valvular heart disease: changing concepts in disease ... · surgery for infective endocarditis who...

Surgery for Infective EndocarditisWho and When?

Bernard D. Prendergast, DM, FRCP; Pilar Tornos, MD, FESC

Infective endocarditis (IE) remains a dangerous conditionwith unchanging incidence and a mortality approaching

30% at 1 year.1,2 Surgery is potentially lifesaving3 and isrequired in 25% to 50% of cases during acute infection and20% to 40% during convalescence.4–7 Operative proceduresare often technically difficult and associated with high risk,not least because patients are frequently extremely sick withmultisystem disease. Nevertheless, indications for surgery areclear in many patients, and international guidelines8,9 providestrong recommendations that are applicable for the majority.These guidelines are not supported by robust clinical evi-dence, however, and clinical decision making is often ham-pered by diverse considerations, including advancing age ofthe overall patient cohort, the presence of extracardiac com-plications or preexistent comorbidity, prior antibiotic therapyof varying duration, and the availability of appropriatesurgical expertise. In this article, we review the evidence basethat supports current clinical practice and attempt to providerecommendations in areas where doubt persists.

The Role of SurgeryThe role of surgery in active IE has expanded progressivelysince early reports of successful outcome.10 Subsequentdeclines in mortality may be attributed to a variety ofimprovements in management, although expeditious surgeryin carefully selected patients has played a major role. Con-temporary data in Europe indicate that surgery is nowundertaken in approximately 50% of patients with IE; themost frequent indications are congestive heart failure (60%),refractory sepsis (40%), embolic complications (18%), andvegetation size (48%), with a combination of these factorsbeing present in many patients.11

Overall surgical mortality in active IE is 6% to 25%, withlong-term survival rates of approximately 70% in mostseries.4–7,12–31 Assessment of the impact of surgery on out-come is difficult, because the patients referred are frequentlythose with severe complications related to virulent organisms.Conversely, the most ill patients (frequently the elderly, withattendant comorbidity) are often deemed unfit for surgery. Ingeneral terms, prognosis is better if surgery is undertaken

early, before cardiac tissue destruction and deterioration inthe overall condition of the patient increase the hazards ofintervention. Final outcome has never been related to theduration and intensity of prior antibiotic treatment, andsurgery should not be delayed when clearly indicated in thevain hope that a sterile operative field can be achieved.

Numerous series have attempted to identify variablespredictive of early and late mortality,4–6,12–25 and these aresummarized in Table 1. However, interpretation is hamperedby the heterogeneous nature of the patients studied and theoutcome measures used. Specifically, the vast majority ofstudies have been single-center, retrospective series enrollingpatients with both native and prosthetic valve IE. Further-more, analysis is inherently biased given the selection ofpatients for surgery who have an anticipated poor outcomebut acceptable operative risk. Although surgery may berecommended and commonly performed for indications suchas embolic complications or persistent infection, it should berecognized that no definitive proof exists of improved out-come in these situations (in contrast to congestive heartfailure due to valvular regurgitation; see below). More recentinvestigations using sophisticated propensity scoring modelshave yielded conflicting results on the benefits of sur-gery,15,22–25 and a future need exists for high-quality prospec-tive assessment. Even with the help of these data, decisionmaking is frequently difficult, and overall management ishighly dependent on the experience of the surgical team (aswell as the individual surgeon) and a strong interaction withcardiology and microbiology colleagues.

Surgical ManagementPreoperative ConsiderationsTransthoracic and transesophageal echocardiography are nowubiquitous, and their utility in the assessment of complica-tions of IE is clearly recognized. Transesophageal imaginghas superior sensitivity and specificity and is recommendedin virtually all patients in whom surgery is contemplated.

Cardiac catheterization is unnecessary for diagnosis andanatomic characterization. Coronary angiography should be

From the Departments of Cardiology (B.D.P.), The John Radcliffe Hospital, Oxford, United Kingdom and Hopital Vall D’Hebron (P.T.), Barcelona,Spain.

Correspondence to Dr B.D. Prendergast, Consultant Cardiologist, The John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UnitedKingdom. E-mail [email protected]

(Circulation. 2010;121:1141-1152.)© 2010 American Heart Association, Inc.

Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIRCULATIONAHA.108.773598

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Valvular Heart Disease: Changing Concepts inDisease Management

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Table 1. Key Articles Assessing Surgical Outcome in IE

First AuthorandReferenceCitation Year Study Design

StatisticalMethods Setting

No. ofSubjects

PatientCharacteristics

In-HospitalMortality,

%

MeanFollow-Up,

y

Long-Term

SurvivalRate, % Summary of Findings

Jault4 1997 Retrospectivesingle-center

surgicalcohort study

Multivariatelogistic

regressionanalysis

France 247 Native valve IEalone; surgery

100%

7.6(Surgicalseries)

6 71 Predictors of operative mortality:age, insidious illness, CHF.

