Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://www.cardiologyres.org

Original Article

Volume 7, Number 4, August 2016, pages 130-139

Prediction of Symptomatic Embolism in Filipinos With Infective Endocarditis Using the Embolic Risk French Calculator

Figure 1. Distribution of cardioembolic events. Embolic events were present on admission (prior to initiation of antibiotic therapy) in 17 patients. The primary outcome (i.e. embolic events during/after initiation of antibiotic therapy) occurred in 25 patients.

Figure 2. Causes of death. Mortality occurred in 25 patients (33%) prior to the 28-day observation period.

**Table 1.** Definition of Variables
Variables collected	Definition/description
Presence of minor emboli on admission	Any minor embolic events present on admission, before the initiation of antibiotic therapy, such as Janeway lesions, Roth spots, splinter hemorrhages, petechial hemorrhages, and subconjunctival hemorrhage.
Presence of major emboli on admission	Any major embolic events present on admission, before the initiation of antibiotic therapy, further defined below.
Organism on blood culture	Organism present on at least two sets of blood cultures
Presence of atrial fibrillation	Persistent or transient atrial fibrillation documented on 12-lead electrocardiogram or on a cardiac monitor.
Length of vegetation	Vegetation length measured in various planes and the maximal length was recorded. For multiple vegetations, the largest length was used for analysis. A vegetation length ≥ 10 mm is considered to be a large vegetation.
Area of vegetation	Computed by the longest length multiplied by the widest width of a single vegetation. For multiple vegetations, the individual computed areas were added. An area of ≥ 18 mm² is considered to be a large vegetation.
Ejection fraction	Echocardiographically derived by the Teicholz method. For studies with wall motion abnormalities, the EF derived by Simpson’s method was recorded.
Significant valvular regurgitation	Defined as a “severe” regurgitant lesion (e.g., severe MR, severe TR).
Location of vegetation	Left-sided vegetations pertain to those located on the left side of the heart, including the MV, AV, endocardium of the LA or LV, or aorta. Right-sided vegetations pertain to those located on the right side, including the TV, PV, endocardium of the RA or RV, or the pulmonary artery.
Prosthetic valve vegetation	Includes mechanical or bioprosthetic valves.

Table 1. Definition of Variables

Variables collected

Definition/description

Presence of minor emboli on admission

Any minor embolic events present on admission, before the initiation of antibiotic therapy, such as Janeway lesions, Roth spots, splinter hemorrhages, petechial hemorrhages, and subconjunctival hemorrhage.

Presence of major emboli on admission

Any major embolic events present on admission, before the initiation of antibiotic therapy, further defined below.

Organism on blood culture

Organism present on at least two sets of blood cultures

Presence of atrial fibrillation

Persistent or transient atrial fibrillation documented on 12-lead electrocardiogram or on a cardiac monitor.

Length of vegetation

Vegetation length measured in various planes and the maximal length was recorded. For multiple vegetations, the largest length was used for analysis. A vegetation length ≥ 10 mm is considered to be a large vegetation.

Area of vegetation

Computed by the longest length multiplied by the widest width of a single vegetation. For multiple vegetations, the individual computed areas were added. An area of ≥ 18 mm² is considered to be a large vegetation.

Ejection fraction

Echocardiographically derived by the Teicholz method. For studies with wall motion abnormalities, the EF derived by Simpson’s method was recorded.

Significant valvular regurgitation

Defined as a “severe” regurgitant lesion (e.g., severe MR, severe TR).

Location of vegetation

Left-sided vegetations pertain to those located on the left side of the heart, including the MV, AV, endocardium of the LA or LV, or aorta. Right-sided vegetations pertain to those located on the right side, including the TV, PV, endocardium of the RA or RV, or the pulmonary artery.

Prosthetic valve vegetation

Includes mechanical or bioprosthetic valves.

