Cardiac Flashcards
What is CHD
Coronary Heart Disease
What is IHD
Ischemic Heart Disease
What exactly is CHD
(4)
The atherosclerosis of the arteries that supply the heart
The arteries which start out smooth and elastic get plaque on their inner walls which can make them more rigid and narrowed
This restricts blood flow to your heart, which can then become starved of oxygen
The plaque can rupture, leading to a heart attack or sudden cardiac death
When this occurs, immediate emergency treatment is necessary to stop the injury from widening, killing additional heart cells, and increasing the risk of complications or death
What are the 5 steps to a heart attack
Plaque rupture
Coronary thrombus
Reduced blood flow
Myocardial ischaemia
Myocardial infarction
What are the steps of progression in CHD?
Angina -> unstable angina -> AMI -> sudden cardiac death
What is ACS
Acute coronary syndrome
What does acute coronary syndrome encompass?
Unstable angina [UA]
Non-ST-segment elevation myocardial infarction (NSTEMI)
ST-segment elevation myocardial infarction (STEMI)
What is NSTEMI
Non-ST-segment elevation myocardial infarction
What is STEMI
ST-segment elevation myocardial infarction
What is stable angina?
Transient episodic chest pain due to myocardial ischaemia, reproducible, frequency constant over time, usually relieved with rest/Nitroglycerin
What is left ventricular hypertrophy [LVH]?
Enlargement and thickening (hypertrophy) of the walls of your heart’s main pumping chamber (left ventricle)
What might cause left ventricular hypertrophy?
High blood pressure or a heart condition that causes the left ventricle to work harder
What is the cardiac muscle cell called?
Myocyte
Comment on myocardial proteins as biomarkers
Size and subcellular distribution of myocardial proteins determines time course of biomarker appearance in the general circulation
Classify laboratory tests used in cardiac disease
(4)
Markers of cardiac tissue damage
Markers of myocardial function
Cardiovascular risk factor markers
Genetic analysis for candidate genes or risk factors
Describe how cardiac markers are used
Ischemia -> hypoxia -> decreased ATP -> cell damage
Reperfusion within 15 to 20 minutes
What is the clinical definition of myocardial infarction?
Myocardial infarction denotes presence of acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischemia
What is the laboratory definition (4th Universal Definition) of myocardial infarction?
The detection of a rise and/or fall of cardiac biomarker values, with at least one of the values being elevated
i.e. > 99th percentile upper reference limit
In addition at least one abnormal change in ECG or imaging changes
What is the preferred biomarker used in detection of Myocardial Infarction?
cTn
Write about cTN
(3)
Cardiac specific form of Troponin (T or I)
The preferred cardiac biomarker of necrosis
It is highly sensitive and specific
What is myocardial injury
Patients with elevated blood troponin levels but without clinical evidence of ischemia
What is ischemia
Diminished blood supply to any tissue or organ of the body, causing a shortage of oxygen
In your own words what is myocardial infarction
Elevated blood troponin levels
AND clinical evidence of ischemia
What specific type of cTn is used in investigation of MI
High-sensitivity cardiac troponin
What are the traditional biochemical markers in myocardial ischemia/necrosis?
(6)
AST activity
LDH activity
LDH isoenzymes
CK-Total
CK-MB activity
CK-Isoenzymes
What are the recent biochemical markers in myocardial ischaemia/necrosis?
CK-MB (mass)
c. Troponins (I or T)
Myoglobin
What are the future biochemical markers in myocardial ischemia?
Ischaemia Modified Albumin
Glycogen Phosphorylase BB
Fatty Acid Binding Protein
Highly Sensitive CRP
What are the eight characteristics of the ideal cardiac biomarker?
Absolute cardiac specificity
Specific for irreversible injury
Early release
High tissue sensitivity
Stable release
Predictable clearance
Complete release (infarct sizing)
Measurable by conventional methods
What were the two main necrosis biomarkers of the past?
Lactate dehydrogenase (LDH)
Aspartate aminotransferase (AST)
What is lactate dehydrogenase?
(2)
Ubiquitous enzyme found in myocytes, skeletal muscle, liver, kidney, platelets and red blood cells
5 major isoenzymes LD1-LD5
What was LD1 and LD2 used to detect?
Myocardial infarction
LD1 used more than LD2
What was LD4 and LD5 used to detect?
