Continuing Education Activity

Chest pain is among the most common symptoms prompting emergency department visits and cardiology evaluations. The etiologies of this symptom range from benign to life-threatening, but immediate assessment must prioritize exclusion of acute coronary syndrome, which includes unstable angina, non-ST-elevation myocardial infarction, and ST-elevation myocardial infarction. Angina, defined as chest discomfort resulting from myocardial ischemia, may present with or without evidence of myocardial infarction. Unlike chest pain in general, angina has a more specific pathophysiologic basis, most often reduced coronary blood flow due to atherosclerotic obstruction.

Risk factors for angina include hypertension, diabetes mellitus, smoking, hyperlipidemia, and a family history of coronary artery disease. The underlying mechanism typically involves an imbalance between myocardial oxygen demand and supply. Angina clinically presents as substernal pressure or tightness, often radiating and exacerbated by exertion or stress. Clinical evaluation is based on electrocardiography, biomarkers, and stress testing or imaging guide diagnosis. Management includes pharmacologic therapy (eg, nitrates, β-blockers, antiplatelet agents), risk factor modification, and revascularization when indicated.

This activity for healthcare professionals is designed to sharpen learners' skills in evaluating and managing angina. Participants will deepen their understanding of the etiology, risk factors, pathophysiology, and clinical presentation of cardiac chest pain, enabling differentiation from noncardiac sources. Evidence-based diagnostic and therapeutic recommendations will be highlighted. Improved competence will enable clinicians to collaborate effectively within interprofessional teams caring for affected individuals.

Objectives:

• Interpret cardiac diagnostic findings, including electrocardiographic changes and serial troponin levels, in relation to chest pain presentation.
• Differentiate acute coronary syndrome presentations from noncardiac chest pain by evaluating symptom duration, observed electrocardiographic changes, and troponin kinetics.
• Apply personalized, evidence-based recommendations for managing angina and mitigating its potential complications.
• Collaborate with the interprofessional healthcare team to ensure efficient triage of patients presenting with chest pain, accurate risk stratification, and effective management of underlying conditions.

Introduction

Chest pain is one of the most common reasons for seeking medical attention in both emergency and outpatient cardiology settings. Among this symptom's various potential causes, cardiac ischemia, particularly acute coronary syndrome (ACS), must be ruled out promptly, given its life-threatening nature.[1]

ACS includes unstable angina, non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI). Meanwhile, stable angina, which corresponds to the presentation of chronic coronary syndrome (CCS), reflects a longstanding and typically exertional manifestation of myocardial ischemia.[2] These conditions result from a mismatch between myocardial oxygen supply and demand caused by flow-limiting atherosclerotic lesions.[3] (Source: Zipes et al, 2019) 

Myocardial ischemia almost always involves the main branches of the coronary arteries, particularly the left anterior descending (LAD) and right coronary (RCA) arteries and their primary divisions. These large-caliber vessels are prone to atherosclerosis, which often progresses insidiously. Lesions that become critical may lead to stable angina but are more often clinically silent.[4]

In most cases, the first clinical manifestation occurs when a plaque ruptures and forms a thrombus, resulting in ACS.[5][6] The pattern of myocardial ischemia or infarction represents the anatomical territory supplied by the affected vessel. For example, LAD occlusion typically leads to anterior wall involvement, while RCA lesions affect the inferior wall. (Source: Hampton, 2019) This vascular distribution aids both diagnosis and prognostic stratification, especially when interpreted through electrocardiography (ECG) and imaging.[7] Smaller distal branches, even if affected, generally do not produce clinically relevant ischemia, are unsuitable for revascularization, and have limited prognostic impact.[8]

A firm grasp of these anatomical, pathophysiological, and clinical relationships is critical for the early and accurate identification of ischemic chest pain. Such foundational understanding is essential for training clinicians in the evaluation and management of coronary artery disease (CAD).

Etiology

Angina most commonly results from atherosclerotic CAD. However, several nonatherosclerotic etiologies have also been identified, including the following:

• Congenital coronary artery anomalies, including anomalous origin, myocardial bridging, and coronary artery fistula
• Coronary artery embolism arising from atrial fibrillation, infective endocarditis, or prosthetic valve thrombi
• Spontaneous coronary artery dissection
• Coronary artery spasm
• Microvascular angina, also known as cardiac syndrome X
• Severe aortic stenosis
• Hypertrophic cardiomyopathy
• Severe anemia or hypoxemia
• Hypertension
• Tachyarrhythmias
• Coronary artery vasculitis
• Radiation-induced CAD
• Infiltrative disorders such as amyloidosis and sarcoidosis 

Both CCS and ACS arise primarily from atherosclerosis affecting the large-caliber epicardial coronary arteries. This pathological process most commonly develops at sites subjected to turbulent flow and shear stress, with frequent involvement of the left main coronary artery, the LAD, the left circumflex (LCx) artery, and the RCA. Clinically significant disease may also occur in major branches of these vessels, including the diagonal branches from the LAD, obtuse marginal branches from the LCx, and the posterior descending artery from the RCA, provided these branches are of sufficient caliber. As mentioned, small-caliber coronary arteries rarely develop clinically meaningful atherosclerosis. Even when such vessels are affected, they typically lack prognostic significance and are not amenable to revascularization procedures.

