Cardiac Biomarkers.ppt

Cardiac Biomarkers: Definitions, Use and Utility

Cardiac Biomarkers: Definitions, Use and Utility

Herbert A. Hartman III, M.D.

Resident, Internal Medicine

University Hospitals/Case Medical Center

PGY-3 Senior Talk

Herbert A. Hartman III, M.D.

Resident, Internal Medicine

University Hospitals/Case Medical Center

PGY-3 Senior Talk

ObjectivesObjectives

1) Present background scientific information concerning cardiac biomarkers including current and historical markers

2) Present information about the medical use and utility of cardiac biomarkers

3) Identify CKMB and TI results in situations where false-positive and false-negative possibilities should be entertained

4) Describe the associations between TI, CKMB and CK in patients with suspected acute coronary syndrome as compared to patients with enzyme elevations in non-ACS situations by using examples

5) Inform audience briefly about ongoing clinical trials regarding use of cardiac biomarkers






DefinitionsDefinitions

“A biomarker is a substance used as an indicator of a biologic state. It is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”--Wikipedia

“Cardiac markers are substances released from heart muscle when it is damaged as a result of myocardial infarction.”

--Wikipedia

Note: As will be discussed, it has been shown that cardiac markers can be released from cardiac tissue as a result of damage from processes other than MI

“A biomarker is a substance used as an indicator of a biologic state. It is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.”--Wikipedia

“Cardiac markers are substances released from heart muscle when it is damaged as a result of myocardial infarction.”

--Wikipedia

Note: As will be discussed, it has been shown that cardiac markers can be released from cardiac tissue as a result of damage from processes other than MI

Diagnosis of Acute Myocardial Infarction

Diagnosis of Acute Myocardial Infarction

Triad of Chest pain, ECG manifestations and elevations of biomarkers of cardiac injury Chest Pain: highly variable and subjective ECG: Objective ST or T-wave changes Biomarker elevations: Objective data defining

ACS/AMI, Right? sometimes

Triad of Chest pain, ECG manifestations and elevations of biomarkers of cardiac injury Chest Pain: highly variable and subjective ECG: Objective ST or T-wave changes Biomarker elevations: Objective data defining

ACS/AMI, Right? sometimes

What biomarkers are good for:What biomarkers are good for:

Diagnosing AMI/ACS Detecting myocardial damage whether due to

AMI or other cardiac process Risk-stratifying patients Commenting on Prognosis

In ACS, pre and post PCI/reperfusion therapy CHF Renal Disease

Stressing interns, confusing residents and worrying cardiology fellows

Diagnosing AMI/ACS Detecting myocardial damage whether due to

AMI or other cardiac process Risk-stratifying patients Commenting on Prognosis

In ACS, pre and post PCI/reperfusion therapy CHF Renal Disease

Stressing interns, confusing residents and worrying cardiology fellows

Which Biomarkers?Which Biomarkers?

CK (CPK)

CK-MB

Troponin-I/T

LD (LDH)

Myoglobin

ALT/AST

Others

CK (CPK)

CK-MB

Troponin-I/T

LD (LDH)

Myoglobin

ALT/AST

Others

Creatine KinaseCreatine KinaseCreatine kinase (CK/CPK) is an enzyme expressed in a number of tissues. Function: it catalyses the conversion of creatine to phosphocreatine degrading ATP to

ADP(In cardiac as well as other tissues, phosphocreatine serves as an energy reservoir for the

rapid regeneration of ATP)

The CK enzyme consists of two subunits, B (brain type) or M (muscle type), Making three different isoenzymes: CK-MM, CK-BB and CK-MB

CK-BB occurs mainly in tissues, rarely of any significance in the bloodstream

Skeletal muscle expresses CK-MM (98%) and low levels of CK-MB (1%)

Sensitive lab tests can pick up these low levels of CK-MB from skeletal muscle

The myocardium has CK-MM at 70% and CK-MB at ~30%

CK therefore, lacks specificity for cardiac damage and needs to be augmented with the MB fraction and Relative Index (RI) to indicate true cardiac damage

Creatine kinase (CK/CPK) is an enzyme expressed in a number of tissues. Function: it catalyses the conversion of creatine to phosphocreatine degrading ATP to

ADP(In cardiac as well as other tissues, phosphocreatine serves as an energy reservoir for the

rapid regeneration of ATP)