**Table 2.** Definition of Major Embolic Events
Major embolic events	Definition of terms
Arterial emboli	Sudden interruption of blood flow to an organ system due to an embolus, presumed by the physician to be from infective endocarditis. This complication is manifested by symptoms of end organ damage. For example, CNS emboli - manifestations would include stroke-like symptoms/neurologic deficits, documented by cranial imaging (CT or MRI). Other examples would include splenic, renal, peripheral, hepatic, retinal, or mesenteric emboli.
Intracranial hemorrhage	Bleeding into the CNS presumed to be due to a CNS emboli, which is not attributable to any other etiology such as hypertension or trauma.
Pulmonary infarcts	Lung injury due to interruption of blood flow to the lungs due to a (pulmonary) embolus. Manifestations may include sudden onset dyspnea, hemoptysis or pulmonary hemorrhage, or hypoxemia not attributable to any other cause. This may be documented by chest radiograph or CT/MRI.
Mycotic aneurysms	Aneurysm arising from bacterial infection of the arterial wall. Manifestations would include end-organ damage attributable to the involved system (i.e. neurologic deficits for CNS mycotic aneurysm, sudden abdominal pain for aortic mycotic aneurysms).

Table 2. Definition of Major Embolic Events

Major embolic events

Definition of terms

Arterial emboli

Sudden interruption of blood flow to an organ system due to an embolus, presumed by the physician to be from infective endocarditis. This complication is manifested by symptoms of end organ damage. For example, CNS emboli - manifestations would include stroke-like symptoms/neurologic deficits, documented by cranial imaging (CT or MRI). Other examples would include splenic, renal, peripheral, hepatic, retinal, or mesenteric emboli.

Intracranial hemorrhage

Bleeding into the CNS presumed to be due to a CNS emboli, which is not attributable to any other etiology such as hypertension or trauma.

Pulmonary infarcts

Lung injury due to interruption of blood flow to the lungs due to a (pulmonary) embolus. Manifestations may include sudden onset dyspnea, hemoptysis or pulmonary hemorrhage, or hypoxemia not attributable to any other cause. This may be documented by chest radiograph or CT/MRI.

Mycotic aneurysms

Aneurysm arising from bacterial infection of the arterial wall. Manifestations would include end-organ damage attributable to the involved system (i.e. neurologic deficits for CNS mycotic aneurysm, sudden abdominal pain for aortic mycotic aneurysms).

**Table 3.** Baseline Clinical Profile Stratified by Outcome (Development of Embolus)
Variable	Total (n = 87) (%)	With embolus⁺ (n = 25) (%)	Without embolus (n = 62) (%)	P-value
⁺Development major embolism after initiation of antibiotic therapy. **Minor embolic events include splinter hemorrhage, Janeway lesions or conjunctival hemorrhage.
Age (mean ± SD)	39.90 (13.98)	36.68 (11.40)	41.19 (14.78)	0.175
> 55 years old	15 (17.24)	2 (8.00)	13 (20.97)	0.147
≤ 55 years old	72 (82.76)	23 (92.00)	49 (79.00)
Male sex	49 (56.32)	16 (64.00)	33 (53.23)	0.359
Presence of minor emboli on admission**	44 (50.57)	15 (60.00)	29 (46.77)	0.264
Mean duration of illness in weeks	7.21 (7.75)	5.00 (5.41)	8.10 (8.38)	0.092
< 6 weeks (acute-subacute)	57 (65.51)	19 (76.00)	38 (61.29)	0.191
≥ 6 weeks (chronic)	30 (34.48)	6 (24.00)	24 (38.71)
Organism on blood culture
Staphylococcus spp.	13 (14.94)	7 (28.00)	6 (9.68)	0.030
Streptococcus viridans	21 (24.14)	7 (28.00)	14 (22.58)	0.593
Gram negative bacteria	11 (12.64)	3 (12.00)	8 (12.90)	0.909
Culture negative	40 (45.98)	8 (32.00)	32 (51.61)	0.097

Table 3. Baseline Clinical Profile Stratified by Outcome (Development of Embolus)

Variable

Total (n = 87) (%)

With embolus⁺ (n = 25) (%)

Without embolus (n = 62) (%)

P-value

⁺Development major embolism after initiation of antibiotic therapy. **Minor embolic events include splinter hemorrhage, Janeway lesions or conjunctival hemorrhage.

