Gilbert Habib. Valve disease MANAGEMENT OF INFECTIVE ENDOCARDITIS TO DIAGNOSE INFECTIVE ENDOCARDITIS?

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1 124 Take the online multiple hoie questions assoiated with this artile (see page 130) HOW Correspondene to: Dr Gilbert Habib, Hôpital Timone, Cardiologie B, Boulevard Jean Moulin, Marseille, Frane; I Valve disease MANAGEMENT OF INFECTIVE ENDOCARDITIS Gilbert Habib Heart 2006; 92: doi: /hrt nfetive endoarditis (IE) is a disease that is ontinually hanging, with new high risk patients, new diagnosti proedures, the involvement of new miroorganisms, and new therapeuti methods. 1 Despite knowledge of these hanges, and onsiderable improvements in diagnosti and therapeuti strategies, IE is still a severe disease. 2 The high morbidity and mortality rate of IE is the onsequene of both the destrutive valvar lesions ausing valve regurgitation and heart failure, and the valvar vegetations with their high emboli potential. Although the inidene of IE is relatively stable, those patients affeted by the disease are older and siker, and the omorbidity rate is high. 3 As soon as the diagnosis of IE is suspeted, the physiian is faed with four speifi problems: First, the diagnosis of IE is still diffiult and is frequently delayed, ausing progressive and irreparable valvar damage. Seond, IE is still assoiated with high in-hospital mortality, ranging from 16 25%, and high inidene of emboli events, ranging from 10 49%, potentially the soure of severe ompliations and sequelae. 4 Third, the optimal therapeuti strategy in these patients is still to be defined and may vary in the individual patient. Fourth, some patients present with speifi features or ompliations and need a speifi management. These four issues will be addressed here. TO DIAGNOSE INFECTIVE ENDOCARDITIS? When to onsider IE? The knowledge of potential at-risk patients may inrease the level of suspiion of IE. Although the absolute number of new ases of IE has not hanged over the last 10 years, the at-risk population has been ompletely modified during this period. Rheumati valve disease is no longer the main underlying disease in IE, and has been replaed by an inreasing number of episodes of IE ourring on intraardia devies, in intravenous drug abusers, and haemodialysis or elderly patients. Nosoomial disease is also muh more frequent. Thus, we have to onsider IE in all these situations. Ourring in suh a broad range of patients and irumstanes, the linial presentation of IE may also be varied, inluding symptoms suh as fever and ardia and non-ardia manifestations. Fever is the most frequent symptom of IE, but may be absent in patients with severe debility or elderly patients, and in the ase of previous antibioti treatment. Fever is frequently intermittent in IE and may be assoiated with weight loss, fatigue, and anorexia. Cardia manifestations inlude ongestive heart failure, new heart murmur, and atrioventriular blok. Severe heart failure in the ontext of IE is generally the onsequene of severe valvar lesions. These patients require lose follow up and frequently urgent surgery is mandatory. Finally, extraardia manifestations may be the first sign of IE, inluding utaneous manifestations (fig 1), splenomegaly, rheumatologial symptoms, neurologial manifestations, or other onsequenes of vegetation embolism (fig 2). In right sided and paemaker lead endoarditis, the linial presentation is frequently atypial and inludes loal and pulmonary symptoms as the first manifestations of the disease. 5 Finally, IE has to be suspeted both in very aute situations inluding ardiogeni or septi shok (fulminant endoarditis) representing life threatening situations, as well as in the ase of more insidious presentations for example, prolonged unexplained fever in whih ase the diagnosis of IE is the main hallenge. In all these situations, ehoardiography and blood ultures have to be performed. How to diagnose IE? IE may be suspeted when non-speifi laboratory abnormalities are present, inluding anaemia, leuoytosis, elevated C reative protein, and sedimentation rate. However, the diagnosis of IE is mainly based on two tests blood ulture and ehoardiography. Heart: first published as /hrt on 19 Deember Downloaded from on 23 July 2018 by guest. Proteted by opyright.