The CK enzyme consists of two subunits, B (brain type) or M (muscle type), Making three different isoenzymes: CK-MM, CK-BB and CK-MB

CK-BB occurs mainly in tissues, rarely of any significance in the bloodstream

Skeletal muscle expresses CK-MM (98%) and low levels of CK-MB (1%)

Sensitive lab tests can pick up these low levels of CK-MB from skeletal muscle

The myocardium has CK-MM at 70% and CK-MB at ~30%

CK therefore, lacks specificity for cardiac damage and needs to be augmented with the MB fraction and Relative Index (RI) to indicate true cardiac damage

CKCK

Needs >two-fold increase with simultaneous increase in CK-MB to be diagnostic for MI

May be problematic for use in patients with very little muscle mass Increases 4-6 hours after onset of MI Peak activity is at 18 to 24 hours Usually has returned to baseline levels by 36 hours False positive (for MI) CK elevation can be seen in:

Significant skeletal muscle injury Significant CNS damage (Stroke/Trauma) Occasionally from GI, renal, urologic disease

*elevations of CK secondary to non-cardiac causes have been noted to increase following a flatter curve, rising and disappearing at a slower pace that a cardiac source

Needs >two-fold increase with simultaneous increase in CK-MB to be diagnostic for MI

May be problematic for use in patients with very little muscle mass Increases 4-6 hours after onset of MI Peak activity is at 18 to 24 hours Usually has returned to baseline levels by 36 hours False positive (for MI) CK elevation can be seen in:

Significant skeletal muscle injury Significant CNS damage (Stroke/Trauma) Occasionally from GI, renal, urologic disease

*elevations of CK secondary to non-cardiac causes have been noted to increase following a flatter curve, rising and disappearing at a slower pace that a cardiac source

CK-MBCK-MB High specificity for cardiac tissue Begins to rise 4-6 hours after onset of infarction Peaks at about 12 hours Returns to baseline at 24-36 hours Can be used to indicate early re-infarction if level normalizes and then increases again Lab test is for mass, not activity; mass assays are reported to be more sensitive.

False positive (for MI) CK-MB elevation can be seen in: Significant skeletal muscle injury *Cardiac injury for reason other than MI

Cardioversion, Defibrillation (ACLS CPR/ICD firing) Blunt chest trauma (MVA/Sports injuries) Cardiac AND non-cardiac surgical procedures Cocaine abuse (vasospasm, tachycardia, perfusion/demand mismatch) Non often elevated in myocarditis, unless severe

High specificity for cardiac tissue Begins to rise 4-6 hours after onset of infarction Peaks at about 12 hours Returns to baseline at 24-36 hours Can be used to indicate early re-infarction if level normalizes and then increases again Lab test is for mass, not activity; mass assays are reported to be more sensitive.

False positive (for MI) CK-MB elevation can be seen in: Significant skeletal muscle injury *Cardiac injury for reason other than MI

Cardioversion, Defibrillation (ACLS CPR/ICD firing) Blunt chest trauma (MVA/Sports injuries) Cardiac AND non-cardiac surgical procedures Cocaine abuse (vasospasm, tachycardia, perfusion/demand mismatch) Non often elevated in myocarditis, unless severe

TroponinTroponin

Troponin is a complex of three regulatory proteins that is integral to non-smooth muscle contraction in skeletal as well as cardiac muscle

Troponin is attached to the tropomyosin sitting in the groove between actin filaments in muscle tissue

Troponin has three subunits, TnC, TnT, and TnI Troponin-C binds to calcium ions to produce a conformational change in TnI Troponin-T binds to tropomyosin, interlocking them to form a troponin-

tropomyosin complex Troponin-I binds to actin in thin myofilaments to hold the troponin-

tropomyosin complex in place Thus far, studies have failed to find a source of Troponin-I outside the heart, but

have found some Troponin-T in skeletal muscle Because of it’s increased specificity, our lab uses Troponin-I

Troponin is a complex of three regulatory proteins that is integral to non-smooth muscle contraction in skeletal as well as cardiac muscle

Troponin is attached to the tropomyosin sitting in the groove between actin filaments in muscle tissue

