troponin use it in all patients with acute heart failure contra
TRANSCRIPT
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HistoryPhysical examCXR
Director Coronary Care Unit And Heart Failure Program San Diego Veterans Hospital
Alan Maisel MD
Professor of Medicine, University of California, San Diego
We don’t need Troponins in Heart Failure- Not yet anyway
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This should
be a real shoot out!
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LOVE BIOMARKERS
HATE BIOMARKERS
One of us is an asshole!
Maisel, JaffeJanuzziDeFillipiMorrowMuellerAnkerFilippatos
Gottlieb PackerStevenson
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+ The Ideal Biomarker
2007 2011
Sensitive and specific Either highly sensitive (diagnosis) OR highly specific (treatment effect)
Reflects disease severity Reflects abnormal physiology/biochemistry
Correlates with prognosis Prognosis is most meaningful if level is clinically actionable
Should aid in clinical decision making Should be used as a basis for specific “biomarker guided-therapy”
Level should decrease following effective therapy “Bio-monitoring” during treatment is an effective surrogate of improvement
Maisel, JACC 2011
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Sensitive and specific Either highly sensitive (diagnosis) OR highly specific (treatment effect)
YES NO
Reflects disease severity Reflects abnormal physiology/biochemistry
YES Sort of
Correlates with prognosis Prognosis is most meaningful if level is clinically actionable
YES Prognostic but is it clinically actionable?
Should aid in clinical decision making
Should be used as a basis for specific “biomarker guided-therapy”
YES NO EVIDENCE
Level should decrease following effective therapy
“Bio-monitoring” during treatment is an effective surrogate of improvement
PROBABLY NO EVIDENCE
Definition of Biomarker Definition of Biomarker
2007 2011 TROPONIN –FOR ACS TROPONIN FOR AHF
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Its my job to unmask the true issues surrounding this debate
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+Excessive Shortness of BreathWe Need Rapid and Accurate
Diagnosis and treatment
THIS COULD BE YOUR MOTHER
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Goals in Diagnosis-
nFor your mothern Rapid n Highly accuraten Non-invasive, if at all possiblen Spare no expense
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Goals in Diagnosis at Baylor
nFor your mother-in-lawn No rush n Mistakes happenn Invasive studies, got no problem with thatn She is cheap, dont go wasting money
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+Signs and Symptoms of HFSigns and Symptoms of HF
nShortness of breath
nEdema
nNeck vein Distension
nS-3
Francis G.S. A M J Med. 2001; 110 (suppl 7A): 375-465.
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+ A chest x-ray can NEVER rule out acute heart failure!
Misses 20% of Echocardiogram proven cardiomegaly
Even worse if done portable
Diagraghm not well distended
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+ Frank has used the cxr to set up his profitable online dating service
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What is our natural instinct for these dyspneic patients?
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“Well, Bob, it looks like a paper cut, but just to be sure. Let’s get an echo.”
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+ Questions about Myocardial Injury and Troponin elevation in AHFn Cause or effect?
n Time course?n Pre-hospitaln In-hospital
n What can we do to prevent or ameliorate it?
n What should we do when it is present?
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Definition of Biomarker Definition of Biomarker
2007 2011 TROPONIN –FOR ACS TROPONIN FOR AHF
Sensitive and specific Either highly sensitive (diagnosis) OR highly specific (treatment effect)
YES NO
Reflects disease severity
Reflects abnormal physiology/biochemistry
YES Sort of
Correlates with prognosis Prognosis is most meaningful if level is clinically actionable
YES YES but what are we going to do about it.
Should aid in clinical decision making
Should be used as a basis for specific “biomarker guided-therapy”
YES NO EVIDENCE
Level should decrease following effective therapy
“Bio-monitoring” during treatment is an effective surrogate of improvement
PROBABLY NO EVIDENCE
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+ Precipitating causes of acute decompensated heart failure
Nieminen MS et al. Eur Heart J 2006;27:2725–2736
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High Sensitivity Troponin
How’s your cardiologist
feel about this?
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“Cards to See for Elevated Troponin”
Once a Troponin is “elevated”, the cat is out of the bag
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+Quote -4-24-09 San Diego Biomarker Meeting R. Jesse MDn “Troponin was great when it was a crappy assay.”
n “Now that it is a good assay, it sucks!”
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*
Detection of hsTnI vs hsTnT in Aussie Normals…
%Detected (>LoD)
100% ARCH hsTnI70% Roche hsTnT10% ARCH TnI
Hickman P, and Koerbin, et. alACT Pathology, Poster 2011
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+ Stages of Heart FailurePrevalence of cTn elevation
D
C
B
A
cTn 25-50%hsTnI ~ 100%
cTnT 10%hsTnT 92%
cTn 0.7-8%hsTnT 25-70%
Symptoms
Structural Abnormalities
Risk Factors
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+
Cappadocia
sST-2
Troponin
Kidney
PCT
Natriuretic peptides
Ddimer
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+
Maisel AS et al. N Engl J Med. 2002;347:161-167.
