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Aims: In left-sided infective endocarditis (IE), a large vegetation >10 mm is associated with higher mortality, yet it is unknown whether surgery during the acute phase opposed to medical therapy is associated with improved survival. We assessed the association between surgery and 6-month mortality as related to vegetation size., Methods and Results: Patients with definite, left-sided IE (2008-2012) from The International Collaboration on Endocarditis prospective, multinational registry were included. We compared clinical characteristics and 6-month mortality (by Cox regression with inverse propensity of treatment weighting) between patients with vegetation size ≤10 mm vs. >10 mm in maximum length by surgical treatment strategy. A total of 1006 patients with left sided IE were included; 422 with a vegetation size ≤10 mm (median age 66.0 years, 33% women) and 584 (median age 58.4 years, 34% women) patients with a large vegetation >10 mm. Operative risk by STS-IE score was similar between groups. Embolic events occurred in 28.4% vs. 44.3% (P < 0.001), respectively. Patients with a vegetation >10 mm was associated with higher 6-month mortality (25.1% vs. 19.4% for small vegetation, P = 0.035). However, after propensity adjustment, the association with higher mortality persisted only in patients with a large vegetation >10 mm vs. ≤10 mm: hazard ratio (HR) 1.55 (1.27-1.90); but only in patients with large vegetation managed medically [HR 1.86 (1.48-2.34)] rather than surgically [HR 1.01 (0.69-1.49)]., Conclusion: Left-sided IE with vegetation size >10 mm was associated with an increased mortality at 6 months in this observational study but was dependent on treatment strategy. For patients with large vegetation undergoing surgical treatment, survival was similar to patients with smaller vegetation size., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: The prognosis of patients with infective endocarditis (IE) remains poor despite the great advances in the last decades. One of the factors closely related to mortality is the development of septic shock (SS). The aim of our study was to describe the profile of patients with IE complicated with SS, and to identify prognostic factors of new-onset SS during hospitalization., Methods and Results: We conducted a prospective study including 894 episodes of IE diagnosed at three tertiary centres. A backward logistic regression analysis was undertaken to determine prognostic factors associated with SS development. Multivariable analysis identified the following as predictive of SS development: diabetes mellitus [odds ratio (OR) 2.06; confidence interval (CI) 1.16-3.68], Staphylococcus aureus infection (OR: 2.97; CI: 1.72-5.15), acute renal insufficiency (OR: 3.22; CI: 1.28-8.07), supraventricular tachycardia (OR: 3.29; CI: 1.14-9.44), vegetation size ≥15 mm (OR: 1.21; CI: 0.65-2.25), and signs of persistent infection (OR: 9.8; CI: 5.48-17.52). Risk of SS development could be stratified when combining the first five variables: one variable present: 3.8% (CI: 2-7%); two variables present: 6.3% (CI: 3.2-12.1%); three variables present: 14.6% (CI: 6.8-27.6%); four variables present: 29.1% (CI: 11.7-56.1%); and five variables present: 45.4% (95% CI: 17.5-76.6%). When adding signs of persistent infection, the risk dramatically increased, reaching 85.7% (95% CI: 61.2-95.9%) of risk., Conclusions: In patients with IE, the presence of diabetes, acute renal insufficiency, Staphylococcus aureus infection, supraventricular tachycardia, vegetation size ≥15 mm, and signs of persistent infection are associated with the development of SS.

Aims: Existing risk models in infective endocarditis (IE) have not investigated whether the prognostic value of clinical parameters is time-dependent. We have explored the potential of time-dependent risk stratification to predict outcome in IE., Methods and Results: We studied 273 patients admitted with IE to two centres (derivation cohort n=192, validation cohort n=81). The derivation cohort was used to identify independent predictors of 6 months mortality at days 1, 8, and 15 (multivariable Cox regression, P<0.05). There were six predictors at day 1, five at day 8, and only three at day 15. Whereas heart failure, thrombocytopenia, and severe comorbidity predicted mortality at all three time-points, other predictors were time-dependent (age, tachycardia, renal impairment at day 1; severe embolic events, renal impairment at day 8). These predictors were incorporated into a time-dependent model. The model was validated in an independent cohort with concordance indices of 0.79 (95% CI 0.68-0.91) at day 1, 0.79 (95% CI 0.65-0.93) at day 8, and 0.84 (95% CI 0.73-0.95) at day 15. Six months mortality was 2.4% in patients deemed as low-risk at all time-points, compared with 78.2% in patients classified as high-risk at any evaluation., Conclusion: Prognostic factors in IE are time-dependent. Time-dependent risk stratification accurately predicts outcome in IE.

Aims: The aim of this study was to evaluate the effect of valve surgery (VS) in infective endocarditis (IE) on 5-year mortality and to evaluate whether conflicting results reported by previous studies could be due to differences in their methodological approaches., Methods and Results: Four hundred and forty-nine patients with a definite left-sided IE were selected from a prospective, population-based study. Association between VS and 5-year mortality was examined with a Cox model. To determine the impact of different methodological approaches, we also analysed the relationship between VS and mortality in our database, according to each method used in the five previous studies. Valve surgery was performed in 240 patients (53%). It was associated with an increase in short-term mortality [within the first 14 post-operative days; adjusted hazard ratio (HR), 3.69; 95% confidence interval (CI), 2.17-6.25; P<0.0001] and a decrease in long-term mortality (adjusted HR, 0.55; 95% CI, 0.35-0.87; P=0.01). At least 188 days of follow-up were required for VS to provide an overall survival advantage. When applying each study's method to our database, we obtained results similar to those reported., Conclusion: Previous conflicting results appear to be related to differences in statistical methods. When using appropriate models, we found that VS was significantly associated with reduced long-term mortality.

