Hit the road Jack!

W. FRANK PEACOCK, MD, FACEP, FACC

Visits130,000,000annually

6.24 Msuspected or actual

cardiac4.1 Msent home non-cardiac

50,000 MIs

3.1 Mnon-cardiac

(50%)

10.4 M chest pain (8.0%)

1.2 MAMI(20%)

1.5 MUA

(24%)

374,400sudden death

(6%)

Myocardial Pain

PneumoniaPneumothorax

Sickle cell

Anemia

Pulmonary Embolus

Musculoskeletal Pain

Aortic Dissection

Mondor’s

SyndromeTietze’s

disease

Herpes

Zoster

Blunt Chest Trauma

Breast

Cancer

Breast Abcess

Contact

Dermatitis

GERD

Boerhave’s

Mallory-

Weiss

Mediastinitis

Lung

Cancer

Anxiety Panic Attack

Breast Implant

Thoracic

Spine Ds

Subdiaphrag

Abcess

Empyema

Amniotic Fluid

Embolus

IVDA Pulm Infarction

Asthma

HsTn (STATISTICAL)DefinitionYoucan’thaveitbothways

Sensitivity

TP/(TP+FN)

Specificity

TN/(TN+FP)

How often is the EKG diagnostic?

2%

N=10,869Pope JH, et al. Missed Diagnosis of Acute Cardiac Ischemia in the ED, NEJM 2000;342:1163-70

10.4 million annual ER CPSTEMI = 208,000

3500 ER’s = 59 STEMI/ER/yr

No ECG ∆ = 10,192,000/yr= 2,912/ER/yr= to find 59

How good are the parts?Than M. Lancet, 2011. DOI:10.1016/S0140-6736(11)60310-3

Sensitivity NPVECG 35.2 89.3POC markers 82.9 96.1TIMI 96.7 97.5POC + ECG 88.8 96.7TIMI + ECG 98.1 98.3ADP 99.3 99.1

How often is the Tn diagnostic?

8%

N=10,869Pope JH, et al. Missed Diagnosis of Acute Cardiac Ischemia in the ED NEJM 2000;342:1163-70

10.4 million annual ER CPTotal NSTEMI = 822,0003500 USA ER’s = 238/ER/yr

9,568,000 –Tn/yr2733 -Tn/ER to find 238

What is the fastest troponin? POC vs the central lab.Locale Hosp

TypeTransp POC

TnCL

CKMBDiff

(mins)ED Univ Pneumo

tube21±0.2(n=1879)

107±2.3(n=1744)

86±2.3

ED Univ Courier 22±0.5(n=855)

72±1.7(n=689)

50±1.5

CCU Rural Nurses 12±0.5(n=471)

147±64.1(n=150)

135±64.1

ED Muni Pneumotube

22±0.8(n=706)

90±0.5(n=185)

68±1.1

ED Univ Pneumo tube

18±0.5(n=698)

52±1.4(n=679)

34±1.4

All 20±0.2(n=4609)

85±1.5(n=3447)

65±1.5

Gaze D et al. Point of Care: The Journal of Near-Patient Testing & Technology. 2004;3:156–158.

5 hospitals4609 Tn POC samples

3447 split and sent to lab for CKMB

How good are the parts?Than M. Lancet, 2011. DOI:10.1016/S0140-6736(11)60310-3

Sensitivity NPVECG 35.2 89.3POC markers 82.9 96.1TIMI 96.7 97.5POC + ECG 88.8 96.7TIMI + ECG 98.1 98.3ADP 99.3 99.1

Howsensitivedoesithavetobe?

• 100,000AnnualERvisits• 8%CP=8k/yr =22/day

• Sn=95%– Miss5outof100– Miss1AMIevery4.5days

• Miss81AMI/yr

• Sn=99.5%– Miss1outof200– Miss1every9days

OK it has to go to the lab, but how about one and done???

Whyisn’t1troponinenough?

• ADAPTandAPACEhadpresentationsat~4hours………….

