SciELO - Scientific Electronic Library Online

 
vol.86 número1Validación externa de ecuaciones de riesgo cardiovascular en el Cono Sur de Latinoamérica: ¿cuál predice mejor?Utilidad de los dispositivos cardíaco-eléctricos con monitoreo a distancia en pacientes pediátricos índice de autoresíndice de materiabúsqueda de artículos
Home Pagelista alfabética de revistas  

Servicios Personalizados

Revista

Articulo

Indicadores

  • No hay articulos citadosCitado por SciELO

Links relacionados

  • No hay articulos similaresSimilares en SciELO

Compartir


Revista argentina de cardiología

versión On-line ISSN 1850-3748

Rev. argent. cardiol. vol.86 no.1 Ciudad Autónoma de Buenos Aires feb. 2018

 

Articulo original

Infective endocarditis in argentina. results of the eira 3 Study

Endocarditis infecciosa en la República Argentina. Resultados del estudio EIRA 3

PATRICIA M. AVELANA1 

MAURO GARCÍA AURELIO1 

SANDRA SWIESZKOWSKI1 

FRANCISCO NACINOVICH1 

LUCÍA KAZELIAN1 

MARIO SPENATO1 

J. HORACIO CASABE1 

SERGIO VARINI1 

HORACIO ZYLBERSZTEJN1 

JUAN A. GAGLIARDI1 

* Universidad de Buenos Aires - Buenos Aires

ABSTRACT:

Background: The clinical and epidemiological characteristics of infective endocarditis (IE), a complex disease with high morbidity and mortality, have changed over time. Our country lacks updated information since the publication of the EIRA 1 and 2 studies (1992 and 2002).

Objective: The aim of this study was to analyze the epidemiology, clinical and microbiological characteristics and hospital outcome of patients with IE.

Methods: A prospective multicenter observational study of patients with definite IE was conducted according to the modified Duke criteria.

results: A total of 502 patients were recruited from 48 centers (69.5% in the Buenos Aires Metropolitan Area). Mean age 60.7±19.3 years and 69.9% (n=351) were men]; 54.64% of patients (n=274) did not present underlying heart disease, 19.9% (n=100) had pros-thetic valves and 38.1% (n=191) had history of a healthcare-related procedure. The diagnosis was made within one month after the first clinical manifestation in 73.3% of cases (n=368) [76.5% (n=384) in the native valve]. The aortic valve was the most commonly affected valve (45.96%; n=230), followed by mitral valve involvement (33%; n=150). The most common germs were Staphylococcus spp in 46.3% of patients (n=232), Streptococcus spp in 28.2% (n=141) and Enterococcus in 12.8% (n=64). Blood cultures were nega-tive in 44 patients (8.76%). Complications: heart failure (30.9%; n=155), peripheral embolism (19.6%; n=98) and abscess (15.5%; n=78). Adequate empirical antibiotic treatment was administered to 62.4% (n=313) of the patients and 43.6% (n=219) underwent surgical treatment. Overall in-hospital mortality was 25.5% (n=128). Age, history of chronic kidney failure, mitral valve disease and heart failure were independent predictors of in-hospital mortality.

Conclusions: A high percentage of patients with IE do not present known prior heart disease. Staphylococcus spp was the most com-mon microorganism. Mortality remains high and similar to the one observed in the EIRA 1 and 2 studies.

Key Words: Infective endocarditis- Epidemiology- Prosthetic cardiac valve- Hospital mortality

RESUMEN:

introducción: La endocarditis infecciosa (EI) es una enfermedad compleja con elevada morbimortalidad, cuyas características clínicas y epidemiológicas han variado. Desde la realización de los Estudios EIRA 1 y 2 (1992 y 2002) no se dispone de información nacional actualizada.

Objetivo: Analizar la epidemiología, características clínicas, microbiológicas y evolución hospitalaria de los pacientes con EI. Material y Métodos: Estudio observacional prospectivo multicéntrico de EI definidas según los criterios de Duke modificados. resultados: En 48 centros, (69.5% Área Metropolitana Buenos Aires), se registraron 502 pacientes; edad 60,7 ± 19,3 años, hombres 69,9% (N=351).

