Hospital Evolution of Patients with Infective Endocarditis in Public Hospital in Belém , Pará , Brazil

The initial event in the development of infective endocarditis (IE) is endothelial injury caused by deposition of immune complexes ─ such as in rheumatic disease ─ or turbulent blood flow ─ as in mitral valve reflux ─ giving rise to nonbacterial thrombotic endocarditis (NBTE)1. The main gateways of microorganisms in the bloodstream are oral cavity, skin and upper airways. During simple procedures, such as dental treatment, transient bacteremia may occur, during which the microorganisms settle on preexisting clots, generating an infected vegetation, which may lead to the destruction of the involved structure, as well as other surgeries in general2-6. Internacional Journal of Cardiovascular Sciences. 2015;28(6):496-503


Introduction
The initial event in the development of infective endocarditis (IE) is endothelial injury caused by deposition of immune complexes ─ such as in rheumatic disease ─ or turbulent blood flow ─ as in mitral valve reflux ─ giving rise to nonbacterial thrombotic endocarditis (NBTE) 1 .
The main gateways of microorganisms in the bloodstream are oral cavity, skin and upper airways.During simple procedures, such as dental treatment, transient bacteremia may occur, during which the microorganisms settle on preexisting clots, generating an infected vegetation, which may lead to the destruction of the involved structure, as well as other surgeries in general [2][3][4][5][6] .
Diagnosis of IE is based on the modified Duke criteria and imaging methods in the recognition of valvular vegetations which, combined with clinical and bacteriological data, enable a more precise diagnosis 1,7 .Echocardiography currently stands out as an essential diagnostic tool, and it identifies complications, provides prognostic information and assists in the proper m a n a g e m e n t o f p a t i e n t s 8 , 9 .T r a n s t h o r a c i c echocardiography (TTE) has a lower cost and greater availability in hospitals, while transesophageal echocardiography (TEE) results in higher accuracy 8,10 .
The choice of echocardiographic modality must consider the clinical pre-test probability of the disease.The employment of TTE is considered appropriate when this probability is between 2-3%, while TEE must be used when the probability is between 4-60% 8, 10,11 .
The evolution of echocardiography, with the possibility of transesophageal tests, allowed viewing changes that were not possible with TTE and even less with the first echocardiography devices.The type of treatment and its time have also changed 12 .
New imaging techniques in cardiology, including magnetic resonance imaging and computed tomography scans have been used in the evaluation of this disease, with promising results 8 .
Advances in laboratory tests allowed faster and more accurate detection of the etiological agents causing the problem and more effective mitigation of these agents 12 .When available for heart surgery or autopsy, pathology tests of the vegetation is the gold standard for diagnosing endocarditis and can suggest its etiology 8 .IE presents high morbidity and mortality with mortality rates of 20-30%, rising up to over 50% in high-risk groups.The prognosis correlates with rapid diagnosis and proper therapy 4,10,13,14 .
Complications may occur by destruction of structures at the site of infection, embolic events, metastatic lesions and immune-mediated infections 2 .
The emergence of congestive heart failure (CHF) secondary to embolization adversely impacts the prognosis of the disease.Other complications include perivalvular and myocardial abscesses 2 .
The time course of disease knowledge enabled advances in diagnostic techniques, especially in echocardiography.In addition, there was a greater possibility of performing heart surgery, even with the infectious process in activity, and new prophylaxis recommendations for antibiotics before intervention procedures 15 .
As for treatment, with early surgical repair, another presentation of the disease appeared, namely prosthesis endocarditis, which is difficult to diagnose and difficult to establish therapeutic management 12 .
With the emergence of new increasingly effective antibiotics, clinical treatment has enabled the cure of endocarditis with or without associated surgical treatment 12 .
According DATASUS 16 , mortality from IE in Pará has been increasing steadily.Within five years (2009 to 2013), 76 deaths from IE were recorded, with an approximate average of 5 deaths/year, ranging from 10 deaths in 2010 to 20 deaths in 2012, without restriction to sex and age.
The total number of deaths in the state of Pará, in individuals aged 15-80, from 2010-2013, was 92,178; of this number, 54 were from IE 14 .There is no data for the years 2014 and 2015.In Belém, state of Pará, there were 23 deaths from IE, as follows: 5 in 2011, 10 in 2012 and 8 in 2013 16 .
Given the few studies on infective endocarditis in Brazil, especially in the last decade 12 and the progressive increase of mortality from IE, due to systemic complications, despite the advances in diagnostic methods and treatment, this study aims to analyze the hospital evolution of patients affected by IE considering the social and demographic profile and the risk factors involved.

