Nstemi
Non-ST-elevation myocardial infarction (NSTEMI) is an acute coronary syndrome characterized by myocardial necrosis with elevated cardiac biomarkers but without persistent ST-segment elevation on electrocardiography.
Definition and Terminology
NSTEMI stands for Non-ST-Elevation Myocardial Infarction. Let's break the name down:
- Non-ST-Elevation = the ST segment on ECG is not persistently elevated (distinguishing it from STEMI)
- Myocardial (myo = muscle, cardial = heart) = heart muscle
- Infarction (Latin infarcire = to stuff/plug) = tissue death due to ischaemia
NSTEMI is one entity within the spectrum of Acute Coronary Syndrome (ACS), which encompasses three conditions unified by a common pathophysiology — acute disruption of coronary blood flow [1][2]:
| Entity | Occlusion | Necrosis | Troponin | ST Elevation |
|---|---|---|---|---|
| Unstable Angina (UA) | Partial/transient | None | Normal | No |
| NSTEMI | Partial occlusion (usually due to critical narrowing) → some myocardial necrosis but not transmural | Subendocardial (partial thickness) | Elevated | No |
| STEMI | Complete occlusion (usually due to acute plaque disruption leading to complete thrombosis) → transmural myocardial necrosis | Transmural (full thickness) | Elevated | Yes (persistent) |
UA and NSTEMI are classified together under NSTE-ACS because they share the same initial management pathway and are distinguished only by the presence or absence of elevated cardiac biomarkers (troponin) [1][2].
Key Conceptual Point
The fundamental difference between NSTEMI and STEMI is the degree of coronary occlusion and the resulting depth of myocardial necrosis. In NSTEMI, the artery is not completely occluded — there is still some residual flow — so the infarction is typically subendocardial (the inner wall, which is most vulnerable to ischaemia because it is furthest from the epicardial blood supply and is most compressed during systole). In STEMI, complete occlusion causes transmural (full-thickness) necrosis.
Acute myocardial infarction (AMI) is defined as myocardial cell death due to prolonged myocardial ischaemia [2]. The 4th Universal Definition requires:
- Rise and/or fall of cardiac troponin (cTn) with at least one value above the 99th percentile upper reference limit (URL)
- Plus at least one of:
- Symptoms of acute myocardial ischaemia
- New ischaemic ECG changes
- Development of pathological Q waves
- Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality (RWMA) in a pattern consistent with an ischaemic aetiology
- Identification of a coronary thrombus by angiography or autopsy
| Type | Mechanism | Relevance to NSTEMI |
|---|---|---|
| Type 1 | Spontaneous MI due to atherosclerotic plaque disruption (rupture, erosion, fissuring) with intraluminal thrombus | Most common cause of NSTEMI |
| Type 2 | MI secondary to supply-demand mismatch without acute plaque event (e.g., anaemia, tachyarrhythmia, hypotension, coronary spasm, coronary embolism) | Common cause; very important to recognize as management differs |
| Type 3 | MI resulting in death when biomarkers unavailable | — |
| Type 4a/b | MI related to PCI / stent thrombosis | Iatrogenic |
| Type 5 | MI related to CABG | Iatrogenic |
Type 2 MI — A Common Exam Pitfall
Not every troponin rise with ischaemic symptoms is a Type 1 MI. A septic patient with tachycardia and hypotension who develops troponin elevation has a Type 2 MI — the coronary arteries may be entirely normal. The treatment here is to fix the underlying cause (treat sepsis), NOT to rush to the cath lab. Always ask: "Is this plaque rupture, or supply-demand mismatch?"
Epidemiology
NSTEMI is the most common form of ACS, accounting for approximately 60–75% of all ACS presentations in developed countries [1][3].
- The incidence of NSTE-ACS has been increasing relative to STEMI over the past two decades, largely due to:
- Improved sensitivity of troponin assays (high-sensitivity troponin, hs-cTn) — cases previously classified as UA are now reclassified as NSTEMI
- Better primary and secondary prevention reducing rates of large STEMI
- Ageing population with more comorbidities predisposing to Type 2 MI
- In-hospital mortality for NSTEMI is lower than STEMI (~3–5% vs ~6–7%), but 6-month and long-term mortality are comparable or even higher for NSTEMI — because NSTEMI patients tend to be older with more comorbidities [1][3]
- Coronary heart disease is one of the leading causes of death in HK (3rd cause after cancer and pneumonia)
- HK has high prevalence of traditional risk factors: hypertension (~27%), diabetes (~10%), dyslipidaemia, and increasing obesity
- Mortality of AMI: 40% overall in 4 weeks (half ≤ 2h due to VF), 6–7% in 30 days for those surviving to hospital [2]
- The Chinese population has a somewhat different risk factor profile: relatively lower rates of familial hypercholesterolaemia but higher rates of smoking in males and diabetes-related CAD
High Yield Epidemiology Point
NSTEMI patients are typically older, more often female, and have more comorbidities (DM, CKD, prior PCI/CABG) compared to STEMI patients. This is why despite lower acute mortality, their long-term outcomes can be worse.
Risk Factors for Coronary Artery Disease
Since NSTEMI arises from coronary atherosclerosis (in the vast majority of Type 1 cases), its risk factors are those of atherosclerotic cardiovascular disease (ASCVD) [2][4]:
| Risk Factor | Mechanism of Atherogenesis |
|---|---|
| Cigarette smoking | Endothelial injury, ↑oxidative stress, ↑platelet activation, ↑LDL oxidation, ↓HDL |
| Hypertension | Mechanical shear stress → endothelial dysfunction → accelerated atherosclerosis |
| Dyslipidaemia (↑LDL-C, ↓HDL-C, ↑TG) | LDL penetrates and accumulates in subendothelial space → oxidized → foam cells → atheroma |
| Diabetes mellitus | Hyperglycaemia → endothelial dysfunction + ↑inflammation + prothrombotic state; insulin resistance → dyslipidaemia |
| Abdominal obesity / Metabolic syndrome | Central adiposity → ↑FFA + adipokines → insulin resistance → dyslipidaemia, HTN, pro-inflammatory and prothrombotic state [4] |
| Physical inactivity | ↓AMPK activation → ↓glucose uptake + ↓FFA metabolism → worsens metabolic syndrome [4] |
| Unhealthy diet | High saturated fat, trans-fat, sodium → ↑LDL, ↑BP |
| Risk Factor | Details |
|---|---|
| Age | M ≥ 45y, F ≥ 55y — age is the strongest risk factor; atherosclerosis is a cumulative process [4] |
| Male gender | Oestrogen is protective pre-menopause (↑HDL, ↓LDL, vasodilatory); risk equalizes post-menopause |
| Family history of premature CVD | 1st degree relative: M < 55y, F < 65y [4] — implies genetic predisposition (e.g., familial hypercholesterolaemia, polygenic risk) |
- Formal assessment recommended if ≥ 40y + ≥ 1 ASCVD risk factor (HK consensus 2016) [4]
- Not needed if patient has overt ASCVD, DM, or ≥ 1 major risk factor → automatically meets threshold for treatment [4]
- Tools include: Framingham Risk Score, ACC/AHA ASCVD Risk Calculator, SCORE risk charts, and regionally validated tools like the Chinese Multiprovincial Cohort Study (CMCS) [4]
Anatomy and Function of the Coronary Arteries
Understanding coronary anatomy is essential because the territory of ischaemia in NSTEMI determines the ECG changes, wall motion abnormalities, and potential complications.
| Artery | Territory Supplied | ECG Leads |
|---|---|---|
| LAD | Anterior wall, anterior septum, LV apex | V1–V4 (anterior), V5–V6/I/aVL (anterolateral if diagonal branches involved) |
| LCx | Lateral wall, posterior wall (if left dominant) | I, aVL, V5–V6 (lateral); may also cause posterior changes |
| RCA | Inferior wall, RV, posterior wall (if right dominant), AV node (in ~90%), SA node (in ~60%) | II, III, aVF (inferior); V3R–V4R (RV); reciprocal V1–V3 for posterior |
- Right dominant (~85%): PDA arises from RCA → RCA supplies inferior wall + posterior wall
- Left dominant (~8%): PDA arises from LCx
- Codominant (~7%): both contribute
The subendocardium (inner third of the myocardial wall) is the watershed zone of coronary perfusion:
- Compressed during systole: intramural pressure is highest here, so perfusion occurs mainly during diastole
- End-artery territory: coronary arteries penetrate from epicardium → endocardium; the subendocardium is the most distal territory
- Highest O₂ demand: the subendocardial fibres have the highest wall stress
This is why partial coronary occlusion in NSTEMI causes subendocardial (not transmural) infarction — there is still enough flow to keep the epicardial layers alive, but the subendocardium crosses the ischaemic threshold first.
Etiology (Focus on Hong Kong)
A. Type 1 NSTEMI — Atherosclerotic Plaque Disruption
This is the classical and most common cause. The sequence is:
Key concept: In NSTEMI, the thrombus is usually non-occlusive (partial) or transiently occlusive. This allows some residual antegrade flow, and collateral flow may also contribute. However, distal embolization of platelet aggregates can cause microvascular obstruction, leading to patchy myocardial necrosis [1][3].
Not all atherosclerotic plaques are equal. The plaques most likely to rupture have:
- Large lipid-rich necrotic core (> 40% of plaque volume)
- Thin fibrous cap (< 65 μm) — this is the protective layer of smooth muscle cells and collagen that separates the thrombogenic core from the bloodstream
- Heavy inflammatory infiltrate — macrophages secrete matrix metalloproteinases (MMPs) that digest collagen → thin the cap
- Few smooth muscle cells (which make collagen to strengthen the cap)
- Positive (outward) remodelling — the plaque grows outward, so angiography may not show significant stenosis until it ruptures
Why Doesn't the Plaque Need to Be Severely Stenotic?
This is a crucial concept. Many NSTEMI events arise from plaques that cause only 30–50% stenosis. These plaques are NOT flow-limiting at baseline (so no exertional angina beforehand), but they are vulnerable to rupture because of their thin cap and large lipid core. This is why some patients present with NSTEMI as their very first manifestation of CAD, without any prior angina. It also explains why stress testing cannot detect all "at-risk" plaques.
Several factors determine whether the thrombus becomes occlusive:
- Plaque erosion (rather than rupture) tends to produce a smaller, more platelet-rich, non-occlusive thrombus → more common in NSTEMI
- Endogenous fibrinolysis may partially dissolve a completely occlusive thrombus, restoring some flow
- Collateral circulation may be better developed in patients with chronic stenosis
- Thrombus composition: NSTEMI thrombi are more "white" (platelet-rich) while STEMI thrombi are more "red" (fibrin and red cell-rich, more organized and resistant to lysis)
Any condition that causes myocardial oxygen supply < demand in the setting of underlying (but stable) CAD or even normal coronaries can cause Type 2 MI:
| Mechanism | Examples |
|---|---|
| ↓ O₂ supply | Anaemia, hypoxia (pneumonia, ARDS, PE), hypotension/shock, coronary vasospasm (Prinzmetal's), coronary embolism (AF, endocarditis), coronary dissection |
| ↑ O₂ demand | Tachyarrhythmia (AF with RVR, SVT), severe hypertension (hypertensive crisis), aortic stenosis, HOCM, thyrotoxicosis, phaeochromocytoma, severe sepsis, cocaine/amphetamine use |
| Cause | Mechanism |
|---|---|
| Coronary vasospasm (Prinzmetal/variant angina) | Intense focal vasospasm of a coronary artery → transient ischaemia; if prolonged, can cause infarction. Often in young patients, smokers, cocaine users. May have normal angiography between episodes |
| Spontaneous coronary artery dissection (SCAD) | Tear in the coronary artery wall → intramural haematoma → luminal compression. Classically in young women, peripartum, fibromuscular dysplasia |
| Coronary embolism | From AF, prosthetic valves, endocarditis, paradoxical embolism (PFO), aortic atheroma |
| Takotsubo cardiomyopathy | Catecholamine-mediated myocardial stunning; can mimic NSTEMI with troponin rise and RWMA but coronaries are normal. Classically in postmenopausal women after emotional/physical stress |
| Myocarditis | Can mimic NSTEMI biochemically (troponin rise) and clinically. Viral (Coxsackie, COVID-19) or autoimmune |
| Cocaine/methamphetamine | Coronary vasospasm + accelerated atherosclerosis + ↑myocardial O₂ demand (tachycardia, hypertension) |
- High smoking prevalence in males (~20% in adult males) — a major modifiable risk factor
- High prevalence of Type 2 DM (~10%) — diabetic patients often have silent ischaemia (autonomic neuropathy blunts anginal symptoms)
- Rising obesity and metabolic syndrome — sedentary lifestyle, dietary westernization
- Hypertension very common (~27% of adults)
- Apical HCM is relatively more prevalent in HK/East Asian populations (25–30% of HCMP in Japan and HK) and can present with chest pain mimicking ACS [2]
Classification
As described above (Types 1–5).
Risk stratification is paramount in NSTEMI because, unlike STEMI (which always requires emergent reperfusion), the timing of invasive management in NSTEMI depends on risk [1][3]:
| Risk Category | GRACE Score | In-hospital Mortality | Management Timing |
|---|---|---|---|
| Very high risk | Clinical criteria (see below) | — | Immediate invasive (< 2h) |
| High risk | > 140 | > 3% | Early invasive (< 24h) |
| Intermediate risk | 109–140 | 1–3% | Invasive (< 72h) |
| Low risk | ≤ 108 | < 1% | Selective invasive / conservative |
GRACE (Global Registry of Acute Coronary Events) score variables: age, heart rate, systolic BP, creatinine, cardiac arrest at admission, ST-segment deviation, elevated cardiac enzymes, Killip class [1][3].
Very high risk criteria (requiring immediate invasive strategy < 2h, like STEMI) [1][3]:
- Haemodynamic instability or cardiogenic shock
- Recurrent or ongoing chest pain refractory to medical treatment
- Life-threatening arrhythmias (VT, VF, cardiac arrest)
- Mechanical complications of MI
- Acute heart failure clearly related to NSTE-ACS
- Recurrent dynamic ST-T wave changes (particularly intermittent ST elevation)
| Class | Clinical Findings | Approximate Mortality |
|---|---|---|
| I | No signs of heart failure | 6% |
| II | Crackles in lower lung fields, S3, ↑JVP | 17% |
| III | Frank pulmonary oedema | 38% |
| IV | Cardiogenic shock | 81% |
Pathophysiology — A Detailed First-Principles Explanation
Atherosclerosis is a chronic inflammatory disease of medium and large arteries:
- Endothelial injury/dysfunction: Risk factors (smoking, HTN, DM, dyslipidaemia) damage the endothelium → ↑permeability to lipoproteins, ↓NO production (NO is vasodilatory and anti-thrombotic)
- LDL infiltration: LDL particles cross the damaged endothelium into the intima → become oxidized (oxLDL)
- Inflammatory response: oxLDL attracts monocytes → enter intima → differentiate into macrophages → engulf oxLDL → become foam cells → fatty streak formation
- Smooth muscle cell migration: SMCs migrate from media to intima, proliferate, and secrete collagen/elastin → forms a fibrous cap over the lipid core
- Plaque maturation: The necrotic core grows (dead foam cells release lipids), the fibrous cap may thin, and the plaque may calcify
- Plaque vulnerability: Inflammatory cells (macrophages, T-cells) release MMPs and cytokines → degrade collagen → thin fibrous cap → vulnerable plaque
The acute event in Type 1 NSTEMI is plaque rupture or erosion:
- Plaque rupture (~60–70% of ACS): The thin fibrous cap tears, exposing the highly thrombogenic lipid-rich necrotic core to flowing blood. This is the most common mechanism in STEMI but also causes NSTEMI.
- Plaque erosion (~30–40%): The endothelium over the plaque denudes without frank rupture of the cap. This tends to produce smaller thrombi and is more common in NSTEMI, younger patients, women, and smokers.
- Calcified nodule (rare, ~5%): Calcified material protrudes through the cap into the lumen.
Exposure of subendothelial collagen and tissue factor → two simultaneous processes:
-
Primary haemostasis (platelet plug):
- Platelet adhesion via vWF-GPIb/IX/V and collagen-GPVI
- Platelet activation: shape change, degranulation (ADP, TXA₂, serotonin)
- Platelet aggregation via GPIIb/IIIa-fibrinogen cross-links
-
Secondary haemostasis (coagulation cascade):
- Tissue factor → Factor VIIa → extrinsic pathway → thrombin generation → fibrin
This is why dual antiplatelet therapy (DAPT) and anticoagulation are both required in NSTEMI — you need to block both arms.
