Long-Term Results After Operations for Active Infective Endocarditis in Native and Prosthetic Valves

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1 Long-Term Results After Operations for Active Infective Endocarditis in Native and Prosthetic Valves Katharina Meszaros, MD, Sladjan Nujic, MS, Gottfried H. Sodeck, MD, Lars Englberger, MD, Tobias König, MS, Florian Schönhoff, MD, David Reineke, MD, Eva Roost-Krähenbühl, MD, Jürg Schmidli, MD, Martin Czerny, MD, and Thierry P. Carrel, MD Department of Cardiovascular Surgery, University Hospital Berne, Berne, Switzerland; Department of Cardiac Surgery, Medical University of Graz, Graz, Austria; Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria Background. The objective of this study was to evaluate the midterm results of patients who underwent operations for active infective endocarditis. Methods. Within a 10-year period, 141 patients with active infective endocarditis received surgical therapy. We assessed outcome, freedom from reinfection, and freedom from reintervention. Prosthetic valve endocarditis was included in this series. Results. Surgical strategies included valve replacement with a tissue valve in 62% of patients and valve repair in 29% of patients. In 29% of patients, reconstruction of the aortomitral continuity, left ventricular outflow tract, or sinus of Valsalva was preferably performed with 1 or more bovine pericardial patches. In-hospital mortality was 11% and postoperative stroke rate was 7%. Multivariate logistic regression revealed multivalve involvement (p 0.052; odds ratio [OR], 5.84; 95% confidence interval [CI], ), preoperative neurologic impairment (p 0.006; OR, 9.71; 95% CI, ), and European system for cardiac operative risk evaluation (EuroSCORE) in quartiles (p 0.023; OR, 2.88; 95% CI, ) to be independent predictors for in-hospital death. One-year and 5-year actuarial survival was 77% and 69%, respectively. One-year and 5-year actuarial freedom from reinfection was 100% and 90%, respectively. Freedom from reoperation at 5 years was 100%. Five-year survival was 74% for single-valve endocarditis and 46% for multivalve endocarditis (p < 0.001). One-year freedom from reinfection was 100% for both single-valve and multivalve endocarditis; 5-year freedom from reinfection was 95% for single-valve endocarditis versus 67% for multivalve endocarditis (p 0.049). Conclusions. Despite a high early mortality during the first year, surgical intervention for active infective endocarditis provided excellent results with regard to freedom from reinfection and reoperation. A strategy of extensive debridement, reconstruction of destroyed cardiac structures using xenopericardium, followed by valve replacement or repair is highly effective and shows favorable long-term outcomes. (Ann Thorac Surg 2012;94: ) 2012 by The Society of Thoracic Surgeons Surgical intervention for active infective endocarditis of native and prosthetic valves sometimes remains challenging, and outcome is highly dependent on the degree of urgency with which the surgical procedure must be performed, the extent of destruction of cardiac structures adjacent to the valve through the infective process, accompanying systemic affections, and classic risk factors such as age or renal insufficiency [1 5]. The aim of this study was to evaluate the early and midterm results in patients who underwent surgical procedures for active infective endocarditis. Accepted for publication April 26, Address correspondence to Dr Czerny, Freiburgstrasse 18, 3010 Berne, Switzerland; martin.czerny@insel.ch. Patients and Methods Patients Within a 10-year period, 141 patients received surgical treatment because of active infective endocarditis. Patient characteristics are described in Table 1. Patients were stratified according to EuroSCORE classifications [6]. An institutional review board approved the study and waived the need for patient consent. Diagnostic Algorithm and Indications for Operation The diagnosis of active infective endocarditis was made according to clinical findings, serial blood sample testing, and imaging, and was confirmed using Duke s criteria. Laboratory examinations included serum leucocyte count, C-reactive protein serum levels, serum calcitonin levels, and serum erythrocyte sedimentation rate. In this series, the indication for surgical treatment was largely based on echocardiographic findings such as significant 2012 by The Society of Thoracic Surgeons /$36.00 Published by Elsevier Inc

