Alberto Riberi

Risk of Embolism and Death in Infective Endocarditis: Prognostic Value of Echocardiography. A Prospective Multicenter Study

Background—The incidence of embolic events (EE) and death is still high in patients with infective endocarditis (IE), and data about predictors of these 2 major complications are conflicting. Moreover, the exact role of echocardiography in risk stratification is not well defined. Methods and Results—In a multicenter prospective European study, including 384 consecutive patients (aged 57±17 years) with definite IE according to Duke University criteria, we tested clinical, microbiological, and echocardiographic data as potential predictors of EE and 1-year mortality. Transesophageal echocardiography was performed in all patients. Embolism occurred before or after IE diagnosis (total-EE) in 131 patients (34.1%) and after initiation of antibiotic therapy (new-EE) in 28 patients (7.3%). Staphylococcus aureus and Streptococcus bovis were independently associated with total-EE, whereas vegetation length >10 mm and severe vegetation mobility were predictors of new-EE, even after adjustment for S aureus and S bovis. One-year mortality was 20.6%. In multivariable analysis, independently of the other predictors of death (age, female sex, creatinine serum >2 mg/L, moderate or severe congestive heart failure, and S aureus) and comorbidity, vegetation length >15 mm was a predictor of 1-year mortality (adjusted relative risk=1.8; 95% CI, 1.10 to 2.82; P=0.02). Conclusions—In IE, vegetation length is a strong predictor of new-EE and mortality. In combination with clinical and microbiological findings, echocardiography may identify high-risk patients who will need a more aggressive therapeutic strategy.

Prosthetic valve endocarditis: who needs surgery? A multicentre study of 104 cases

Objectives: To identify the prognostic markers of a bad outcome in a large population of 104 patients with prosthetic valve endocarditis (PVE), and to study the influence of medical versus surgical strategy on outcome in PVE and thus to identify patients for whom surgery may be beneficial. Design: Multicentre study. Methods and results: Among 104 patients, 22 (21%) died in hospital. Factors associated with in-hospital death were severe co-morbidity (6% of survivors v 41% of those who died, p  =  0.05), renal failure (28% v 45%, p  =  0.05), moderate to severe regurgitation (22% v 54%, p  =  0.006), staphylococcal infection (16% v 54%, p  =  0.001), severe heart failure (22% v 64%, p  =  0.001), and occurrence of any complication (60% v 90%, p  =  0.05). By multivariate analysis, severe heart failure (odds ratio 5.5) and Staphylococcus aureus infection (odds ratio 6.1) were the only independent predictors of in-hospital death. Among 82 in-hospital survivors, 21 (26%) died during a 32 month follow up. A Cox proportional hazards model identified early PVE, co-morbidity, severe heart failure, staphylococcus infection, and new prosthetic dehiscence as independent predictors of long term mortality. Mortality was not significantly different between surgical and non-surgical patients (17% v 25%, respectively, not significant). However, both in-hospital and long term mortality were reduced by a surgical approach in high risk subgroups of patients with staphylococcal PVE and complicated PVE. Conclusions: Firstly, PVE not only carries a high in-hospital mortality risk but also is associated with high long term mortality and needs close follow up after the initial episode. Secondly, congestive heart failure, early PVE, staphylococcal infection, and complicated PVE are associated with a bad outcome. Thirdly, subgroups of patients could be identified for whom surgery is associated with a better outcome: patients with staphylococcal and complicated PVE. Early surgery is strongly recommended for these patients.

The timing of surgery influences mortality and morbidity in adults with severe complicated infective endocarditis: a propensity analysis

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.

Dramatic Reduction in Infective Endocarditis-Related Mortality With a Management-Based Approach

BACKGROUND Despite improvements in medical and surgical therapy, infective endocarditis (IE) is still associated with a severe prognosis and remains a therapeutic challenge. We aimed to evaluate the impact of a standardized diagnostic and therapeutic protocol on mortality and to correlate the outcome with compliance with our management-based protocol. METHODS We conducted an observational before-after study that included 333 consecutive patients treated for IE at a referral center from 1991 to 2006, which was divided into 2 periods: period 1 (1991-2001), before implementation of our therapeutic protocol (n = 173), and period 2 (2002-2006), after implementation of our protocol (n = 160). Our protocol was created by a multidisciplinary task force including a sampling of biological specimens, the use of only 4 antimicrobial agents, a standardized duration of treatment, standardized surgical indications, and 1 year of close follow-up. Because our protocol was based on a local consensus by physicians and surgeons, it was not possible to randomize the study. RESULTS The 1-year mortality significantly decreased from 18.5% during period 1 to 8.2% during period 2 (hazard ratio, 0.41; 95% confidence interval, 0.21-0.79 [P = .008]). After multivariable analysis, the management during period 2 remained a strong protective factor (adjusted hazard ratio, 0.26; 95% confidence interval, 0.09-0.76 [P = .01]). During period 2, we observed a statistically significantly better compliance in antimicrobial therapy and fewer cases of renal failure. Deaths by embolic events and multiple organ failure syndrome also significantly decreased during period 2. CONCLUSION A dramatic reduction in mortality was observed during this study, suggesting that a management-based approach has a significant impact on IE outcome.

