Hit the road Jack! W. FRANK PEACOCK, MD, FACEP, FACC

Hit the road Jack! W. FRANK PEACOCK, MD, FACEP, FACC

Visits 130,000,000 annually 10.4 M chest pain (8.0%) 4.1 M sent home non-cardiac 6.24 M suspected or actual cardiac 50,000 MIs 3.1 M non-cardiac (50%) 1.2 M AMI (20%) 1.5 M UA (24%) 374,400 sudden death (6%)

Musculoskeletal Pain Blunt Chest Trauma Mediastinitis IVDA Pulm Infarction Anxiety Pulmonary Embolus Panic Attack Breast Abcess Aortic Dissection Pneumothorax Empyema Pneumonia Breast Implant Tietze s disease Mondor s Syndrome Thoracic Spine Ds GERD Asthma Herpes Zoster Contact Dermatitis Breast Cancer Mallory- Weiss Subdiaphrag Abcess Sickle cell Anemia Lung Cancer Amniotic Fluid Embolus Myocardial Pain Boerhave s

Hs Tn (STATISTICAL) Definition You can t have it both ways Sensitivity Specificity TP/(TP+FN) TN/(TN+FP)

How often is the EKG diagnostic? 2% 10.4 million annual ER CP STEMI = 208,000 3500 ER s = 59 STEMI/ER/yr No ECG = 10,192,000/yr = 2,912/ER/yr = to find 59 N=10,869 Pope JH, et al. Missed Diagnosis of Acute Cardiac Ischemia in the ED, NEJM 2000;342:1163-70

How good are the parts? Than M. Lancet, 2011. DOI:10.1016/S0140-6736(11)60310-3 Sensitivity NPV ECG 35.2 89.3 POC markers 82.9 96.1 TIMI 96.7 97.5 POC + ECG 88.8 96.7 TIMI + ECG 98.1 98.3 ADP 99.3 99.1

How often is the Tn diagnostic? 8% 10.4 million annual ER CP Total NSTEMI = 822,000 3500 USA ER s = 238/ER/yr 9,568,000 Tn/yr 2733 -Tn/ER to find 238 N=10,869 Pope JH, et al. Missed Diagnosis of Acute Cardiac Ischemia in the ED NEJM 2000;342:1163-70

What is the fastest troponin? POC vs the central lab. 5 hospitals 4609 Tn POC samples 3447 split and sent to lab for CKMB Locale Hosp Type Transp POC Tn ED Univ Pneumo tube ED Univ Courier 22±0.5 (n=855) 21±0.2 (n=1879) CCU Rural Nurses 12±0.5 (n=471) ED Muni Pneumo 22±0.8 (n=706) tube ED Univ Pneumo 18±0.5 tube (n=698) All 20±0.2 (n=4609) CL CKMB 107±2.3 (n=1744) 72±1.7 (n=689) 147±64.1 (n=150) 90±0.5 (n=185) 52±1.4 (n=679) 85±1.5 (n=3447) Diff (mins) 86±2.3 50±1.5 135±64.1 68±1.1 34±1.4 65±1.5 Gaze D et al. Point of Care: The Journal of Near-Patient Testing & Technology. 2004;3:156 158.

How good are the parts? Than M. Lancet, 2011. DOI:10.1016/S0140-6736(11)60310-3 Sensitivity NPV ECG 35.2 89.3 POC markers 82.9 96.1 TIMI 96.7 97.5 POC + ECG 88.8 96.7 TIMI + ECG 98.1 98.3 ADP 99.3 99.1

How sensitive does it have to be? 100,000 Annual ER visits 8% CP = 8k/yr = 22/day Sn = 95% Miss 5 out of 100 Miss 1 AMI every 4.5 days Miss 81 AMI/yr Sn=99.5% Miss 1 out of 200 Miss 1 every 9 days

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

Why isn t 1 troponin enough? ADAPT and APACE had presentations at ~4 hours. Your cutpoint is? Lets say 13 pg/ml Mrs Jones normally lives at 4 She presents 45 minutes after CP onset Tn is 12 (300% increase from baseline)