2 Ann Thorac Surg MESZAROS ET AL 2012;94: ACTIVE INFECTIVE ENDOCARDITIS OPERATIONS 1205 Table 1. Descriptive Characteristics of the Cohort Characteristic N (Overall 141) Demographics Age, median (IQR) 60 (43 71) Female, n (%) 30 (21%) Chronic health conditions Hypertension, n (%) 54 (38%) Diabetes, n (%) 27 (19%) COPD, n (%) 11 (8%) Serum creatinine level 200 mmol/l, n (%) 36 (26%) Coronary artery disease, n (%) 6 (4%) LV function 30%, n (%) 6 (4%) Peripheral artery occlusive disease, n (%) 6 (4%) HIV positivity, n (%) 4 (3%) Risk factors IV drug abuse, n (%) 20 (14%) Bicuspid aortic valve, n (%) 21 (15%) Iatrogenic cause, n (%) 23 (16%) Previous valve replacement, n (%) 25 (18%) Location and microbiologic features Aortic valve, n (%) 90 (64%) Mitral valve, n (%) 67 (48%) Tricuspid valve, n (%) 8 (6%) More than 1 affected valve, n (%) 22 (22%) Positive microbiology, n (%) 113 (80%) Staphylococcus spp, n (%) 49 (35%) Unless otherwise indicated, data are numbers (percentage). COPD chronic obstructive pulmonary disease; HIV human immunodeficiency virus; IQR interquartile range; IV intravenous; LV left ventricular. valve insufficiency, an increasing abscess cavity, the size and mobility of the vegetation ( 1.5 cm or growing vegetations despite adequate antibiotic treatment), and the presence of clinical symptoms such as embolization or recurrent shivering and fever with adequate antibiotic treatment. Finally, new onset of atrioventricular block was considered indicative. According to the individual clinical situation, operation was performed when systemic infectious values were decreasing, in the ideal case after antibiotic treatment lasting 4 to 6 weeks. Surgical Treatment Algorithm The surgical approach was similar irrespective of the affected valves and consisted of complete removal of the infected native tissue, extensive local debridement, and reconstruction of the affected structures such as the left ventricular outflow tract, aortomitral continuity, or the atrioventricular continuity with a bovine pericardial patch. Valve replacement or reconstruction was performed as appropriate. Homografts were used only in patients with extensive destruction of the aortic root. Antibiotic Treatment Algorithm Antibiotic therapy was given according to the guidelines of the European Society for Cardiology that address active infective endocarditis in culture-positive as well as culture-negative situations [7]. The most appropriate antibiotic treatment was applied when the type of bacteria was identified. In case of favorable clinical evolution (absence of fever or weight loss), normalization of infectious measurements (erythrocyte sedimentation rate, C- reactive protein serum levels, white blood cell count), and normalized imaging results, antibiotics were discontinued 6 weeks after surgery. Otherwise antibiotic treatment was continued. Data Collection and Follow-Up Protocol Patients were enrolled in a strict follow-up protocol that required clinical, laboratory, and echocardiographic evaluations at 3, 6, and 12 months, and annually thereafter. Preoperative and Postoperative Neurologic Injury and Imaging Whenever possible, preoperative neurologic imaging was performed by means of magnetic resonance imaging or computed tomography. Only in patients with hemodynamic instability who underwent emergency operations was preoperative neurologic imaging not performed. These patients underwent neurologic imaging postoperatively when they were in a hemodynamically stable condition. Statistical Analysis Continuous data are presented as the median and interquartile range (range from the 25th to the 75th percentile). Discrete data are given as counts and percentages. Overall survival and freedom from reinfection were calculated according to the method of Kaplan and Meier. A multivariate logistic model was applied to assess the strongest independent risk factor for in-hospital death after adjustment for possible confounding factors. Preoperative risk factors as defined by the EuroSCORE in quartiles, redo operations, ventricular septal defect, need for mechanical ventilation or circulatory support, emergency operations, preoperative neurologic deficits, and persistent bacteremia requiring previous septic noncardiovascular operations were included in the final model. Results of the logistic regression model are given as the odds ratio (OR) and the 95% confidence interval (CI). Regression diagnostics and overall model fit were performed according to standard procedures. A 2-sided p value less than 0.05 was considered statistically significant. All calculations were performed with SPSS, version 20.0 software for MacOSX (SPSS Inc, Chicago, IL). Results In-Hospital Mortality In-hospital mortality was 11%. One patient died during the surgical procedure because of massive septic shock in which severe vasoplegia developed without any pharmacologic response. All other patients died of multiorgan failure as a sequela of the underlying infective process.

