Diagnosis, Risk Stratification, and Initial Management Planning in Acute Coronary Syndromes
Learning Objective
Apply diagnostic and classification criteria to assess ACS and guide initial management.
I. Clinical Manifestations & Presentation
Acute myocardial ischemia manifests with chest discomfort and associated symptoms; atypical or silent presentations are common in women, elderly and diabetics.
Typical chest pain:
- Quality: pressure, tightness, heaviness
- Location: substernal; may radiate to jaw, left arm or shoulder
- Duration: >20 minutes, constant
- Triggers: exertion or emotional stress; not reliably relieved by rest or nitrates
Associated symptoms:
- Diaphoresis, dyspnea, nausea/vomiting, palpitations, syncope
Atypical presentations:
- Epigastric discomfort, indigestion, profound fatigue
High-risk groups for silent or atypical ACS:
- Diabetes, older age, female sex
Key Pearl: Suspect ACS in Specific Populations
Always suspect ACS in diabetics or elderly with unexplained dyspnea or fatigue, even without classic chest pain.
II. Diagnostic Modalities
Rapid integration of ECG, biomarkers and echocardiography confirms myocardial ischemia and guides urgency of care.
A. Electrocardiography
- Obtain 12-lead ECG within 10 minutes of presentation
- STEMI criteria:
- New ST elevation ≥1 mm in ≥2 contiguous leads (V2–V3 criteria higher in men/women)
- New or presumed new LBBB in appropriate context
- NSTEMI/UA patterns: ST depression ≥0.5 mm, T-wave inversion, transient changes
- Serial ECGs every 15–30 min if initial tracing is nondiagnostic and suspicion persists
Key Pearl: Importance of Serial ECGs
Early and repeat ECGs detect evolving ischemia—don’t rely on a single normal tracing.
B. Cardiac Biomarkers
- High-sensitivity troponin I/T (hs-cTn): rise and/or fall above the 99th percentile confirms MI
- Serial sampling at 0 and 1–2 hours accelerates rule-in/rule-out
- Δ change (20–50% relative increase) supports acute event over chronic elevation
- CK-MB: useful for detecting reinfarction; less sensitive/specific than troponin
- Pitfalls: chronic troponin elevation in CKD or structural heart disease; always correlate with clinical/ECG data
Key Pearl: Interpreting Troponin Levels
A single normal troponin early after symptom onset does not exclude MI—always perform serial assays.
C. Echocardiography
- Identify new regional wall motion abnormalities (RWMA) as markers of acute ischemia
- Assess left ventricular ejection fraction and mechanical complications (MR, VSD)
- Differentiate ACS from myocarditis or stress cardiomyopathy via RWMA patterns
Key Pearl: Value of Portable TTE
Portable TTE is invaluable when ECG or biomarkers are inconclusive or alternate diagnoses are considered.
III. Risk Stratification Tools
TIMI and GRACE scores quantify ischemic risk and guide the timing of invasive evaluation.
A. TIMI Score for NSTE-ACS
Seven 1-point criteria:
- Age ≥65 years
- ≥3 CAD risk factors (HTN, hyperlipidemia, DM, smoking, family history)
- Known CAD (≥50% stenosis)
- Aspirin use in past 7 days
- ≥2 anginal events in prior 24 h
- ST deviation ≥0.5 mm
- Elevated cardiac markers
Score: 0–2 low risk; 3–4 intermediate; 5–7 high risk
Limitation: underestimates risk in elderly or renal-impaired patients
Key Pearl: TIMI Score and Invasive Strategy
TIMI ≥3 supports early invasive strategy in NSTE-ACS.
B. GRACE Score
Variables: age, HR, SBP, creatinine, Killip class, cardiac arrest at admission, ST deviation, elevated enzymes
Provides in-hospital and 6-month mortality risk (continuous scale)
GRACE >140 signifies high risk—favors immediate/early cath
Key Pearl: GRACE Score Superiority
GRACE outperforms TIMI for mortality prediction in complex patient populations.
Comparison Table: TIMI vs GRACE
| Feature | TIMI Score | GRACE Score |
|---|---|---|
| Variables | 7 binary | 8 continuous & categorical |
| Risk estimates | 14-day composite (death/MI) | In-hospital & 6-month mortality |
| Ease of use | Bedside calculation | Online calculator |
| Strength | Simplicity | Superior discrimination |
| Limitation | Less accurate in high-risk | Requires more data inputs |
IV. Mortality Prediction & Clinical Application
Mortality models inform invasive versus conservative management and prognosis.
- In-hospital vs 6-month models guide short-term and mid-term risk discussions
- High-risk features driving urgent invasive management:
- Ongoing chest pain, hemodynamic instability, life-threatening arrhythmias
- GRACE >140 or Killip class ≥II
- STEMI: immediate reperfusion is indicated regardless of score
- NSTEMI/UA: use scores to decide timing of angiography and resource allocation
Key Pearl: Consistent Application of Risk Scores
Failure to apply risk scores consistently can delay necessary invasive interventions in high-risk ACS.
