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Biomarkers in cardiac diseases Biomarkers in cardiac diseases

Biomarkers in cardiac diseases - PowerPoint Presentation

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Biomarkers in cardiac diseases - PPT Presentation

FAINELLI Manon BOGÓ Ákos Szakács Júlia MD Department of Pathophysiology Numbers Cardiovascular diseases The most frequent cause of death 75 millions of death year Important concerns in developed countries ID: 460526

heart biomarkers myocardial death biomarkers heart death myocardial cardiac 2012 acute failure injury ischemic type specific clinical research diseases

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Slide1

Biomarkers in cardiac diseases

FAINELLI ManonBOGÓ Ákos

Szakács Júlia M.D. Department of PathophysiologySlide2

Numbers…

Cardiovascular diseases The most frequent cause of death 7.5 millions of death/ yearImportant concerns in developed countriesSlide3

Cardiac diseases

Ischemic heart diseases: hypoxia or anoxia as a result of decrease or arrest of oxygen deliveryACS: obstruction of coronary arteries by a thrombus

Ischemic diseases

Stable angina

Acute coronary syndrome (ACS)

NSTEMI

STEMI

Myocardial

infarction (MI)

Unstable anginaSlide4

Cardiovascular risk factors

AgeGeneticsSmokingArterial HypertensionType II diabetes mellitusInflammatory markers : CRP,

endothelin…Protective factors:HDL-level Slide5

Atherosclerosis

Progressive complex chronic inflammatory diseaseaccumulation ofoxidized LDL i

nflammatory cellscalcifications and of fibrosisleading to plaque formationthis set modifies the intima of large

and medium artery vesselsSlide6

Atherosclerosis

Essentials of Pathophysiology: Concepts of Altered Health

State; C. MATTSON PORTH and G.MATFINSlide7

Myocardial infarction (MI)

Acute myocardial ischemia leading to myocardial necrosisDiagnosisCardiac biomarker levelsAnd at least of this items :C

linical symptoms of ischemiaModification of ST-segmentPathological Q wavesDemonstration of loss cardiac muscle or function Thrombus into coronary artery

Clinical

classification

Type

1

: spontaneous MI due to ATS

Type 2

: secondary to an ischemic imbalance (e.g. coronary spasm, emboli, anemia)

Type 3

: sudden cardiac death when biomarkers value are not available with new ischemic ECG changes or new LBBB

Type 4 and 5: MI related to revascularization proceduresEuropean Heart Journal (2012) 33, 2551–2567

Slide8

Clinical symptoms of MI

chest pain (>20min) not affected by position changing),not relieved by

nitroglycerineradiation of pain to the lower jaw or the left-arm, even gastric pain. Less specific symptoms: nausea or vomiting,

dyspnea,asthenia palpitations,sweating

fainting

European Heart Journal (2012) 33, 2551–2567 Slide9

Heart failure

abnormality of the structure or the function of myocardium, which prevents enough oxygen delivery to satisfy the metabolic needs of the tissues, at a normal filling blood pressure2 categoriesHeart failure with Preserved Ejection

Fraction (HF-PEF)Heart Failure with Reduced Ejection Fraction (HF-REF)Different states AsymptomaticAcute

ChronicCompensated/DecompensatedCongestiveClinical classification: NYHA

European Heart Journal (2012) 33, 1787–1847 Slide10

Clinical symptoms and signs of HF

Clinical symptomsBreathlessnessOrthopneaParoxysmal nocturnal dyspneaReduced exercise tolerance

AstheniaSignsElevated jugular venous pressureHepatojugular reflux, hepatomegalyGallop rhythm (3rd heart sound)

Laterally displaced apical impulseCardiac murmurPeripheral edemaPulmonary crepitations

European Heart Journal (2012) 33, 1787–1847

Heart

failure

in

a

nutshell

(From: rickolddoc.wordpress.com)Slide11

BIOMARKERS

Definition:

-measurable and quantifiable biological parameter-suitable for early diagnosis, prognosis, follow-up and risk stratification-cardiospecific with

enough released concentration levels-easily measurable (

quick and adapted to

emergency

situations

)

-

accurate

-

reproducible-cost-effective

Chan D, Ng L.L. Biomarkers in acute myocardial infarction. BMC Med. 8:34 2010.Slide12