Long-term survival good exceptfor neurological complications

and mitral valve IE.

Castillo5 2000 Prospectivesingle-centercohort study

Simplegroup

comparisons

Spain 138 Native valve IE69%, PVE

31%; surgery51%

Overall 21;surgical

21,medical 20

(P�NS)

10 71 Early surgery associated withgood long-term results and no

increase in mortality. Not acomparative study.

Alexiou12 2000 Retrospectivesingle-center

surgicalcohort study


regressionanalysis

UK 118 Native valve IE70%, PVE

30%; surgery100%

7.6(Surgicalseries)

10 73 Predictors of operative mortality:CHF, impaired LV function.

Predictors of recurrence: PVE.Predictors of late mortality:

myocardial invasion,reoperation. Predictors of poor

long-term survival:coagulase-negative

staphylococcus, annularabscess, long ICU stay.

Wallace13 2002 Retrospectivesingle-centercohort study


regressionanalysis

UK 208 Native valve IE68%, PVE

32%; surgery52%

Overall 18;impact ofsurgery

notreported

0.5 73 Duration of illness, age, gender,site of infection, organism, and

LV function did not predictoutcome. Abnormal white cellcount, raised creatinine, �2

Duke criteria, or visiblevegetation conferred poor

prognosis.

Hasbun14 2003 Retrospectivemulticentercohort study


regressionanalysis

USA 513 Native valve IEalone; surgery

45%

Notreported

0.5 74 Mortality associated withcomorbidity, abnormal mentalstatus, CHF, nonstreptococcal

IE, or medical therapy.Prognostic classification

proposed.

Vikram15 2003 Retrospectivemulticentercohort study

Propensityanalysis


45%

Notreported

0.5 74 Valve surgery associated withreduced mortality afteradjustment for baseline

variables and propensity scores.Benefits of surgery greatest in

patients with CHF.

Habib16 2005 Retrospectivemulticentercohort study


regressionanalysis

France 104 PVE alone;surgery 49%

Overall 21;surgical

17,medical 25

(P�NS)

2.7 62 Predictors of in-hospitalmortality: CHF, S aureus.Predictors of long-term

mortality: early PVE,comorbidity, CHF,

staphylococcal infection, newprosthetic dehiscence. Mortalityreduced by surgery in high-risksubgroups with staphylococcalinfection and complicated PVE.

Delahaye17 2007 Prospectivemulticenterpopulation-

based survey


regressionanalysis

France 559 Native valve IE85%, PVE

15%; surgery47%

Overall 17;surgical

14,medical 19

(P�NS)

Notreported

Notreported

Predictors of mortality: CHF,immunosuppression, insulindependent DM, left-sided IE,septic shock, coma, cerebralhemorrhage, high C-reactive

protein.

(Continued)

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Table 1. Continued

First AuthorandReferenceCitation Year Study Design

StatisticalMethods Setting

No. ofSubjects

PatientCharacteristics

In-HospitalMortality,

%

MeanFollow-Up,

y

Long-Term

SurvivalRate, % Summary of Findings

SanRomán18

2007 Prospectivemulticentercohort study


regressionanalysis


36%; surgery28%

Overall 21 Notreported

Notreported

Predictors of high risk:interhospital transfer, AV block,acute onset, CHF, periannular

complications, S aureusinfection.

Revilla19 2007 Prospectivemulticentercohort study


regressionanalysis


34%; surgery100%

Overall 36;native

valve 32,PVE 45(surgicalseries)

Notreported

Notreported

Poor clinical outcome afterurgent surgery. Persistentinfection and renal failure

associated with higher mortality.

Hill20 2007 Prospectivesingle-centercohort study


regressionanalysis

Belgium 193 Native valve IE66%, PVE

34%; surgery63%

Notreported

0.5 78Overall

(26 if CIto

surgery)

Predictors of mortality: age, Saureus, CI to surgery (present in

50% of deaths).

Remadi21 2007 Prospectivemulticentercohort study


regressionanalysis

France 116 S aureus IEalone; nativevalve IE 83%,

PVE 17%;surgery 47%

Overall 26;surgical

16,medical 34(P�0.05)

3 57 Predictors of mortality:comorbidity, CHF, severe sepsis,PVE, major neurological events.Early surgery associated with

improved outcome.

Wang6 2007 Prospectivemulticentercohort study


regressionanalysis

Globalregistry

556 PVE alone;surgery 49%

Overall 23;impact ofsurgery

notreported

Notreported

Notreported

Predictors of in-hospitalmortality: age,

healthcare-associated infection,S aureus infection, CHF, stroke,intracardiac abscess, persistent

bacteremia.

Aksoy22 2007 Prospectivesingle-centercohort study

Propensityscore

matching:logistic

regressionanalysis

USA 426 Native valve IE69%, PVE

19%, “other”12%; surgery

29%

Overall 17;left-sided

IE: surgical12,

medical 18

5 Surgical�48,

medical�28

Factors associated with surgicaltreatment: age, interhospital

transfer, staphylococcalinfection, CHF, intracardiac

abscess, hemodialysis with IVcatheter. Surgery associated

with long-term benefit. Factorsassociated with mortality: DM,

paravalvular infection, indwellingIV catheter.