Aims: To determine whether the timing of surgery could influence mortality and morbidity in adults with complicated infective endocarditis (IE)., Methods and Results: In 291 consecutive adults with definite IE who underwent surgery during the active phase, we compared those operated on within the first week of antimicrobial therapy (n=95) to those operated on later (n=191). The impact of the timing of surgery on 6-month mortality, relapses, and postoperative valvular dysfunctions (PVD) was analysed using propensity score (PS) analyses. After stratification of the cohort into quintiles based on the PS, ≤1st week surgery was associated with a trend of decrease in 6-month mortality in the quintile of patients with the most likelihood of undergoing this early surgical management [quintile 5: 11% vs. 33%, odds ratio (OR)=0.18, 95% CI (confidence interval) 0.04-0.83, P=0.03]. Patients of this subgroup were younger, were more likely to have Staphylococcus aureus infections, congestive heart failure, and larger vegetations. Besides, ≤1st week surgery was associated with an increased number of relapses or PVD (16% vs. 4%, adjusted OR=2.9, 95% CI 0.99-8.40, P=0.05)., Conclusion: Surgery performed very early may improve survival in patients with the most severe complicated IE. However, a greater risk of relapses and PVD should be expected when surgery is performed very early.

Aims: Institutional-based studies of infective endocarditis (IE) are limited by referral bias. Longitudinal population-based data were used to overcome such bias to provide a contemporary profile of IE and specifically investigate the importance of health care-associated IE and age., Methods and Results: Between 2000 and 2006, 1536 consecutive adult admissions with IE were identified in the Australian state of New South Wales using a state-wide database. The annual incidence was 4.7 per 100 000 (95% CI 4.4-4.9) being highest in patients aged between 80 and 84 years. The most frequent causative organism was Staphylococcus aureus (32%). Surgery was performed in 20% and the 6-month mortality was 18%. During the study period, the median age of patients increased from 61 to 65 years (P = 0.02), but microbiology, surgery, and mortality rates remained stable. Health care-associated IE was identified in 30% and was associated with older age, diabetes, renal impairment, heart failure, and infection with methicillin-resistant Staphylococcus aureus and enterococcus. Even after adjustment for these differences, recent health care exposure was an independent predictor of mortality (hazard ratio 1.62, 95% CI 1.34-1.96)., Conclusion: Contemporary IE contributes to health care-related infection, occurs in an increasingly elderly population, and remains a condition with unacceptably high mortality.

Aims: To analyse the risk of death according to the type of cerebrovascular complications (CVC) during infective endocarditis (IE) and to analyse the determinants of outcome in patients with IE and a CVC., Methods and Results: In two referral centres, 496 consecutive patients with definite IE were prospectively included. Cerebral CT scan was performed in 453 patients. During a mean 2.9 year follow-up, 139 (28%) patients died and CVC occurred in 109 (22%) patients. Stroke was an independent predictor of death, although no significant excess mortality was observed in patients with silent CVC or transient ischaemic attack (TIA). Among CVC patients, mortality was predicted by the presence of a mechanical prosthetic valve IE and a low Glasgow Coma Scale. When valvular surgery was performed in patients after CVC, neurologic exacerbation was rare [4 (6.3%) patients] and was observed only in patients with symptomatic stroke. Among CVC patients, survival was better in operated patients when compared with patients treated conservatively despite theoretical indication for surgery (P < 0.0001). However, the latter group had more comorbidities (P = 0.007) and a lower Glasgow Coma Scale (14.6 +/- 1 vs. 12 +/- 4, P < 0.0001)., Conclusion: Patients with silent CVC or TIA have a relatively good prognosis, whereas those with stroke have significant excess mortality particularly in case of mechanical prosthetic valve IE or impaired consciousness. Valvular surgery can be safely performed after silent CVC or TIA and may improve survival in selected patients with stroke.

Aim: There is no agreement in the best cutoff time to distinguish between early- and late- onset prosthetic valve endocarditis (PVE). Our objectives are to define early-onset PVE according to the microbiological spectrum and to analyse the profile and short-term prognosis of this entity., Methods and Results: The microbiological profile of 172 non-drug users, who were patients with PVE, were compared according to the time elapsed from surgery among 640 endocarditis diagnosed between 1996 and 2004. There were no differences in the microbiological profile of patients with PVE occurred within 2 months of valve replacement and those accounting between 2 and 12 months. The proportion of coagulase-negative Staphylococci (CNS) was higher during the first year post-intervention (37 vs. 18%, P = 0.005) and Streptococci viridans were more common after 1 year (18 vs. 1%, P = 0.001). The percentage of methicilin-resistant CNS strains was higher before 1 year (77 vs. 30%, P = 0.004). Early-onset PVE represented 38% of all episodes of PVE, CNS being the most frequent isolated microorganisms (37%), most of them methicilin resistant (77%). In-hospital mortality of patients who needed urgent surgery was 46% and elective surgery 25%. Overall, in-hospital mortality was 38% and no differences were seen between surgical and medical groups (32 vs. 45%, P = 0.30). Periannular complications were associated with higher in-hospital mortality (60 vs. 27%, P = 0.007)., Conclusion: According to the microbiological profile, the most appropriate cutoff time to distinguish between early- and late-onset PVE was 1 year. Methicilin-resistant CNS are the most frequent pathogens and periannular complications, the only risk factor for in-hospital mortality.

