**3. Results**

The data collected represented the fields of a database in the Visual Fox Pro program. Data were processed using the Excel, Epi Info, Systat and SPSS programs for measurement of the power association between the prediction and outcome variables using the following tests:

**a.** for qualitative variables CHI square test or Fischer exact test (if expected cell size was less

**b.** for quantitative variables: T test (Student test), ANOVA test or U test depending on the

• For quantitative variables analysis of simple linear and multivariate regression and correla-

No sample size assumptions have been made. No confirmatory statistical hypothesis was prespecified, but a detailed analysis plan was defined before the database was locked. Continuous data are expressed as mean ± SD. Discrete variables are expressed as counts (percentages).

According to the exposure level to the risk factors, data were grouped on the presence of an EE and the type of the treatment (surgical intervention or medical therapy). For each exposure level, there were introduced the number of patients with an EE (cases) and the number of

• a relative risk >1 was considered unfavorable; for these patients, the occurrence of an EE

patients without an EE (controls). The confounders were controlled by stratification.

Data interpretation was performed taking into account the following hypothesis:

was increased due to the presence of the group characteristic by the RR value;

The main methods of statistical correlation used in the study were the following:

samples volumes and Kruskal Wallis nonparametric tests.

• Relative risk calculation and the 95% confidence interval; • Calculation of the positive and negative predictive value.

**Figure 2.** Patient distribution by vegetations site (229 patients).

than 5)

74 Advanced Concepts in Endocarditis

tion coefficient calculation;

1. The incidence of the EE in patients with IE (diagnosed on Duke criteria) was 51.27% (121 patients). There were no significant differences for the occurrence of EE according to sex, age, fever presence, anemia, vegetation site or the presence of a significant regurgitation murmur (**Figure 3**).

2. The univariate analysis has shown a significant correlation between the EE presence and IE with staphylococcus, IE of the right heart, the length and mobility of vegetation. The only independent predictors for the EE revealed by the multivariate regression analysis were: the maximum length > 15 mm (RR = 4.92, p = 0.0001) and the increased mobility of the VEG with the maximal angle > 60.7 degree ± 12 (RR= 8.2, p = 0.003) (**Figure 4**). The univariate regression analysis has shown a significant correlation between the presence of an EE and the following parameters:


The multivariate regression analysis showed that the only echographic independent predictors of the EE were:


The maximum length of the VEG more than 15 mm increased the embolic risk by 4.92 times and its value between 10 mm and 15 mm by 1.84 times. Values less than 10 mm of the maximum length of the VEG turned out to be protective for EE, the associated RR being 0.92.

Values more than 5 mm of the maximum thickness of the VEG have increased the risk of the EE occurrence among our patients by 2.71 times. For thinner VEG, under 5 mm, the risk for EE was significantly reduced. The narrowest diameter (respectively the neck thickness—lneck) less than 3 mm increased the risk for EE by 1.8 times. Regarding the mobility of the VEG, it significantly influenced the frequency of EE occurrence. Thus, the maximal angle of the VEG displacement between 400 and 600 increased by 4.7 times the risk for EE and for its values more than 600, by 8.2 times. The analysis by etiologic agent of IE showed a higher risk of EE in IE with *Staphylococcus aureus* and with Gram-negative bacteria. As other studies also showed, the likelihood of EE occurrence is higher in IE on right heart, the presence of infectious pro-

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3. The differences between the patients with and without EE according to echocardiographic

Thus, the maximum length of the VEG was nearly twice in patients who suffered an EE com-

In addition, the maximum thickness of the VEG measured by TEE was higher with about 3.3 mm in patients in group B. The ratio between the thickness of the VEG neck and the maximum thickness of the VEG was higher in patients without an EE (0.78 in group A respectively 0.42 in group B). In the same way, the VEG mobility (which was estimated by the measurement of the maximal angle of displacement of the vegetation was about three times bigger in patients