3 1206 MESZAROS ET AL Ann Thorac Surg ACTIVE INFECTIVE ENDOCARDITIS OPERATIONS 2012;94: Cause of Active Infective Endocarditis Fourteen percent of patients were active intravenous drug abusers at the time of diagnosis. Fifteen percent of patients had a bicuspid aortic valve. Eighteen percent of patients had already undergone some kind of valve replacement, and 16% of patients had an iatrogenic underlying cause of disease. In 50% of the iatrogenic causes, a dental procedure was identified as the most possible underlying cause. In the remaining patients, the cause of active infective endocarditis could not be defined (Table 1). The distribution of valves affected is also shown in Table 1. The germs isolated are given in detail in Table 2. Table 2. Distribution of Endocarditis-Causing Organisms Microorganism N Percentage of (Overall 141) Overall Abiotrophia defectiva (Streptococcus) n, (%) Beta-hemolytic Streptococcus n, % (%) Chlamydia pneumoniae n, (%) Coagulase-negative % Staphylococcus n, (%) Culture-negative n, (%) % Enterococcus faecalis n, (%) % Enterococcus n, (%) % Granulicatella adiacens (Streptococcus viridans) n, (%) Lactobacillus n, (%) Staphylococcus aureus n, (%) % S epidermidis n, (%) % S lugdunensis, Enterococcus gallinarum n, (%) S milleri n, (%) S sanguinis, n (%) Streptococcus not further classified n, (%) S agalactiae n, (%) S anginosus n, (%) S anginosus-milleri n, (%) S bovis n, (%) % S dysgalactiae n, (%) S gallolyticus n, (%) S gordonii n, (%) % Streptococcus group D n, (%) S infantarius n, (%) S milleri n, (%) % S mitis n, (%) % S mutans n, (%) % S oralis n, (%) S pneumoniae n, (%) S pyogenes n, (%) S sanguinis n, (%) S viridans n, (%) % Tropheryma whippeli n, (%) % Table 3. Preoperative Characteristics of the Cohort Characteristic N (Overall 141) Indication for surgery Septic shock, n (%) 18 (13%) Persistent fever, n (%) 38 (27%) Valve annular abscess, n (%) 48 (34%) Preoperative stroke, n (%) 28 (20%) Preoperative peripheral embolism, n (%) 4 (3%) Preoperative ventricular septal defect, n (%) 4 (3%) Higher grade AV block, n (%) 9 (6%) Timing of surgical procedure Emergency (within 24 h), n (%) 38 (27%) Urgency (within 72 h), n (%) 73 (52%) Elective, n (%) 12 (9%) Preoperative assessment Additional EuroSCORE, median (IQR) 8 (6 12) Mechanical ventilation, n (%) 12 (9%) Mechanical cardiac support, n (%) 4 (3%) Catecholamine support, n (%) 4 (3%) Other surgical procedure before cardiac 8 (6%) operation, n (%) Unless otherwise indicated, data are numbers (percentage). AV atrioventricular; EuroSCORE European system for cardiac operative risk evaluation; IQR interquartile range. Indication for and Time Point of Surgical Intervention The presence/development of an annular abscess was the most frequent indication for surgical intervention in this cohort of patients. This morphologic finding was rarely associated with greater than or equal to seconddegree atrioventricular block and developed most often in the noncoronary part of the annulus. Common indications for surgical intervention included persistent or recurrent fever, including septic shivering despite adequate antibiotic therapy, and preoperative stroke. The remaining indications are described in Table 3. Fifty-two percent of patients underwent operation on an urgent basis, whereas 27% underwent operation on an emergency basis (Table 3). Reconstructive Surgical Procedures After complete removal of the infected native tissue and extensive local debridement, reconstruction of the destroyed