Aims: Surgery in patients with infective endocarditis (IE) can be elective (upon completion of antibiotic treatment) or urgent (before antibiotic treatment has ended) when the clinical course is unfavourable. However, urgent surgery for left-sided endocarditis is associated with high mortality. The aims of this study were to describe the profile of patients with left-sided endocarditis who underwent urgent surgery and to analyse the factors that predicted mortality., Methods and Results: Among 508 consecutive episodes of IE, 391 were left-sided and 89 required urgent surgery. The main reasons for urgent surgery were heart failure that did not respond to medication (72%) and persistent infection despite appropriate antibiotic treatment (31%). Thirty-two patients (36%) died during their hospital stay. Univariate analysis identified renal failure, septic shock, Gram-negative bacteria, persistent infection, and surgery for persistent infection as factors associated with mortality. Multivariate analysis confirmed only persistent infection and renal insufficiency as factors independently associated with a poor prognosis., Conclusion: Patients with IE who need urgent surgery have a poor clinical course. Heart failure, the main cause of urgent surgery, was not associated with higher mortality. However, persistent infection and renal failure were factors associated with higher post-surgical mortality.

Aims: The aim here is to analyse epidemiology, optimal treatment, and predictors of 6-month mortality in infective endocarditis (IE)., Methods and Results: A prospective observational cohort study included 193 patients with 203 episodes of definite IE by the modified Duke criteria. Thirty-four percent of episodes involved prosthetic valves. Thirty-three percent of episodes were nosocomial. Forty-three percent included staphylococci, 26% streptococci, and 17% enterococci. At least one complication occurred in 79% of the episodes and 63% had surgical intervention. Six-month mortality was 22%: 33% for staphylococci, 24% for enterococci, and 8% for streptococci. Seventy-four percent of patients with a contraindication to surgery died when compared with 7% with medical treatment without a contraindication and 16% with surgical treatment. In multivariable logistic regression, predictors of 6-month mortality were age (P=0.03), the causative microorganism (P=0.04), and treatment group (P<0.001)., Conclusion: Compared with older series, we observed more prosthetic valve IE, nosocomial IE, and surgery. Staphylococcus aureus and Enterococcus faecalis were predominant microorganisms. Age, staphylococci, and a contraindication to surgery predicted 6-month mortality. Nearly half of deaths had a contraindication to surgery. Six-month mortality did not differ significantly between patients who received surgical treatment as against those who received medical treatment without a contraindication to surgery.

Aims: To analyse the characteristics of infective endocarditis (IE) in patients with diabetes mellitus (DM), and to evaluate the prognostic significance of DM according to insulin use., Methods and Results: A total of 559 patients with definite IE including 75 patients (13%) with DM (insulin use n = 22; oral antidiabetic n = 53) were evaluated. Comparison of insulin-DM, oral-DM, and non-DM patients showed an older age (66 +/- 13, 66 +/- 10, 58 +/- 17, respectively; P = 0.004) in DM patients, and more frequent IE on prosthetic valves (32, 11, and 15%, respectively; P = 0.068) in insulin-DM patients. Oral streptococci (0, 8, and 18%, respectively; P = 0.016) were less frequently the causative organism than staphylococci (64, 26, and 29%, respectively; P = 0.002) in insulin-DM patients. Vegetations, dehiscence, abscess, and regurgitation rates did not differ among the three groups, nor did cardiac surgery rates (32, 47, and 48%, respectively; P = 0.334), but in-hospital mortality was higher in insulin-DM patients (50, 19, and 15%; P < 0.001). In multivariable analysis, independently of other determinants of death (age, IE location, Staphylococcus aureus, history of heart failure, immunosuppression, creatinine serum), insulin-DM was a predictor of death (OR, 4.69; 95% CI, 1.77-12.44), whereas oral-DM was not., Conclusion: IE prognosis in insulin-DM patients is poor due to the coexistence of host and pathogen factors. Insulin-DM patients with IE may require specific management.

Aims: To evaluate the diagnostic usefulness of serial serum C-reactive protein determinations in monitoring the outcome of infective endocarditis (IE)., Methods and Results: C-reactive protein, erythrocyte sedimentation rate (ESR), and white blood cell count (WBC) were measured from admission until week 10 in 129 patients with 134 episodes of IE. Need for cardiac surgery and final outcome were assessed until 3 months from admission. Data were evaluated using extensive statistical analyses. The fall in serum C-reactive protein or WBC was significantly faster when a patient had an uncomplicated recovery than when complications developed or death ensued, but no such behaviour was observed in ESR. None of the 80 patients who had normal C-reactive protein by week 10 died of IE. Moreover, none of the 22 patients who had normal C-reactive protein by week 4 needed cardiac surgery and only two of the 33 patients who had normal C-reactive protein by week 6 needed cardiac surgery, both after successful medical treatment of IE. Of the 87 patients whose WBC normalized within 4 weeks, six died and 15 needed valve surgery., Conclusion: The normalization of C-reactive protein proved to be a good predictor of a favourable late outcome (surgery, death) of IE. Also WBC count proved useful in the assessment of patients with IE, but the value of ESR was negligible.