El 54,64% de los pacientes (N= 274) no presentó cardiopatía subyacente.

El 38,1% (N=191) tenía antecedentes de un procedimiento asociado al cuidado de la salud. En el 73,3% (N=368) se realizó el diagnóstico dentro del mes de la primera manifestación clínica. La localización más frecuente fue la aórtica, tanto en EI por válvulas nativas como protésicas (48,24%/N=233) seguida de mitral (25,88%/N=125). Los gérmenes más frecuentes fueron: Staphylococcus spp 46,3% (N=210), Streptococcus spp 28,2% (N=128) y Enterococcus spp 12,8% (N=58). En 9,56% (N=48) de los casos los hemocul-tivos fueron negativos. Complicaciones: insuficiencia cardíaca (30,9%/N=155), embolias periféricas (19,6%/N=98) y absceso (15,5%/ N=78). El 62,4% (N= 313) recibió tratamiento antibiótico empírico adecuado y el 43,4% tratamiento quirúrgico (N= 218). Mortalidad hospitalaria global: 25,5% (N=128). La edad, el antecedente de insuficiencia renal, la afección de la válvula mitral y la presencia de insuficiencia cardíaca fueron predictores de mortalidad hospitalaria.

Conclusiones: Existe un elevado porcentaje de pacientes con EI sin enfermedad cardíaca previa conocida. El Staphylococcus spp fue el germen causal más frecuente. La mortalidad se mantiene elevada, y similar a la de los estudios EIRA 1 y 2.

Palabras clave: Endocarditis; Epidemiología; Válvulas protésicas cardiacas; Mortalidad hospitalaria.

INTRODUCTION

Infective endocarditis (IE) is a complex disorder that has always awakened great interest. (1) Although it is not a very common disease, it causes great impact on those who suffer from it, as more than 50% of the patients with IE experience some kind of severe com-plication in the course of the disease. Despite a bet-ter knowledge of the pathophysiology of the disease, the availability of more precise diagnostic tools, and more efficient antibiotics (ATB), the mortality of IE has not changed significantly over the past 40 years. Overall in-hospital mortality rate is 11-25% (and can be higher depending on the microorganism involved) and 30-40% at one year. (2, 3) In our country, mortal-ity is still high, between 23.5% [EIRA (Endocarditis Infecciosa en la República Argentina) in 1993] (4) and 24.3% (EIRA 2 in 2002). (5)

The clinical characteristics and the epidemiology of IE have evolved over the past 50 years. (6,7) The factors contributing to these changes include the use of intravenous drugs, cardiovascular surgery, different types of heart valve prostheses and permanent cath-eters which may produce healthcare-associated IE.

There is limited information about the character-istics of IE in developing countries. The EIRA study was the first nationwide multicenter study analyzing the epidemiological profile of IE in our region. The study described the clinical characteristics, therapeu-tic management, and morbidity and mortality of the disease in Argentina in the early nineties. (4)

Thereafter, a new survey was conducted in 2002 (EIRA 2) (5) comparing the characteristics of IE and the changes that had occurred during the 10-year pe-riod between both studies, showing important differ-ences as those observed in developed countries.

Our country lacks updated information since the publication of the EIRA 2 study. For this reason, and due to the high mortality rate and the changing profile of the disease, it is important to know its current status in a heterogeneous region as Argentina. The Coun-cil on Clinical Cardiology and Therapeutics “Tiburcio Padilla” and the Research Area of the Argentine Soci-ety of Cardiology decided to conduct a new registry of all the patients admitted with diagnosis of definite IE to public or private medical centers nationwide with working groups consisting of cardiologists and infec-tologists. The aim of this registry was: 1) to analyze the predisposing factors, clinical characteristics, diag-nostic methods used, therapeutic approach and hospital outcome of the patients, and 2) to determine the predictors of morbidity and mortality.