4. The rate of the EE occurred after starting the antibiotic treatment was 23.14% (28 patients) and simple linear and multivariate regression analysis found only in two independent predictors. These independent predictors for the occurrence of the EE, once antibiotic treatment has been started were the length of the VEG more than 15 mm and a high mobility of the VEG with maximal angle of displacement of long axis during the cardiac cycle >65 degrees (**Figure 5**). Thus, the maximum length of the VEG more than 15 mm increased the risk for EE occurrence by 7.1 times, the maximum width more than 5 mm increased the EE risk by 3.2 times and a neck/thickness ratio < 0.5 increased the EE risk by 3.5 times. Regarding the VEG mobility, the maximal angle of displacement values between 40 and 60 degrees increased the risk of the EE occurrence by 4.1 times and for its values >650, by 9.2 times. The IE due to a staphylococcal infection was associated with a more frequent EE occurrence, but the VEG localization on the right or left heart do not influence at the same level the EE risk as before the beginning the antibiotic treatment.

pared with patients without an EE (about 12.6 mm and respectively about 6.2 mm).

who suffered an EE (25.1 degrees in group A and respectively 71.8 degrees in group B).

**Echographic parameters Embolic event p value**

Maximum length (mm) 6.2 ± 0.03 12.6 ± 0.04 <0.001 Maximum thickness (mm) 3.9 ± 0.01 7.2 ± 0.02 <0.003 Neck/thickness ratio 0.78 ± 0.2 0.42 ± 0.2 <0.001 Maximal angle of displacement of the vegetation 25.1 ± 10 71.8 ± 14 <0.0001

**Table 1.** Echographic differences between patients with IE who suffered or without EE.

**No Yes**

cess on the tricuspid valve increasing the risk for EE by 3.8 times.

parameters of VEG are shown in **Table 1**.

**Figure 4.** The relative risks for the occurrence of an EE depending on different echo parameters.

Values more than 5 mm of the maximum thickness of the VEG have increased the risk of the EE occurrence among our patients by 2.71 times. For thinner VEG, under 5 mm, the risk for EE was significantly reduced. The narrowest diameter (respectively the neck thickness—lneck) less than 3 mm increased the risk for EE by 1.8 times. Regarding the mobility of the VEG, it significantly influenced the frequency of EE occurrence. Thus, the maximal angle of the VEG displacement between 400 and 600 increased by 4.7 times the risk for EE and for its values more than 600, by 8.2 times. The analysis by etiologic agent of IE showed a higher risk of EE in IE with *Staphylococcus aureus* and with Gram-negative bacteria. As other studies also showed, the likelihood of EE occurrence is higher in IE on right heart, the presence of infectious process on the tricuspid valve increasing the risk for EE by 3.8 times.

3. The differences between the patients with and without EE according to echocardiographic parameters of VEG are shown in **Table 1**.

Thus, the maximum length of the VEG was nearly twice in patients who suffered an EE compared with patients without an EE (about 12.6 mm and respectively about 6.2 mm).

In addition, the maximum thickness of the VEG measured by TEE was higher with about 3.3 mm in patients in group B. The ratio between the thickness of the VEG neck and the maximum thickness of the VEG was higher in patients without an EE (0.78 in group A respectively 0.42 in group B). In the same way, the VEG mobility (which was estimated by the measurement of the maximal angle of displacement of the vegetation was about three times bigger in patients who suffered an EE (25.1 degrees in group A and respectively 71.8 degrees in group B).

4. The rate of the EE occurred after starting the antibiotic treatment was 23.14% (28 patients) and simple linear and multivariate regression analysis found only in two independent predictors. These independent predictors for the occurrence of the EE, once antibiotic treatment has been started were the length of the VEG more than 15 mm and a high mobility of the VEG with maximal angle of displacement of long axis during the cardiac cycle >65 degrees (**Figure 5**). Thus, the maximum length of the VEG more than 15 mm increased the risk for EE occurrence by 7.1 times, the maximum width more than 5 mm increased the EE risk by 3.2 times and a neck/thickness ratio < 0.5 increased the EE risk by 3.5 times. Regarding the VEG mobility, the maximal angle of displacement values between 40 and 60 degrees increased the risk of the EE occurrence by 4.1 times and for its values >650, by 9.2 times. The IE due to a staphylococcal infection was associated with a more frequent EE occurrence, but the VEG localization on the right or left heart do not influence at the same level the EE risk as before the beginning the antibiotic treatment.