Age (mean ± SD)

39.90 (13.98)

36.68 (11.40)

41.19 (14.78)

0.175

> 55 years old

15 (17.24)

2 (8.00)

13 (20.97)

0.147

≤ 55 years old

72 (82.76)

23 (92.00)

49 (79.00)

Male sex

49 (56.32)

16 (64.00)

33 (53.23)

0.359

Presence of minor emboli on admission**

44 (50.57)

15 (60.00)

29 (46.77)

0.264

Mean duration of illness in weeks

7.21 (7.75)

5.00 (5.41)

8.10 (8.38)

0.092

< 6 weeks (acute-subacute)

57 (65.51)

19 (76.00)

38 (61.29)

0.191

≥ 6 weeks (chronic)

30 (34.48)

6 (24.00)

24 (38.71)

Organism on blood culture

Staphylococcus spp.

13 (14.94)

7 (28.00)

6 (9.68)

0.030

Streptococcus viridans

21 (24.14)

7 (28.00)

14 (22.58)

0.593

Gram negative bacteria

11 (12.64)

3 (12.00)

8 (12.90)

0.909

Culture negative

40 (45.98)

8 (32.00)

32 (51.61)

0.097

**Table 4.** Distribution According to Predisposing Cardiac Condition by Echocardiography
Predisposing cardiac condition	Frequency (n = 87) (%)
Valvular heart disease (rheumatic and non-rheumatic)	59 (68%)
Mitral stenosis	25
Mitral valve prolapse	14
Aortic stenosis	9
Congenital heart disease (CHD)	15 (17%)
Ventricular septal defect	8
Patent ductus arteriosus	3
Repaired CHD	2
Pulmonic stenosis	1
Prosthetic valve endocarditis	5 (7%)
Unknown or no underlying predisposition	8 (11%)

Table 4. Distribution According to Predisposing Cardiac Condition by Echocardiography

Predisposing cardiac condition

Frequency (n = 87) (%)

Valvular heart disease (rheumatic and non-rheumatic)

59 (68%)

Mitral stenosis

Mitral valve prolapse

Aortic stenosis

Congenital heart disease (CHD)

15 (17%)

Ventricular septal defect

Patent ductus arteriosus

Repaired CHD

Pulmonic stenosis

Prosthetic valve endocarditis

5 (7%)

Unknown or no underlying predisposition

8 (11%)

**Table 5.** Components of the French Risk Calculator
Variable	Total (n = 87) (%)	With embolus⁺ (n = 25) (%)	Without embolus (n = 62) (%)	P-value
⁺Major embolic events included any arterial emboli, intracranial hemorrhage, pulmonary infarcts, or mycotic aneurysms. *P value < 0.05.
Mean age (SD)	39.86 (13.95)	36.72 (11.39)	41.13 (14.75)	0.183
Presence of diabetes mellitus	18 (20.69)	6 (24.00)	12 (19.35)	0.628
Major emboli prior to admission	18 (20.69)	11 (44.00)	7 (11.29)	0.001*
Atrial fibrillation	23 (26.44)	12 (48.00)	11 (17.74)	0.004*
Length of vegetation on 2D echocardiogram
< 10 mm	51 (58.62)	7 (28.00)	44 (70.97)	< 0.001*
≥ 10 mm	35 (40.23)	18 (72.00)	17 (27.42)	< 0.001*
Staphylococcus aureus on blood culture	8 (9.20)	6 (24.00)	2 (3.23)	0.002*
Mean score on French calculator (SD)	5.13 (4.33)	8.68 (5.75)	3.69 (2.48)	< 0.001*

Table 5. Components of the French Risk Calculator

Variable

Total (n = 87) (%)

With embolus⁺ (n = 25) (%)

Without embolus (n = 62) (%)

P-value

⁺Major embolic events included any arterial emboli, intracranial hemorrhage, pulmonary infarcts, or mycotic aneurysms. *P value < 0.05.

