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KARDIÁLNE BIOMARKERY – PRÍNOS ALEBO CHAOS ? MUDr. K atar ína Daňová, PhD. ODDELENIE LABORATÓRNEJ MEDICÍNY, NÚSCH, a.s. BRATISLAVA. UNIVERZÁLNA DEFINÍCIA INFARKTU MYOKARDU KRITÉRIÁ MYOKARDIÁLNEHO INFARKTU MYOKARDIÁLNA NEKRÓZA :

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KARDIÁLNE BIOMARKERY – PRÍNOS ALEBO CHAOS ? MUDr. K atar ína Daňová, PhD.

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Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

KARDILNE BIOMARKERY PRNOS ALEBO CHAOS ?

MUDr. Katarna Daov, PhD.

ODDELENIE LABORATRNEJ MEDICNY, NSCH, a.s. BRATISLAVA


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

UNIVERZLNA DEFINCIA INFARKTU MYOKARDU

KRITRI MYOKARDILNEHO INFARKTU

MYOKARDILNA NEKRZA :

DETEKCIA VZOSTUPU A/ALEBO POKLESU KARDILNYCH BIOMARKEROV PREDNOSTNE TROPONNOV S ASPO JEDNOU HODNOTOU NAD 99 PERCENTIL HORNHO REFERENNHO LIMITU

S ASPO JEDNM DKAZOM MYOKARDILNEJ ISCHMIE Z NASLEDUJCICH :

SYMPTMY ISCHMIE MYOKARDU

NOV ZMENY ST SEGMENTU, BTR

VVOJ NOVCH Q VN

STRATA VIABILITY

PORUCHY KINETIKY MYOKARDU

ESC/ ACCF / AHA / WHF expert consensus document

Universal Definition of Myocardial Infarction

Thygesen, K., Alpert, J.S., White, H.D. on behalf of the Joint Task Force for the Redefinition of Myocardial Infarction. Eur. Heart J., 28, 2007, 2525-2538.


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

Kritri poadovan pre urenie diagnostickej rozhodovacej hodnoty (cut off, decision limit) stanovenie koncentrcie 99 percentilu referennho sboru klinicky zdravch osb s analytickou nepresnosou CV 10%

ESC/ ACCF / AHA / WHF expert consensus document

Universal Definition of Myocardial Infarction

Thygesen, K., Alpert, J.S., White, H.D. on behalf of the Joint Task Force for the Redefinition of Myocardial Infarction. Eur. Heart J., 28, 2007, 2525-2538.

ACC / AHA GUIDELINE REVISION

ACC /AHA Guidelines for the Management of Patients With Unstable Angina / Non-ST Elevation Myocardial Infarction. Anderson, J.L. et al. J. Am. Coll. Cardiol., 50, 2007, 7.

National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical Issues for Biochemical Markers of Acute Coronary Syndromes. Clin. Chem., 53, 2007, 4.

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers of Acute Coronary Syndromes. Clin. Chem., 53, 2007, 4.


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

Distribcia hodnt hs cTnT vzdravej populcii

Saenger, A.K., Beyrau, R., Braun, S. et al.: Multicenter analytical validation of ahigh-sensitive troponin T assay. Clin. Chim. Acta, 412, 2011, 784-754.

Giannitsis, E., Kurz, K., Hallermayer, K. et al.: Analytical validation of high-sensitivity cardiac troponin T assay.. Clin. Chem., 56, 2010, 254-261.


Pr iny zv enia koncentr cie tropon nu bez aterotromb zy koron rnych art ri

Priny zvenia koncentrcie troponnu bez aterotrombzy koronrnych artri

Demand ischemia

supraventrikulrna tachykardia/AF, LVH, anmia, hypotenzia

Priame pokodenia myokardu

kontzia, kardioverzia, infiltratvne ochorenia m.,myokarditis,Htx,

chemoterapia

Myokardilne preptie

kongestvne SZ, PE, Pcna hypertenzia alebo COPD

CHRI

Sepsa/systmov zpalov procesy

Intrakranilna patolgia

krvcanie do mozgu, MCP

Daubert, M.A., Jeremias, A.: The utility of troponin measurement to detect

myocardial infarction: review of the current findings. Vascular health and risk

management, 6, 2010, 691-699.