Hepatic or skeletal muscle injury
What was LD2, LD3 and LD4 used to detect?
Platelets/lymphatic
What was aspartate aminotransferase, and what was is used for
Found in skeletal muscle, liver, rbcs and myocardium
Mitochondrial AST and Cytoplasmic AST
MAST higher in severe tissue injury
Isoenzymes not fractionated for clinical use
Takes 6-8 hours to be detected, peak at 18-24hours, return to normal after 4 to 5 days
What are the necrosis biomarkers used today
(3)
Myoglobin
Creatinine Kinase [CK] -> CK-MB Isoenzyme (cardiac)
Cardiac Troponin T [cTnT] and I [cTNI]
What is myoglobin and why is it used as a cardiac biomarker, are there any limitations?
(6)
The major protein responsible for O2 supply of striated muscle
Found in cytoplasm of cardiac and skeletal muscle cells
Cleared by kidneys - RF up
It is released into blood rapidly (as early as 1 hour) after damage to muscle cell
Early detectable, more sensitive but non-cardiospecific
High negative predictive value -> rule out myocardial necrosis with a negative predictive value approx 9%
Write about creatinine kinase and it’s isoenzymes
(4)
CK exists in skeletal muscle, heart, brain mostly but also in small intestine, tongue, diaphragm, uterus and prostate
CK is formed by two subunits, B and M and thus has 3 isoforms: CK-MB, CK-BB and CK-MM
CK-MB predominates in cardiac muscle -u p to 45% of total CK in cardiac muscle and less than 1% of total CK in skeletal muscle
Not recommended for routine MI
Write about how CK-MB measurements used to be taken
Was measured by immuno-inhibition method which can give falsely elevated results due to the presence of atypical CK and CKBB and at times this lead to the misdiagnosis of acute coronary syndrome
Write about how CK-MB measurements are taken now
(2)
We measure the concentration of CK-MB [CK-MB Mass] protein using the sandwich antibody technique
This is more sensitive than the measurement of CK-MB activity
Write about skeletal muscle injury and CK
(3)
7 fold increase in total CK on a per-gram basis
Potential for release of substantial CK-mB upon injury as body mass of skeletal muscle is 100-fold higher than myocardial muscle
Because of this we use the CK-MB index
What is the CK-MB index
(CK-MB mass/Total CK)*100
What does a CK-MB index greater than 2.5% indicate?
Myocardial source of muscle injury
What is the main issue with using CK measurements
(2)
If both myocardial and skeletal muscle injury occur
Skeletal muscle CK-MB may confound the CK-MB index by masking the relatively subtle myocardial Ck-MB and effectively swamping it
What are troponins?
(3)
Also called the troponin complex
A complex of three regulatory proteins (troponin C, troponin I and troponin T)
They are integral to muscle contraction in skeletal muscle and cardiac muscle but not in smooth muscle
What does TnC do?
Binds to calcium ion
What does TnC do?
Binds to calcium ions
What does TnI do?
Binds to actin and inhibits actin-myosin interaction
What does TnT do?
Binds to tropomyosin, attaching to thin filament
What are the cardiac specific isoforms of troponin
cTnI = cardiac Troponin I
cTnT = cardiac troponin T
What was the main issue with cTnI assays?
Lack of industry standardization as there were many different manufacturers
This has been resolved
What is the main issue with cTnT assays
Only one manufacturer (Roche)
They have the intellectual property rights for use of this test
Which troponin should you measure, CTnI or cTnT
It doesn’t matter, either will work
How long will cTnT last?
10-14 days
How long will cTnI last?
4 to 7 days
What are considered the early markers of myocardial necrosis?
CK-MB
Ck isoforms
Troponin (T or I)
Myoglobin (earliest)
What are considered the late markers of myocardial necrosis
Troponin I but especially T
What does clinical history + ECG changes mean
STEMI
What does clinical history - ECG changes + elevated troponin mean
NSTEMI
What does clinical history - ECG changes - elevated troponin mean
Unstable angina
What does a normal ECD and normal cTn mean for the patient
(3)
Low risk of death/AMI
Candidate for early discharge
Reconsider the diagnosis of ACS (acute cardiac ischemia)
What does a normal ECG but high cTn mean for the patient?
