How should cardiac biomarkers be utilized in an adult presenting with chest pain to diagnose acute coronary syndrome and assess for heart failure?

Cardiac Biomarkers in Acute Coronary Syndrome and Heart Failure

Immediate Biomarker Strategy for Suspected ACS

Cardiac troponin (cTnI or cTnT) is the mandatory first-line biomarker and must be measured immediately in all adults presenting with chest pain suggestive of acute coronary syndrome. 1, 2

Troponin Measurement Protocol

• Obtain high-sensitivity cardiac troponin (hs-cTn) as soon as possible upon presentation, with results available within 60 minutes. 2

• Repeat troponin measurement at 8–12 hours after symptom onset if the initial sample was drawn within 6 hours of symptom onset and is negative. 1, 2, 3

• For high-sensitivity troponin assays, repeat measurement 1–2 hours after initial collection; for conventional troponin assays, repeat at 3–6 hours. 2

• Cardiac troponin is the preferred marker over CK-MB due to superior sensitivity and specificity—it detects myocardial damage in approximately one-third of unstable angina patients who have normal CK-MB. 1, 3

Diagnostic Interpretation

• A positive troponin result requires both an increase and/or decrease in troponin with at least one value above the 99th percentile of the upper reference limit. 2

• Troponin elevation alone does not diagnose acute myocardial infarction—you must also document at least one of the following: ischemic symptoms, new ischemic ECG changes, development of pathological Q-waves, new regional wall motion abnormality on imaging, or intracoronary thrombus on angiography. 2

• Troponin remains elevated for up to 2 weeks after myocardial injury, allowing detection of recent infarction even in delayed presentations. 1, 3

Risk Stratification Based on Troponin

• Troponin >0.1 ng/mL indicates high risk for death or nonfatal MI and mandates aggressive antithrombotic therapy and early invasive strategy. 3

• Troponin 0.01–0.1 ng/mL indicates intermediate risk. 3

• Normal troponin suggests lower immediate risk but does not exclude unstable angina—clinical assessment and ECG findings remain critical. 3

• Patients with both troponin and CK-MB elevation carry the highest short-term (24-hour and 30-day) risk of death or MI; isolated troponin elevation without CK-MB elevation also confers increased 30-day risk. 1

Role of CK-MB

• CK-MB by mass assay is an acceptable second-choice marker when troponin is unavailable, but it is less sensitive for detecting minor myocardial damage. 1

• CK-MB is most useful for detecting early reinfarction or periprocedural MI because it returns to normal within 36 hours, whereas troponin remains elevated for 2 weeks. 1

• CK-MB loses specificity in skeletal muscle disease, injury, or surgery, and has low sensitivity during very early MI (<6 hours) or late presentations (>36 hours). 1

Myoglobin and Other Early Markers

• Myoglobin has high early sensitivity and may be considered in conjunction with troponin for very early detection (<6 hours), but its very low specificity (elevated in any skeletal muscle injury) and rapid return to normal limit its clinical utility. 1, 3

• Routine use of myoglobin or other early markers is not generally recommended. 1

Natriuretic Peptides for Heart Failure Assessment

BNP and NT-proBNP in Acute Dyspnea

• BNP or NT-proBNP testing is recommended in the acute setting to rule out or confirm the diagnosis of heart failure in patients presenting with dyspnea. 1

• For BNP, a cutoff of 100 pg/mL provides 90% sensitivity, 76% specificity, and 81% diagnostic accuracy for acute heart failure. 1

• For NT-proBNP, use age-adjusted cutoffs: <450 pg/mL for patients <50 years and <900 pg/mL for patients ≥50 years to diagnose acute heart failure; NT-proBNP <300 pg/mL has 99% negative predictive value for ruling out acute heart failure. 1

• BNP or NT-proBNP testing in the emergency department improves diagnostic accuracy, reduces time to discharge, and decreases total cost of treatment compared with clinical assessment alone. 1

Limitations and Pitfalls

• Do not use BNP or NT-proBNP testing routinely in patients with an obvious clinical diagnosis of heart failure—it adds no value. 1

• Natriuretic peptide testing should not replace conventional clinical evaluation or echocardiographic assessment of left ventricular structure and function. 1

• Routine BNP or NT-proBNP testing is not warranted for making specific therapeutic decisions in acute or chronic heart failure because evidence for treatment guidance remains incomplete. 1

Prognostic Value in ACS

• BNP or NT-proBNP may be considered to supplement global risk assessment in patients with acute coronary syndrome, as elevated levels predict adverse outcomes. 3

Troponin Elevation in Heart Failure Without ACS

• In advanced or decompensated heart failure, transient or persistent troponin elevation may occur without obvious myocardial ischemia and is associated with poor long-term prognosis. 1

• The utility of routine troponin assessment in chronic heart failure and the appropriate therapeutic approach to elevated troponin in non-ACS settings remain undetermined. 1

Critical Timing and Integration

• Obtain a 12-lead ECG within 10 minutes of presentation alongside immediate troponin measurement—these are the two essential diagnostic elements for suspected ACS. 1, 2

• Incorporate the time from symptom onset into your interpretation of biomarker results, because the release pattern of cardiac biomarkers is time-dependent. 1

• If the initial ECG is nondiagnostic but clinical suspicion remains high, obtain serial ECGs at 15–30 minute intervals to detect evolving ST-segment changes. 1

Multimarker Approaches

• Besides troponin, no other biomarkers have consistently proven useful for selecting specific treatments in ACS. 4

• Troponin has been validated for guiding antithrombotic, antiplatelet, and invasive treatment decisions. 4

• Multimarker strategies combining natriuretic peptides with inflammatory markers (e.g., myeloperoxidase, high-sensitivity CRP) may enhance diagnostic yield for cardiac dysfunction screening, but prospective validation is lacking. 1

Common Pitfalls to Avoid

• A single normal troponin does not rule out ACS—serial measurements are mandatory because sensitivity is low in the first 6 hours after symptom onset. 1, 2

• Do not assume a normal physical examination excludes myocardial infarction—uncomplicated MI can present with entirely normal findings. 2, 5

• Familiarize yourself with the diagnostic cutoffs and assay generation used in your local hospital laboratory, as multiple troponin methods exist with different reference ranges. 1

• Do not use nitroglycerin response to differentiate cardiac from non-cardiac chest pain—esophageal spasm and other conditions also respond to nitroglycerin. 2, 5