Cardiac Markers

system of valves regulate flow

SVC/IVC -> RA -> Tricuspid -> RV -> Pulm valve -> Pulm trunk -> Lungs -> LA -> mitral valve -> LV -> aortic valve -> aorta -> systemic body

Pump facts

• Supports ALL organ systems

• Avg life time 2.76B beats

• Intrinsic "electrical" system supports function

• Metabolic - ATP & active peptides synthesis

cardiac pathophysiology

ischemic injury

conduction/rhythm abnormalities

valvular pathology

infection

pump failure (CHF)

intra-chamber thrombosis

ischemic injury

not enough blood d/t inclusion - plaque, thrombus

conduction/rhythm abnormalities

SA node

AV node

Purkinje fibers

valvular pathology

congenital

Ca

ID

infection pathophysiology

rheumatic heart disease

endocarditis - endocardium

myocarditis - myocardium

pericarditis - pericardial sac

pump failure (CHF) pathophysiology

HTN

Pulm intrinsic

intra-chamber thrombosis

move out to brain, lungs

ACS

sudden imbalance between myocardial oxygen supply and demand

most often occurs in coronary arteries

• Sustained ischemia results in injury to & eventual death of cardiac muscle cells (myocytes)

  • Acute myocardial infarction (AMI)

• Commonly d/t plaque rupture & thrombosis

Causes 20% of all deaths and CVD 40% of deaths

3 types: NSTEMI, STEMI, unstable angina

ruling in vs ruling out

NSTEMI

EKG important

STEMI

urgent need for intervention

unstable angina

better navigated w/ high sensitivity troponin

ruling in AMI

high dx sensitivity w/ limited false (-)

have condition, test (+)

ruling out AMI

high dx specificity w/ limited false (+)

if don’t have condition, test (-)

ideal cardiac biomarker

• Early detection

• Rapid, sensitive, & specific dx

• Component for risk stratification

• Assess success of reperfusion after thrombolytic procedure

• Detect reocclusion and reinfarction

  • Particularly early

  • Enzymes don't tend to de-elevate until 5 days post-infarct

• Determine timing of an infarction and infarct size

• Detect procedural-related perioperative MI during cardiac or noncardiac surgery

• Perfect test does not yet exist

cardiac markers

serum myoglobin

CK (CPK)

CK-MB

troponins most sensitive/specifc (most common)

serum myoglobin

found in striated muscle

not at all cardiac specific

expected to rise early - 1hr after muscle damage occurs

values peak 8-12 hrs, WNL at 24 hrs

rarely used in eval of ACS - overly sensitive

CK (CPK)

nonspecific - in heart, muscle, intestines, brain

released into blood if structures damaged

declines faster, some clinicians prefer for early re-injury

CK-MB

more cardiac specific

declines faster, some clinicians prefer for early re-injury

troponins most sensitive/specific (best option)

complex of 3 protein subunits - regulatory complex for excitation-relaxation of myofibrillar filament

critical dx and estimating size of myocardial injury - rise 4-6 hrs

very specific marker, limited false (-) d/t high sensitivity

troponin 3 protein subunits

Trop C - Ca binding

Trop I - Inhibitory - most commonly used d/t high sensitivity

Trop T - tropomyosin-binding

how troponin used

TnT elevated in - ACS, acute MI

TnT takes 4-6 hrs to be detected after injury - remains elevated 1 wk or more, high levels = death of cardiac tissue

POTC TnI level testing

highly-sensitive (hs) troponin

improved analytical sensitivity - early dx (ability to r/i or r/o by 2-3 hrs insead of 6 hrs)

Hs-cTnT and hs-cTnI tests available

timing of troponin sampling

blood samples drawn at presentation (0 hr) - often hrs after clinical sxs onset

r/o AMI w/ blood draws at 0, 3, 6, & 9-12 hrs

highly sensitive troponin may just do test at time 0, 1, and 2-3 hrs - change in levels helps verify presence of an MI

interpreting troponins

elevated TnT or TnI = cardiac damage - may not be caused by MI

could be - myocarditis, cocaine-induced coronary artery spasm, severe HF, cardiac trauma (surgery, MVA), PE

normal troponin values

TnI </= 0.04 ng/mL

probable if >0.4 ng/mL

between 0.04 and 0.39 likely some sort of heart issu

Pt p/w chest pain Workup

EKG

CXR

troponin - 0.39ng/mL, not high enough to confirm acute MI (repeat 3-6 hrs)

older woman MI CP

abd/epigastric pain

shoulder pain

N/V

congestive HF

ineffective ventricular function l/t fluid retention w/ pulm fluid accumulation

initial insults sets up cascade of neurohormonal responses

l/t ventricular wall stress and remodeling

CHF etiologies

CAD

HTN

valvular disease

myocarditis

pericardial disease

biomarkers in CHF

B-type Natriuretic protein (BNP)