Mean age (SD)

39.86 (13.95)

36.72 (11.39)

41.13 (14.75)

0.183

Presence of diabetes mellitus

18 (20.69)

6 (24.00)

12 (19.35)

0.628

Major emboli prior to admission

18 (20.69)

11 (44.00)

7 (11.29)

0.001*

Atrial fibrillation

23 (26.44)

12 (48.00)

11 (17.74)

0.004*

Length of vegetation on 2D echocardiogram

< 10 mm

51 (58.62)

7 (28.00)

44 (70.97)

< 0.001*

≥ 10 mm

35 (40.23)

18 (72.00)

17 (27.42)

< 0.001*

Staphylococcus aureus on blood culture

8 (9.20)

6 (24.00)

2 (3.23)

0.002*

Mean score on French calculator (SD)

5.13 (4.33)

8.68 (5.75)

3.69 (2.48)

< 0.001*

**Table 6.** Echocardiographic Profile Stratified by Outcome (Development of Embolus)
Variable	Total (n = 87) (%)	With embolus⁺ (n = 25) (%)	Without embolus (n = 62) (%)	P-value
⁺Development major embolism after initiation of antibiotic therapy. ⁺⁺Left atrial volume index. ⁺⁺⁺Vegetation area was computed by multiplying the longest length with the widest width. *P-value < 0.05.
Overall cardiac structure and function
Mean ejection fraction (SD)	60.92 (11.57)	60.32 (12.70)	61.16 (11.18)	0.761
Ejection Fraction < 45%	11 (12.64)	5 (20.00)	6 (9.68)	0.190
Mean LAVI (mL/m²)⁺⁺	44.56 (29.84)	41.40 (25.76)	45.84 (31.44)	0.533
LAVI > 34 mL/m²	54 (62.07)	17 (68.00)	37 (59.68)	0.469
Significant valvular regurgitation	39 (44.83)	12 (48.00)	27 (43.55)	0.706
Number of vegetations
0 vegetation	5 (5.75)	2 (8.00)	3 (4.84)	0.566
1 vegetation	64 (73.56)	16 (64.00)	48 (77.42)	0.199
> 1 vegetation	18 (20.69)	7 (28.00)	11 (17.74)	0.285
Size and characteristics of the vegetation
Vegetation length (mean ± SD)	8.45 (6.11)	10.60 (6.49)	7.58 (5.78)	0.036*
Vegetation length ≥ 10 mm	35 (40.23)	16 (64.00)	19 (30.65)	0.004*
Vegetation length > 15 mm	14 (16.09)	6 (24.00)	8 (12.90)	0.202
Vegetation area (mean ± SD)⁺⁺⁺	70.40 (85.22)	112.72 (100.97)	53.33 (72.09)	0.003*
Vegetation area ≥ 18 mm²	50 (57.47)	21 (84.00)	29 (46.77)	0.001*
Mobile vegetation	61 (70.11)	21 (84.00)	40 (64.52)	0.072
Presence of abscess	6 (6.90)	2 (8.00)	4 (6.45)	0.796
Location of vegetation
Left-sided vegetation	79 (90.80)	21 (84.00)	58 (93.55)	0.163
Right-sided vegetation	10 (11.49)	5 (20.00)	5 (8.06)	0.114
Valvular involvement
Mitral location	56 (64.37)	17 (68.00)	39 (62.90)	0.653
Aortic location	21 (24.14)	7 (28.00)	14 (22.58)	0.593
Tricuspid/pulmonic location	8 (9.20)	5 (20.00)	3 (4.84)	0.027*
Multiple valves	19 (21.84)	8 (32.00)	11 (17.74)	0.145
Prosthetic valves	3 (3.45)	1 (4.00)	2 (3.23)	0.858
No valves (endocardium)	10 (11.49)	3 (12.00)	7 (11.29)	0.925

Table 6. Echocardiographic Profile Stratified by Outcome (Development of Embolus)

Variable

Total (n = 87) (%)

With embolus⁺ (n = 25) (%)

Without embolus (n = 62) (%)

P-value

⁺Development major embolism after initiation of antibiotic therapy. ⁺⁺Left atrial volume index. ⁺⁺⁺Vegetation area was computed by multiplying the longest length with the widest width. *P-value < 0.05.

