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Carlos-A. Mestres, MD, PhD, FETCS Consultant Cardiovascular Surgery Hospital Clínico. University of Barcelona Barcelona. Spain. Infective endocarditis is an uncommon disease associated to significant morbidity and mortality. As in any infection within the cardiovascular surgery,

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slide1

Carlos-A. Mestres, MD, PhD, FETCS

Consultant

Cardiovascular Surgery

Hospital Clínico. University of Barcelona

Barcelona. Spain

slide2

Infective endocarditis is an uncommon disease

associated to significant morbidity and mortality.

As in any infection within the cardiovascular surgery,

early diagnosis and aggresive management are

indicated

Infective endocarditis is a medical & surgical disease

which must be managed by a multidisciplinary

team with shared interests

slide3

The Team

The Hospital Clinico of Barcelona Endocarditis Study

Group is a multidisciplinary group specifically

dedicated to the study and treatment of infective

endocarditis and cardiovascular infections operational

for 25 years

Infectious Diseases (6), Cardiovascular Surgery (3), Microbiology (3),

Surgical Pathology (1), Echocardiography (2)

slide4

The Team

* Infectious Diseases

J.M.Miró, A.Moreno, A. Del Río, N. De Benito, X.Claramonte, J.P.Horcajada

* Cardiovascular Surgery

C.A.Mestres, R.Cartañá, S.Ninot, J.L.Pomar

* Microbiology

M.Almela, F.Marco, C.García

* Surgical Pathology

J.Ramírez, N.Pérez

* Echocardiography

J.C.Paré, M.Azqueta, M.Sitges

slide5

Infective Endocarditis

What have we learned?

What have we changed?

What are we doing?

Where are we going?

An overview

slide6

A - Short Courses of Therapy for Infective Endocarditis

B - Infective Endocarditis in Drug Abusers (IVDAs)

C – Surgical experience

slide7

Potential number of candidates for short-courses of therapy

for right-sided MSSA endocarditis in IVDAs at the

Hospital Clínic of Barcelona, Spain (1979-98)

Types of endocarditis

in IVDAs

MSSA

N (%)

N

- Right-sided IE

- Left-sided IE

- Mixed IE

Total

142

46

16

204

104 (73%)

16 (35%)

10 (64%)

130 (64%)

2 wk Tx*

40%

* According to methicillin-susceptibility, HIV status and CD4 cell counts (>200/µL)

slide8

Short Courses of Therapy for Infective Endocarditis

CONCLUSIONS

5. Patients allergic to penicillin who must receive vancomycin with or without an aminoglycoside must be treated during 4 wks

6. In our 25-year experience, one of every five episodes of native valve IE (general population + IVDAs) and almost one of every two episodes of IE in IVDAs were considered potential candidates for these short courses (2 wks) of therapy

slide9

Infective Endocarditis in IVDAs & HIV infection

SUMMARY

1. The incidence of IE in IVDA in the AIDS era is decreasing probably due to the change of the drug administration habits in order to avoid HIV-infection

2. HIV-infected IVDA have a higher ratio of right-sided IE and S. aureus endocarditis than HIV-negative IVDA with IE

3. Mortality between HIV-infected or non-HIV-infected IVDA with IE is similar. However, mortality among HIV-infected IVDA is higher in IVDA with less than 200 CD4+ cells/µL or with AIDS criteria

slide10

Infective Endocarditis in IVDAs & HIV Infection

SUMMARY

4. IVDA with non-complicated MSSA right-sided IE can be succesfully treated with an IV short-course regimen of nafcillin or cloxacillin plus an aminoglycoside during 2 weeks, although the addition of an aminoglycoside may be avoided or reduced to the first 3-7 days

5. Tricuspid valve replacement using mitral homografts can be a safely alternative to tricuspid valvulectomy for those IVDA with endocarditis who need right heart surgery

“Long-term results after cardiac surgery in patients infected with the human immunodeficiency virus type-1 (HIV-1)”

