Cardiac markers

cardiac function test for mbbs/bds/bmlt

1. CARDIAC MARKERS
Binaya Tamang

5. •Acutecoronarysyndrome:Asuddencardiac
disorderswithsimilarsymptoms[stable,
unstableanginaandAMI]
•Angina:chestpainoftenassociatedwithdecreased
oxygensupply(ischemia)toheartmuscle.
•Stable:increaseswithphysicalexerciseorstressand
normalizesatrest
•Unstable:occurswhilerestingtoo.SignforAMI

6. •Acutemyocardialinfarction:myocardialnecrosisasaresultofinterruptionofbloodsupplytoanareaofcardiacmuscle.
•Mainlycausedbyatherosclerosisofcoronaryartery.
•Alsocalled“heartattack”.
•TWOtypesSTEMIandNSETMI[basedonECG]
•STEMIortransmuraltype:severeinjuryandSTsegmentdepression.
•NSETMIorsubendocardialtype:lesssevereandNoSTsegmentelevation.DeveloppathologicQwaves

10. •Congestiveheartfailure:ineffectivepumpingoftheheartàaccumulation(congestion)offluidinthelung.
•Mightoccursdueto
•MIattackandcoronaryarterydisease
•cardiacstiffness
•leftventriculardysfunction
•Valvularheartdisease.
•Uncontrolledarrythmiaandcardiacmyopathies.
•BNPandNT-proBNParemeasured.
•Pulmonaryedemaandgeneralizededema

11. •Cardiac arrythmia: variation in the normal heart
beat or normal rhythm. Normal 60-100 bpm.
•Sinus rhythmàSA node
•Atrial rhythmàatria/atrial fibrillation
•Ventricular rhythmàventricle
•< 60 bpm or bradycardia
•>100 bpm or tachycardia
•Infective Heart Disease : most common heart
disease caused by infection are:
•rheumatic heart disease[sore throat], infective
endocarditis[brushing], and pericarditis.

15. •Cardiacbiomarkersarepaneloftestused
todetectcardiacdisease.
•Theyincludeenzymes,hormonesand
proteins.
•Theyshowupinthebloodàhearthas
beenunderseverestressandbecome
severeinjured.

16. An ideal cardiac marker
•High specificity and sensitivity
•Ability to be used as a monitor of prognosis and
therapy
•Rapid, easy-to-perform, and cost effective
•Absent or not detectable in normal

17. Cardiac Biomarker
qEnzyme markers:
•Creatine kinase –MB( CK-MB)
•Lactate dehydrogenase-LDH
•AST/SGOT
qNon Enzyme markers•Myoglobin
•Cardiac Troponin ( cTnI and cTnT)

18. Other new/novel markers
[ more study ]
•Glycogen phosphorylase B•Ischemia modified albumin (IMA)•Heart type fatty acid binding protein
•Pregnancy-Associated Plasma Protein A
•Lipoprotein-Associated Phospholipase A2
•hsCRP
•Homocysteine level

19. Marker start PeakDuration of
elevation
AST12-24 hr24-48 hr4-6 days
LDH-1 24 –48 hr 48 –72 hr7 –10 days
CK-MB 4 –6 h12-24 h2 –3 days
Cardiac
Troponins
2-6 hr 18-24 hr4-14 days
Myoglobin1-4 hr6 –12 hr24 hr
IMAFew
minutes
6 hr12 hr
TIME GRAPH

20. Creatine kinase

21. Creatine kinase
•It is Dimeric enzyme.
•Found in skeletal muscle, heart and brain.
•Two peptide subunits –B ( brain) and M (muscle).
•Three cytosolic isoenzymes:
üCK-BB (CK-1)-Brain
üCK-MB (CK-2)-Cardiac
üCK-MM (CK-3)-skeletal muscle
•CK-MB is found predominantly in heart in comparison to
skeletal muscle and rises after MI at 4-8 hrs.

22. •CK-MMispresentinlargeamountinskeletalmuscle
andalsoinCardiacmuscle[approx.80%].
•CK-BBispredominantlypresentinbrainanddoesn’t
comeintobloodunlessBBBisdamaged.
•AlthoughhelpfulindiagnosisMIatearlystage,less
usefulforconfirmationinlatestage[normalizesby3
days].
CK-MMCK-MB
•Skeletal muscle95-98%Approx. 2-5%
•Cardiac muscle80-90%10-20%

23. qReference interval (CK activity)
•Total CK
•Men: 24-190 U/L
•Women: 24-170 U/L
•CK MB: <25 U/L
•After onset of symptomàrises at 4-6 hrs.àpeak at 24
hrs. and normalizes at 2-3 days.
•Concomitant skeletal muscle injury should be ruled out as
CK-MB has low specificity.
•To add in interpretation of CK-MB in diagnosis of AMIà
% Relative Index.