TTE Transthoracic echocardiography TEE Transesophageal echocardiography

METHODS

Selected prediction equations

A multicenter and prospective registry was designed for a cohort of patients with definite IE. Each center selected one cardiologist and one infectologist/bacteriologist as responsi-ble of conducting the registry.

Eligible patients >18 years admitted with clinical diagnosis of definite IE according to the modified Duke criteria (8, 9) were enrolled in the study (Appendix 1).

Patients with confirmed or potential alternative diagnosis, possible IE and those without specific treatment for IE during initial hospitalization were excluded from the study.

Data were collected through the web using a specially de-signed electronic worksheet. Data on clinical history, predis-posing factors, physical examination, complementary tests, microbiological tests and treatments were collected, as well as the information about procedures during hospitalization, hospital outcome and complications.

defnition of main events:

- Persistent fever: Persistent of intermittent fever ≥38 ºC after 1 (one) week of appropriate ATB treatment.

- Complications: Heart failure (HF), heart valve regur-gitation, bleeding, embolism (location), cardiogenic or septic shock, systolic blood pressure ≤90 mmHg in the presence of adequate preload and in the absence of ino-tropic support; or systolic blood pressure ≤80 mmHg in the presence of adequate preload and inotropic support.

- Other complications: Acute myocardial infarction (pres-ence of at least two of the following criteria: chest pain lasting 30 minutes or more, development of pathologi-cal Q waves - duration >0.4 sec or depth >1/3 R wave - or ST-segment elevation >1 mm lasting more than 30 minutes, and total CK or CK-MB values exceeding twice the upper reference limit), conduction disturbances and renal failure.

- All-cause mortality: In-hospital mortality due to cardiovascular and non-cardiovascular causes.

Statistical analysis

Qualitative variables are presented as frequency tables and percentages. Quantitative variables are expressed as mean ± standard deviation (SD), or median and interquartile range (IQR 25-75), according to their distribution,

Discrete variables were analyzed using contingency tables and for continuous variables, Student’s t test, the Kruskall-Wallis test for unmatched groups, or the analysis of variance (ANOVA) were used, as applicable. The strength of the association between the variables was expressed as odds ratio (OR) with its corresponding 95% confidence in-terval (95% CI). The association of mortality (the dependent variable) with the independent variables (age, H F, sepsis, use of inotropic agents, among others) was analyzed using a univariate logistic regression model. Significant associations were studied using multivariate logistic regression analysis to estimate the probability of the association independently of other factors. A p value <0.05 was considered statistically significant. All the calculations were performed using Epi-Info 7.2 and Stata/SE v13.0™ software package.

ethical considerations

The study was approved by the Argentine Society of Cardiol-ogy Ethics Committee.

RESULTS

General characteristics

From September 2013 to March 2016, 502 patients from 48 centers of 13 Argentine provinces were in-cluded in the study (65.9% were from the Buenos Aires Metropolitan Area; 82.3% had cardiovascular surgery capabilities, 89.4% were able to perform au-tomated blood cultures and 91.7% had TEE capabili-ties). Infective endocarditis was defined by 2 major criteria in 89.6% of the cases, by 1 major and 3 mi-nor criteria in 4.6% and by histopathology in 5.8%. Mean age was 60.7±19.3 years and 69.9% were men. A history of underlying heart disease was present in 45.36% of the cases (Figure 1). Diabetes (23.5%) and chronic kidney failure (16.5%) were the most common underlying noncardiovascular conditions. Neoplasms were present in 12.1% of the patients, and 21.3% of these patients had metastasis. A predisposing event related to health care was found in 38.1% of the cases; among them, an endovascular procedure (31.9%) was the most common clinical situation associated with IE, followed by dental procedures (12.6%). Previous IE was reported by 8.96% of the patients.

