Mauricio de Nassau MachadoI,II; Marcelo Arruda NakazoneI,II,III; Jamil Ali Murad-JúniorI; Lilia Nigro MaiaIV
CG: Control group
CI: Confidence interval
CVS: Cardiac valve surgery
SG: Study group
EuroSCORE: European System for Cardiac Operative Risk Evaluation
HR: Hazard ratio
ICU: Intensive care unit
IE: Infective endocarditis
SD: Standard deviation
Surgical mortality for infective endocarditis (IE), while declining in the last decades, stands out as an important cause of death in native or prosthetic valve interventions [1-3], justifying early diagnosis and appropriate antibiotic therapy as key points to the success of the treatment .
Clinical complications and treatment failure may suggest surgical valve replacement for IE by up to 60% of cases [5-7]. However, due to possible association between increased incidence of postoperative complications and mortality, the real benefit of early surgical intervention on IE remains doubtful .
In the absence of adequate treatment, IE can be fatal. Despite the medical and surgical treatment being able to modify the course of disease, mortality remains high, ranging from 17% to 36% of cases according to the population studied [9,10]. In this context, this study evaluated the mortality of patients undergoing cardiac valve surgery (CVS) in the presence of IE in an attempt to identify independent predictors of 30-day mortality in a regional referral center.
This study evaluated 837 patients admitted to the São José do Rio Preto Medical School Cardiac Surgery Postoperative Intensive Care Unit after CVS from January 2003 to May 2010. This Brazilian Hospital is a regional tertiary referral service with 540 beds for a population demand of 1.5 million inhabitants. In this research, patients were divided into two groups: (SG) study group, subjects undergoing CVS in the presence of IE; and (CG) control group, consisting of patients with CVS performed in the absence of IE. The analysis was conducted as a prospectively historical type, including gathering information on the local computer database. The constitution of SG considered the recent recommendations of the American College of Cardiology / American Heart Association for IE surgical approach . This study was approved by the São José do Rio Preto Medical School Ethics Committee (6079/2010) and, because of its observational nature, the informed consent was waived.
We evaluated demographic data, clinical outcomes and complications occurred in the postoperative period, and 30-day all cause mortality. Categorical data are presented as absolute numbers and percentages, and continuous variables as mean ± standard deviation (SD) or median and interquartile, when applicable. Categorical data were compared by chi-square test or Fisher's exact test and continuous variables were compared using the nonparametric Mann-Whitney test. Survival curve was constructed to demonstrate the outcome of 30-day mortality for both groups. The Cox regression analysis was used to determine independent predictors of 30-day mortality. Hazard ratio (HR) and 95% confidence intervals (95% CI) were calculated for predictors of mortality. The analysis was performed with the SPSS software (version 20) and P value < 0.05 (two-tailed) was considered statistically significant.
In our series, 64 (8%) patients underwent CVS in the presence of IE, and 37.5% had surgical intervention in multiple valves. In the SG there was predominance of males (67%) lower body mass index (23kg/m2), greater value for European System for Cardiac Operative Risk Evaluation (EuroSCORE) (9 points), and greater cardiopulmonary bypass time (100.5 min) compared to CG (47%, P = 0.002, 24 kg/m2, P = 0.028, 90 min, P = 0.020 and 4 points, P <0.001, respectively). Table 1 shows the demographic and baseline characteristics of all groups.
The analysis of clinical outcomes demonstrated that the EG had a higher percentage of subjects with prior cardiac valve surgery (47%), higher prolonged intensive care unit (ICU) length of stay (over 14 days) (16%) and need for dialysis (9%) compared to CG (28%, P = 0.001; 7%, P = 0.020 and 2%, P = 0.002, respectively, Table 2). Consequently, patient sunder going CVS in the presence of IE had higher 30-day mortality (17%) compared to those without active infection (9%, P = 0.038).
The following variables were included in the univariate Cox analysis: age (years), male gender, body mass index (kg/m2), readmission to intensive care, diabetes mellitus, CVS in the presence of IE, multiple valve surgery, acute kidney injury, dialysis, left ventricular systolic dysfunction moderate or severe, redo surgery, reoperation for bleeding, tracheal reintubation and type I neurological injury. Table 3 shows the variables associated with 30day mortality, highlighting age (P = 0.007), acute kidney injury (P = 0.004), dialysis (P = 0.026), redo surgery (P = 0.026), reoperation for bleeding (P = 0.013), tracheal reintubation (P <0.001) and type I neurological injury (P <0.001) as independent predictors of death determined by multivariate Cox regression model. Cardiac valve surgery in the presence of infective endocarditis was a predictor of death in the non adjusted analysis (HR = 1.96, 95% CI = 1.04 - 3.70, P = 0.038, Figure 1). However, after adjustment for predictors in the multivariate model, this variable was not independent (P = 0.06).
