NON ST ELEVATION ACUTE CORONARY SYNDROME

NON ST ELEVATION ACUTE CORONARY SYNDROME (NSTE-ACS)

 Definition

NSTE-ACS includes:

• NSTEMI (Non-ST Elevation Myocardial Infarction) → myocardial necrosis + ↑ troponin
• Unstable Angina (UA) → ischemia(ECG CHANGES) without necrosis (normal troponin)

 PATHOPHYSIOLOGY 

• Plaque rupture/erosion → platelet activation → thrombus formation
• Partial or intermittent occlusion (NOT complete like STEMI)
• Leads to subendocardial ischemia

 CLINICAL FEATURES

Typical symptoms

• Rest angina >20 min
• Crescendo angina
• Retrosternal chest pain (pressure/heaviness)
• Radiation → arm/jaw
• Associated:
• Dyspnea
• Diaphoresis
• Nausea

Atypical 

• Elderly, diabetics, females:
• Epigastric pain
• Isolated dyspnea
• Silent ischemia

DIFFERENTIAL DIAGNOSIS

• Pulmonary embolism
• Aortic dissection
• Pericarditis
• GERD
• Musculoskeletal pain

ECG FINDINGS (ESC 2023)

• ST depression ≥0.5 mm in ≥2 contiguous leads
• T wave inversion ≥1 mm ≥2 contiguous leads
• Transient ST elevation (<20 min)
• Dynamic changes → highly suggestive

Wellens syndrome

• Deep/biphasic T waves in V2–V3
• Critical proximal LAD stenosis
• Pain-free ECG finding
• DO NOT DO stress test → immediate angiography

Normal ECG ≠ exclude NSTE-ACS

 CARDIAC BIOMARKERS

 Diagnosis (Universal Definition of MI)

• Rise/fall of troponin with at least one value above the 99th percentile upper reference limit (URL). + ≥1:
• Ischemic symptoms
• ECG changes
• Imaging evidence

DIAGNOSTIC ALGORITHM (ESC 0/1-HOUR PROTOCOL)

hs-Troponin strategy:

• 0 hour → baseline
• 1 hour → repeat

A. RULE-OUT ZONE (LOW RISK)

Criteria (general ESC concept; assay-specific cutoffs apply):

• Very low hs-cTn (near limit of detection)
• OR low hs-cTn + no significant rise at 1 hour

B. RULE-IN ZONE (HIGH RISK)

Criteria:

• Markedly elevated hs-cTn
• OR significant rise within 1 hour

C. OBSERVATION ZONE (INTERMEDIATE)

Criteria:

• Values between rule-in and rule-out
• Uncertain delta change

 Action:

• Repeat troponin (2–3 hr)
• Clinical reassessment
• Imaging if needed

Non-Invasive Testing in Suspected NSTE-ACS 

1. Coronary CT Angiography (CCTA)

Guideline Indications

Use when:

• Acute chest pain with:

No ischemic ECG changes

Negative serial hs-cTn

Low or intermediate risk

• Suspected CAD where diagnosis remains uncertain
• Alternative to stress testing
• Evaluation before discharge in low-risk NSTE-ACS

2. Exercise Stress ECG

Indications

Only if ALL are present:

•  ACS ruled out
• Able to exercise
• Resting ECG interpretable

ECG Must Not Have

• LBBB
• Ventricular paced rhythm
• Significant baseline ST depression
• Pre-excitation (WPW)
• Digoxin effect

3. Stress Imaging

Includes:Stress Echo/Nuclear MPI/Stress CMR/PET Perfusion

Indications

• Patient cannot exercise

Examples:Frailty/Severe arthritis/Stroke/Peripheral arterial disease

• ECG Uninterpretable

Examples:LBBB/Pacemaker/LVH with strain/Digoxin use

• Intermediate-risk CAD

Need assessment of ischemic burden.

• Prior Revascularization

• Previous PCI
• Previous CABG

Functional assessment often preferred over simple anatomic imaging.

