PROTOCOLLI DI RULE-OUT E RULE-IN CON LE NUOVE TROPONINE AD ALTA SENSIBILITÀ - GIANFRANCO CERVELLIN - ACEMC
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Protocolli di rule-out e rule-in con le
nuove troponine ad alta sensibilità
Gianfranco Cervellin
Dipartimento Interaziendale Provinciale Emergenza-Urgenza
Provincia di Parma
…e quattro!!!
Aug. 2018 epub ahead of print
1. Criteria for myocardial injury: Detection of an elevated cTn value above the 99th percentile URL is defined as myocardial injury. The injury is considered acute if there is a rise and/or fall of cTn values. 2. Clinical criteria for MI: The clinical definition of MI denotes the presence of acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischaemia.
Siamo qui a perdere
del tempo?
Emergency Medicine Journal, 2018
30 ottobre 2018
Percentage of healthy population with measurable values
Access hsTnI: 97% AccuTnI: 31%
Ieri: Oggi:
ng/mL ng/L
X 1000!!!Ieri: Oggi:
URL TnI = 0.06 URL HS-TnI =
ng/mL (60 ng/L) 10.5 ng/L (♀)
17.8 ng/L (♂)Ieri: Oggi:
LOD non indicato LOD = 2.3 ng/L
Cioè: valori tra 2.3 e 10.5 ng/L (♀),
o tra 2.3 e 17.8 ng/L (♂)
sono «NORMALI»!Ann Transl Med 2016;4(10):193
Contemporary Tn
HS TnIschemic Non-ischemic
• We have, for the first time, correlated the 99th centile thresholds of cTn to the approximate mass of myocardium undergoing complete necrosis. • Necrosis of just 40mg of myocardium, equivalent to 0.015% of the heart, sufficient to increase serum concentrations above the 99th centile. • This volume is much too small to detect by noninvasive imaging.
Ci cambierà la vita?
• We analyzed data from 48,594 patients admitted because of symptoms suggesting an acute coronary syndrome • Introducing hs-cTnT into clinical practice has led to the recognition of a large proportion of patients with minor cardiac troponin increases (14 to 49 ng/l), the majority of whom do not have MI. • Although a heterogeneous group, these patients remain at high risk, and the adjusted mortality rate started to increase at the level of the 99th percentile in healthy controls.
• Chronic troponin elevations truly mirror a pathophysiological process that is distinct from the acute increase more typically observed in patients with myocardial infarction. • It seems now unquestionable that the assessment of these cardiospecific biomarkers would provide a net incremental benefit for cardiovascular risk assessment, not only in patients with established coronary artery disease, but also in the general population.
J Lab Precis Med 2017;2:60 • The high sensitivity of the assay with its very high negative predictive value for AMI if < LoD predestines it for a rule out test.
Does the test change diagnosis?
1
0,9
0,8
0,7
0,6
UA
0,5
NSTEMI
0,4
0,3
0,2
0,1
0Circulation. 2013;127:2452-2457
Non più scelte dicotomiche (negativo/positivo)
La moltiplicazione dei grigi
Non-AMI AMI First generation troponin immunoassays
Non-AMI AMI Contemporary troponin immunoassays
Non-AMI AMI Highly sensitive troponin immunoassaysCome in altri casi… Più si affina il test, più il clinico deve diventare competente.
To rule-in or to rule-out? That is the question!
Emerg Med J 2018;35:192–197 • What are we trying to rule out? → It is imperative for the ED physician to understand that ruling out an acute myocardial infarction (AMI) is not the same as ruling out ACS. • What is the acceptable risk of missed events? → No diagnostic test in medicine is 100% accurate. → However, when considering early rule-out strategies, it is generally considered that clinicians will accept a miss-rate for MACE between 0% and 1%.
Absolute or relative???
J Lab Precis Med 2018;3:43
Chi offre di meno?
12 ore 1 ora
6 ore 2 ore
3 orea.D. 2013
!!!
“Non chiedere mai alla gallina se l’uovo è buono!”
Dan Peterson (Evanstone, USA 1936)The performance of the 1 h algorithm to rule in and rule out acute MI in patients presenting with chest pain to the emergency department has not been tested within an RCT. The best management of patients assigned to the ‘observational zone’ according to the 1 h algorithm remains to be defined.
Not tested in RCT????
!!!
Circulation, 2013
«… le discese ardite, e le risalite…»
Dov’è il mio paziente?
• Criteria for determining a pathological rise between two serial cTn values are assay- dependent and continue to evolve. • The ability to define a changing pattern will also depend on timing. For example, around peak values, it may be difficult to observe a changing pattern of values.
• Blood samples for the measurement of cTn should be drawn on first assessment (designated as 0 h) and repeated 3 – 6 h later, or earlier with hs-cTn assays. • Sampling beyond 6 h may be required if further ischaemic episodes occur, or in high- risk patients. There are still some patients who may rule in late (at 6 h).
Some patients with acute myocardial injury presenting late after the onset of acute MI (>12- 18 h) and who are on the downslope of the time- concentration curve may require longer periods of time for a changing pattern to be detected.
Quindi:
troponina in discesa non
equivale a rule-out!!!• A single sample rule out strategy using a very low value (in many cases the LoD of the assay) has high sensitivity for myocardial injury and therefore high negative predictive value to exclude MI. This strategy should not be used in those who present early, i.e. < 2 h after the onset of chest discomfort.
The Lancet oct. 2015
The Lancet oct. 2015
The Lancet oct. 2015 The NPV of cardiac troponin concentrations less than 5 ng/L at presentation is excellent in patients with a normal ECG (99.7%), and remains remarkably good even in those with possible myocardial ischemia on the ECG (98.1%)
• To rule out AMI with 1 test in the ED, the hs-cTnI cutoff value must be set below the 99th percentile, at the limit of detection of the assay. • Clinicians cannot simply relax and let hs-cTn make the diagnoses.
When cTn results and the clinical presentation are strikingly discordant, rare analytically false test results should also be considered by clinicians, and the laboratory should be contacted in order to rule out analytical interferences. No assay is perfect.
Se un’aspirina fa bene, due faranno meglio?
Circulation. 2018;138:989–999 Measuring both cardiac troponin T (hs-cTnT) and cardiac troponin I (hs-cTnI) for the diagnosis of acute myocardial infarction does not consistently increase overall diagnostic accuracy as compared with measurement of the individual troponins.
16 aprile 2018
Cosa è successo con l’introduzione di hs TnI?
- 21% dosaggi Troponina richiesti dal Pronto Soccorso
da Marzo a MaggioCosa è successo con l’introduzione di hs TnI?
Confronto 2017 - 2018
Maggio % Giugno % Settembre %
Reparto ‘17 ‘18 ‘17 ‘18 ‘17 ‘18
PRONTO
SOCCORSO 2105 2077 -1% 1943 1727 -11% 2049 1827 -11%
Nel periodo: accessi totali + 3.3%Cosa è successo con l’introduzione di hs TnI?
PRELIEVI SERIALI di troponina al
Pronto Soccorso
2° prelievo: 12% → 27% → 25%
3° prelievo: 12.5% → 6.7% → 5.7%
PRONTO Numero e % pazienti per numero prelievi
SOCCORSO
10 Settembre/10
Marzo 2018 Maggio 2018 Ottobre 2018
1 Prelievo 1337 73% 942 65% 959 69%
2 Prelievo 229 12% 394 27% 348 25%
3 Prelievo 230 12.5% 97 6.7% 79 5.7%
4 Prelievo 29 1.58% 12 0.828% 8 0.573%
5 Prelievo 8 0.436% 4 0.276% 1 0.072%
6 Prelievo 2 0.109%Diagnosing myocardial injury in the high-sensitivity troponin era
Giuseppe Lippi, Gianfranco Cervellin
In press
Table 2. Current paradigms and unresolved issues of high-sensitivity
cardiac troponins
• Cardiac troponins are generic biomarkers of myocardial injury
• Cardiac troponins I and T are two different proteins
• Standardization of immunoassays remains still poor
• The time between symptom onset and blood collection is a major
determinant of diagnostic performance
• Diagnostic performance varies according to the diagnostic
thresholds
• Diagnostic performance varies when cardiac troponin changes are
calculated as absolute or percent variationBayes +
Gauss +
Osler =
_________
Buona MedicinaPerfino l'eternità, un tempo, durava di più. Stanislaw Jerzy Lec Leopoli, 1909 – Varsavia, 1966
Il futuro del POCT? Piattaforma diagnostica unica. Disegnata per trasformare radicalmente la cura dei pazienti: un’unica piattaforma di alta qualità analitica.
Nuova tecnologia POCT • Touch screen, strumento portatile • Fingerstick per campioni di sangue • Test strip multicanale a basso costo • Controllo di alta precisione su ciascun canale • Controlli On-Board • Conservazione a temperatura ambiente
INR Test Performance
7.0
6.0
• Clinical samples
n=230
5.0
• Total test time 10
Lumira INR
4.0
to 90 seconds
3.0
• 3uL sample
y = 0.9424x + 0.1555
R² = 0.9497
volume
2.0
• Samples
1.0 referenced against
Roche Coaguchek
0.0 XS
0.0 1.0 2.0 3.0 4.0 5.0 6.0 7.0
Coaguchek XS INRHigh Sensitivity Troponin-i - Rule Out Focus
Comparison of 99th percentile
and % samples measurable
in a healthy population
Confidential and Proprietary Copyright © 2017 LumiraDx Group Ltd. All Rights Reserved, Worldwide. For discussion purposes only. Subject to executed non-disclosure agreementLa prospettiva:
2018 2019 2020 2021 2022
INR TROPONIN I DROGHE D’ABUSO JE
IMMUNOASSAY D-DIMERO HCV C-PEPTIDE LEPTOSPIRA
CHIMICA CLINICA CRP HBV K+/ NA+/ CL-/CA HAT
ELECTROLITI LIPIDI EMATOLOGIA EV71
COAGULAZIONE BNP HIV TORCH 0157
TEST CELLULARI Nt-proBNP HIV AG / P24 HAV
HCG HBSAG SIFILIDE STREP B
HBA1c HIV AG/P24/ SIFILIDE PCT
GLUCOSE NOROVIRUS EBV VITAMINA D
LACTATE LEGIONELLA BORDETELLA OSTEO MARKER
HMP VIRUS STREPTOCOCCUS HAEMOPHILUS ETC….
TSH PNEUMONIAE CHIKUNGUNYA
ROTAVIRUS CHAGAS
DENGUE MALARIA POTASSIO
IGG/IGM/NS1 ALT/AST FERRITINA
FLU A/B B12-FOLATI
STREP A CMP
ADENOVIRUS BMP
RSV
H PYLORI
C. DIFF
PSA
HBSAG
ANTI SALMONELLA
TIPHY
MOLECOLARI FLU A/B MDX C DIFICILE MDX
GONORRHOEA RSV MDX HCV MDX
STREP A MDX
CHLAMYDIA/GC MDXWow!!!
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