Although atherosclerosis accounts for the vast majority of ACS presentations, nonatherosclerotic mechanisms contribute to a minority of cases. One such mechanism is coronary vasospasm, which involves the transient constriction of an epicardial artery, producing reversible myocardial ischemia or infarction. This condition occurs more frequently in younger individuals and may be triggered by cold exposure, psychological stress, or certain medications. Diagnosis is often supported by a favorable response to nitrates or confirmed through provocation testing.[9]

Spontaneous coronary artery dissection is a rare, nontraumatic, and nonatherosclerotic cause of ACS characterized by a tear within the coronary arterial wall. The condition predominantly affects young or peripartum women and is frequently underrecognized. Intravascular imaging offers optimal visualization, and conservative management is generally preferred unless ongoing myocardial ischemia is present.[10]

Coronary embolism, while uncommon, accounts for approximately 3% of ACS cases. The most frequent embolic sources include infective endocarditis, atrial fibrillation, and prosthetic valve thrombosis.[11] Less common causes encompass bioprosthetic valve thrombosis, Libman-Sacks endocarditis, and paradoxical embolism through a patent foramen ovale.

Iatrogenic coronary artery dissection is a rare but serious complication of coronary catheterization, particularly during percutaneous coronary intervention (PCI). This form of dissection typically results from mechanical trauma caused by guidewires or catheters and may necessitate emergency stenting or, in certain cases, surgical bypass.[12]

Epidemiology

Cardiovascular diseases (CVDs) constitute the leading cause of mortality worldwide, accounting for approximately 17.9 million deaths annually, representing about 32% of global mortality. Myocardial infarction and stroke collectively account for approximately 85% of these deaths. (Source: World Health Organization, 2019)

CAD, the most prevalent clinical manifestation of CVD, affected an estimated 315 million individuals globally in 2022.[13] (Source: Stark et al, 2024) A 2023 meta-analysis reported a global myocardial infarction prevalence of approximately 3.8% among individuals younger than 60 years and 9.5% among those aged 60 and older.[14] True coronary syndromes are uncommon in individuals younger than 40 unless specific risk factors, including familial hypercholesterolemia, vasculitis, cocaine use, and congenital coronary anomalies, are present.

Hemodynamically significant coronary atherosclerosis, typically defined as luminal narrowing of 70% or more, is frequently asymptomatic until plaque rupture and thrombosis precipitate ACS. In many cases, the first clinical presentation of CAD occurs as an acute myocardial infarction. Recent studies have also raised concern about the potential risk posed by nonobstructive plaques, suggesting that even less severe lesions may contribute to ACS through inflammation or mechanical instability. These observations reinforce the need for heightened clinical vigilance and a renewed focus on early detection and screening strategies, given the often-undetected burden of silent ischemia and the propensity for plaque rupture.

Pathophysiology

CCS results from atherosclerotic plaque formation within the coronary arteries, producing flow-limiting stenoses. These lesions demonstrate a luminal narrowing of 50% or greater in the left main coronary artery or at least 70% in other major coronary vessels. Such obstructions diminish coronary perfusion during exertion or stress, resulting in effort-induced myocardial ischemia. Although ischemia may manifest as stable angina, many lesions remain clinically silent. Despite their apparently stable morphology, significant plaques retain the potential for future destabilization, precipitating ACS. The resultant mismatch between myocardial oxygen demand and supply in the presence of hemodynamically significant yet stable plaque produces reproducible and predictable symptoms.

ACS arises from sudden plaque rupture or erosion, leading to thrombus formation and acute obstruction of coronary blood flow. STEMI results from complete and sustained coronary artery occlusion, causing transmural myocardial ischemia and necrosis if prompt reperfusion is not achieved. NSTEMI and unstable angina typically arise from partial thrombotic occlusion of a coronary artery, producing subendocardial or intermittent ischemia within the affected myocardial territory (see Image. Coronary Artery Changes and Corresponding Types of Angina).[15]

History and Physical

Clinical Presentation of Chronic Coronary Syndrome

CCS, or stable angina, typically affects patients aged 40 years or older. Symptoms are usually absent at rest, and physical examination findings are generally unremarkable. Chest pain occurs during physical exertion or emotional stress and is reproduced consistently with efforts of similar intensity. Infrequent or inconsistent pain during exertion does not support a diagnosis of stable angina. The pain shares the same qualitative features as in ACS—constricting, retrosternal, often radiating, diffuse, and lasting several minutes, relieved promptly with rest. In CCS, the pain is predictable and may be triggered by exertion and relieved by rest or nitrate administration.

