BioRemarkable Symposium

Transcription

1 BACC BioRemarkable Symposium Acute Myocardial infarction Stefan Blankenberg University Heart Center Hamburg London, September 7th, 2017 Universitätsklinikum Hamburg-Eppendorf

2 Third Universal-Definition of MI BACC Type 1 and 2

3 Conventional Troponin BACC

4 @BACCSTUDY Westermann, Nature Reviews 2017 BACC

5 Comparison of troponin assays BACC Apple F et al., Clin Chem, 2012

6 Korley T and Jaffe A JACC, 2013 BACC

7 BACC

8 Sensitive Troponin BACC Chest pain onset < 3 hours Chest pain onset < 3 hours Keller T et al. NEJM, 2009 Reichlin T et al. NEJM, 2009

9 Troponin Dynamik BACC

10 BACC Serial hstni determination dynamics within 3 hours protocol On Admission 0h Serially 3h PPV PPV 82.6 % % % % % % % % NPV NPV

11 Korley T and Jaffe A JACC, 2013 Bedeutung von Sensitivität und Spezifität BACC

12 BACC Early decision making is crucial ESC Guideline Roffi 2015 Eur Heart J Stefan Blankenberg

13 12 sites on 3 continents BACC

14 1 hour concept BACC 95% CI % 95% CI %

15 Background: Troponin assays BACC High sensitive troponin T (Elecsys, Roche Diagnostics, Switzerland) High sensitive troponin I (ARCHITECT i2000sr, Abbott Diagnostics, USA) Measureable inthe general population: 25% 96% Apple 2012 Clin Chem

16 BACC Study BACC Clincial routine utilizing a hs-tnt assay and clinical treatment based on ESC guidelines: 0 hour hstnt 3 hours hstnt + clinical judgement, imaging & ECG to establish final diagnosis 12 months follow-up 0 hour hstni 1 hour hstni 3 hours hstni without additional information Neumann*, Sörensen* 2016 JAMA Cardiology06/2016

17 BACC Rule-Out 6 ng/l vs 27 ng/l BACC Suggested 1-hour algorithm NSTEMI rule-out: hstni < 6 ng/l at 0h and 1h Cut-off Time after admission NPV NSTEMI 1 (95% CI) Sensitivity NSTEMI 1 (95% CI) NPV NSTEMI (95% CI) Sensitivity NSTEMI (95% CI) 6 ng/l 1-hour 3-hour 99.7 ( ) ( ) 99.1 ( ) ( ) 99.0 ( ) 99.5 ( ) 97.6 ( ) 98.8 ( ) 27 ng/l (99 th percentile) 1-hour 3-hour 98.4* ( ) 99.1 # ( ) 89.6 ( ) 94.3 ( ) 94.8* ( ) 96.8 # ( ) 77.5 ( ) 87.1 ( ) P<0.05 for 6 ng/l at * 1h or # 3h NPV: negative predictive value; NSTEMI 1: non STEMI type 1

18 BACC Rule-In BACC Suggested 1-hour algorithm NSTEMI rule-in: hstni after 1h > 6 ng/l and a delta of 12 ng/l to 0h Criteria to diagnose patient as NSTEMI PPV NSTEMI 1 (95% CI) Specificity NSTEMI 1 (95% CI) PPV NSTEMI (95% CI) Specificity NSTEMI (95% CI) Troponin I 1-hour > 6 ng/l and absolute delta from 0h to 1h troponin I 12 ng/l 82.8 ( ) 98.0 ( ) 87.1 ( ) 98.0 ( ) Troponin I 3-hour > 6 ng/l and absolute delta from 0h to 3h troponin I 12 ng/l 78.6 ( ) 96.8 ( ) 84.6 ( ) 96.8 ( ) PPV: positive predictive value; NSTEMI 1: non STEMI type 1

19 Outcome after 1 year BACC

20 Baseline rule-out BACC cohort NPV % Non-AMI Hs-TnI Neumann*, Sörensen* Clinical Chemistry accepted Stefan Blankenberg

21 Baseline rule-out + low risk ECG BACC cohort NPV % Non-AMI Hs-TnI Neumann*, Sörensen* Clinical Chemistry accepted Stefan Blankenberg