- Partial occlusion → reduced but not absent coronary flow
- Subendocardial ischaemia first (most vulnerable zone, as explained above)
- If ischaemia is prolonged (typically > 20 minutes of severe ischaemia), irreversible injury begins:
- ATP depletion → failure of Na⁺/K⁺-ATPase → cell swelling → membrane disruption
- Calcium overload → mitochondrial dysfunction → cell death
- Release of intracellular contents: troponin, CK-MB, myoglobin into the bloodstream
- Troponin release → detected by blood tests (this is what defines NSTEMI vs UA)
- Regional wall motion abnormality → detectable on echo
- Electrical instability → arrhythmias (ischaemic myocardium has altered conduction and repolarization)
- Inflammatory response → attracts neutrophils, then macrophages → scar formation over days-weeks
This is a critical concept:
- ST elevation reflects transmural injury current — when the full thickness of the myocardium is ischaemic, the injury current is directed toward the epicardium → ST elevation in overlying leads
- In NSTEMI, only the subendocardium is affected → the injury current points from epicardium toward the endocardium (i.e., away from the overlying electrode) → this manifests as:
- ST depression (the most common ECG finding in NSTEMI)
- T-wave inversion (repolarization abnormality from subendocardial ischaemia/injury)
- Or even a normal ECG (if the affected territory is small or in an area poorly represented on standard 12-lead ECG, e.g., posterior wall, LCx territory)
ECG Pitfall in NSTEMI
A normal ECG does NOT exclude NSTEMI. Up to 30–40% of NSTEMI patients may have a non-diagnostic initial ECG. This is why serial ECGs and troponin measurements are essential. The LCx territory is notoriously under-represented on a standard 12-lead ECG — consider posterior leads (V7–V9) if clinical suspicion is high.
Clinical Features
A. Symptoms (with Pathophysiological Basis)
The typical presentation of NSTEMI is acute onset retrosternal chest pain/discomfort that occurs at rest or with minimal exertion, lasting > 20 minutes, and NOT fully relieved by sublingual GTN [1][2][3].
| Feature | Description | Pathophysiological Basis |
|---|---|---|
| Character | Dull, constricting, crushing, squeezing, "heavy", burning, aching; often described as "discomfort" rather than "pain" | Visceral pain from myocardial ischaemia → stimulation of cardiac sympathetic afferents (C7–T4) → poorly localized visceral sensation |
| Location | Retrosternal (central chest) | Heart is a midline structure; visceral afferents enter the spinal cord bilaterally |
| Radiation | Left arm, both arms, shoulders, jaw, neck, epigastrium, interscapular region | Referred pain: cardiac afferents share spinal cord segments (C7–T4) with somatic dermatomes of the arm (T1–T2), jaw (trigeminal nucleus convergence), and shoulder (C3–C5 phrenic) |
| Duration | Typically > 20 minutes (if < 20 min and resolving, may be UA) | Prolonged ischaemia needed for irreversible necrosis; < 20 min may represent transient ischaemia only |
| Precipitants | May occur at rest (unlike stable angina which is exertional) | Acute plaque event → fixed supply reduction regardless of demand |
| Response to GTN | May partially relieve but typically does not fully resolve | GTN causes venodilation (↓preload → ↓wall stress → ↓O₂ demand) and some coronary vasodilation, but cannot overcome a mechanical obstruction from thrombus |
| Levine's sign | Clenched fist placed over sternum when describing pain | Classic gestural descriptor of anginal chest pain |
Three recognized clinical presentations of NSTE-ACS [1][3]:
- Prolonged (> 20 min) rest angina
- New-onset angina (de novo) — Class II or III (CCS classification)
- Crescendo angina — worsening in frequency, duration, or severity of previously stable angina (at least CCS III)
| Symptom | Pathophysiological Basis |
|---|---|
| Diaphoresis (sweating) | Sympathetic activation from pain + haemodynamic stress → widespread sympathetic discharge → eccrine gland activation |
| Nausea / Vomiting | Vagal stimulation (especially with inferior MI — the inferior surface is rich in vagal afferents) + pain-mediated nausea |
| Pallor | Sympathetic vasoconstriction → diversion of blood from skin to vital organs |
| Palpitations | Sympathetic activation → ↑HR; may also indicate ischaemia-mediated arrhythmia |
| Symptom | Pathophysiological Basis |
|---|---|
| Dyspnoea | LV systolic dysfunction from ischaemia/necrosis → ↑LV end-diastolic pressure → ↑LA pressure → pulmonary venous congestion → ↑pulmonary interstitial fluid → stimulates J-receptors → sensation of breathlessness |
| Orthopnoea / PND | Same mechanism but exacerbated by supine position (↑venous return → ↑preload → ↑pulmonary congestion) |
| Lightheadedness / Syncope | ↓CO from severe LV dysfunction or arrhythmia → ↓cerebral perfusion |
This is extremely important for exams. Up to 30–40% of NSTEMI patients present atypically, particularly:
- Elderly (> 75y) — may present with confusion, fatigue, or "just not feeling right"
- Diabetics — autonomic neuropathy damages the cardiac sensory afferents → painless MI (they may present with dyspnoea as an "anginal equivalent")
- Women — more likely to have atypical pain quality (sharp, pleuritic) or present with fatigue, nausea, dyspnoea
- Post-operative patients — pain may be attributed to surgery
- Renal failure patients — altered pain perception
Exam High Yield: Anginal Equivalents
In patients who cannot perceive typical anginal pain (diabetics, elderly), the first symptom may be an "anginal equivalent" — most commonly exertional dyspnoea, but also fatigue, nausea, diaphoresis, or syncope. Always have a low threshold for ECG and troponin in these populations.
B. Signs (with Pathophysiological Basis)
Physical examination in NSTEMI is often unremarkable but is critical for:
- Assessing haemodynamic status and complications
- Identifying alternative diagnoses
- Identifying precipitating factors
| Sign | Pathophysiological Basis |
|---|---|
| Anxiety, distress | Pain and sympathetic activation |
| Pallor, cool/clammy skin | Sympathetic vasoconstriction; if severe, suggests cardiogenic shock (↓CO → ↓peripheral perfusion) |
| Diaphoresis | Sympathetic activation |
| Cyanosis (if severe) | Pulmonary oedema → impaired gas exchange → hypoxaemia |
| Xanthomas, xanthelasma, arcus senilis | Indicate underlying dyslipidaemia — a major risk factor for CAD [2][4] |
| Sign | Pathophysiological Basis |
|---|---|
| Tachycardia | Sympathetic activation (compensatory for ↓CO and pain); or arrhythmia |
| Bradycardia | Vagal stimulation (especially inferior MI → AV nodal ischaemia as RCA supplies AV node in ~90%) |
| Hypotension | ↓CO from extensive LV dysfunction or RV infarction or arrhythmia → cardiogenic shock |
| Hypertension | Pain and sympathetic activation → vasoconstriction + ↑HR; or pre-existing HTN as risk factor |
| Irregular pulse | Arrhythmia: AF (atrial ischaemia/stretch), VT/VF (ventricular ischaemia), heart block (conduction system ischaemia) |
| Displaced, dyskinetic apex beat | LV dilatation from prior MI or acute severe LV dysfunction; dyskinetic suggests regional wall motion abnormality [2] |
| S3 gallop | ↑LVEDP → rapid ventricular filling into a dilated, poorly compliant ventricle → turbulent flow. Indicates significant LV systolic dysfunction [2] |
| S4 gallop | ↓LV compliance from ischaemia (ischaemic myocardium becomes stiff) → atrial contraction against a stiff ventricle → S4 |
| New systolic murmur | Critical sign! Could indicate: (1) Papillary muscle dysfunction/rupture → acute MR (harsh pansystolic murmur at apex radiating to axilla); (2) VSD → harsh pansystolic murmur at left sternal edge with thrill; (3) Functional MR from LV dilatation |
| ↑JVP | Right heart failure (from RV infarction in inferior MI, or biventricular failure); or mechanical complication (cardiac tamponade from free wall rupture → ↑↑JVP with Kussmaul's sign) |
| Pericardial friction rub | Pericarditis (early post-MI pericarditis occurs 1–3 days post-MI due to transmural inflammation) |
| Sign | Pathophysiological Basis |
|---|---|
| Bibasal crackles / crepitations | Pulmonary oedema from LV failure → ↑pulmonary capillary hydrostatic pressure → transudation of fluid into alveoli |
| Wheeze ("cardiac asthma") | Peribronchial oedema compresses small airways → expiratory wheezing |
| Pink frothy sputum | Severe pulmonary oedema → rupture of engorged pulmonary capillaries → blood-tinged transudate in alveoli [5] |
| Sign | Pathophysiological Basis |
|---|---|
| Peripheral oedema | Right heart failure → ↑systemic venous pressure → ↑capillary hydrostatic pressure → fluid extravasation |
| Signs of peripheral vascular disease (absent pulses, bruits, trophic changes) | Indicates widespread atherosclerosis — if present in peripheral arteries, coronary involvement is very likely [2] |
| Carotid bruits | Indicates carotid atherosclerosis → marker of generalized atherosclerotic burden [2] |
| Delayed capillary refill (> 2 sec) | ↓CO → peripheral vasoconstriction → poor tissue perfusion |
| Oliguria (from catheter) | ↓renal perfusion from ↓CO → ↓GFR → ↓urine output |
| Sign | Possible Alternative/Precipitant |
|---|---|
| Unequal BP between arms (> 20 mmHg difference) | Aortic dissection (crucial to exclude before anticoagulation) |
| Absent femoral pulses | Aortic dissection involving descending aorta |
| Pericardial rub with distant heart sounds | Pericardial effusion/tamponade |
| Unilateral absent breath sounds | Pneumothorax |
| Fever | Pneumonia, myocarditis, endocarditis (as cause of coronary embolism) |
| Conjunctival pallor | Anaemia → Type 2 MI (supply-demand mismatch) |
| Thyroid goitre, lid lag, tremor | Thyrotoxicosis → Type 2 MI (↑O₂ demand) [2] |
| Needle track marks | IV drug use → infective endocarditis → coronary embolism |
Must-Do on Physical Examination in ACS
Always perform these in any patient with suspected ACS:
- BP in both arms — to exclude aortic dissection (a mimic AND a contraindication to thrombolysis/anticoagulation)
- Auscultate for new murmurs — to detect mechanical complications (papillary muscle rupture → acute MR, VSD)
- Assess for signs of heart failure — Killip class determines prognosis and management intensity
- Check peripheral pulses — for PVD (marker of generalized atherosclerosis) and aortic dissection
- Look for precipitants — anaemia, thyrotoxicosis, tachyarrhythmia
| Pathophysiology | Clinical Feature | Why? |
|---|---|---|
| Myocardial ischaemia → cardiac sympathetic afferents | Chest pain (visceral, poorly localized) | Shares spinal segments C7–T4 → referred to arms, jaw |
| Sympathetic activation | Tachycardia, diaphoresis, pallor, hypertension | Compensatory catecholamine surge |
| Vagal activation (esp. inferior MI) | Bradycardia, nausea, vomiting | RCA supplies vagal-rich inferior surface |
| LV systolic dysfunction | ↓CO → hypotension, S3, displaced apex | Ischaemic myocardium loses contractility |
| ↑LVEDP → pulmonary congestion | Dyspnoea, orthopnoea, crackles | Backward failure into pulmonary circulation |
| RV infarction | ↑JVP, hypotension, clear lungs | RV cannot pump blood forward; backward congestion into systemic veins |
| Papillary muscle dysfunction | New MR murmur | Ischaemic papillary muscle can't hold mitral leaflets → regurgitation |
| Electrical instability | Arrhythmias (AF, VT, VF, heart block) | Ischaemic tissue has altered conduction and automaticity |
High Yield Summary
Definition: NSTEMI = acute myocardial infarction with troponin elevation but WITHOUT persistent ST elevation on ECG. Part of the NSTE-ACS spectrum (with UA).
Key Pathophysiology: Atherosclerotic plaque rupture/erosion → partial coronary thrombosis → reduced (but not absent) flow → subendocardial necrosis → troponin release.
Risk Factors: The classic ASCVD risk factors — smoking, HTN, DM, dyslipidaemia, obesity, family history, age, male sex.
Presentations: (1) Prolonged rest angina > 20 min, (2) New-onset severe angina, (3) Crescendo angina. Watch for atypical presentations in elderly, diabetics, women.
Cardinal symptom: Retrosternal crushing/squeezing chest pain, may radiate to arms/jaw, associated with diaphoresis, nausea, dyspnoea.
Key exam findings: Often unremarkable. Look for haemodynamic compromise (tachycardia, hypotension, S3, crackles), new murmurs (mechanical complications), signs of precipitants (anaemia, thyrotoxicosis), and signs excluding mimics (BP both arms for dissection).
Risk stratification: GRACE score determines timing of invasive strategy. Very high risk criteria → immediate invasive (< 2h).
Always remember: Check BP in both arms, auscultate for new murmurs, assess Killip class, look for precipitating causes of Type 2 MI.
Active Recall - NSTEMI Clinical Features and Pathophysiology
[1] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf [2] Senior notes: Ryan Ho Cardiology.pdf (Section 3.2 Coronary Artery Disease, Section 3.2.2 ACS) [3] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf [4] Senior notes: Ryan Ho Endocrine.pdf (Section on ASCVD risk assessment and metabolic syndrome) [5] Senior notes: Ryan Ho Critical Care.pdf (Section 1.3.4 Management of Cardiogenic Shock)
Differential Diagnosis of NSTEMI
When a patient presents with acute chest pain and you are considering NSTEMI, your brain must simultaneously run through a structured differential diagnosis. The reason is twofold: (1) some of these mimics are equally or more lethal than NSTEMI and require entirely different treatments (e.g., giving anticoagulation for presumed NSTEMI when the patient actually has aortic dissection is catastrophic); and (2) some conditions cause troponin elevation without coronary plaque events (Type 2 MI, myocarditis, Takotsubo) and managing them as Type 1 MI leads to inappropriate invasive strategy.
The best way to think about the differential is by organ system and then by acuity/severity. The lecture slides provide an excellent table that we will use as our backbone [1][3].
Differential diagnoses of acute coronary syndromes in the setting of acute chest pain [1]:
| Cardiac | Pulmonary | Vascular | Gastrointestinal | Orthopaedic | Other |
|---|---|---|---|---|---|
| Myopericarditis | Pulmonary embolism | Aortic dissection | Oesophagitis, reflux, or spasm | Musculoskeletal disorders | Anxiety disorders |
| Cardiomyopathies | (Tension) pneumothorax | Symptomatic aortic aneurysm | Peptic ulcer, gastritis | Chest trauma | Herpes zoster |
| Tachyarrhythmias | Bronchitis, pneumonia | Stroke | Pancreatitis | Muscle injury/inflammation | Anaemia |
| Acute heart failure | Pleuritis | Cholecystitis | Costochondritis | ||
| Hypertensive emergencies | Cervical spine pathologies | ||||
| Aortic valve stenosis | |||||
| Takotsubo syndrome |
Relative frequency from the landmark Fruergaard et al. (1996) study, also cited on lecture slides [1]:
- Gastrointestinal 42%
- Ischaemic heart disease 31%
- Chest wall syndrome 28%
- Pericarditis 4%
- Pleuritis 2%
- Pulmonary embolism 2%
- Lung cancer 1.5%
- Aortic aneurysm 1%
- Aortic stenosis 1%
- Herpes zoster 1%
Exam Pearl
In clinical practice and exams, the most important differentials to actively exclude are the "Big 5 Killers" of acute chest pain: ACS (STEMI/NSTEMI), aortic dissection, pulmonary embolism, tension pneumothorax, and oesophageal rupture (Boerhaave syndrome). These are all life-threatening, and each requires a completely different management pathway. Missing one is potentially fatal.