Despite the current knowledge including prevention, diagnosis and treatment, IE remains a not rare cause of hospitalization with high morbidity and mortality [12,13]. In our analysis, we found 8% of valve-related surgery approaching to IE, percentage similar to that observed in national, North American and European casuistic [14-16]. Moreover, we confirmed high 30-day mortality (17%) for patients undergoing CVS in the presence of active infection, as recently reported by Prendergast & Tornos (ranging from 6% to 25%) . However, the surgical approach in the presence of IE wasn't confirmed as an independent predictor of death in our series.
Our series of patients considered subjects with high severity disease transferred from other hospitals for surgery treatment with established diagnosis of IE, justified by the infection refractory to medical treatment. In this context, factors such as age, comorbidities, clinical presentation and surgical technique used in valve approach can influence the postoperative results [18,19]. Although there is no statistical difference between the groups in age, this variable was found as an independent predictor of 30-day mortality in patients with IE, reinforcing results of Murdoch et al. . Furthermore, in contrast to data of Chirillo et al. , the prevalence diabetes mellitus was similar between the groups do not representing a risk factor for poor clinical outcome in patients with active IE undergoing CVS. Although evidenced greater proportion of male gender and lower body mass index in EG, these parameters were not associated with worse postoperative prognosis. The higher cardiopulmonary bypass duration in this group may reflect the greater surgical difficulty for a complete removal of the cardiac valve in patients with IE .
The International Collaboration on Endocarditis-Prospective Cohort Study  reported 17.7% of overall in-hospital mortality for patients with IE, while Wallace et al.  reported 15% mortality in the group undergoing medical treatment and 22% for those who underwent additional surgery. Still, the hospital mortality in patients with valvular abscess due to complications of IE has been reported as 19.2% in Brazilian patients . Similarly, the present study found a hospital mortality rate of 17% at 30 days for patients undergoing CVS due to IE and prolonged ICU length of stay, probably reflecting the severity of sepsis in these individuals [24-26]. However, the anatomical location of the valve infection was similar among the groups, confirming the absence of its association with clinical complications, including mortality, reflecting results previously presented by Rostagno et al. .
In this context, the presence of signs of heart failure, persistent infection, acute kidney injury, thrombocytopenia, paravalvular abscess at echocardiography and need for urgent surgery are indicated as predictors of hospital mortality [27-29]. Several studies have associated renal dysfunction with worse prognosis in the evolution and treatment of IE, reporting sepsis, lesions in glomerular architecture and antibiotic toxicity as etiologic factors [22,30,31]. Results of this analysis confirmed the acute kidney injury requiring dialysis as independent predictors of hospital mortality.
This study demonstrated that reoperation, including re-exploration due to postoperative bleeding, was also a predictor of 30-day mortality. Attempting to decrease perioperative mortality for valve replacement surgery in the presence of IE, Musci et al.  recently proposed valvuloplasty as an effective alternative in previously selected cases, with consequent reduction in the need for reoperation and recurrent infections, but this surgical modality was not evaluated in this analysis. Besides these factors, the type I neurological injury and tracheal reintubation stood out as predictors of mortality in patients undergoing CVS in the presence of IE, in agreement with previous studies [33,34]. In this case, the manifestation of encephalopathy due to cardiovascular surgical procedure or severe sepsis, characterized by altered mental status or focal neurological deficit without evidence of impairment in anatomical imaging methods may have contributed definitely to returning to invasive mechanical ventilation and consequent high risk of in-hospital deaths.
Studies related to IE approach are limited by its low relative frequency, the huge variability of the population affected and their underlying risk factors, represented mostly by series of case reports or single centers experience. In our sample, due to the small number of valve involvement by IE, there was limitation in demonstrating the relationship between prognosis, native or prosthetic valve involvement and etiologic agent identified in blood cultures, a fact worsen by the wide range of pathogens involved in its manifestation, affecting the scope and statistical power to draw definitive conclusions. Further investigations are needed to evaluate whether more sensitive prognostic markers may improve the detection of high-risk patients for whom aggressive surgical valve treatment during an IE can really contribute to the reduction of in-hospital mortality.
