Chest Pain: What Could Be Causing It

How Common Is Chest Pain, and Why Does It Have So Many Causes

Chest pain is the second most common reason for emergency department visits in the United States, generating approximately 6.5 million presentations annually according to CDC National Hospital Ambulatory Medical Care Survey data [1]. The chest houses the heart, lungs, esophagus, major blood vessels, ribs, muscles, and a dense network of nerves. Pain originating from any of these structures can feel remarkably similar, which makes differential diagnosis both high-stakes and genuinely difficult.

A 2010 analysis published in the BMJ found that among patients presenting to primary care with chest pain, musculoskeletal causes accounted for 49% of cases, while stable coronary artery disease explained only 11% [2]. The picture shifts in the emergency department. A multicenter study by Backus et al. (N=2,440) demonstrated that 5.1% of ED chest pain patients had acute coronary syndrome, 8.4% had other cardiac diagnoses, and the remaining 86.5% had non-cardiac etiologies [3]. These numbers carry a clear message: most chest pain is not a heart attack, but the small percentage that is demands rapid identification.

The visceral afferent nerve fibers from the heart, esophagus, and other thoracic organs converge on the same spinal cord segments (T1-T5). This convergence explains why a patient with acid reflux can experience burning substernal pressure that mimics angina almost exactly [4]. A 2005 systematic review by Katerndahl and Trammell found that physicians could not reliably distinguish cardiac from non-cardiac chest pain based on history alone, achieving correct classification in only 69-84% of cases [5].

Cardiac Causes: When the Heart Is the Problem

Cardiac causes account for approximately 13.5% of all ED chest pain presentations [3]. Acute coronary syndrome (ACS), including ST-elevation myocardial infarction (STEMI), non-ST-elevation MI (NSTEMI), and unstable angina, represents the most dangerous subset. The classic presentation involves substernal pressure or squeezing radiating to the left arm or jaw, accompanied by diaphoresis and dyspnea. But "classic" is misleading.

A landmark analysis from the National Registry of Myocardial Infarction (N=434,877) published in JAMA found that 33% of patients with confirmed MI did not present with chest pain at all [6]. Women, patients with diabetes, and adults over age 75 were most likely to have atypical presentations. Dr. John Canto, the study's lead author, noted: "The absence of chest pain in acute MI is associated with a significant treatment delay and a nearly threefold increase in hospital mortality."

Beyond ACS, other cardiac causes include:

Stable angina. Predictable exertional chest tightness relieved by rest or nitroglycerin within 5 minutes. Coronary artery disease confirmed by stress testing or angiography affects roughly 20.1 million U.S. adults according to AHA 2023 statistics [7].

Pericarditis. Sharp, pleuritic pain that worsens when lying flat and improves when leaning forward. Often preceded by a viral illness. ECG shows diffuse ST elevation without reciprocal changes.

Aortic dissection. Sudden, tearing pain radiating to the back. This is rare (2.6-3.5 per 100,000 person-years) but carries 1-2% mortality per hour if untreated [8]. A systolic blood pressure differential greater than 20 mmHg between arms raises suspicion.

Myocarditis. Post-viral chest pain with troponin elevation in younger patients. Cardiac MRI with late gadolinium enhancement confirms the diagnosis.

How the HEART Score Changes Chest Pain Triage

The HEART score (History, ECG, Age, Risk factors, Troponin) has become the dominant risk stratification tool for undifferentiated chest pain in the emergency department. Each element receives 0-2 points for a total ranging from 0 to 10.

A prospective validation study by Backus et al. (N=2,440) found that patients scoring 0-3 had a 30-day major adverse cardiac event (MACE) rate of just 1.7%, while those scoring 7-10 had a MACE rate of 72.7% [3]. The 2021 ACC/AHA Chest Pain Guidelines formally endorsed the HEART score as a Class I recommendation for evaluating acute chest pain in the ED, stating: "The HEART score is recommended for risk stratification in patients with acute chest pain to identify patients who are candidates for early discharge" [9].

Patients in the low-risk category (score 0-3) can often be discharged directly from the ED without further cardiac testing, which reduces unnecessary admissions and healthcare spending. A 2020 Annals of Emergency Medicine cluster-randomized trial (N=31,621) demonstrated that HEART Pathway implementation decreased objective cardiac testing by 12.1% without any increase in missed MI at 30 days [10].

The score is not perfect. It performs less well in patients under 40 and does not account for pulmonary embolism or aortic dissection. These diagnoses require separate risk assessment tools like the Wells score or the aortic dissection detection risk score (ADD-RS).

Gastrointestinal Causes: The Great Mimics

Gastroesophageal reflux disease (GERD) is the single most common cause of non-cardiac chest pain, responsible for an estimated 25-60% of cases depending on the study population [11]. The pain is typically burning, substernal, worse after meals or when supine, and may respond to antacids. The overlap with cardiac pain is substantial enough that an empiric proton pump inhibitor (PPI) trial is sometimes used diagnostically. A 2005 American Journal of Gastroenterology meta-analysis found the PPI test had a pooled sensitivity of 80% and specificity of 74% for identifying GERD-related chest pain [12].

Esophageal spasm produces sudden, intense squeezing pain that can be indistinguishable from angina. Barium swallow may show a "corkscrew esophagus," and high-resolution manometry confirms the diagnosis. Calcium channel blockers or peppermint oil can reduce spasm frequency.