Methods
An observational, descriptive, prospective case series study with analysis of medical records of 18 patients with infective endocarditis from Hospital Gaspar Vianna in Belém, PA, Brazil, from January 2010 to April 2015.The program BioEstat version 5.3 was used for statistical analysis.Adherence chi-squared non-parametric test was applied and significance level of 5% (p<0.05) was adopted as statistically significant difference.

Results
Twenty medical records of patients registered with ICD I33.0 (IE by ICD-10) were found.It was possible to collect data from 18 patients because two died in 2010 and the medical records were found not for analysis in the hospital files.
The most common complications found in patients with IE after diagnosis was valvular impairment (26.5%), followed by congestive heart failure and sepsis, with no significant difference (p=0.598)(Table 1).
Regarding the complications, there was a higher incidence of two complications (in 6 patients; 33.3%) and the highest number of complications was four (in 2 patients; 11.1%) (Table 2).
Regarding the time to diagnosis from the onset of symptoms, median of 14 days in hospital stay, ranging from 6-90 days, was found.From the onset of symptoms to diagnosis, the time observed was the median of 40.5 days with a minimum of 2 and maximum of 210 days.For  3).
blood samples taken.As for imaging, transthoracic echocardiography was requested for all patients, but in none of them transesophageal echocardiography was performed.
In the decision to maintain clinical treatment as the therapy of choice, two major modified Duke criteria were used (Table 4).It was found that among the major criteria, the most observed ones were positive echocardiography with oscillating intracardiac mass on the valve or other support structures, plus valve regurgitation, which did not exist previously.
The most commonly used diagnostic method was the clinical diagnosis (Duke criteria and sociodemographic profile) in all patients studied, as well as all patients had  As for the criteria that defined the decision for surgical treatment in patients with native valve, there was significant difference between them (p=0.0014).A percentage of 33.3% of patients with aortic or mitral regurgitation associated with heart failure (severe impairment) that did not exist previously (Table 4) was reached.
In the choice of surgical treatment for patients with prosthetic valve, valve function was the most frequent criterion (27.8%) (Table 4).
There was no significant difference (p=0.2661) between the established treatments.However, there was a higher proportion of clinical-surgical treatments (Table 5).