Mestres CA et al. Eur J Cardio-thorac Surg 2003; 23:1007-1016

slide11

Epidemiology

1990 - 2000

Diagnosis of IE 421

IV (IVDA) drug abuse 104

General population 317

Native IE 213

PVE 75

Pacemaker/AICD 29

Admissions/yr >50

slide12

“Infective endocarditis in intravenous drug abusers and HIV-1 infected patients”

J.M.Miró, A. del Río, C.A.Mestres

Infect Dis Clin North Am 2002; 16:273-295

“Infective endocarditis not related to intravenous drug abuse in HIV-1-infected patients: report of eight cases and review of the literature”

J.E.Losa, J.M.Miró, A. Del Río, A.Moreno-Camacho, F.Gracia, X.Claramonte, F.Marco, C.A.Mestres, M.Azqueta, J.M.Gatell and the Hospital Clinic Endocarditis Study Group

Clin Microbiol Infect 2003; 9:45-54

“Surgical treatment of pacemaker and defibrillator lead endocarditis. The impact of electrode lead extraction on outcome”

A.del Río, I.Anguera, J.M.Miró, L.Mont, Fowler VG Jr, M.Azqueta, C.A.Mestres and the Hospital Clinic Endocarditis Study Group

Chest 2003; 124:1451-1459

slide16

ICE

Presumed intravascular catheter source by region

International Collaborationon Endocarditis

slide17

Specific indications

Mechanical valve

Young, “good” ring, cured IE

Bioprosthesis

Elderly (?), “good” ring, cured IE

Homograft

Complicated IE, abscess, annular destruction

slide18

The complicated root

  • Root abscess
  • Aorto-cavitary fistula
the spanish aorto cavitary fistula endocarditis working group

L770 - AORTO-CAVITARY FISTULIZATION IN COMPLICATED ENDOCARDITIS. CLINICAL AND ECHOCARDIOGRAPHIC FEATURES OF 76 CASES (1992-2001) AND PROGNOSTIC FACTORS OF MORTALITY

42nd ICAAC. San Diego, CA. September 27-30, 2002

The Spanish Aorto-cavitary Fistula Endocarditis Working Group

slide21

No clinical infective endocarditis (IE) series have been performed studying the development of aorto-cavitary fistulas (ACF) as a result of spread of infection from valvular tissue towards perivalvular structures. Our aims were to investigate the clinical, echocardiographic and microbiologic features and prognostic factors of in-hospital mortality in patients with IE and ACF.

Retrospective and multicentre study at 11 Spanish and 1 North-american Hospitals in patients with IE and ACF.

slide22
Spread of infection in infective endocarditis (IE) from valvular structures to the surrounding perivalvular tissue results in periannular complications.

Rupture of abscesses and pseudoaneurysms in the sinuses of Valsalva result in the development of aorto-cavitary fistulas and intracardiac shunts.

Aorto-cavitary fistula formation is an unusual complication of IE. An incidence of 1% of all cases of IE has been estimated. Fistulization of perivalvular abscesses occurs in 6-9% of cases.

Basic considerations

slide23

* Multicenter, international, retrospective, descriptive study performed between 1992 and 2001

* Infective endocarditis diagnosed according to Duke criteria

* Aorto-cavitary fistulization documented by TTE/TEE

* Univariate analysis of prognostic factors of mortality

slide24

ACF n Cases IE n Incidence %

General population

Native valve

Aortic

Mitral

Other

PVE

Aortic

Mitral

Other

Pacemaker

IV Drug abusers

OVERALL

69

38

38

--

--

31

31

--

--

--

7

76

3147

2105

1056

930

119

872

536

326

10

170

1534

4681

2.2

1.8

3.6

---

---

3.5

5.8

---

---

---

0.4

1.6

slide25

Clinical characteristics

NVE=45 PVE=31 All=76

Mean age (y)

Male gender

Previous valve disease

Comorbidity

Mechanical ventilation

IV drug abuse

Duration of symptoms (d)

Duration to Dx of ACF (d)

CHF

Neuro events

Renal failure

Peripheral emboli

Complete AV block

50.9±18.7*

36 (80%)

13 (28%)

18 (40%)

6 (13%)

7 (16%)

24.5±18.7

36.2±31.6

31 (69%)