Detailed Differential Diagnosis — Condition by Condition
A. Life-Threatening Cardiovascular Differentials
The most important immediate distinction is STEMI vs NSTEMI, because STEMI requires emergent reperfusion (primary PCI or fibrinolysis) whereas NSTEMI requires risk-stratified timing [1][2][3].
| Feature | NSTEMI | STEMI |
|---|---|---|
| ECG | ST depression, T-wave inversion, or normal | Persistent ST elevation with reciprocal ST depression ± pathological Q waves [2] |
| Occlusion | Partial / non-occlusive | Complete / persistent |
| Troponin | Elevated (rise and/or fall) | Elevated (usually higher peak) |
| Urgency | Risk-stratified invasive strategy | Emergent reperfusion < 120 min (PCI) or < 12h (fibrinolysis) |
Note that STEMI is NOT the only cause of ST elevation — the lecture slides specifically highlight these ECG pitfalls / false positives [3]:
- Benign early repolarization
- LBBB
- Pre-excitation
- Brugada syndrome
- Peri-/myocarditis
- Pulmonary embolism
- Subarachnoid haemorrhage
- Metabolic disturbances such as hyperkalaemia
- Failure to recognize normal limits for J-point displacement
- Lead transposition or use of modified leads configuration
- Cholecystitis
ECG false negatives for MI [3]:
- Prior Q waves and/or persistent ST elevation
- Paced rhythm
- LBBB
LBBB Pitfall
LBBB appears on both the false-positive AND false-negative lists. A new LBBB in the context of acute chest pain should be treated as STEMI-equivalent until proven otherwise, but a pre-existing LBBB makes ECG diagnosis of acute MI very difficult. Use the Sgarbossa criteria to help: concordant ST elevation ≥ 1 mm is most specific [2].
This is the differential you must not miss because giving anticoagulation + antiplatelet therapy (the standard NSTEMI treatment) to a patient with aortic dissection is potentially fatal (promotes haemorrhage into the false lumen).
| Feature | NSTEMI | Aortic Dissection |
|---|---|---|
| Pain onset | Gradual (over minutes) | Sudden onset, maximal at onset [2][6] |
| Pain quality | Crushing, squeezing | Tearing, ripping, "knife-like" [3][7] |
| Pain radiation | Arms, jaw | Through to back (interscapular) [3][7] |
| BP | Variable | Unequal BP between arms (> 20 mmHg); may be hypertensive or hypotensive |
| Pulse | Usually present | May have absent/unequal pulses (if dissection flap obstructs branch vessels) |
| CXR | Usually normal | Widened mediastinum, irregular/wavy aortic outline, widening of aortic silhouette [7] |
| ECG | ST depression / T inversion | Usually normal; may show STEMI if dissection involves coronary ostium (especially RCA → inferior ST elevation) — this is a treacherous mimic |
| Troponin | Elevated | Usually normal unless coronary involvement |
| Definitive Ix | Coronary angiography | CT angiography (CTA): identification of true and false lumens; compressed true lumen is the key finding; true lumen is usually smaller, false lumen is usually larger [7] |
Why can aortic dissection mimic NSTEMI? Because:
- The dissection flap can extend to involve the coronary ostia (usually the RCA because it arises from the anterior/right aortic sinus, which is most often affected by Type A dissection) → genuine coronary malperfusion → myocardial ischaemia with troponin rise
- The pain itself can be severe and central, mimicking angina
PE causes acute chest pain ± dyspnoea ± haemoptysis [3][8]. It can mimic NSTEMI because:
- Both cause troponin elevation (PE raises troponin via RV strain/ischaemia from acute pressure overload)
- Both cause ST-T changes on ECG
- Both can present with chest pain + dyspnoea + haemodynamic compromise
| Feature | NSTEMI | PE |
|---|---|---|
| Pain quality | Crushing, central | Pleuritic (sharp, worse with inspiration) unless massive (then central/crushing) [3] |
| Associated symptoms | Diaphoresis, nausea | Dyspnoea (usually predominant), haemoptysis (late, with infarction) [8], unilateral leg swelling (DVT) |
| ECG | ST depression, T inversion | Sinus tachycardia (most common); right heart strain pattern: S1Q3T3, RBBB, T inversion V1–V4, RAD [5] |
| Troponin | Elevated (Type 1 MI) | May be mildly elevated (RV strain — this is a Type 2 mechanism) |
| D-dimer | Non-specific | Elevated (sensitive but not specific) |
| Risk factors | CAD risk factors | Virchow's triad: stasis, endothelial injury, hypercoagulability (recent surgery, immobilization, malignancy, OCP, prior VTE) |
| Definitive Ix | Coronary angiography | CTPA |
Why does PE cause troponin elevation? Acute massive PE → sudden ↑RV afterload → RV dilatation and wall stress → RV subendocardial ischaemia (the RV coronary perfusion is compromised when RV wall tension exceeds coronary perfusion pressure) → troponin leak. This is a Type 2 MI mechanism and does NOT warrant antiplatelet/anticoagulant therapy as for ACS — it requires PE-specific treatment (therapeutic anticoagulation, ± thrombolysis if massive).
Typically presents with sudden onset pleuritic chest pain + dyspnoea. In tension pneumothorax, there is progressive cardiovascular collapse (tachycardia, hypotension, ↑JVP, tracheal deviation). The key distinguishing feature is unilateral absent breath sounds + hyperresonance — these are absent in NSTEMI. CXR confirms.
B. Cardiac Non-ACS Differentials
Acute pericarditis is a classic mimic of ACS [1][3].
| Feature | NSTEMI | Acute Pericarditis |
|---|---|---|
| Pain quality | Crushing, pressure | Sharp, knife-like [3] |
| Positional change | Unrelated to position | Worse lying flat, better sitting forward/leaning forward |
| Respiratory variation | Minimal | Aggravated by respiratory movement [3] |
| Radiation | Arms, jaw | Trapezius ridge (characteristic and almost pathognomonic for pericardial pain) [3] |
| P/E | ± S3/S4 | Pericardial friction rub (scratchy, 3-component, best heard with patient leaning forward) |
| ECG | ST depression, T inversion | Diffuse concave ST elevation (saddle-shaped), PR depression (> 0.5–0.8 mm), never reciprocal ST depression in opposite leads, never in aVR, J/T > 25% in V6, shorter QTc [2] |
| Troponin | Elevated | May be mildly elevated if myocarditis component (myopericarditis); but troponin rise is usually modest |
| Inflammatory markers | Usually normal | ↑CRP, ↑ESR |
Why does pericarditis cause ST elevation? The inflamed pericardium (visceral layer, which is actually epicardium) creates an injury current across the entire epicardial surface → diffuse (not territorial) ST elevation. Because it is diffuse and concave ("smiley face"), it differs from the convex, territorial ST elevation of STEMI.
Takotsubo syndrome is specifically listed as a cardiac differential [1]. It mimics NSTEMI closely:
- Chest pain + troponin elevation + ECG changes (may show ST elevation, T-wave inversion, or QT prolongation)
- Regional wall motion abnormalities on echo (classically apical ballooning with basal hyperkinesis)
- But coronary angiography shows no obstructive CAD
Why does it happen? Catecholamine surge (from emotional or physical stress) → direct catecholamine toxicity to myocytes (especially apical, which has highest density of β-adrenergic receptors) + microvascular spasm → transient stunning. Typically in postmenopausal women.
Tachyarrhythmias (e.g., SVT, AF with rapid ventricular rate, VT) can cause chest pain and troponin elevation (Type 2 MI) via increased O₂ demand and decreased diastolic filling time (↓coronary perfusion) [1]. The key is that the arrhythmia is the primary event — treating the arrhythmia resolves the ischaemia.
Acute heart failure and hypertensive emergencies can cause troponin elevation through supply-demand mismatch (↑wall stress → ↑O₂ demand; ↓coronary perfusion from ↑LVEDP) [1]. Again, this is Type 2 MI. Flash pulmonary oedema with severely elevated BP points toward hypertensive emergency rather than primary ACS, although the two can coexist.
Aortic valve stenosis causes anginal chest pain because LVH from chronic pressure overload → ↑O₂ demand + ↓coronary flow reserve (subendocardial compression) [1][2]. Troponin may be mildly elevated. The key is the classic murmur: harsh crescendo-decrescendo systolic murmur at right upper sternal border radiating to carotids.
10. Pneumonia / Bronchitis / Pleuritis
Pneumonia and pleuritis cause pleuritic chest pain (sharp, worse with inspiration/cough) + respiratory symptoms (productive cough, fever, dyspnoea) [1][2][6]. CXR shows consolidation. There is no troponin elevation (unless pneumonia triggers Type 2 MI via sepsis/tachycardia/hypoxia).
D. Gastrointestinal Differentials
Gastrointestinal causes are actually the most common cause of chest pain overall (42% in the Fruergaard study) [1].
Oesophagitis, reflux, or oesophageal spasm is the most common GI mimic of angina [1][2][6]. Why is it so confusing?
- The oesophagus lies immediately posterior to the heart — both share visceral afferents entering the same spinal cord segments (T1–T5)
- Oesophageal spasm can cause retrosternal squeezing pain that even responds to GTN (GTN relaxes oesophageal smooth muscle too!)
- Key distinguishing features: relationship to meals, postural component (worse lying down), burning quality, response to antacids/PPIs, absence of ECG changes
Peptic ulcer and gastritis — epigastric pain that may be confused with inferior MI (which can present as epigastric discomfort). Look for relationship to meals, NSAID/alcohol use, Helicobacter pylori history.
Pancreatitis causes severe epigastric pain radiating to the back — can mimic inferior MI. Key: ↑↑amylase/lipase, risk factors (gallstones, alcohol).
Cholecystitis — RUQ pain radiating to right shoulder (diaphragmatic irritation), Murphy's sign positive. Interestingly, cholecystitis can cause ST-T changes on ECG (via vagal reflexes or shared splanchnic innervation), which is why it appears on the false-positive list for ST elevation [3].
15. Musculoskeletal Chest Wall Pain / Costochondritis
Musculoskeletal disorders, chest trauma, muscle injury/inflammation, costochondritis [1][2][6]. The hallmark is reproducible tenderness on palpation. Pain is often sharp, worsened by movement or palpation, and localized (can point to it with one finger). Pain typically occurs after exertion, not during (unlike angina which occurs during exertion) [2]. ECG and troponin are normal.
Costochondritis (Tietze syndrome if with swelling) — inflammation of the costochondral junctions, typically at 2nd–5th costochondral joints. Tender on palpation.
F. Other Differentials
Herpes zoster — dermatomal pain (burning, sharp) that may precede the rash by 48–72 hours. If thoracic dermatome T1–T6, can mimic cardiac pain. Once the vesicular rash appears, diagnosis is clear [1].
Anxiety disorders — chest tightness, palpitations, hyperventilation, paraesthesias, sense of doom. Diagnosis of exclusion in the acute setting — never dismiss chest pain as anxiety without first excluding life-threatening causes. Young patient without risk factors, normal ECG, normal troponin, with clear psychological stressor.
Anaemia listed as "Other" on the differential table [1]. Severe anaemia (↓O₂ carrying capacity) can cause chest pain via supply-demand mismatch, especially in patients with underlying CAD. This is a Type 2 MI mechanism. Check Hb — conjunctival pallor, tachycardia, flow murmur on auscultation.
Not all troponin elevations mean ACS. The following conditions cause troponin rise through non-ACS mechanisms:
| Condition | Mechanism of Troponin Rise |
|---|---|
| Myocarditis | Direct myocyte injury from inflammation |
| Takotsubo | Catecholamine-mediated myocyte injury |
| PE (massive) | RV strain → subendocardial ischaemia |
| Aortic dissection (with coronary involvement) | Coronary malperfusion |
| Sepsis / Critical illness | Supply-demand mismatch, direct myocyte injury |
| Renal failure | ↓Clearance of troponin + chronic myocardial injury |
| Tachyarrhythmias | ↑O₂ demand, ↓diastolic perfusion time |
| Heart failure (acute/chronic) | ↑Wall stress → subendocardial ischaemia |
| Cardiac contusion (trauma) | Direct mechanical myocyte damage |
| Post-cardiac procedures (PCI, CABG, ablation) | Iatrogenic myocyte injury (Type 4/5 MI) |
Clinical Decision Point
When you see elevated troponin, always ask: Is this a Type 1 MI (plaque event) or something else? The answer determines everything — Type 1 MI needs DAPT + anticoagulation + invasive strategy. Type 2 MI needs treatment of the underlying cause. Non-ischaemic troponin elevation (myocarditis, Takotsubo, CKD) needs specific management. The clinical context, ECG pattern, and echo findings help you differentiate.
| Condition | Pain Character | ECG | Troponin | Key Distinguishing Feature |
|---|---|---|---|---|
| NSTEMI | Crushing, central, > 20 min | ST depression / T inversion / normal | Elevated (rise/fall) | Risk factors, typical anginal features |
| STEMI | Similar but often more severe | Persistent ST elevation + reciprocal changes | Elevated (higher peak) | ECG is definitive |
| Aortic dissection | Tearing, maximal at onset, radiates to back | Usually normal (or inferior STEMI if RCA involved) | Usually normal | Unequal arm BP, widened mediastinum on CXR |
| PE | Pleuritic ± central if massive | Sinus tachycardia, S1Q3T3, RBBB, T inv V1–4 | Mild elevation (RV strain) | Dyspnoea predominant, DVT signs, D-dimer, CTPA |
| Pericarditis | Sharp, positional, ↑inspiration, → trapezius | Diffuse concave ST elevation + PR depression | ± mild elevation | Pericardial rub, ↑CRP/ESR |
| Takotsubo | Anginal, post-stress | ST elevation/T inversion/QTc prolongation | Elevated (modest) | Apical ballooning on echo, normal coronaries |
| GERD/oesophageal spasm | Burning, retrosternal, postprandial | Normal | Normal | Response to PPI/antacids, relation to meals |
| Musculoskeletal | Sharp, localized, reproducible on palpation | Normal | Normal | Tender on palpation, worsened by movement |
| Pneumothorax | Sudden, pleuritic, unilateral | May show low voltage | Normal | Absent breath sounds, hyperresonance, CXR |
The lecture slides present a systematic framework for working diagnosis at admission [3]:
Admission → Working Suspicion of ACS → ECG:
- Persistent ST elevation → STEMI
- ST/T abnormalities + Troponin positive → NSTEMI
- ST/T abnormalities + Troponin negative → Unstable Angina
- Normal / undetermined ECG → need serial troponin and clinical reassessmentThe key triage algorithm from the hs-troponin slides [1]:
- Stable patients: 12-lead ECG → if no ST elevation → blood sampling at 0h and 1h
- 0h hs-cTn very low and no chest pain → Rule-out MI → consider differential diagnosis → possible outpatient management
- 0h hs-cTn low and no 1h change → Rule-out → observation
- Relevant 1h change or high 0h value → Rule-in → CCU + angiography
- All others → observe → 3h hs-cTn + echocardiography
High Yield Summary — Differential Diagnosis of NSTEMI
Must-exclude life-threatening mimics: Aortic dissection (tearing, back, unequal BP), PE (pleuritic, dyspnoea, D-dimer/CTPA), tension pneumothorax (absent breath sounds), oesophageal rupture.
Must-exclude cardiac mimics: STEMI (persistent ST elevation), pericarditis (sharp, positional, diffuse concave ST elevation + PR depression, rub), Takotsubo (post-stress, apical ballooning, normal coronaries).
Common non-cardiac causes: GERD (most common overall), musculoskeletal (reproducible tenderness), anxiety.
Always distinguish Type 1 MI from Type 2 MI: Type 1 = plaque event → DAPT + anticoagulation + invasive. Type 2 = supply-demand mismatch → treat the cause.
Troponin is not ACS-specific: myocarditis, PE, Takotsubo, sepsis, CKD, tachyarrhythmias all raise troponin without coronary plaque events.
Active Recall - Differential Diagnosis of NSTEMI
References
[1] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (pp. 15–17, 27) [2] Senior notes: Ryan Ho Cardiology.pdf (Sections 2.1, 3.2.2 ACS, pp. 54, 128–129) [3] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (pp. 13, 26, 30, 57) [5] Senior notes: Ryan Ho Critical Care.pdf (p. 17) [6] Senior notes: Ryan Ho Fundamentals.pdf (pp. 199, 203) [7] Senior notes: felixlai.md (Section on Aortic Dissection differential diagnosis and CTA findings) [8] Senior notes: Ryan Ho Haemtology.pdf (p. 131, VTE spectrum)
Diagnostic Criteria for NSTEMI
The diagnosis of NSTEMI rests on a precise set of criteria. Let's build this from first principles — you need evidence of myocardial necrosis (troponin) in the context of myocardial ischaemia (clinical, ECG, or imaging evidence), and critically, the ECG must not show persistent ST elevation (which would make it STEMI instead).