2 Figure 1 Cutaneous manifestations in infetive endoarditis. (A) Osler s node in a patient with hypertrophi obstrutive ardiomyopathy and streptooal endoarditis. (B) Severe purpuri lesions in a woman with staphylooal paemaker endoarditis. (C) Digital hipporatism in a patient with hroni streptooal infetive endoarditis. Blood ulture is the best method for identifiation of the miroorganisms ausing IE. Blood ultures are positive in about 90% of ases, but may be negative in ases of intraellular or fastidious pathogens or after previous antibioti treatment. Performing blood ultures before any antibioti treatment is thus mandatory when IE is suspeted. Ehoardiography has to be performed in all ases of suspeted IE. It ombines the advantages of identifying vegetations, absesses, and new prostheti dehisene, whih are the hallmarks of IE, assessing the severity of valve damage, deteting ardia ompliations, and prediting prognosis and emboli risk. 6 Transthorai ehoardiography (TTE) must be performed first, and has a sensitivity of about 75% for the diagnosis of vegetations. Transoesophageal ehoardiography (TOE) is mandatory in ases of doubtful transthorai examination, in prostheti and paemaker IE, and when an absess is suspeted. TOE enhanes the sensitivity of TTE to about 85 90% for the diagnosis of vegetations, and the additive value of TOE is even more important for the diagnosis of absesses and, more generally, perivalvar extension, inluding false aneurysms, perforations, and fistulas. Figures 3 and 4 illustrate the exellent orrelation between ehoardiographi and anatomi findings. However, both ehoardiography and blood ultures may be falsely negative in some patients. To reonile suh Figure 2 Peripheral manifestations of infetive endoarditis (IE). (A) Large myoti aneurysm of the ilia artery, whih was suessfully treated by interventional atheterisation. (B) Cerebral infartion demonstrated by omputed tomographi san in a patient with staphylooal IE. (C) Emboli obstrution of the left anterior desending (arrow) oronary artery in a 45 year old patient with Streptoous bovis endoarditis. (D) Same patient after suessful emergeny perutaneous transluminal oronary angioplasty. 125 Heart: first published as /hrt on 19 Deember Downloaded from on 23 July 2018 by guest. Proteted by opyright.

3 126 Figure 3 Ehoardiographi/anatomi orrelations. Myoti aneurysm of an aorti leaflet (arrow). AO, aorta; LA, left atrium; LV, left ventrile; RV, right ventrile. differing linial pitures and underline the value of both blood ultures and ehoardiography, Durak et al 7 proposed new riteria for IE (table 1). The value of these riteria has been largely onfirmed by several studies, 8 giving a mean sensitivity of about 80% for the diagnosis of IE. However, we must remember that Duke riteria were developed to help epidemiologial and linial researh studies and not for their appliation to linial pratie. In addition, despite suessive attempts at refinement, the diagnosti riteria have some limitations, and are of very limited value in some subgroups. Sometimes diffiult? In linial pratie, the diagnosis of IE remains diffiult in three main situations: in the ase of normal or doubtful ehoardiography in IE affeting intraardia devies in blood ulture negative IE (BCNIE). Negative ehoardiography findings may be observed in about 15% of ases of IE. The most frequent explanations for negative ehoardiography are very small or absent vegetations and diffiulties in identifying vegetations in the presene of pre-existent severe lesions (mitral valve prolapse, degenerative lesions, prostheti valves). Conversely, false diagnosis of IE may our in other situations for example, it may be diffiult to differentiate between vegetations and thrombi, usp prolapse, ardia tumours, myxomatous hanges, Lambl s exresenes, strands, or non-infetive vegetations (maranti endoarditis). Similarly, diagnosis of a perivalvar absess may be diffiult, even with the use of TOE, when ehoardiography is performed very early in the ourse of the disease, or in the immediate postoperative period following aorti root replaement or Bentall proedure. In these latter situations, a thikening of the aorti wall may be observed in the absene of IE, mimiking absess formation. More importantly, a normal ehoardiogram does not ompletely rule out IE, even if TOE is performed in expert hands, and a repeat examination has to be performed where there is a high level of linial suspiion. Infetive endoarditis affeting intraardia devies is a growing disease. Paemaker endoarditis is a diffiult diagnosis, espeially in its hroni forms, in whih loal symptoms, pneumonia, or even spondylitis may be the first symptoms of the disease. 5 In both paemaker lead IE and prostheti valve IE (PVIE), the diagnosis is frequently delayed, and both ehoardiography and blood ultures are more frequently negative than in IE affeting native valves. Heart: first published as /hrt on 19 Deember Downloaded from Figure 4 Ehoardiographi/anatomi orrelations. Large vegetations on the two mitral leaflets (arrow). on 23 July 2018 by guest. Proteted by opyright.