Clinical Presentation of Acute Coronary Syndrome

In current cardiovascular practice, any chest pain reported between the ears and the umbilicus in patients aged 40 years or older should prompt evaluation for potential ACS. However, true ischemic chest pain typically presents as retrosternal (occasionally high epigastric), nonstabbing, and persistent, lasting at least 20 minutes at rest. This pain always involves a broad area, often radiates, and is commonly accompanied by autonomic manifestations, such as diaphoresis and nausea. Pain lasting only seconds or less than 5 minutes is rarely cardiac in origin. Likewise, pain localized to an area smaller than a coin generally excludes a cardiac cause. Ischemic pain is not triggered by respiration, movement, or palpation, and is difficult to ignore. Among all features, pain duration remains the most critical diagnostic clue.

In STEMI, the pain is continuous, severe, and independent of exertion, lasting 12 to 24 hours if untreated. This pain typically subsides as myocardial necrosis progresses and does not respond to nitroglycerin. Pain in NSTEMI and unstable angina follows a progressive pattern, with recurrent episodes appearing at rest or following exertion, typically of recent onset. In contrast, pain that occurs exclusively with exertion and remains predictable is characteristic of stable angina. Episodes in NSTEMI and unstable angina may be prolonged or severe, often resolve with rest, and usually respond to nitrate administration. Chest pain lasting 15 to 20 minutes or longer at rest and recurring in the absence of anti-ischemic therapy is characteristic. A single episode that does not recur during observation raises suspicion for a noncardiac etiology.

Physical examination findings are typically unremarkable. Manifestations such as acute pulmonary edema, malignant arrhythmias, cardiac arrest, or hemodynamic instability strongly indicate ACS and warrant immediate intervention. Syncope rarely reflects myocardial infarction, as ventricular tachycardia seldom self-terminates and usually progresses to ventricular fibrillation, making transient syncope an unlikely ACS presentation. ACS may present atypically in patients with diabetes, lacking chest pain and instead manifesting with marked malaise.[16] (Source: Bellicini, 2025)

Evaluation

Is This Chronic Coronary Syndrome?

Stable angina, a form of CCS, should be considered in the evaluation of chest discomfort. The diagnosis is supported when pain is reproducible, occurring consistently with a specific level of exertion or emotional stress, and follows a predictable pattern that resolves within a few minutes of rest, rather than appearing sporadically. Symptoms that occur at rest or lack a consistent exertional pattern warrant exclusion of ACS or reconsideration of the diagnosis.

At baseline, the resting ECG is usually normal and does not show changes suggestive of ongoing or recent ischemic injury. Minor or nonspecific ECG findings are not indicative of ischemia. Similarly, the baseline echocardiogram is normal unless a prior myocardial infarction has occurred. When exercise ECG or imaging-based stress testing, such as stress echocardiography or myocardial scintigraphy, is performed, anginal symptoms should be reproduced and associated with definitive findings such as ST-segment depression, regional wall motion abnormalities (eg, akinesis or hypokinesis), or perfusion defects.[17] Mild upsloping ST depression is a common physiological response to exercise and should not be mistaken for ischemia.

Notably, most critical coronary stenoses do not result in stable angina. In such cases, provocative testing reveals objective evidence of ischemia, including ECG changes, wall motion abnormalities, or perfusion defects, despite the absence of symptoms.[18]

Is This Acute Coronary Syndrome?

ECG interpretation remains a cornerstone in the diagnosis of cardiac ischemia. Accurate assessment must be integrated with symptom timing, pain characteristics, and high-sensitivity troponin (hs-troponin) values.[19] In the presence of chest pain, the ECG must show clear ischemic changes in STEMI, NSTEMI, or angina. Nonspecific alterations are not indicative of ischemia. A normal ECG during active chest pain strongly suggests a noncardiac origin.

In STEMI, the ECG typically reveals diagnostic findings on the initial recording, as pain is continuous. Marked and persistent ST-segment elevation appears in 2 or more contiguous leads and persists until coronary obstruction is relieved or transmural necrosis occurs, typically within 12 to 24 hours. Pathological Q waves and deep T-wave inversions subsequently develop, indicating completed infarction. Posterior infarction presents as reciprocal ST depression in leads V1 through V3, reflecting the mirror image of true posterior ST elevation. This pattern requires the same level of clinical urgency. In the presence of left bundle branch block, the diagnosis of STEMI may be established using the Sgarbossa criteria.[20]

Hs-troponin levels begin to rise within an hour of continuous ischemic chest pain and typically peak between 12 and 24 hours. Concentrations may remain within the reference range during the initial phase of myocardial injury. Myocardial infarction may be reasonably excluded if hs-troponin levels remain normal 3 hours after the onset of continuous pain. Measurement of troponin concentrations must not delay urgent reperfusion therapy in STEMI, as ECG findings and symptom duration establish the diagnosis.

