CardiologyTier 2Topic

Blood tests, such as troponin and B-type natriuretic peptide

Two biomarkers, two questions

Two biomarker families that answer different questions:
- Troponin: is there myocardial injury? (not "is there an MI?")
- Natriuretic peptide: is there raised ventricular filling pressure? (not "is there heart failure?")
*Both are far better at ruling OUT than ruling in. Their negative predictive value is what earns them their place*

Troponin is among the most frequently ordered tests in Australian EDs
hs-cTn assays detect a measurable troponin in >50-90% of healthy adults - which is what makes serial change, not a single value, the diagnostic unit
~2/3 of raised troponins in an unselected medical inpatient population are not primary coronary events
BNP/NT-proBNP is not universally available or MBS-rebated in Australian primary care - access varies by state and by hospital

Troponin

cTnI and cTnT are cardiac-specific structural proteins of the thin filament
- Released on reversible membrane injury and on necrosis - *"troponin rise" means myocyte injury, not infarction*
Kinetics (conventional assay): rise from 2-3 h, peak 18-24 h, detectable up to 7-14 days
- hs-cTn shortens the blind period to ~1-2 h - the basis of accelerated pathways
cTnT is elevated in skeletal myopathy and in renal failure more than cTnI
*A single normal troponin very early after symptom onset does not exclude MI* - repeat

Natriuretic peptides

Ventricular wall stretch -> proBNP -> cleaved to BNP (active) + NT-proBNP (inactive)
BNP: natriuresis, vasodilatation, dec RAAS/sympathetic activity
Half-life: BNP ~20 min; NT-proBNP ~60-120 min; NT-proBNP is renally cleared and rises more with CKD
Sacubitril inhibits neprilysin -> BNP rises, NT-proBNP does not. Use NT-proBNP to monitor anyone on ARNI

A. Troponin - myocardial injury vs infarction

Myocardial injury = cTn above the 99th percentile upper reference limit (URL)
- Acute if there is a rise and/or fall; chronic if stable
Myocardial infarction = myocardial injury PLUS clinical evidence of ischaemia (symptoms, new ischaemic ECG change, new Q waves, imaging evidence of new loss of viable myocardium or new RWMA, or intracoronary thrombus)
Fifth Universal Definition of MI (2026) - two changes that matter:

1. Sex-specific 99th percentile URLs are now required - a single unisex cut-off systematically under-diagnoses MI in women

2. The numbered types have been replaced by three clinical categories:

New category	Was	Mechanism
Primary MI	Type 1	Acute coronary atherothrombosis - plaque rupture/erosion
Secondary MI	Type 2	Oxygen supply-demand mismatch from another acute illness - tachyarrhythmia, sepsis, anaemia, hypoxaemia, hypotension, hypertensive crisis, spasm, embolism
Procedure-related MI	Types 4a/4b/4c, 5	PCI, stent thrombosis, restenosis, CABG

Type 3 (sudden death with ischaemic features before biomarkers could be drawn) is retained conceptually within primary MI
MINOCA - MI with non-obstructive coronaries: a working diagnosis, not a final one. Work up with CMR (myocarditis, takotsubo, infarct pattern), intracoronary imaging (plaque disruption), spasm provocation

B. Accelerated rule-out pathways

ESC 0/1 h (or 0/2 h) hs-cTn algorithm - the current standard
- Rule OUT: very low baseline cTn (with chest pain >3 h), or low baseline and no significant 1 h delta
- Rule IN: high baseline, or a significant 1 h delta
- "Observe" zone in between -> repeat at 3 h + imaging
Australasian ADAPT protocol: rule out ACS if TIMI score 0, hs-cTn negative at 0 and 2 h, and no new ischaemic ECG change
- EDACS-ADP is the more widely used descendant
*Assay-specific cut-offs - always use the local laboratory's numbers, not remembered ones*

C. Raised troponin without primary coronary disease

Cardiac - myocarditis, takotsubo, HF (acute or chronic), tachyarrhythmia, cardiac contusion, ablation/cardioversion/device shock, infiltrative disease (amyloid), cardiotoxic chemotherapy
Non-cardiac - PE (RV strain, prognostic), sepsis, critical illness, CKD, stroke and SAH, aortic dissection, severe hypertension, extreme exertion, rhabdomyolysis
*A raised troponin in any of these is prognostic, not an indication for angiography*
Analytical false positives: heterophile antibodies, macro-troponin complexes, fibrin strands, haemolysis

D. Natriuretic peptides

Use: rule-out of heart failure in the undifferentiated breathless patient
NT-proBNP rule-out thresholds:
- <125 ng/L (non-acute/ambulatory)
- <300 ng/L (acute presentation)
BNP >100 pg/mL for HF: sensitivity ~90%, specificity ~76%, accuracy ~83%
Age-stratified rule-in thresholds for acute dyspnoea (NT-proBNP): >450 (<50 yrs), >900 (50-75), >1800 (>75)

Raises NP	Lowers NP
Age, female sex	Obesity (the big one - a "normal" level does NOT exclude HF in the obese)
AF (use a higher cut-off, ~200 pg/mL BNP)	Flash pulmonary oedema (too early)
Renal impairment	Constrictive pericarditis, HFpEF (relatively lower)
RV strain - PE, pulmonary hypertension, COPD	Sacubitril: NT-proBNP falls, BNP rises
Sepsis, critical illness, high-output states, anaemia
Cardiotoxic chemotherapy, myocarditis

Result	Action
Troponin rise + fall + ischaemic symptoms/ECG	ACS pathway: antiplatelets, anticoagulation, risk-stratify (GRACE), invasive angiography timing by risk
Stable, chronically raised troponin	Do not chase it. Investigate the underlying cardiac/renal disease
Secondary MI (demand ischaemia)	Treat the precipitant - rate control, transfusion, oxygenation, source control. Routine angiography is not the answer; assess for underlying CAD after recovery
Rule-out by 0/1 h algorithm, low risk	Discharge with outpatient assessment. No routine stress test in the ED
NT-proBNP below rule-out threshold	HF effectively excluded - look for another cause of dyspnoea
NT-proBNP raised	Echocardiography - the NP does not make the diagnosis, it selects who gets the echo

NP-guided titration of HF therapy is NOT recommended - titrate to guideline doses and symptoms, not to a number
Serial NP has prognostic value: a fall by discharge predicts fewer readmissions
Troponin surveillance in cardiotoxic chemotherapy, and pre-operative hs-cTn in high-risk non-cardiac surgery, are prognostic uses (MINS), not diagnostic ones

CKD - raises both troponin and NT-proBNP; use serial change, not absolute value
AF - raises BNP independent of HF
Obesity - lowers NP; amyloidosis - both markedly raised, disproportionate to symptoms
PE - raised troponin and BNP both indicate RV strain and worse prognosis
Sepsis and critical illness - both raised; independent mortality markers
Sacubitril/valsartan - dissociates BNP from NT-proBNP
Cardiotoxic chemotherapy, immune checkpoint inhibitor myocarditis (troponin is the screening test)

Any troponin elevation, from any cause, predicts worse outcome - the magnitude tracks with mortality
Persistently raised hs-cTn in stable populations predicts incident HF, CAD and death
NT-proBNP is one of the strongest single prognostic markers in heart failure, at diagnosis and serially
An unexplained raised troponin deserves a diagnosis, not a repeat test
Follow-up: pair every abnormal marker with the imaging test that explains it - echo for a raised NP, and a considered decision about ischaemic assessment for a raised troponin

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