Clinical and laboratory fndings

Diagnosis of IE was made within 1 month after symp-tom onset in 73.3% of cases and after 6 months in 2.4%. Fever was preset in 88.4% of the patients admit-ted and 27.7% had clinical evidence of HF (Table 1). Petechiae were observed in 14.8% of the patients and 7.2% presented at least one immunologic phenom-enon (Janeway lesions in 52.8 % of the cases) Mean erythrocyte sedimentation rate was 70.6±35.1 mm.

echocardiographic fndings and localization

Echocardiography was performed in 99.4% of the cases and 82.3% also underwent TEE. In 80% of the cases the investigators reported that TEE provided additional information and the examination had to be repeated at least once in 35.1% of the cases until evidence of IE was found. The main echocardiographic findings were: visible vegetations, 45.4% of aortic veg-etations presenting with median size 8 (5-13) mm ×5 (3-8) mm and 31.2% of mitral vegetations with median size 10 (6-16) mm × 6 (3-9) mm; 41.7% aortic regurgitation (46.9% severe), 41.7% mitral regurgi-tation (31.6% severe); 19.4% annulus abscess; 14.4% valve perforation and 4.5% periprosthetic dehiscence (31.9% of the episodes on the prosthetic valve). Left ventricular systolic function was preserved in 75.2% of the patients. Table 2 details de distribution of IE localization.

Microbiological characteristics

Causative microorganisms were identified through blood cultures in 91.24% of the episodes, with the fol-lowing distribution: 87.2% were gram positive cocci (Staphylococcus spp 53.0%, Streptococcus spp 32.3.2% and Enterococcus 14.6%), 7.9% gram negative bacili, 0.9% polymicrobial and 2% mycotic (Table 3). Blood cultures were negative in 44 patients (8.76%).

Clinical course

Adequate empirical antibiotic treatment was admin-istered to 62.4% of the patients. The most frequently observed complications are shown in Figure 2. Median hospital stay was 28 days (IQR 25-75: 15-45). During this period, surgery was indicated to 56.9% of the pa-tients and 220 of them (43.6% of the total number of patients) underwent surgery (elective surgery in 67, emergency surgery in 33 and urgency procedure in 120). Surgery was not performed in 61 cases despite it was indicated.

Median time from hospital admission to surgery was 12 (5-21) days and 75 patients (34.1%) were op-erated on before day 7. The most common causes to indicate surgery were: valve regurgitation (138 patients, 49.5%), HF (68 patients, 24.4%), annulus abscess (66 patients, 23.7%), mobile vegetation (56 patients, 23,7%) and embolism (50 patients, 17.9%). Heart failure (54.5%) was the main indication of early surgery (before day 7), followed by valve regurgitation (45.5%). The surgical procedures were: on the aortic valve, and consisted of valve replacement with bio-prosthesis (61 patients) and mechanical prosthesis (56 patients), homograft (9 patients) and aortic valve re-pair (3 patients); on the mitral valve, procedures were

Fig. 1. Distribution of underlying cardiac diseases

22

ARGENTINE JOURNAL OF CARDIOLOGY / VOL 86 N° 1 / FEBRUARY 2018

valve replacement with bioprosthesis (20 patients) and mechanical prosthesis (30 patients), and mitral valve repair (14 patients); tricuspid valve repair (8 pa-tients); and pacermaker or implantable cardioverter defibrillator removal (44 patients). The Ross proce-dure was not performed in any case. Thirteen patients underwent valve surgery combined with coronary ar-tery bypass grafting.

Global mortality was 25.5%. Univariate analysis of mortality is presented in Table 4. Mortality was 27.4% in patients with heart valve disease and 10.5% in those with cardiac device-related IE (p=0.03). Con-versely, mortality was 22.0% in patients undergoing surgery and 59.0% in those with indication of surgery who were not operated on. In patients without indica-tion of surgery mortality was 20.7%.