8 (18%)

20 (44%)

8 (18%)

5 (11%)

60.2±13.4*

20 (65%)

31 (100%)

9 (29%)

1 (3%)

0

29.8±37.7

44.1±55.5

16 (52%)

4 (13%)

8 (26%)

7 (23%)

6 (19%)

54.7±17.2

56 (74%)

44 (59%)

27 (36%)

7 (9%)

7 (9%)

26.7±27.9

39.4±42.8

47 (62%)

12 (16%)

28 (37%)

15 (20%)

11 (14%)

slide26

Pathogens

NVE=45 PVE=31 All=76

Staphylococcus spp

S.aureus

CNS

Streptococcus spp

VGS

S.bovis

Other streptococci

Enterococcus spp

Culture negative

Other (HACEK)

17 (38%)*

13 (29%)*

4 (9%)*

16 (35%)

10 (22%)

2 (4%)

4 (9%)

2 (4%)

5 (11%)

7 (15%)

18 (58%)*

3 (10%)*

15 (48%)*

9 (29%)

5 (16%)

--

4 (13%)

2 (6%)

--

2 (6%)

35 (46%)

16 (21%)

19 (25%)

25 (33%)

15 (20%)

2 (3%)

8 (10%)

4 (5%)

5 (6%)

9 (12%)

NVE vs PVE groups (p<0.05)

slide27

Echocardiography

Diagnostic yield of TTE and TEE

slide28

Native

N=45

Prosthetic

N=31

Total

N=76

Echo findings

Patients with vegetations

Mean maximal veg. size (mm)

Vegetations > 10 mm

Patients with abscess

Mean maximal abscess diameter

Abscess > 10 mm

Ventricular septal defect

Mean EF (%)

Mean LVEDD (mm)

Multivalvular infection

96 %*

11.5

49 %

71 %

10 mm

44 %

21 %

62.5

55.2

33 %

65 %*

12.1

70 %

87 %

15 mm

67 %

19 %

60.5

54.4

26%

83 %

11.7

56 %

78 %

12 mm

54 %

20 %

61.7

54.9

30 %

*Native vs prosthetic, p < 0.05

slide29
Fistulized sinus of Valsalva (SV)

Right SV

Left SV

Non coronary SV

Fistulized cardiac chamber (%)

Right atrium

Right ventricle

Left atrium

Left ventricle

Multiple

Moderate/severe regurgitation

Native

N=45

Prosthetic

N=31

Total

N=76

Echo findings

44%

35%

20%

18%

31%

22%

13%

11%

64%*

26%

42%

32%

16%

16%

32%

19%

13%*

26%*

37%

38%

25%

17%

25%

26%

16%

12%

49%

* Native vs prosthetic, p < 0.05

slide30
Surgical treatment

Time to surgery

< 24 hours

2 - 7 days

> 7 days

Closure of fistula (%)

Simple

Pericardial patch

Gore-tex patch

Valve replacement

Bioprosthesis

Mechanical

Homograft

Native

N=45

Prosthetic

N=31

Total

N=76

87%

33%

36%

31%

41%

46%

13%

95%

28%

49%

18%

87%

11%

52%

37%

41%

52%

7%

89%

19%

52%

19%

87%

24%

42%

34%

41%

48%

11%

92%

24%

50%

18%

slide31
In-hospital mortality

- Surgical group (N=66)

- Medical group (N=10)

Native

N=45

Prosthetic

N=31

Total

N=76

16 (36%)

13/39 (33%)

3/6 (50%)

15 (48%)

15/27 (55%)

0/4 (-)

31 (41%)

28 (42%)

3 (30%)

Medical

N=3

Surgical

N=28

Cause of death

- Multiorgan failure

- Sudden death

- Septic shock

- Cardiogenic shock

- Hemorrhage

33%

33%

-

33%

-

23%

10%

26%

19%

23%

slide32
Lost for follow-up

Follow-up (mo., mean, range)

Residual fistula

Late CHF

Late valvular replacement

Late death

Medical *

N=7

Surgical

N=38

2

4

36 (1-96)*

-

3

0

1

29 (1-144)*

5 (11%)

7 (16%)

5 (11%)

3 ( 7%)

* The 3 patients who died w/o surgery had fatal co-morbid conditions. The remaining

7 patients did not undergo surgery because they did not have cardiac failure,

severe valvular regurgitation and echocardiographical abscess.

slide33
Age > 65years

Male gender

Prosthetic endocarditis

Symtoms duration >30 d.