(4)
Intermediate risk of death/AMI
Evaluation for other risk indicators (e.g. history of IHD, CHF or DM)
Aggressive anti-thrombotic rx
Consider early cardiac cath for those with other risk indicators
What does ST-Segment depression with no elevation of troponin mean for the patient
(4)
Intermediate risk of death/AMI
Evaluation for other risk indicators (e.g. history of IHD, CHF or DM)
Aggressive anti-thrombotic rx
Consider early cardiac cath for those with other risk indicators
What does ST-segment depression with cTn elevation mean for the patient?
(3)
High risk of death/AMI
Aggressive anti-thrombotic rx
Urgent cardiac cath
What does other ECG changes that ST segment with elevated cTn mean for the patient?
(3)
High risk of death/AMI
Aggressive anti-thrombotic rx
Urgent cardiac cath
What does other ECG change than ST-segment depression with no change in cTn mean for the patient?
(2)
Heterogenous group of patients
Needs further evaluation
When is serial sampling done?
(2)
This is done for cardiac markers when the initial results are negative e.g. at admission
Sampling done again at 6-9 hours later and after 12 hours is recommended if still negative but suspicion still high
What are four biomarkers still in development?
Heart-Type Fatty Acid Binding Protein (FABPs)
Carbonic anhydrase (III) (CAIII)
Ischemia Modified Albumin
Glycogen phosphorylase BB (GPBB)
Write about Heart-Type Fatty Acid-Binding Protein(7)
Abundant in cytoplasm of striated muscle
Specifically and reversibly bound to long chain fatty acids
Found in Myo and Skeletal muscle -> same isoform of FABP, (H-FABP)
Content in skeletal muscle is only 10-30% of that found in cardiac muscle
Very good tissue/plasma ratio
Released soon after onset of MI-early marker
Increased less than 3 hours after MI and returns 12 to 24 hours later
Write about carbonic anhydrase (III) (CAIII)
Cytosolic protein - exclusively in type 1 (slow-switch) skeletal muscle
Myogoblin: CAIII -> from skeletal muscle in 3:1 ration
Not present in myocardium
Combining CAIII and myoglobin is proposed to improve specificity of myoglobin as an early marker for MI
Write about Ischemia Modified ALbumin
(5)
Albumin’s ability to bind to cobalt is reduced during myocardial ischemia (N-terminal)
It rises within minutes of ischemia, stays up for 6-12 hours and normalises within 24 hours
Elevated after enduring sports
Inhibited by endogenous lactate-limited used in DKA, SEPSIS, CKD
Less specific-cancers, liver disease
Write about glycogen phosphorylase BB
(6)
A glycolytic enzyme which plays an essential role in the regulation of carb metabolism
It functions to provide energy supply for muscle contraction
Three isoenzymes in humans
- GP-LL in liver
- GP- MM in muscle
- GP- BB in brain
Write about GP-BB
(6)
Predominant isoenzyme in myocardium
With the onset of tissue hypoxia when glycogen is broken down, GP-BB is converted from structurally bound to cytoplasmic form
In AMI GP-BB increases 1-4 after onset of chest pain
It peaks before CK-MB and cTnT
IT returns to normal after 1 to 2 days
It is not cardiac specific
Write about cardiac natriuretic peptides
(3)
Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and pro-peptide forms
Family of peptides secreted by cardiac atria + ventricles with potent diuretic, natriuretic and vascular smooth muscle relaxing activity
Levels of these neuro-hormonal factors can be measured in blood
What are three clinical uses of Natriuretic peptides especially BNP/N-terminal pro-BNP?
Detection of LV dysfunction
Screening for heart disease
Differential diagnosis of dyspnea
What is angiography/arteriography?
A medical imaging technique used to visualise the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins and the heart chambers
What is coronary artery bypass surgery?
(2)
Surgery which improves the blood flow to the heart with a new route or ‘bypass’ around a section of clogged or diseased artery
The surgery involves sewing a section of vein from the leg or artery from the chest or another part of the body to bypass a part of the diseases coronary artery
What is the pathophysiology of ACS?
(6)
Pro-inflammatory cytokines such as IL-6
Plaque destabilisation - MPO
Plaque Rupture - sCD40L
Acute Phase Reactants - hs -CRP
Ischemia - IMA
Necrosis - cTnT and cTnI