The independent predictors of hospital mortality

Table 2. Location of IE

Native valve

333

68.94

Aortic

153

45.96

Mitra I

110

33.03

Aortic and mitral

28

8.40

Tricuspid

40

12.01

Pulmonary

0.60

Prosthetic valve

103

21.32

Aortic

80

77.68

Mitral

15

14.56

Aortic and mitral

5.82

Tricuspid

Pulmonary

1.94

Table 1. Clinical data at admission

Fever

443

88.4

sepsis

233

46.5

severe sepsis

80

16.0

Septic shock

56

11.1

Heart failure

139

27.7

Petechiae

74

14.8

immunologic phenomena Osler’s nodes Janeway lesions roth’s spots

36 15 19 9

7.2 41.7 52.8 25.0

Embolism

154

30.7

Spleen enlargement

54

10.8

New murmur

160

31.9

Worsening murmur

65

13.0

Conduction disturbances

45

9.0

Arrhythmias

52

10.4

were: age > 65 years, history of chronic kidney fail-ure, mitral valve compromise and HF on admission or during hospitalization (Table 5).

DISCUSSION

The EIRA 3 study represents the largest series of co-hort studies of patients with definite IE in our country and Latin America.

Unlike other cardiovascular diseases, IE is a condi-tion with low incidence that still has elevated mortal-ity and severe complications despite improvements in diagnosis and treatment.

For this reason, it is important to carry out regis-tries and to know the information of our country, as the situation of the disease under study may emerge from these registries. Effectively, this registry demon-strates that the high-risk profile of the patients and the frequency of the most pathogenic microorganisms as Staphylococcus aureus are increasing, and could be the reason of the high mortality observed. (3, 6)

The registry also shows that the age of the popula-

Streptococcus spp

- Viridans

- Bovis

- Others

Enterococcus spp

Staphylococcus spp

S. Aureus Coagulase-negative

HACEK

Other Gram-negative

Polymicrobial

Mycotic

Others

Global (n=454) n (%)

128 (28.2) 82 (64.1) 26 (20.3) 20 (15.6)

58 (12.8)

210 (46.3)

148 (70.5) 56 (26.7)

9 (2.0)

27 (5.9)

4 (0.9)

9 (2.0)

9 (2.0)

Native valve IE

(n=310)

N (%)

97 (31.3) 60 (61.9) 22 (22.7) 15 (15.5)

37 (11.9)

145 (46.8)

119 (82.1) 22 (15.2)

5 (16)

14 (4.5)

4 (1.3)

5 (16)

3 (1.0)

Prosthetic valve IE (n=94) N (%)

21 (22.3) 14 (66.7)

3 (14.3)

4 (19.0)

18 (19.1)

37 (39.4)

14 (37.8) 23 (62.2)

4 (4.3)

7 (7.4)

2 (2.1)

5 (5.3)

Table 3. Microbiology

inFectiVe enDOcArDitis in ArgentinA: eirA 3 / patricia M. Avellana et al.

23

Fig. 2. Incidence of complications during hospitalization. AMI: Acute myocardial infarction. Echo: Echocar-diogram. ATB: Antibiotic. HF: Heart failure. CNS: Central nervous system).

AM i

Abscess

perforation

Fistula by echo

periprosthetic leak

Fever despite adequate AtB treatment

new-onset HF

Worsening HF

conduction disturbances

Arrhythmias

sudden death

Dehiscence/leak

chordal rupture

cns events

peripheral embolism

recurrent embolism during treatment

Mycotic aneurysm

new-onset renal failure

Table 4. Univariate analysis of in-hospital mortality

Variable

Ahve

(n=374)

(74.5%)

n %

Dead

(n=128)

(25.5%)

