Cardiac Assessment - Part 1

Describe the heart.

• pump of the cardiovascular system

  • sends deoxygenated blood to lungs and pumps oxygenated blood to every cell

  • oxygen drives metabolism of glucose → ATP

Describe the red blood cells?

• membrane sacks packed with hemoglobin

  • if membrane ruptures (hemolysis), hemoglobin / red-cell enzymes spill into serum

  • matters for LD-1 test

Describe the brain?

• 2% of body weight but consumes 20% of oxygen

  • constant, high demand

Describe the coronary arteries.

• feeds the heart

• left coronary artery supplies the larger, more critical territory

• left sided-blockage is more dangerous

What is an ischemia?

• reduced blood (oxygen) supply to the heart muscle

• reversible if brief

What is an angina?

• chest pain from ischemia with NO CELLULAR NECTOSIS

• troponin: normal

• less severe event

What is an Acute MI?

• ischemia lasting long enough (roughly 30+ minutes) to kill muscle cell

• troponin ↑

What is Atherosclerosis?

• hardening of the arteries over many years

• driven by abnormal lipid accumulation

What separates and Angina from Infarction?

• Angina

  • no necrosis

  • troponin: normal

• Infarction

  • kills cell

  • troponin ↑

How does plaque form?

• precipitating event

• Anaerobic switch

• Ischemia-modified albumin (IMA)

Describe the precipitating event in plaque formation.

• damage to epithelium

  • inner lining of coronary vessels

• lipids accumulate, and cellular involvement and clotting follow

Describe the anerobic switch in plaque formation.

• oxygen0starved muscle switches to anaerobic metabolism

• lactate increases

• ↑ lactate → ischemia

• K⁺ and acidosis occur

Describe the Ischemia-modified albumin (IMA) in plaque formation.

• measured by the albumin cobalt-binding (ACB) test

• reflects ischemia before necrosis

• during ischemia the N-terminus of albumin losses ability to bind cobalt

  • early sensitive ischemic marker

When a muscle cell is suddenly worked hard, normal glucose metabolism can NOT regenerate ATP fast enough, so what enzymes act to protect the energy reserve?

• creatine kinase (CK)

• myokinase

• adenylate kinase (MK)

What does creatine kinase do?

• regenerates ATP by transferring a phosphate from creatine phosphate → ADP

What does myokinase / adenylate kinase (MK) do?

• combines two ADP molecules into one ATP and one AMP

What does an ECG do?

• detect the electrical consequences of heart muscle injury and gives rapid diagnosis / prognostic information

• BUT its findings depend on the location, extent, and timing of ischemia / necrosis

When should repeat ECGs be done

• when symptoms persist

• suspicion remains high

When doing an ECG, what must it be interpreted with?

• clinical findings and serial troponin

What is a cardiac marker?

• molecule that leaks from heart-muscle cells into blood when they are damaged

• high sensitivity cardiac troponin is the preferred biomarker

What is used for the current Practice Cardiac marker?

• high sensitive troponin

  • covers early / late presentation in one test

  • helps diagnose MI

• serial change against an assay-specific 99th percentile cutoff , NOT a fixed clock time

What different markers can be used for an acute MI?

• Myoglobin

• CK-MB

• LD-1

• Troponin I

• Troponin T

Describe Myoglobin

appears: 1-3 hr

Peaks: 6-9 hr

stays elevated: 24 h

cardiac specificity: low

Describe CK-MB

appears: 3-6 r

peaks: 24 hr

stays elevated: 2-3 days

cardiac specificity: moderate

Describe Troponin I

appears: 1-3 h

peaks: 12-18 hr

stays elevated: 5-9 days

cardiac specificity: high

Describe Troponin T

appears: 1-3 hr

peaks: 10-12 hr

stays elevated: 10-14 days

cardiac specificity: high

Describe LD-1

appears: 12 hr

peaks: 3-6 days

stays elevated: 10 days

cardiac specificty: moderate (flip)

What is myoglobin?