• Yourcutpoint is?Letssay13pg/mL– Mrs Jonesnormallylivesat4– Shepresents45minutesafterCPonset– Tn is12(300%increasefrombaseline)

Oneanddone?• Metaanalysisof23papers– Elecsys hs TnT atEDpresentation– LOD=5ng/L,LOQ=13ng/L

(thelowestTnT thathasCVof≤10%)

– 99th%ile ofhealthypop=14ng/L• Results

– N=9428– Pre-testprobabilityofAMI21%– Mostpatientspresentedwithin12hrs ofsymptomonset• studymedians3.5-6.3hrs

• Using14ng/Lcutpoint– Sn=89.5%

• (95%CI86.3%to92.1%),

– Sp=77.1%(68.7%to83.7%).

• Cutpoints determinemissrate– For100consecutivepatients– 5ng/Lwillmiss2-3AMI– 3ng/Lwillmiss0AMI

BMJ

Reichlin T. N Engl J Med 2009;361:858-67.

718 consecutiveED suspect AMI

MI/USA 238 (33.1%)

Chest Pain Protocol VS. ADP

A CHEST PAIN PROTOCOL

A series of activities to identify a patient as:

1) Having an event

2) Being at risk for having an event

AN ACCELERATED DIAGNOSTIC PROTOCOL

A series of activities to identify the patient as:

1) NOT having an event

2) Being at low risk for having an event

WhyanADP?AcceleratedDiagnosticProtocol

• ReasonforanADP• ERdocsvsriskscores

–Docsareriskadverse–Docsalwaysadmitmorethanscores

Whydoweadmitsooomany?

LAWYER

ER Dr.

ADP is for discharging! Maybe that is a good idea?

ADP1) Non-Dx ECG2) (-) Tn x23) Low Risk Score

Risk Scores▪TIMI▪HEART▪EDACS▪CRUSADE▪GRACE

TIMI Risk Score: 2 week MACE

4.78.3

13.2

19.9

26.2

40.9

051015202530354045

0/1 2 3 4 5 6/7

▪ Risk factors:▪ Age ≥65 years▪ ≥3 risk factors for CAD▪ Prior coronary stenosis ≥50%

▪ ST-segment deviation on ECG

▪ ≥2 anginal events in last 24 hours

▪ Use of ASA in last 7 days▪ Elevated serum cardiac

markers CK-MB or troponin

Each risk factor is = 1 point, and total represents TIMI Risk ScoreEvent rates (all-cause mortality, MI, or UTVR) increase with each 1-point increase in score

Number of Risk Factors1R

ate

of C

ompo

site

En

dpoi

nt

(Day

s 1-

14),

%

Antman EM et al. JAMA. 2000;284:835-842.

How good are the parts?Than M. Lancet, 2011. DOI:10.1016/S0140-6736(11)60310-3

Sensitivity NPVECG 35.2 89.3POC markers 82.9 96.1TIMI 96.7 97.5POC + ECG 88.8 96.7TIMI + ECG 98.1 98.3ADP 99.3 99.1

HEART Score for 6 week MACE

Hx: Hi =2, Mod =1, Slight =0

ECG: Sig ST dep =2, NS repol =1, Nl =0

Age: ≥65 =2, 45-65 =1, ≤ 45 =0

Risks: ≥3 =2, 1-2 =1, 0=0

Tn: ≥3x ULN =21-3 ULN =1≤ ULN =0

Low risk = 0-3; <2% MACE risk

RISKSHyperchole, HTN, DMTobbacco(+) FH, Obesity

MACE = AMI, PCI, CABG, (+) cath, death

HEART Pathway Randomized Trial

▪ 282 ED suspected ACS patients, randomized to HEART or standard tx

▪ HEART N=141, with score < 4, negative Tn at 0 and 3 hours▪ 75 low risk, 56 discharged

▪ Standard care N=141, per ACC/AHA guidelines▪ X low risk, 26 discharged.

▪ Results: No MACE in either arm▪ HEART lower objective cardiac testing; 68.8 vs 56.7% (P=0.048)▪ lower LOS; 9.9 vs 21.9 hours (P=0.013)▪ higher early discharges by 21.3% (39.7% versus 18.4%; P<0.001).