n %

Male sex

261 72.5

80 62.5

Age

59.8 ± 18.7

65.2 ± 18.5

Age >65

years

165 46.3

75 58.6

0.63

0.41 - 0.97

0.034 0.004

1.64

1.08 - 2.47

0.017

Diabetes

87

24.4

29

23.0

0.92

0.57 - 1.49

0.75

COPD

40

12.0

13

11.1

0.92

0.47 - 1.78

0.79

CKF

48

13.4

32

25.8

2.25

1.36 - 3.73

0.001

Coronary artery disease

68

19.9

18

16.1

0.77

0.43 -1.36

0.36

Prevbus HF

50

14.0

31

26.1

2.16

1.29 - 3.58

0.002

Prevbus IE

31

8.7

12

9.4

1.10

0.55 - 2.21

0.79

Malignancy

39

11.1

22

17.5

1.70

0.96 - 2.99

0.06

previous congenital heart defect

39

10.9

6.3

0.56

0.25 - 1.22

0.14

Prevbus native valve disease

150

46.0

52

50.0

1.17

0.75 - 1.83

0.48

Prevbus device or heart valve replacement

127

35.3

43

33.6

0.93

0.60 - 1.42

00.73

Prevbus hospitalization

199

56.1

78

60.9

1.22

0.81 - 1.85

0.34

previous moderate-to-severe lV dysfunction

34

9.7

19

16.1

1.78

0.97 - 3.26

0.059

Fever on admissbn

322

89.9

111

88.1

0.83

0.44 - 1.57

0.56

HF on admissbn

85

23.6

51

39.8

2.14

1.39 - 3.29

0.0004

Aortic valve disease

195

54.6

71

55.9

1.05

0.70 - 1.58

0.80

Mitral valve disease

108

30.1

56

43.8

1.81

1.19 - 2.74

0.004

Abscess by ecocardiography

68

19.0

29

19.5

1.04

0.62 - 1.73

0.89

positive blood cultures

319

91.7

110

90.9

0.90

0.44 - 1.88

0.79

New-onset HF

46

12.8

48

37.8

4.12

2.56 - 6.62

<0.0001

Worsening HF

29

8.1

28

22.6

3.29

1.87 - 5.80

<0.0001

HF on admissbn or during hospitalization

102

28.3

74

57.8

3.46

2.28 - 5.27

<0.0001

COPD: Chronic obstructive pulmonary disease. CKF: Chronic kidney failure. HF: Heart failure. LV: Left ventricular.

Table 5. Multivariate logistic regres-sion analysis of mortality

tion has increased across the different EIRA studies, from 51.3 years in the EIRA 1 (4) to 58.1 in the EIRA 2 (5) and 60.4 years in the current registry. This trend is consistent with other more recent registries. (3) In ac-cordance with other findings, our registry confirmed male predominance in the incidence of IE with a ra-tio of 2:1. This could be due to the protective effect of circulating estrogens in women of childbearing age. (10) In addition, as women develop cardiovascular dis-ease later than men, the onset of degenerative disease would be delayed over time.

The classic description made by Osler more than a century ago has been left behind, when most of the patients presented rheumatic valve disease as a pre-disposing factor with community-acquired bactere-mia. In this sense, almost half of the patients did not present known structural cardiac disease while one third presented IE as consequence of a medical pro-cedure (healthcare-associated IE), emphasizing the importance of prevention in this new scenario. Degen-erative disease is the most common predisposing factor, whereas the role of rheumatic valve disease in our country is becoming less frequent. (7). There is also an increasing trend in the episodes of prosthetic valve IE compared with the previous registries and in agree-ment with international records (3) (EIRA 1: 8.5% (4), EIRA 2: 19.2% (5), EIRA 3: 20.7%).

In most cases (71.36%), the diagnosis was made within the first month, probably due to the high inci-dence of acute IE with more evident manifestations. In addition, the greater use of TEE could also contribute to the early diagnosis, as this method provided definite information for the diagnosis in 80% of the patients. However, the high clinical suspicion of the disease motivated repeated echocardiograms in 35.1% of the cases until the presence of IE was confirmed.

In Argentina, Staphylococcus aureus is still the most common microorganism involved as in the EIRA 2 study, (5) but the difference with Streptoccocus viri-dans is even more marked in the present study. Prob-ably, this could be due to the high incidence of health care-associated IE and to exposure to invasive proce-dures predisposing to this type of infections caused by microorganisms as Staphylococcus aureus, which, in contrast with Streptococci, do not need the presence of preexistent heart valve disease (11) and infect pa-tients without predisposing structural heart disease.