Troponin has three subunits, TnC, TnT, and TnI Troponin-C binds to calcium ions to produce a conformational change in TnI Troponin-T binds to tropomyosin, interlocking them to form a troponin-

tropomyosin complex Troponin-I binds to actin in thin myofilaments to hold the troponin-

tropomyosin complex in place Thus far, studies have failed to find a source of Troponin-I outside the heart, but

have found some Troponin-T in skeletal muscle Because of it’s increased specificity, our lab uses Troponin-I

More about TroponinMore about Troponin

Laboratory range definition: Cutoff is set at 99th percentile of a normal

reference population, variation of less than 10% Since troponin levels are virtually undetectable

in normal subjects, this 99th percentile corresponds to <0.06

-heparin in sample can result in lowered values

Laboratory range definition: Cutoff is set at 99th percentile of a normal

reference population, variation of less than 10% Since troponin levels are virtually undetectable

in normal subjects, this 99th percentile corresponds to <0.06

-heparin in sample can result in lowered values

Troponin UseTroponin Use

Troponin-I levels begin to rise 2-3 hours after onset of MI and roughly 80% of patients with AMI will have positive values at 3 hours

Elevations in Troponin-I and Troponin-T can persist for up to 10 days after MI

Therefore it has good utility for retrospectively diagnosing AMI

Remember, CK-MB returns to baseline by 48 hours Troponin release can also be precipitated by other

conditions that cause myocardial damage

Troponin-I levels begin to rise 2-3 hours after onset of MI and roughly 80% of patients with AMI will have positive values at 3 hours

Elevations in Troponin-I and Troponin-T can persist for up to 10 days after MI

Therefore it has good utility for retrospectively diagnosing AMI

Remember, CK-MB returns to baseline by 48 hours Troponin release can also be precipitated by other

conditions that cause myocardial damage

Troponin Influence on PrognosisTroponin Influence on Prognosis

Since normal people have virtually nil levels of troponin in serum, it is thought that detectable levels indicate chronic disease even if not acute myocardial damage

Degree of elevation of Troponin value can give prognostic information Some data suggest that the 72-96 hour peak TI value

correlates with infarct size. This is not necessarily true with other biomarkers

Since normal people have virtually nil levels of troponin in serum, it is thought that detectable levels indicate chronic disease even if not acute myocardial damage

Degree of elevation of Troponin value can give prognostic information Some data suggest that the 72-96 hour peak TI value

correlates with infarct size. This is not necessarily true with other biomarkers

Lab DetailsLab Details

Run in chemistry section of UH lab on sample of patient serum Red top tube (you may need to draw for yourself someday)

Type of chemistry reaction: CK/CK-MB: Radioimmunoassay Troponin: Immunoassay

An immunoassay is a biochemical test that measures the concentration of a substance in serum or urine, using the reaction of a specific antibody (often monoclonal Ab) or antibodies to bind to its antigen. To determine a numerical result (as in cardiac biomarkers), the response of the fluid being measured must be compared to standards of a known concentration. One of the most common methods is to label either the antigen or the antibody with an enzyme (EIA), radioisotope (RIA), magnetic labels (MIA) or fluorescence.

Run in chemistry section of UH lab on sample of patient serum Red top tube (you may need to draw for yourself someday)

Type of chemistry reaction: CK/CK-MB: Radioimmunoassay Troponin: Immunoassay

An immunoassay is a biochemical test that measures the concentration of a substance in serum or urine, using the reaction of a specific antibody (often monoclonal Ab) or antibodies to bind to its antigen. To determine a numerical result (as in cardiac biomarkers), the response of the fluid being measured must be compared to standards of a known concentration. One of the most common methods is to label either the antigen or the antibody with an enzyme (EIA), radioisotope (RIA), magnetic labels (MIA) or fluorescence.

Other BiomarkersOther Biomarkers LD (LDH)

Used in the past along with aminotransferases to diagnose AMI. LD is non-specific for cardiac tissue, which contains LD-1. However, pancreas, kidney, stomach tissue and red cells also contain LD-1. In the setting of AMI, LD rises at about 10 hours, peaks at 24-48 hours, and remains elevated for up to 8 days.

Myoglobin Ubiquitous small-size heme protein released from all damaged tissues. Increases often occur

more rapidly than TI and CK. Not utilized often for AMI/cardiac damage assessment because of its very rapid metabolism (short plasma half-life) causing short burst increases that are difficult to assess clinically, as well as its lack of specificity for cardiac tissue.