Biologick variabilita short and long term biological variation in hs ctnt

Biologick variabilitaShort and longterm biological variation in hs cTnT

Short-term Long-term

Variable (0-4 h) (0-8 weeks)

Analytical variation

CVA %a53.5 98

Biological variation

CVI % 48.2 94

CVG % 85.9 94

II 0.84 1.4

RCV, log-normal increase, %b 84.6 315

Mean increase, % 58 103.4

Mean decrease, % 57.5 87

a Based on duplicate results.

b Cls of 80 % and 95 % were used to calculate the RCV for short- and long-term biological variation, respectively.

Vasile, V.C., Saenger, A.K., Kroning, J.M., Jaffe, A.S.: Biological and analytical variability of anovel high-sensitivity cardiac troponin T assay. Clin. Chem., 56, 2010, 1086-1090.


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

Biologick variabilita

Short and longterm biological variation in cTnl

Short-term Long-term

Variable (0-4 h) (0-8 weeks)

Analytical variation

CVA %a 8.3 15

Biological variation

CVI % 9.7 14

CVG % 57 63

II 0.21 0.39

RCV: log normal increase, % + 46 + 81

RCV: log-normal decrease, % - 32 - 45

a Based on duplicate results.

Wu, A.H.B., Lu, Q.A., Todd, J. et al.: Short- and long- term biological variation in cardiac troponin Imeasured with ahigh-sensitivity assay: implications for clinical practice. Clin. Chem., 55, 2009, 52-58.


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

hs cTnT aAKS

Giannitsis, E., Kurz, K., Hallermayer, K. et al.: Analytical validation of high-sensitivity cardiac troponin T assay.. Clin. Chem., 56, 2010, 254-261.


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

hs cTnT apredikcia rizika

Omland, T., de Lemos, J.A., Sabatine, M.S. et al.: Asensitive cardiac troponin T assay in stable coronary artery disease. N. Engl. J. Med., 361, 2009, 2538-2547.


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

  • Zvery I.

  • Najvyia diagnostick presnos u AKS

  • Zlepen senzitivita, obzvl upacientov

  • skrtkou dobou od zaiatku symptmov

  • vasnej dkaz nekrzy myokardu

  • Diferencilnu diagnostiku aktnych

  • koronrnych syndrmov

  • Prognostick vznam stanovenia hs cTn


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

  • Zvery IIa.

  • ast pozitivita nlezov - zven

  • analytick senzitivita a presnos vmenou

  • za niiu diagnostick pecificitu, cut-off pre

  • rzne klinick stavy?

  • Nutnos serial testing

  • Stanovenia kritickch rozdielov, ak je

  • signifikantn zmena koncentrcie? RCV? ,

  • delta change?


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

  • Zvery IIb.

  • Stanovenie asovch algoritmov vyetren

  • (3-6? 6-9?)

  • Vplyv veku, pohlavia ?


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

  • Zvery III.

  • Vyetrenie troponnov by sa vdy malo robi

  • v klinicky odvodnench prpadoch.

  • Zven koncentrcie troponnov by sa mali

  • vdy vyhodnocova vklinickom kontexte.


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

BNP / NT-proBNP ...

Satelitn sympzium Roche, XVI. kongres SKS, Bratislava, 22. septembra 2011

Satelitn sympzium Roche, XVI. kongres SKS, Bratislava, 6. oktbra 2011


Bnp nt probnp

BNP/NT-proBNP

NP sa vyluuj zo srdca ako odpove na tlakov a/alebo objemov preaenie.

