31ptTing, et al – smaller, bland cerebral infarcts 31pt11

operative mortality 19%operative mortality 19% survivors (81%)survivors (81%)

5pt with cerebral hemorrhage 5pt with cerebral hemorrhage CVA CVA others: others:

12% exacerbated CNS sxs 12% exacerbated CNS sxs 16% unchanged16% unchanged 20% partial resolution 20% partial resolution 52% complete resolution52% complete resolution

Other studies have shown complete neurologic Other studies have shown complete neurologic recovery in pt with coma or dense hemiparesis recovery in pt with coma or dense hemiparesis after valve replacement, but recommended delay after valve replacement, but recommended delay if bleedif bleed22

1Ting, et al. Ann Thorac Surg 51:18-22, 19912Zisbrod, et al. Circulation 76:V109-V112, 1987 (suppl V)

Ruptured mycotic aneurysm in MCA territory (causative agent: Aspergillus)

Emboli - CerebralEmboli - Cerebral single cerebral embolus not indication for single cerebral embolus not indication for

surgery unless assoc with large mobile veg surgery unless assoc with large mobile veg and that further CNS injury might preclude and that further CNS injury might preclude meaningful chance at meaningful chance at recovery/rehabilitationrecovery/rehabilitation

bland infarct – if stable hemodynamics, 2-3 bland infarct – if stable hemodynamics, 2-3 wks Abx before considering surgery to wks Abx before considering surgery to minimize provoking further CNS injuryminimize provoking further CNS injury

hemorrhagic infarct – surgery postponed as hemorrhagic infarct – surgery postponed as long as possible – optimally if full course long as possible – optimally if full course Abx can be given and recovery of Abx can be given and recovery of neurologic dysfxnneurologic dysfxn

Extravalvular ExtensionExtravalvular Extension annular abscessannular abscess

operative mortality 19-43% (vs >75% operative mortality 19-43% (vs >75% medically treated)medically treated)11

extensive tissue necrosis/structural damage extensive tissue necrosis/structural damage including interventricular septum, including interventricular septum, conduction system, and fibrous skeleton of conduction system, and fibrous skeleton of heartheart

In NVE mitral (1-5%) < aortic (25-50%)In NVE mitral (1-5%) < aortic (25-50%) clinically have more valvular regurgitationclinically have more valvular regurgitation hi risk (staph/fungal, new heart block, PVE) hi risk (staph/fungal, new heart block, PVE)

should undergo TEE (90% detection vs 50% should undergo TEE (90% detection vs 50% TTE)TTE)

1Moon, et al. Prog Cardiovasc Dis 1997 Nov-Dec 40(3) p246

ECHO findings in Annular abscessECHO findings in Annular abscess anterior or posterior Ao root wall anterior or posterior Ao root wall

thickness≥ 10mmthickness≥ 10mm perivalvular density in IVS ≥ 14mmperivalvular density in IVS ≥ 14mm sinus of valsalva defect/aneurysmsinus of valsalva defect/aneurysm rocking of prosthetic valverocking of prosthetic valve Sens and Spec 85% if 1 of above seenSens and Spec 85% if 1 of above seen

Cormier et al. Eur Heart J 1995 (16) suppl B 68-71

Otto. Textbook of Clinical Echocardiography 2nd Ed. Chp 13

TTE (L) and TEE (R) showingevidence of AV vegetation and paravalvular abscess

communicating Ao root communicating Ao root abscessabscess

Dec 2001 ECHO case of the month, www.acc.org

Extravalvular ExtensionExtravalvular Extension

Conduction disturbances in 30% Conduction disturbances in 30% with abscess vs <2% if no abscesswith abscess vs <2% if no abscess 11stst degree > 7d, new 2 degree > 7d, new 2ndnd or 3 or 3rdrd degree degree

block requires eval for abcess - TEEblock requires eval for abcess - TEE

Meta-analysisMeta-analysis

Moon, et al. Prog Cardiovasc Dis. 1997

Moon, et al. Prog Cardiovasc Dis 1997

Predictors of operative mortalityPredictors of operative mortality

Moon, et al. Prog Cardiovasc Dis 1997

ConclusionsConclusions

Combined medical/surgical rx of selected Combined medical/surgical rx of selected populations offers substantial morbidity and populations offers substantial morbidity and mortality benefit.mortality benefit.

careful attention to hemodynamic status, careful attention to hemodynamic status, infecting organism (staph aureus, fungi, infecting organism (staph aureus, fungi, GNR), valve(s) involved (AV), clinical GNR), valve(s) involved (AV), clinical manifestations (emboli, abscess, conduction manifestations (emboli, abscess, conduction abnl, CHF), and findings on imaging abnl, CHF), and findings on imaging (TTE/TEE, etc) allow a tailored approach to (TTE/TEE, etc) allow a tailored approach to proper Rx in each patient to minimize proper Rx in each patient to minimize morbidity and mortalitymorbidity and mortality

ConclusionsConclusions