Overall cardiac structure and function

Mean ejection fraction (SD)

60.92 (11.57)

60.32 (12.70)

61.16 (11.18)

0.761

Ejection Fraction < 45%

11 (12.64)

5 (20.00)

6 (9.68)

0.190

Mean LAVI (mL/m²)⁺⁺

44.56 (29.84)

41.40 (25.76)

45.84 (31.44)

0.533

LAVI > 34 mL/m²

54 (62.07)

17 (68.00)

37 (59.68)

0.469

Significant valvular regurgitation

39 (44.83)

12 (48.00)

27 (43.55)

0.706

Number of vegetations

0 vegetation

5 (5.75)

2 (8.00)

3 (4.84)

0.566

1 vegetation

64 (73.56)

16 (64.00)

48 (77.42)

0.199

> 1 vegetation

18 (20.69)

7 (28.00)

11 (17.74)

0.285

Size and characteristics of the vegetation

Vegetation length (mean ± SD)

8.45 (6.11)

10.60 (6.49)

7.58 (5.78)

0.036*

Vegetation length ≥ 10 mm

35 (40.23)

16 (64.00)

19 (30.65)

0.004*

Vegetation length > 15 mm

14 (16.09)

6 (24.00)

8 (12.90)

0.202

Vegetation area (mean ± SD)⁺⁺⁺

70.40 (85.22)

112.72 (100.97)

53.33 (72.09)

0.003*

Vegetation area ≥ 18 mm²

50 (57.47)

21 (84.00)

29 (46.77)

0.001*

Mobile vegetation

61 (70.11)

21 (84.00)

40 (64.52)

0.072

Presence of abscess

6 (6.90)

2 (8.00)

4 (6.45)

0.796

Location of vegetation

Left-sided vegetation

79 (90.80)

21 (84.00)

58 (93.55)

0.163

Right-sided vegetation

10 (11.49)

5 (20.00)

5 (8.06)

0.114

Valvular involvement

Mitral location

56 (64.37)

17 (68.00)

39 (62.90)

0.653

Aortic location

21 (24.14)

7 (28.00)

14 (22.58)

0.593

Tricuspid/pulmonic location

8 (9.20)

5 (20.00)

3 (4.84)

0.027*

Multiple valves

19 (21.84)

8 (32.00)

11 (17.74)

0.145

Prosthetic valves

3 (3.45)

1 (4.00)

2 (3.23)

0.858

No valves (endocardium)

10 (11.49)

3 (12.00)

7 (11.29)

0.925

**Table 7.** Univariate Analysis to Predict Development of Embolic Events during Admission
Variable	Relative risk	95% CI	P-value
⁺Included in the final model of multivariate analysis. *High risk embolic events using the embolic risk French calculator were set at > 7% risk at 1 month (see references).
High risk for embolic events (> 7%)*	20.27	5.95 - 69.05	< 0.001*
Age > 55	0.33	0.07 - 1.57	0.163
Diabetes mellitus	1.04	0.32 - 3.34	0.945
Minor embolism prior to therapy	1.71	0.66 - 4.38	0.266
Major embolism prior to therapy	8.62	2.73 - 27.23	< 0.001*
Atrial fibrillation	3.85	1.41 - 10.52	0.009*
Ejection fraction < 45%	2.33	0.64 - 8.49	0.199
Left-sided vegetation	0.36	0.08 - 1.58	0.176
More than one vegetation	1.80	0.61 - 5.36	0.289
Vegetation length ≥ 10 mm	4.02	1.51 - 10.71	0.005*
Vegetation length ≥ 15 mm	2.13	0.65 - 6.94	0.209
Area of vegetation ≥ 18 mm²	5.97	1.84 - 19.44	0.003*
Staphylococcus aureus on culture	3.63	1.08 - 12.21	0.037*