Tleyjeh23 2007 Retrospectivesingle-centercohort study

Matchedpropensityanalysis


24%

Notreported

0.5 Surgical73,

medical76

No survival benefits associatedwith surgery despite correctionfor timing and early operative

deaths. Prospective studyrecommended.

Tleyjeh24 2008 Retrospectivesingle-centercohort study

Propensityanalysis


24%

Notreported

0.5 Surgical73,

medical76

Strong correlation betweenpropensity score and timing of

surgery. Individual effect ofeach variable difficult to

measure.

Thuny25 2009 Retrospectivesingle centerobservationalcohort study

Propensityanalysis

France 291 Native valve IE82%, PVE

18%; surgery100%

Notreported

6 months 13% Very early surgery (�7 days)associated with improved

survival (especially in highestrisk patients) but greaterlikelihood of relapse or

post-operative valve dysfunction.

CHF indicates congestive heart failure; PVE, prosthetic valve endocarditis; NS, not significant; UK, United Kingdom; LV, left ventricle; ICU, intensive care unit; USA,United States; CI, contraindication; IV, intravenous; DM, diabetes mellitus; and AV, atrioventricular.

Prendergast and Tornos Surgery for Infective Endocarditis 1143



considered in men �40 years of age, postmenopausalwomen, and those with a history of ischemic heart disease oran adverse risk factor profile, although caution is necessary inthe presence of large aortic vegetations that may be dislodgedby catheter manipulation. Alternative noninvasive techniquessuch as multislice CT or MRI may be used if available.

Oral anticoagulation is associated with adverse outcome inIE, particularly during the first 2 weeks, when embolic risk ishighest and surgical decisions are usually necessary.32 Anti-coagulants should be discontinued in this phase if possible.If essential (for example, in those with prosthetic valveendocarditis that affects a mechanical valve), then a switchto intravenous unfractionated heparin is recommended.Whenever possible, the primary source of infection re-sponsible for IE should be eliminated before cardiacsurgical intervention.

Intraoperative Management

ImagingThe operating table is an inappropriate place for cardiacdiagnosis, and full anatomic characterization is requiredbefore surgery is undertaken. Perioperative transesophagealechocardiography is a useful tool to determine the exactlocation and extent of infection,33 assist the choice of recon-struction procedure, validate the surgical result, and guideperioperative hemodynamic management.

MicrobiologyThe excised native or prosthetic valve should be sent to themicrobiology laboratory in physiological saline for immedi-ate culture. A Gram’s stain is useful for immediate diagnosis,and molecular examination of excised valve tissue may playa role, particularly in culture-negative patients.34

Surgical TechniqueThe 2 primary objectives of surgery are control of infectionand reconstruction of cardiac morphology.35 The mode ofsurgery (replacement versus repair) or type of prosthesisused (mechanical versus biological) has no influence onoperative mortality,36 although repair techniques, whenapplicable, offer long-term advantages, including a re-duced risk of late complications (notably, recurrent IE) andobviation of the need for lifelong anticoagulation.37 Ho-mografts offer a reduced risk of recurrent infection in aorticIE,38 although their use remains controversial owing to ahigher risk of late complications.39 Cardiac transplantationmay be considered in extreme cases with recurrent prostheticvalve endocarditis.40

Indications for SurgeryTables 2 and 3 present information on indications for andtiming of surgery, and the Figure presents surgical indicationsin native valve IE. However, it is important to remember thatno randomized controlled trials are available to guide currentpractice. Nor are they likely; such studies would be difficultto perform owing to the diversity of patients with IE, therelatively small numbers available for study, and potentialethical concerns if surgery were to be withheld in controlpatients. What available evidence, therefore, guides currentpractice and international recommendations?

Congestive Heart Failure Due toValvular RegurgitationAmong the complications of IE, congestive heart failure hasthe greatest impact on prognosis.14,15 Studies from the 1970sand 1980s compared medical and surgical treatment ofcongestive heart failure complicating IE and demonstrated aconsistent reduction in mortality after surgery, from a rangeof 56% to 86% to a range of 11% to 35%.41,42 Although nocorrection was made for underlying comorbidity, similarresults were reported in 2 more recent Scandinavian stud-ies,26,43 in which the best results were obtained with earlyintervention within 1 week of presentation. Early valvesurgery in patients with congestive heart failure is associatedwith a substantial reduction in mortality compared withmedical therapy alone,5,15,21,22,44 and this scenario is now themost common and clearest indication for surgery, beingpresent in 72% of patients who underwent early interventionin a recent European series.19

