ECG, Exercise Testing and Cardiac Biomarkers

ECG Interpretation

Systematic technical assessment

Interpretation should begin with confirmation of patient identity, indication, timing, prior ECG comparison, and technical quality. Standard calibration is 25 mm/s and 10 mm/mV; hence 1 small square is 40 ms horizontally and 0.1 mV vertically. Limb lead reversal is common in examinations: right arm/left arm reversal produces negative P-QRS-T in lead I with apparent right axis deviation; dextrocardia additionally causes poor R-wave progression. Artefact may mimic atrial flutter, ventricular tachycardia, or pacemaker spikes and should be suspected when the apparent rhythm is dissociated from a normal pulse or QRS timing.

Rate, rhythm, axis, and intervals

Sinus rhythm requires an upright P wave in lead II, negative P in aVR, and a constant PR interval with each P followed by a QRS. Rate is estimated by 300 divided by the number of large squares between R waves, or by counting QRS complexes in 10 seconds and multiplying by 6 for irregular rhythms. Axis is normally approximately −30° to +90°; left axis deviation suggests left anterior fascicular block, inferior myocardial infarction, ventricular pre-excitation, or LV hypertrophy, whereas right axis deviation suggests right ventricular strain, pulmonary hypertension, lateral infarction, or left posterior fascicular block.

Measurement	Normal adult value	Key pathological implications
PR interval	120–200 ms	>200 ms: first-degree AV block; <120 ms: pre-excitation, junctional rhythm
QRS duration	<120 ms	≥120 ms: bundle branch block, ventricular rhythm, hyperkalaemia, sodium-channel blockade
QTc	<450 ms men, <470 ms women	>500 ms confers materially increased torsades de pointes risk
ST deviation	Isoelectric, minor variation	Ischaemia, pericarditis, early repolarisation, LV aneurysm, electrolyte/drug effects

QT correction is most often by Bazett’s formula, QTc = QT/√RR, although it overcorrects at high heart rates and undercorrects at low rates; Fridericia’s formula is preferable in tachycardia and in drug studies. Congenital or acquired long QT is potentiated by hypokalaemia, hypomagnesaemia, bradycardia, macrolides, fluoroquinolones, antipsychotics, methadone, and class Ia/III antiarrhythmics.

Conduction disease and tachyarrhythmia discrimination

AV block is classified by site and behaviour: Mobitz I is progressive PR prolongation before a dropped beat, usually nodal and often benign; Mobitz II is intermittent non-conducted P waves without PR prolongation, typically His-Purkinje disease and a pacing indication if persistent or symptomatic. Complete heart block shows AV dissociation with escape rhythm: narrow QRS escape implies junctional origin; broad, slow escape implies infranodal disease and higher risk.

Bundle branch block should be diagnosed morphologically, not merely by QRS width. Right bundle branch block has rsR′ in V1 and broad terminal S waves in I/V6. Left bundle branch block has broad/notched R waves in I, aVL, V5–V6, absent septal Q waves, and deep S waves in V1; it obscures ordinary ST-segment interpretation. In suspected infarction with LBBB or ventricular pacing, use Sgarbossa criteria: concordant ST elevation ≥1 mm, concordant ST depression ≥1 mm in V1–V3, or excessively discordant ST elevation ≥5 mm. The modified Sgarbossa criterion, ST elevation/S-wave depth ≤−0.25, improves sensitivity for acute coronary occlusion while maintaining good specificity.

For a regular broad-complex tachycardia, presume ventricular tachycardia until proven otherwise, especially in structural heart disease. Features favouring VT include AV dissociation, capture or fusion beats, extreme axis, concordance across precordial leads, QRS >140 ms in RBBB pattern or >160 ms in LBBB pattern, and Brugada or Vereckei algorithm positivity. Misdiagnosing VT as supraventricular tachycardia with aberrancy and giving verapamil may cause cardiovascular collapse.

Ischaemia, infarction, and repolarisation patterns

ST-elevation myocardial infarction criteria require new ST elevation at the J point in two contiguous leads: generally ≥1 mm, except V2–V3 where thresholds are ≥2.5 mm in men <40 years, ≥2.0 mm in men ≥40 years, and ≥1.5 mm in women. Posterior infarction presents with horizontal ST depression and tall R waves in V1–V3; posterior leads V7–V9 are diagnostic with ST elevation ≥0.5 mm, or ≥1 mm in men <40 years. Right ventricular infarction is suggested by inferior STEMI with ST elevation in V1 or V4R.