Detection of a rise and/or fall of cardiac biomarker values (preferably cardiac troponin, cTn) with at least one value above the 99th percentile upper reference limit (URL) [2][3]:
Plus at least one of:
| Criterion | What It Means | Why It's Needed |
|---|---|---|
| 1. Symptoms of ischaemia | Chest pain/discomfort with typical anginal features, or anginal equivalents (dyspnoea in diabetics/elderly) | Clinical evidence that the troponin rise is ischaemic in origin, not from another cause (e.g., sepsis, PE) |
| 2. New or presumed new significant ST-T changes or new LBBB | ST depression ≥ 0.5 mm, T-wave inversion ≥ 1 mm in ≥ 2 contiguous leads, or new LBBB | ECG evidence of ischaemia/injury; for NSTEMI specifically, there must NOT be persistent ST elevation |
| 3. Development of pathological Q waves | Q wave ≥ 30 ms wide and ≥ 1 mm deep in ≥ 2 contiguous leads (or QS in V2–V3) | Indicates established necrosis (usually appears later — implies completed infarction) |
| 4. Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality (RWMA) | New akinesis/hypokinesis on echo or cardiac MRI in a coronary territory distribution | Structural evidence that myocardium has been damaged |
| 5. Identification of an intracoronary thrombus by angiography or post-mortem | Direct visualization of thrombus at coronary angiography or autopsy | Pathological confirmation of the mechanism (plaque event + thrombosis) |
The Key Distinguishing Point: NSTEMI vs STEMI
Both NSTEMI and STEMI satisfy the universal definition of MI. The distinction is made on ECG: STEMI has persistent ST elevation (or new LBBB) meeting specific voltage criteria, while NSTEMI does not. This distinction is made at the point of first ECG because it determines the urgency of reperfusion — STEMI needs emergent PCI/fibrinolysis, NSTEMI needs risk-stratified timing.
This is crucial and often misunderstood. A single elevated troponin is not sufficient to diagnose acute MI — you need a dynamic pattern (rise and/or fall), because:
- Chronic troponin elevation (e.g., in CKD, stable HF) is usually stable — no dynamic change → this represents chronic myocardial injury, NOT acute MI
- Acute MI causes sudden myocyte death → troponin is released acutely → the value rises from baseline, peaks, then falls as troponin is cleared
The lecture slides illustrate the timing of biomarker release [1]:
- Rising cTn values from below to > 99th percentile → acute MI
- Detectable cTn values > 99th percentile with a delta (change) → acute MI
- cTn values > 99th percentile but declining delta or no significant change → chronic myocardial injury (e.g., CKD, stable HF)
The 3rd/4th Universal Definition classifies MI into types that guide the diagnostic workup and management [2]:
| Type | Description | Diagnostic Criteria |
|---|---|---|
| Type 1 | Spontaneous MI due to primary coronary event (plaque erosion/rupture, fissuring, or dissection) | Standard criteria above |
| Type 2 | MI secondary to ischaemia due to imbalance between O₂ demand and supply (coronary spasm, anaemia, hypotension) | Standard criteria above, but the clinical context identifies a precipitant other than plaque rupture |
| Type 3 | Sudden cardiac death | Symptoms of ischaemia + new ischaemic ECG changes or LBBB; but death occurring before blood samples could be obtained or before appearance of biomarkers in blood |
| Type 4a | MI associated with PCI | ↑cTn > 5 × 99th URL (if normal baseline); or ↑cTn > 20% (if baseline elevated and stable) + symptoms/ECG/angiographic/imaging criteria |
| Type 4b | MI associated with verified stent thrombosis | Verified stent thrombosis in coronary angiography or autopsy + rise/fall of cTn with ≥ 1 value above 99th URL |
| Type 5 | MI associated with CABG | ↑cTn > 10 × 99th URL (if normal baseline cTn) + new pathological Q/LBBB or angiographic new graft/native artery occlusion or imaging evidence |
Criteria for prior (old) MI [3]:
- Development of new pathological Q waves with or without symptoms
- Imaging evidence of a region of loss of viable myocardium that is thinned and fails to contract, in the absence of a non-ischaemic cause
- Pathological findings post-mortem of a healed or healing myocardial infarction
Diagnostic Algorithm
This is the cornerstone of modern NSTEMI diagnosis and was heavily emphasised on the lecture slides [1]. The algorithm uses high-sensitivity cardiac troponin (hs-cTn) — assays that can detect troponin concentrations 10–100× lower than conventional assays — to rapidly triage patients into three pathways.
The algorithm applies to patients presenting with suspected NSTE-ACS who do NOT have an indication for immediate invasive angiography [1].
Key thresholds for the 0h/1h algorithm (assay-specific — values differ between manufacturers) [1]:
| Pathway | hs-cTnT (Roche Elecsys) | hs-cTnI (Abbott ARCHITECT) | What to Do |
|---|---|---|---|
| Rule-out | 0h < 5 ng/L AND no significant 1h change | 0h < 2 ng/L AND 1h delta < 2 ng/L | Consider differential diagnosis; possible outpatient management |
| Observe | Does not meet either | Does not meet either | Repeat at 3h + echo + clinical reassessment |
| Rule-in | 0h ≥ 52 ng/L OR 1h delta ≥ 5 ng/L | 0h ≥ 64 ng/L OR 1h delta ≥ 6 ng/L | Admit CCU + angiography |
Why 0h/1h and Not Just One Measurement?
A single troponin at presentation may be falsely low if the patient presents very early (troponin has not had time to rise) or may be chronically elevated (CKD, HF). The delta (change between 0h and 1h/2h) captures the dynamic rise that indicates acute myocyte death. A patient with hs-cTnT of 20 ng/L at 0h and 45 ng/L at 1h has a significant rise — this is acute MI. A patient with 20 ng/L at both time points likely has chronic elevation — this is NOT acute MI.
Exam High Yield: Very Low hs-cTn at 0h
If the 0h hs-cTn is very low (below the limit of detection or assay-specific cut-off) AND the patient has been symptomatic for > 3 hours, the NPV for MI is > 99%. These patients can often be safely discharged with outpatient follow-up. But if symptom onset was < 1–2 hours ago, a very low 0h value does NOT rule out MI — you must wait for the 1h sample.
Certain patients bypass the troponin algorithm entirely and go straight to the cath lab (< 2 hours) [1][9]:
Very high risk criteria (immediate invasive strategy) [1][9]:
- Haemodynamic instability or cardiogenic shock
- Acute heart failure presumed secondary to ongoing myocardial ischaemia
- Life-threatening arrhythmias or cardiac arrest after presentation
- Mechanical complications
- Recurrent dynamic ECG changes suggestive of ischaemia
After NSTEMI is confirmed, the GRACE risk score determines the timing of the invasive strategy [1][9]:
Risk Calculator for 6-Month Post-discharge Mortality [1]:
| Variable | Points |
|---|---|
| Age | 0 (< 30) to 100 (≥ 90) |
| Resting heart rate | 0 (< 50) to 46 (≥ 200) |
| Systolic blood pressure | 0 (≥ 200) to 58 (< 80) — note inverse relationship |
| Serum creatinine | 1 (0–0.39) to 28 (≥ 4) |
| History of CHF | 24 |
| History of MI | 12 |
| Elevated cardiac biomarkers | 15 |
| No in-hospital PCI | 14 |
| ST-segment depression | 11 |
| Killip class | Included in scoring |
Timing of invasive strategy based on GRACE score [1][9]:
| Risk | GRACE Score | Strategy |
|---|---|---|
| Very high risk | Clinical criteria above | Immediate (< 2h) |
| High risk | > 140 or confirmed NSTEMI diagnosis based on ESC algorithms, or transient ST elevation, or dynamic ST/T changes | Early/inpatient transfer (< 24h) |
| Intermediate | 109–140 | Invasive within 72h |
| Low risk | Patients without very-high or high-risk features and a low index of suspicion for unstable angina | Selective invasive: determine (if required) risk and therapeutic strategy |
Investigation Modalities — Detailed Interpretation
A. Electrocardiography (ECG)
Perform 12-lead ECG as soon as possible — ideally within 10 minutes of first medical contact [1][2][6].
The ECG is the single most important initial investigation because it immediately dichotomises the patient into STE-ACS vs NSTE-ACS, which determines the entire management pathway. It is cheap, fast, non-invasive, and available everywhere.
NSTE-ACS ECG features [2]:
- ST depression
- T-wave changes (inversion or flattening)
- ± some loss of R waves (if infarcted)
Let's understand each finding from first principles:
| ECG Finding | Pathophysiological Basis | Specifics |
|---|---|---|
| ST depression | Subendocardial injury current directed from epicardium toward endocardium (away from surface electrode) → negative deflection in the ST segment | ≥ 0.5 mm (0.05 mV) in ≥ 2 contiguous leads is significant; horizontal or downsloping is more specific than upsloping |
| T-wave inversion | Altered repolarization sequence from ischaemic myocardium — ischaemic cells repolarize earlier (shortened APD) → repolarization wave reverses direction | ≥ 1 mm in ≥ 2 contiguous leads with prominent R wave |
| Normal ECG | Small area of ischaemia, or territory poorly represented on standard 12-lead (e.g., posterior wall/LCx) | Up to 30–40% of NSTEMI patients may have a non-diagnostic initial ECG — this is why serial ECGs are essential |
| Transient ST elevation | Intermittent complete occlusion that self-resolves (e.g., cyclic thrombus formation and lysis, or vasospasm on top of partial occlusion) | If captured, indicates very high risk — treat as immediate invasive |
Special ECG patterns to recognise [2]:
- Wellens syndrome: deeply inverted or biphasic T waves in V2–V3 → highly specific for critical LAD stenosis → extremely high risk for extensive anterior wall MI in the subsequent days/weeks [2]
- ST elevation in aVR with widespread ST depression (most prominent in leads I, II, V4–6): usually indicates left main stem occlusion [2]
- Pseudonormalization of T wave: transient normalization of T wave from an inverted form → indicates transient recanalization of coronary artery → prone to restenosis [2]
ECG pitfalls — false positives for ST elevation (i.e., NOT STEMI) [3]:
- Benign early repolarization, LBBB, pre-excitation, Brugada syndrome, peri-/myocarditis, pulmonary embolism, subarachnoid haemorrhage, hyperkalaemia, cholecystitis, lead transposition
ECG pitfalls — false negatives (may miss MI) [3]:
- Prior Q waves and/or persistent ST elevation, paced rhythm, LBBB
Serial ECGs: 12-lead ECG stat and repeat at least daily × 3 days (more frequently in severe cases) [2][6]. The rationale is that the initial ECG may be normal or non-diagnostic, and ischaemic changes may evolve over hours.
When standard 12-lead ECG is non-diagnostic but clinical suspicion remains high:
- Posterior leads (V7–V9): for posterior wall MI (LCx or RCA territory) — ST elevation ≥ 0.5 mm
- Right-sided leads (V3R–V6R): for RV infarction complicating inferior MI — ST elevation ≥ 1 mm in V4R
B. Cardiac Biomarkers
Cardiac enzymes: cTnT, cTnI, CK-MB [7] — but in modern practice, hs-cTn has replaced CK-MB as the primary biomarker.
| Biomarker | Rises | Peaks | Normalises | Key Points |
|---|---|---|---|---|
| hs-cTnT / hs-cTnI | 1–3 hours | 12–24 hours | 5–14 days | Gold standard; most sensitive and specific for myocardial necrosis; enables 0h/1h rule-in/rule-out algorithm |
| CK-MB | 3–4 hours | 12–24 hours | 48–72 hours | Less sensitive/specific than troponin; historically used but now mainly for detecting reinfarction (because it normalises faster — a second rise indicates new event) |
| Myoglobin | 1–2 hours | 6–8 hours | 24 hours | Very early marker but NOT cardiac-specific (also from skeletal muscle); now largely obsolete |
Why is troponin so specific for myocardial injury?
- Troponin I and T are structural proteins of the cardiac sarcomere (part of the thin filament regulatory complex)
- The cardiac isoforms (cTnI and cTnT) have unique amino acid sequences not found in skeletal muscle
- When myocytes undergo necrosis, the cell membrane ruptures and troponin leaks into the bloodstream
- hs-cTn assays can detect concentrations as low as a few ng/L, enabling very early diagnosis
Cardiac enzymes daily × 3 days (repeat troponin 6–12h later if 1st Tn is normal) [2][6] — this catches late presenters and slow-rising troponin curves.
This is critical for interpretation — an elevated troponin does NOT automatically mean "send to cath lab":
| Category | Examples |
|---|---|
| Type 2 MI | Tachyarrhythmia, hypotension, anaemia, respiratory failure, sepsis |
| Acute non-ischaemic myocardial injury | Myocarditis, Takotsubo, cardiac contusion, cardioversion, ablation, cardiotoxic drugs |
| Chronic myocardial injury | CKD (most common cause of chronically elevated troponin), HF, infiltrative cardiomyopathy, amyloidosis |
| Extracardiac | PE (RV strain), severe sepsis, burns, stroke/SAH, extreme exercise |
The key distinguishing factor is the clinical context + dynamic pattern (rise/fall vs stable).
Basic bloods: CBC, L/RFT, lipid profile (≤ 24h), aPTT/INR (as baseline for heparin) [2][6]
| Test | Why | What to Look For |
|---|---|---|
| CBC | R/o anaemia (Type 2 MI trigger), assess platelet count (baseline for antiplatelet/anticoagulant safety), WBC (infection/inflammation as precipitant) | ↓Hb, ↓PLT, ↑WCC |
| RFT (U&E, Creatinine) | Renal function affects drug dosing (enoxaparin, fondaparinux need renal adjustment), creatinine is a GRACE score variable, CKD independently worsens prognosis | ↑U/Cr (shock-induced AKI) [5]; eGFR for drug dosing |
| LFT | Baseline before statin; hepatic congestion from HF (↑ALT/AST); shock liver [5] | ↑transaminases |
| Lipid profile (within 24h) | Must be taken within 24h of admission because lipid levels fall after acute MI (acute phase response ↓LDL) and remain low for weeks; early measurement reflects true baseline | ↑LDL, ↓HDL guide secondary prevention |
| Fasting glucose / HbA1c | Screen for DM (a major modifiable risk factor); hyperglycaemia at presentation is an independent predictor of worse outcome even in non-diabetics | ↑glucose, ↑HbA1c |
| aPTT / INR | Baseline before initiating heparin; also screens for pre-existing coagulopathy | Needed for monitoring UFH therapy |
| ABG / VBG + lactate | Assess oxygenation, acid-base status; lactic acidosis indicates poor tissue perfusion [5] | ↓PaO₂, metabolic acidosis, ↑lactate (cardiogenic shock) |
| BNP / NT-proBNP | Assess degree of myocardial wall stress / heart failure; prognostic marker in ACS (higher BNP → worse outcome) | ↑BNP correlates with LV dysfunction severity |
CXR: usually non-diagnostic in ACS; look for other causes (e.g., aortic dissection, PE, pneumonia or pneumothorax) [2][6]
| Finding | Significance |
|---|---|
| Normal | Does NOT exclude NSTEMI (the heart and lungs are often normal-appearing) |
| Pulmonary oedema (upper lobe diversion, Kerley B lines, bilateral fluffy opacities, bat-wing pattern) | Indicates LV failure complicating MI → Killip class II–III |
| Cardiomegaly (CTR > 0.5) | Pre-existing cardiomyopathy, chronic HF, pericardial effusion |
| Widened mediastinum, irregular aortic outline | Aortic dissection [7] — must be actively excluded |
| Focal consolidation | Pneumonia (may be the precipitant for Type 2 MI, or an alternative diagnosis) |
| Absent lung markings with visible pleural line | Pneumothorax |
Echocardiography is the key bedside imaging tool in NSTEMI. It is recommended:
- At presentation if diagnosis is uncertain (RWMA supports ischaemic aetiology)
- In all patients to assess LV function (LVEF is the strongest predictor of long-term survival [2])
- To detect mechanical complications
| Finding | Significance |
|---|---|
| Regional wall motion abnormality (RWMA) — hypokinesis, akinesis, or dyskinesis in a coronary territory distribution | Supports diagnosis of MI; territory identifies culprit vessel (e.g., anterior akinesis → LAD) |
| LVEF assessment | LVEF < 50% associated with significantly increased event risk regardless of severity of ischaemia [2]; guides need for HF therapy and ICD consideration |
| Valvular assessment | New MR (papillary muscle dysfunction/rupture), assess pre-existing AS/AR |
| Mechanical complications | VSD (colour Doppler shows shunt), free wall rupture (pericardial effusion/tamponade), LV aneurysm/pseudoaneurysm |
| RV function | RV infarction (RV dilatation, ↓TAPSE) in inferior MI |
| Pericardial effusion | May indicate post-MI pericarditis, LV free wall rupture, or aortic dissection (if root involved) [7] |
| Normal echo | Does NOT exclude NSTEMI (small subendocardial infarcts may not produce detectable RWMA) |
Echocardiography is also mentioned in the hs-cTn algorithm observation pathway: 3h hs-cTn + echocardiography [1].