Moderate or severe CHF

Renal failure

Neurologic symptoms

S.aureus infection

Vegetation >10 mm

Patients with periannular abscess

Periannular abscess > 10 mm

Moderate or severe AR

Fistulized sinus of Valsalva

Fistulized cardiac chamber

EF <65%

Urgent or emergency surgery

OR – 95%CI p

2.8 (1.0-7.9)

0.8 (0.2-2.4)

2.5 (0.9-6.8)

0.8 (0.2-2.6)

2.2 (0.7-5.1)

1.8 (0.7-5.1)

0.6 (0.1-2.8)

1.2 (0.4-3.6)

1.2 (0.4-3.6)

1.6 (0.5-5.5)

2.3 (0.7-7.3)

0.8 (0.3-2.1)

-

-

1.1 (0.4-3.1)

2.7 (0.9-7.8)

0.05

0.6

0.07

0.7

0.15

0.2

0.5

0.8

0.7

0.4

0.14

0.7

0.9

0.2

0.8

0.06

slide34

Limitations

* Ascertainment bias – multicenter nature

* Severity of CHF higher – low-grade shunts

underdiagnosed

* High-risk profles of surgical candidate

* Not comparable to medically treated

* Not comparing medical and surgical patients

slide42

Actuarial freedom from death, heart failure requiring hospital admission and repeat surgery in patients with periannular complications surviving the index hospitalization. A. patients referred to surgical therapy

slide44
* Aorto-cavitary fistulization in IE is an unfrequent event and occurs in patients with aortic endocarditis with high grade of local tissue destruction.

* It was associated with staphylococci and streptococci native-valve IE and with coagulase-negative staphylococci prosthetic valve IE.

* In-hospital mortality was high even when most patients were referred to surgical treatment.

* Congestive heart failure identified the subgroup of patients with the worst prognosis.

Conclusions

slide45

Prosthetic valve endocarditis

  • What?
  • When?
  • Who?
  • Why?
slide47

Methods

* International Collaboration on Endocarditis Merged Database

* Large, multicenter, international registry of patients with definite

endocarditis by Duke criteria

* Clinical, microbiological, echocardiographic variables to determine

* Those factors associated with the use of surgery in PVIE

* Logistic regression analysis

* Propensity score to match surgery vs medical therapy

slide51

Logistic regression analysis of variables independently

associated with in-hospital mortality in patients with PVIE

and matched propensity for surgical treatment

slide52

Conclusions

* Despite the frequent use of surgery for the treatment of PVIE

this condition continues to be associated with high in-hospital

mortality

* After adjustment for factors related to surgical intervention,

brain embolism and S. aureus infection were independently

associated with in-hospital mortality and a trend toward a

survival benefit of surgery was evident

slide53

Echocardiographic (TTE) Follow-up

Year Patient TTE TTE FU Last TTE NYHA

Before After (Yrs)

1991 AMG Veg 28 mm Mild TR 13 Severe TR II

Large RV

1991 RPO Veg 22 mm Severe TR 13 Severe TR II

Severe TR Large RV Large RV

Large RV

1992 PER Veg 30 mm Severe TR 5 Severe TR I

Severe TR Ruptured Large RV

chordae

1994 JLF Veg 22 mm Mild TR 1 Mild TR I

1996 JFG Veg 28 mm Mild TR 1 Severe TR I

Severe TR

slide54

Echocardiographic (TTE) Follow-up

Year Patient TTE TTE FU Last TTE NYHA

Before After (Yrs)