4 Table 1 Duke riteria for infetive endoarditis (IE) 7 Major riteria Blood ultures positive for IE Typial miroorganisms onsistent with IE: Viridans streptooi, Streptoous bovis, HACEK group, Staphyloous aureus; or Community aquired enterooi, in the absene of a primary fous; or Miroorganisms onsistent with IE from persistently positive blood ultures; or Single positive blood ulture for Coxiella burnetii or phase I IgG antibody titre.1:800 Evidene of endoardial involvement Ehoardiogram positive for IE: Vegetation Absess New partial dehisene of prostheti valve New valvar regurgitation Minor riteria Predisposition, predisposing heart ondition, injetion drug use Fever, temperature.38 C Vasular phenomena, major arterial emboli, septi pulmonary infarts, myoti aneurysm, intraranial haemorrhages, Janeway s lesions Immunologi phenomena: glomerulonephritis, Osler s nodes, Roth s spots, rheumatoid fator Mirobiologial evidene: positive blood ulture but does not meet a major riterion Diagnosis of IE is definite in the presene of: two major riteria, or one major and three minor riteria, or five minor riteria. Diagnosis of IE is possible in the presene of: one major and one minor riteria, or three minor riteria. HACEK, Heamophilus, Atinobaillus, Cardiobaterium, Eikenella, Kingella For these reasons, Duke riteria have a low sensitivity and annot reasonably be applied in these two populations, even when proposed modifiations are applied. Blood ulture negative IE is the third situation in whih the diagnosis of IE is partiularly diffiult. BCNIE is observed in about 10% of ases and may be explained in the majority of patients by prior antibioti treatment, underlying the need to perform blood ultures in high risk patients before any antibioti treatment, when they present with fever. In a reent series, 9 63 ases of BCNIE were studied, in whih previous antibioti treatment had been administered in half of the patients. In another signifiant group of patients with BCNIE, blood ultures are negative beause of diffiulty in isolating ertain miroorganisms, inluding Coxiella burnetii, Bartonella speies, Tropheryma whipplei, Bruella speies, Chlamydia speies, Aspergillus speies, and Legionella speies. In another more reent series, 10 among 348 ases of BCNIE, 167 (48%) were assoiated with C burnetii, 99 (28%) with Bartonella speies, and 5 (1%) with rare, fastidious agents of endoarditis (T whipplei, Abiotropha elegans, Myoplasma hominis, Legionella pneumophila). Among 73 ases without aetiology, 58 reeived antibioti treatment before blood ultures. Several methods of identifiation have been proposed to enhane the sensitivity of detetion of these miroorganisms, inluding serology, isolation from another site, mirosopy of the exised valve, polymerase hain reation (PCR) identifiation of the exised valve, 11 or even histology of the valve. 12 Serology is nearly always systematially performed when IE is suspeted. Serology is partiularly useful for the diagnosis of Q fever. Reently, positive serology for Q fever was added as a major Duke riterion and this modifiation has been shown to improve the sensitivity of Duke riteria. 13 PCR of the exised valve must be performed in all ases of BCNIE and has been shown to be a very useful adjunt to blood ultures and serology for the diagnosis of IE. However, PCR results may remain positive several months after IE is resolved, and must be interpreted with aution. Finally, histologi examination of the infeted valve may also be useful in diffiult ases, and histologi riteria have been reently proposed. 