4. Myocardial Perfusion Imaging (MPI)

Includes:SPECT/PET

Indications

• Intermediate-risk stable chest pain
• Suspected ischemia
• Prior PCI/CABG
• Equivocal exercise ECG
• Assessment of ischemic burden

5. Cardiac MRI (CMR)

ACS-Related Indications

MINOCA-Myocardial Infarction with Non-Obstructive Coronary Arteries

CMR can differentiate:

• True MI
• Myocarditis
• Takotsubo cardiomyopathy

Troponin Positive but Cath Normal

Suspected Myocarditis

Typical findings:

• Edema
• Late gadolinium enhancement

Suspected Takotsubo Syndrome

Characteristic wall-motion abnormalities.

Viability Assessment

Before revascularization in ischemic cardiomyopathy.

Infiltrative Cardiomyopathy

Examples:

• Amyloidosis
• Sarcoidosis

 RISK STRATIFICATION

 GRACE Score (GUIDELINE PREFERRED)

• Predicts mortality
• Guides invasive strategy

TIMI Score –simpler, less accurate

MANAGEMENT 

—Conservative / Non-Invasive Strategy

Management:

• Serial ECGs
• Serial hs-cTn measurements
• Coronary CTA or stress testing before discharge or shortly after discharge
• Angiography only if ischemia is demonstrated

—NSTE-ACS: Timing of Invasive Strategy (2025 ACC/AHA & Contemporary Guideline-Based Approach)

 1. ANTIPLATELET THERAPY 

 A. ASPIRIN (MANDATORY)

• Loading: 150–300 mg PO (chewed)
  OR 75–250 mg IV
• Maintenance: 75–100 mg OD lifelong
• Give immediately on suspicion
• Contraindication: active bleeding, true allergy

 B. P2Y12 INHIBITORS (SECOND AGENT IN DAPT)

–if early invasive planned– Routine pretreatment NOT recommended,Give AFTER coronary anatomy known.

-Non Invasive strategy—Clopidogrel/Ticagrelor recommended 

1. TICAGRELOR (PREFERRED)

• Loading: 180 mg
• Maintenance: 90 mg BD

 Preferred in most NSTE-ACS
Works regardless of CYP metabolism

Side effects:

• Dyspnea
• Bradyarrhythmia

 Avoid:

• Active bleeding
• Prior intracranial hemorrhage

2. PRASUGREL

• Loading: 60 mg
• Maintenance: 10 mg OD (5 mg if <60 kg or elderly)

 Preferred if PCI planned and anatomy known by angiography(The recommendation is largely based on the ISAR-REACT 5 trial.In ACS patients planned for an invasive strategy, a prasugrel-based strategy resulted in fewer ischemic events (death, MI, stroke) than a ticagrelor-based strategy without a significant increase in major bleeding. This led ESC to recommend that prasugrel should be considered in preference to ticagrelor in ACS patients undergoing PCI)

 Avoid:

• Prior stroke/TIA (absolute)
• Age >75 (relative)
• Weight<60kg (relative)

3. CLOPIDOGREL

• Loading: 300–600 mg
• Maintenance: 75 mg OD

 Use when:

• High bleeding risk
• Oral anticoagulant use
• Cost issues

 Duration of DAPT

1. Standard: 12 months(Class I Recommendation to reduce MACE.)
2. Shortened (3–6 months) → high bleeding risk(Ticagrelor Monotherapy After 1 Month For ACS patients undergoing PCI who tolerate DAPT:(2025 ACC/AHA)

• Prior intracranial hemorrhage
• Recurrent GI bleeding
• Severe anemia
• Advanced age with frailty
• Severe CKD

3. Extended (>12 months(18months,24 months,30 months) → high ischemic risk + low bleeding risk 

• Prior MI
• Diffuse multivessel CAD
• Diabetes mellitus
• Recurrent ACS
• Multiple stents
• Complex PCI
• Prior stent thrombosis

4. Patients Requiring Long-Term Oral Anticoagulation

Examples:

• Atrial fibrillation
• Mechanical valve
• Venous thromboembolism

Recommendation

Triple therapy:for only 1–4 weeks

• Aspirin
• Clopidogrel
• Oral anticoagulant

Stop aspirin and Continue: Clopidogrel + anticoagulant

This significantly reduces bleeding risk

2. ANTICOAGULATION MANDATORY-(until revascularization or discharge)

 A. FONDAPARINUX (ESC FIRST-LINE )

• Dose: 2.5 mg SC OD

 Preferred due to:

• Lowest bleeding risk
• Once daily dosing

 IMPORTANT:
If PCI done → ADD UFH bolus (to prevent catheter thrombosis)

Avoid if:eGFR <20 ml/min

 B. LOW MOLECULAR WEIGHT HEPARIN (ENOXAPARIN)

• Dose: 1 mg/kg SC BD

 Adjust:eGFR <30 → 1 mg/kg OD

 Avoid switching between heparins

C. UNFRACTIONATED HEPARIN (UFH)

• Bolus: 60–70 U/kg
• Infusion: 12–15 U/kg/hr

 Monitor aPTT (1.5–2.5× control)

 D. BIVALIRUDIN (PCI SETTING)

• Bolus: 0.75 mg/kg
• Infusion: 1.75 mg/kg/hr

 3. GP IIb/IIIa INHIBITORS (SELECTIVE USE)

Drugs:

• Abciximab
• Tirofiban
• Eptifibatide

 Indications (ESC)

• High thrombus burden
• No-reflow / bailout PCI

 NOT routine

 4. ANTI-ISCHEMIC THERAPY

 A. NITRATES(Not routinely lifelong)

 Dose

• SL: 0.4 mg every 5 min (max 3 doses)
• IV infusion(Acute phase only): 5–10 µg/min → titrate

 Avoid:

• Hypotension
• RV infarction
• PDE-5 inhibitor use

In NSTE-ACS, long-acting nitrates (e.g. isosorbide mononitrate, isosorbide dinitrate):

 ESC/ACC: They are symptomatic drugs only, not disease-modifying.

 WHEN ARE THEY INDICATED?

1. Persistent/Recurrent Angina after stabilization

 If patient continues to have chest pain despite:

• Beta-blockers
• Revascularization (PCI)

2. Patients NOT suitable for revascularization

3. Vasospastic (Prinzmetal) component

 Along with calcium channel blockers

Isosorbide mononitrate

• 30–60 mg OD → titrate up to 120 mg

Isosorbide dinitrate

• 10–40 mg BD/TDS

 Continuous exposure → tolerance develops Therefore:

• Give nitrate-free interval (10–12 hrs/day)

 B. BETA-BLOCKERS

• Metoprolol:
• IV: 5 mg every 5 min (max 15 mg)
• Oral(Preferred): 25–50 mg BD
• Carvedilol: 3.125 mg BID → target 25 mg BID (50 mg/day)

 Avoid:

• Acute HF
• Cardiogenic shock
• Bradycardia
• NOTE-AECOPD is contraindication Not COPD

Duration: At least 12 months
 Lifelong if:

• LV dysfunction
• Prior MI
• Ongoing ischemia

 C. CALCIUM CHANNEL BLOCKERS

• Diltiazem / Verapamil

Use if:

• Beta-blocker contraindicated
• Vasospasm

 5. STATINS (HIGH-INTENSITY — MANDATORY LIFELONG)

• Atorvastatin: 40–80 mg OD
• Rosuvastatin: 20–40 mg OD

 Start early (within 24 hrs)

 6. ACE INHIBITORS / ARBs( longterm )

• Start within 24 hrs if:
• LV dysfunction
• Diabetes
• Hypertension

Example:

• Ramipril 2.5 mg → titrate
• Enalapril 2.5 mg BD

 7. MINERALOCORTICOID RECEPTOR ANTAGONISTS(Long term)

• Eplerenone / Spironolactone

       If:EF ≤40% + HF/DM

 8. ADDITIONAL IMPORTANT DRUGS

 A. MORPHINE (SELECTIVE)

• Dose: 2–5 mg IV

Use cautiously (may delay P2Y12 absorption)

B. PROTON PUMP INHIBITORS

• Indication:High GI bleed risk

C. OXYGEN Only if SpO₂ <90%