2001 ERA Severe TR Trivial TR pod Po Death

2002 LML Veg 20 mm Trivial TR pod Po Death

Severe TR Large RV

Large RV

2002 JGR Veg 30 mm Mild TR 2.5 Mild TR I

Severe TR

slide55

Outcomes

Year Patient FU Drug addiction Recurrent HIV Outcome

(Yrs) relapse endocarditis stage

1991 AMG 6 Yes 14 mos B3 Alive

(Corynebacterium spp) Late Reop

1991 RPO 6 Yes 48, 58, 63 mos B2 Alive

(MSSA all cases) No Reop

1992 PER 5 No No A2 Alive

Late Reop

1994 JLF 2.5 Yes No A3 Death

Overdose

1996 JFG 8.5 Yes 7, 12 mos A2 Alive

(MSSA) No reop

slide56

Year Patient FU Drug addiction Recurrent HIV Outcome

(Yrs) relapse endocarditis stage

2001 ERA PO N N C3 Death

2002 LML PO N N B2 Death

2002 JGR 2.5 N No A1 Alive

slide57

The most complex situation

Fibrous Skeletal destruction

slide58

Acute pectoralis major myositis in an

otherwise healthy young male

slide59
25-year-old male

Smoker ½ pack/day

Occasional recreational drugs. NO iv abuse

Job: Waiter. Physically fit. Contact sports (judo, full-contact…)

  • In the past 2 years 4 episodes of abscess requiring surgical drainage (hand, foot, knee, axilla)
  • No other personal nor familiar medical history of interest
  • 5-day left upper limb and upper left chest pain accompanied by high-degree fever (39°C), chills and malaise
slide60
Aortic root replacement with a 20-22 mm cryopreserved aortic homograft

Intraoperative findings: Massive AR due to perforation of the right coronary cusp on a morphologically normal aortic valve. Full root subaortic abscess extending towards the left atrial roof

Aortic cross-clamp 73 min – CPB 189 min

Left ventricular failure and myocardial edema after CPB. Sternum open. Intraaortic ballon pump support

outcome i
Postop unstable hemodynamics. Urgent TTE showed anterior-septoapical hypokinesia

Urgent coronary angiogram showed 70% LMCA stenosis with remaining normal coronaries

August 12, 2004: Off-pump LIMA-LAD bypass graft and delayed sternal closure

August 12, 2004 2/2 + blood cultures (ORSA)

Outcome - I
outcome ii
Early favourable postop. Improved condition, no congestive heart failure

August 14, 2004, 2/2 negative blood cultures. Trasnsferred to ward August 22, 2004. Good condition with low-degree fever (37°C)

August 24, 2004 new control TTE

Outcome - II
surgery ii
September 1, 2004 – Homograft replacement with a 21 mm SJM Toronto-Root porcine heterograft

Surgical findings: Subaortic circumferential detachment of the normal functioning homograft. Extensive lesions of the entire fibrous body. Left atrial fistula

Post-repair severe mitral regurgitation

Profound left ventricular failure. LVAD Abiomed BVS-5000 implanted

All samples to Microbiology

Surgery - II
outcome iv
September 2, 2004 – Unstable under maximal intropic support and LVAD. No further conventional surgery indicated. Decision to include in emergency WL for heart transplantation

September 3, 2004 – Orthotopic heart transplantation

Outcome - IV
slide65

Final diagnosis

1. Community-acquired ORSA myositis

2. Acute aortic root ORSA infective endocarditis

3. Heart transplantation

endocarditis and heart transplantation
1: Galbraith AJ et al. Cardiac transplantation for prosthetic valve endocarditis in a previously transplanted heart. J Heart Lung Transplant. 1999; 18:805-806

2: Blanche C et al. Heart transplantation for Q fever endocarditis. Ann Thorac Surg. 1994; 58:1768-1769

3: Pulpon LA et al. Recalcitrant endocarditis successfully treated by heart transplantation. Am Heart J 1994; 127:958-960

4: Park SJ et al. Heart transplantation for complicated and recurrent early prosthetic valve endocarditis. J Heart Lung Transplant. 1993; 12:802-803.