1.0
0.8
0.6
0.4
0.2
0.0
0.0 0.2 0.4 0.6 0.8 1.0
1-Specificity
Sens
itivi
ty
Final Diagnosis Heart Failure
Final Diagnosis NOT Heart Failure
BNP 100 pg/mL“Test positive”
673 227
BNP <100 pg/mL“Test negative”
71Sensitivity
=90%
615Specificity
=73%
Positivepredictive value=75%
Negative predictive value=90%
BNP=50 pg/mL
BNP=80 pg/mL
BNP=100 pg/mL
BNP=150 pg/mL
BNP=125 pg/mL
Accuracy is 90%Accuracy is 90%
Optimal cut-off point determined @ 100 pg/mL
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+
* P <0.0001
Clarification of Diagnosis & BNPClarification of Diagnosis & BNPIn
deci
sion 43%
11%0%5%
10%15%20%25%30%35%40%45%
Clinical Evaluation
Clinical Evaluation and BNP
BNP reduces clinical indecision by 74%
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+
McCullough, Maisel et al., Circulation 2002 106:416-422
BNP levels adds to the physicianBNP levels adds to the physician’’s abilitys ability
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Definition of Biomarker Definition of Biomarker
2007 2011 TROPONIN –FOR ACS TROPONIN FOR AHF
Sensitive and specsific Either highly sensitive (diagnosis) OR highly specific (treatment effect)
YES NO
Reflects disease severity Reflects abnormal physiology/biochemistry
YES Sort of
Correlates with prognosis Prognosis is most meaningful if level is clinically actionable
YES YES but is it clinically actionable?
Should aid in clinical decision making
Should be used as a basis for specific “biomarker guided-therapy”
YES NO EVIDENCE
Level should decrease following effective therapy
“Bio-monitoring” during treatment is an effective surrogate of improvement
PROBABLY NO EVIDENCE
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In-Hospital Mortality According to Conventional cTnI or cTnT Quartile
Patients with Acute Decompensated Heart Failure
Peacock WF IV et al. N Engl J Med 2008;358:2117-2126.
Ischemic heart disease was NOT a useful discriminator of troponin statusor mortality with a positive troponin result
Data from the ADHERE Registry
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Troponin and BNP Can work together
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In-Hospital Mortality Risk by Initial BNP and Cardiac Troponin Levels
48,629 (63%) out of 77,467 pt episodes had BNP assessment at initial evaluation42,636 (87.6%) with troponin I or T along with BNP levelsFonarow GC Am J Card 2008;101:231-7.
P<0.0001
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+
SampleSample
Changes in hscTnl (Nanosphere) and Mortalityin Acute Heart Failure
Euro J Hrt Failure, January 2011Euro J Hrt Failure, January 2011
Mortality and readmissionMortality and readmission(38 subjects)(38 subjects)
Trop
onin
I (n
g/L)
Trop
onin
I (n
g/L)
Event freeEvent free(106 subjects)(106 subjects)
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+hscTnl (Nanosphere) and Mortality inAcute Heart Failure
Eve
nt fr
eeE
vent
free
(dea
th o
r rea
dmis
sion
)(d
eath
or r
eadm
issi
on)
Euro J Hrt Failure, Jan 2011Euro J Hrt Failure, Jan 2011DaysDays
Troponin <23.25 ng/LTroponin <23.25 ng/L(59 subjects)(59 subjects)
Troponin >23.25 ng/LTroponin >23.25 ng/L(85 subjects)(85 subjects)
Discharge TroponinDischarge Troponin
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+Prognostic implications of a rising cTnT levelRELAX-AHF
Metra M. et al. J Am Coll Cardiol. 2013;61:196-206
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+hs cTnT change during acute HF hospitalizationInsights from RELAX-AHF
Metra M. et al. J Am Coll Cardiol. 2013;61:196-206
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+ Changes in BNP Mirror changes in PAW* Changes in BNP Mirror changes in PAW* During Treatment of Acute Heart FailureDuring Treatment of Acute Heart Failure
Kazenegra, Maisel, A. et al. J Cardiac Failure, Vol. 7, No. 1, 2001
N = 15 (responders)
PAW
(mm
Hg)
Hours
BN
P (pg/ml)
15171921232527293133
baseline 4 8 12 16 20 24 6007008009001000110012001300
PAWBNP
*Pulmonary artery wedge.
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+BNP trends during hospitalization and BNP trends during hospitalization and subsequent prognosis upon hospital subsequent prognosis upon hospital dischargedischarge
Highest baseline, greatest change;
highest discharge level= worse
prognosis
Lowest Pre-dischargeBNP= best prognosis
LowestBaseline
BNP Level=second best prognosis
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+Serial BNP for Guiding Treatment Serial BNP for Guiding Treatment During Hospitalization?During Hospitalization?
Courtesy of Damien Logeart.
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Logeart D et al. J Am Coll Cardiol 2004;43(4):635-41.