22 BACC Neumann, Clin Chem

23 Optimal threshold to rule out at presentation with hs-ctni 0 h Aim: to define a threshold that identifies patients with suspected acute coronary syndrome at presentation as low risk of myocardial infarction for immediate discharge Derivation: n=4,870 consecutive patients across hospitals in Scotland, UK Validation: n=1,434 consecutive patients in Minneapolis, USA Index myocardial infarction, subsequent myocardial infarction or cardiac death at 30 days Shah AS et al Lancet

24 Optimal threshold to rule out at presentation with hs-ctni h 99.5 Negative predictive value (95% CI) women men Troponin concentration on presentation, ng/l n=4,870 NPV is 99.6% (95% CI 99.3 to 99.8) at troponin concentrations <5 ng/l Shah AS et al Lancet

25 Westermann, Nature Reviews 2017

26 2015 ESC Guidelines for non-st-elevation MI, EHJ 2015

27 Methods Aim: To validate the diagnostic performance of the ESC 0/1-Hour Algorithm Population: - pooled patient-level data from two prospective studies (APACE and BACC) - unselected patients presenting with symptoms suggestive of MI to the ED - 14 centers in six European countries - patients with STEMI excluded Final diagnosis: centrally adjudicated by two independent cardiologists. Investigational biomarkers: Hs-cTnT (Elecsys) and hs-ctni (Architect) blood concentrations were measured at presentation and after one hour.

28 Results ESC 0/1-Hour Algorithm A High-sensitivity cardiac troponin T (Elecsys ) Early presenters n=1289

29 Results ESC 0/1-Hour Algorithm B High-sensitivity cardiac troponin I (Architect ) Early presenters n=1289

30 Cardiac procedure Myocardial injury with cell death marked by cardiac troponin elevation Non-cardiac major procedure Myocardial injury Tachy-/bradyarrhythmia Myocardial infarction Type 1 vs. Type 2 MI Clinical evidence of acute myocardial ischemia with rise and/or fall of cardiac troponin Heart failure Renal failure Third Universal Definition of Myocardial Infarction

31 Mechanisms leading to myocardial ischemia in the absence of coronary plaque rupture. Sandoval

32 Type 2 Myocardial Infarction: Mechanisms 25% 20% 15% 10% 5% 0% 19% Main trigger tachydysrhythmias: ~30% US cohort (Sandoval/Apple 2015): 36% 10% Saaby Am J Med 2013 Sandoval CCJ 2015

33 BACC Development of a diagnostic prediction model for patients with type 2 myocardial infarction Johannes T. Neumann, Nils A. Sörensen, Nicole Rübsamen, Francisco Ojeda, Thomas Renne, Tanja Zeller, Mahir Karakas, Stefan Blankenberg, Dirk Westermann Universitätsklinikum Hamburg-Eppendorf

34 BACC Universal definition of myocardial infarction Patients with myocardial infarction Acute treatment Type 1 MI: Acute plaque disruption with intraluminal thrombus Urgent angiography Type 2 MI: Imbalance of oxygen supply and demand Treatment of underlying cause (hypertension, heart failure, arrhythmias, ) 1. What are the differences in cardiovascular outcome? 2. How to differentiate these two subtypes in the emergency department? Thygesen 2012 Eur Heart

35 BACC Results: Outcome Patients with myocardial infarction Follow-up events Type 1 MI: Acute plaque disruption with intraluminal thrombus Death: (13.8%) Rehospitalisation: (33.8%) Revascularization: (12.0%) Type 2 MI: Imbalance of oxygen supply and demand Death: (9.4%) Rehospitalisation: (19.3%) Revascularization:

36 BACC Results: Multivariable Regression Beta (95% CI) OR (95% CI) p-value Female sex 1.27 (0.67, 1.90) 3.57 (1.96, 6.67) <0.001 No radiating chest pain 1.62 (0.96, 2.34) 5.08 (2.62, 10.43) <0.001 Baseline hs-tni 40.8 ng/l 1.30 (0.74, 1.89) 3.68 (2.10, 6.61) <0.001 SCORE Characteristic Categories Points Female Sex Yes 1 No 0 Radiating chest pain No 1 Yes 0 Baseline Troponin hs-tni 40.8 ng/l 1 hs-tni > 40.8 ng/l 0 Probability of T2MI (%) 100% 80% 60% 40% 20% 0% 72% 42% 17% 5%

37 Application of high sensitivty troponin BACC Patient with chest pain/ resuscitation Rapid rule-out Observe Rapid diagnosis low hs-tn low risk differential diagnoses ruled out Grayzone high hs-tn / Delta High risk symptoms

38 Thank you Stefan Blankenberg