Congestive heart failure is usually the result of valvularregurgitation, which may develop acutely as a result ofperforation of a native valve or bioprosthetic valve leaflet orrupture of infected mitral chordae. Rarer causes include valveobstruction by bulky vegetations and sudden intracardiacshunts from fistulous tracts or prosthetic dehiscence. Acuteaortic regurgitation is poorly tolerated and usually rapidlyprogressive. Urgent surgery is indicated regardless of thestatus of the infection, particularly when evidence of pulmo-nary edema or cardiogenic shock exists, or echocardiographicevidence of rapidly rising left ventricular end-diastolic pres-sure (premature closure of the mitral valve). Acute mitralregurgitation may be better tolerated as a consequence ofoffloading into the left atrium and pulmonary bed; however,acute pulmonary edema may develop as a result of the rapidincrease in left atrial pressure, and urgent surgical interven-tion is frequently required.

Patients with less dramatic presentation may respond wellto initial medical therapy with diuretics and short-termafterload reduction with vasodilator therapy. No clear evi-dence exists to guide management strategy in this situation,and many physicians and surgeons are reluctant to recom-mend early surgery. Thus, in the absence of other immediateindications, intervention may be postponed in the short termto allow a brief period of antibiotic therapy under carefulclinical and echocardiographic observation. Conversely, mildcongestive heart failure at initial presentation may progressinsidiously despite appropriate antibiotic therapy, usuallywithin the first month of treatment. Delayed surgery in thesecircumstances is unacceptable, being associated with a dra-matic rise in operative mortality45 as a consequence ofprogressive cardiac decompensation and exposure of thepatient to secondary risks of the disease and its treatment.

In the occasional patient with well-tolerated valvular re-gurgitation and no other indication for surgery, medicalmanagement with antibiotics is recommended under strictclinical and echocardiographic control. Surgery can then beconsidered at a later stage after healing of the infection,depending on tolerance of the valve lesion. This strategy maybe particularly attractive in the elderly comorbid patient whopresents extreme surgical risk and in the young patient for




whom valve replacement may pose lifelong hazard, particu-larly in females of childbearing potential.

The surgical approach in IE patients with congestive heartfailure is tailored to the extent of distortion of the valve andits surrounding structures. Prosthetic replacement is requiredin the majority, although innovative techniques of valverepair are increasingly applicable, especially when infectioninvolves the mitral valve.37 Ruptured mitral chordae may berepaired with a combination of leaflet resection, chordalreattachment or transposition, and annular support, andleaflet perforations are often amenable to repair with asmall pericardial patch, provided that valve integrity andmotion are preserved.

Periannular ExtensionExtension of IE beyond the valve annulus is associated withincreased mortality, development of congestive heart failure,and a higher likelihood of surgery.46 Periannular extension iscommon, affecting 10% to 40% of patients with native valveIE, and is most frequent in IE that affects the aortic valve,when abscess expansion near the membranous septum andatrioventricular node may result in heart block. Periannularinfection is of even greater concern in prosthetic valveendocarditis, occurring in 56% to 100% of patients, andaccounts for high mortality in this group.47

Diagnosis is achieved by a high index of suspicion,particularly when fever and inflammatory markers fail to

Table 2. Indications for Surgery in IE

Congestive heart failure*

Congestive heart failure caused by severe aortic or mitral regurgitation or, 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 pulmonaryhypertension

Congestive heart failure as a result of prosthetic dehiscence or obstruction

Periannular extension

Most patients with abscess formation or fistulous tract formation

Systemic embolism†

Recurrent emboli despite appropriate antibiotic therapy

Large vegetations (�10 mm) after 1 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)

Cerebrovascular complications‡

Silent neurological complication or transient ischemic attack and other surgical indications

Ischemic stroke and other surgical indications, provided that cerebral hemorrhage has been excluded and neurological complications are not severe (eg,coma)

Persistent sepsis

Fever or positive blood cultures persisting for �5 to 7 days despite an appropriate antibiotic regimen, assuming that vegetations or other lesions requiringsurgery persist and that extracardiac sources of sepsis have been excluded

Relapsing IE, especially when caused by organisms other than sensitive streptococci or in patients with prosthetic valves

Difficult organisms

S aureus IE involving a prosthetic valve and most cases involving a left-sided native valve

IE caused by other aggressive organisms (Brucella, Staphylococcus lugdunensis)

IE caused by multiresistant organisms (eg. methicillin-resistant S aureus or vancomycin-resistant enterococci) and rare infections caused by Gram-negativebacteria

Pseudomonas aeruginosa IE

Fungal IE

Q fever IE and other relative indications for intervention

Prosthetic valve endocarditis

Virtually all cases of early prosthetic valve endocarditis

Virtually all cases of prosthetic valve endocarditis caused by S aureus

Late prosthetic valve endocarditis with heart failure caused by prosthetic dehiscence or obstruction, or other indications for surgery

*Surgery should be performed immediately, irrespective of antibiotic therapy, in patients with persistent pulmonary oedema or cardiogenic shock. If congestive heartfailure disappears with medical therapy and there are no other surgical indications, intervention can be postponed to allow a period of days or weeks antibiotictreatment under careful clinical and echocardiographic observation. In patients with well tolerated severe valvular regurgitation or prosthetic dehiscence and no otherreasons for surgery, conservative therapy under careful clinical and echocardiographic observation is recommended with consideration of deferred surgery afterresolution of the infection, depending upon tolerance of the valve lesion.