5: DiSesa VJ et al. Heart transplantation for intractable prosthetic valve endocarditis. J Heart Transplant. 1990; 9:142-143

Endocarditis and Heart Transplantation
endocarditis and heart transplantation1
“Heart transplantation could be an alternative, not a contraindication, when in Infective Endocarditis all other measures have failed” (1)Endocarditis and Heart Transplantation

Galbraith AJ Cardiac transplantation for prosthetic valve endocarditis

in a previously transplanted heart. J Heart Lung Transplant. 1999 Aug;18(8):805-6

slide69

Conclusions

* IE is a very serious pathology

* It is not popular

* Highly demanding

* Suboptimal results

* Team approach

* Risk takers

slide70

Parsonnet score

Single centre – Subjective factors – Overestimates risk

Cleveland score

Single centre – Excludes non CABG – Leads to gaming

EuroScore

Large multicentre database – Fit for all adult cardiac

surgical patients – Even correlates with STS

slide71

EuroSCORE

Additive

Score % mortality

0 – 2

3 – 5

6 – 8

9 – 11

12>

0.88 – 1.51

2.62 – 3.51

6.51 – 8.37

14.02 – 19.12

31.00 – 42.32

slide72

EuroSCORE

Its predictive accuracy has been established

Only the additive model has been validated

Inconsistencies among the additive and logistic

models when applied to the high-risk patients

slide74

Reasons to predict mortality in Cardiac Surgery

1. Helping to determine indications for surgery

2. Quality monitoring

Additive EuroScore works well for most purposes

slide75

Considerations

The relationship between risk factors is not additive

Combined impact of two or more factors on operative

risk may be more than simple sum

Logistic score more realistic

slide76

The reality

* Infective endocarditis is a high-risk situation

* There is lack of data regarding risk assessment

before valve surgery

slide77

Aim of the study

To validate the EuroSCORE preoperative

stratification risk model in infective endocarditis

slide78

Population

Period Jan 95 – Jan 04

Patients 147

Mean age 56.33 ± 15.95

Male gender 69.4%

slide82

Characteristics

Active endocarditis 91.2%

IV Drug addicts 10.9%

HIV+ 5.4%

ESR – HD 3.4%

Reoperation 27.2%

slide84

Type of operation

Emergency 29.9%

Urgent 21.8%

Elective 46.9%

slide85

EuroSCORE

Additive

Range

Mean

Median

2 – 19

10.15 ±3.81

10

slide86

EuroSCORE

Logistic

Range

Mean

Median

1.51 – 94.17% EM

25.59 ± 20.81

18.95

slide87

Results

Overall in-hospital mortality 32.7%

  • Intraoperative death
  • 30 days po
  • Regardless the length of stay
slide88

Results

Receiver operating characteristics (ROC) curves

Asymptotic 95% confidence interval

Area > 0.7 Good correlation

Area > 0.8 Very good correlation

Area > 0.9 Excellent correlation

slide99

Comments

There is a very good correlation between logistic

EuroSCORE and mortality for the entire group

Division in subgroups yields a decrease in statistical

power but correlation is almost the same in all subgroups

The area is good in the prosthetic valve IE although non

significant by position

slide100

Comments

The area is very good for Gram – and polymicrobial

although with low statistical power

There is statistical power for significance in the

Staphylococci and Streptococci groups

slide101

Limitations

Small sample size

Statistical power decreases when analyzing subgroups

Just preliminary results

slide102

When to use Logistic EuroScore?

  • To calculate a precise and realistic risk prediction for a very high-risk patient, particularly when the indication for surgery may not be clear

- To monitor quality of care in institutions where a substantial proportion of patients are of very high-risk

- To help in the further study of risk modelling by groups and institutions with a scientific interest in the subject

- To carry out normal stratification in institutions with easy availability of accesible information technology, especially where high-risk surgery forms a substantial part of the workload

slide103

The Future of risk stratification

* Larger sample size

* More institutions involved

* Subgroup analysis (Pathogens, abscess…)

* Team approach

* The role of ICE

* Changing our approach to patients?

* Quality assurance

slide104

Conclusions

* IE is a very serious pathology

* It is not popular

* Highly demanding

* Suboptimal results

* Team approach

* Risk takers

ad