Territory	Typical ECG leads	Likely culprit artery
Inferior	II, III, aVF	RCA in most; LCx in left dominance
Anterior/septal	V1–V4	LAD
Lateral	I, aVL, V5–V6	LCx, diagonal, obtuse marginal
Posterior	ST depression V1–V3; elevation V7–V9	RCA or LCx

Pathological Q waves are ≥40 ms wide, ≥2 mm deep, or ≥25% of the following R wave in two contiguous leads, excluding aVR and often III in isolation. Hyperacute T waves are broad-based and regional; they precede ST elevation and must be distinguished from hyperkalaemia, which produces diffuse tall, narrow, tented T waves, PR prolongation, P-wave flattening, QRS widening, and ultimately sine-wave morphology.

Chamber enlargement, electrolyte and drug signatures

LV hypertrophy is suggested by Sokolow–Lyon voltage, S in V1 plus R in V5/V6 >35 mm, or Cornell voltage, R in aVL plus S in V3 >28 mm in men or >20 mm in women; “strain” denotes lateral ST depression and T-wave inversion from abnormal repolarisation, not necessarily acute ischaemia. Right ventricular hypertrophy is suggested by right axis deviation, dominant R in V1, and deep S in V5–V6.

• Hyperkalaemia: peaked T waves usually from K⁺ >5.5 mmol/L; QRS widening and sine wave often >7.0 mmol/L, though ECG sensitivity is imperfect.
• Hypokalaemia: ST depression, T flattening, prominent U waves, apparent QT prolongation due to QU fusion.
• Hypocalcaemia: QT prolongation via prolonged ST segment; hypercalcaemia shortens QT.
• Digoxin effect: downsloping “scooped” ST depression, T flattening, shortened QT; toxicity causes atrial tachycardia with block, ventricular ectopy, bidirectional VT, or AV block.
• Sodium-channel blockade such as tricyclic overdose: QRS >100 ms predicts seizures, >160 ms predicts ventricular arrhythmias; terminal R in aVR >3 mm is characteristic.

Exercise Testing

Principles and indications

Exercise testing provokes a controlled increase in myocardial oxygen demand by raising heart rate, systolic blood pressure, contractility and wall stress. In flow-limiting epicardial coronary stenosis, coronary vasodilator reserve is exhausted and subendocardial ischaemia may produce exertional symptoms, ST-segment deviation, arrhythmia or abnormal haemodynamics. The standard test is symptom-limited treadmill exercise ECG, usually using the Bruce protocol, with continuous 12-lead monitoring and blood pressure measurement at each stage.

For MRCP purposes, exercise ECG is no longer the preferred diagnostic test for stable chest pain in many UK pathways: NICE recommends CT coronary angiography as first-line investigation for typical or atypical angina, with functional imaging when anatomical significance is uncertain. Exercise testing remains important for assessing exercise capacity, prognosis, chronotropic competence, exercise-induced arrhythmias, post-myocardial infarction risk stratification, pre-operative functional capacity, evaluation of exertional symptoms, and occasionally when CTCA or stress imaging is unavailable or inappropriate.

Protocols, targets and termination

Parameter	Key examination values
Bruce protocol	3-minute stages; stage 1 is 1.7 mph at 10% gradient, increasing speed and gradient each stage.
Target heart rate	≥85% of age-predicted maximum heart rate; maximum ≈ 220 − age in years. Failure to reach this without ischaemia reduces sensitivity.
Workload	Reported in metabolic equivalents; 1 MET = 3.5 mL O2/kg/min. Achieving >10 METs generally indicates low annual cardiac mortality.
Rate-pressure product	Heart rate × systolic BP; surrogate for myocardial oxygen demand. A low peak value may reflect poor effort, chronotropic incompetence or beta-blockade.

Absolute contraindications include acute myocardial infarction within 2 days, ongoing unstable angina, uncontrolled symptomatic arrhythmia, decompensated heart failure, acute myocarditis or pericarditis, severe symptomatic aortic stenosis, acute pulmonary embolism or infarction, acute aortic dissection, and inability to exercise safely. Relative contraindications include left main coronary stenosis, moderate stenotic valvular disease, severe hypertension at rest, tachyarrhythmias or bradyarrhythmias, high-grade atrioventricular block, hypertrophic obstructive cardiomyopathy with severe gradient, electrolyte disturbance and significant pulmonary hypertension.

Termination is mandatory for limiting angina, severe dyspnoea, syncope or presyncope, sustained ventricular tachycardia, new neurological symptoms, signs of poor perfusion, ST elevation ≥1 mm in non-infarct leads, or a fall in systolic BP >10 mmHg despite increasing workload if accompanied by ischaemia. Relative termination criteria include horizontal or downsloping ST depression >2 mm, marked axis shift, increasing chest pain, fatigue, wheeze, leg claudication, systolic BP >250 mmHg or diastolic BP >115 mmHg.