12 As in patients with paemaker lead IE or PVIE, Duke riteria are diffiult to apply in patients with negative blood ulture. Despite several proposed modifiations to the Duke riteria, it is lear that they annot be effetive in all situations. No published riteria an replae linial judgement in the diagnosis of IE. HOW TO ASSESS THE RISK OF EMBOLISM AND DEATH IN INFECTIVE ENDOCARDITIS Who is at risk of embolism? Emboli events are a frequent and life threatening ompliation of IE. 4 They are related to the migration of ardia valvar vegetations into the major arterial beds, inluding brain, lungs, spleen, and oronary arteries (fig 5). Embolism is assoiated with an inreased morbidity and mortality in IE. Thus, an aurate predition of the emboli risk is a desirable goal. Embolism ours in 20 40% of IE, but its inidene dereases to 9 21% after initiation of antibioti treatment. Embolism may be asymptomati in about 20% of patients with IE and must be diagnosed by systemati non-invasive imaging. Ehoardiography plays a key role in prediting emboli events. Several fators have been assoiated with an inreased risk of embolism, inluding the size and mobility of vegetations, the loalisation of the vegetation on the mitral valve, the inreasing or dereasing size of the vegetation under antibioti treatment, some miroorganisms (staphylooi, Streptoous bovis, Candida speies), and biologial markers. However, although still ontroversial, the size and mobility of the vegetations are the most potent independent preditors of new emboli events in patients with IE. In a reent series of 384 patients, 14 an emboli event was observed in 131 (34.1%) patients; among them 28 (7.3%) ourred after the initiation of antibioti treatment. By multivariable analysis, fators assoiated with a new emboli event were vegetation. 10 mm in length (odds ratio (OR) 9) and severe vegetation mobility (OR 2.4). Thus, patients with vegetations longer than 10 mm are at higher risk of embolism, and this risk is partiularly high in patients with very large 127 Heart: first published as /hrt on 19 Deember Downloaded from on 23 July 2018 by guest. Proteted by opyright.

5 128 Figure 5 Number of emboli events by site of embolisation in our series of 365 patients with 131 (34%) emboli events (some patients had more than one site of embolisation). (. 15 mm) and mobile vegetations. The risk of embolism has been found to be higher in mitral valve IE ompared with aorti valve IE in some studies, but this trend was not onfirmed by reent series. Finally, the risk of embolism is highest during the first days following the initiation of antibioti treatment and dereases after two weeks. For this reason, if surgery is deided upon beause of a large vegetation to redue the risk of new embolism, it must be performed early during the first week of antibioti treatment, beause the risk of embolism is greatest during this period. Who is at risk of death? Mortality is still high in IE, although it has delined in reent years. Mortality in IE may be assoiated with fators related to the patient himself or to fators related to the disease, the former being potentially preventable. Thus, the identifiation of fators assoiated with inreased mortality is a ruial hallenge, as it will allow the identifiation of high risk subgroups in whih an aggressive strategy will be potentially useful. Several markers have previously been identified in past studies, inluding age, ourrene of ompliations, staphylooal infetion, serum reatinine onentration, o-morbidity, and prostheti valve IE. The most omprehensive study has reently been published by Hasbun et al. 15 They studied six month mortality in a series of 513 patients with ompliated IE. They found that o-morbidity, abnormal mental status, moderate to severe ongestive heart failure, staphylooal infetion, and medial treatment were independent preditors of mortality. Large vegetations (. 15 mm) were also assoiated with a worse prognosis in a reent series. 14 Ehoardiography appears to be preditive of the risk of both embolism and death in IE. WHAT IS THE OPTIMAL THERAPEUTIC STRATEGY IN INFECTIVE ENDOCARDITIS? Optimal treatment of IE is based on the ombination of prolonged and adapted antibioti treatment with surgial exision of all the infeted tissues in about 50% of patients. Antioagulant treatment and aspirin are not indiated in infetive endoarditis (unless another indiation exists) and are ontraindiated in IE with severe erebral ompliations or myoti aneurysms. Although surgial treatment has been shown to have a benefiial effet on outome in IE, 16 the type and optimal timing of surgery are still debated and may vary among patients and entres. Conservative surgery is more and more frequently performed in mitral valve IE. In a reent series of 78 patients