Coronary angiography is the definitive investigation — it directly visualises the coronary anatomy and identifies the culprit lesion [1][2].
In patients with NSTE-ACS, the lecture slides presented a meta-analysis of early vs delayed invasive strategy [1]:
- Meta-analysis of 17 randomised trials showed no significant difference in all-cause mortality (OR 0.90, 0.78–1.04), but trends toward benefit in high-risk subgroups
- This is why risk stratification (GRACE score) determines timing rather than a blanket "all patients get immediate angiography"
Findings at angiography [1]:
| Finding | Interpretation |
|---|---|
| Significant stenosis (≥ 70%, or ≥ 50% for LMS) | Culprit lesion identified; revascularization considered |
| Ambiguous/hazy lesion, calcification, tortuosity/eccentricity | May require further intravascular imaging |
| Normal or near-normal coronaries (≤ 50% stenosis) | MINOCA (MI with no obstructive coronary atherosclerosis) — 1–14% of all MIs [2] |
Adjunctive intravascular imaging [1]:
- IVUS (intravascular ultrasound) or OCT (optical coherence tomography) imaging findings
- Can differentiate: Erosion vs Nodule vs Rupture — this is important because plaque erosion may be managed differently from plaque rupture
- Helps when the angiographic appearance is ambiguous
Vessel disease burden guides management [2]:
- 1VD: usually PCI
- 2VD or 3VD: Heart Team discussion (PCI vs CABG)
- LMS disease: usually CABG (highest mortality if untreated)
G. Non-Invasive Cardiac Imaging (Before or After Angiography)
These are used either for risk stratification in lower-risk patients ruled out for acute MI, or for further workup of MINOCA.
Referenced in the hs-cTn algorithm for low-intermediate risk patients in the rule-out pathway [1].
| Feature | Details |
|---|---|
| Role | Non-invasive alternative to invasive coronary angiography; excellent NPV (99–100%) for excluding significant CAD [2] |
| Best for | Low-intermediate pre-test probability (PTP 15–50%) [2]; younger patients |
| Significant stenosis | ≥ 70% stenosis (≥ 50% for LMS) [2] |
| Limitations | Severe obesity, CKD (contrast nephropathy), prior CABG, prior stenting (metal artefact), Agatston calcium score > 400 (↓specificity) [2] |
| Calcium scoring | Agatston score > 100 generally correlated with significant risk of CAD; zero calcium score cannot rule out stenosis in symptomatic individuals [2] |
Used for patients in whom acute MI has been ruled out but CAD is still suspected, or for risk stratification post-NSTEMI before discharge.
| Modality | Principle | Best For |
|---|---|---|
| Exercise tolerance test (ETT) | Exercise → ↑HR → ↑myocardial O₂ demand → unmask ischaemia on ECG; +ve test = horizontal or downsloping ST depression ≥ 0.1 mV (1 mm) 80 ms after J point [2] | Low-intermediate PTP, normal baseline ECG, not on anti-ischaemic drugs [2] |
| Stress echocardiography | Exercise or dobutamine stress → new RWMA indicates inducible ischaemia | When ETT is non-diagnostic or baseline ECG abnormal |
| Myocardial perfusion imaging (MPI / SPECT) | Coronary steal phenomenon: with stress, vessels supplying normal myocardium dilate → blood siphoned away from stenosed territory → appears as "cold spots" [10]; ischaemia = cold spots with stress only; infarct = cold spots at rest + stress | When ETT is non-diagnostic; also assesses myocardial viability |
| Cardiac MRI | Assess RWMA, oedema (T2-weighted), late gadolinium enhancement (fibrosis/scar vs viable myocardium) | MINOCA workup (distinguishes MI from myocarditis/Takotsubo); viability assessment |
Stress testing or CCTA is recommended for the rule-out pathway in the hs-cTn algorithm for low and intermediate risk patients [1].
| Investigation | Timing | Purpose | Key Findings |
|---|---|---|---|
| 12-lead ECG | Within 10 min | Triage STE vs NSTE-ACS | ST depression, T inversion, normal, Wellens, de Winter |
| hs-cTn | 0h, 1h (±3h) | Confirm/exclude MI | Rise and/or fall > 99th URL |
| CBC | Admission | Exclude anaemia, baseline PLT | ↓Hb, ↓PLT |
| RFT | Admission | Drug dosing, GRACE score, AKI | ↑Cr, ↓eGFR |
| Lipid profile | Within 24h | Baseline for secondary prevention | ↑LDL |
| Glucose / HbA1c | Admission | Screen DM, prognostic | ↑glucose |
| aPTT / INR | Admission | Baseline for anticoagulation | |
| BNP / NT-proBNP | Admission | Prognostic, HF assessment | ↑ = worse prognosis |
| CXR | Admission | Exclude mimics, assess HF | Pulmonary oedema, widened mediastinum |
| Echocardiography | Early (within 24h) | LVEF, RWMA, complications | Hypo/akinesis, ↓LVEF, new MR, VSD |
| Coronary angiography | Risk-stratified timing | Identify culprit, guide revascularization | Stenosis, thrombus, vessel disease burden |
| CCTA | Post-rule-out (if indicated) | Exclude significant CAD non-invasively | NPV > 99% |
| Stress testing | Post-stabilization or post-rule-out | Functional significance, risk stratification | Inducible ischaemia |
The clinical spectrum, working diagnosis, and final diagnosis framework from the lecture slides [1][3]:
Clinical presentation ranges from oligo/asymptomatic → increasing chest pain → persistent chest pain → cardiogenic shock/acute HF → cardiac arrest [1].
Working diagnosis is made by combining: [3]
- ECG: persistent ST/T abnormalities vs normal/undetermined
- Biochemistry: troponin positive vs troponin negative
Final diagnosis [3]:
- Persistent ST elevation + troponin positive → STEMI
- ST/T abnormalities + troponin positive → NSTEMI
- ST/T abnormalities or normal ECG + troponin negative → Unstable Angina
High Yield Summary — Diagnosis of NSTEMI
Diagnostic Criteria (4th Universal Definition): Rise and/or fall of hs-cTn with ≥ 1 value above 99th percentile URL PLUS ≥ 1 of: ischaemic symptoms, new ST-T changes or LBBB, pathological Q waves, imaging evidence of new RWMA/loss of viable myocardium, or intracoronary thrombus on angiography. Must NOT have persistent ST elevation.
Algorithm: ESC 0h/1h hs-cTn algorithm — Rule-out (very low/low hs-cTn with no delta), Observe (intermediate), Rule-in (high or significant delta). Very high risk patients bypass algorithm → immediate angiography < 2h.
Risk Stratification: GRACE score determines timing of invasive strategy — immediate (< 2h), early (< 24h), or within 72h.
Key Investigations: ECG (within 10 min), hs-cTn (0h/1h/±3h), baseline bloods (CBC, RFT, lipids within 24h, glucose, coagulation), CXR (exclude mimics), echo (LVEF + RWMA + complications), coronary angiography (definitive, risk-stratified timing).
Troponin Pitfalls: Single elevated value is insufficient — need rise/fall pattern. Chronic elevation (CKD, HF) is NOT acute MI. Many non-ACS causes of troponin elevation exist.
LVEF is the strongest predictor of long-term survival in CAD patients.
Active Recall - NSTEMI Diagnosis and Investigations
[1] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (pp. 11, 26, 33, 50) [2] Senior notes: Ryan Ho Cardiology.pdf (pp. 116–117, 127–129, 142) [3] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (pp. 26, 30, 35, 48, 57) [5] Senior notes: Ryan Ho Critical Care.pdf (pp. 17, 22) [6] Senior notes: Ryan Ho Fundamentals.pdf (p. 203) [7] Senior notes: felixlai.md (Diagnosis section — cardiac enzymes, CXR, ECG, echocardiogram, CTA) [9] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (p. 48) [10] Senior notes: Ryan Ho Diagnostic Radiology.pdf (pp. 43, 57)
Management of NSTEMI
The management of NSTEMI is conceptually different from STEMI. In STEMI, the artery is completely occluded and every minute counts — you rush to open it. In NSTEMI, there is still some residual flow, so you have time to stabilise the patient, risk-stratify, and then decide on the optimal timing and approach for revascularisation. Thrombolysis has no benefit in NSTE-ACS and may even be harmful [2] — this is a critical exam point.
The management framework divides neatly into:
- Immediate / Acute management (first 24–48 hours)
- Invasive strategy (risk-stratified timing of coronary angiography ± revascularisation)
- Long-term / Secondary prevention
1. Immediate / Acute Management (First 24–48 Hours)
These are essential supportive measures that apply to ALL patients with suspected or confirmed NSTEMI [2][6]:
| Measure | Details | Rationale |
|---|---|---|
| Inform on-call cardiologist | Early specialist involvement | Guides decision on invasive strategy timing |
| Admit CCU if high-risk | High-risk = ongoing chest pain, ↓BP, APO, ventricular arrhythmia [2][6] | Continuous monitoring, immediate defibrillation access |
| Bed rest with continuous ECG monitoring | Telemetry for arrhythmia detection | Ischaemic myocardium is electrically unstable — VT/VF can occur without warning |
| Correct precipitating factors | Anaemia, hypoxia, tachyarrhythmia [2] | If a Type 2 MI component exists, correcting the precipitant may be more important than the cath lab |
| O₂ supplementation | Keep SaO₂ > 90% and PaO₂ > 60 mmHg [2] | Hypoxia worsens ischaemia; but routine high-flow O₂ in normoxic patients is NOT recommended (may cause vasoconstriction and is not beneficial) |
| Nil by mouth or soft diet + stool softener | Ileus common in patients with acute MI [2] | Vagal stimulation from straining (Valsalva) can cause bradycardia/arrhythmia; soft diet in case emergent PCI/CABG needed |
| Explain nature of disease | Allay anxiety [2] | Anxiety → sympathetic activation → ↑HR, ↑BP → ↑myocardial O₂ demand → worsens ischaemia |
Analgesia is required if nitrates are insufficient for symptom relief [2].
| Drug | Dose | Mechanism | Why It Helps |
|---|---|---|---|
| IV morphine | 2.5–5 mg IV, repeat PRN | μ-opioid receptor agonist → central analgesia + anxiolysis + venodilation | ↓Distress, ↓adrenergic drive → ↓SVR, ↓BP, ↓risk of ventricular arrhythmias [2]; venodilation → ↓preload → ↓myocardial O₂ demand |
| IV metoclopramide (Maxolon) | 5–10 mg [2] | D₂ antagonist — antiemetic | Morphine causes nausea/vomiting (stimulates CTZ); also MI itself causes vagal-mediated nausea |
| ± Sedation (diazepam 2–5 mg PO TDS) | [2] | Benzodiazepine — GABA-A agonist | Anxiolysis → ↓sympathetic drive |
Morphine Caution
While morphine provides excellent symptom relief, there is observational evidence that it may delay absorption of oral P2Y12 inhibitors (by slowing gastric motility) and was associated with worse outcomes in some registries. Current guidelines (ESC 2023) recommend cautious use — give it when needed for pain, but do not use routinely. Always co-administer an antiemetic.
2. Acute Pharmacotherapy
This is the core of NSTEMI management. Think of it as four pillars: Antiplatelet, Anticoagulant, Anti-ischaemic, and Disease-modifying (statin + ACEI/ARB). Each pillar targets a specific aspect of the pathophysiology.
Pillar 1: Antiplatelet Therapy
The thrombus in NSTEMI is platelet-rich ("white thrombus"). Platelet activation occurs through multiple pathways — you need to block at least two to be effective. This is why we use dual antiplatelet therapy (DAPT) = aspirin + P2Y12 inhibitor.
| Feature | Details |
|---|---|
| Mechanism | Irreversibly inhibits cyclooxygenase-1 (COX-1) → blocks thromboxane A₂ (TXA₂) synthesis → TXA₂ is a potent platelet activator and vasoconstrictor |
| Why irreversible matters | Platelets are anucleate — they cannot synthesize new COX-1. So one dose of aspirin disables TXA₂ production for the entire 7–10 day lifespan of that platelet |
| Dose | Loading: 150–300 mg (chewed for rapid buccal absorption); Maintenance: 75–100 mg daily [1][11] |
| Duration | Indefinitely (lifelong) in all patients with CAD [1][2][11] |
| Contraindications | True aspirin allergy (urticaria, angioedema, bronchospasm), active GI bleeding, severe bleeding diathesis |
| If aspirin intolerant | Clopidogrel 75 mg daily as alternative when ASA is not tolerated because of hypersensitivity or GI intolerance [11] |
P2Y12 is an ADP receptor on platelets. ADP is released from dense granules of activated platelets → activates neighbouring platelets (amplification loop). Blocking P2Y12 breaks this amplification.
The lecture slides present the antiplatelet algorithm for NSTEMI [1]:
| Drug | Mechanism | Dose | Key Points |
|---|---|---|---|
| Ticagrelor | Reversible, direct-acting P2Y12 antagonist (does NOT require metabolic activation) | Loading 180 mg; Maintenance 90 mg BD [11] | Recommended first-line P2Y12 inhibitor for NSTEMI [1][11]; can be given as pretreatment before angiography; faster onset (~30 min) and more potent than clopidogrel; Side effects: dyspnoea (adenosine reuptake inhibition), bradycardia |
| Prasugrel | Irreversible thienopyridine; requires single-step hepatic activation (faster and more predictable than clopidogrel) | Loading 60 mg; Maintenance 10 mg QD | Given after defining coronary anatomy (i.e., at time of PCI, not as pretreatment) [1]; more potent than clopidogrel; C/I: prior stroke/TIA (↑ICH risk), age ≥ 75y (↑bleeding without mortality benefit), body weight < 60 kg (↑bleeding — consider 5 mg maintenance) |
| Clopidogrel | Irreversible thienopyridine; requires two-step hepatic activation via CYP2C19/3A4 (pro-drug) | Loading 300–600 mg; Maintenance 75 mg QD | Used if ticagrelor and prasugrel are not available or contraindicated [1][11]; slowest onset (~2–6h); significant inter-individual variability (CYP2C19 polymorphisms → poor metabolizers get inadequate platelet inhibition); Caveat: clopidogrel interacts with PPI (inhibit CYP2C19/3A4 activation → treatment failure) [2] |
Antiplatelet strategy based on the lecture slide algorithm [1]:
At first medical contact (NSTEMI):
- Pretreatment: Ticagrelor (preferred) OR Clopidogrel (if ticagrelor not available or contraindicated) [1]
- No established role for prasugrel pretreatment [1]
If PCI is performed:
- Prasugrel (after defining coronary anatomy) or ticagrelor — choice based on contraindications and precautions [1]
- Consider cangrelor in patients not pretreated [1] — cangrelor is an IV P2Y12 inhibitor with ultra-rapid onset and offset (half-life ~3–6 min), useful as a bridge when oral P2Y12 cannot be given
- Clopidogrel if prasugrel and ticagrelor are not available or contraindicated [1]
If CABG is needed:
- Withdraw ticagrelor for 5 days and prasugrel for 7 days [1] — to reduce perioperative bleeding (platelets need time to regenerate unblocked populations)
- Withdraw clopidogrel for 5 days [1]
If no revascularisation (medical management):
- Continue P2Y12 inhibitor as per medical management pathway
At discharge [1]:
- If PCI performed: continue prasugrel or ticagrelor
- If previously treated with clopidogrel, switch to ticagrelor [1]
- If CABG performed: resume ticagrelor or clopidogrel as soon as possible [1]
- DAPT maintained over 12 months unless there are contraindications or an excessive risk of bleeding [11]
- After 12 months, aspirin continues indefinitely; P2Y12 inhibitor may be stopped or continued based on ischaemic vs bleeding risk assessment
DAPT Duration — The Balancing Act
The 12-month DAPT duration is a compromise between ischaemic risk (stent thrombosis, recurrent MI — favouring longer DAPT) and bleeding risk (favouring shorter DAPT). In patients with high bleeding risk (HBR), DAPT may be shortened to 3–6 months. In patients with high ischaemic risk and low bleeding risk, extended DAPT beyond 12 months (or even with low-dose rivaroxaban — the COMPASS trial) may be considered.
| Feature | Details |
|---|---|
| Examples | Abciximab (monoclonal antibody), eptifibatide (cyclic peptide), tirofiban (non-peptide) |
| Mechanism | Block the GPIIb/IIIa receptor on platelet surface — this is the final common pathway of platelet aggregation (GPIIb/IIIa cross-links platelets via fibrinogen bridges). Blocking this receptor = most potent antiplatelet effect possible |
| Indication | For selected patients only [2] — typically used peri-procedurally during PCI in high-risk situations (e.g., large thrombus burden, no-reflow) |
| Route | IV only (not oral) |
| Risk | Major bleeding, thrombocytopaenia |
The coagulation cascade is activated alongside platelet activation at the site of plaque disruption. Thrombin generation → fibrin mesh stabilises the platelet plug. Anticoagulation prevents thrombus propagation.