ALT/AST Used as surrogate markers of cellular damage in the past. Very non-specific so not used for

assessment of myocardial damage any longer H-FABP

Heart-type fatty acid binding protein Kinetically similar to myoglobin but more specific to cardiac tissue which contains a greater

percentage of this protein than skeletal muscle May also have role in prediction- prognosis in patients with NSTEMI Current studies ongoing to further evaluate its utility

LD (LDH) Used in the past along with aminotransferases to diagnose AMI. LD is non-specific for cardiac

tissue, which contains LD-1. However, pancreas, kidney, stomach tissue and red cells also contain LD-1. In the setting of AMI, LD rises at about 10 hours, peaks at 24-48 hours, and remains elevated for up to 8 days.

Myoglobin Ubiquitous small-size heme protein released from all damaged tissues. Increases often occur

more rapidly than TI and CK. Not utilized often for AMI/cardiac damage assessment because of its very rapid metabolism (short plasma half-life) causing short burst increases that are difficult to assess clinically, as well as its lack of specificity for cardiac tissue.

ALT/AST Used as surrogate markers of cellular damage in the past. Very non-specific so not used for

assessment of myocardial damage any longer H-FABP

Heart-type fatty acid binding protein Kinetically similar to myoglobin but more specific to cardiac tissue which contains a greater

percentage of this protein than skeletal muscle May also have role in prediction- prognosis in patients with NSTEMI Current studies ongoing to further evaluate its utility

UH LaboratoryUH LaboratoryCK (U/L) Normal Range: 0-215

CKMB (ng/mL)

RELATIVE INDEX- RI (%MB OF CK)

CKMB <7 and RI <4% :Negative

CKMB <7 and RI >4% :Equivocal

CKMB >=7 and RI <4% :Equivocal

CKMB >=7 and RI >4% :Positive

TROPONIN I

LESS THAN 0.07 NG/ML: NEGATIVE

0.07 - 0.5 NG/ML: CONSISTENT WITH POSSIBLE CARDIAC DAMAGE AND POSSIBLE INCREASED CLINICAL RISK.

>0.5 NG/ML: CONSISTENT WITH CARDIAC DAMAGE, INCREASED CLINICAL RISK AND MYOCARDIAL INFARCTION.

CK (U/L) Normal Range: 0-215

CKMB (ng/mL)






TROPONIN I




Timing SummaryTiming Summary

TEST ONSET PEAK DURATION

CK/CK-MB 3-12 hours 18-24 hours 36-48 hours

Troponins 3-12 hours 18-24 hours Up to 10 days

Myoglobin 1-4 hours 6-7 hours 24 hours

LDH 6-12 hours 24-48 hours 6-8 days

Elevated cardiac biomarkers in non-ACS situations


The ACC/AHA task force states that “clinical evidence of myocardial ischemia” is necessary in addition to biochemical evidence because biochemical markers can be elevated in numerous other physiologic scenarios

Some as previously described with CK and TI Others: sepsis, hypovolemia, atrial fibrillation, PE, HF,

myocarditis, myocardial contusion, renal failure and tachycardia

In patients with low pre-test probability of CHD or ACS, increased cardiac biomarkers may skew analysis and diagnosis causing “tunnel vision”

The ACC/AHA task force states that “clinical evidence of myocardial ischemia” is necessary in addition to biochemical evidence because biochemical markers can be elevated in numerous other physiologic scenarios

Some as previously described with CK and TI Others: sepsis, hypovolemia, atrial fibrillation, PE, HF,

myocarditis, myocardial contusion, renal failure and tachycardia

In patients with low pre-test probability of CHD or ACS, increased cardiac biomarkers may skew analysis and diagnosis causing “tunnel vision”



Situations of prolonged myocyte ischemia--cell membrane breaks down releasing myofibril cell components into the bloodstream

Tachy/bradyarrhythmias (reduced diastolic coronary filling time), prolonged/profound hypotension, HF-acute and chronic, pulmonary hypertension

CPR/Cardiac contusion Electrical Cardioversion/ICD firing PE, pericarditis, myocarditis Sepsis (SIRS)-- secondary both to hypotension as well as direct effects of

inflammatory mediators and myocardial oxygen demand-supply mismatch) Apical Ballooning syndrome-- “Takotsubo Cardiomyopathy” Chemotherapy, e.g. Adriamycin, Herceptin Toxins, cocaine Extreme exertion--Marathons, ultramarathons, Military basic training LVH--leads to subendocardial ischemia by increased O2 demand from increased mass HF--discussed separately