25. qPercentage relative index (%RI)
%RI = (CK-MB mass/↑ed total CK ) X 100%
Ratio
•< 3.0 = skeletal muscle injury
•>5.0= indicative of AMI
•3-5= gray zone [ neither ‘black’ nor ‘white’àstill care]
qCK-MB mass is more good indicator than CK-MB activity.

26. However, CK-MBhas now
been replaced
by
CardiacTroponin which
are more specific

27. •Troponin complex is present in the thin filament
of muscle àmuscle contraction
•3 types
•Troponin-C[ binds calcium]
•Troponin-I[ inhibitory unitàbinds to actin]
•Troponin-T[ binds with tropomyosin]
Cardiac troponin

28. •bothcardiacandskeletalmuscle.
•Differencebetweenskeletal&cardiactroponin.
•CTnI:31aminoacidlongerthanskeletaltrop.
•CTnT:11a.alongerthansklt.Trop.
•CTnCissimilarwithskeletal.
•Hence,CTnIandTarespecificcardiacmarkerbutnotCTnC.
vNormal range
•C Tn T: < 0.1 ng/ml
•C Tn I: < 0.4 ng/ml.
•Hs-c Tn T: < 4 ng/L, 4-10 ng/L moderate and >10 ng/L
high

30. •AMIàthetroponincomplexandfreetroponinin
subunitsarereleasedintothebloodstream.
•UnlikeCK-MB,ànotfoundintheNormalserumàmore
specific
•CTnaremainly3-6%cytoplasmicfractionand94-97%
myofibrilboundfraction.
•So,earlyreleasefromcytoplasmicfractionandslow
releasedfromboundfractionàremainselevatedfor
longerdaysàlatediagnosis

32. Cardiac troponin vs CK-MB
•High cardio specific
•Prolonged elevation
•Very sensitive to minor degree of MI injury
•Not present in serum of Normal
•Excellent prognostic marker

33. CTn I vs CTn T
Specific to heart muscle
↓
Initially both were treated equal
↓
By time, False positive in ESRD patient [ CTn T]
↓
CTn t Antibody cross reacts with 0.5-2 % with skeletal
muscle Troponin too.
↓
So, CTnI is used more.

34. Myoglobin
•isanoxygen-bindinghemeproteinthatispresentinboth
cardiacandskeletalmuscle.
•lacksspecificity
•itsclinicalusefulnessàearlyreleasefromdamagedcardiac
orskeletalmuscleàEarliestmarker.
•Rapidfall[thanCK-MBandtroponin]àRapidlyclearedby
kidneyàAgainincreasesinRe-ATTACK.

35. •Appear1-2hr,peak6-9h,normalby18-24
•Ifmyoglobinconcentrationsremainwithinthereference
range8hoursaftertheonsetofchestpain,AMIcan
essentiallyberuledout.
•GFRalsowilleffect.10minhalflife.
•Measuredbyimmunoassaymethod:30-90ng/mL

36. Biomarkers of older days
qAspartate aminotransferase (AST)
•12-24 hr ,24-48 hr, 4-6 days.
•Older days
•Not early detection, not specific [ many disease]
•Not used these days
qLactatedehydrogenase[manyisoenzyme]
•Usedinolderdays
•Highlynonspecific[manyisoenzymes]
•Riseslatebutstaysfor7-10days
•Notusedthesedays

38. Flipped ratio=LDH1:LDH2

39. Ischemia modified albumin
[IMA] [52 to 116 kU/L]

40. Ischemia modified albumin[IMA]
•Itmeasureschangesàoccurinalbumininischemic
condition[Lackofoxygen]
•UnderIschemiaàfreeradicalàconfirmationalchange
albuminàalteritsabilitytobindtransitionmetals,suchas
cupperorcobalt.
•Startswithinfewminutes,peakat6hrandnormalat12hr.
•DonebyAlbumincobaltbindingtest

42. Congestive heart failure
qNatriureticpeptide:hormone
•AtrialNPàproducedbyatrialmyocytes
•BrainNPàProducedbyventricularmyocytes[isolated
fromporcinebraintissue].
•C-typeNPàunknown
•Clinicallyimp:BNPandNTproBNP.
•Releasedfromcardiacventriclesmyocytesinresponseto
stretch.
CHF likely to occur
•BNP : >100 pg/ml
•NT pro-BNP: >400 pg/ml

43. Ventricular stretch/ischemia/HTN

44. Pregnancy-Associated Plasma
Protein A [PAPP-A]
•Isametalloproteinase
•Majorcontributorforprogressionof
atherosclerosisàincreasesplaqueformation
•Highinunstableplaqueincomparisonof
stableplaque.
•Stillnotstandardizedassayandreference
interval

45. Lipoprotein-Associated Phospholipase
A2
•LP-PLA2, also known as platelet-activating factor acetyl-hydrolase
•Synthesized by inflammatory cell [monocyte & lymphocytes]
•Cleave ox. Lipid àinduce lipid fragment
•Which is more atherogenicàIncreases endothelial adhesion.
•Marker for plaque instability.
•Researches has focused to see the role LP-PLA2 in stroke.