Comparison of clinical and echocardiographic characteristics of Streptococcus bovis endocarditis with that caused by other pathogens

The aim of our study was to compare the clinical, echographic, and prognostic features of Streptococcus bovis (S. bovis) endocarditis with those caused by other streptococci and pathogens in a large sample of patients with definite endocarditis by Duke criteria, using transesophageal echocardiography. Two hundred six patients (149 men, mean age 57 +/- 15 years) with a diagnosis of infective endocarditis formed the study population. All patients underwent multiplane transesophageal echocardiography and blood cultures. Cerebral, thoracoabdominal computed tomographic scan was performed in almost all patients (95%). All patients with S. bovis endocarditis underwent colonoscopy. Incidence of S. bovis endocarditis in our sample was 19%. Patients with S. bovis endocarditis were older than other groups. Multiple valve involvement, native valves, and large vegetations (>10 mm) were more frequent in patients with S. bovis. There was a significantly higher occurrence of embolism in the S. bovis group. Splenic embolism and multiple embolisms were significantly more frequent in patients with S. bovis. Gastrointestinal lesions, anemia, and spondylitis were observed more frequently with S. bovis endocarditis. In addition to the requirement for gastrointestinal examination for S. bovis endocarditis, our study underlines the need for systematic screening for vertebral and splenic localizations, and suggests the use of early surgery to prevent the high risk of embolism in these patients.

Excess mortality and morbidity in patients surviving infective endocarditis

BACKGROUND Mortality and morbidity associated with infective endocarditis may extend beyond successful treatment. The primary objective was to analyze rates, temporal changes, and predictors of excess mortality in patients surviving the acute phase of endocarditis. The secondary objective was to determine the rate of recurrence and the need for late cardiac surgery. METHODS An observational cohort study was conducted at a university-affiliated tertiary medical center, among 328 patients who survived the active phase of endocarditis. We used age-, sex-, and calendar year-specific mortality hazard rates of the Bouches-du-Rhone French district population to calculate expected survival and excess mortality. The risk of recurrence and late valve surgery was also assessed. RESULT Compared with expected survival, patients surviving a first episode of endocarditis had significantly worse outcomes (P = .001). The relative survival rates at 1, 3, and 5 years were 92% (95% CI, 88%-95%), 86% (95% CI, 77%-92%), and 82% (95% CI, 59%-91%), respectively. This excess mortality was observed during the entire follow-up period but was the highest during the first year after hospital discharge. Most of the recurrences and late cardiac surgeries also occurred during this period. Women exhibited a higher risk of age-adjusted excess mortality (adjusted excess hazard ratio, 2.0; 95% CI, 1.05-3.82; P = .03). Comorbidity index, recurrence of endocarditis, and history of an aortic valve endocarditis in women were independent predictors of excess mortality. CONCLUSIONS These results justify close monitoring of patients after successful treatment of endocarditis, at least during the first year. Special attention should be paid to women with aortic valve damage.

Association of mild hyperhomocysteinemia with cardiac graft vascular disease

In non-transplant patients mild hyperhomocysteinemia is an independent risk factor for vascular disease. The aim of this study was to determine whether hyperhomocysteinemia is associated with graft vascular disease. Fasting total plasma homocysteine was assessed in 18 patients with graft vasculopathy and 18 transplanted patients without graft vasculopathy matched for age, sex and the time since transplant. All were on cyclosporin. Graft vasculopathy was defined at coronary angiography as stenoses > or = 25%, or aneurysms. We found that hyperhomocysteinemia ( > or = 15 micromol/l) is common among transplanted heart recipients and significantly more frequent in the patients with graft vasculopathy (17/18 versus 11/18). Accordingly, the mean homocysteinemia was significantly higher in the group with graft vasculopathy (23.6+/-7.8 versus 16.9+/-7.1 micromol/l, P=0.01). The elevation of homocysteine plasma levels in the heart transplant recipients has probably multiple causes. The main cause seems to be renal failure. Additional causes could be azathioprine treatment or genetic polymorphisms. These results suggest that besides the immunological factors, homocysteine can play an additional role in the pathogenesis of graft vascular disease.