NT-proBNP

B-type Natriuretic protein (BNP)

pharmaco active hormone

released form heart in response to volume stretch - ventricular dysfunction (fluid retention/volume), BNP release physiologic attempt to compensate

causes - Na diuresis and vasodilation, blockade RAAS

can use as marker of txt - decrease as fluid retention improves

NT-proBNP

produced at same time as BNP from common precursor

levels increase in response to same mechanism as BNP

higher in elderly women than men

lower in obese pts

more elevated in LV dysfunction

use of markers

if normal, dx CHF highly unlikely

both levels rise early in HF - amount of increase correlates w/ ventircular dysfunction

levels stay elevated as long as dysfunction persists

can be elevated d/t - diastolic dysfunction, PE, COPD

usually CHF if clinical picture fits - BNP >500pg/mL, NT-proBNP >450pg/mL (<50y/o), >900pg/mL (>50y/o)

useful in predicting pt outcomes

elevated hsTnT or hsTnI predictive cardiac mortality in hospitalized pts

BNP can be useful monitoring CHF status

pathology of bleeding disorders

genetic - hemophilia VIII

inadequate synthesis - liver dysfunction

lack of substrate - Vit K deficiency

consumptive - platelets and factors

pathology of thrombotic disorders

genetic - Factor V Leiden

consumptive

meds - OCPs, chemo

systemic illness - cancer, autoimmune dysfunction (antiphospholipid syndrome)

infections

intrinsic clotting pathway (PTT)

activated if internal injury to blood vessels

extrinisic clotting pathway (PT)

activated if external injury to blood vessels

common pathways

• Activated by convergence of intrinsic and extrinsic at activation of Factor X to Factor Xa

• l/t conversion of fibrinogen to fibrin and clot formation

intrinsic pathway

Factor XII - Factor XI - Factor IX - Factor VIII - Factor X (common pahway)

extrinsic pathway

tissue factor (TF) - Factor VII - Factor X (common pathway)

common pathway

Factor X - Factor V - Prothrombin - Thrombin - Fibrinogen - Fibrin

clotting function tests

protime (PT)

international normalized ratio (INR)

activated partial thromboplastin time (aPTT)

protime (PT) test

time to takes to clot after adding tissue factor

international normalized ratio (INR) test

standardized look at PT between labs

activated thromboplastin time (aPTT) test

more sensitivity of PTT

used more commonly time takes to clot after adding phospholipid

clotting function test uses

eval status of bleeding disorders - Hemophilia (aPTT may be prolonged)

monitor anticoag therapy - coumadin (PT & INR), heparin (aPTT)

abnormal d/t disease - cancer, liver disease, DIC (1st excessive clotting then bleeding)

PT normal & panic values

WNL - 11-13 sec

Urgent Attention - >30sec

INR normal & panic values

WNL 1.0-1.5

Urgent attention >4.5

aPTT normal & panic values

WNL 30-40sec

Urgent >100sec

anticoag therapeutics

• Heparin, LM heparins (Enoxaparin)

• Direct thrombin inhibitors (Dabigatran)

• Direct Factor Xa inhibitors (Apixaban)

• Vit K antagonists (Warfarin/Coumadin)

  • Be consistent w/ K consumption

• Tissue plasminogen activators (thrombolytic-Alteplase)

• Platelet inhibitors (Clopidogrel)

clotting clinical correlations

• Coumadin disrupts Vit K dependent clotting factors in all pathways including factors II, VII, IX, X

  • Majority of impact on extrinsic & intrinsic common pathways

  • Monitored primarily w/ PT/INR

• Heparin primary impact on intrinsic & common pathways

  • Monitored w/ aPTT

onset of action/monitoring

• PT/INR start to increase 24-36 hrs after starting oral warfarin/Coumadin

  • Full antithrombotic effect may take ~5 days

  • Monitored regularly until stable

  • Vit K rich foods can reduce therapeutic impact of Coumadin

• Heparin given IV or SC and works very quickly (20-60min)

bridging protocol - if hospital pt needs anticoag

• Start warfarin orally and heparin IV/SC

• Target aPTT 1.5-2.0x reference normal level

• Usually PT/INR goal 2.0-3.0 for clot prevention

  • May be higher target range if recurrent clots, PE, mechanical heart valve

• Once PT/INR in therapeutic range, heparin can be stopped

DOAC becoming more common than warfarin/coumadin/heparin

• Effective in 4hrs-2 days

• If able to start DOAC, do it