Meta analysis of 23 papers Elecsys hs TnT at ED presentation LOD=5 ng/l, LOQ=13 ng/l (the lowest TnT that has CV of 10%) 99th %ile of healthy pop =14 ng/l Results N=9428 Pre-test probability of AMI 21% Most patients presented within 12 hrs of symptom onset study medians 3.5-6.3 hrs One and done? Using 14 ng/l cutpoint Sn= 89.5% (95% CI 86.3% to 92.1%), Sp=77.1% (68.7% to 83.7%). Cutpoints determine miss rate For 100 consecutive patients 5 ng/l will miss 2-3 AMI 3 ng/l will miss 0 AMI BMJ

718 consecutive ED suspect AMI MI/USA 238 (33.1%) Reichlin T. N Engl J Med 2009;361:858-67.

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

Why an ADP? Accelerated Diagnostic Protocol Reason for an ADP ER docs vs risk scores Docs are risk adverse Docs always admit more than scores

Why do we admit sooo many? ER Dr. LAWYER

ADP is for discharging! Maybe that is a good idea? Risk Scores ADP 1) Non-Dx ECG 2) (-) Tn x2 3) Low Risk Score TIMI HEART EDACS CRUSADE GRACE

TIMI Risk Score: 2 week MACE 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 Rate of Composite Endpoint (Days 1-14), % 45 40 35 30 25 20 15 10 5 0 40.9 26.2 19.9 13.2 8.3 4.7 0/1 2 3 4 5 6/7 Number of Risk Factors 1 Each risk factor is = 1 point, and total represents TIMI Risk Score Event rates (all-cause mortality, MI, or UTVR) increase with each 1-point increase in score 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 NPV ECG 35.2 89.3 POC markers 82.9 96.1 TIMI 96.7 97.5 POC + ECG 88.8 96.7 TIMI + ECG 98.1 98.3 ADP 99.3 99.1

HEART Score for 6 week MACE MACE = AMI, PCI, CABG, (+) cath, death 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 RISKS Hyperchole, HTN, DM Tobbacco (+) FH, Obesity Tn: 3x ULN =2 1-3 ULN =1 ULN =0 Low risk = 0-3; <2% MACE risk

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-ADP Emergency 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 Pain occurred or worsened with inspiration Pain is reproduced with palpation +5-4 -6 Low Risk Criteria EDACS Score <16 No new ECG ischemia Negative 0 and 2h Tn

PEARL Comparing Scores EDACS HEART-2 PEARL data set: 7 Eds N=458 Patient with suspected ACS HEART -1 TIMI GRACE Dr documented risk of MI before Tn results as Low, Moderate, or High 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 cutpoint Low 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 1 HEART-2 0-2 18.9 TIMI 0 7 GRACE 49 3.2 EDACS 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 patients 7.0 (TIMI) 728,000 18.9 (HEART) 1,965,600 34.3 (EDACS) 3,567,200 77% (TRAPID) 8,008,000

High Sensitivity Troponin in the USA FDA clears blood test to help diagnose patients with a suspected MI Jan 19, 2017 The FDA granted a 510(k) clearance for the Elecsys Troponin T Gen 5 STAT blood test for patients with a suspected MI.

Increased Troponin Sensitivity = More ED Discharges Patients Discharged Early (%) 70 60 50 40 30 20 10 0 9.8 ASPECT 1 ctni 50 ng/l 20.0 ADAPT 2 ctni 30 ng/l 38.6 APACE 3 ctni 26.2 ng/l 63.4 TRAPID-AMI 4 ctnt 12 ng/l; Δ1 hour 3 ng/l 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.

2015 ESC Guidelines The NPV for MI in patients assigned rule-out exceeded 98% in several large validation cohorts Eur Heart J. 2016 Jan 14;37(3):267-315.

Will the ESC guidelines work in the US? hsctnt and I at 0 and 3 h postpresentation Purpose: validate the ESC Working Group on Acute Cardiac Care rule-in algorithm 1061 hstni 985 hstnt Sn of 99th %ile to R/O AMI HsTnI 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