structures, such as the left ventricular outflow tract, the aortomitral continuity, or the atrioventricular continuity, was performed using a xenopericardial patch in 29% of patients. Root replacement was performed in 14% of patients either by homograft (3%) or by a composite graft (11%). Isolated valve replacement with a tissue prosthesis was done in 62% of patients and valve reconstruction was performed in 29% of patients, mostly in the mitral position (Table 4). Preoperative and Postoperative Neurologic Injury and Imaging Twenty-six of 141 patients exhibited preoperative neurologic injury. Whenever possible, neurologic imaging by

4 Ann Thorac Surg MESZAROS ET AL 2012;94: ACTIVE INFECTIVE ENDOCARDITIS OPERATIONS 1207 Table 4. Surgical Characteristics of the Cohort Characteristic N (Overall 141) Surgical strategy Valve reconstruction, n (%) 41 (29%) Biological valve replacement, n (%) 88 (62%) Homograft, n (%) 4 (3%) Aortic root replacement, n (%) 16 (11%) Concomitant CABG, n (%) 19 (14%) Additional procedures, n (%) 41 (29%) ECC in minutes, median (IQR) 116 (85 170) Aortic clamp time in minutes, median 81 (60 124) (IQR) In-hospital outcome Hospital stay in days, median (IQR) 12 (8 19) Intraoperative death, n (%) 1 (1%) In-hospital death, n (%) 15 (11%) Postoperative stroke, n (%) 10 (7%) Postoperative atrial fibrillation, n (%) 8 (6%) Postoperative renal failure, n (%) 10 (7%) Permanent pacemaker implantation, n (%) 21 (15%) Unless otherwise indicated, data are number (percentage). CABG coronary artery bypass grafting; ECC extracorporal circulation; IQR interquartile range. Table 5. Preoperative Neurologic Injury/Imaging Neurologic Injury/Imaging N (Overall 141) Vigilance impairment 9 (6.38%) Hemisyndrome/abscess, n (%) 9 (6.38%) Asymptomatic, abnormal neurologic 5 (3.54%) imaging results, n (%) Intracerebral bleeding, n (%) 2 (1.41%) Mycotic aneurysm/subarachnoid 1 (0.79%) bleeding, n (%) Table 6. Risk Factors for Intrahospital Death Multivariate Logistic Regression Variable p OR (95% CI) Multivalve involvement ( ) Preoperative neurologic injury ( ) Preoperative ventricular septal ( ) defect Preoperative mechanical support ( ) Reoperation ( ) Emergency procedure ( ) EuroSCORE (quartiles) ( ) Previous septic noncardiac ( ) operation Persistent bacteremia ( ) p Hosmer-Lemeshow test. CI confidence interval; EuroSCORE European system for cardiac operative risk evaluation; OR odds ratio. means of magnetic resonance imaging or computed tomography was performed preoperatively in all patients; in only 2 cases of hemodynamic instability could preoperative imaging not be performed. Preoperative neurologic symptoms were classified as shown in Table 5. Five patients with preoperative neurologic injury showed persistent neurologic impairment postoperatively, 4 of them died during hospitalization; in 2 patients the mortality was related to the neurologic situation. The first patient experienced massive bleeding in the basal ganglia, the second patient died 4 weeks postoperatively; he was deeply comatose with a Glasgow Coma Scale score of 3 before operation and did not show neurologic recovery. In 5 patients, preoperative neuroimaging proved the occurrence of cerebral emboli, but the patients did not exhibit clinical symptoms. Five of 141 (3.5%) patients showed new onset of neurologic symptoms postoperatively; the first patient was diagnosed with cerebrovascular insult; he died because of therapy-refractory multiorgan failure. The second patient exhibited transient left-sided hemiparesis