Situations of prolonged myocyte ischemia--cell membrane breaks down releasing myofibril cell components into the bloodstream

Tachy/bradyarrhythmias (reduced diastolic coronary filling time), prolonged/profound hypotension, HF-acute and chronic, pulmonary hypertension

CPR/Cardiac contusion Electrical Cardioversion/ICD firing PE, pericarditis, myocarditis Sepsis (SIRS)-- secondary both to hypotension as well as direct effects of

inflammatory mediators and myocardial oxygen demand-supply mismatch) Apical Ballooning syndrome-- “Takotsubo Cardiomyopathy” Chemotherapy, e.g. Adriamycin, Herceptin Toxins, cocaine Extreme exertion--Marathons, ultramarathons, Military basic training LVH--leads to subendocardial ischemia by increased O2 demand from increased mass HF--discussed separately

Biomarkers in Renal FailureBiomarkers in Renal Failure

CAD is highly prevalent in patients with end-stage renal disease and patients on dialysis. HTN and DM are very prevalent in this population ESRD itself as well as dialysis change normal homeostatic mechanisms

for lipids, calcium and electrolytes Like HF patients, it has been found that ESRD patients nay have low

levels of troponin elevations chronically without evidence of myocardial damage, although the mechanism and significance are not known.

Possible reasons parallel those for HF: significant LVH, endothelial dysfunction, loss of cardiomyocyte

membrane integrity and possibly impaired renal excretion

CAD is highly prevalent in patients with end-stage renal disease and patients on dialysis. HTN and DM are very prevalent in this population ESRD itself as well as dialysis change normal homeostatic mechanisms

for lipids, calcium and electrolytes Like HF patients, it has been found that ESRD patients nay have low

levels of troponin elevations chronically without evidence of myocardial damage, although the mechanism and significance are not known.

Possible reasons parallel those for HF: significant LVH, endothelial dysfunction, loss of cardiomyocyte

membrane integrity and possibly impaired renal excretion

Biomarkers in Renal FailureBiomarkers in Renal Failure

Increasing evidence suggests that chronically elevated troponin levels indicate a worse long-term prognosis for cardiovascular outcomes in this patient population

False positives have been reported with use of troponin-T in ESRD patients but not as much with troponin-I

CK: plasma concentrations are elevated in 30-70% of dialysis patients at baseline, likely secondary to skeletal myopathy, intramuscular injections and reduced clearance

CK-MB: 30-50% of dialysis patients exhibit an elevation in the MB fraction >5% without evidence of myocardial ischemia

Therefore, the most specific marker for suspected AMI in ESRD patients is Troponin-I with an appropriate sequential rise

Increasing evidence suggests that chronically elevated troponin levels indicate a worse long-term prognosis for cardiovascular outcomes in this patient population

False positives have been reported with use of troponin-T in ESRD patients but not as much with troponin-I

CK: plasma concentrations are elevated in 30-70% of dialysis patients at baseline, likely secondary to skeletal myopathy, intramuscular injections and reduced clearance

CK-MB: 30-50% of dialysis patients exhibit an elevation in the MB fraction >5% without evidence of myocardial ischemia

Therefore, the most specific marker for suspected AMI in ESRD patients is Troponin-I with an appropriate sequential rise

Biomarkers in Heart FailureBiomarkers in Heart Failure

It has been reported that small elevations in TI are chronically found in patients with heart failure, without current symptoms of ischemia

In these studies, the presence of TI remained an independent predictor of death

On the same note, a positive TI in a hospitalized patient with ADHF is associated with a higher in-hospital mortality 8% vs. 2.7% P<0.001 (data from Peacock et al. reference at end)

The presumed mechanism of cardiac troponin release in HF is from myocardial strain-volume and pressure overload of both ventricles causing

excessive wall tension leading to decreased subendocardial myocyte perfusion.