**Table 1.** Echographic differences between patients with IE who suffered or without EE.

**Figure 4.** The relative risks for the occurrence of an EE depending on different echo parameters.

**Figure 3.** The occurrence of an embolic event depending on clinical parameters. Mean age: group A—48.7 ± 5 years;

group B—46.9 ± 6 years.

76 Advanced Concepts in Endocarditis

or in patients surviving or dying during acute IE. In addition, no significant correlation was found between VEG size and IE location or type of infective organism. VEG with a maximal diameter of >10 mm were associated with a 50% incidence of EE, compared with a 42% incidence of emboli in patients with VEG measuring less or equal to 10 mm. Inter observer variability was higher with respect to vegetation shape, mobility, and attachment characteristics. Echocardiographic VEG characteristics were not helpful in defining the

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Heinle et al. found that patients with a maximum VEG diameter > 10 mm had a significantly higher incidence of EE than those with < or = 10 mm (p < 0.05). There were no significant differences in the frequency of emergent valve replacement between patients with aortic value and mitral valve IE. The maximum size and total score reflecting mobility, extent and consistency of VEG using two-dimensional echocardiography provide useful information to predict

Another prospective TEE study, however, found no clear correlation of VEG size with embolization, and transthoracic and TEE characteristics of VEG were not helpful in defining embolic

De Castro used multivariate analysis and identified echocardiographic accessible risk factors for subsequent embolism a VEG size of more than 10 mm and mitral valve involvement [8]. Risk factors associated with in-hospital increased mortality rate were embolism, a vegetation size of more than 10 mm, and *Staphylococcus aureus* IE. Also, precise echocardiographic visualization of VEG helps to stratify patients into a high-risk sub-group, needing early prophy-

Overall, these data are compatible with previous observations that in general, mitral VEG, regardless their size, are associated with higher rates of embolization (25%) than aortic VEG (10%) [10]. On the other hand, the highest embolic rate (37%) has been seen in the subset of patients with mitral VEG attached to the anterior rather than the posterior mitral leaflet. In particular, mobile VEG attached to the mitral valve with a maximal diameter > 10 mm may be prone to EE [10]. In a retrospective study, Deprele et al. analyzed the risk factors for systemic emboli in IE [13]. They found that the risk of emboli was 57% when the VEG measured >10 mm and only 22% when it was <10 mm (p = 0.003). The mobility of the VEG was also a risk factor: 48% if the vegetation was mobile; and 9% if fixed (p = 0.003). Sex, age, pathogen, antibiotic treatment, type of valve and the number and position of the VEG were not found to be risk factors. With multivariate analysis, only

The effect of VEG size on embolic potential was specific to the infecting organism, with large VEG independently predicting EE only in the setting of streptococcal IE [13, 17–19]. In contrast, staphylococcal or fungal IE appears to carry a high risk of embolization that is indepen-

The evolution of VEG size revealed by TEE appears to predict EE; however an increase in VEG size revealed by TEE over 4–8 weeks of antibiotic therapy. In patients with IE and increasing VEG size, the EE rate among was twice that of patients with static or decreasing VEG size. In

risk of embolic complications in patients with IE [5].

the occurrence of EE in patients with IE [6].

risk in patients with IE [8].

lactic surgical intervention.

mobility was identified as a risk factor.

dent of the VEG size.

**Figure 5.** Correlation between clinical and echo parameters and the appearance of the embolic events after the antibiotic treatment has been started.