In NSTEMI, the characteristic finding is ST-segment depression in 2 or more leads during the ischemic episode. However, ECG changes may be transient and often normalize once pain subsides, particularly when the episode lasts less than 20 minutes or is precipitated solely by exertion and relieved by rest, as in unstable angina. In contrast, a single episode occurring at rest and lasting more than 20 to 30 minutes generally produces persistent ECG abnormalities, most commonly ST-segment depression, even after symptom resolution. Chest pain is unlikely to be ischemic when ECG changes are absent or limited to minor, nonspecific alterations following a prolonged episode.

The duration and extent of myocardial ischemia in NSTEMI correlate with hs-troponin concentrations. A rising curve is typically detectable on serial sampling following continuous chest pain lasting more than 20 to 30 minutes, becoming evident within 1 to 2 hours after symptom onset. Myocardial infarction may be excluded if hs-troponin concentrations remain within the reference range 3 hours after pain onset. In confirmed cases, troponin T concentrations generally exceed several hundred nanograms per liter (ng/L).

Modest hs-troponin elevations, typically ranging from 100 to 300 ng/L for troponin T or 500 to 1,000 ng/L for troponin I, are more characteristic of conditions associated with increased cardiac workload, such as sustained tachycardia or pressure overload, even in the presence of angiographically normal coronary arteries. Individuals with prior coronary artery bypass grafting (CABG) frequently demonstrate baseline hs-troponin concentrations in the several hundred ng/L range despite the absence of acute ischemia. 

Echocardiographic Findings in Acute Coronary Syndrome

Echocardiography serves as a fundamental tool in evaluating myocardial infarction by identifying regional wall motion abnormalities that correspond to the affected coronary artery territory. Occlusion of the LAD results in akinesia or hypokinesia of the anterior wall, anterior septum, and apex, with proximal LAD involvement potentially extending to adjacent lateral segments. In right-dominant coronary systems, RCA occlusion typically causes akinesia of the inferior wall, often involving the posterior wall and inferoseptal segments. Proximal or extensive RCA occlusions can lead to septal abnormalities extending from basal regions to mid or apical levels. Occlusion of the LCx leads to hypokinesia of the lateral wall, with posterior wall involvement commonly observed in left-dominant circulation.

Wall motion abnormalities often remain confined to the apical segments of the heart when the culprit lesion affects a distal coronary branch. Basal portions of the inferior and posterior walls may appear akinetic even without ischemia, as these regions are structurally integrated into the fibrous cardiac skeleton (annulus fibrosus). This normal finding should not be mistaken for a pathological condition.

Among mechanical complications visible on echocardiography, acute severe mitral regurgitation is the most significant and commonly encountered issue. This condition typically arises from ischemic dysfunction of 1 or both papillary muscles, which become akinetic during anterior or inferior infarctions, rather than from papillary muscle rupture, which is rare. The resulting abrupt valvular insufficiency frequently leads to acute pulmonary edema and hemodynamic deterioration.

Other mechanical complications, such as rupture of the ventricular septum or free wall, as well as pseudoaneurysm, are now rare and may be detected using echocardiography. Prompt identification of these complications via echocardiography is critical due to their high mortality risk and the necessity for urgent intervention.

Treatment / Management

Chronic Stable Angina

The management of chronic stable angina focuses on symptom relief, improvement of quality of life, and reduction of long-term cardiovascular risk. Optimal therapy integrates revascularization strategies with pharmacologic interventions, including disease-modifying agents and medications directed at alleviating ischemic symptoms.

Revascularization procedures and considerations

Significant CAD accompanied by chronic stable angina or silent ischemia warrants consideration of revascularization when 1 or more of the following conditions are present:

• Refractory angina despite optimal medical therapy
• Extensive ischemia identified on noninvasive testing (eg, at least 10% myocardium at risk on imaging)
• High-risk coronary anatomy, such as left main or multivessel disease

The goals of revascularization include symptom relief, improved quality of life, and better long-term prognosis. Both PCI and CABG are appropriate treatment options, with the choice determined by anatomical complexity, comorbidities, and patient preference.

Disease-modifying therapy

Interventions in this category reduce cardiovascular risk and improve long-term outcomes. Daily aspirin (75-100 mg) or clopidogrel (for patients who are aspirin-intolerant) is recommended, along with high-intensity statins for all patients with clinical atherosclerotic CVD. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) benefit patients with diabetes, chronic kidney disease, hypertension, or reduced left ventricular ejection fraction (LVEF). Essential lifestyle modifications include smoking cessation, regular aerobic exercise, blood pressure and glycemic control, adherence to a Mediterranean diet, weight optimization, and avoidance of nonsteroidal anti-inflammatory drugs and excessive alcohol.

