A 62-year-old woman from Mumbai with a 10-year history of hypertension and dyslipidemia presents with recurrent episodes of chest pain occurring at rest over the past 2 days. Each episode lasts 15–20 minutes and is relieved by sublingual nitroglycerin within 5 minutes. She denies any chest pain at present. Vital signs are stable: BP 132/86 mmHg, HR 78/min. Physical examination is unremarkable. A 12-lead ECG performed during a pain-free interval shows T-wave flattening in leads V2–V4. Troponin I measured immediately and repeated 3 hours later are both negative (<0.04 ng/mL). What is the most likely diagnosis and the next best step in management?

Explanation

## Clinical Diagnosis: Unstable Angina **Key Point:** This patient presents with unstable angina (UA), a form of acute coronary syndrome (ACS) characterized by new or worsening angina without myocardial necrosis (negative troponin). ### Diagnostic Criteria for Unstable Angina | Criterion | Patient Finding | Significance | |-----------|-----------------|---------------| | Chest pain character | Substernal, relieved by nitrates | Typical anginal pattern | | Onset pattern | At rest, recurrent over 2 days | **New or worsening angina = unstable** | | Duration | 15–20 minutes | Consistent with angina (not MI if <30 min) | | ECG changes | T-wave flattening in V2–V4 | Suggests anterior wall ischemia | | Troponin (×2) | Negative at 0 and 3 hours | **Rules out NSTEMI; confirms UA** | | Response to nitrates | Complete relief | Confirms coronary ischemia | **High-Yield:** The distinction between UA and NSTEMI hinges on **cardiac biomarkers**. Both present with ACS symptoms and ECG changes, but: - **UA** = ACS without myocardial necrosis (troponin negative) - **NSTEMI** = ACS with myocardial necrosis (troponin positive) Troponin measured at 0 and 3 hours rules out NSTEMI in this case. ### Pathophysiology of Unstable Angina ```mermaid flowchart TD A[Coronary atherosclerotic plaque]:::outcome --> B[Plaque rupture or erosion]:::outcome B --> C[Platelet aggregation + thrombus formation]:::outcome C --> D{Thrombus severity?}:::decision D -->|Partial occlusion| E[Subendocardial ischemia]:::outcome D -->|Complete but transient| F[Brief ischemia, no necrosis]:::outcome E --> G[UA: ECG changes + negative troponin]:::outcome F --> G D -->|Sustained complete occlusion| H[NSTEMI: ECG changes + positive troponin]:::outcome ``` **Clinical Pearl:** UA is a **high-risk ACS variant**. Despite negative troponin, these patients have significant coronary stenosis (often >70%) and are at risk for progression to NSTEMI or STEMI. They require admission, intensive antiplatelet/anticoagulant therapy, and early invasive evaluation. ## Management of Unstable Angina **Mnemonic: UA Management = DAPT + AC + Beta + Early Cath** - **D**ual antiplatelet therapy (aspirin + P2Y12 inhibitor) - **A**nticoagulation (UFH, LMWH, or fondaparinux) - **B**eta-blocker and ACE inhibitor - **E**arly coronary angiography (within 24–72 hours) ### Immediate Actions 1. **Admit to hospital** (coronary care unit or high-dependency unit) 2. **Dual antiplatelet therapy:** - Aspirin 300 mg loading dose - P2Y12 inhibitor (clopidogrel 600 mg, ticagrelor 180 mg, or prasugrel 60 mg) 3. **Anticoagulation:** Unfractionated heparin or low-molecular-weight heparin 4. **Beta-blocker:** To reduce myocardial oxygen demand 5. **Nitrates:** For symptom relief (sublingual or IV) 6. **Coronary angiography:** Within 24–72 hours to identify culprit lesion and guide revascularization (PCI or CABG) **High-Yield:** Serial troponin measurement (at 0, 3, and 6 hours) is mandatory in suspected ACS. Negative troponin at 3 hours does NOT exclude UA; the diagnosis is confirmed by clinical presentation + ECG changes + negative biomarkers. [cite:Harrison 21e Ch 297]