†In all cases, surgery for the prevention of embolism must be performed very early since embolic risk is highest during the first days of therapy.‡Surgery is contraindicated for at least one month after intracranial haemorrhage unless neurosurgical or endovascular intervention can be performed to reduce

bleeding risk.




settle despite appropriate antibiotic therapy. The developmentof new atrioventricular block is highly predictive of abscessformation, and diagnosis is best confirmed by transesopha-geal echocardiography.

Untreated, abscess cavities may progress to create fistuloustracts with resultant intracardiac or pericardial shunts. Thisdevastating complication was associated with a mortality rateof 41% in the largest collected series, despite surgicalintervention in 87% of the patients.48 Factors associated withmortality included moderate to severe congestive heart fail-ure, prosthetic valve involvement, and need for an urgentoperative procedure. Despite these gloomy statistics, medicaltherapy is insufficient, with no prospect of cure, and urgentsurgery is indicated, even when the patient remains hemody-namically stable.

Surgery for periannular extension involves drainage ofabscess cavities, excision of necrotic tissue, and closure offistulous tracts where appropriate. Valve replacement isusually necessary, and use of aortic homografts or stentlessvalves may be considered when extensive destruction ofperiannular supporting tissues poses surgical difficulties.49,50

Complete heart block that requires a permanent pacemaker iscommon in the postoperative period.

A limited number of patients may be suitable for medicaltherapy alone.51 These include those with small abscesscavities (�1 cm), sensitive organisms, and no evidence ofcoexistent heart block or valve destruction. Serial monitoringwith transesophageal echocardiography is mandatory both

during antibiotic therapy and in the immediate period aftercompletion of treatment.

Systemic EmbolismSystemic embolism occurs in 22% to 50% of patients with IEand is frequently accompanied by devastating clinical conse-quences.52,53 The central nervous system is most frequentlyaffected, accounting for 65% of embolic events, 90% ofwhich arise in the distribution of the middle cerebral artery.53

However, no vascular bed is spared, and emboli may involvethe lungs, coronary arteries, spleen, liver, bowel, and periph-eral vasculature. Embolic complications may also be clini-cally silent in up to a quarter of cases and only detected bysystematic imaging.54,55

The highest rate of embolic complications is seen inleft-sided IE, especially when infection is related to Staphy-lococcus aureus, Candida, HACEK (Haemophilus parainflu-enzae, H aphrophilus, H paraphrophilus, Actinobacillus ac-tinomycetemcomitans, Cardiobacterium hominis, Eikenllacorrodens, and Kingella species), and Abiotrophia organisms.Although embolic complications may arise at any stage in thenatural history of IE, most events occur before the diagnosisis made or within 2 weeks thereafter. Importantly andspecifically in relation to the timing of surgery, severalindependent studies have confirmed that embolic risk fallsdramatically during or after the first 2 to 3 weeks ofsuccessful antibiotic therapy.52,56,57 For example, recent datafrom the International Collaboration on Endocarditis demon-strated that the incidence of stroke in patients receivingappropriate antimicrobial therapy was 4.8/1000 patient-daysduring the first week of therapy, which fell to 1.7/1000patient-days in the second week and lower thereafter.57

Identification of factors predictive of embolic complica-tions (and thereby identification of which patients will benefitfrom earliest surgery) has been the subject of detailedinvestigation. Several echocardiographic and clinical param-eters have been associated with increased risk of embolism,including the size and mobility of vegetations,52,54,56–61 loca-tion on the mitral valve,56,58,59,61 increasing size while antibi-otic therapy is being given,56,60 infection with specific micro-organisms (staphylococci,56 Streptococcus bovis,62 Candidaspecies), previous embolism,56 multivalvular infection,58 andbiological markers.63 Overall, risk of new embolism is great-est in patients with large (10 to 15 mm) mobile vegetations,especially in staphylococcal IE that involves the mitral valve.This risk is greatest during the first few days of antibiotictherapy, and the benefits of surgery to prevent embolism aretherefore greatest at this time; deferred surgery after 2 to 3weeks for this indication alone is of little value. A lowthreshold for early surgery is most appropriate for patients inwhom a conservative procedure (isolated excision of thevegetation and/or valve repair) is likely or when other factorspredict adverse outcome (eg, severe valvular regurgitation orinfection with a difficult microorganism). In others, thelong-term hazards associated with a mechanical prosthesismay not justify early intervention.

Timing of Surgery in Patients WithCerebrovascular ComplicationsNeurological events arise in 20% to 40% of patients with IE,mainly as a consequence of vegetative embolism,53,55,64 and

Table 3. Timing of Surgery

Emergency surgery (within 24 hours)

Native (aortic or mitral) or prosthetic valve endocarditis and severecongestive heart failure or cardiogenic shock caused by:

Acute valvular regurgitation

Severe prosthetic dysfunction (dehiscence or obstruction)

Fistula into a cardiac chamber or the pericardial space

Urgent surgery (within days)

Native valve endocarditis with persisting congestive heart failure, signs ofpoor hemodynamic tolerance, or abscess

Prosthetic valve endocarditis with persisting congestive heart failure,signs of poor hemodynamic tolerance, or abscess

Prosthetic valve endocarditis caused by staphylococci or Gram-negativeorganisms

Large vegetation (�10 mm) with an embolic event

Large vegetation (�10 mm) with other predictors of a complicatedcourse

Very large vegetation (�15 mm), especially if conservative surgery isavailable

Large abscess and/or periannular involvement with uncontrolled infection

Early elective surgery (during the in-hospital stay)

Severe aortic or mitral regurgitation with congestive heart failure andgood response to medical therapy

Prosthetic valve endocarditis with valvular dehiscence or congestive heartfailure and good response to medical therapy

Presence of abscess or periannular extension

Persisting infection when extracardiac focus has been excluded

Fungal or other infections resistant to medical cure




are most common in those with S aureus infection.53,55 Theclinical spectrum of complications is wide and includesischemic or hemorrhagic stroke, transient ischemic attack,silent cerebral embolism, symptomatic or asymptomatic my-cotic aneurysm, cerebral abscess, meningitis, toxic encepha-lopathy, and seizure. All manifestations are associated withexcess mortality.55,65 As described above, rapid diagnosis andinitiation of appropriate antibiotic therapy are fundamental inthe prevention of a first or recurrent neurological event.

Most patients with a neurological complication have atleast 1 other indication for cardiac surgery. Although inherentconcerns exist about the role of surgery in these situations(fear of neurological deterioration or perioperative cerebralbleeding), these risks are low after a silent cerebral embolismor transient ischemic attack,55 and surgery can be performedwithout delay. Similarly, cardiac surgery is not contraindi-cated after an ischemic stroke, although evidence on optimaltiming is conflicting owing to a lack of controlled stud-ies.55,66–69 Nevertheless, surgery should not be delayed whenindicated for congestive heart failure, uncontrolled infection,abscess, or persistent high embolic risk, provided that cere-bral hemorrhage has been excluded by cranial CT andneurological damage is not severe (eg, coma). In thesecircumstances, cardiac surgery can be performed with rela-tively low neurological risk (3% to 6%) and a good chance ofcomplete neurological recovery.69 Neurological prognosis ismore dismal in the presence of intracranial hemorrhage, andcardiac surgery should be postponed for at least 1 month.66,67

Earlier surgery may be contemplated in the occasional patientwith cerebral bleeding from an isolated mycotic aneurysm, inwhom neurosurgical or endovascular intervention may pro-duce a sufficient reduction in the risk of recurrent bleeding topermit cardiopulmonary bypass.70 In these circumstances, use

of a bioprosthesis (or valve repair when applicable) ispreferred to avoid the need for long-term anticoagulation.

Persistent SepsisPersistent bacteremia despite appropriate antibiotic therapyand in the absence of an extracardiac source (for example, asplenic, vertebral, or renal abscess) implies ongoing intracar-diac sepsis and is an indication for early surgery. Thissituation is more common with aggressive organisms, includ-ing S aureus,21 and when vegetations are bulky and resistantto antibiotic penetration. Current guidelines indicate thatsurgery should be considered if fever or positive bloodcultures persist after 7 days of appropriate therapy.

An important distinction is the patient who developsrecurrent fever after initially favorable progress. In thissetting, antibiotic sensitivity or an alternative source ofinfection (including the possibility of central-line coloniza-tion) is likely, and surgery should only be considered oncethese have been excluded with confidence. Relapse afterinitially successful treatment is more common in nonstrepto-coccal IE and in patients with prosthetic valve endocarditis,and early surgery should be considered in these patients.

Difficult OrganismsSeveral microbial agents are resistant to therapy and merit avigorous surgical approach, particularly when other relativeindications coexist. S aureus IE is characterized by anaggressive clinical course associated with severe valvulardamage, large vegetations, embolic complications, and over-all poor prognosis.18,21,71 Early surgery should be consideredin all cases affecting a prosthetic valve and most casesaffecting a left-sided native valve if an immediate response isnot obtained with appropriate antibiotic therapy.

Figure. Surgical indications in native valve IE.




Pseudomonas aeruginosa is an uncommon cause of IEusually associated with nosocomial infection. Although med-ical therapy may suffice in right-sided disease, this is rarelyeffective in left-sided disease, and surgery offers the bestprospect of complete cure.72

Coxiella burnetii, the agent responsible for Q fever, isresistant to medical cure, and recolonization after successfulvalve surgery is a frequent event. Surgery is recommended inpatients with congestive heart failure, prosthetic valve endo-carditis, and uncontrolled infection,73 and prolonged postop-erative antimicrobial therapy (18 to 24 months) guided by theresults of serology is recommended to prevent recurrence.74

Brucella IE is characterized by an aggressive course withfrequent valve destruction, congestive heart failure, andabscess formation. Antimicrobial therapy alone is rarelyeffective, and early surgery is recommended.75 Similarly,Staphylococcus lugdunensis is an aggressive coagulase-negative staphylococcus with a high rate of cardiac tissuedestruction and indicates a need for early valve surgery.76

Fungal IE, secondary to infection with Candida or As-pergillus, is often complicated by bulky vegetations, meta-static infection, periannular spread, and embolic events.Penetration of antifungal agents (notably, amphotericin B)into infected material is poor, and surgery is almost alwaysnecessary, particularly when complications are present.77

Long-term (potentially lifelong) antifungal therapy with anoral azole may have the ability to suppress infection inselected patients, and this approach may be considered inthose who are otherwise unfit for surgery.78

Surgery provides the only means of eradication of infectionwhen IE is caused by multiresistant organisms, includingmethicillin-resistant S aureus and vancomycin-resistant en-terococci. Careful microbiological liaison is essential todetermine appropriate antibiotic management during the post-operative period.

Prosthetic Valve EndocarditisProsthetic valve endocarditis accounts for 10% to 20% ofmost series, with an overall incidence of 0.1% to 2.3% perpatient-year.6,79 Cases may be classified as early or latedepending on whether infection arises within 1 year ofsurgery or later. The aortic valve is most frequently affected,and metallic prostheses and bioprostheses are equally suscep-tible. Early surgery is required in approximately 50% ofpatients, and in-hospital mortality approaches 30%.6,16,36

Furthermore, long-term follow-up is frequently complicatedby recurrent infection, hemodynamic complications, need forrepeat surgery, and death.

The incidence of early-onset prosthetic valve endocarditishas fallen dramatically in the past 3 decades as a result ofimprovements in surgical technique, perioperative antibioticmanagement, and operating room sterility. Early infectionpeaks 2 months after surgery and is most often due tocoagulase-negative staphylococci or S aureus.6 Spread ofinfection beyond the points of attachment of the valveprosthesis is almost inevitable, and root abscesses and valvedehiscence (with resultant instability of the prosthesis orparavalvular leak) arise in 60% of cases. Surgical treatmentresults in improved survival at both immediate and long-term

follow-up and reduced incidence of relapse or need for repeatsurgery compared with medical therapy.80 When indicated,surgery is best performed early, especially when infection iscaused by S aureus.81,82 Operations are frequently technicallydemanding, requiring radical debridement and reconstruction,and these procedures are best undertaken by an experiencedsurgical team. Reflecting this, rates of recurrent prostheticvalve endocarditis are high at 6% to 15%, and further surgeryfor this indication or dysfunction of the newly implantedprosthesis is required in up to 25% of patients.83,84

The microbial spectrum of late prosthetic valve endocar-ditis mirrors that of native valve disease. Aggressive tissuedestruction is less frequent, and early antibiotic therapy isable to effect a cure in many patients, especially those inwhom infection is caused by a sensitive organism, for whomsurgery is often unnecessary.85 An exception is late prostheticvalve endocarditis due to S aureus, for which the prognosis isdismal.86

Special SubgroupsThe ElderlyValvular heart disease is increasingly frequent in the agingpopulation, and elderly patients undergo an increasing varietyof invasive medical interventions. Patients �65 years of agehave an increased risk of IE, and diagnosis in this group maybe particularly difficult because of delayed presentation,subtle clinical signs, and frequent use of pragmatic andempirical antibiotic therapy before hospital admission.87

Overall outcome is poor,88,89 and although attendant comor-bidity may complicate decision making, age alone is not apreclusion to surgery.90

Intravenous Drug UsersIntravenous drug users predominate in series of young peo-ple, and the overall incidence of IE in this group is 1% to 5%per year.91 The tricuspid valve is infected in �70% of cases,and the majority have no known preexisting cardiac dis-ease.91,92 S aureus species predominate, although unusualinfections including P aeruginosa, fungi, Bartonella, Salmo-nella, and Listeria may also be encountered, particularly inthose who are infected with the human immunodeficiencyvirus, for whom the outcome is inversely related to the CD4count.93

This group of patients presents particular managementdifficulties because of their drug-seeking behavior and poorcompliance with treatment. They often struggle with pro-longed hospitalization as a result. Medical therapy is usuallyrecommended, and short-course therapy and oral regimensmay be considered in view of the difficulties with compli-ance. Surgery is occasionally required for complications ofleft-sided disease when indications are the same as fornon-drug users. The threshold for intervention and choice ofsurgical approach may be altered, however, in individualpatients in whom recurrence of infection due to continueddrug abuse or compliance with anticoagulant therapy presentsa dilemma94; use of a homograft may be worthy of consid-eration in these situations. Infection with the human immu-nodeficiency virus is not a contraindication to cardiac sur-gery, and postoperative complications, including mortality,




are not increased in this group.95 Furthermore, concerns thatcardiac surgeons may be exposed to significant risk ofacquiring infection with human immunodeficiency virus fromthese patients have proved unfounded. With drug-inducedpreoperative reduction of viral load, use of appropriateprecautions, and chemoprophylaxis in the event of needlestick injury, no definite transmission to a surgeon duringcardiac surgery has been reported.

Right-Sided EndocarditisA conservative approach is recommended for the majority ofpatients with IE affecting the tricuspid or pulmonary valve.96

Recurrent pulmonary emboli are not an indication for sur-gery, which is only needed if fever persists despite 3 weeks ofappropriate antibiotic treatment in the absence of a pulmo-nary abscess.28 Surgical options include debridement of theinfected area, vegetation excision with either valve preserva-tion or valve repair, and excision of the tricuspid valve, withprosthetic valve replacement.96,97 Tricuspid valvectomy with-out use of a prosthesis has been advocated in extreme casesbut may be associated with severe postoperative right-sidedheart failure, particularly in patients with pulmonary hyper-tension as a result of multiple pulmonary emboli. Preserva-tion of the native pulmonary valve is recommended wheneverpossible, and use of a homograft or xenograft is preferred ifreplacement is unavoidable.

Device-Related EndocarditisThe incidence of IE related to permanent pacemakers, im-plantable defibrillators, and (rarely) other intracardiac devicesis rising as a consequence of their widespread use.98 Man-agement is difficult, and entire system removal is necessary,although advances in percutaneous techniques mean thatinvolvement of the cardiac surgeon is usually not required.When needed, surgery requires adequate exposure underextracorporeal circulation to allow complete removal offoreign material and excision of all infected contact lesions atthe level of the tricuspid valve, right atrium, free wall of theright ventricle, and distal superior vena cava.99 Eradication ofinfection is essential before implantation of a new system,which itself may require a second surgical approach.

Postoperative ManagementA detailed discussion of postoperative management andfollow-up is beyond the scope of this article and covered inpublished European guidelines.100 In the vast majority ofpatients, a total duration of 6 weeks of antibiotic therapy isrecommended regardless of the timing of surgery. Positivecultures of excised valve tissue usually reflect intended earlyvalve surgery and do not indicate the need for a prolonged6-week course of postoperative antibiotic therapy. In the rarecircumstances in which surgery is performed late and valvecultures remain positive, the duration of postoperative treat-ment should be discussed with the microbiological team andtailored to the circumstances and characteristics of the indi-vidual patient. A postoperative transthoracic echocardiogramafter completion of antibiotic therapy is helpful to confirmcure and provides a new baseline to facilitate long-termfollow-up.

Survivors of surgery are a high-risk group for recurrent IE,and patients should be made aware of the need to seek earlymedical advice for fever or other potentially concerningsymptoms. Similarly, family physicians caring for this cohortshould be made aware of the need for blood culture samplingbefore use of empirical antibiotic therapy. Prosthetic valve IEis potentially avoidable, and patient education about theimportance of dental and skin hygiene, avoidance of unnec-essary medical instrumentation (eg, intravenous cannulas,urinary catheterization), and use of antibiotic prophylaxis atthe time of appropriate invasive procedures is essential in thisgroup.

ConclusionsSurgery has an established role in the management of IEacross a wide range of patients, a role that appears poised toincrease as the complexity of patients with this difficultcondition rises and the benefits of earlier surgery emerge. Aslarge international research collaborations become estab-lished, the future may see a more robust evidence base toguide management strategy. Nevertheless, decision making inindividual patients will remain difficult, with the best out-comes obtained as a result of expert multidisciplinary collab-oration between the cardiologist, microbiologist, and cardiacsurgeon. Only with such interaction will the questions of whoand when seem easier.

Sources of FundingThe work of Dr Prendergast is supported by the Oxford PartnershipComprehensive Biomedical Research Centre with funding from theDepartment of Health’s National Institute for Health ResearchBiomedical Research Centres funding scheme. The views expressedin this publication are his and not necessarily those of the Depart-ment of Health.

DisclosuresDrs Prendergast and Tornos are nucleus members of The EuropeanSociety of Cardiology Working Group on Valvular Heart Diseaseand contributed to the 2009 European Society of Cardiology Guide-lines on the Management of Infective Endocarditis. Both authorsacknowledge the stimulating discussions with other Guidelines TaskForce members which helped shape the views expressed within thismanuscript.

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KEY WORDS: infection � surgery � valves � endocarditis � patient selection




Bernard D. Prendergast and Pilar TornosSurgery for Infective Endocarditis: Who and When?

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