There is a correlation of elevated BNP and TI release myocyte death- continued wall tension and other mediator stimulation

(sympathetic stimulation, increased renin-AII system, inflammatory cytokines) is thought to lead to progressive myocyte apoptosis and cardiac dysfunction

It has been reported that small elevations in TI are chronically found in patients with heart failure, without current symptoms of ischemia

In these studies, the presence of TI remained an independent predictor of death

On the same note, a positive TI in a hospitalized patient with ADHF is associated with a higher in-hospital mortality 8% vs. 2.7% P<0.001 (data from Peacock et al. reference at end)

The presumed mechanism of cardiac troponin release in HF is from myocardial strain-volume and pressure overload of both ventricles causing

excessive wall tension leading to decreased subendocardial myocyte perfusion.

There is a correlation of elevated BNP and TI release myocyte death- continued wall tension and other mediator stimulation

(sympathetic stimulation, increased renin-AII system, inflammatory cytokines) is thought to lead to progressive myocyte apoptosis and cardiac dysfunction

Case 1Case 1

62 yo male with PMH of HTN x20 years, DM II x 10 years presents with 2 hours of mid-sternal chest pain radiating to left arm and jaw, with associated SOB and diaphoresis. He was given O2, ASA 325mg and SL NTG en-route by EMS. Upon arrival to ED his CP is 5/10, somewhat relieved by the nitro, His ECG shows TWI in v2-v6. BP 150/100, P115, R18, 96% 2L NC

62 yo male with PMH of HTN x20 years, DM II x 10 years presents with 2 hours of mid-sternal chest pain radiating to left arm and jaw, with associated SOB and diaphoresis. He was given O2, ASA 325mg and SL NTG en-route by EMS. Upon arrival to ED his CP is 5/10, somewhat relieved by the nitro, His ECG shows TWI in v2-v6. BP 150/100, P115, R18, 96% 2L NC

Case 1 DiscussionCase 1 Discussion

What is your pre-test probability for ACS before you get cardiac biomarkers in this patient?

Which biomarkers to you think will be positive at this time? In 12 hours?

Will you wait for the biomarker results to start treatment for ACS?

What is your pre-test probability for ACS before you get cardiac biomarkers in this patient?

Which biomarkers to you think will be positive at this time? In 12 hours?

Will you wait for the biomarker results to start treatment for ACS?

Timing RevisitedTiming Revisited

TEST ONSET PEAK DURATION

CK/CK-MB 3-12 hours 18-24 hours 36-48 hours

Troponins 3-12 hours 18-24 hours Up to 10 days

Myoglobin 1-4 hours 6-7 hours 24 hours

LDH 6-12 hours 24-48 hours 6-8 days

Case 2Case 2

55 yo female with no significant PMH but positive FHx for early MI in her brother at 48 years, and her father at 56 years, presents with mid-epigastric pain episodes lasting 1hr each, off and on for the last 24 hours after her labor Day BBQ (1st episode 24hrs ago), and she thinks her right arm is “tingly.” The last episode was 2 hours ago, but the pain is gone now. The ED gave her 1” nitropaste, 81mg asa x4 and Lovenox 1mg/kg, as well as Zofran and Morphine. Her ECG shows TWI in lead II. Pulse is 100. Other VS WNL.

55 yo female with no significant PMH but positive FHx for early MI in her brother at 48 years, and her father at 56 years, presents with mid-epigastric pain episodes lasting 1hr each, off and on for the last 24 hours after her labor Day BBQ (1st episode 24hrs ago), and she thinks her right arm is “tingly.” The last episode was 2 hours ago, but the pain is gone now. The ED gave her 1” nitropaste, 81mg asa x4 and Lovenox 1mg/kg, as well as Zofran and Morphine. Her ECG shows TWI in lead II. Pulse is 100. Other VS WNL.


What is your pre-test probability of ACS in this patient and how are you going to utilize your blood tests?

Obviously the ED physician felt this was likely to be ACS, do you agree?

If her troponin comes back as 0.07 with a normal CK and CK-MB what will you do?

What is your pre-test probability of ACS in this patient and how are you going to utilize your blood tests?

Obviously the ED physician felt this was likely to be ACS, do you agree?

If her troponin comes back as 0.07 with a normal CK and CK-MB what will you do?