Antianginal therapy

Antianginal therapy aims to relieve symptoms and improve functional capacity, particularly in patients who have undergone partial revascularization or present with lesions unsuitable for intervention, such as in multivessel disease. β-blockers serve as 1st-line agents, especially after myocardial infarction or during episodes of resting heart rate elevation. Calcium channel blockers are divided into nondihydropyridines, such as verapamil and diltiazem, which slow the heart rate and improve angina, and dihydropyridines, like amlodipine and felodipine, which are preferred when bradycardia is a concern. Long-acting nitrates provide additional symptom relief but require nitrate-free intervals to maintain efficacy. Ranolazine effectively controls angina without impacting blood pressure or heart rate. Sublingual nitroglycerin offers rapid relief during acute angina episodes.

ST-Elevation Myocardial Infarction

STEMI results from complete and acute coronary artery occlusion, producing transmural myocardial ischemia. Immediate reperfusion is critical to limiting infarct size and reducing mortality.[21] Cardiac catheterization should be initiated without delay, with PCI performed within a door-to-balloon time of 90 minutes or less. Fibrinolytic therapy should be administered when PCI cannot be completed within 120 minutes, unless contraindicated, followed by urgent transfer for rescue PCI if necessary.

Initial medical therapy includes a loading dose of aspirin (162-325 mg) and a P2Y12 receptor inhibitor, such as ticagrelor, clopidogrel, or prasugrel, administered before angiography, particularly when PCI is planned. CABG is rarely required in the acute setting of STEMI, as primary PCI is almost always pursued. Early administration of a P2Y12 inhibitor enhances procedural outcomes.

Anticoagulation is always indicated. Unfractionated heparin is preferred during PCI, although enoxaparin is an acceptable alternative. Bivalirudin may be used in patients at high risk for bleeding. Fondaparinux is appropriate when fibrinolysis is administered but should not be used alone during PCI.

Additional supportive measures include nitrate administration, which may be used if systolic blood pressure exceeds 90 mm Hg, to reduce preload and myocardial oxygen demand. β-blockers lower heart rate and myocardial oxygen consumption, contributing to overall ischemia control.[22]

Postreperfusion management guideline-directed medical therapy

Dual antiplatelet therapy should be maintained for a minimum of 12 months following STEMI. High-intensity statin therapy is recommended for all patients unless contraindicated. Ezetimibe may be added when low-density lipoprotein cholesterol targets are not achieved or high-risk features are present. The addition of a nonstatin lipid-lowering agent is recommended for patients receiving maximally tolerated statin therapy who have a low-density lipoprotein cholesterol level exceeding 70 mg/dL. A fasting lipid profile should be obtained 4 to 8 weeks after initiation or modification of lipid-lowering therapy.

All patients with STEMI or NSTEMI should receive oral β-blocker therapy within the first 24 hours after presentation, provided no contraindications exist, such as acute heart failure, cardiogenic shock, a PR interval exceeding 0.24 seconds, 2nd- or 3rd-degree atrioventricular block, or severe bradycardia. Long-term β-blocker therapy (≥3 years) is recommended for all patients with prior myocardial infarction, particularly those with left ventricular dysfunction. β-blockers with demonstrated mortality benefit are strongly indicated in patients with an LVEF less than or equal to 40%, prior ventricular arrhythmia following myocardial infarction, recurrent ischemia or angina, or postinfarction hypertension not adequately controlled with other agents.

ACEIs or ARBs are indicated in patients with an LVEF at or below 40%, anterior infarction, diabetes mellitus, or chronic kidney disease. Mineralocorticoid receptor antagonists (MRAs) should be considered for patients with an LVEF not exceeding 40% and either heart failure or diabetes, provided renal function and serum potassium levels remain within acceptable limits. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are increasingly utilized following myocardial infarction, particularly in patients with heart failure with reduced ejection fraction or diabetes mellitus. Lifestyle modification is a fundamental component of management and includes smoking cessation, dietary optimization, regular physical activity, and weight control.

Non-ST-Elevation Myocardial Infarction and Unstable Angina

NSTEMI and unstable angina result from partial or transient coronary artery occlusion, leading to subendocardial ischemia and myocardial injury. Although immediate reperfusion is not required, early invasive management is essential in selected cases to reduce complications and optimize outcomes.

Initial medical management includes administration of aspirin as a loading dose of 162 to 325 mg. In patients with NSTEMI scheduled for PCI beyond 24 hours, early initiation of a P2Y12 inhibitor may be considered to reduce the likelihood of a major adverse cardiac event (MACE).