Nie s pecifick pre HF ani pre ochorenie srdca.

Januzzi, J.L., Chen-Tournoux, A.A., Moe,G.: Amino-terminal pro-B-type natriuretic peptide testing for the diagnosis or exclusion of heart failure in patients with acutesymptoms. Am.J.Cardiol., 101, 2008, Suppl.


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

BNP a NT-proBNP a srdcov zlyhanie

Vyhodnotenie pacienta v aktnom stave

Odhad prognzy

Monitoring a riadenie/vedenie lieby


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

Koncentrcia NT-proBNP u pacientov s aktnou dyspnoe poda konenej diagnzy

Januzzi, J.L. Jr., Camargo, C.A., Anwarudin, S. et all.: The N-terminal pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am.J.Cardiol., 95, 2005.


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

Vzah medzi koncentrciou NT-proBNP a krtkodobou mortalitou aktneho srdcovho zlyhania

Januzzi, J.L. Jr., van Kimmenade, R., Lainchbury, J. et al.: NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients. The international collaborative of NT-proBNP study. Eur.Heart.J., 27, 2006.


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

o spsobuje falon negatvne koncentrcie NP ?

Niekedy sa to stva bez vysvetlenia!

Mitrlna regurgitcia

Pcny edm

Terminlne tdium SZ

Chronick, viac kompenzovan SZ

Ne-systolick SZ

obezita

Omland, 2010


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

Z V E R Y I.

NP s nepecifickm markerom postihnutia srdca, ale tie sasne novm markerom kardiovaskulrneho rizika.

NP maj zsadn vznam pre diagnostiku SZ (vyia diagnostick efektivita ne EKG, RTG a klinick prznaky).

Rozhodujca je jednak negatvna prediktvna hodnota, ale aj zvyujca sa pravdepodobnos SZ so stpajcimi koncentrciami BNP, NT-proBNP.

Na zklade NP sa ned spoahlivo odli zlyhvanie pravej od zlyhvania avej komory.

Interpretciu vsledkov treba robi s ohadom na vek pacientov (obezita, renlne zlyhanie).


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

Z V E R Y II.

NP maj vrazn prognostick potencil (plnovanie odberov, absoltne hodnoty, zmeny v ase).

Prognostick vznam vvoj SZ, koronrnych prhod, kardiologick vysoko rizikov pacienti, ben populcia.

Posdenie prognzy aktne dekompenzovanho chronickho zlyhania NT-proBNP nad 1 000 ng/l (dlhodob) prognza, nad 5 000 ng/l (krtkodob prognza).

Pokles koncentrcie NP o 30 % v odpovedi na liebu je znakom dobrej prognzy.

Medzi BNP a NT-proBNP nie s rozdiely v diagnostickej efektivite medzi producentmi rznych sprav.


Z v e r y iii

Z V E R Y III.

Existuj vznamn rozdiely medzi hodnotami poskytovanmi jednotlivmi diagnostickmi spravami.

Medzi metdami stanovenia BNP existuje vek heterogenita.

Medzi metdami NT-pro BNP existuje podstatne menia variabilita.

Predanalytick podmienky s podstatne nronejie pri stanoven BNP.

Vplyv fyzickej zae na stanovenie BNP a NT-proBNP.

Nevyjasnen niektor skutonosti fragmentcia molekl, glykozylcia molekl, skren imunoreaktivita. Klinick vpovedn hodnotu neovplyvuj.

Dynamick zmeny koncentrci v patologickch situcich s natoko vrazn, e biologick variabilita lohu NP v klinickej praxi nezniuje.

Oba druhy vyetren nie s tandardizovan.


Kardi lne biomarkery pr nos alebo chaos mudr k atar na da ov phd

akujem Vm za pozornos

Satelitn sympzium Roche, XVI. kongres SKS, Bratislava, 6. oktbra 2011


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