Congreso Nacional del Laboratorio Clínico 2016

Transcription

1 Can biomarkers help us make a better use of cardiac imaging for myocardial ischaemia rule-out in the Emergency Department? Alessandro Sionis Director Acute and Intensive Cardiac Care Unit Hospital de la Santa Creu i Sant Pau Universitat de Barcelona Barcelona Spain 1

2 Disclosures (last 5 years) Speaker: Singulex Research grants: Roche, Singulex, Ministerio de Economía y Competividad, Sociedad Española de Cardiología Royalties: No 2

3 Emergency Department Visits (United States) 130 M ED visits each year 10.4 M chest pain (8%) 4.1 M Sent home as non-cardiac 6,24 M Suspected ACS (63%) 50,000 MI Higher death High Liability 3,1 M non-cardiac (50%) High Volume Potentially high-risk Actually low-risk 1,2 M AMI (20%) High Risk 1,5 M UA (24%) 374,000 Sudden death (6%) 3

4 Clinical Case 56 year-old woman Several episodes of chest pain in the past 2 weeks Last episode 3 hours before coming to the ED Asymptomatic on arrival Past history of type 2 diabetes and hypercholesterolemia Treatment: metformin 850mg twice daily and simvastatin 20mg daily 4

5 10 min 5

6 The Diamond-Forrester Model Updated PTP <15% PTP 15-65% PTP 66-85% PTP>85% Genders TSS. European Heart Journal 2011;32:1316

7 The Diamond-Forrester Model Updated PTP <15% PTP 15-65% PTP 66-85% PTP>85% Genders TSS. European Heart Journal 2011;32:1316

8 Clinical Case: ECG 8

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10 Third universal definition of Myocardial Infarction (MI) MI can be diagnosed within the first 24h after admission in the presence of Symptoms & Signs of cardiac ischaemia Maximal cardiac troponin (ctn) concentration above the reference 99 th percentile (p99 th ) A rising and/or falling pattern in serial ctn measurements Clinical laboratories should Measure the ctn p99 th with the lowest analytical imprecision possible (CV ideally <10%) Identify whether a rise and/or fall of ctn are significant and indicate of MI (kinetics, delta) 1 ESC/ACCF/AHA/WHF

11 High-sensitivity ctn assays. Characteristics Improved (less) analytical imprecision at the 99th percentile Corresponding Hs-assays LoD (ng/l) 99 th (ng/l) %CV at 99 th 10% CV (ng/l) High sensitive 1 ctni High sensitive 2 ctni High sensitive 3 ctni High sensitive 4 ctnt Clinical sensitivity to detect cardiac necrosis is improved Counterpoint is lower specificity in comparison to earlier ctn assays that has lead to development of serial testing algorhytms 11

12 Management of Patients With Suspected ACS hstn<uln hstn>uln Alternative 1-h protocol Pain >6h Pain <6h hstn >5x ULN and high-risk presentation Assay specific threshold at 0 and 1 h hstn no change Painfree, Grace score<140, differential diagnosis excluded Re-test hstn at 3h hstn change and at 1 value >ULN hstn no change Rule-out Observe Rule-in Discharge /Stress testing NSTEACS Treatment Work-up differential diagnosis Ferencik M. Eur Heart Jour 2016;37:

13 0h/1h Rule-in Rule-out out Algorithm of NSTEACS Using hs-ctn 2015 ESC NSTEACS Guidelines 13

14 APACE hs-ctn 1-hour Algorithm 436 Patients hstnt 0h <12ng/L and delta 1h <3 ng/l Others 0h >52 ng/l or delta 1h >5 ng/l Rule out Observe Rule in Results 250 patients (60%) Sensitivity: 100% NPV: 100% 101 patients (23%) Prevalence of AMI 8% 76 patients (17%) Specificity: 97% PPV: 84% Reichlin T et al. Arch Intern Med 2012;172:

15 0h <12ng/L and delta 1h <3 ng/l TRAPID hs-ctn 1-hour Algorithm 1282 Patients With Chest Pain Others 0h >52 ng/l or delta 1h >5 ng/l Rule out Observe Rule in 813 patients (63.4%) NPV: 99.1% 285 patients (22.2%) Prevalence of AMI 22.5% 184 patients (14.4%) PPV: 77.2% Mueller C et al. Ann Emerg Med 2016 (DOI: /j.annemergmed ) 15

16 Clinical Case: Labs hstnt: 8 ng/l (0h) LDL cholesterol: 156 mg/dl HbA1C: 7% Rest normal 16

17 Clinical Case: Labs hstnt: 8 ng/l (0h) 11 ng/l (2h) 17

18 Management of Patients With Suspected ACS hstn<uln hstn>uln Alternative 1-h protocol Pain >6h Pain <6h hstn >5x ULN and high-risk presentation Assay specific threshold at 0 and 1 h Re-test hstn at 3h Rule-out hstn no change hstn change and at least one value >ULN hstn no change Observe Painfree, Grace score<140, differential diagnosis excluded Rule-in Discharge /Stress testing NSTEACS Treatment Work-up differential diagnosis Ferencik M. Eur Heart Jour 2016;37:

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20 Grey Area With current hstn protocols 20-25% of patients fall into the grey zone (further observation needed) Most of the times work-up will require testing with one or more imaging modalities with an additional time of at least 6-8 hours before AMI can confidently excluded Several potential problems related with this approach: Increased costs and variable availability Waiting time (ED overcrowding) Reimbursement issues (some countries) 20

21 What Do The ESC Guidelines Say? Recommendations for Imaging in Patients With Suspected NSTEACS In patients with no recurrence of chest pain, normal ECG findings and normal levels of cardiac troponin (preferably high-sensitivity), but suspected ACS, a non-invasive stress test (preferably with imaging) for inducible ischaemia is recommended before deciding on an invasive strategy. I A 64, 74, 113, 114 Echocardiography is recommended to evaluate regional and global LV function and to rule in or rule out differential diagnoses. I C MDCT coronary angiography should be considered as an alternative to invasive angiography to exclude ACS when there is a low to intermediate likelihood of CAD and when cardiac troponin and/or ECG are inconclusive. IIa A 80 21

22 Rybicki FJ et al. JACC 2016;67:853 22

23 Clinical Case: CCTA The attending physician requested CCTA that was normal 23

24 Caveats Related to Use and Performance of Different Imaging Modalities In spite of recommendations the choice of the imaging modality will be largely determined by availability and local expertise Functional versus anatomical tests Occasionally more than one modality will be necessary Current tools are imperfect 24

25 Characteristics of Commonly Used Diagnostic Non-invasive Testing Diagnosis of CAD Sensitivity (%) Specificity (%) Exercise ECG Exercise stress echocardiography Exercise stress SPECT Dobutamine stress echocardiography Dobutamine stress MRI Vasodilator stress echocardiography Vasodilator stress SPECT Vasodilator stress MRI Coronary CTA Vasodilator stress PET

26 Can We Do Better? TRUE-2 Study Prospective observational study Unselected patients consulting to ED for chest pain with initial nondiagnostic ECG Rule-out with very hs-tni (Singulex ) versus hs-tnt (Roche ) based on 99 th percentile Ongoing 26

27 Take Home Messages With the advent of increasingly sensitive c-tn assays early-rule-out and rapid rule-in (time to MI diagnosis) can be reliably achieved hs-tn will play a key role in more cost-efficient triaging of chest pain patients and avoidance of ED overcrowding By doing so it will also likely contribute to a better use of cardiac imaging Singulex hs-tni assay, with improved analytical sensitivity and detectability, can potentially outperform existing hs-tn assays No matter what assay is used all algorithms must still be applied in conjunction with clinical judgment and patient history 27

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