Anticoagulation should be initiated promptly and continued until either the completion of PCI or, in conservatively managed cases, hospital discharge. Nitrates are indicated when systolic blood pressure exceeds 100 mm Hg, offering symptomatic relief by reducing myocardial oxygen demand through preload and afterload reduction. β-blockers similarly decrease heart rate and myocardial oxygen consumption in the absence of contraindications such as bradycardia, relieving symptoms and improving cardiac efficiency. Morphine is reserved for persistent chest pain that does not respond to nitrates.

High-risk patients, identified by elevated cardiac troponin levels, dynamic ECG changes, or a Global Registry of Acute Coronary Events (GRACE) score greater than 140, should undergo coronary angiography within 24 hours of presentation. Intermediate-risk patients are typically given invasive treatment within 72 hours. Immediate angiography (ie, within 2 hours) is warranted in the setting of ongoing ischemia despite medical therapy, hemodynamic instability, or life-threatening arrhythmias.

Secondary prevention includes dual antiplatelet therapy for 12 months and high-intensity statin therapy, with the addition of ezetimibe when low-density lipoprotein cholesterol targets are unmet. β-blockers, ACEIs, ARBs, MRAs, and SGLT2 inhibitors are prescribed based on LVEF and comorbid conditions. Lifestyle optimization, encompassing smoking cessation, a heart-healthy diet, regular physical activity, and maintaining a healthy weight, is a cornerstone of long-term management.[23]

Differential Diagnosis

Chest pain on exertion that is retrosternal, pressure-like, and relieved by rest or nitrates strongly suggests myocardial ischemia in adults older than 40 to 45, particularly in the presence of established cardiovascular risk factors. Angina is an uncommon diagnosis among younger patients, and alternative etiologies should be considered in this group unless specific underlying predispositions are known.

Acute chest pain of uncertain origin necessitates a broader diagnostic approach. The diagnostic approach should encompass the conditions outlined below.

Coronary Syndromes

These conditions include stable and unstable angina, NSTEMI, and STEMI. Coronary syndromes are most frequently observed in middle-aged and older adults. These diseases are uncommon in individuals younger than 40 years unless specific high-risk factors, such as familial hypercholesterolemia, vasculitis, cocaine use, or congenital coronary anomalies, are present.

Hypertensive Crisis

A hypertensive crisis is characterized by an acute and severe elevation in blood pressure that increases myocardial workload and oxygen demand. This hemodynamic stress may provoke angina or produce ischemic-type chest discomfort, particularly in patients with known or silent CAD. Although not classified as a primary coronary syndrome, a hypertensive crisis may unmask previously unrecognized myocardial ischemia.

Arrhythmias

Abnormal heart rhythms, particularly atrial fibrillation with rapid ventricular response, may precipitate an imbalance between myocardial oxygen supply and demand. This mismatch can result in chest discomfort resembling angina, especially among individuals with underlying CAD.

Mechanical Cardiovascular Complications

These pathologies include aortic dissection, which typically presents with sudden, severe, tearing pain in the chest or back. Although aortic dissection is a life-threatening emergency, it occurs far less frequently than acute myocardial infarction among the causes of serious chest pain.

Pulmonary Embolism

Pulmonary embolism comprises a critical diagnosis in the evaluation of acute chest pain. This condition typically presents with acute, pleuritic, and lateralized chest pain consistently accompanied by dyspnea. Similar pain characteristics may occur when the pleura is involved in conditions such as pneumothorax, pneumonia, and pleuritis. The pain in these disorders is usually sharp, well-localized, positional, and exacerbated by respiration or coughing—features that distinguish it from the retrosternal, pressure-like discomfort typical of angina.

Infective or Inflammatory Myocardial Disease

Conditions like myocarditis are more common in younger individuals and often follow a viral illness by 1 or 2 weeks. Chest pain associated with myocarditis may resemble angina but tends to be continuous and unrelated to exertion. Cardiac biomarkers are persistently elevated, and although the clinical presentation may mimic ACS, ECG findings are generally nonspecific or atypical.[24]

Tamponade-Related Conditions

These disorders primarily include pericarditis and mediastinitis. Pericarditis typically produces sharp, positional chest pain that improves when the patient leans forward. The condition often follows viral infection or occurs in association with autoimmune disease or uremia, and it is frequently accompanied by pericardial effusion.[25] Although rare, mediastinitis constitutes a surgical emergency characterized by severe retrosternal pain, often accompanied by pericardial effusion. This condition usually develops in a well-defined clinical context, such as esophageal rupture or mediastinal tumor invasion.

Staging

Risk Stratification

Several validated tools are available to assess patients with suspected ACS according to their clinical presentation, troponin assay results, age, ECG findings, and cardiovascular risk factors. Risk stratification assists in determining prognosis and guiding the appropriate diagnostic and therapeutic approach.