Heparin/LMWH at diagnosis [2][6]
| Drug | Mechanism | Dosing | Monitoring | Key Points |
|---|---|---|---|---|
| Enoxaparin (LMWH) | Low-molecular-weight fractionated heparin → more reliable pharmacokinetics [12]; preferentially inhibits Factor Xa (anti-Xa:anti-IIa ratio ~3:1) | 1 mg/kg SC BD (reduce to 1 mg/kg QD if eGFR < 30) | No routine monitoring needed [12] (but can check anti-Xa levels in obesity, renal impairment) | Preferred over UFH in most NSTEMI patients; continue until revascularisation or for duration of hospital stay (usually up to 8 days) |
| Fondaparinux | Retains active pentasaccharide sequence of heparin → only binds Factor Xa [12] | 2.5 mg SC QD | No monitoring | Can be used in heparin-induced thrombocytopaenia (HIT) [12]; lowest bleeding risk among parenteral anticoagulants; ESC guidelines recommend fondaparinux as preferred in NSTE-ACS if no immediate invasive strategy planned; must add UFH bolus at time of PCI (fondaparinux alone is insufficient for catheter-related thrombosis) |
| Unfractionated heparin (UFH) | Binds to antithrombin → ↑its affinity for thrombin and Factor Xa → inhibits both [12] | Weight-based: 60–70 U/kg bolus (max 5000 U) then 12–15 U/kg/h infusion | aPTT 1.5–2.0× control [12] | Preferred when rapid reversal may be needed (renal impairment, ↑bleeding risk, peri-procedural during PCI/CABG) [12]; reversal: protamine; half-life ~4 hours [12] |
| Bivalirudin | Direct thrombin inhibitor (DTI) — binds thrombin directly without needing antithrombin as a cofactor | 0.75 mg/kg IV bolus then 1.75 mg/kg/h infusion during PCI | ACT monitoring during PCI | Alternative to UFH + GPIIb/IIIa inhibitor during PCI; lower bleeding risk; useful in HIT |
Why NOT Thrombolysis in NSTEMI?
No benefit if done routinely in NSTE-ACS. Thrombolysis may even be harmful (not thrombotic occlusion → no benefit at all) [2]. The thrombus in NSTEMI is typically a non-occlusive, platelet-rich "white thrombus" adherent to the plaque surface — fibrinolytics target fibrin-rich "red thrombus" (as in STEMI). Giving fibrinolytics in NSTEMI exposes the patient to bleeding risk without addressing the platelet-rich thrombus, and may paradoxically activate the coagulation cascade.
Pillar 3: Anti-Ischaemic Therapy
These drugs reduce myocardial O₂ demand and/or increase O₂ supply, relieving ischaemia and pain.
| Feature | Details |
|---|---|
| Mechanism | Block β₁-adrenergic receptors in the heart → ↓heart rate + ↓contractility + ↓BP → ↓myocardial O₂ demand; also ↑diastolic filling time (slower HR = longer diastole = more coronary perfusion time) |
| Indication | Beta-blockers unless contraindicated [11]; given to all stable patients if no C/I [2] |
| Examples | Metoprolol (Betaloc) 25–100 mg BD [2]; bisoprolol, carvedilol |
| Contraindications | Bradycardia, AV block, ↓BP, asthma [2] |
| NOT contraindicated in | HF (actually beneficial long-term), COPD (use cardioselective β₁), peripheral vascular disease [2] |
| Why first-line | The ONLY anti-anginal class with proven mortality benefit post-MI (↓arrhythmia, ↓reinfarction, ↓sudden death) |
| Feature | Details |
|---|---|
| Mechanism | Arteriovenous dilatation by release of NO → (1) ↑supply by dilating coronary arteries and redistributing perfusion from epicardial to endocardial sites; (2) ↓demand by venodilation (major) → ↓preload and arteriodilation (modest) → ↓afterload [2] |
| Indication | Nitrates (long-acting or short-acting as PRN) in the presence of angina [11] |
| Acute use | Sublingual GTN 0.3–0.6 mg Q5min up to max 1.2 mg in 15 min; or GTN spray (acts quicker) up to 3 sprays in 15 min [2]; IV GTN infusion for ongoing pain (start 5–10 μg/min, titrate to pain relief and BP) |
| Note | Should rest sitting while taking nitrates (standing → syncope; supine → ↑venous return → ↑preload) [2] |
| Contraindications | Hypotension (SBP < 90), severe aortic stenosis (dependent on preload), RV infarction (dependent on preload → nitrates ↓preload → ↓↓CO → profound hypotension), recent PDE-5 inhibitor use (sildenafil within 24h, tadalafil within 48h — synergistic hypotension) |
| Long-term | Long-acting nitrates for angina prophylaxis; use daily with nitrate-free interval of 8–10h (to prevent tolerance) [2] |
| Feature | Details |
|---|---|
| Indication | Calcium antagonists (diltiazem or verapamil) if contraindications to beta-blockers and no heart failure [11]; ± DHP CCB (e.g., amlodipine) if persistent discomfort despite β-blocker [2] |
| Non-DHP (diltiazem, verapamil) | ↓HR + ↓contractility + ↓conduction (similar to β-blockers); useful when β-blockers contraindicated; C/I in HF (negative inotropy), combination with β-blockers (risk of profound bradycardia/heart block) |
| DHP (amlodipine, nifedipine) | Primarily vasodilation → ↓afterload + coronary vasodilation; can be added to β-blockers safely; avoid short-acting nifedipine (reflex tachycardia → worsens ischaemia) |
Pillar 4: Disease-Modifying Therapy
These drugs do not primarily relieve acute symptoms but fundamentally alter disease progression and improve long-term survival.
| Feature | Details |
|---|---|
| Mechanism | HMG-CoA reductase inhibitor → ↓hepatic cholesterol synthesis → ↑LDL receptor expression → ↑LDL clearance from blood; also pleiotropic effects: plaque stabilisation (↓inflammation, ↑fibrous cap thickness), endothelial function improvement, anti-thrombotic |
| Indication | High-intensity statin always (≤ 24h) [2]; should be started regardless of baseline cholesterol level [2] |
| Drug and dose | Atorvastatin 40–80 mg or rosuvastatin 20–40 mg (high-intensity = expected ≥ 50% LDL reduction) |
| LDL target | < 1.4 mmol/L AND ≥ 50% reduction from baseline (ESC 2019/2023 — note this is stricter than the older target of < 1.8 mmol/L in the senior notes [2]) |
| If target not achieved | Add ezetimibe (blocks intestinal cholesterol absorption via NPC1L1 transporter); if still not at target, add PCSK9 inhibitor (evolocumab or alirocumab — monoclonal antibodies that ↓PCSK9 → ↑LDL receptor recycling → ↓↓LDL) |
| Timing | Lipid profile should be ordered ≤ 24h of admission [2] (because acute phase response ↓LDL after 24h) |
| Baseline monitoring | LFT, CK as baseline before starting statin [2] |
| Feature | Details |
|---|---|
| Mechanism | ACEI: blocks angiotensin-converting enzyme → ↓Angiotensin II → ↓vasoconstriction, ↓aldosterone, ↓cardiac remodelling, ↓sympathetic activation; ARB: blocks AT1 receptor directly |
| Indication | ACEI for patients with CHF, LV dysfunction (EF < 40%), hypertension, or diabetes [11]; β-blockers, ACEI/ARB always (≤ 24h) [2] |
| Examples | Ramipril 2.5–10 mg QD, perindopril 2–8 mg QD, lisinopril; ARB (e.g., valsartan, candesartan) if ACEI-intolerant (usually due to cough — ACEI ↑bradykinin → cough) |
| Why post-MI | After MI, the RAAS is activated → LV remodelling (dilatation, fibrosis) → progressive HF. ACEI/ARB block this cascade → ↓remodelling → ↓HF → ↓mortality |
| C/I | Bilateral renal artery stenosis, hyperkalaemia, pregnancy, angioedema (ACEI-specific) |
| Feature | Details |
|---|---|
| Drug | Spironolactone 25–50 mg QD or eplerenone 25–50 mg QD |
| Indication | MRA if LVEF ≤ 40% + HF/DM [2] |
| Mechanism | Blocks aldosterone → ↓sodium/water retention, ↓cardiac fibrosis, ↓potassium wasting |
| Monitoring | Watch for hyperkalaemia (especially with ACEI/ARB); monitor K⁺ and renal function |
3. Invasive Strategy — Coronary Angiography and Revascularisation
Two main strategies (AHA/ACC 2014) [2]:
- Invasive strategy: invasive coronary angiography in ≤ 2h (immediate), ≤ 24h (early), 25–72h (delayed)
- Ischaemia-driven strategy: invasive coronary angiography only if: (1) refractory angina at risk of failing medical therapy; (2) objective evidence of ischaemia on non-invasive stress test; (3) clinical indicators of very high prognostic risk score [2]
Risk stratification before discharge for ischaemia-guided strategy [2]:
- Non-invasive stress testing for low/intermediate risk patients free of ischaemia at rest or with low-level activity for ≥ 12–24h
- Non-invasive imaging test to evaluate LV function in patients with definite ACS
| Option | Indication | Details |
|---|---|---|
| PCI with stenting | Simple vascular anatomy (1VD, 2VD), no proximal disease [2] | Drug-eluting stent (DES) preferred over bare-metal stent (BMS) — DES has polymer coating that elutes antiproliferative drug (e.g., everolimus, zotarolimus) → ↓in-stent restenosis |
| CABG | 3VD, LMS disease, complex anatomy, high surgical risk features [2]; failed PCI; mechanical complications | Uses arterial (internal mammary artery — IMA) or venous (saphenous vein) grafts to bypass the stenosis; IMA grafts have superior long-term patency (~95% at 10 years vs ~50% for vein grafts) |
| Heart Team discussion | Multivessel disease, borderline anatomy | A Heart Team approach is recommended when care decisions are unclear — interventional cardiologist + cardiac surgeon + referring physician decide together based on anatomy (SYNTAX score), comorbidities, and patient preference |
Intravascular imaging during PCI [1]:
- IVUS or OCT imaging findings can differentiate: erosion vs nodule vs rupture — guiding treatment strategy
- Used when lesion is ambiguous: hazy lesion/calcification, tortuosity/eccentricity [1]
4. Long-Term / Secondary Prevention
This is arguably the most important part of NSTEMI management — the acute event is treated, but without secondary prevention, the patient will have another event. The lecture slides specifically identify this section [11].
Summary table of long-term drug therapy [2][11]:
| Drug Class | Drug and Dose | Duration | Rationale |
|---|---|---|---|
| Aspirin | 75–100 mg daily [11] | Indefinitely | Anti-thrombotic: prevents recurrent arterial thrombosis |
| P2Y12 inhibitor | Ticagrelor 90 mg BD or clopidogrel 75 mg QD [11] | 12 months (then reassess) | DAPT prevents stent thrombosis and recurrent plaque events |
| High-intensity statin | Atorvastatin 40–80 mg or rosuvastatin 20–40 mg | Indefinitely | Plaque stabilisation, ↓LDL, ↓ASCVD events |
| β-blocker | Metoprolol 25–100 mg BD [2] | Indefinitely (especially if LVEF < 40%) | ↓Sudden death, ↓reinfarction, ↓LV remodelling |
| ACEI/ARB | Ramipril, perindopril / valsartan | Indefinitely (especially if LVEF < 40%, DM, HTN) | ↓LV remodelling, ↓mortality |
| MRA | Spironolactone or eplerenone | Indefinitely if LVEF ≤ 40% + HF/DM | ↓Cardiac fibrosis, ↓mortality |
Risk factor modulation [2]:
| Risk Factor | Target / Intervention | Why |
|---|---|---|
| Smoking | Drastic ↓MI risk after just 1 year of cessation; doubles 5-year mortality if continues [2] | Smoking cessation is the SINGLE most effective lifestyle intervention for secondary prevention |
| Hyperlipidaemia | High-dose statins for aggressive ↓lipid (regardless of serum cholesterol level) → ↓mortality [2]; LDL < 1.4 mmol/L | Ongoing lipid deposition drives plaque progression |
| Hypertension | Target < 130/80 mmHg | ↓Afterload → ↓myocardial O₂ demand → ↓LV remodelling |
| Diabetes | HbA1c < 7%; prefer SGLT2i or GLP-1 agonist (cardiovascular benefit) | Hyperglycaemia → endothelial dysfunction → accelerated atherosclerosis |
| Lifestyle | Regular exercise, maintain ideal body weight, Mediterranean diet [2] | ↓Insulin resistance, ↓inflammation, ↑HDL, ↓BP |
| Weight | Maintain ideal body weight (↓co-morbidity) [2] | Central obesity drives metabolic syndrome |
Takes 4–6 weeks to replace necrotic tissue by fibrotic tissue → restrict physical activities until then, offer cardiovascular rehabilitation [2].
- Usually: mobilise in 2 days, discharge in 3–5 days, resume work in 4–6 weeks [2]
- Cardiac rehabilitation programme: supervised exercise training + psychosocial support + education → proven ↓mortality and ↓readmission
Special Considerations
Warfarin only if otherwise indicated [2] — i.e., not routinely for NSTEMI, but indicated if the patient has:
- AF (for stroke prevention)
- LV thrombus (post-MI mural thrombus)
- Mechanical heart valves
- VTE
In patients requiring both DAPT and OAC (e.g., NSTEMI + AF), triple therapy (aspirin + P2Y12 + OAC) carries very high bleeding risk → current practice uses a shortened triple therapy period (1 week to 1 month) followed by dual therapy (OAC + single antiplatelet, usually clopidogrel) for up to 12 months, then OAC alone.
| Drug | Absolute Contraindications | Relative Contraindications |
|---|---|---|
| Aspirin | True allergy, active GI bleed | History of peptic ulcer (cover with PPI) |
| Ticagrelor | Active bleeding, prior ICH, severe hepatic impairment | Concomitant strong CYP3A4 inhibitors, bradycardia-prone patients |
| Prasugrel | Prior stroke/TIA, active bleeding | Age ≥ 75y, weight < 60 kg |
| Clopidogrel | Active bleeding | CYP2C19 poor metabolisers (genetic testing available), concomitant PPI [2] |
| β-blockers | Bradycardia, AV block, hypotension, asthma [2] | Severe peripheral arterial disease (symptomatic), decompensated HF (start after stabilisation) |
| Nitrates | Hypotension (SBP < 90), RV infarction, recent PDE-5 inhibitor, severe AS | — |
| ACEI | Bilateral renal artery stenosis, pregnancy, angioedema, hyperkalaemia | ↓Renal function (monitor closely) |
| Statins | Active liver disease, pregnancy | Myopathy risk (monitor CK if symptomatic) |
| Thrombolysis | ABSOLUTELY CONTRAINDICATED in NSTE-ACS [2] | — |
High Yield Summary — Management of NSTEMI
Acute Management: CCU admission (if high-risk), continuous ECG monitoring, O₂ to keep SaO₂ > 90%, analgesia (IV morphine + Maxolon if nitrates insufficient), correct precipitants.
Four Pharmacological Pillars:
- Antiplatelet: Aspirin (loading 150–300 mg, then 75–100 mg daily indefinitely) + P2Y12 inhibitor (ticagrelor preferred, clopidogrel if CI, prasugrel after anatomy defined). DAPT for 12 months.