V. Timing of Invasive Strategy
Angiography timing is stratified as immediate (<2 h), early (<24 h) or delayed (>24 h) based on risk and clinical features.
- Immediate (<2 h): refractory angina, cardiogenic shock, dynamic ECG changes, mechanical complications
- Early (<24 h): intermediate/high-risk NSTE-ACS (TIMI ≥3, GRACE >140)
- Delayed (>24 h): low-risk NSTE-ACS after stabilization and noninvasive testing
- Consider institutional resources, bleeding risk and comorbidities when scheduling
Key Pearl: Reducing Door-to-Cath Times
Predefined activation criteria and checklists reduce door-to-cath times and improve outcomes.
ISCHEMIA Trial Implications
- In stable patients with moderate-severe ischemia, a conservative strategy was non-inferior to routine early invasive management for major events
- High-risk ACS patients were excluded—findings do not apply to STEMI or unstable high-risk NSTEMI
- Ongoing debate persists for intermediate-risk NSTE-ACS; tailor decisions via multidisciplinary discussion
Key Pearl: ISCHEMIA Trial Context
ISCHEMIA supports selective invasive strategy in stable moderate-risk patients but does not change the need for immediate intervention in high-risk ACS.
VI. Integration into Initial Management Plan
Synthesize presentation, ECG, biomarkers and risk scores to develop a rapid, protocolized care pathway; pharmacists ensure safe and timely pharmacotherapy and coordination.
A. Diagnostic-to-Treatment Pathway
B. Initial Pharmacotherapy
| Class | Agent(s) | Mechanism | Loading/Maintenance | Monitoring & Pitfalls |
|---|---|---|---|---|
| Aspirin | Aspirin | COX-1 inhibitor; ↓TXA₂ | 162–325 mg chew once, then 81–162 mg/day | GI bleeding; hypersensitivity |
| P2Y₁₂ inhibitors | Clopidogrel, Ticagrelor, Prasugrel | ADP receptor blockade | Clop 600 mg/75 mg; Tica 180 mg/90 mg BID; Pras 60 mg/10 mg daily | Bleeding; ticagrelor dyspnea; prasugrel contraindicated in stroke/TIA |
| Anticoagulants | UFH, Enoxaparin, Bivalirudin | Thrombin/Xa inhibition | UFH: bolus 60 U/kg + infusion; Enox 1 mg/kg q12h; Bivi 0.75 mg/kg + 1.75 mg/kg/h | Monitor aPTT (UFH), anti-Xa (Enox), renal dosing; bleeding risk |
| Nitrates | Nitroglycerin | NO-mediated vasodilation | SL 0.4 mg q5 min ×3; IV 5–200 µg/min | Hypotension; right-ventricular infarct caution |
| Analgesics | Morphine | Opioid analgesic; venodilation | 2–4 mg IV q5–15 min PRN | Hypotension; respiratory depression; may ↓P2Y₁₂ absorption |
Key Pearl: Pharmacotherapy Sequencing and Adjustments
Give aspirin before P2Y₁₂ inhibitors; adjust anticoagulants for renal function and bleeding risk.
C. Multidisciplinary Communication
- Pharmacists verify doses, check interactions and monitor labs
- Standardized order sets and checklists align timing across pharmacy, cardiology and ICU teams
- Regular multidisciplinary rounds promote real-time adjustments and prevent delays
Clinical Vignette
A 68-year-old diabetic woman presents with dyspnea and mild chest discomfort. ECG shows ST depression in V4–V6; hs-troponin rises from 22 to 90 ng/L at 2 h. Her GRACE score is 158. Initiate DAPT (aspirin + ticagrelor), UFH infusion, and plan early (<24 h) angiography. Pharmacist adjusts enoxaparin for CrCl 45 mL/min and confirms SL nitrates for symptom relief.
References
- Rao SV, O’Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the management of patients with acute coronary syndromes. Circulation. 2025;151:e771–e862.
- Thomas JJ, Brady WJ. Acute Coronary Syndrome. In: Medicine and Surgery, Section Three Cardiac System. Elsevier; 2018:891–928.
- O’Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction. Circulation. 2013;127:e362–e425.
- Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60(16):1581–1598.
- Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes. Circulation. 2014;130:e344–e426.
- Gulati M, Levy PD, Mukherjee D, et al. 2021 AHA/ACC/ASE/CHEST/SAEM/SCCT/SCMR guideline for the evaluation and diagnosis of chest pain. Circulation. 2021;144:e368–e454.
- Pope JH, Selker HP. Diagnosis of acute cardiac ischemia. Emerg Med Clin North Am. 2003;21(1):27–59.