The Thrombolysis in Myocardial Infarction (TIMI) score is a clinical risk assessment tool designed for patients with unstable angina or NSTEMI. This classification predicts the likelihood of all-cause mortality, new or recurrent myocardial infarction, and the need for urgent revascularization within 14 days. The following risk factors are each assigned one point in the TIMI scoring system:

• Age at least 65 years
• Presence of 3 or more risk factors for CAD, including hypertension, diabetes mellitus, dyslipidemia, smoking, or a family history of premature CAD
• Known CAD with stenosis greater than or equal to 50%
• Aspirin use within the past 7 days, indicating possible aspirin failure
• Two or more episodes of angina within the preceding 24 hours
• ST-segment deviation of at least 0.5 mm, either depression or transient elevation
• Elevated cardiac biomarkers, such as troponin or creatine kinase-myocardial band (CK-MB)

Patients with a TIMI score of 0 to 2 are considered low-risk and are typically treated conservatively with noninvasive testing. Individuals with a score of 3 to 4 are categorized as intermediate risk, for whom an early invasive strategy may be appropriate. A TIMI score of 5 or higher indicates high risk, warranting early angiography and aggressive management with antiplatelet agents, anticoagulation, and revascularization when indicated.

Other widely used risk assessment models include the GRACE and HEART (history, ECG, age, risk factors, and troponin) scores. Both these tools integrate clinical, laboratory, and ECG parameters to refine risk prediction and guide patient management.

Advanced and Targeted Evaluation of Chest Pain

The subsequent diagnostic and management approach depends on the patient’s clinical presentation, initial evaluation, and risk stratification findings. Patients presenting with STEMI are considered high-risk regardless of scoring results and require immediate reperfusion therapy through PCI or thrombolysis. Individuals with NSTEMI or unstable angina should undergo an early invasive strategy within 24 hours if classified as high-risk. Patients with intermediate risk undergo an invasive approach within 24 to 72 hours or receive functional stress imaging when the diagnosis remains uncertain. In low-risk cases, noninvasive stress testing, such as an exercise tolerance test, nuclear perfusion imaging, or stress echocardiography, is appropriate.

For patients with stable chest pain, further evaluation is guided by pretest probability of CAD, as follows:

• Low pretest probability (<15%): Routine cardiac testing is unnecessary, and alternative causes should be investigated.
• Intermediate pretest probability (15%-85%): Noninvasive functional or anatomic imaging may be considered.
• High pretest probability (>85%): Direct referral for invasive coronary angiography is warranted.

When pulmonary embolism is suspected, computed tomography (CT) pulmonary angiography serves as the preferred diagnostic modality. If aortic dissection is a concern, a CT aortogram should be performed. A D-dimer assay is indicated as an initial screening test in patients with low-to-intermediate risk for pulmonary embolism.

Prognosis

The prognosis of chest pain is highly variable and depends on the underlying etiology. In patients with angina secondary to CAD, outcomes are closely related to the severity of myocardial ischemia, the degree of left ventricular dysfunction, and the presence of comorbid conditions. Stable angina is generally associated with a favorable prognosis when managed with optimal medical therapy and lifestyle interventions. Nevertheless, progression to ACS remains a concern in individuals with multivessel disease or inadequately controlled cardiovascular risk factors.

Unstable angina and NSTEMI represent higher-risk presentations of CAD. Biomarker elevation is absent in unstable angina. However, the short-term risk of myocardial infarction or death remains substantial in the absence of aggressive management. Risk stratification tools, such as the GRACE score, assist in guiding prognosis and therapeutic decisions.

STEMI exhibits a more variable prognosis. Early reperfusion through PCI or thrombolysis markedly improves survival. Outcomes worsen with delays in presentation, failure to achieve timely revascularization, or the development of complications such as heart failure, arrhythmias, or cardiogenic shock. Untreated STEMI carries a high short-term mortality, reaching up to 15% to 20% at 30 days. Mortality decreases to approximately 5% to 7% with prompt reperfusion. Long-term outcomes are largely determined by left ventricular function and adherence to secondary prevention strategies.

Short-term mortality in NSTEMI is lower than in STEMI, but long-term mortality is higher due to older age and the presence of comorbid conditions. CCS generally has an annual mortality of approximately 1% to 2% when optimally treated. Risk increases in the presence of left main or triple-vessel disease or an LVEF less than 40%.[26]

Noncardiac chest pain generally has excellent cardiac outcomes. However, persistent symptoms related to underlying conditions, such as anxiety or musculoskeletal disorders, may significantly impair quality of life if left unaddressed. Early recognition of high-risk features, including rest-associated chest pain, ECG abnormalities, and troponin elevation, is essential for optimizing clinical outcomes. Isolated troponin elevation, ie, occurring in the absence of clinical or ECG evidence of ischemia, is insufficient to predict coronary events and must be interpreted in context.