operated on between 1990 and 1999 for IE, (81%) benefited from onservative surgery with good short term and long term results. In aorti IE, homograft surgery is frequently used, and has been shown to be partiularly useful in patients with perivalvar involvement. In IE early surgery must be performed in three irumstanes: In the ase of severe ongestive heart failure related to aute mitral or aorti regurgitation. In a reent series of 513 IE patients, (40%) were operated on. The benefit of surgery was partiularly high in patients with moderate to severe heart failure. In the ase of persistent or partiularly severe infetion. Current guidelines 18 reommend surgery when fever and bateraemia are evident for more than 7 10 days despite adequate antibioti treatment. Absess formation, perivalvar involvement, and fungal IE are also onsidered indiations for early surgery. Emboli indiations for surgery are more ontroversial. Surgery is usually performed in ases of reurrent emboli despite appropriate antibioti treatment. Beause of inreased risk of embolism in patients with vegetations Infetive endoarditis: key points The mortality in IE remains high (10 20% in-hospital mortality) The at-risk patients are hanging, with more nosoomial infetions, haemodialysis patients, elderly patients, intravenous drug abusers, and intraardia devie infetions Ehoardiography and blood ulture remain the two main tests for the diagnosis of IE, but both may be negative in some patients New diagnosti tehniques, inluding polymerase hain reation (PCR) and histology of the exised valves, may be useful in these patients Ehoardiography plays a key role in the management of IE: for diagnosis, detetion of ompliations, follow up, and prognosti assessment of patients Heart: first published as /hrt on 19 Deember Downloaded from on 23 July 2018 by guest. Proteted by opyright.

6 . 10 mm in length, surgery must also be performed in the presene of a large vegetation (. 10 mm) following one or more linial or even asymptomati emboli events, or when the presene of the large vegetation is assoiated with known other preditors of a ompliated ourse (heart failure, persistent infetion under treatment, absess, prostheti valve). Surgery may also be onsidered in the presene of very large (. 15 mm) and mobile vegetations, even in the absene of previous embolism or other prognosti markers. The reently published Euro Heart Survey revealed that the size of the vegetation was one of the reasons for surgery in 54% of ases of native valve IE, and in 25% of PVIE. 2 Finally, the deision of whether or not to operate early in infetive endoarditis is always diffiult and remains speifi for the individual patient. The benefit of surgery must be weighed against the operative risk and take into aount the linial status of the patient and the o-morbidities. MAY THE MANAGEMENT OF PATIENTS WITH IE BE DIFFERENT IN SOME SUBGROUPS? IE affeting intraardia devies A quite different and more aggressive therapeuti strategy is needed in patients with intraardia devies. Patients with prostheti valve IE are more diffiult to treat by antibioti therapy alone, and surgial treatment is more frequently needed than for native valves. Surgery is generally onsidered in early PVIE and must be reommended in PVIE ompliated by valve dysfuntion, absess formation, ondution abnormalities, and large vegetations, partiularly if staphylooi are the infeting agents. However, even with the use of an aggressive surgial strategy, PVIE is still assoiated with high in-hospital and long term mortality. 