Lab investigation of cardiac disease

Question 1

What are cardiac markers?

Answer 1

• Located in the myocardium
• Released in response to cardiac overload, cardiac injury and cardiac failure
• Can be measured in blood samples

Question 2

What can we use cardiac markers for?

Answer 2

• Rule in/out an acute MI
• Confirm an old MI (present to A&E days later)
• Help to define therapy
• Monitor success of therapy
• Diagnosis of heart failure
• Risk stratification of death

Question 3

What makes a good marker?

Answer 3

• Analytical - cost-effective, simple to perform, quick, precise and accurate
• Clinical - easy detection of disease, sensitivity vs specificity, prognostic value, ability to improve pt outcome

Question 4

Why is CHD so bad?

Answer 4

• 82.5k deaths a year
• 10 deaths an hour!
• Blockage of the coronary arteries through plaque build up - causes occlusion of a vessel
• Not enough oxygen to the heart muscle and tissue = necrosis

Question 5

How do atheromatous plaques develop?

Answer 5

• Initial lesions to complicated lesions
• From first decade, you can see beginnings of lipid accumulation
• Macrophages infiltrate and you get development of foam cells
• Ongoing inflammation causes a build up of the lipid core which can become calcified - hardened arteries
• Significant plaque build up will cause complete occlusion and ongoing thrombosis -> cell death and necrosis

Question 6

Chronic vs acute CHD

Answer 6

Chronic ischaemic heart disease - stable angina, variant angina, silent myocardial ischaemia
- chest pain but not significant for an MI

Acute coronary symptoms

• unstable angina
• NSTEMI
• STEMI

Question 7

How can angina lead to a heart attack?

Answer 7

• Angina from a plaque with fibrous cap in the coronary artery - still sufficient blood flow
• Cap ruptures, blood clot forms around the rupture blocking the artery -> heart attack - significant blockage for necrosis

Question 8

What is important to define the type of CHD?

Answer 8

Have very different treatment, prognosis and management

Question 9

Give 7 causes of chest pain

Answer 9

• Broken rib
• Collapsed lung
• Nerve infection (shingles)
• Pulled muscle
• Infection
• Heary burn
• Pericarditis
• Pulmonary embolism
• Angina
• MI

Question 10

How do we assess CHD?

Answer 10

• medical history
• risk factors
• presenting signs and symptoms
• ECG
• biomarkers
• imaging/scans

Question 11

STEMI VS NSTEMI

Answer 11

• An ST elevated MU is caused by complete obstruction of a coronary artery, causing damage that involved the full thickness of the heart muscle
• A non-ST elevation MI is caused by partial obstruction of a coronary artery, and causes damage that doesnt involve the full thickness of the heart wall

Question 12

What is the criteria for acute MI?

Answer 12

• Evidence of myocardial necrosis with acute ischaemia
• detection of rise and/or fall of cardiac biomarker values (troponin)
• symptoms of ischaemia
• New or presumed new ST-T changes or new left bundle branch block
• Development of pathological Q waves in ECG
• Imaging of new loss of viable myocardium
• Identification of intraoronary thrombus by angiography or autopsy

Question 13

How long does it take for ischaemic cells to die in myocardial injury?

Answer 13

• irreversible injury typially requires 30 mins of ischaemia
• High risk that 80% of cardiac cells within 3 hours, almost 100% by 6 hours
• Cellular contents leak out through membrane, dependent on size and solubility
• Conc gradient from inside to outside is important

Question 14

What cell constituents leak out first in MI?

Answer 14

• Ions (e.g. K, P) leak out first, small components can leak out without membrane damage - ATP pump failure
• Metabolites (e.g. lactate or adenosine) are slightly larger, peaks after 1 hr
• Macromolecule start to leak out after 6 hours when the membrane starts to break down - peaks around 2 hours

Question 15

What are the markers of myocardial damage?

Answer 15

• Cardiac specific markers troponin-T and troponin=I
• Creatine kinase increased 90% MIs, but less specific as also released from skeletal muscle
• Heart-specific isoforms of creatine phosphokinase (CPK-MB)
• Myoglobin raised early but has short duration - less specific for heart damage

Question 16

What are troponins?

Answer 16

• Complex is a component of the thin filaments in striated muscle, complexed to actin
• 3 types - T (myosin binding), I (inhibits actomyosin ATPase), C (calcium binding)
• 3 different proteins structurally unrelated with each other
• Cardiac troponin T and I differ significantly from T and I in skeletal muscle

Question 17

What are the advantages of looking at cardiac troponins?

Answer 17

• An index of cardiac damage - peaks significantly
• Blood levels related to severity of cardiac damage - much larger peak in acute vs minor
• Predicts major adverse cardiac events such as MI (rule out myocarditis as no ongoing necrosis shown)

Question 18

How do we detect troponin?

Answer 18

• ELISA
• Specific capture antibody that is coated on to plates or an absorbent membrane
• Measures protein troponins present in our blood
• Secondary antibody recognises a different epitope on the protein, which has a signal attached that can cause a colour change
• Change determines the presence of
  cardiac troponins in the blood
• false positives come from non-specific Abs in blood

Question 19

What are the differential diagnoses seen with high-sensitive cardiac troponin T (hs-cTnT)?

Answer 19

• Depending on the concentration of hs-cTnT, you can differentiate between different degrees of severity
• Healthy -> stable angina -> micro AMI -> small AMI -> large AMI -> very large AMI
• conc increases exponentially

Question 20

What are the main causes of heart failure?

Answer 20

• Coronary artery disease
• Chronic hypertension
• Cardiomyopathy
• Heart valve disease
• Arrhythmias - AF, VT
• Infective endocarditis
• PE, COPD
• Alcohol and drugs (cocaine)

Question 21

What are 8 symptoms of congestive heart failure?

Answer 21

• Shortness of breath
• Swelling of feet and legs
• Chronic lack of energy
• Difficulty sleeping due to breathing probs
• Swollen or tender abdomen with loss of appetite
• Cough with frothy sputum
• increased urination at night
• Confusion and/ or impaired memory

Question 22

What are natriuretic peptides?

Answer 22

• If heart is pumping too much volume, the vessels will stretch leading to damage of the walls
• heart releases natriuretic peptides to try and reverse this
• Natriuretic - increases urine output - work on renal system to increase sodium and water loss - reduced BV

Question 23

What are the different types of NP?

Answer 23

• Atrial NP - atrial stretch
• Brain NP - ventricular dilation
• Both natriuretic, vasorelaxant and RAAS inhibition
• CNP - endothelial, vasorelaxant and CNS effects

Question 24

How do we measure plasma natriuretic peptides?

Answer 24

• Precursor protein is composed of peptide with an N-terminus that gets cleaved off to form the active peptide
• Dont want ANP around all the time, stored in secretory granules as larger molecules
• Can measure the active markers and also n-terminus portions - useful as they have longer half-life, released in higher conc and easier to detect

Question 25

What are the advantages of n-terminal precursor forms over ANP and BNP?

Answer 25

• Longer half life
• Higher plasma concentrations
• Less sensitive to rapid fluctuations

Question 26

In what situations will plasma ANP and BNP be markedly raised?

Answer 26

• Congestive heart failure
• Aortic stenosis
• Dilated cardiomyopathy
• Hypertrophic cardiomyopathy
• MI
• Chronic renal failure