- Anticoagulant: Enoxaparin (LMWH) or fondaparinux or UFH — NOT thrombolysis (harmful in NSTE-ACS).
- Anti-ischaemic: β-blocker (first-line, proven mortality benefit), nitrates (symptom relief), CCB (if β-blocker CI and no HF).
- Disease-modifying: High-intensity statin (within 24h, regardless of cholesterol), ACEI/ARB (especially if LVEF < 40%, DM, HTN), MRA (if LVEF ≤ 40% + HF/DM).
Invasive Strategy: Risk-stratified by GRACE score — immediate (< 2h) for very high risk, early (< 24h) for high risk, within 72h for intermediate risk, selective for low risk.
Revascularisation: PCI for simple anatomy (1–2VD); CABG for 3VD/LMS; Heart Team decision for complex cases.
Secondary Prevention: Lifelong aspirin + statin + ACEI/ARB + β-blocker; smoking cessation (most effective single intervention); DM/HTN/lipid control; cardiac rehabilitation.
Critical Point: Thrombolysis is CONTRAINDICATED in NSTEMI. Prasugrel is contraindicated in prior stroke/TIA. Always check contraindications before prescribing.
Active Recall - NSTEMI Management
References
[1] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (pp. 40, 50, 55) [2] Senior notes: Ryan Ho Cardiology.pdf (pp. 122, 132, 136, 138–139, 144) [3] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (pp. 39, 48) [5] Senior notes: Ryan Ho Critical Care.pdf (p. 22) [6] Senior notes: Ryan Ho Fundamentals.pdf (p. 203, 217) [11] Lecture slides: GC 028. Accelerating chest pain_Acute coronary (1).pdf (pp. 54–55) [12] Senior notes: Ryan Ho Haemtology.pdf (pp. 132–133)
Complications of NSTEMI
Complications of NSTEMI are the reason this condition kills. Understanding them requires you to think about what happens when a segment of myocardium dies and the downstream mechanical, electrical, and systemic consequences of that necrosis. While NSTEMI typically causes subendocardial (partial-thickness) infarction — and therefore mechanical complications are less common than in STEMI — they absolutely still occur, and all patients must be monitored for them. The risk of any complication correlates with the size of infarction and degree of LV dysfunction.
- Heart failure
- Arrhythmias
- VSD (anterior MI)
- Mitral regurgitation complicating papillary muscle dysfunction (inferior MI)
- Pericarditis
Acute mechanical complications from MI [13]:
- Shock: large area (~40%) myocardium involved
- VSD: transmural infarct and rupture of muscular septum
- MR: rupture of papillary head
- Tamponade: free wall rupture, myocarditis, pericarditis, iatrogenic
- Anyone of these is high risk for mortality [13]
I will organise complications by timing and mechanism, explaining the pathophysiology from first principles for each.
| Timing | Complications |
|---|---|
| Immediate (minutes–hours) | Arrhythmias (VF, VT, bradycardia, heart block), cardiac arrest, cardiogenic shock |
| Early (hours–days) | Pump failure / acute HF, mechanical complications (VSD, papillary muscle rupture → MR, free wall rupture → tamponade), peri-infarction pericarditis, post-ACS ischaemia |
| Late (days–weeks) | Ventricular remodelling, LV aneurysm, mural thrombus → systemic embolism, Dressler syndrome, arrhythmias during convalescent phase |
| Long-term (weeks–months–years) | Chronic heart failure, recurrent ACS, sudden cardiac death |
I. Arrhythmias
Arrhythmias are the most common complication of MI and the leading cause of death in the first hour (before patients even reach hospital). Why? Because ischaemic myocardium becomes electrically unstable:
- Ischaemia → ATP depletion → failure of Na⁺/K⁺-ATPase → altered resting membrane potential → abnormal automaticity
- Ischaemia → heterogeneous conduction (some fibres conduct slowly, others are blocked) → creates substrate for re-entrant circuits
- Electrolyte shifts: K⁺ leaks out of damaged cells → local hyperkalaemia in ischaemic border zone → altered repolarisation
- Catecholamine surge (from pain and haemodynamic stress) → ↑automaticity, ↓VF threshold
Each arrhythmia type has specific management [2]:
| Arrhythmia | Mechanism | Presentation | Management |
|---|---|---|---|
| VF | Re-entry in ischaemic ventricular myocardium; totally disorganised ventricular electrical activity → no effective cardiac output | Cardiac arrest, pulseless | Prompt defibrillation per ACLS algorithm [2]; unsynchronised shock starting at 200 J (biphasic); CPR between shocks; adrenaline + amiodarone per protocol |
| Pulseless VT | Rapid monomorphic re-entrant circuit in ventricular myocardium → rate too fast to allow adequate ventricular filling → no effective CO | Cardiac arrest, pulseless | Treat as VF — defibrillation per ACLS algorithm |
| Stable sustained monomorphic VT | Same mechanism but some CO maintained due to slightly lower rate or preserved LV function | Palpitations, hypotension, chest pain, syncope | Treat as VT until proven otherwise in the setting of ACS [2]; Amiodarone 150 mg IV over 10 min (repeat if needed), then 600–1200 mg infusion/24h; or Lignocaine 50–100 mg IV bolus then 1–4 mg/min; Procainamide 20–30 mg/min loading; Synchronised cardioversion starting at 100 J if haemodynamic compromise [2] |
| Sustained polymorphic VT | Multiple re-entrant circuits, often related to ongoing ischaemia or QT prolongation | Haemodynamic collapse | Unsynchronised cardioversion starting at 200 J [2]; correct electrolytes (Mg²⁺, K⁺); treat ongoing ischaemia |
| Accelerated idioventricular rhythm (AIVR) | Reperfusion arrhythmia — enhanced automaticity in Purkinje fibres as blood flow is restored | Regular wide-complex rhythm at 60–120 bpm, usually haemodynamically stable | Generally benign and self-limiting; no specific treatment; actually a sign of successful reperfusion |
Cardiac arrest: coronary artery disease accounts for 85% of all cardiac arrests [14]. VF/pulseless VT are shockable rhythms — 80% reversed by defibrillation but 10% decrease in survival per minute delay [14].
Exam High Yield: VF in First Hour
The commonest cause of death in the first hour after MI is VF. This is why early defibrillation (chain of survival) is so critical. Paradoxically, VF in the very early phase of MI (within first 48h) does NOT independently predict long-term mortality if the patient survives — it is a transient phenomenon related to acute ischaemia, not a marker of permanent substrate abnormality.
| Arrhythmia | Mechanism | Typical Territory | Management |
|---|---|---|---|
| Symptomatic sinus bradycardia | Ischaemia of SA node (supplied by RCA in ~60%) or excessive vagal tone (especially inferior MI) | Inferior MI | Atropine 0.3–0.6 mg IV bolus; pacing if unresponsive to atropine [2] |
| 1st degree AV block / Mobitz Type I (Wenckebach) | AV nodal ischaemia (AV node supplied by RCA in ~90%); increased vagal tone | Inferior MI | Conservative [2] — usually transient; observe closely |
| Mobitz Type II 2nd degree / Complete (3rd degree) heart block | Ischaemia of His bundle or bundle branches (more distal conduction system — supplied by LAD septal perforators) | Anterior MI (more dangerous) | Pacing [2]; conservative under careful monitoring as alternative if inferior MI with narrow QRS escape rhythm and adequate rate [2] |
| New bifascicular block + 1st degree AVB, alternating BBB | Extensive ischaemia of the conduction system from large anterior MI | Anterior MI | Indication for temporary pacing (anterior infarct → ↑risk of sudden asystole) [2] |
Why is conduction block in anterior MI more dangerous than in inferior MI? In inferior MI, the block is usually at the AV node level (supra-Hisian) → the escape rhythm is junctional (narrow QRS, reliable, 40–60 bpm). In anterior MI, the block is infra-Hisian (His bundle or bundle branches) → the escape rhythm is ventricular (wide QRS, unreliable, 20–40 bpm) → much higher risk of asystole and death.
| Arrhythmia | Mechanism | Management |
|---|---|---|
| AF / Atrial flutter | Common and frequently transient; can be a sign of impending or overt LVF [2]; atrial ischaemia → altered atrial conduction; atrial stretch from ↑LA pressure (backward failure) | Digoxin 0.25 mg IV/PO stat, then 0.25 mg PO q8h ×2 more doses (loading), maintenance 0.0625–0.25 mg daily; Diltiazem 10–15 mg IV over 5–10 min then 5–15 μg/kg/min; Amiodarone 5 mg/kg IV over 60 min loading, maintenance 600–900 mg/24h [2] |
| PSVT | AV nodal re-entry or accessory pathway re-entry, triggered by catecholamine surge | Cardioversion if severe haemodynamic compromise or intractable ischaemia; ATP 10–20 mg IV bolus → verapamil 5–15 mg IV slowly (C/I if BP low or on BB) [2] |
II. Pump Failure (Heart Failure / Cardiogenic Shock)
This is the second most common cause of death in MI (after arrhythmias in the immediate phase).
Mechanism: a downward spiral exacerbating myocardial ischaemia [2]:
- ↓Systolic function → ↓coronary perfusion → ↓supply → ischaemia
- ↓Diastolic function → ↑pulmonary congestion → hypoxaemia → ischaemia
This creates a vicious cycle: infarction → ↓CO → ↓coronary perfusion → extension of infarction → further ↓CO → death.
Indicates extensive myocardial damage → poor prognosis (↑likelihood of other complications) [2].
Cardiogenic shock occurs when ~40% of LV myocardium is involved [13].
| Class | Signs | Mortality |
|---|---|---|
| I | No clinical signs of HF | ~6% |
| II | Crackles < 50% lung fields, or S3, or ↑JVP | ~17% |
| III | Crackles > 50% lung fields (frank pulmonary oedema) | ~38% |
| IV | SBP < 90 mmHg + peripheral vasoconstriction (cardiogenic shock) | ~81% |
RV dysfunction (↓CO without APO, 5%): usually occurs in inferior MI [2]:
- Bedside echo should show non-compressible IVC (indicating ↑RA pressure)
- Swan-Ganz catheter to monitor PCWP (indicates volume status) → volume expansion with colloids/crystalloids if low or normal [2]
- Avoid nitrates, diuretics, and vasodilators — the RV-dependent circulation needs preload to push blood through the pulmonary circuit; reducing preload causes catastrophic ↓CO
- This is why you must always check for RV involvement in inferior MI (V4R ST elevation)
LV dysfunction (N/↓CO with APO, 95%) [2]:
- Vasodilators (esp ACEI) if BP stable (± PCWP monitoring)
- Inotropes: dopamine 2.5 μg/kg/min if SBP ≤ 90 mmHg, increase by 0.5 μg/kg/min increments; consider dobutamine 5–15 μg/kg/min when high-dose dopamine needed [2]
- → IABP (intra-aortic balloon pump) with view for catheterisation ± revascularisation [2]
RV Infarction — The Preload Trap
A patient with inferior MI + RV infarction (hypotension, ↑JVP, clear lungs) is treated with IV fluids, NOT diuretics or nitrates. If you give nitrates to this patient (thinking "MI = nitrates"), the resulting drop in preload can cause fatal cardiovascular collapse. Always check V4R for RV involvement before giving nitrates in inferior MI.
III. Mechanical Complications
These are the most dramatic and lethal complications of MI. They typically require emergency surgical intervention and carry very high mortality even with surgery.
VSD: transmural infarct and rupture of muscular septum [13]
| Feature | Details |
|---|---|
| Incidence | ~0.1% of MI [2]; complicates anterior MI (LAD) [3] |
| Timing | Usually ~24h from MI but may occur up to 2 weeks [2] |
| Pathophysiology | Usually complicates anterior MI (LAD) esp if extensive MI with poor collateral; rupture occurs at margin of necrotic and non-necrotic myocardium [2] |
| Consequence | L-to-R shunting → sudden haemodynamic deterioration + new onset pansystolic murmur (to right lower sternal border) [2]; volume overload of RV → RV failure |
| Clinical presentation | Usually develops RV failure [2]; acute dyspnoea, hypotension, new harsh PSM with thrill at LLSB |
| Differentiation from acute MR | Both present with new PSM + haemodynamic deterioration. VSD → murmur loudest at LLSB with thrill, develops RV failure, oxygen step-up from RA→RV on catheterisation. Acute MR → murmur loudest at apex radiating to axilla, develops LV failure / APO |
| Diagnosis | Echo (colour Doppler shows shunt); RH catheterisation (O₂ step-up in RV) [2] |
| Management | Observe with delayed surgery if stable; emergency cardiac catheterisation followed by repair if unstable [2]; Note that surgical repair of MI-related VSD is associated with relatively high mortality [2] |
MR: rupture of papillary head [13]; mitral regurgitation complicating papillary muscle dysfunction (inferior MI) [3]
| Feature | Details |
|---|---|
| Anatomy | The posteromedial papillary muscle is supplied by a SINGLE artery (usually PDA from RCA) making it vulnerable to infarction. The anterolateral papillary muscle has dual supply (LAD + LCx) and is less vulnerable |
| Spectrum | Ranges from mild MR (papillary muscle dysfunction from ischaemia — reversible) to catastrophic acute severe MR (partial or complete papillary muscle rupture — requires emergency surgery) |
| Pathophysiology | Necrosis of papillary muscle → loss of structural support for mitral leaflets → leaflet prolapse/flail → acute severe MR → massive volume overload of a non-compliant LA → acute pulmonary oedema → cardiogenic shock |
| Clinical presentation | Sudden acute pulmonary oedema with new pansystolic murmur at apex radiating to axilla; note: in severe acute MR, the murmur may be soft or absent because the massive regurgitant volume equalises LA and LV pressures rapidly → ↓pressure gradient → ↓murmur |
| Diagnosis | Echo (flail leaflet, severe MR on colour Doppler, hyperdynamic LV) |
| Management | Afterload reduction (IV nitroprusside or IABP) to encourage forward flow; emergency mitral valve surgery (repair or replacement) — medical therapy alone carries near-100% mortality |
Tamponade: free wall rupture [13]
| Feature | Details |
|---|---|
| Incidence | < 1% (uncommon); 50% occurs ≤ 5 days, > 90% occurs ≤ 2 weeks [2] |
| Risk factors | First MI (no prior ischaemic preconditioning), anterior/lateral location, older age, female sex, hypertension, delayed or no reperfusion |
| Pathophysiology — Complete rupture | Blood pumped into pericardial cavity → cardiac tamponade; usually presents with sudden profound right HF + shock followed by PEA and death [2] |
| Pathophysiology — Incomplete rupture | Ventricular defect sealed by pericardial tissue and thrombus → presents with persistent/recurrent pleuritic chest pain [2] (pseudoaneurysm) |
| Diagnosis | Should be made clinically supported by ECG/CXR/echo features of cardiac tamponade [2]; Beck's triad (hypotension, muffled heart sounds, ↑JVP); pulsus paradoxus; PEA on monitor |
| Management | Emergency percutaneous pericardiocentesis → surgical repair if blood aspirated [2] |
Mechanical Complications — Time Course
A useful way to remember: mechanical complications typically occur in the first 1–14 days post-MI, corresponding to the period when necrotic tissue is softest (before fibrotic scar has formed). The infarcted tissue is weakest at around days 3–7, which is when rupture risk peaks. This is why patients are kept on bed rest and physical activity is restricted for 4–6 weeks.
IV. Pericardial Complications
Peri-infarction pericarditis (PIP): common on 2nd/3rd day post-MI, occurs in 1.2% of MI patients [2].
| Feature | Details |
|---|---|
| Pathophysiology | Transmural necrosis → inflammation of the overlying visceral pericardium (epicardium). Note: this is more common in STEMI than NSTEMI because NSTEMI is typically subendocardial (non-transmural). However, it can still occur in NSTEMI if the infarction extends to the epicardial surface |
| S/S | Development of a different pain: positional, sharp pleuritic, especially at trapezius ridge; pericardial rub (diagnostic) [2] |
| ECG | New widespread ST elevation or PR depression beyond typically anatomic regional boundary [2] |
| Management | Paracetamol ± aspirin (650 mg Q6–8h) ± opiate-based analgesia (usually self-limited); avoid NSAIDs/steroids 7–10 days after acute MI due to ↑risk of aneurysm/rupture [2] |
Why avoid NSAIDs/steroids? They inhibit the inflammatory/healing response → impair scar formation → thinning of the infarct wall → ↑risk of ventricular aneurysm and free wall rupture.