• small oxygen binding globulin found in all muscle

  • essentially a one-subunit relative of hemoglobin

How is myoglobin used?

• very small soi it diffuses in the blood faster than CK-MB

• earliest marker to rise

• sensitive / nonspecific

• value was a negative predictor and not used when hs-cTn is available

Describe Creatine Kinase

• isoenzyme: dimer of M (muscle) and B (brain) subunits

  • CK-1 BB: brain / smooth muscle

  • CK-2 MB: cardiac / skeletal muscle

  • CK-3 MM: predominant in skeletal / cardiac muscle

what is Macro-CK type 1?

• CK bound to immunoglobin

• may be found in healthy elderly women

What is Macro-CK type 2?

• mitocondrial CK

• may be found in patients with advanced malignancy

What cna Both Macro-CKs do?

• cause persistently elevated results

What methods are used to measure Creatine kinase (CK)?

• coupled reactions

  • Oliver Rosalki

  • Alternate method

Describe the Oliver Rosalki method for measuring creatine kinase.

CK → hexokinase → G-6-PDH

reads NADPH

Describe the alternate method for measuring creatine kinase.

CK → pyruvate kinase → lactate dehydrogenase

follows NADH at 340 nm

What are sources of errors for creatine kinase?

• hemolysis and exercise

• CK-MB has largely been replaced by cardiac troponin

Why is Creatine kinase (CK) not specific?

• total CK rises 50-100x in acute MI but also in musclular dystrophy

  • total CK is NOT a specific indicator

• only the MB fraction points to the heart

What is the reference range for total CK?

• 25 - 170 U/L

What is Lactate dehydrogenase (LD)?

• tetramer of H (heart) and M (muscle) subunits

• giving 5 isoenzymes

Describe the isoenzymes of Lactate Dehydrogenase (LD).

• LD-2 > LD-1

  • after an MI, LD-1 rises over LD-2 “flip”

  • ( LD-1 > 40% of total is abnormal)

• LD-1 is a late marker

  • used for patients presenting days after the event

What is the LD-1 trap?

• RBC are rich in LD-1

  • slight hemolysis releases LD-1 and causes a non diagnostic false elevation

• reject a hemolyzed sample

• LD isoenzymes are NO LONGER recommended for routine MI diagnosis

  • use troponin

What is the gold standard for MI diagnosis?

• Troponin

What is troponin?

• regulatory protein complex of muscle contraction

• has 3 subunits

• the quiz repeatedly tests which ones matter

Describe Troponin C (TnC).

• role: binds calcium

• not used as a marker: no cardiac specific form

Describe Troponin I (TnI).

• role: inhibits actomyosin ATPase

• used as a marker, highly cardiac specific

Describe Troponin T (TnT).

• role: binds tropomyosin

• used as cardiac marker

What is cTnI trusted?

• it is NOT expressed in skeletal muscle and stays largely free in blood after injury so the antibody binds it cleanly

Why is cTnI trusted over cTnT?

• cTnT can be falsely elevated in muscular dystrophy and end stage renal disease

• CTnI is NOT

What does elevated troponin indicate?

• myocardial injury but does NOT by itself establish an MI

• diagnosis of MI requires a rise / fall in troponin + clinical evidence of ischemia

What is serial testing for troponin?

• validated pathways sample at presentation and 1-2 hours later

• decision limits use 99-percentile upper reference / may be sex specific

• results from different manufacturer assay are not interchangeable

What specimen are used for testing troponin?

• serum or heparinized plasma

• some also accept EDTA plasma or whole blood

How are samples used for troponin stored?

• 14 days refrigerated

• 8 weeks at -20 C

How does a troponin assay work?

• two antibody-sandwich immunoassay

  • solid phase antibody capture cTnI

  • second enzyme labeled antibody binds a different epitope

  • substrate produces a signal = to cTnl present