Aims: To investigate the clinical features, echocardiographic characteristics, management, and prognostic factors of mortality of aorto-cavitary fistulization (ACF) in infective endocarditis (IE). Extension of infection in aortic valve IE beyond valvular structures may result in peri-annular complications with resulting necrosis and rupture, and subsequent development of ACF. Aorto-cavitary communications create intra-cardiac shunts, which may result in further clinical deterioration and haemodynamic instability., Methods and Results: In a retrospective multi-centre study over 4681 episodes of IE, a total of 76 patients with ACF [1.6%, confidence interval (CI) 95%: 1.2-2.0%] diagnosed by echocardiography or during surgery were identified. Fistulae were found in 1.8% of cases of native valve IE and in 3.5% of cases of prosthetic valve IE from the general population and in 0.4% of drug abusers. PVE was present in 31 (41%) cases of ACF. Transthoracic and transoesophageal echocardiography detected the fistulous tracts in 53 and 97% of cases, respectively. Peri-annular abscesses were detected in 78% of cases, fistulae originated in similar rates from the three sinuses of Valsalva, and the four cardiac chambers were equally involved in the fistulous tracts. Heart failure (HF) developed in 62% of cases and surgery was performed in 66 (87% CI 95% 77-93%) patients with a mortality of 41% (95% CI 30-53%) in the overall population. Multivariate analysis identified HF (OR 3.4, CI 95% 1.0-11.5), prosthetic IE (OR 4.6, CI 95% 1.4-15.4) and urgent or emergency surgical treatment (OR 4.3, CI 95% 1.3-16.6) as variables significantly associated with an increased risk of death. Major complications during follow-up (death, re-operation, or re-admission for HF) among the five operative survivors with residual fistulae occurred in 20 and 100% of patients at 1 and 2 years, respectively., Conclusion: Aorto-cavitary fistulous tract formation is an uncommon but extremely serious complication of IE. In-hospital mortality was exceptionally high despite aggressive management with surgical intervention in the majority of patients. Prosthetic IE, urgent surgery, and the development of HF identify the subgroup of patients with IE and ACF that have significantly increased risk of in-hospital death.

Aims: Infective endocarditis (IE) is more and more frequent in elderly persons and it has been associated with various clinical, bacteriological, and prognostic features. The aim of the study was to define the clinical, echographic, and prognostic characteristics of IE in a large population of elderly patients from four European centres (three French, one Italian)., Methods and Results: Three hundred and fifteen consecutive patients with definite IE underwent clinical evaluation, echocardiography, blood cultures, and follow-up. Patients were separated into three groups: group A: 117 patients aged <50 years, group B: 111 patients aged >50 and <70 years, group C: 87 patients aged >70 years. Elderly patients (group C) presented more frequently than other groups with digestive or urinary portal of entry, pacemaker endocarditis, and anaemia. S bovis endocarditis was less frequent and S aureus endocarditis more frequent in younger (group A) patients than in other groups. No difference was observed among groups concerning echocardiographic data as well as the incidence and localization of embolic events. Elderly patients were operated on as frequently as younger patients and their operative risk was similar than in other groups (11%, 3%, and 5% in groups C, B, and A, respectively, P=ns). Overall mortality in elderly patients was low (17%) but significantly higher than in younger patients (10% in group A, 7% in group B, P=0.02). By multivariate analysis, the only risk factors for in-hospital mortality were age (P=0.003), prosthetic valve (P=0.002), and cerebral embolism (P=0.006). Conversely, surgical management was associated with a lower in-hospital mortality (P=0.03)., Conclusions: In this largest series of elderly patients with IE, IE in elderly carries specific features when compared with younger patients, although the echographic characteristics and embolic risk are similar. The overall mortality rate in elderly patients is higher than in younger, but the mortality in operated patients is low and similar than that of younger patients.

Aims: Secondary involvement of the mitral valve is well documented in primary aortic valve endocarditis. A poorly considered, but probably important causative mechanism, involving both left-sided valves, is 'mitral kissing vegetation'. This results from large aortic vegetations prolapsing into the left ventricular outflow tract and making contact with the ventricular aspect of the anterior mitral leaflet thus causing secondary infection., Methods and Results: In 192 consecutive patients with aortic valve endocarditis, two to 18 (7.6+/-2.6) serial transoesophageal echocardiographic examinations were analysed per patient to demonstrate the development of mitral kissing vegetation on initially competent, morphologically normal mitral leaflets. In 19 patients (9.9%) with aortic valve endocarditis, mitral kissing vegetation was diagnosed within 11.6+/-9.0 (range 1-31) days following primary transoesophageal echocardiography. In all patients with mitral kissing vegetation, vegetations attached to aortic cusps were >6 mm. On hospital admission, patients with aortic valve endocarditis plus mitral kissing vegetation presented more often with a positive sepsis score, embolic events, renal failure and had larger aortic valve vegetations (9.9+/-3.3 vs 5.7+/-2.3 mm). Prognosis of aortic valve endocarditis plus mitral kissing vegetation was unfavourable (P<0.005) when compared to patients with aortic valve endocarditis alone., Conclusion: In aortic valve endocarditis early echocardiographic detection of mitral kissing vegetation and timely surgery may preserve the mitral valve apparatus, and favourably influence the long-term prognosis., (Copyright 2001 The European Society of Cardiology.)

Aims: The purposes of this study were to determine the clinical features and to identify prognostic factors of abscesses associated with infective endocarditis., Methods and Results: During a 5-year period from January 1989, 233 patients with perivalvular abscesses associated with infective endocarditis were enrolled in a retrospective multicentre study. Of the patients, 213 received medical surgical therapy and 20 medical therapy alone. No causative microorganism could be identified in 31% of cases. Sensitivity for the detection of abscesses was 36 and 80%, respectively using transthoracic and transoesophageal echocardiography. Surgical treatment consisted of primary suture of the abscess (38%), insertion of a felt aortic or mitral ring using Teflon or pericardium (42%), or debridment of the abscess cavity (20%). The 1 month operative mortality was 16%. Actuarial rates for overall survival at 3 and 27 months in operated patients were 75 +/- 10% and 59 +/- 11%, respectively. Increasing patient age, staphylococcal infection, and fistulization of the abscess were found to be independent risk factors in both 1 month and overall operative mortality. Renal failure was a risk factor predictive of operative mortality at 1 month, whereas uncontrolled infection and circumferential abscess were regarded as risk factors predictive of overall operative mortality., Conclusion: The data determined prognostic factors of abscesses associated with infective endocarditis.