Inflammation

CRPPeak and return to the base line are too lateCorrelation with MIcan help to stratify, to screen ischemic heart disease and seems to be a prognostic factor of acute or chronic HF

But lack of specificity -> prentraxin-3 = treatmentOther inflammatory proteinsIL-6 and TNF-α: asymptomatic HF screening

PaPPA: risk of cardiovascular death and future MI predictionSlide13

Oxidative stress : indirect markers

Plasmaoxidized low density lipoproteins 8-isoprostane urinary levels correlate with matrix

metalloproteinases levels: predicting the risk of ventricular remodeling and more severe HF Myeloperoxidase: death caused by HF or MIUric acids indicates detrimental prognosis in HFSlide14

Neurohormones

Activation of S

ympathetic nervous systemNorepinephrin ↑Renin-angiotensine-aldosterone system

Components ↑Predictors of mortality

Gerald W. Dorn II Circulation Research. 2011;108:1270-1283Slide15

Big Endothelin-1

Elevated level post-MIPredictor of death and hospitalizationCTproET1 is in use for measurement

Arginin VasopressinElevated level post-MIPersistently → heart failure / mortality

For measurements: Copeptin(in combination with cTns

)Slide16

Biomarkers

Copeptin is

marked on this illustration post-MI

Kehl

DW,

Iqbal

N,

Fard

A,

Kipper

BA, De La

Parra

Landa A, Maisel AS. Biomarkers

in acute myocardial injury

. Translational Research. 159:252-64. 2012 Slide17

Myocyte injury

Severe cardiac disease

impairs the heartInjury of cardiac muscle

→ release of biomarkersBiomarkers reach

the

circulation

with

delays

http://slideplayer.com/slide/258211/Slide18

Biomarkers

Following

Tissue Ischemia

Kehl

DW,

Iqbal

N,

Fard

A,

Kipper

BA, De La

Parra

Landa

A, Maisel AS.

Biomarkers in acute myocardial injury. Translational Research. 159:252-64. 2012 Slide19

Choline

Component of cell membrane (not

specific)Ischemia, necrosis, ACSPredictor of

cardiac arrest or death

H-FABP

Cytosolic

,

low

molecular

weight

protein

Mainly expressed in myocardiumAssociated

with MI, heart failure and death

Combined with cTnI → higher sensitivity and NPVSlide20

Ischemia

modified albumin (IMA)Most frequent plasma

proteinIschemia → not able to

bind divalent ion albumin cobalt

binding

test

Rapid

elevation

Contradictory

results

Hs-Tn

High

sensitivity troponin assays Slide21

Biomarkers

Following

necrosis

Kehl

DW,

Iqbal

N,

Fard

A,

Kipper

BA, De La

Parra

Landa

A,

Maisel

AS.

Biomarkers

in acute myocardial injury. Translational Research. 159:252-64. 2012 Slide22

Cardiac troponins (

cTns)Complex of three regulatory proteinscTnI and cTnT

is in useSpecificity!Widest diagnostic windowPreferred for MI detection and diagnosis

Indicate poor prognosis The only biomarkers influencing the treatmentSlide23

Creatine

kinase (CK-MB)BM isotype – specific for myocardiumFormer „gold standard” in MI diagnostics

Predictor of hospitalization and deathLess sensitive /specificMyoglobin

Cytoplasmic heme proteinNot specific!

Earlier

Early

AMI

detection

(

often

in

combination

with cTns)Slide24

Biomarkers

Induced

by myocyte stretch

Kehl

DW,

Iqbal

N,

Fard

A,

Kipper

BA, De La

Parra

Landa

A,

Maisel AS. Biomarkers in acute myocardial injury. Translational

Research. 159:252-64. 2012 Slide25

Myocyte stress

N-terminal pro-B-type

natriuretic peptide (NT-proBNP)Inactive

by-product of pro-BNP cleavageMI, heart failure and possibly

ACS

too

Others

MR-proANP

MR-proAdrenomedullin

ST2 (plus IL-33)Slide26

Conclusion

Nowadays, no perfect biomarkerNeed more studiesLeads to a multimarker strategiesSlide27

Thank you for your attention !