postoperatively; magnetic resonance imaging showed ischemia of the precentral right-sided gyrus. Neurologic symptoms disappeared until discharge. The third patient was an intravenous drug abuser preoperatively; he had massive intracerebral bleeding postoperatively, so the therapy was changed to palliation. This patient died during intensive care. The fourth and fifth patients both experienced postoperative cerebral embolization, and both died during their hospital stays because of severe vasoplegia and subsequent multiorgan failure. Risk Factors for In-Hospital Death After Surgery Multivariate logistic regression revealed multivalve involvement (p 0.052; OR, 5.84; 95% CI, ), preoperative neurologic injury (p 0.006; OR, 9.71; 95% CI, ), and EuroSCORE in quartiles (p 0.023; OR, 2.88; 95% CI, ) to be independent predictors for in-hospital death (Table 6). Follow-Up One-year and 5-year actuarial survival was 77% and 69%, respectively (Figs 1, 2). One-year and 5-year actuarial freedom from reinfection was 100% and 90%, respectively (Fig 3). Freedom from reoperation at 5 years was 100%. All patients were available for clinical follow-up. Single-Valve Versus Multivalve Endocarditis Ninety-day survival was 91% for single-valve endocarditis and 66% for multivalve endocarditis; 180-day survival was 86% (single-valve endocarditis) and 55% (multivalve endocarditis) (p 0.001) (Fig 4). One-year survival was 84% (single-valve endocarditis) and 46% (multivalve endocarditis); 5-year survival was 74% for single-valve endocarditis and 46% for multivalve endocarditis (p 0.001) (Fig 5). One-year freedom from reinfection was 100% for both single-valve and multivalve endocarditis; 5-year freedom from reinfection was 95% for single-valve endocarditis versus 67% for multivalve endocarditis (p 0.049) (Fig 6).

5 1208 MESZAROS ET AL Ann Thorac Surg ACTIVE INFECTIVE ENDOCARDITIS OPERATIONS 2012;94: Fig 1. Ninety- and 180-day overall survival. Fig 3. Freedom from reinfection. Comment Despite high in-hospital mortality and an adverse outcome during the first year, surgical intervention for active infective endocarditis provides excellent results with regard to freedom from reinfection as well as freedom from reoperation. A strategy of extensive reconstruction of the cardiac structures affected or destroyed by the infective process in combination with valve replacement or repair is highly effective and is followed by favorable long-term outcome. Our hospital mortality was fairly high but comparable to other recent series [2, 5, 8]. Despite adequate antibiotic treatment, the use of cardiopulmonary bypass in a clinical situation in which the infectious process is not completely controlled, along with the usual responses to surgical trauma, caused significant vasoplegia requiring high doses of vasopressor therapy to maintain sufficient perfusion pressures during and immediately after the surgical procedure. In some instances, it would have been preferable to delay surgical intervention until the infectious process was fully controlled, but rapid deterioration of the clinical condition because of valve insufficiency or the destructive process itself required accelerated surgical treatment. The number of active intravenous drug abusers was lower than in other series [9, 10]. This is an interesting observational finding that mainly reflects the structure of Fig 2. One- and 5-year overall survival. Fig 4. Ninety- and 180-day survival in single-valve endocarditis (SVE) versus multivalve endocarditis (MVE).