Aims: In infective endocarditis, the true incidence of embolic events and metastatic infections remains unknown probably because a large number of events are asymptomatic. The consequences of the prognosis of such events have never been evaluated by a prospective follow-up. This study aimed to assess the incidence of symptomatic or asymptomatic embolic events and metastatic infections in definite infective endocarditis and to determine whether these events carry a risk of mortality., Methods and Results: From January 1991 to December 1993, 102 patients with suspected or known infective endocarditis were referred to our institution. Among them, we selected 68 patients (50 males, 18 females, mean age = 52.7 years) exhibiting definite infective endocarditis according to the Duke University criteria. Blood cultures were positive in 49 cases (72%). Echocardiography revealed valvular vegetations in 55 cases (81%). Irrespective of the clinical presentation, patients were examined radiologically by cerebral computed tomography scanning (n = 60), magnetic resonance imaging (n = 3), abdominal computed tomography scanning (n = 32) or abdominal echocardiography (n = 20). Depending on the symptoms, thoracic computed tomography scanning (n = 22), pulmonary angiography (n = 2), ventilation-perfusion scintigraphy (n = 4), or gallium citrate radionuclide scanning (n = 7) were also performed. All patients were prospectively followed-up for a mean period of 21.4 +/- 17.5 months. In 35 patients (51%), 51 embolic or metastatic events were revealed, involving the central nervous system (n = 23), spleen (n = 7), kidney (n = 5), lung (n = 5), liver (n = 4), bone and joint (n = 4), iliac (n = 2) or mesenteric (n = 1) arteries. During the hospital stay, the mortality rate was higher in patients exhibiting embolic or metastatic events (20 vs 12%), but the difference did not reach statistical significance. Kaplan-Meier analysis demonstrated no difference in long-term follow-up., Conclusion: Our data suggest that embolic or metastatic events had a high incidence (51%) during infective endocarditis, but were not associated with significant attributable mortality.

Prosthetic valve endocarditis is considered to be associated with a more severe prognosis than native valve endocarditis. Among other factors, inappropriate visualization of vegetations in prosthetic valve endocarditis by transthoracic echocardiography is responsible for this observation. Since the introduction of transoesophageal echocardiography into clinical practice the diagnostic sensitivity and specificity of the detection of vegetations located on prosthetic valves have been enhanced. Therefore we aimed to determine and compare the prognosis of prosthetic valve endocarditis and native valve endocarditis in the era of this improved diagnostic approach. One hundred and six episodes of infective endocarditis in 104 patients were seen at our institution between 1989 and 1993. Eighty patients (77%) had native valve endocarditis and 24 (23%) had late prosthetic valve endocarditis. In the latter group two patients had recurrent infective endocarditis. Patients with prosthetic valve endocarditis were older (mean age 64 vs 54 years in native valve endocarditis; P < 0.001) and the majority was female (62% vs 38% in native valve endocarditis; P < 0.05). In prosthetic valve endocarditis, infection of a valve in the mitral position predominated (65% vs 30% in native valve endocarditis; P < 0.01), whereas in native valve endocarditis more than half the cases had isolated aortic valve endocarditis (51% vs 27% in prosthetic valve endocarditis; P < 0.01). In prosthetic valve endocarditis more cases were caused by Staphylococcus aureus (31% vs 14% in native valve endocarditis; P = 0.08), whereas in native valve endocarditis the most frequent organisms were streptococci (29% vs 19% in prosthetic valve endocarditis; P = 0.12). Differences in the clinical features of native valve endocarditis and prosthetic valve endocarditis could not be found except for a higher rate of embolism in native valve endocarditis (40% vs 19% in prosthetic valve endocarditis; P < 0.05). Vegetations could be detected by transthoracic echocardiography more frequently in native valve endocarditis (71% vs 15% in prosthetic valve endocarditis; P < 0.0001). Transoesophageal echocardiography visualized vegetations in 95% of the episodes of native valve endocarditis and in 80% of the episodes of prosthetic valve endocarditis (P = 0.09). Thus, the diagnostic gain by transoesophageal echocardiography was greatest in prosthetic valve endocarditis. Patients with native valve endocarditis had significantly larger vegetations than patients with prosthetic valve endocarditis (P < 0.05 for length, P < 0.001 for width). The median time to diagnosis was similar in native valve endocarditis and prosthetic valve endocarditis (31 vs 28 days). Surgery was performed in 74% of patients with native valve endocarditis and in 58% of those with prosthetic valve endocarditis; the median time delay between the diagnosis of infective endocarditis and surgery tended to be shorter in prosthetic valve endocarditis than in native valve endocarditis (45 vs 60 days). The in-hospital mortality and the mortality during a follow-up of 22 +/- 10 months did not significantly differ between native valve endocarditis and prosthetic valve endocarditis (21% vs 17%; 28% vs 25%). In summary in the era of transoesophageal echocardiography, late prosthetic valve endocarditis does not seem to carry a worse prognosis than native valve endocarditis. This can be attributed in part to the improved diagnostic accuracy achieved by transoesophageal echocardiography leading to comparable diagnostic latency periods in both patient groups. Finally, better characterization of vegetations on prosthetic valves by transoesophageal echocardiography allows early lifesaving surgery in patients with prosthetic valve endocarditis.