Dea
th o
r R
eadm
issi
on (%
)
Follow-Up (Days)
100
75
50
25
0
0 30 60 90 120 150 180
Predischarge BNP >700 ng/Ln=41, events=38
p<0.0001
p<0.0001
1
5.1
15.2
Hazard Ratiosof 2nd and 3rd
Versus 1st BNP Range
Predischarge BNP 350-700 ng/L n=50, events=30
Predischarge BNP <350 ng/Ln=111, events=18
BNP on Discharge Predictive of EventsBNP on Discharge Predictive of Events
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+ The discharge NP level may be the most The discharge NP level may be the most important level of all!!!important level of all!!!
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HistoryPhysical examCXR
Troponins??
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+ What about HFPEF?
Paulus WJ, JACC 2013, Stasch JP JCI, 2006
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Can Troponin out perform clinical judgement?
This should probably be studied in the ED, like it was for heart
failure
Guess my Tropo
nin
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+ What about Jenner differences?Gender
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à Women are more complex than men!
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+ The Ideal Biomarker
2007 2011
Sensitive and specific Either highly sensitive (diagnosis) OR highly specific (treatment effect)
Reflects disease severity Reflects abnormal physiology/biochemistry
Correlates with prognosis Prognosis is most meaningful if level is clinically actionable
Should aid in clinical decision making Should be used as a basis for specific “biomarker guided-therapy”
Level should decrease following effective therapy “Bio-monitoring” during treatment is an effective surrogate of improvement
Maisel, JACC 2011
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+ What we know
n It is elevated in most patients with acute heart failure
nThe higher it is the worse the outcomes
n Its better of it goes down during hospitalization than if it doesn’t
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+ What we don’t know- and we need to know before we regularly use troponins
n Is there a certain elevation above which we should start an ACS work-up? ( heparin, ASA, maybe cath)
n If elevated, what do we do?n Admit?n Start meds that reduce subendocardial ischemia (nitrates,
etc)?
n If it is still high at discharge what do we do?n Cath?n Early follow up?n More vigorous medical Rx?
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+
I think we caught you a little naked here, Frank !
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+ Frank’s Assessment of Patient with Dyspnea
For Your Mothern History, physical exam by
top gun attending
n Pulse oximetry
n ECG within 5 minutes
n CBC, chem panel
n BNP or NT-pro BNP
n sST2
n D-dimer, if indicated
n CXR PA and Lateral
n Troponin- maybe one
• Wait in a side room for a few hours
• History, physical exam by 1st year med student
• ABG• Portable CXR• 25 troponins and• Rectal exam
Mother-in-law
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+ Biomarkers are clinical TOOLS.
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+ A hammer is a GOOD tool…
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+ …but a fool with a good tool is STILL a fool.
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+ rebuttal
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+ Markers Rule!
I
Markers
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+
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+
A quiz for Parents
Frank Peacock MD
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+
Your child is being eaten by a camel. Do you……
a) Save your child. or
b) Take a photo
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+
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+ Number of HF Biomarker Reports in PubMed in the past 10 years
BNP introduced into clinical practice
All publications
HF biomarker pubs
van Kimmenade & Januzzi. Clin Chem 2012.
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+ Stratifying risk of readmission after Acute HF
The Cardiologist and HospitalSame game, but different perspective
The Cardiologist: the long view The Hospital: short-term accuracy
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+A CALL TO ACTION: THE TIME IS NOW
nGOOD BIOMARKERS ARE AVAILABLEnNATRIURETIC
PEPTIDESnTROPONINnST-2nPROCALCITONINnBUNnCREATININE
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+Mortality Risk Increases With ST2 Levels
Rehman SU, Mueller T, Januzzi JL et al. J Am Coll Cardiol. 2008;52:1458-65.
One
Yea
r M
orta
lity
(%)
ST2 Decile
One-year mortality exceeded 50% in the highest decile.
1 2 3 4 5 6 7 8 9 10
60
50
40
30
20
10
0
P < 0.001
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= dead or LVAD (n=6)
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+
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+ Multivariate Analysis of ST2, BNP, and cTnT: Serial ST2 Testing Dominates Multimarker Model
P < 0.001
Saenger AK, Miller WL, Lueke AJ et al. Circulation. 2012;126:A19365.
P<0.001 P = 0.02
Outcomes: Heart failure hospitalization, transplant or death. Patients followed for 2 years.
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+Stratifying short-term risk after AHFWorking together to improve short-term outcomes?
Biomarker Integration in Discharge Planning
sST2
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A combination of Natriuretic Peptide and PCT can be used to better diagnose dyspneic patients
Maisel Eur J HF 2012
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Improved Management of heart failure with ProcAlCiTonin
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Biomarkers willMake bad doctors worse and good doctors better!
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+
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Being an MD at a distance Football game Airport getting phone calls
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…or just relaxing
Being an MD at a distanceWhat’s
his BNP ?Can I join?
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+ Being an MD at a distanceAirport get phone calls
Watching Television
Or just relaxing
What’s hisBNP ?
Can I
join?
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+