6 Ann Thorac Surg MESZAROS ET AL 2012;94: ACTIVE INFECTIVE ENDOCARDITIS OPERATIONS 1209 Fig 5. One- and 5-year survival in single-valve endocarditis (SVE) versus multivalve endocarditis (MVE). the society and the drug-preventing regional programs. Likewise the percentage of HIV- positive patients was negligibly low. The number of patients with a bicuspid aortic valve, however, was fairly high. This underlines the increased vulnerability of bicuspid aortic valves for any kind of acute and chronic infectious and noninfectious processes [11]. It was interesting to observe that iatrogenic causes were rather high in this series; moreover, 50% of the patients with iatrogenic causes of endocarditis had a recent dental procedure in the history. This emphasizes the importance of antibiotic prophylaxis in all patients with a prosthetic cardiac implant or a structural defect of a native heart valve. Interestingly, the guidelines of the European Society of Cardiology regarding this particular topic have been weakened recently [7]. A substantial number of our patients were operated on within 72 hours of presentation, which is rather unusual. This might well have contributed to the mortality rate of 11% and its main cause severe vasoplegia and endorgan failure. The justification for early operation was an ongoing destructive process within the aortic root followed by uncontrollable septic signs despite adequate antibiotic therapy. The most recognized surgical approach in active infective endocarditis in a native or prosthetic valve favors complete removal of the infected material followed by debridement and reconstruction of the destroyed tissues with xenopericardium [12]. This represents the prerequisite for successful long-term results. We were successful with this approach in the majority of patients and could avoid implantation of a homograft. In a few situations, replacement with a mini-root homograft remained the only option to reconstruct the left ventricular outflow tract. Unfortunately, if reoperation is required after homograft implantation, it is usually challenging because of the extensive calcification of the neo-root [13]. Almost 20% of patients in our cohort exhibited neurologic injury, or abnormal neurologic imaging results showed a history of cerebral embolization before operation. As could be expected, postoperative persistence or new onset of neurologic deficits was associated with worse outcome and an in-hospital mortality of 80% for this subgroup of patients; in half of these cases, Staphylococcus aureus was the causative organism. Neurologic events as the most frequent complication in patients with infective endocarditis are strongly correlated with a severe prognosis [14 16]. A recent study showed neurologic deficits to be a major determinant of mortality regardless of the underlying clinical symptoms, especially in cases of infection with S aureus, leaving less than one third of patients alive without disabilities [16]. Accordingly, the remaining 2 patients with postoperative onset of stroke in our cohort could be discharged without any neurologic impairment. However from our data we are not able to give a clear recommendation in favor of early or delayed surgical intervention with regard to neurologic complications. Multivariate logistic regression revealed multivalve involvement, preoperative neurologic impairment, and EuroSCORE to be independent predictors for in-hospital death. The fact that multivalve involvement is associated with higher in-hospital mortality as well as lower longterm survival, in particular, is a new finding and may enhance alertness. The attrition rate within the first year after operation was substantial, but long-term survival proved favorable, and freedom from reinfection was high as was freedom from reoperation. Multivalve involvement is clearly a surrogate for either a far more advanced local destructive Fig 6. Freedom from reinfection in single-valve endocarditis (SVE) versus multivalve endocarditis (MVE).