In the same sense, Enterococcus is the microor-ganism involved in almost 13% of the cases and, as Staphylococcus aureus, is associated with invasive

procedures, nosocomial infections and involvement of weakened older adults or with comorbidities. This sce-nario has also been observed in other series reported. (12)

Blood cultures were negative in 8.6% of the IE episodes, below the values reported in both the ICE-PCS (11.1%) (3) and the EIRA 2 (10.8%) (5) studies but above those reported by Fournier et al. (5%). (13) Despite IE with negative blood cultures could have greater long-term mortality, we have not found differ-ences in the outcome of these patients, in agreement with the publication of Ferrera et al. (13)

During hospitalization, the incidence of complications as H F, persistent sepsis and embolism was high, with a trend toward indication of early surgery in the active stage of the disease. (14-16) More than 40% of the patients underwent surgical treatment. This per-centage is similar to the one observed in other inter-national registries and represents one of the differ-ences with the EIRA 2 study in which only 24% of the patients underwent surgery. (5) However, not all the patients with indication of surgery were operated on, similar to what happens in other parts of the world, and this fact could contribute to greater mortality. (17)

In-hospital mortality is still high, similar to the one observed in the previous registries (23.5%, 24.3% and 25.5% in EIRA 1, EIRA 2 and EIRA 3, respectively; p=0.87) despite better management, and in contrast with other cardiovascular diseases.

Again, as in the EIRA 2 study, the outcome of the disease can be determined at the patient’s bedside. Age and HF are still independent predictors of mor-tality, with the addition of history of chronic kidney failure and mitral valve disease in this study. Early identification of patients with these risk factors may help with early contact or referral of these patients to tertiary centers with multidisciplinary and specialized “endocarditis team” as recommended by the latest EI guidelines. (7, 18-22)

Study limitations

The EIRA studies are observational registries in which the main limitations are the collection bias and the type of centers incorporated to the investigation.

Serological tests that could have clarified those cases with negative blood cultures were not performed.

Although this registry does not pretend to be representative of the complete reality of IE in Argentina, it offers elements of analysis that could help to improve the identification and management of the dis-ease. We believe it is a very important stimulus for all the investigators interested in knowing the reality of this disease in order to improve its management.

CONCLUSIONS

Throughout the decades, patients with IE have high clinical risk and are increasingly older. Staphylococcus aureus is the most common microorganism, followed by Streptococcus viridans. Despite improvements in diagnosis and treatment, mortality is still high and similar to the one observed in previous registries. The identification of independent predictors of in-hospital mortality, as history of chronic kidney failure, mitral valve compromise and the development of HF could help establish strategies to improve the results.

Conficts of interest

None declared. (See authors’ conflicts of interest forms on the website/Supplementary material).

acknowledgments

The authors thank the centers and investigators participa-ting in this study for their invaluable and indispensable par-ticipation and cooperation for the development of this pro-ject, and Mrs. Liliana Capdevila for her valuable and great support as administrative secretary in the present study.

REFERENCES

1. Mylonakis E, Calderwood SB. Infective endocarditis in adults. N Engl J Med 2001;345:1318-30. http://doi.org/dwsk8x

2. Durack D T. Infective endocarditis. Infectious Disease Clinics of North America 2002;16:xv-xix. http://doi.org/bbq4pf

3. Murdoch DR, Corey GR, Hoen B, Miro JM, Fowler VG, Jr., Bay-er AS, et al. Clinical presentation, etiology, and outcome of infec-tive endocarditis in the 21st century: the International Collabora-tion on Endocarditis-Prospective Cohort Study. Arch Intern Med 2009;169:463-73. http://doi.org/b7j98w

4. Casabe JH, Hershson A, Ramos MS, Barisani JL, Pellegrini C, Varini S. Endocarditis infecciosa en la República Argentina. Complicaciones y Mortalidad. Rev Argent Cardiol 1996;64:39-45.

