infective endocarditis: medical vs. surgical treatment · infective endocarditis: medical vs....
TRANSCRIPT
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Infective Endocarditis:
Medical vs. Surgical Treatment
The Surgeon’s perspective
Ohio-ACC Spring Summit at Ritz-Carlton, Cleveland
on Wednesday, April 19, 2017, 3:30-4:30 p.m.
Gösta Pettersson, M.D., Ph.D.
Professor CWRU
Department of Cardiovascular Surgery
Cleveland Clinic
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No Disclosures
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Infective Endocarditis is a
FATAL DISEASE
Notoriously Difficult to Treat
WHY?
Medical Management or Surgery?
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IE is a FATAL DISEASE
CASE: 49 year old male
• Severe burn to > 20% of his body
• Respiratory failure - 3 weeks on vent
• Bacteremia: Serratia and MRSA
• Cardiogenic Shock, Hypoxemia, Pulmonary
Edema, Systemic Pulmonary Artery Pressure
• 2nd degree heart block
Medical Management or Surgery?
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Native valve endocarditis
CASE: Chest X-ray 49 yo male,
Serratia & MRSA
Medical Management or Surgery?
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Endocarditis Survival
Natural and Modified History 100
80
60
40
20
0 0 2 4 6 8 10 12
Months
%
Staph Aureus
Acute IE
Strep Viridans
Sub Acute IE
Medical
+ Surgical
GP, SH, NS, EHB 2017
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Probability of success with medical
therapy in endocarditis P
rob
ab
ilit
y
of
su
ccess
Time from onset of infection
PVE NVE
Presymptomatic
stage
Shrestha 2017
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This is the Wrong Question when
it is a matter of Operate or let die
and
Everyone gets Medical Treatment!
Medical Management or Surgery?
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0
20
40
60
80
100
120
140
160
2002 2004 2006 2008 2010 2012 2014
#
Cleveland Clinic Surgery for Active IE 2002-
2015
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Infectious Endocarditis (IE)
Disease Stages
• Bacteremia & Endocardial damage
(Valve Disease)
• Adherence
• Vegetations / Biofilm
• Embolism
• Release of Enzymes
• Tissue Disintegration
• Cusps and Leaflets
• Invasion & Destruction
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Difficult to treat: Organisms Hide and
Thrive in Vegetations / Biofilm
Wozniak DJ, Parsek MR. F1000Prime Rep 2014
• Biofilm matrix protects organism
• Planktonic cells / Persister cells
• Quorum sensing / Resistance genes
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Native Valve Endocarditis
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Prosthetic Valve Endocarditis
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LVOT
LCA
RCA
CS
AVN AVN
A-V block caused by RA Invasion and
His bundle and A-V Node destruction!
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Medical treatment YES!
What can the Surgeon add?
• Remove infected necrotic tissue and foreign material
• Restore cardiac integrity
• Restore valve function
and thereby makes the patient and infection
curable and…
• Removes a source of embolism
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Current Indications for Surgery
• Heart failure / valve regurgitation
• Unresponsive sepsis
• Advanced invasive pathology
• Infected prosthetic valve
• Large mobile vegetations, >10-15mm
• Recurrent Sepsis/IE and Prosthetic Valve
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• Neurological complication, Cerebral bleeding
• Patient is TOO old, TOO sick …
• Active local & systemic infection
• TOO difficult surgery, TOO high risk
− Highest Mortality Valve Surgery
• Questionable benefit, Lack of RCTs:
− Referral, Selection and Survival bias
Current Hesitations / Delays
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2012 - Finally ONE randomized trial!
Kang et al. Early surgery versus conventional treatment for infective endocarditis. N Engl J Med 2012;366:2466-73
University of Ulsan, Seoul, South Korea. [email protected]
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N Engl J Med Editorial:
Gordon, Steven M, Pettersson, Gosta B. Infective
Endocarditis - When Does It Require Surgery? N
Engl J Med 2012; 366;2519-2521
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Valve involved
Mitral 23 (59) 22 (59)
Aortic 11 (28) 11 (30)
Aortic and mitral 5 (13) 4 (11)
Vegetation diameter 14.1±3.5 13.5±3.2
Valvular disease:
Sev. stenosis 3 (8) 1 (3)
Sev. regurgitation 36 (92) 36 (97)
Early
Surgery
(N = 37)
no. (%)
Conventional
Treatment
(N = 39)
no. (%)
Kang et al, N ENGL MED 2012
N = 76
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Probability of Death, Embolism, or recurrent IE –
Very Different! P
rob
ab
ility
of
Com
po
site E
nd P
oin
t
1.0
0.8
0.6
0.4
0.2
0.0 0 3 6 9 12
0.3
0.2
0.1
0.0 0 3 6 9 12
P = 0.009 by log-rank test
Conventional treatment
Early surgery
Kang et al, N ENGL MED 366;26 June 2012
Months since Randomization
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Outcomes after Conventional
Treatment, N = 39 • Died 1
• Urgent surgery 27
• Discharged 11
− Sudden death 1
− Surgery 3
• Recurrent IE 1
− Symptomatic 4
−Remained asymptomatic 3
Kang et al, N ENGL MED 2012
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Implications of Kang’s RCT:
• Validated current Class I Indications
• Large Vegetations and Severe Valve Dysfunction:
Operate, don’t wait!