7 1210 MESZAROS ET AL Ann Thorac Surg ACTIVE INFECTIVE ENDOCARDITIS OPERATIONS 2012;94: process or any kind of impaired immune response [17]. This is also reflected by the higher rate of reinfection in patients after multivalve involvement. These patients obviously represent a subgroup at a higher risk and may therefore need a more intensive surveillance protocol during follow-up. Limitations and Strengths of This Study This report has all the limitations of a single-center retrospective analysis, and it is certainly true that the time point of surgery was preset by clinical and echocardiographic assessment. The strength of this study is that we reported a series of consecutive patients and did not exclude subgroups at risk, such as those with prosthetic valve endocarditis or multivalve involvement. As such this report gives a clear picture of the long-term results in highly challenging patients and their fairly good outcomes. In summary, despite high in-hospital mortality and an adverse outcome during the first year after surgical intervention, such intervention for active infective endocarditis provides excellent results with regard to freedom from reinfection and freedom from reoperation. A strategy of extensive reconstruction of the cardiac structures affected or destroyed by the infective process in combination with valve replacement or repair is highly effective and is followed by favorable long-term outcomes. References 1. Tleyjeh IM, Steckelberg JM, Georgescu G, et al. The association between the timing of valve surgery and 6-months mortality in left-sided infective endocarditis. Heart 2008;94: Gaca JF, Sheng S, Daneshmand MA, et al. Outcomes for endocarditis surgery in North America: a simplified risk scoring system. J Thorac Cardiovasc Surg 2011;141: Revilla A, Lopez J, Vilacosta I, et al. Clinical and prognostic profile of patients with infective endocarditis who need urgent surgery. Eur Heart J 2007;28: Prendergast BD, Tornos P. Surgery for infective endocarditis: who and when? Circulation 2010;121: Aksoy O, Sexton DJ, Wang AP, et al. Early surgery in patients with infective endocarditis: a propensity score analysis. Clin Infect Dis 2007;44: Nashef SA, Roques F, Michel P, Gauducheau E, Lemeshow S, Salamon R. European system for cardiac operative risk evaluation (EuroSCORE). Eur J Cardiothorac Surg 1999; 16: Habib G, Hoen B, Tornos P, et al. Guidelines on the prevention, diagnosis, and treatment of infective endocarditis (new version 2009): the Task Force on the Prevention, Diagnosis, and Treatment of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the International Society of Chemotherapy (ISC) for Infection and Cancer. Eur Heart J 2009;30: Tugtekin SM, Alexiou K, Wilbring M, et al. Native infective endocarditis: which determinants of outcome remain after surgical treatment? Clin Res Cardiol 2006:95: Ota T, Gleason TG, Salizzoni S, Wei LM, Toyoda Y, Bermudez C. Midterm surgical outcomes of noncomplicated active native valve endocarditis: single-center experience. Ann Thorac Surg 2011;91: Gottardi R, Bialy J, Devyatko E, et al. Midterm follow-up of tricuspid valve reconstruction due to active infective endocarditis. Ann Thorac Surg 2007;84: Tribouilloy C, Rusinaru D, Sorel C, et al. Clinical characteristics and outcome of infective endocarditis in adults with bicuspid aortic valves: a multicentre observational study. Heart 2010;96: Czerny M, von Allmen R, Opfermann P, et al. Self-made pericardial tube graft: a new surgical concept for treatment of graft infections after thoracic and abdominal aortic procedures. Ann Thorac Surg 2011;92: Joudinaud TM, Baron F, Raffoul R, et al. Redo aortic root surgery for failure of an aortic homograft is a major technical challenge. Eur J Cardiothorac Surg 2008; 33: Sonneville R, Mourvillier B, Bouadma L, Wolff M. Management of neurological complications of infective endocarditis in ICU patients. Ann Intensive Care 2011; 20: Snygg-Martin U, Gustafsson L, Rosengren L, et al. Cerebrovascular complications in patients with left-sided infective endocarditis are common: a prospective study using magnetic resonance imaging and neurochemical brain damage markers. Clin Infect Dis 2008;47: Sonneville R, Mirabel M, Hajage D, et al. Neurologic complications and outcomes of infective endocarditis in critically ill patients: The ENDOcardite en REAnimation prospective multicenter study. Crit Care Med 2011;39: Sheikh AM, Elhenawy AM, Maganti M, Armstrong S, David TE, Feindel CM. Outcomes of double valve surgery for active infective endocarditis J Thorac Cardiovasc Surg. 2009;138: