Cardiac Biomarkers

What is a biomarker?

measurable substance that is specific to the organ or tissue and is released in proportion to the degree of disease

• greater damage = greater disease

WHat are the cardiac biomarkers?

• B-type natiuretic peptide (BNP)

• N-terminal pro-B-type natriuretic peptide (NTproBNP)

• Cardiac troponin I (cTnI)

• Atrial natriuretic peptide (ANP)

• N-terminal pro-atrial natriuretic peptide (NTproANP)

How can we assess cardiac health/disease?

• auscultation

• Radiographs

• Echocardiogram

• Blood markers (cTnI or BNP)

• Cardiac MRI

• Endomyocardial biopsy

Natriuretic peptides are formed as _____________ and then cleaved to _______ immediately.

pre-pro-hormones; pro-hormones

What natriuretic peptides are stored as granules in atrial tissue?

pro-BNP and pro-ANP

Which has a higher concentration of storage: pro-ANP or pro-BNP?

pro-ANP

The N-terminal end of natriuretiuc peptides is the _____ group while the C-terminal end is the _____ group.

amino; carboxyl

What terminal end of natriuretic peptides is the active hormone?

C-terminal end

What do Natriuretic peptides do?

• inhibit tubular sodium uptake in the collecting ducts → water and sodium excretion

• Vasodilation

______ overload → atrial/ventricular _______ → NPs released to _______ water/sodium.

volume; stretch; excretion

Chronic volume overload causes an ______ in BNP/ANP production in the myocardium.

increase

Natriuretic peptides are always “fighting” the effects of Upregulation of what system in volume overload?

RAAS

Where are natriuretic peptides receptor-C found?

kidney and endothelium

What is the purpose of Natriuretic peptide receptor-C?

binds active peptides to remove them from the bloodstream

What is the function of neural endopeptidase?

lysosomal degradation found in the vascular endothelium

How are inactive segements of natriuretic peptides removed from the body (ex: NTproBNP)?

passive renal secretion

In what cardiac diseases are NP increased production and release?

• MMVD

• DCM

• HCM

What is MMVD?

incompetent mitral valve where blood leaks backwards into the LA during systole which increases volume/pressure in LA and causes stretch → increased peptides

How does DCM lead to increased natriuretic peptides?

• reduced LV systolic function

• poor CO

• Increased volume/pressure in LV → stretch

  • LV and LA volume overload

How does HCM lead to increased natriuretic peptides?

• reduced lumen size

• Reduced LA emptying

• Increased volume and pressure in LA → strecth

Which is more stable: Active hormone or inactive?

Inactive

What is the inactive form of BNP?

NTproBNP

Most research uses ______ due to technical ease of handling.

NTproBNP

Cardiac troponin I

troponin subunits associated with tropomyosin in cardiac and skeletal muscle

Which subunit is asssociauted with cardiac disease for troponin?

I

Cardiac troponin I is mostly bound to the _______ unit.

contractile

What happens when a cardiomyocyte is damaged in regards to troponin I?

• cTnI leaks into the interstitium

• Taken yp by cardiac lymphatics

• CTnI in systemic circulation and passively excreted by kidneys

Cardiac troponin I is _____ not _____ for cardiac damage.

sensitive; specific

What diseases cause elevations in cTnI?

• inflammation of myocardium

• Infection of myocardium

• Neoplasia in myocardium

• Ventricular arrythmias

• Trauma (HBC)

True or False: The severity of elevations of cTnI is equal to the severity of damage.

TRUE

True or False: Every animal needs cardiac biomarkers measured.

FALSE - minimize false positives

A 1 yo DSH who is clinically healthy without any prior history or clinical signs of CV disease has a _____ probability of disease and a ______ risk of false positives when measuring NTproBNP.

low; high

You have a cat presenting for surgery and ausculatate a murmur. On BW, you run a NTproBNP and it is high. What is the likelihood it has disease and what should you do next?

HIGH; echo

An adult cat presents sneezing and in respiratory distress. You want to R/O CHF or primary respiratory disease and preform an NRproBNP. The test comes back low. The chances of the cat being in CHF is _____

low

What is the point of care test used for NTproBNPO in cats?

SNAP feline cardio pet proBNP test

What is the cut off value for detection on the SNAP test?

100pmol/L

How quickly can you get results from the SNAP test?

10 mins

True or False: There is a SNAP test available for proBNP in dogs.

FALSE

Each 100pmol/L increase is a ____% hazard increase for disease.

7

Increased NTproBNP means a ______ mortality.

HIGH

True or False: If both NTproBNP and cTnI are increased in a cat with MMVD, it increases the risk of death by 6x.

TRUE

True or False: A change in value of NTproBNP-BNP is dependent on the disease.

FALSE - biological variability (use average)

A cTnI level of _____ indicates AV nodal fibrosis.

0.006ng/mL (LOW)

A cTnI level of _____ indicates myocardial damage and indicates you should test for ______.

9,5ng.mL (HIGH); myocarditis

You find a dog in 3rd degree AV block. What are your three differentials and how do you test it?

• Myocardial damage: HIGH cTnI → test for myocarditis

• Excess vagal tone: atropine → sinus tachy → evaluate for systemic dz

• AV nodal fibrosis: LOW cTnI → no further testing

Why is no further testing needed for AV nodal fibrosis?

It is a normal aging change