Although hospital mortality rate for patients undergoing cardiac valve surgery due to refractory infective endocarditis remains high in the Brazilian population, the surgical approach during an active infection is not confirmed as an independent predictor of death in our series.
In this case, age, acute kidney injury, dialysis, redo surgery, re-exploration for bleeding, tracheal reintubation and type I neurological injury stand out as predictors of in-hospital mortality (30 days) in this population.
1. Kuyvenhoven JP, van Rijk-Zwikker GL, Hermans J, Thompson J, Huysmans HA. Prosthetic valve endocarditis: analysis of risk factors for mortality. Eur J Cardiothorac Surg. 1994;8(8):420-4. [MedLine]
2. Wang A, Athan E, Pappas PA, Fowler VG Jr, Olaison L, Paré C, et al. Contemporary clinical profile and out come of prosthetic valve endocarditis. JAMA.2007;297(12):1354-61. [MedLine]
3. Shimokawa T, Kasegawa H, Matsuyama S, Seki H, Manabe S, Fukui T, et al. Long-term outcome of mitral valve repair for infective endocarditis.AnnThorac Surg. 2009;88(3):733-9.
4. Mylonakis E, Calderwood SB. Infective endocarditis in adults. N Engl J Med. 2001;345(18):1318-30. [MedLine]
5. Hoen B, Alla F, Selton-Suty C, Béguinot I, Bouvet A, Briançon S, et al. Changing profile of infective endocarditis: results of a 1-year survey in France. JAMA. 2002;288(1):75-81. [MedLine]
6. Tornos P, Iung B, Permanyer-Miralda G, Baron G, Delahaye F, Gohlke-Bärwolf Ch, et al. Infective endocarditis in Europe: lessonsfromtheEuroheartsurvey. Heart.2005;91(5):571-5. [MedLine]
7. Gutierrez-Martin MA, Galvez-Aceval J, Araji OA. Indications for surgery and operative techniques in infective endocarditis in the present day. Infect Disord Drug Targets. 2010;10(1):32-46. [MedLine]
8. Feringa HH, Bax JJ, Klein P, Klautz RJ, Braun J, van der Wall EE, et al. Outcome after mitral valve repair for acute and healed infective endocarditis. Eur J Cardiothorac Surg. 2006;29(3):367-73. [MedLine]
9. Bishara J, Leibovici L, Gartman-Israel D, Sagie A, Kazakov A, Miroshnik E, et al. Long-term outcome of infective endocarditis: the impact of early surgical intervention. Clin Infec Dis. 2001;33(10):1636-43.
10. Lalani T, Cabell CH, Benjamin DK, Lasca O, Naber C, Fowler VG Jr, et al; International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) Investigators. Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis: use of propensity score and instrumental variable methods to adjust for treatment-selection bias. Circulation. 2010;121(8):1005-13. [MedLine]
11. Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr, Faxon DP, Freed MD, et al. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients with Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2008;118(15):e523-661. [MedLine]
12. Baddour LM, Wilson WR, Bayer AS, Fowler VG Jr, Bolger AF, Levison ME, et al; Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease; Council on Cardiovascular Disease in the Young; Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia; American Heart Association; Infectious Diseases Society of America. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005;111(23):e394-434. [MedLine]
13. Rostagno C, Rosso G, Puggelli F, Gelsomino S, Braconi L, Montesi GF, et al. Active infective endocarditis: Clinical characteristics and factors related to hospital mortality. Cardiol J. 2010;17(6):566-73. [MedLine]
14. Ribeiro GS, Tartof SY, Oliveira DW, Guedes AC, Reis MG, Riley LW, et al. Surgery for valvular heart disease: a population-based study in a Brazilian urban center. PLoS One. 2012;7(5):e37855. [MedLine]
15. Daneshmand MA, Milano CA, Rankin JS, Honeycutt EF, Shaw LK, Davis RD, et al. Influence of patient age on procedural selection in mitral valve surgery. Ann Thorac Surg. 2010;90(5):1479-85.