19 Paemaker lead IE (PMLIE) is a life threatening form of IE, with high morbidity and mortality. In almost all ases of PMLIE, surgial or perutaneous removal of all the implanted material is neessary, together with prolonged antibioti treatment. Neurologial ompliations Cerebral ompliations represent the seond ause of death in IE, after ongestive heart failure. The inidene of erebral ompliations varies from 25 56% and mortality ranges from 21 83% in these patients. Cerebral ompliations may result from two main mehanisms. The migration of ardia valvar vegetations into the erebral arteries, ausing erebral infartion. Cerebral arteries and the spleen are the most frequent sites of embolisation in left sided IE, erebral embolism being observed in 20% of patients with IE in our experiene. Cerebral embolism may present as a stroke of varying severity assoiated with fever, or may be asymptomati and deteted only by omputed tomography (CT) san. Cerebral hemorrhage may ompliate erebral infartion or be the onsequene of the rupture of a myoti aneurysm. The reported inidene of erebral myoti aneurysm is 1.2 5%. It may present with headahes, meningitis, or severe erebral haemorrhage. Myoti aneurysms an be deteted either by CT san, or magneti resonane angiography, but the gold standard remains onventional erebral angiography. Myoti aneurysms may heal with antibioti treatment in 50% of ases. The main problem in these patients is the optimal timing of valve surgery, when needed. The best therapeuti strategy in patients with erebral ompliations is still debated. Some authors reommend delaying ardia surgery for at least two Emboli events in IE: key points Embolism ours in 20 40% of IE ases, but its inidene dereases to 9 21% after initiation of antibioti treatment The risk of embolism is espeially high during the first two weeks following the initiation of antibioti treatment Embolism may be asymptomati in about 20% of patients with IE and must be diagnosed by systemati non-invasive imaging The brain and spleen are the most frequent sites of embolism in IE Patients with large vegetations (. 10 mm) have a higher risk of embolism. Very large (. 15 mm) and mobile vegetations are assoiated with an inreased mortality weeks after erebral infartion and for at least one month after erebral hemorrhage, arguing that the risk of neurologial deterioration or death is very high when surgery is performed during the first two weeks after a stroke. 20 Conversely, other authors reported a very low rate of neurologial deterioration in these patients when surgery was performed very soon after an emboli infartion. 21 Although reent guidelines 18 reommend early surgery (, 72 hours) in the ase of foal defiit without haemorrhage on CT san, surgery must be delayed in the presene of more severe neurologial symptoms or erebral hemorrhage, unless surgery is formally indiated beause of severe ongestive heart failure. CONCLUSION IE is undergoing a period of hange, with the oexistene of patients with the lassi form of infetion with a predominane of streptooal infetion, and the emergene of new at-risk patients with a growing inidene of nosoomial endoarditis and infetions affeting intraardia devies. The fat that IE has several manifestations limits the usefulness of any diagnosti riteria and also limits the effiay of the usual prophylati methods. The last deade has seen onsiderable improvements onerning diagnosti proedures, surgial tehniques, and identifiation of patients at high risk of embolism and death. The hallenge for the next 10 years will be to redue the morbidity and mortality of IE, whih remain unaeptably high. An aggressive therapeuti strategy in those patients most at risk, ombined with a multidisiplinary approah, will be neessary if we are to ahieve this goal. Additional referenes appear on the Heart website In ompliane with EBAC/EACCME guidelines, all authors partiipating in Eduation in Heart have dislosed potential onflits of interest that might ause a bias in the artile REFERENCES 1 Myonakis E, Calderwood SB. Infetive endoarditis in adults. N Engl J Med 2001;345: Exellent review on infetive endoarditis. 2 Tornos P, Iung B, Permanyer-Miralda G, et al. Infetive endoarditis in Europe: lessons from the Euro Heart Survey. Heart 2005;91: Moreillon P. Infetive endoarditis. Lanet 2004;363: Reent review on risk fators, pathogenesis, and management of infetive endoarditis. 4 Habib G. Emboli risk in subaute baterial endoarditis. Role of transesophageal ehoardiography. Curr Cardiol Rep 2003;5: Klug D, Laroix D, Savoye C, et al. Systemi infetion related to endoarditis on paemaker leads. Clinial presentation and management. Cirulation 1997;95: Heart: first published as /hrt on 19 Deember Downloaded from on 23 July 2018 by guest. Proteted by opyright.