Fifty-three patients (42 men; 11 women) with Streptococcus bovis infective endocarditis attended a tertiary cardiology hospital between 1980 and 1991, and constituted 11% of the total number of infective endocarditis cases hospitalized there during that period. The mean age was 59 +/- 15 years; 15 had previously suffered valvular disease (12) or had a valvular prosthesis (3); one patient had had a previous infective endocarditis. The infective episode involved the aortic valve in 26 patients, both the aortic and mitral valves in 18 patients, the mitral valve only in six and other valves in three. Echocardiographic examination showed one or more vegetations in 44 patients. Cardiac failure was diagnosed in 35 patients and embolic episodes in 22, of whom 11 were cerebrovascular accidents. The patients became afebrile 19 +/- 39 days after starting antibiotic treatment. Valve replacement was performed in 37 patients during their initial hospitalization, and in four during follow-up. After a mean follow-up of 4.6 +/- 3.1 years with a 100% follow-up, 15 patients died: 1 preoperatively, one in the first 30 days after operation, 13 later (8141 operated patients and 5/12 non-operated patients). Actuarial survival was 73% at 5 years. Gastrointestinal signs were present in 12 patients; 43 patients (81%) had a full colonic examination which showed polyps in 20 patients and adenocarcinomas in seven. Of 11 late deaths four were related to a malignant colonic tumour. This study confirms that Streptococcus bövis infective endocarditis is 'relatively benign', but it stresses the frequency and potential severity of the associated colonic lesions, requiring colonoscopy and making the treatment of high risk lesions mandatory.

The outcome of infective endocarditis remains poor. It has an overall mortality of around 30%, rising in high-risk subgroups to 50% and 100%. The prognosis can be improved by identification of high-risk patients and special management. Patients with infective endocarditis are found to be at high risk for death or serious complications when one or more of the following factors exist: old age (especially > 60 years old), delayed diagnosis, staphylococcal infection, aortic valve endocarditis, large valvular vegetation, congestive heart failure, embolization in the central nervous system or coronary artery, prosthetic valve infection, recurrent events, and failed antibiotic therapy. These factors often coexist and interrelate with one another. Early diagnosis and active treatment are critical for a better clinical outcome. However, infective endocarditis is difficult to diagnose because of the atypical clinical manifestations and frequent negative results from blood culture. Echocardiography plays an indispensable role in the diagnosis and management of suspected or known infective endocarditis. By detecting and monitoring certain pathological changes associated with the disease, e.g. vegetation, abscess formation, or valvular destruction, echocardiography helps to diagnose the disease early, to identify patients at high risk, to monitor the patients, and to optimize the timing and mode of surgical intervention. Serious complications can thus be avoided or cured at an early stage and the prognosis significantly improved.

Three problems hamper the prognosis of patients who survive the initial phase of infective endocarditis (IE): the rate of IE recurrence is 0.3-2.5/100 patient years, about 60% of patients will have to be operated on at some time, 20-30% during the initial stay, 30-40% during the following 5-8 years; five-year survival after the hospital phase is about 75% in previous reports and 85% in more recent papers. Death is mainly due to heart failure. We looked at the long-term survival of 330 patients with IE who were hospitalized in our institution in 1970-1982, and at the potential influence of 10 factors: age, gender, previous heart disease, microorganism, location of IE, onset of IE, congestive heart failure (CHF) at onset, CHF during the first year, persistent fever, surgery at the acute phase. Global survival was 75% at 6 months, and 57% at 5 years. The only non-significant factor was IE location. The annual instantaneous risk of death was 0.55 at 6 months, 0.18 at 1 year, then 0.03. After one year, the only prognostic factor was age. The relative risk of dying among patients with IE who survived the first year, as compared to the risk of dying among the general population, was 3.27. The IE prognosis is not uniform. Mortality is high during the initial phase, but after one year the risk of dying is low, although still above that of the general population. Part of the risk is probably the direct consequence of IE, but part is due to the course of the underlying heart disease.

Optimal timing of surgery in infective endocarditis (IE) depends mainly on the haemodynamic tolerance of the patient. Emergency surgery is required in cases of refractory heart failure due to valvular lesions, intracardiac fistulas and high grade cardiac conduction abnormalities caused by septal abscesses. Surgery must be considered in all patients who have undergone a transient episode of heart failure such as a pulmonary oedema and it must be early--within 2 or 3 weeks of starting antibiotic therapy in patients with aortic regurgitation. Bacteriological indications are less frequent: persistent sepsis beyond the first week in spite of medical therapy, mycotic IE or prosthetic valve endocarditis caused by Gram-negative or staphylococcal organisms. Some complications may swing the argument in favour of surgery: detection of root abscesses or mycotic aneurysms using transoesophageal echocardiography, and systemic embolisms with persistent, large and mobile vegetative lesions. Mortality rate depends on the haemodynamic status but also on the severity of anatomical lesions, on the type of endocarditis (native or prosthetic valve), on the type of surgery and on bacterial aetiologies. It varies between 5% and 30%. The late postoperative outcome is good. The actuarial survival rate at 8 years was 70% in our series of 31 patients with aortic regurgitation and early surgery. In mitral regurgitation, conservative surgery is possible in most cases. In our department, 48 patients with mitral bacterial lesions have been operated on with conservative surgery without operative mortality. IE was active in 14, recent in 12 and had occurred earlier in 22.(ABSTRACT TRUNCATED AT 250 WORDS)

Among 101 consecutive patients operated on for native infective aortic valve endocarditis (53 males, 48 females, mean age 39 years), 69 presented various forms of infectious extension to the surrounding areas. Twenty-six lesions were noted in the aortic roots: 18 annular abscesses, one abscess of the Valsalva sinus and seven aortic wall destructions. Among the subaortic valve pathology, 27 cases of septal lesions were noted and in one case the mitral fibrous trigone was involved. The mitral apparatus was infected in 26 cases, the tricuspid valvule in one case. Both tricuspid and mitral valvular replacements had to be performed in five cases. Among the 16 postoperative atrioventricular blocks, 14 needed a pacemaker. The most frequent causative microorganisms were Staphylococcus aureus and Streptococcus. Surgical management of the lesions consisted of extensive debridement followed by either simple repair of defects or complex reconstructions involving pericardial or synthetic patches or other more complex operations. Early and late mortality rates were 8.5% and 16%; early and late reoperation rates were 6% and 9.5%, respectively. The mean follow-up time was 148 months (12-265 months) with a survival rate of 74% (SE: +/- 0.08) at 10 years. We conclude that, although surgical correction of infective endocarditis may need a complex approach, it provides good results with an acceptable surgical risk.