16. Holzhey DM, Shi W, Borger MA, Seeburger J, Garbade J, Pfannmüller B, et al. Minimally invasive versus sternotomy approach for mitral valve surgery in patients greater than 70 years old: a propensity-matched comparison. Ann Thorac Surg. 2011;91(2):401-5. [MedLine]
17. Prendergast BD, Tornos P. Surgery for infective endocarditis: who and when? Circulation. 2010;121(9):1141-52. [MedLine]
18. Nunes MC, Gelape CL, Ferrari TC. Profile of infective endocarditis at a tertiary care center in Brazil during a seven-year period: prognostic factors and in-hospital outcome. Int J Infect Dis.2010;14(5):e394-8. [MedLine]
19. Arnoni AS, Castro Neto J, Arnoni RT, Almeida AFS, Abdulmassih Neto C, Dinkhuysen JJ, et al. Endocardite infecciosa: 12 anos de tratamento cirúrgico. Rev Bras Cir Cardiovasc. 2000;15(4):308-19. Visualizar artigo
20. Murdoch DR, Corey GR, Hoen B, Miró JM, Fowler VG Jr, Bayer AS, et al; International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) Investigators. Clinical presentation, etiology, and outcome of infective endocarditis in the 21st century: the International Collaboration on Endocarditis-Prospective Cohort Study. Arch Intern Med. 2009;169(5):463-73. [MedLine]
21. Chirillo F, Bacchion F, Pedrocco A, Scotton P, De Leo A, Rocco F, et al. Infective endocarditis in patients with diabetes mellitus. J HeartValve Dis.2010;19(3):312-20.
22. Wallace SM, Walton BI, Kharbanda RK, Hardy R, Wilson AP, Swanton RH. Mortality from infective endocarditis: clinical predictors of outcome. Heart. 2002;88(1):53-60. [MedLine]
23. Pomerantzeff PM, Almeida Brandão CM, Albuquerque JM, Oliveira JL Jr, Dias AR, Mansur AJ, et al. Risk factor analysis of hospital mortality in patients with endocarditis with ring abscess. J Card Surg. 2005;20(4):329-31. [MedLine]
24. Gabbieri D, Dohmen PM, Linneweber J, Grubitzsch H, von Heymann C, Neumann K, et al. Early outcome after surgery for active native and prosthetic aortic valve endocarditis. J Heart Valve Dis. 2008;17(5):508-24.
25. Ribeiro DGL, Silva RP, Rodrigues Sobrinho CRM, Andrade PJN, Ribeiro MVV, Mota RMS, et al. Infective valve endocarditis treated by surgery: analysis of 64 cases. Rev Bras Cir Cardiovasc. 2005;20(1):75-80. Visualizar artigo
26. Dias AR, Pomerantzeff PM, Brandão CMA, Dias RR, Grinberg M, Lahoz EV, et al. Surgical treatment of active infectious endocarditis: a study of 361 surgical cases. Rev Bras Cir Cardiovasc. 2003;18(2):172-7. Visualizar artigo
27. Revilla A, López J, Vilacosta I, Villacorta E, Rollán MJ, Echevarría JR, et al. Clinical and prognostic profile of patients with infective endocarditis who need urgent surgery. Eur Heart J. 2007;28(1):65-71. [MedLine]
28. Hanai M, Hashimoto K, Mashiko K, Sasaki T, Sakamoto Y, Shiratori K, et al. Active infective endocarditis: management and risk analysis of hospital death from 24 years'experience. Circ J. 2008;72(12):2062-8. [MedLine]
29. Alonso-Valle H, Fariñas-Alvarez C, García-Palomo JD, Bernal JM, Martín-Durán R, Gutiérrez Díez JF, et al. Clinical course and predictors of death in prosthetic valve endocarditis over a 20-year period. J Thorac Cardiovasc Surg. 2010;139(4):887-93. [MedLine]
30. Netzer RO, Zollinger E, Seiler C, Cerny A. Infective endocarditis: clinical spectrum, presentation and outcome. An analysis of212 cases 1980-1995. Heart. 2000;84(1):25-30. [MedLine]
31. Oakley CM, Hall RJ. Endocarditis: problems: patients being treated for endocarditis and not doing well. Heart. 2001;85(4):470-4. [MedLine]
32. Musci M, Hübler M, Pasic M, Amiri A, Stein J, Siniawski H, et al. Surgery for active infective mitral valve endocarditis: a 20-year, single-center experience. J Heart Valve Dis. 2010;19(2):206-14.
33. Heiro M, Nikoskelainen J, Engblom E, Kotilainen E, Marttila R, Kotilainen P. Neurologic manifestations of infective endocarditis: a 17-year experience in a teaching hospital in Finland. Arch Intern Med. 2000;160(18):2781-7. [MedLine]
34. Tugtekin SM, Alexiou K, Wilbring M, Daubner D, Kappert U, Knaut M, et al. Native infective endocarditis: which determinants of outcome remain after surgical treatment? Clin Res Cardiol.2006;95(2):72-9. [MedLine]
Article receive on domingo, 15 de julho de 2012