7 130 6 Kemp WE, Citrin B, Byrd BF. Ehoardiography in infetive endoarditis. South Med J 1999;92: Exellent review about the role of ehoardiography in IE. 7 Durak DT, Lukes AS, Bright DK. New riteria for diagnosis of infetive endoarditis: utilization of speifi ehoardiographi findings. Am J Med 1994;96: Referene series allowing definition of atual riteria for endoarditis. It inluded for the first time ehoardiography as a major riterion. 8 Habib G, Derumeaux G, Avierinos JF, et al. Value and limitations of the Duke riteria for the diagnosis of infetive endoarditis. J Am Coll Cardiol 1999;33: Lamas CC, Eykin SJ. Blood ulture negative endoarditis: analysis of 63 ases presenting over 25 years. Heart 2003;89: Houpikian P, Raoult D. Blood ulture-negative infetive endoarditis in a referene enter: etiologi diagnosis of 348 ases. Mediine 2005;84: The largest series to date onerning BCNIE. 11 Greub G, Lepidi H, Rovery C, et al. Diagnosis of infetious endoarditis in patients undergoing valve surgery. Am J Med 2005;118: Lepidi H, Durak DT, Raoult D. Diagnosti methods, urrent best praties and guidelines for histologi evaluation in infetive endoarditis. Infet Dis Clin North Am 2002;16: Fournier PE, Casalta JP, Habib G, et al. Modifiation of the diagnosti riteria proposed by the Duke endoarditis servie to permit improved diagnosis of Q fever endoarditis. Am J Med 1996;100: Thuny F, Di Salvo G, Belliard O, et al. Risk of embolism and death in infetive endoarditis: prognosti value of ehoardiography. A prospetive multienter study. Cirulation 2005;112: MULTIPLE CHOICE QUESTIONS 15 Hasbun R, Vikram HR, Barakat LA, et al. Compliated left-sided native valve endoarditis in adults: risk lassifiation for mortality. JAMA 2003;289: Largest single entre study defining the prognosti fators in IE. 16 Vikram HR, Buenonsejo J, Hasbun R, et al. Impat of valve surgery on 6- month mortality in adults with ompliated, left-sided native valve endoarditis. A propensity analysis. JAMA 2003;290: Iung B, Rousseau-Paziaud J, Cormier B, et al. Contemporary results of mitral valve repair for infetive endoarditis. J Am Coll Cardiol 2004;43: Horstkotte D, Follath F, Gutshik E, et al. The task fore on infetive endoarditis of the European Soiety of Cardiology. Guidelines on prevention, diagnosis and treatment of infetive endoarditis. Eur Heart J 2004;25: Current European reommendations onerning the management of infetive endoarditis with omplete review. 19 Habib G, Tribouilloy C, Thuny F, et al. Prostheti valve endoarditis: who needs surgery? A multientre study of 104 ases. Heart 2005;91: Eishi K, Kawazoe K, Kuriyama Y, et al. Surgial management of infetive endoarditis assoiated with erebral ompliations. Multienter retrospetive study in Japan. J Thora Cardiovas Surg 1995;110: Piper C, Wierner M, Shulte HD, et al. Stroke is not a ontraindiation for urgent valve replaement in aute infetive endoarditis. J Heart Valve Dis 2001;10: Additional referenes appear on the Heart websit Eduation in Heart Interative ( There are six multiple hoie questions assoiated with eah Eduation in Heart artile (these questions have been written by the authors of the artiles). Eah artile is submitted to EBAC (European Board for Areditation in Cardiology; for 1 hour of external CPD redit. How to find the MCQs: Clik on the Online Learning: [Take interative ourse] link on the table of ontents for the issue online or on the Eduation in Heart olletion ( Free aess: This link will take you to the BMJ Publishing Group s online learning website. Your Heart Online user name and password will be reognised by this website. As a Heart subsriber you have free aess to these MCQs but you must register on the site so you an trak your learning ativity and reeive redit for ompleted ourses. How to get aess: If you have not yet ativated your Heart Online aess, please do so by visiting and entering your six digit (all numeri) ustomer number (found above your address label with your print opy). If you have any trouble ativating or using the site please ontat subsriptions@bmjgroup.om Case based Heart: You might also be interested in the interative ases published in assoiation with Heart ( Heart: first published as /hrt on 19 Deember Downloaded from on 23 July 2018 by guest. Proteted by opyright.