Table 7. Univariate Analysis to Predict Development of Embolic Events during Admission

Variable

Relative risk

95% CI

P-value

⁺Included in the final model of multivariate analysis. *High risk embolic events using the embolic risk French calculator were set at > 7% risk at 1 month (see references).

High risk for embolic events (> 7%)*

20.27

5.95 - 69.05

< 0.001*

Age > 55

0.33

0.07 - 1.57

0.163

Diabetes mellitus

1.04

0.32 - 3.34

0.945

Minor embolism prior to therapy

1.71

0.66 - 4.38

0.266

Major embolism prior to therapy

8.62

2.73 - 27.23

< 0.001*

Atrial fibrillation

3.85

1.41 - 10.52

0.009*

Ejection fraction < 45%

2.33

0.64 - 8.49

0.199

Left-sided vegetation

0.36

0.08 - 1.58

0.176

More than one vegetation

1.80

0.61 - 5.36

0.289

Vegetation length ≥ 10 mm

4.02

1.51 - 10.71

0.005*

Vegetation length ≥ 15 mm

2.13

0.65 - 6.94

0.209

Area of vegetation ≥ 18 mm²

5.97

1.84 - 19.44

0.003*

Staphylococcus aureus on culture

3.63

1.08 - 12.21

0.037*

**Table 8.** Multivariate Analysis to Predict Embolic Events
Variable	Relative risk	95% CI	P-value
⁺Independent predictors of embolic events with P value < 0.05. *High risk embolic events using the embolic risk French calculator were set at > 7% risk at 1 month.
High risk score for embolic events (> 7%)*	15.12	4.19 - 54.54	< 0.001⁺
Vegetation area ≥ 18 mm²	6.39	1.55 - 26.31	0.010⁺
Major embolism prior to therapy	5.18	1.32 - 20.35	0.018⁺

Table 8. Multivariate Analysis to Predict Embolic Events

Variable

Relative risk

95% CI

P-value

⁺Independent predictors of embolic events with P value < 0.05. *High risk embolic events using the embolic risk French calculator were set at > 7% risk at 1 month.

High risk score for embolic events (> 7%)*

15.12

4.19 - 54.54

< 0.001⁺

Vegetation area ≥ 18 mm²

6.39

1.55 - 26.31

0.010⁺

Major embolism prior to therapy

5.18

1.32 - 20.35

0.018⁺

**Table 9.** Multiple Logistic Regression to Predict Primary and Secondary Outcomes
Variable	Embolic event (primary endpoint)	Composite of death and embolic events	Death
*High risk score pertains to a high embolic risk score at one month, calculated using the French calculator. RR: relative risk; NS: not significant.
High risk score (> 7%)*	15.12	< 0.001	13.56	< 0.001	6.2	0.003
Vegetation area ≥ 18 mm²	6.39	0.010	NS	NS
Emboli prior to admission	5.18	0.018	13.75	0.002	NS
Ejection fraction ≤ 45%	NS	NS	9.91	0.004

Table 9. Multiple Logistic Regression to Predict Primary and Secondary Outcomes

Variable

Embolic event (primary endpoint)

Composite of death and embolic events

Death

P-value

*High risk score pertains to a high embolic risk score at one month, calculated using the French calculator. RR: relative risk; NS: not significant.

High risk score (> 7%)*

15.12

< 0.001

13.56

< 0.001

6.2

0.003

Vegetation area ≥ 18 mm²

6.39

0.010

Emboli prior to admission

5.18

0.018

13.75

0.002

Ejection fraction ≤ 45%

9.91

0.004