Mahler S. Circ Cardiovasc Qual Outcomes. 2015 March ; 8(2): 195–203

EDACS-ADPEmergency Department Assessment Chest Pain Score -Accelerated Diagnostic Procedure

Characteristic Parameter Points

History 18-50 yo with CAD, or >2 risk factors

+4

Age 18-45 +2

46-50 +4

51-55 +6

56-60 +8

61-65 +10

66-70 +12

71-75 +14

76-80 +16

81-85 +18

>85 +20

Characteristic Parameter Points

Sex Male +6

Signs and Symptoms

Diaphoresis +3

Arm or shoulder radiation

+5

Painoccurred or worsened with inspiration

-4

Pain is reproduced with palpation

-6

Low Risk Criteria§EDACS Score <16§No new ECG ischemia §Negative 0 and 2h Tn

PEARLComparing Scores

▪ PEARL data set: 7 EdsN=458

▪ Patient with suspected ACS

▪ Dr documented risk of MI before Tn results asLow, Moderate, or High

TIMI

GRACE

HEART-2

EDACS

HEART-1

Singer A. Am JEM, 2017, Jan 5. pii: S0735-6757(17)30003-7. doi: 10.1016/j.ajem.2017.01.003. [Epub ahead of print]

Scores: standard cutpointLow risk

definition

N % with AMI Sensitivity

Clinical Low 136 5.9 (3.0-11.2) 88.7 (78.5-94.7)

HEART 0-3 146 4.1 (1.9-8.7) 91.5 (81.9-96.5)

TIMI 0 26 0 (0-12.9) 100 (93.6-100)

GRACE <51 14 7.1 (1.3-31.5) 98.6 (91.4-99.9)

EDACS <16 195 1.0 (0.2-4.1) 97.1 (89.1-99.5)

Singer A. Am J EM. 2017 Jan 5. pii: S0735-6757(17)30003-7. doi: 10.1016/j.ajem.2017.01.003.

Performance: Sensitivity set at 99% Sensitivity set at 99%

Cutoff % Low Risk Clinical -- --HEART-1 0 1HEART-2 0-2 18.9TIMI 0 7GRACE 49 3.2EDACS 12 34.3

Singer A. Am J EM. 2017 Jan 5. pii: S0735-6757(17)30003-7. doi: 10.1016/j.ajem.2017.01.003.

How many will the ADP D/C?10.4 million annual ER CP 3500 USA ER’s

ED D/C rate # of patients7.0 (TIMI) 728,000

18.9 (HEART) 1,965,60034.3 (EDACS) 3,567,20077% (TRAPID) 8,008,000

HighSensitivityTroponinintheUSA

• FDAclearsbloodtesttohelpdiagnosepatientswithasuspectedMI

• Jan19,2017– TheFDAgranteda510(k)clearancefortheElecsys TroponinTGen5STATbloodtestforpatientswithasuspectedMI.

Patie

nts

Dis

char

ged

Early

(%)

1) Than M, Cullen L, Reid C, et al. Lancet. 2011;377:1077-84. 2) Than M, Cullen L, Aldous S, et al. J Am Coll Cardiol. 2012;59(23):2091-8.3) Cullen L, Mueller C, Parsonage WA, et al. J am Coll Cardiol. 2013;62(14):1242-9. 4) Mueller C, Giannitsis E, Christ M, et al. Ann Emerg Med. 2016;68(1):76-87.

TRAPID-AMI4cTnT ≤ 12 ng/L; Δ1 hour ≤ 3 ng/L

APACE3

cTnI ≤ 26.2 ng/LASPECT1

cTnI ≤ 50 ng/LADAPT2

cTnI ≤ 30 ng/L

70

60

50

40

30

20

10

0

Increased Troponin Sensitivity = More ED Discharges

38.6

20.0

63.4

9.8

2015 ESC Guidelines

▪ The NPV for MI in patients assigned ‘rule-out’ exceeded 98% in several large validation cohorts

Eur Heart J. 2016Jan 14;37(3):267-315.

Will the ESC guidelines work in the US?

▪ hscTnT and I at 0 and 3 h post-presentation

▪ Purpose: validate the ESC Working Group on Acute Cardiac Care rule-in algorithm

1061 hsTnI985 hsTnT

Sn of 99th %ileto R/O AMIHsTnI 93.2%HsTnT 94.8%

Pickering JW, et al. Heart 2016;0:1–9.

How quickly can I make a decision?

▪ECG… 10’▪Tn (central lab)… 90’

▪Risk Score (EDACS)▪Some admitted

▪Repeat Tn @ 3 hrs▪Returns for decision…. ~4 hours