Interpretation and diagnostic performance

A positive exercise ECG classically requires ≥1 mm horizontal or downsloping ST depression measured 60–80 ms after the J point in contiguous leads during exercise or early recovery. Upsloping ST depression is less specific unless marked, usually ≥1.5–2 mm. ST elevation ≥1 mm in leads without pathological Q waves suggests transmural ischaemia or coronary spasm and is high risk. Ischaemic changes occurring at low workload, persisting >5 minutes into recovery, or accompanied by hypotension imply extensive coronary disease or left main/proximal LAD disease.

Overall sensitivity for obstructive coronary artery disease is approximately 65–70% and specificity 70–80%, but performance varies substantially with pre-test probability, sex, baseline ECG and ability to exercise. False positives are more common in women, left ventricular hypertrophy, digoxin therapy, hypokalaemia and hypertensive response; false negatives occur with single-vessel disease, inadequate workload, beta-blockade, balanced ischaemia or good collateralisation. The test is uninterpretable for ischaemia when baseline abnormalities obscure ST analysis, notably left bundle branch block, ventricular pacing, pre-excitation, resting ST depression >1 mm, or digoxin effect; stress imaging is preferred.

Risk stratification

The Duke treadmill score integrates exercise duration, ST deviation and angina to estimate prognosis:

Duke treadmill score = exercise time in minutes on Bruce protocol − 5 × maximum ST deviation in mm − 4 × angina index, where angina index is 0 for none, 1 for non-limiting angina and 2 for exercise-limiting angina.

Duke score	Risk category	Approximate implication
≥ +5	Low risk	Annual mortality usually <1%; often managed medically if symptoms controlled.
−10 to +4	Intermediate risk	Further anatomical or functional imaging usually required.
≤ −11	High risk	Annual mortality often >3%; consider invasive coronary angiography depending on clinical context.

Additional adverse markers include exercise capacity <5 METs, inability to reach 85% predicted maximum heart rate, chronotropic incompetence, ventricular arrhythmias during recovery, delayed heart-rate recovery and abnormal blood pressure response. Heart-rate recovery is autonomically mediated; a fall of ≤12 beats/min at 1 minute after exercise, or ≤18 beats/min after 1 minute of active recovery, is associated with increased mortality. A fall in systolic BP during exercise is particularly concerning for severe ischaemia, left ventricular dysfunction or outflow obstruction.

Exercise stress imaging and cardiopulmonary exercise testing

Where baseline ECG is uninterpretable or diagnostic accuracy must be improved, exercise may be coupled with echocardiography or radionuclide perfusion imaging. Exercise stress echocardiography detects inducible regional wall-motion abnormality, with typical sensitivity 80–85% and specificity 80–90% for obstructive coronary disease. Myocardial perfusion scintigraphy has sensitivity around 85–90% and specificity 70–80%, but exposes patients to ionising radiation. Exercise is preferred over pharmacological stress when feasible because exercise capacity, symptoms, blood pressure and rhythm responses provide independent prognostic information.

Cardiopulmonary exercise testing measures breath-by-breath oxygen uptake, carbon dioxide production and ventilation, and is useful when dyspnoea is unexplained, before major surgery, and in advanced heart failure. Peak VO₂ <14 mL/kg/min, or <12 mL/kg/min in patients receiving beta-blockers, has historically supported consideration of cardiac transplantation in systolic heart failure. Anaerobic threshold <11 mL/kg/min is associated with increased peri-operative risk. These values must be interpreted with effort, respiratory exchange ratio, haemoglobin, pulmonary limitation and skeletal muscle conditioning in mind.

Cardiac Biomarkers

Troponin and the diagnosis of myocardial infarction

Cardiac troponin I and T are the central biomarkers for acute coronary syndromes because they reflect cardiomyocyte injury with high myocardial tissue specificity. They are regulatory thin-filament proteins; circulating troponin is released initially from a small cytosolic pool and subsequently from structurally bound myofibrillar protein, explaining the prolonged elevation after infarction. A diagnosis of myocardial infarction requires acute myocardial injury, defined by a rise and/or fall in cardiac troponin with at least one value above the assay-specific 99th centile upper reference limit, plus clinical evidence of myocardial ischaemia, such as symptoms, new ischaemic ECG changes, imaging evidence, or angiographic thrombus. Troponin elevation alone is not synonymous with type 1 MI.

High-sensitivity cardiac troponin assays detect troponin in at least 50% of healthy individuals and achieve a coefficient of variation ≤10% at the 99th centile. Typical 99th centiles are assay-dependent; for Roche high-sensitivity cardiac troponin T, the commonly quoted threshold is approximately 14 ng/L, although sex-specific thresholds and platform-specific cut-offs increasingly matter. High-sensitivity assays rise within 1–3 hours of symptom onset, peak at 12–24 hours, and may remain elevated for 5–7 days for troponin I and up to 10–14 days for troponin T.