Prediction of Symptomatic Embolism in Infective Endocarditis: Construction and Validation of a Risk Calculator in a Multicenter Cohort

OBJECTIVES The aim of this study was to develop and validate a simple calculator to quantify the embolic risk (ER) at admission of patients with infective endocarditis. BACKGROUND Early valve surgery reduces the incidence of embolism in high-risk patients with endocarditis, but the quantification of ER remains challenging. METHODS From 1,022 consecutive patients presenting with definite diagnoses of infective endocarditis in a multicenter observational cohort study, 847 were randomized into derivation (n = 565) and validation (n = 282) samples. Clinical, microbiological, and echocardiographic data were collected at admission. The primary endpoint was symptomatic embolism that occurred during the 6-month period after the initiation of treatment. The prediction model was developed and validated accounting for competing risks. RESULTS The 6-month incidence of embolism was similar in the development and validation samples (8.5% in the 2 samples). Six variables were associated with ER and were used to create the calculator: age, diabetes, atrial fibrillation, embolism before antibiotics, vegetation length, and Staphylococcus aureus infection. There was an excellent correlation between the predicted and observed ER in both the development and validation samples. The C-statistics for the development and validation samples were 0.72 and 0.65, respectively. Finally, a significantly higher cumulative incidence of embolic events was observed in patients with high predicted ER in both the development (p < 0.0001) and validation (p < 0.05) samples. CONCLUSIONS The risk for embolism during infective endocarditis can be quantified at admission using a simple and accurate calculator. It might be useful for facilitating therapeutic decisions.

Clinical characteristics and outcome of infective endocarditis in adults with bicuspid aortic valves: a multicentre observational study

Objective To analyse characteristics and outcomes of infective endocarditis (IE) on bicuspid aortic valves (BAV) and to compare the risk of death according to the presence or absence of BAV. Design 5-year observational study. Setting Population of 856 patients with definite IE according to the Duke criteria from two tertiary centres (Amiens and Marseille, France). Patients 310 consecutive patients with definite native aortic valve IE enrolled between 1991 and 2007. Interventions Patients underwent transthoracic and transoesophageal echocardiography during hospitalisation. Surgery was performed on a case-by-case basis according to conventional guidelines. Main outcome measures In-hospital mortality and 5-year overall mortality. Results Patients with BAV IE (n=50, 16%) were younger, had fewer comorbidities and a higher frequency of aortic perivalvular abscess (50%). Presence of BAV (OR 3.79 (1.97–7.28); p<0.001) was independently predictive of abscess formation. Early surgery was performed in 36 BAV patients (72%) with a peri-operative mortality of 8.3%, comparable to that of patients with tricuspid aortic valve IE (p=0.89). BAV was not independently predictive of in-hospital mortality (OR 0.89 (0.28–2.85); p=0.84) or 5-year survival (HR 0.71 (0.37–1.36); p=0.30). Age, comorbidities, heart failure, Staphylococcus aureus and uncontrolled infection were associated with increased 5-year mortality in BAV patients. Conclusion BAV is frequent in adults with native aortic valve IE. Patients with BAV IE incur high risk of abscess formation and require early surgery in almost three-quarters of cases. IE is a severe complication in the setting of BAV and warrants prompt diagnosis and treatment.

Infective Endocarditis: Prevention, Diagnosis, and Management

Infective endocarditis (IE) is among the most severe infectious disease, the prevention of which has not decreased its incidence. The age of patients and the rate of health care-associated IE have increased as a consequence of medical progress. The prevention strategies have been subjected to an important debate and nonspecific hygiene measures are now placed above the use of antibiotic prophylaxis. Indeed, the level of evidence of antibiotic prophylaxis efficiency is low and the indications of its prescription have been restricted in the recent international guidelines. In cases carrying a high suspicion of IE, efforts should be made to rapidly identify patients with a definite or highly probable diagnosis of IE and to find the causative pathogen to ensure that appropriate treatment, including urgent valvular surgery, begins promptly. Although echocardiography remains the main accurate imaging modality to identify endocardial lesions associated with IE, it can be negative or inconclusive especially in cases of prosthetic valve or other intracardiac devices. Recent studies demonstrated the diagnostic value of other imaging strategies including cardiac computed tomography (CT), positron emission tomography/CT, radiolabelled leukocyte single-photon emission CT/CT, and cerebral magnetic resonance imaging. Novel perspectives on the management of endocarditis are emerging and offer a hope for decreasing the rate of residual deaths by accelerating the processes of diagnosis, risk stratification, and instauration of antimicrobial therapy. Moreover, the rapid transfer of high-risk patients to specialized mediosurgical centres (IE team), the development of new surgical modalities, and close long-term follow-up are of crucial importance.