Complications

Complications after ACS may be classified as mechanical, electrical, or hemodynamic. These events are more common in STEMI due to extensive myocardial necrosis but can also occur in NSTEMI, requiring vigilance during any episode of clinical deterioration. Heart failure may develop with or without hemodynamic compromise and warrants prompt management with diuretics, supplemental oxygen, and ventilatory support as indicated. Hemodynamically unstable patients may require inotropic therapy and mechanical circulatory support. In selected cases, intra-aortic balloon pump placement prior to PCI may be appropriate for extensive infarction accompanied by severe mitral regurgitation and hypotension, even in the absence of overt cardiogenic shock, given the high risk of further deterioration.

Mechanical complications, including ventricular septal defect, acute mitral regurgitation secondary to papillary muscle rupture, and free wall rupture, predominantly occur in STEMI and frequently necessitate urgent surgical intervention. Tachyarrhythmias, such as ventricular tachycardia or ventricular fibrillation, as well as bradyarrhythmias, including atrioventricular block, commonly arise within the first 48 hours and require management tailored to severity and recurrence. Pericarditis or Dressler syndrome may present days to weeks postinfarction and generally respond to nonsteroidal anti-inflammatory drugs and colchicine. Anticoagulation should be avoided in the presence of a large pericardial effusion.

Early recognition and intervention are critical to reduce mortality and improve long-term outcomes. Continuous clinical monitoring, telemetry for arrhythmia detection, and repeat echocardiography, particularly if clinical status deteriorates, are essential for identifying significant mechanical complications, such as acute mitral regurgitation or septal rupture.

Deterrence and Patient Education

The effective management of angina involves not only accurate diagnosis and pharmacologic therapy but also patient education and behavioral interventions aimed at minimizing symptom burden and preventing progression to acute coronary events. Patients should be informed about the characteristic features of cardiac chest pain, including retrosternal discomfort, a pressure-like sensation precipitated by exertion or emotional stress, and relief with rest. Emphasis should be placed on the fact that brief, sharp, or well-localized pain is rarely cardiac in origin, thereby reducing unnecessary anxiety and inappropriate emergency visits.

Risk factor modification is the cornerstone of long-term management. Patients must understand the critical importance of smoking cessation, as complete elimination substantially reduces cardiovascular risk. Strict blood pressure and lipid control, achieved through adherence to prescribed medications and dietary modification, lowers the likelihood of adverse events. Tight glycemic control in diabetes slows the progression of CAD.[27] Moderate aerobic exercise should be encouraged. However, any new or exercise-induced chest discomfort warrants prompt evaluation.

Essential elements of patient education include instruction on the proper use of sublingual nitrates, as well as clear guidance to seek immediate medical attention for chest pain lasting longer than 20 minutes at rest or persisting despite nitrate administration. Clinicians should assist patients in distinguishing true angina from benign causes of chest discomfort, enhancing self-management and reducing unnecessary utilization of emergency services.[28] Patients should also understand that isolated troponin elevations, ie, without classic ischemic symptoms or ECG changes, do not necessarily indicate infarction. Interpretation must consider the full clinical picture.[29]

Explaining the rationale for diagnostic investigations, including stress testing, coronary CT angiography, and troponin measurement, helps alleviate patient anxiety, improve adherence to recommendations, and foster shared decision-making. This approach supports a collaborative clinical relationship and contributes to improved patient outcomes.[30]

Enhancing Healthcare Team Outcomes

Accurate evaluation of chest pain, particularly in differentiating true angina from noncardiac causes, relies on an interprofessional approach grounded in clinical judgment, effective communication, and a commitment to patient safety. Physicians and advanced practice providers direct diagnostic decision-making based on clinical history, ECG findings, and biomarker profiles. Nurses play a critical role in early symptom recognition, ongoing monitoring, and reinforcement of patient education, particularly regarding the features of ischemic pain and the correct use of medications such as sublingual nitrates. Emergency personnel must be prepared to identify high-risk features, including prolonged rest pain or evolving ECG abnormalities, and coordinate prompt interventions to prevent delays.

Consistent and clear communication among team members ensures that dynamic changes, such as recurrent chest pain or hemodynamic instability, are escalated without delay. A flattened team hierarchy empowers nurses and frontline staff to report key clinical observations that may trigger timely reassessment. Shared strategies, including standardized chest pain pathways, early discharge protocols for low-risk patients, and structured follow-up planning, enhance safety, reduce unnecessary admissions, and support patient-centered care. By coordinating roles, applying sound clinical reasoning, and maintaining open communication, the interprofessional team optimizes diagnostic accuracy and patient outcomes in the management of angina and acute chest pain.

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Disclosure: Maria Giulia Bellicini declares no relevant financial relationships with ineligible companies.

Disclosure: Pirbhat Shams declares no relevant financial relationships with ineligible companies.