Discussion
Incidence of IE in the world remained relatively stable from 1950 to 2000, with 3.6 to 7.0 cases per 100,000 patients/year.In areas with higher concentration of populations at high risk of infection, especially among patients depending on intravenous (IV) drugs, the incidence of IE may reach 11.6/100,000 individuals 18 .
This would represent an expectation of 18-35 cases per year during the period of the study, and in populations at high risk for endocarditis, an "n" of 58 could be estimated for the state of Pará, based on about 2,518.570admissions recorded in the years of the study in DATASUS, which equates to an average of 503,714 hospital admissions/year.
Considering that total admissions in HCGV from January 2010 to December 2014 was 23,038 cases, an average of 4,068 patients/year, one patient/year, that is, 5 patients over five years would be expected.The finding was four times higher than the world estimate (20 patients).
The number found is partially due to the fact that HCGV is a reference in Pará for the treatment of cardiovascular diseases and hemodialysis, thereby increasing the local incidence for infective endocarditis.
The sociodemographic profile observed is consistent with that found in a previous study 18 in which, on a global level, endocarditis affects more men than women, in a ratio of 2:1, but the average age of patients gradually increased, and is currently 57.9 years (interquartile range 43.2-71.8years).The incidence of endocarditis by age increased from 5 cases per 100,000 people/year among individuals <50 years of age to 15-30 cases per 100,000 people/year among individuals from the sixth to the eighth decade of life 18 .
A study carried out in Chile 19 identified the average age of patients of 49.9 years of age and higher prevalence of males.A number of cases followed between 2006 and 2011 at a public hospital in Rio de Janeiro had an average age of 47.2 19,20 .In another study, the predominant age range was 40.0-53.5,mostly males, at a ratio of 2.5:1 21 .
The level of education of patients differs from a crosssectional study that deals with the dental health conditions presented by adults with heart disease with IE, in preparation for cardiac surgery, which showed a The most prevalent outcome was death (50.0%) followed by 33.3% of patients with improved discharge and 16.7% that dropped treatment with no medical initiative (Table 6).
higher prevalence of patients with incomplete primary education (48.6%).In the same study, the most frequent household income was up to two minimum wages, which corresponds to the finding of two to four minimum wages 22 .
In a case series 21 studying risk factors, the authors found 9.0% of patients with dental infection, 3.0% with history of hemodialysis, 3.0% with diabetes mellitus m and 6.0% with history of alcoholism.
The risk factors for developing IE occur more frequently in individuals with pre-existing heart diseases, with greater predisposition of involvement of the native valve 1,23 .However, the involvement of mechanical prostheses presents greater risk in the first three months, equating to the risk of the native valve after five years of evolution.The presence of intracardiac devices such as pacemakers and implantable defibrillators can serve as support for thrombi and vegetations 1,24 .
However, the risk factors in developed countries have shifted from rheumatic disease (most often in the mitral valve by aortic valve) and congenital heart disease to the use of intravenous medication, degenerative valve disease in the elderly, intracardiac devices, infections originated in health services and hemodialysis 1,18,25 .
The finding of the most affected heart valve was consistent with the findings of another study that found higher prevalence of mitral and aortic valves 26 .Infections of the tricuspid and/or pulmonary valve occur more in intravenous drug users and as a complication related to deep vascular catheter infection.The pulmonary valve is rarely affected 26 .
Valvular impairment was the most frequent complication (Table 1).Comparative studies showed embolisms and CHF as the main complications of IE 20 .
Although the time between the onset of symptoms and diagnosis has ranged between 2 and 210 days, the average length of hospital stay was lower than that found by Franco et al. 21, who found an average of 67 days with a minimum of 4 and maximum of 224 days (Table 3).
In the diagnosis by the Duke criteria, blood culture and TTE were auxiliary methods in the diagnosis, the latter being decisive for the diagnosis, perhaps because echocardiogram is the cornerstone diagnosis in infective endocarditis, with specificity value higher than 95% and sensitivity close to 70% 19 .
The presence of two major Duke criteria or one major and three minor criteria were used, and among the major criteria, the most prevalent one was positive echocardiography with oscillating intracardiac mass on the valve or other support structures, in addition to valve regurgitation that did not exist previously.
For the decision of medical and surgical treatment of patients with native valve IE, two criteria were used: severe valvular impairment and vegetation greater than 10 mm.For those with prosthetic valve, the most frequent criterion was valvular impairment (Table 4).This result is corroborated by some studies in which patients with echocardiographic characteristics of high risk underwent early surgery, specifically those patients with vegetation bigger than 10 mm 2,27-29 .
In a little more than half of the patients, the criteria for choosing surgical treatment were not described in the medical records.It is assumed that the absence of such information in the medical record is due to the hospital's medical-surgical practice that takes the failure of antibiotic therapy as a criterion.
The most prevalent treatment was clinical-surgical therapy followed up by clinical therapy (Table 5).This finding is consistent with the cases series held in Rio de Janeiro, which showed 64.0% of patients undergoing surgical treatment 29 and another study done in Chile, with 37.7% 19 .
Three patients dropped the treatment, one of whom dropped it before transthoracic echocardiogram, which was detrimental to the patient' inclusion following the Duke criterion, so the patient's diagnosis was based on clinical and demographic characteristics.
The most frequent outcome of the patients studied was death (Table 6), a rate much higher than that observed in the Chilean study of 33 cases of IE, which found 6.0% of mortality 21 and another study with 151 cases of IE, in a hospital in Rio de Janeiro, which found 32.0% of deaths 20 .
The finding of 50.0%mortality is probably related to the number of risk factors presented by the patients.It was observed that patients who evolved to death also had two or more complications.
Gaps found in the medical records, particularly with respect to risk factors and clinical and demographic profile generated some difficulty in the execution of this study, in addition to social damage, since the availability

Table 1 Complications experienced by patients after diagnosis of infective endocarditis
17is study was approved by the Research Ethics Committee of the institution under nº 1.030.404/2015according to the CNS Resolution 466/12.Because it is a retrospective study, Informed Consent Form was not required.The inclusion criteria were: patients who were part of the hospital's spontaneous demand, with infective endocarditis, of both sexes, aged ≥18 and ≤90 or with reported IE, with positive blood culture tests, echocardiogram and/or histopathology tests conducted in HCGV, as well as those with a diagnosis established by the modified Duke criteria17.Patients with incomplete medical records and those who were no longer in the hospital files were excluded.
* p=0.598 (chi-square test)The following sociodemographic variables were collected from the medical records: age, sex, education, average monthly household income and origin.Risk factors: mitral valve prolapse, rheumatic disease, complex congenital heart disease, use of intravenous drugs, septal hypertrophy, previous dental procedure, hemodialysis, diabetes mellitus, HIV infection, mechanical valve prosthesis or bioprosthetic valve, type of pathogens (determined through blood test results or histopathology test results), affected cardiac valves, medical complications after IE, diagnostic method used and the type of treatment performed (clinical and clinical-surgical).

Table 6 Outcome of patients with infective endocarditis
p=0.0002 (chi-square test)