troponin use it in all patients with acute heart failure contra

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

This should

be a real shoot out!

LOVE BIOMARKERS

HATE BIOMARKERS

One of us is an asshole!

Maisel, JaffeJanuzziDeFillipiMorrowMuellerAnkerFilippatos

Gottlieb PackerStevenson

+ 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

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

Its my job to unmask the true issues surrounding this debate

+Excessive Shortness of BreathWe Need Rapid and Accurate

Diagnosis and treatment

THIS COULD BE YOUR MOTHER

Goals in Diagnosis-

nFor your mothern Rapid n Highly accuraten Non-invasive, if at all possiblen Spare no expense

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

+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.

+ 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

+ Frank has used the cxr to set up his profitable online dating service

What is our natural instinct for these dyspneic patients?

“Well, Bob, it looks like a paper cut, but just to be sure. Let’s get an echo.”

+ 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?

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

+ Precipitating causes of acute decompensated heart failure

Nieminen MS et al. Eur Heart J 2006;27:2725–2736

High Sensitivity Troponin

How’s your cardiologist

feel about this?

“Cards to See for Elevated Troponin”

Once a Troponin is “elevated”, the cat is out of the bag

+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!”

*

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

+ 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

+

Cappadocia

sST-2

Troponin

Kidney

PCT

Natriuretic peptides

Ddimer

+

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

+

* 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%

+

McCullough, Maisel et al., Circulation 2002 106:416-422

BNP levels adds to the physicianBNP levels adds to the physician’’s abilitys ability

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

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

Troponin and BNP Can work together

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

+

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)

+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

+Prognostic implications of a rising cTnT levelRELAX-AHF

Metra M. et al. J Am Coll Cardiol. 2013;61:196-206

+hs cTnT change during acute HF hospitalizationInsights from RELAX-AHF

Metra M. et al. J Am Coll Cardiol. 2013;61:196-206

+ 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.

+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

+Serial BNP for Guiding Treatment Serial BNP for Guiding Treatment During Hospitalization?During Hospitalization?

Courtesy of Damien Logeart.

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

+ The discharge NP level may be the most The discharge NP level may be the most important level of all!!!important level of all!!!

HistoryPhysical examCXR

Troponins??

+ What about HFPEF?

Paulus WJ, JACC 2013, Stasch JP JCI, 2006

Can Troponin out perform clinical judgement?

This should probably be studied in the ED, like it was for heart

failure

Guess my Tropo

nin

+ What about Jenner differences?Gender

à Women are more complex than men!

+ 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

+ 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

+ 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?

+

I think we caught you a little naked here, Frank !

+ 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

+ Biomarkers are clinical TOOLS.

+ A hammer is a GOOD tool…

+ …but a fool with a good tool is STILL a fool.

+ rebuttal

+ Markers Rule!

I

Markers

+

+

A quiz for Parents

Frank Peacock MD

+

Your child is being eaten by a camel. Do you……

a) Save your child. or

b) Take a photo

+

+ 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.

+ 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

+A CALL TO ACTION: THE TIME IS NOW

nGOOD BIOMARKERS ARE AVAILABLEnNATRIURETIC

PEPTIDESnTROPONINnST-2nPROCALCITONINnBUNnCREATININE

+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

= dead or LVAD (n=6)

+

+ 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.

+Stratifying short-term risk after AHFWorking together to improve short-term outcomes?

Biomarker Integration in Discharge Planning

sST2

A combination of Natriuretic Peptide and PCT can be used to better diagnose dyspneic patients

Maisel Eur J HF 2012

Improved Management of heart failure with ProcAlCiTonin

Biomarkers willMake bad doctors worse and good doctors better!

+

Being an MD at a distance Football game Airport getting phone calls

…or just relaxing

Being an MD at a distanceWhat’s

his BNP ?Can I join?

+ Being an MD at a distanceAirport get phone calls

Watching Television

Or just relaxing

What’s hisBNP ?

Can I

join?

+