Biomarker	Rise	Peak	Return to baseline	Main examination relevance
High-sensitivity cTnI/cTnT	1–3 h	12–24 h	cTnI 5–7 d; cTnT 10–14 d	Preferred biomarker for myocardial injury and MI diagnosis
CK-MB	3–6 h	18–24 h	48–72 h	Occasionally useful for suspected reinfarction after recent MI
Myoglobin	1–2 h	6–9 h	Within 24 h	Early but very non-specific; largely obsolete

Dynamic change and rapid rule-in/rule-out pathways

The Fourth Universal Definition of MI emphasises rise and/or fall to distinguish acute injury from chronic myocardial injury. Absolute delta changes are generally superior to percentage changes at low concentrations. The European Society of Cardiology endorses 0/1-hour and 0/2-hour algorithms using assay-specific thresholds. For Roche hs-cTnT, commonly used 0/1-hour criteria are: rule-out if baseline is <5 ng/L, provided symptom onset was more than 3 hours earlier, or if baseline is <12 ng/L with a 1-hour change <3 ng/L; rule-in if baseline is ≥52 ng/L or the 1-hour change is ≥5 ng/L. Intermediate results require repeat testing and clinical risk assessment.

These algorithms have very high negative predictive value for MI, typically >99% in appropriately selected low-risk emergency department populations, but positive predictive value is lower because troponin detects injury rather than mechanism. The APACE studies underpinned accelerated diagnostic pathways, and implementation studies such as High-STEACS demonstrated increased detection of myocardial injury and type 2 MI, with more nuanced downstream management rather than indiscriminate angiography.

Interpreting elevated troponin: differential diagnosis

Troponin elevation should be classified mechanistically. Type 1 MI reflects atherothrombotic plaque rupture or erosion. Type 2 MI reflects oxygen supply–demand imbalance, for example tachyarrhythmia, severe anaemia, hypoxaemia, hypotension, hypertensive crisis or sepsis, with evidence of ischaemia. Acute non-ischaemic myocardial injury includes myocarditis, Takotsubo cardiomyopathy, pulmonary embolism, contusion, cardioversion, ablation and cardiotoxic chemotherapy. Chronic myocardial injury is common in chronic kidney disease, structural heart disease, heart failure and stable coronary disease; concentrations are often persistently elevated but relatively stable.

• Renal failure: troponin T is more frequently chronically elevated than troponin I; diagnosis of acute MI depends on a significant rise/fall plus ischaemic context.
• Pulmonary embolism: troponin elevation indicates right ventricular strain and worse prognosis, but does not diagnose ACS.
• Myocarditis: troponin may be markedly raised with unobstructed coronaries; ECG and cardiac MRI are often decisive.
• Heart failure: low-grade troponin elevation is prognostic and may reflect wall stress, subendocardial ischaemia, inflammation or apoptosis.

Natriuretic peptides

BNP and NT-proBNP are released predominantly from ventricular myocardium in response to stretch, wall stress and neurohormonal activation. ProBNP is cleaved into biologically active BNP, with a half-life of approximately 20 minutes, and inactive NT-proBNP, with a half-life of approximately 60–120 minutes. Values are diagnostic aids and powerful prognostic markers in heart failure, but they do not define aetiology.

Clinical setting	Rule-out / referral threshold	Interpretation
Non-acute suspected heart failure, ESC	BNP <35 pg/mL or NT-proBNP <125 pg/mL	Heart failure unlikely
Acute dyspnoea, ESC	BNP <100 pg/mL or NT-proBNP <300 pg/mL	Acute heart failure unlikely
NICE chronic heart failure pathway	NT-proBNP >2000 ng/L	Urgent specialist assessment and echocardiography within 2 weeks
NICE chronic heart failure pathway	NT-proBNP 400–2000 ng/L	Specialist assessment and echocardiography within 6 weeks
NICE chronic heart failure pathway	NT-proBNP <400 ng/L	Heart failure less likely; consider alternative diagnoses

Natriuretic peptide concentrations rise with age, renal dysfunction, atrial fibrillation, pulmonary hypertension and acute coronary syndromes, and are lower in obesity. Sacubitril/valsartan increases BNP by inhibiting neprilysin-mediated degradation, whereas NT-proBNP remains interpretable and is preferred for monitoring response. In MRCP-style questions, a low natriuretic peptide is most useful as a rule-out test; an elevated result mandates echocardiography rather than confirming heart failure in isolation.

Older and adjunctive biomarkers

CK-MB has inferior sensitivity and specificity to troponin but may help when reinfarction is suspected within days of an index MI because it normalises faster. Myoglobin is sensitive very early but lacks cardiac specificity and is rarely used in contemporary pathways. Inflammatory markers such as C-reactive protein have prognostic associations in atherosclerosis but no routine diagnostic role in ACS. The examination priority is therefore: interpret troponin dynamically and clinically, use natriuretic peptides to evaluate suspected heart failure, and avoid treating biomarker positivity as a diagnosis independent of context.