Objective: To update data on incidence and characteristics of infective endocarditis in France., Background: Numerous studies have shown that the incidence and course of infective endocarditis remain stable in spite of advances in treatment and of prophylactic recommendations., Methods: A survey of all consecutive cases of infective endocarditis was conducted over 12 months in all the institutions of three French regions., Results: Data were collected from 415 cases of definite (32%), probable (53%), and possible (15%) infective endocarditis. The adjusted annual incidence was 24.3 cases per million inhabitants. Thirty-four percent of the patients had no previously known heart disease, 33% had native valve disease, 22% had a prosthetic valve, and 11% had miscellaneous underlying conditions. Infective endocarditis was located solely on the mitral valve in 39%, solely on the aortic valve in 36%, and on the tricuspid valve in 6%. Echocardiography showed a vegetation on the mitral valve in 39%, on the aortic valve in 29%, and on the tricuspid valve in 8%. The causal microorganism was identified in 92%; it was a Streptococcus in 58%, and a Staphylococcus in 23%. Twenty patients were intravenous drug users, and 45 had had a medical or a surgical procedure, which might be associated with the occurrence of infective endocarditis. During the first 2 months after admission, 24% of the patients underwent surgery, and 17% of all patients died., Conclusions: Despite medical and surgical advances, infective endocarditis remains frequent and severe in France.

Long-term results after prosthetic heart valve replacement are usually presented in actuarial terms, which do not take into account the background mortality of the general population. The calculations of the relative survival, which is the ratio between the observed survival in a group of patients during a specified time interval and the survival expected from the general population experience, permit correction for important demographic variables. We have analysed the long-term relative survival rates in a consecutive series of 841 Norwegian patients who, on the basis of clinical symptoms, underwent aortic (AVR, n = 617), mitral (MVR, n = 146), and double (AVR + MVR, n = 78) valve replacement between June 1977 and January 1985. The follow-up was closed on May 1st 1986, was 100% complete and included 2056 patient-years. The actuarial survival data for the total cohort was 75.1%, and for AVR, MVR and DVR, 77.9, 69.7 and 63.0%, respectively. The corresponding figures for the relative survival were 83.5, 87.0, 76.6 and 69.1%, respectively. Within the subgroup undergoing AVR, our analysis demonstrated a poor prognosis in those who were operated for pure aortic regurgitation or endocarditis, as well as in those who received the smallest valve size prosthesis due to a narrow aortic root. In this analysis, as in the analysis of the total material, we observed that the differences between survival in the patients and in the general population were of smaller magnitude when based on relative survival rates than when analysed in the standard (actuarial) way.(ABSTRACT TRUNCATED AT 250 WORDS)

Criteria defined by von Reyn were applied to 86 cases of bacterial endocarditis. Neurologic complications (NC) were categorized according to Pruitt definitions. Neurologic accidents were observed in 48 cases. They were the first clinical manifestation in 20 patients. Neurologic events were of poor prognosis in BE, mortality increasing from 26% in patients without NC to 83% in patients with NC (P less than 0.01). Two factors affect the incidence of NC: first, the location of endocarditis with 76% of NC in mitral valve endocarditis compared with 37% in other cases (P less than 0.005); and second the infecting organism: 71% of NC in staphylococcus aureus endocarditis versus 45% in endocarditis with other bacteria (P less than 0.02). Cerebral embolism was the most common NC (25 cases) related to an occlusion of the middle cerebral artery in 21 cases with a fatal outcome in 19 patients. Other NC included 15 intracranial hemorrhages with the evidence of an aneurysm in 4 cases, 6 septic meningitis, 2 macroscopic abscesses, and 2 multiple microscopic abscesses. This study emphasizes the high rate and severity of NC in staphylococcal mitral endocarditis despite antibiotic therapy and supports early surgery in this group of bacterial endocarditis.

Seventy-eight consecutive episodes of infective endocarditis on native valves have been prospectively treated and followed-up after discharge from 1975 to 1982 (mean follow-up period 31 months). Twenty one patients needed valvular replacement in the active phase of the disease. Overall mortality was 15 cases, 7 from the medical group and 8 from the surgical group. At last clinical control 21 from the 46 survivors of the medical group remained asymptomatic, 17 had needed valvular replacement, 5 had died 2 of congestive heart failure and 3 (addicts) were lost to follow-up. From the 13 survivors of the surgical group 8 remained asymptomatic with good prosthetic function, 4 had needed reoperation due to severe periprosthetic leak and 1 died suddenly during follow-up. Figures at the end of follow-up showed that 28% of the initial patients had died, 39% carried a valvular prosthesis and 28% remained asymptomatic. A retrospective analysis of factors predictive of poor prognosis has been carried out.