5. Ferreirós E, Nacinovich F, Casabe JH, Modenesi JC, Swieszkowski

5, Cortes C, et al. Epidemiologic, clinical, and microbiologic profile of infective endocarditis in Argentina: a national survey. The Endocarditis Infecciosa en la Republica Argentina-2 (EIRA-2) Study. Am Heart J 2006;151:545-52. http://doi.org/bvbstk

6. Hoen B, Alla F, Selton-Suty C, Beguinot I, Bouvet A, Briancon S,

et al. Changing profile of infective endocarditis: results of a 1-year survey in France. JAMA 2002;288:75-81. http://doi.org/dxcwx9

7. Kazelian LR, Vidal LA, Neme R, Gagliardi JA. [Active infective endocarditis: 152 cases]. Medicina (B Aires) 2012;72:109-14.

8. Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic find-ings. Duke Endocarditis Service. Am J Med 1994;96:200-9. http:// doi.org/d6fqb5

9. Li JS, Sexton DJ, Mick N, Nettles R, Fowler VG, Jr., Ryan T, et al. Proposed modifications to the Duke criteria for the diagnosis of infective endocarditis. Clin Infect Dis 2000;30:633-8. http://doi.org/ fhc6jq

10. Bakir S, Mori T, Durand J, Chen Y F, Thompson JA, Oparil S. Estrogen-induced vasoprotection is estrogen receptor dependent: evidence from the balloon-injured rat carotid artery model. Circula-tion 2000; 101: 2342-4. http://doi.org/chtk

11. Moreillon P, Que YA. Infective endocarditis. Lancet 2004;363:139-49. http://doi.org/dj28fc

12. Chirouze C, Athan E, Alla F, Chu VH, Ralph Corey G, Selton-Suty C, et al. Enterococcal endocarditis in the beginning of the 21st century: analysis from the International Collaboration on Endocar-ditis-Prospective Cohort Study. Clin Microbiol Infect 2013;19:1140-7. http://doi.org/f2ztj7

13. Fournier PE, Thuny F, Richet H, Lepidi H, Casalta J P, Arzouni J P, et al. Comprehensive diagnostic strategy for blood culture-nega-tive endocarditis: a prospective study of 819 new cases. Clin Infect Dis 2010;51:131-40.

14. Ferrera C, Vilacosta I, Fernandez C, Lopez J, Olmos C, Sarria C, et al. Reassessment of blood culture-negative endocarditis: its profile is similar to that of blood culture-positive endocarditis. Rev Esp Car-diol (Engl Ed) 2012;65:891-900. http://doi.org/f2fsf3

15. Kang DH, Kim YJ, Kim SH, Sun BJ, Kim DH, Yun SC, et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med 2012;366:2466-73. http://doi.org/chtm

16. Hoen B, Duval X. Infective endocarditis. N Engl J Med 2013;369:785. http://doi.org/chtn

17. Fernandez-Hidalgo N, Tornos Mas P. Epidemiology of infective endocarditis in Spain in the last 20 years. Rev Esp Cardiol (Engl Ed) 2013;66:728-33. http://doi.org/f2kq8c

18. Cahill TJ, Baddour LM, Habib G, Hoen B, Salaun E, Pettersson GB, et al. Challenges in Infective Endocarditis. J Am Coll Cardiol 2017;69:325-344. http://doi.org/f9pg2b

19. Modenesi JC, Ferreirós ER, Swieskowski S, Nacinovich FM, Cortés C, Cohen Arazi H, et al. Predictores de mortalidad intrahospital-aria de la endocarditis infecciosa en la República Argentina: resultados del EIRA-II. Rev Argent Cardiol 2005;73:283-290.

20. Consenso de Endocarditis Infecciosa. Rev Argent Cardiol 2016;84:2-49.

21. Baddour LM, Wilson WR, Bayer AS, Fowler VG, Tleyjeh IM, Ry-bak MJ et al. Infective endocarditis in adults: diagnosis, antimicrobi-al therapy, and management of complications: A scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132:1435-1486 http://doi.org/chtp

nota

SEC Working Group fpr the ESC 2015 Guidelines on the man-agement of infective Endocarditis. Comment on the ESC 2015 Guidelines for the Management of Infective Endocarditis. Rev Esp Cardiol. 2016;69:7-10. [ Links ]

Creative Commons License This is an open-access article distributed under the terms of the Creative Commons Attribution License