UH LaboratoryUH LaboratoryCK (U/L) Normal Range: 0-215

CKMB (ng/mL)






TROPONIN I




CK (U/L) Normal Range: 0-215

CKMB (ng/mL)






TROPONIN I




Case 3Case 3

73 yo AAM presents to clinic for routine HF check. By office scale he has gained 10# since last visit 2 months ago. He admits to sleeping upright and has1block DOE. He denies angina/chest pain. In-office ECG is notable for strain pattern. He is diagnosed with HF exacerbation and direct admitted. AMI panel is drawn and CK is 250, MB is 8, TI is 1. BNP is 3500. 2nd TI is 1.2 and 3rd is 1.1. He is hypertensive but stable.

73 yo AAM presents to clinic for routine HF check. By office scale he has gained 10# since last visit 2 months ago. He admits to sleeping upright and has1block DOE. He denies angina/chest pain. In-office ECG is notable for strain pattern. He is diagnosed with HF exacerbation and direct admitted. AMI panel is drawn and CK is 250, MB is 8, TI is 1. BNP is 3500. 2nd TI is 1.2 and 3rd is 1.1. He is hypertensive but stable.


What is the likely explanation for this patient’s elevated cardiac biomarkers?

How do you plan to manage this patient from here? Does he need to be in the CICU? Does he need further enzyme studies?

What is the likely explanation for this patient’s elevated cardiac biomarkers?

How do you plan to manage this patient from here? Does he need to be in the CICU? Does he need further enzyme studies?

Case 4Case 4

44 yo AAF with ESRD secondary to HTN on dialysis (HD x 7 years) presents with chest pain at dialysis. Her end-HD BP was 190/100 and she reports a headache. ECG shows Q-waves in the inferior leads but no acute changes. She got her flu shot at dialysis today. You draw AMI panel and CK is 300, MB 15, RI 4% and TI is 1.13

44 yo AAF with ESRD secondary to HTN on dialysis (HD x 7 years) presents with chest pain at dialysis. Her end-HD BP was 190/100 and she reports a headache. ECG shows Q-waves in the inferior leads but no acute changes. She got her flu shot at dialysis today. You draw AMI panel and CK is 300, MB 15, RI 4% and TI is 1.13


If her serial enzymes stay at the same levels what is her general Cardiovascular prognosis?

Given the story, what other findings do you expect on her ECG?

What is the likely physiological mechanism for her elevated CK? Her TI?

She refuses cath. What is the best, simplest way to attenuate her cardiovascular mortality?

If her serial enzymes stay at the same levels what is her general Cardiovascular prognosis?

Given the story, what other findings do you expect on her ECG?

What is the likely physiological mechanism for her elevated CK? Her TI?

She refuses cath. What is the best, simplest way to attenuate her cardiovascular mortality?

ReferencesReferences1) Zethelius, B. et al. Use of multiple Biomarkers to Improve

the Prediction of Death from Cardiovascular Causes. NEJM 2008;358;2107-16.

2) Peacock, F. et al. Cardiac Troponin and Outcome in Acute Heart Failure. NEJM 2008;358:2117-26.

3) Brunwald, E. Biomarkers in Heart Failure. NEJM 2008;358:2148-59

4) Foy, A and Weitz, H. When to Suspect a false-positive cardiac troponin. Resident and Staff Physician 2008;54(4):32-36.

5) Jaffe, A. Troponins, creatine kinase, and CK isoforms as biomarkers of cardiac injury. Up-To-Date. 2008.

6) Henrich, W. Serum cardiac enzymes in patients with renal failure. Up-To-Date. 2008.

7) Gibson, C. Elevated serum cardiac troponin concentration in the absence of an acute coronary syndrome. Up-To-Date. 2008.

1) Zethelius, B. et al. Use of multiple Biomarkers to Improve the Prediction of Death from Cardiovascular Causes. NEJM 2008;358;2107-16.

2) Peacock, F. et al. Cardiac Troponin and Outcome in Acute Heart Failure. NEJM 2008;358:2117-26.

3) Brunwald, E. Biomarkers in Heart Failure. NEJM 2008;358:2148-59

4) Foy, A and Weitz, H. When to Suspect a false-positive cardiac troponin. Resident and Staff Physician 2008;54(4):32-36.

5) Jaffe, A. Troponins, creatine kinase, and CK isoforms as biomarkers of cardiac injury. Up-To-Date. 2008.

6) Henrich, W. Serum cardiac enzymes in patients with renal failure. Up-To-Date. 2008.

7) Gibson, C. Elevated serum cardiac troponin concentration in the absence of an acute coronary syndrome. Up-To-Date. 2008.

Objectives:Objectives:











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