Post cardiac injury (Dressler) syndrome: in weeks/months post-MI, usually subsides in a few days [2].
| Feature | Details |
|---|---|
| Mechanism | Probably autoimmunity due to release of cardiac antigens into pericardial space [2] — exposed intracellular proteins (myosin, troponin) act as neoantigens → immune response → autoimmune pericarditis |
| S/S | Persistent fever, pericarditis, pleurisy with compatible history of prior cardiac injury [2] |
| Investigations | Often associated with ↑inflammatory markers (↑WCC, CRP/ESR) with pericardial ± pleural effusion [2] |
| Management | High-dose aspirin/NSAID (e.g., indomethacin 25–50 mg TDS ×1–2 days), colchicine ± steroid [2] |
Note: unlike early peri-infarction pericarditis, Dressler syndrome occurs weeks later when the scar is more mature, so NSAIDs/steroids are safer to use (the acute rupture risk window has passed).
Indicated by symptoms/ECG changes + new rise in cTn > 20% or to > 5× ULN (if normal baseline) [2].
| Feature | Details |
|---|---|
| Cause of post-PCI MI | Side branch occlusion (60%), stent complications, microembolisation [2] |
| Post-thrombolysis | Up to 50% have post-infarct angina (due to residual stenosis); should consider early (6–24h) coronary angiography/PCI in all thrombolysis patients [2] |
| Management | High risk → prompt coronary angiography/PCI + IV GPIIb/IIIa inhibitor (if dynamic ECG changes) [2] |
Most common in (1) anterior STEMI (2) LAD infarct (3) large infarct with EF < 30% [2].
| Feature | Details |
|---|---|
| Mechanism | Ventricular thrombus due to wall motion abnormality/aneurysm → risk of embolisation in non-anticoagulated documented LV thrombus is 10–15% [2]; atrial thrombus due to AF [2] |
| Consequences | Stroke, ischaemic limb — classically occurring 1–3 weeks after MI [2] |
| Prevention | Anticoagulation indicated to prevent systemic embolisation [2] |
| Drug | Warfarin: for established venous thrombosis or embolisation; echocardiographic evidence of LV thrombus [3] |
Why does the thrombus form? After infarction, the affected wall becomes akinetic or dyskinetic → blood stagnates in front of the non-moving wall (Virchow's triad: stasis) → combined with the pro-thrombotic state of acute MI → mural thrombus formation. Anterior MI is highest risk because the LV apex is a natural recess where blood pools.
VII. Ventricular Remodelling, Aneurysm, and Chronic Heart Failure
After MI, the infarct zone undergoes a process of remodelling [2]:
- Infarct expansion (days): thinning and stretching of the necrotic segment → ↑wall stress
- Neurohormonal activation: RAAS + sympathetic system activated to compensate for ↓CO → but chronic activation is maladaptive (vasoconstriction → ↑afterload; salt/water retention → volume overload; direct myocardial toxicity)
- Global remodelling (weeks–months): the remaining non-infarcted myocardium hypertrophies to compensate → initially adaptive, but progressive dilatation, fibrosis, and contractile dysfunction develop → chronic heart failure
This is precisely why ACEI/ARB, β-blockers, and MRA are given long-term — they block the neurohormonal cascade and slow/prevent adverse remodelling.
Ventricular aneurysm: occurs in 8–15% with STEMI, especially those with persistent occlusion [2].
| Feature | Details |
|---|---|
| Location | 70–85% at anterior or apical walls → due to LAD total occlusion without collateral [2] |
| Consequences | Acute decompensated HF with angina (wasted mechanical energy to enlarge aneurysm); ventricular arrhythmia due to myocardial irritation; systemic embolisation (mural thrombus occurs in > 50%) [2] |
| Diagnosis | Paradoxical impulse on chest wall (outward when systole); ECG: persistent ST elevation and Q despite reperfusion; CXR: unusual bulge from cardiac silhouette; Echo: diagnostic [2] |
| Management | Oral anticoagulation if documented mural thrombus; aneurysmectomy + CABG if intractable ventricular arrhythmias or heart failure refractory to medical therapy [2] |
Why does ST elevation persist? The aneurysmal segment is a thin sack of scar tissue that does not depolarise normally. During diastole, the surrounding normal myocardium is at resting potential while the scar creates a persistent injury current → chronic ST elevation in the overlying leads. This is one of the ECG false positives for acute STEMI (along with early repolarisation, pericarditis, etc.).
Since many NSTEMI patients undergo PCI, you must know PCI-specific complications [2]:
| Complication | Timing | Mechanism | Prevention |
|---|---|---|---|
| Stent thrombosis (1–2%) | Acute (< 24h), subacute (< 30d), late (< 1y); MAJORITY < 30d [2] | Formation of thrombus at exposed stent surface before endothelialisation [2]; presents with severe STEMI or cardiac death | DAPT (aspirin + P2Y12 inhibitor) until endothelialisation [2] |
| In-stent restenosis (ISR) | Usually ≥ 6–9 months after stenting [2] | Intimal proliferation leading to gradual re-stenosis at stent sites [2]; presents with recurrent stable angina | Drug-eluting stent (DES) to prevent intimal proliferation [2] |
| Side branch occlusion | Periprocedural | Stent jails the ostium of a side branch → occlusion | Careful technique, bifurcation stenting if needed |
The lecture slides present a critical prognostic concept [3]:
- In-hospital mortality: NSTEMI (3–5%) < STEMI (6–7%)
- However, 1-year mortality: NSTEMI ≈ STEMI (or even higher)
- Mortality after discharge continues to accumulate in NSTEMI patients more steeply than STEMI
Why? NSTEMI patients are typically:
- Older
- Have more comorbidities (DM, CKD, multivessel disease, prior MI)
- More likely to have incomplete revascularisation (multivessel disease)
- More likely to have recurrent events
This is why aggressive secondary prevention and complete revascularisation planning are so important in NSTEMI.
| Category | Complication | Key Pathophysiology | Timing | High-Yield Management Point |
|---|---|---|---|---|
| Electrical | VF/VT | Re-entry in ischaemic myocardium | Minutes–hours | Defibrillation per ACLS |
| Electrical | Heart block | AV node/His ischaemia | Hours–days | Pacing if infra-Hisian |
| Electrical | AF | Atrial ischaemia/stretch | Hours–days | Rate control; sign of LVF |
| Pump failure | Acute LV failure / APO | Extensive myocardial damage | Hours–days | Vasodilators, inotropes, IABP |
| Pump failure | Cardiogenic shock | ≥ 40% LV involvement | Hours–days | Inotropes → IABP → revascularisation |
| Pump failure | RV infarction | RCA occlusion | Hours | Volume expansion, avoid nitrates |
| Mechanical | VSD | Septal rupture at necrotic margin | 24h–2 weeks | Echo; surgical repair (high mortality) |
| Mechanical | Papillary muscle rupture → MR | Single-vessel supply to posteromedial PM | Days | Emergency MV surgery |
| Mechanical | Free wall rupture → tamponade | Transmural necrosis, weakest at days 3–7 | 1–14 days | Pericardiocentesis → surgery |
| Pericardial | Peri-infarction pericarditis | Epicardial inflammation | Day 2–3 | Aspirin; avoid NSAIDs early |
| Pericardial | Dressler syndrome | Autoimmune | Weeks–months | NSAIDs, colchicine ± steroids |
| Embolic | LV mural thrombus → stroke | Stasis over akinetic wall | 1–3 weeks | Anticoagulation |
| Structural | LV aneurysm | Scar thinning and expansion | Weeks–months | Anticoagulation; surgery if refractory |
| Post-PCI | Stent thrombosis | Thrombus on exposed stent | < 30 days (majority) | DAPT compliance |
| Post-PCI | In-stent restenosis | Neointimal proliferation | ≥ 6–9 months | DES |
| Ischaemic | Recurrent MI | Residual disease, new plaque event | Anytime | Secondary prevention |
High Yield Summary — Complications of NSTEMI
Arrhythmias are the most common complication and leading cause of early death (VF in first hour). Continuous ECG monitoring is mandatory. Treat bradycardia with atropine or pacing; VT/VF with defibrillation and antiarrhythmics per ACLS.
Pump failure occurs as a downward spiral of ischaemia and dysfunction. LV failure (95%) is treated with vasodilators and inotropes. RV failure (5%, inferior MI) requires volume loading — avoid nitrates and diuretics.
Mechanical complications (VSD, papillary muscle rupture, free wall rupture) are surgical emergencies with very high mortality. They typically occur in the first 1–14 days when necrotic tissue is weakest. A new murmur + haemodynamic deterioration = emergency echo.
Pericardial complications: early peri-infarction pericarditis (day 2–3, treat with aspirin, avoid NSAIDs); late Dressler syndrome (weeks–months, autoimmune, treat with NSAIDs + colchicine).
Thromboembolism: mural thrombus in akinetic segments (especially anterior/apical) → 10–15% risk of embolisation → anticoagulate.
LV remodelling: progressive dilatation and dysfunction → chronic HF. Prevented by ACEI/ARB + β-blocker + MRA.
Long-term mortality in NSTEMI equals or exceeds STEMI due to older age, more comorbidities, and recurrent events — aggressive secondary prevention is paramount.
Active Recall - Complications of NSTEMI
References
[2] Senior notes: Ryan Ho Cardiology.pdf (pp. 124, 131, 139–142, 144) [3] Lecture slides: GC 088. Sudden Severe Chest Pain.pdf (pp. 5, 38, 51, 56) [13] Lecture slides: Cardiac Surgery Tutorial_Prof. D Chan.pdf (p. 31) [14] Senior notes: Ryan Ho Critical Care.pdf (p. 28)
High Yield Summary
Definition: NSTEMI = acute myocardial infarction with troponin elevation but WITHOUT persistent ST elevation on ECG. Part of the NSTE-ACS spectrum (with UA).
Key Pathophysiology: Atherosclerotic plaque rupture/erosion → partial coronary thrombosis → reduced (but not absent) flow → subendocardial necrosis → troponin release.
Risk Factors: The classic ASCVD risk factors — smoking, HTN, DM, dyslipidaemia, obesity, family history, age, male sex.
Presentations: (1) Prolonged rest angina > 20 min, (2) New-onset severe angina, (3) Crescendo angina. Watch for atypical presentations in elderly, diabetics, women.
Cardinal symptom: Retrosternal crushing/squeezing chest pain, may radiate to arms/jaw, associated with diaphoresis, nausea, dyspnoea.
Key exam findings: Often unremarkable. Look for haemodynamic compromise (tachycardia, hypotension, S3, crackles), new murmurs (mechanical complications), signs of precipitants (anaemia, thyrotoxicosis), and signs excluding mimics (BP both arms for dissection).
Risk stratification: GRACE score determines timing of invasive strategy. Very high risk criteria → immediate invasive (< 2h).
Always remember: Check BP in both arms, auscultate for new murmurs, assess Killip class, look for precipitating causes of Type 2 MI.
High Yield Summary
Must-exclude life-threatening mimics: Aortic dissection (tearing, back, unequal BP), PE (pleuritic, dyspnoea, D-dimer/CTPA), tension pneumothorax (absent breath sounds), oesophageal rupture.
Must-exclude cardiac mimics: STEMI (persistent ST elevation), pericarditis (sharp, positional, diffuse concave ST elevation + PR depression, rub), Takotsubo (post-stress, apical ballooning, normal coronaries).
Common non-cardiac causes: GERD (most common overall), musculoskeletal (reproducible tenderness), anxiety.
Always distinguish Type 1 MI from Type 2 MI: Type 1 = plaque event → DAPT + anticoagulation + invasive. Type 2 = supply-demand mismatch → treat the cause.
Troponin is not ACS-specific: myocarditis, PE, Takotsubo, sepsis, CKD, tachyarrhythmias all raise troponin without coronary plaque events.
High Yield Summary
Diagnostic Criteria (4th Universal Definition): Rise and/or fall of hs-cTn with ≥ 1 value above 99th percentile URL PLUS ≥ 1 of: ischaemic symptoms, new ST-T changes or LBBB, pathological Q waves, imaging evidence of new RWMA/loss of viable myocardium, or intracoronary thrombus on angiography. Must NOT have persistent ST elevation.
Algorithm: ESC 0h/1h hs-cTn algorithm — Rule-out (very low/low hs-cTn with no delta), Observe (intermediate), Rule-in (high or significant delta). Very high risk patients bypass algorithm → immediate angiography < 2h.
Risk Stratification: GRACE score determines timing of invasive strategy — immediate (< 2h), early (< 24h), or within 72h.
Key Investigations: ECG (within 10 min), hs-cTn (0h/1h/±3h), baseline bloods (CBC, RFT, lipids within 24h, glucose, coagulation), CXR (exclude mimics), echo (LVEF + RWMA + complications), coronary angiography (definitive, risk-stratified timing).
Troponin Pitfalls: Single elevated value is insufficient — need rise/fall pattern. Chronic elevation (CKD, HF) is NOT acute MI. Many non-ACS causes of troponin elevation exist.
LVEF is the strongest predictor of long-term survival in CAD patients.
High Yield Summary
Acute Management: CCU admission (if high-risk), continuous ECG monitoring, O₂ to keep SaO₂ > 90%, analgesia (IV morphine + Maxolon if nitrates insufficient), correct precipitants.
Four Pharmacological Pillars:
- Antiplatelet: Aspirin (loading 150–300 mg, then 75–100 mg daily indefinitely) + P2Y12 inhibitor (ticagrelor preferred, clopidogrel if CI, prasugrel after anatomy defined). DAPT for 12 months.
- Anticoagulant: Enoxaparin (LMWH) or fondaparinux or UFH — NOT thrombolysis (harmful in NSTE-ACS).
- Anti-ischaemic: β-blocker (first-line, proven mortality benefit), nitrates (symptom relief), CCB (if β-blocker CI and no HF).
- Disease-modifying: High-intensity statin (within 24h, regardless of cholesterol), ACEI/ARB (especially if LVEF < 40%, DM, HTN), MRA (if LVEF ≤ 40% + HF/DM).
Invasive Strategy: Risk-stratified by GRACE score — immediate (< 2h) for very high risk, early (< 24h) for high risk, within 72h for intermediate risk, selective for low risk.
Revascularisation: PCI for simple anatomy (1–2VD); CABG for 3VD/LMS; Heart Team decision for complex cases.
Secondary Prevention: Lifelong aspirin + statin + ACEI/ARB + β-blocker; smoking cessation (most effective single intervention); DM/HTN/lipid control; cardiac rehabilitation.
Critical Point: Thrombolysis is CONTRAINDICATED in NSTEMI. Prasugrel is contraindicated in prior stroke/TIA. Always check contraindications before prescribing.
High Yield Summary
Arrhythmias are the most common complication and leading cause of early death (VF in first hour). Continuous ECG monitoring is mandatory. Treat bradycardia with atropine or pacing; VT/VF with defibrillation and antiarrhythmics per ACLS.
Pump failure occurs as a downward spiral of ischaemia and dysfunction. LV failure (95%) is treated with vasodilators and inotropes. RV failure (5%, inferior MI) requires volume loading — avoid nitrates and diuretics.
Mechanical complications (VSD, papillary muscle rupture, free wall rupture) are surgical emergencies with very high mortality. They typically occur in the first 1–14 days when necrotic tissue is weakest. A new murmur + haemodynamic deterioration = emergency echo.
Pericardial complications: early peri-infarction pericarditis (day 2–3, treat with aspirin, avoid NSAIDs); late Dressler syndrome (weeks–months, autoimmune, treat with NSAIDs + colchicine).
Thromboembolism: mural thrombus in akinetic segments (especially anterior/apical) → 10–15% risk of embolisation → anticoagulate.
LV remodelling: progressive dilatation and dysfunction → chronic HF. Prevented by ACEI/ARB + β-blocker + MRA.
Long-term mortality in NSTEMI equals or exceeds STEMI due to older age, more comorbidities, and recurrent events — aggressive secondary prevention is paramount.
Hypertension
Hypertension is a chronic elevation of systemic arterial blood pressure (≥130/80 mmHg) that increases the risk of cardiovascular, cerebrovascular, and renal complications.
Stable Angina
Stable angina is a predictable pattern of chest pain or discomfort caused by myocardial ischemia that occurs with exertion or emotional stress and is relieved by rest or nitroglycerin.