• Well designed RCTs are possible
• …and DO impress and move the medical
community!
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…and there seems to be minimal
penalty to be paid for operating for
IE in the active phase!
(…unless the Organism is
Insensitive to given Anti Microbial
Treatment!)
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Residual Surgical Issues
• Neurological complications
• Other embolic complications
− Spleen, spine, other
− Mycotic aneurysms
• High early mortality
−Highest risk valve surgery!
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YANAGAWA ET AL CIRCULATION 2016
IE & STROKE: Early vs. Delayed Surger?
No Dogmas – risk vs. benefits!
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18% Aortic &
Mitral
n = 773
31% Mitral
51% Aortic
CCF Active Left-sided IE 2002-12
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1% Previous Repair n = 395
58% PVE 41% NVE
Isolated Aortic Valve IE (AV)
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9% Previous
Repair
n = 237
28% PVE 63% NVE
Isolated Mitral Valve IE (MV)
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20
40
60
80
100
0 1 2 3 4 5 6 7
Years
%
NVE
PVE
P=.6
Survival: Native vs. Prosthetic Valve IE
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20
40
60
80
100
0 1 2 3 4 5 6 7
%
Years
Survival: Non-Invasive vs. Invasive IE
Invasive
p=0.01
Non-Invasive
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20
40
60
80
100
1 2 3 4 5 6 7
Years
%
0
AV
MV
AV+MV Aortic P=.75
Mitral P=.001
AV+MV P=.02
Non-Invasive vs. Invasive IE by Valve
Invasive
Non-Invasive
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20
40
60
80
100
0 1 2 3 4 5 6 7
%
Years
Invasive p=0.001
Non-Invasive
MV: Non-Invasive vs. Invasive IE
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Mitral
0 20 40 60 80 100 20
0
20
40
60
80
100
120
140
160
180
Low Propensity Score (%) High Risk
Nu
mbe
r o
f P
atie
nts
Aortic
Invasiv
e V
alv
e
MV Patients’ Propensity Scores (55)
55 matched pairs: Blue = AV
Green = MV
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20
40
60
80
100
1 2 3 4 5 6 7
Years
%
0
AV-unmatched
AV-matched MV-matched
MV-unmatched
Non-Invasive vs. Invasive: AV vs. MV (Matched vs. Unmatched)
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2. MV Pathology:
MV Invasion is to AV grove!
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Invasive Disease by Involved Valve Invasion only on left side!
%
100
60
20
0 Aortic
Invasive
Non-Invasive
40
80
Mitral AV+MV Right Sided
69% 35%
68%
0.7%
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Right-Sided IE
• More often I.V. Drug Use
• Septic Pulmonary Embolism
• Non-Invasive / Still Staph. Aureus
• Indications for surgery
− Large Vegetations / Embolism Prevention
− Severe TR with CHF and elevated PVR / low CO
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IE SURGERY IS NOT EASY: 4 months post 2nd Homograft reoperation for
endocarditis – dehisced homograft!
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Reoperation or Hospice??
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Pitfalls
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Pitfalls
• Too Late - Preoperative Stroke
• Too Early - Hemorrhagic stroke
• Organism insensitive to given antimicrobial
• Incomplete debridement
• Missed invasive lesions = Incomplete debridement
• Misinterpretation of Anatomy and Pathology
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The Surgeons cannot avoid Referral
and Survival Bias!
• Referral bias = Appropriate patient selection!
• Survival bias = Surgeons can only consider
surgery on live patients!
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Endocarditis Survival
Natural and Modified History 100
80
60
40
20
0 0 2 4 6 8 10 12
Months
%
Staph Aureus
Acute IE
Strep Viridans
Sub Acute IE
Medical
+ Surgical
GP, SH, NS, EHB 2017
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Probability of success with medical
therapy in endocarditis P
rob
ab
ilit
y
of
su
ccess
Time from onset of infection
PVE NVE
Presymptomatic
stage
Shrestha 2017
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Once there is an indication for surgery –
OPERATE!
• Leaky valves won’t become competent!
• Disintegrated tissue will not regrow!
• Infective endocarditis is not a reason to postpone
an operation otherwise indicated but the opposite!
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Should all PVE be Treated
Surgically?
Yes, unless
• very recent onset
• uncertain diagnosis and good valves
• …and minimal echo findings, bacteremia cleared, no
further embolic events, and patient is well!
• prohibitively high surgical risk
− Low expectation of success and close follow up
47
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Success with endocarditis surgery
requires experience, lots of experience!
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