Fifty six cases of tricuspid infective endocarditis (TIE) were seen over a period of 15 years. The patients were divided into three groups, on the basis of the site of entry: (a) Thirty one TIE after abortion (6 cases) or in association with drug addiction (25 cases) are characterized by the young age of the patients and the organism (29 staphylococci), the existence of repeated pulmonary emboli and the relatively favourable prognosis (3 deaths). (b) Twelve TIE due to an intravenous infusion catheter (9 cases) or a visceral site of entry: older patients, resistant organisms (3 gram negative bacilli, 8 staphylococci, 5 of which were methicillin-resistant) and with poor prognosis (8 deaths). (c) Thirteen TIE where the site of entry was unidentified, running a sub-acute course, 7 due to streptococci, and often associated with involvement of the left side of the heart, which was the dominant prognostic feature (6 deaths). Mortality was 30%. Of predominant importance in prognosis was the sensitivity of the organism: 6 deaths out of 9 TIE due to methicillin-resistant Staphylococcus aureus and 3 out of 31 TIE due to a sensitive staphylococcus (P less than 0.01). Seventeen underwent surgery. Tricuspidectomy (8 patients) should be reserved for cases of uncontrolled infection. Surgery is not justified by the persistence of pulmonary emboli.

Renal involvement (RI)--defined as proteinuria greater than 150 mg per 24 h with haematuria or impaired glomerular filtration rate--was studied in 80 patients with infective endocarditis (IE). Proteinuria was measured quantitatively and further differentiated by the SDS-polyacrylamide-gel electrophoresis. RI was found in 40 patients (50%) with proteinuria from 150 to 8000 mg per 24 h. SDS-PAGE revealed a tubular protein pattern in 17 patients, a glomerular pattern in 6 and a glomerulo-tubular pattern in 17. Mortality rate was significantly higher in patients with RI (40%) than in those without (7.5%), and was not related to the type of infected valve, infective organisms, method of treatment (surgical or medical) or embolic events. Following successful treatment of IE, 18 out of 23 patients showed complete normalization of renal function. Renal involvement in patients with IE may be of prognostic significance--indicating an impaired prognosis.

From 1972 to 1982, 22 patients were admitted for prosthetic valve endocarditis on homografts (3), bioprostheses (2) or mechanical prostheses (17). Staphylococcus epidermidis was the most common aetiologic agent in early-onset endocarditis and streptococci in late-onset. Echo-cardiographic or cinefluoroscopic findings enhanced diagnosis mainly in advanced stages of the disease. Despite medical therapy and prompt reoperation in most cases, mortality remains high: 66%, 80% in the early group, 50% in the late group; the prognosis was definitely improved, however, by surgical treatment.

Three hundred and seventy eight patients with infectious endocarditis (IE) were studied, including 299 cases of native IE [154 subacute (SIE), 145 acute (AIE)] and 79 cases of prosthetic endocarditis (PIE). One hundred and fifty patients were operated on (40%): 117 for haemodynamic complications, 10 for bacteriological indications and 23 for mixed indications (112 patients in the acute phase). Complications were more frequent in AIE than in SIE, in PIE than in native IE. Surgery is more urgent in aortic insufficiency and in Oslerian mitral stenosis (7 cases) than in mitral insufficiency. Eight tricuspid valvulectomies were performed. In 5 cases out of 11 rupture syndrome was cured without surgery. The patient's clinical condition contra-indicated surgery in 63 cases. The surgical mortality was 51/150 (34%). It was significantly lower in SIE (21%) than in AIE (39%), in native IE than in PIE (53%), after antibiotic therapy than in the acute phase. Mortality was not higher when surgery was performed before the 8th day of antibiotherapy but perivalvular leaks were more common (31% vs 4%, P less than 0.01). Mortality was higher when the culture of valve was positive than when it was negative (45% vs 26%, P less than 0.06). However, surgery should be immediately considered in cases of haemodynamic complications.

Twenty-five consecutive unequivocal cases of Staphylococcus aureus endocarditis in a single centre over 5 years were reviewed. Despite an unusually high proportion of prosthetic infections an early mortality of only 16% was observed. Analysis reveals that early diagnosis and prompt effective antibiotic chemotherapy were important factors in achieving this low mortality. Monotherapy with an isoxazolyl penicillin (flucloxacillin) was shown to be as effective as combination therapies, and there was a significant association between the use of aminoglycosides and subsequent renal damage.

Forty years after the first 'recoveries' obtained by antibiotherapy and twenty years after the first success of early valvular replacement, the mortality of infective endocarditis (IE) is still significant. The present study has been undertaken to clarify the factors which influence the prognosis of IE.

One hundred and six patients were analysed in order to assess the effect of a more aggressive surgical policy in relation to the delays in diagnosis of infective endocarditis. The average duration of symptoms before diagnosis was 9.7 weeks, even though the patients had sought medical advice at a relatively early stage of their illness (2.2 weeks). Three of the 29 (10.3%) patients who were treated surgically died and all three were operated upon five weeks or later after diagnosis. Seventy-seven patients did not have surgery and 15 died (19.5%). The outcome of surgical treatment for prosthetic valve endocarditis was no worse than for native valve endocarditis. The mortality of prosthetic valve endocarditis including early infections was 32% with medical but only 10% with surgical management compared with 14.5% and 10.5% in native valve endocarditis. Endocarditis cannot always be prevented but earlier diagnosis would reduce mortality and prevent complications. When medical treatment is failing then surgery should be considered early and urgently particularly in staphylococcal infection or when large mobile vegetations are recognized; surgery is mandatory in fungal endocarditis. Earlier diagnosis would greatly reduce the current high incidence of surgery, but that depends on a much heightened index of suspicion amongst both general practitioners and hospital physicians.