Cardiac Biomarkers: Clinical Utility

Joseph T

Consultant Lead Cardiologist and Electrophysiologist, Kauvery Heartcity, Trichy

Case Presentation

Case 1

A 55-year-old patient with a history of DM, HT, CKD

On Examination

Fever, Chest pain – 2 h

Vitals

ECG – Normal

CPK MB positive, Troponin T positive (quantitative)

Question

Acute Coronary Syndrome

  1. Yes
  2. No

Investigation

The criteria for type 1 MI include detection of a rise and/or fall of cTn with at least one value above the 99th percentile and with at least one of the following Symptoms of acute myocardial ischemia,

  1. New ischemic electrocardiographic (ECG) changes,
  2. Development of pathological Q waves,
  3. Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology,
  4. Identification of a coronary thrombus by angiography including intracoronary imaging or by autopsy.
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Answer

Acute Coronary Syndrome

  1. Yes
  2. No

Definition of Biomarker

  1. A biomarker is a substance used as an indicator of a biological state that is objectively measured.
  2. Indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.

Example

  1. CPK MB
  2. Troponins I and T
  3. Hs – TROP
  4. BNP/NT BNP
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Cut-off Values

For both cTnT and cTnI, the definition of an abnormally increased level is a value exceeding that of 99% of a reference control group.

Cut off-of Trop T: 0.1 ng/ml and Trop I: 0.5 ng/ml.

Sensitivity and Specificity – Quantitative

With serial sampling up to 12 h after presentation, cTn offers a sensitivity > 95% and a specificity of 90%.

Single sample – sensitivity of 70-75%

Troponin I vs T

No convincing answer for superiority

Troponin I

Troponin T
Trop I more specific Some Trop T in muscle
Trop I lack standardization Trop T only by Roche
Trop I more appropriate in CKD

Trop I assay

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Current AHA guidelines for cTn measurement recommend testing on presentation and again at 8-12 h post symptom onset and the National Academy of Clinical Biochemistry recommends an early marker at 0-6 h and a definitive marker at 6-9 h post-presentation.

Highly Sensitive Troponin

The definition of high-sensitivity cTn is not clearly established, but last-generation assays can detect cTn in approximately 95% of normal individuals.

New 5th generation hs-cTn T and I assays can detect troponin at concentrations 10-100 fold lower than conventional assays.

Increases the sensitivity of cTn in the first few hours after coronary occlusion.

The Negative Predictive Value (NPV) of hs-cTn assays is 95% for AMI exclusion when patients are tested on arrival at the ED.

These hs-cTn assays have allowed the diagnostic cut-off to be lowered to the level of the 99th percentile or lower while maintaining precision at a CV of <10%

For hs-cTn assays – single sample sensitivity 90%, specificity 90%, and the NPV 97-99%.

Moreover, among patients presenting within 3 h of chest pain, high-sensitivity assays – sensitivity 80-85%.

October Report

KHC

KCN

TOTAL
Hs Trop T 0 0 0
Trop I 74 (70) 167 (100) 241
Trop T 276 (201) 8 (8) 284

B Type Natriuretic Peptide (BNP)

Hormones are released in response to volume expansion and increased intra cardiac pressure.

BNP has diuretic, natriuretic and hypotensive effects.

BNP is found in the myocardium and released by the ventricles.

NT – BNP: stable molecule and longer half-life.

October Report

KHC

KCN

TOTAL
NT BNP 66 (10) 79 (18) 145
BNP 2 0 2

Cut-off levels

100-400 pg/ml (90 % predictive value)

Low in obesity, Flash pulmonary edema

Higher in elderly, females, renal failure (NT – BNP) or volume overload state.

Case Series 2

A 42 year old patient with a history of HTN

On Examination

Atypical angina for 12 h, Sweating.

Vitals

ECG – ST elevation in Lead 2, 3, avf

Echo – Normal

Question

1. ACS

2. Not ACS

Investigation

Troponins CPK MB – Negative

CRP – negative

D dimer – positive, Non-specific, Good Negative predictive value.

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Answer

1. ACS

2. Not ACS

Case 3

A 75-year-old patient with a history of COPD, CKD, CAD – Class 3 Dyspnea

Vitals

ECG – sinus tachy, Q3 T3

Echo – RA, RV dilated, severe TR

Investigation

Troponin T positive

D dimer positive

NT -BNP elevated

Diagnosis

  1. Pulmonary Embolism
  2. Heart Failure
  3. COPD exacerbation
  4. Confusion

No Overdoing

Appropriate test for appropriate Scenario

Point of care cardiac markers

  1. There are many commercial POC kits for the measurement of biomarkers including cTn, CKMB, myoglobin and BNP/NT-proBNP.
  2. Shown to reduce turn-around times compared with standard testing.
  3. It has been recommended that if std lab testing exceeds a max 60-min turn-around time (avg – 65-128 min) or 25% of decision time, then a POC device should be implemented.
  4. Turnaround time for our lab – 45 min.

Triple Test

  1. Trop
  2. NT – BNP
  3. D – dimer

At 8 h – 90% sensitivity.

Qualitative troponins are sensitive and specificity – 85% if troponins cross more than 0.5 ng/ml.

Less than 6 h = HS trop is the only marker.

NT BNP is not for CKD.

Conclusion

  1. Measurement of biomarkers may be useful in conjunction with risk assessment to improve diagnosis, treatment and prognosis.
  2. Insufficient data at present to recommend novel biomarkers.
  3. Be wary of confounding factors.
Joseph

Dr. T. Joseph

Interventional Cardiologist & Electrophysiologist

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