Esophageal hypersensitivity. Some patients have normal acid exposure and normal motility but experience chest pain from heightened visceral perception. This condition, now termed "functional chest pain of presumed esophageal origin" under the Rome IV criteria, may respond to low-dose tricyclic antidepressants. A randomized trial of imipramine 50 mg nightly (N=60) showed a 52% reduction in chest pain episodes versus placebo [13].

Peptic ulcer disease and biliary colic occasionally present as lower chest or epigastric pain. These are less commonly confused with cardiac disease but merit consideration in patients with appropriate risk factors.

Musculoskeletal Causes: More Common Than Most Patients Expect

Chest wall pain is the most frequent cause of chest pain in the primary care setting. The Marburg Heart Score study published in the BMJ found that musculoskeletal causes accounted for 49% of chest pain presentations to general practitioners [2]. Patients are often surprised by this diagnosis because they associate chest pain exclusively with the heart.

Costochondritis is inflammation of the costochondral or costosternal joints. It produces sharp, localized, reproducible tenderness at the junction of the ribs and sternum. It affects ribs 2-5 most frequently and may follow upper respiratory infection, repetitive strain, or occur without clear cause. Treatment is NSAIDs and reassurance. Pain typically resolves within weeks, though some cases persist for months.

Tietze syndrome resembles costochondritis but involves visible swelling of a single costochondral joint, usually the second or third rib. It is less common and tends to affect adults under 40.

Muscle strain. The intercostal muscles, pectoralis major, and serratus anterior can all produce chest pain after unaccustomed exercise, heavy lifting, or prolonged coughing. The pain worsens with movement, deep breathing, or palpation. History of recent physical activity typically clarifies the diagnosis.

Thoracic spine pathology. Degenerative disc disease, vertebral compression fractures, and thoracic radiculopathy can refer pain anteriorly to the chest wall. These conditions are underrecognized. A provocative maneuver called the "doorbell sign," applying pressure to the thoracic spinous processes, may reproduce the chest pain and point toward a spinal origin [14].

Pulmonary Causes: Breathing-Related Chest Pain

Pulmonary conditions typically produce pleuritic pain, meaning it sharpens with inspiration, coughing, or deep breathing. This character helps distinguish them from cardiac causes, which are usually pressure-like and unrelated to respiration.

Pulmonary embolism (PE) deserves particular attention because it is both common and frequently missed. A 2006 JAMA study found that PE was the most common missed diagnosis contributing to preventable deaths in hospitalized patients [15]. Chest pain in PE is usually sudden-onset and pleuritic, accompanied by dyspnea and tachycardia. The Wells score and D-dimer testing guide the diagnostic pathway, with CT pulmonary angiography serving as the confirmatory test.

Pneumothorax causes abrupt, unilateral, pleuritic chest pain with dyspnea. Tall, thin young men and patients with underlying lung disease (COPD, cystic fibrosis) are at highest risk. Primary spontaneous pneumothorax has an incidence of 7.4-18 per 100,000 males per year [16]. Small pneumothoraces (<2 cm rim on chest X-ray) may be managed conservatively with observation.

Pneumonia and pleuritis. Infectious or inflammatory involvement of the lung parenchyma or pleura produces fever, cough, and pleuritic chest pain. Chest X-ray or point-of-care ultrasound confirms the diagnosis.

Asthma and reactive airway disease can cause chest tightness that patients describe as pain. This is particularly common in younger patients and those with exercise-induced bronchospasm.

Psychological Causes: The Anxiety-Chest Pain Connection

Panic disorder and generalized anxiety disorder are present in 30-40% of patients evaluated for non-cardiac chest pain, a rate roughly four times higher than in the general population [17]. Panic attacks produce sudden chest tightness, palpitations, shortness of breath, diaphoresis, and a sense of impending doom. The symptom overlap with ACS is striking.

A prospective study by Huffman et al. published in the Annals of Internal Medicine found that 25% of patients presenting to the ED with chest pain met criteria for a current panic disorder, yet only 2% received this diagnosis during their visit [18]. The result is a pattern of repeated ED visits, serial cardiac testing, and escalating anxiety.

Psychological causes should be diagnoses of inclusion, not exclusion. Simply ruling out cardiac disease does not reassure most anxious patients. Cognitive behavioral therapy (CBT) has the strongest evidence base. A 2007 Cochrane review found that CBT reduced chest pain frequency by 33% and improved quality of life at 3-12 months compared to usual care [19]. SSRIs, particularly sertraline and paroxetine, also reduce non-cardiac chest pain episodes, though data from large randomized trials remain limited.

Diagnostic Workup: What Tests to Expect

The evaluation of chest pain follows a structured sequence aimed at rapidly identifying or excluding life-threatening causes before pursuing less urgent diagnoses.

Immediate assessment. ECG within 10 minutes of arrival is the standard for all ED chest pain presentations. High-sensitivity cardiac troponin (hs-cTn) measurement at presentation and at 1-3 hours enables the 0/1-hour or 0/3-hour rule-out algorithms endorsed by the ESC. The 0/1-hour algorithm rules out MI in over 60% of patients at first blood draw [20].

Risk stratification. The HEART score, TIMI score, or GRACE score guides disposition decisions. Low-risk patients may be discharged; intermediate-risk patients may undergo stress testing or coronary CT angiography; high-risk patients proceed to invasive angiography.

Imaging. Chest X-ray remains the initial imaging study for most chest pain presentations. CT pulmonary angiography is ordered when PE is suspected. Coronary CT angiography (CCTA) has gained favor as a first-line test in low-to-intermediate risk chest pain. The SCOT-HEART trial (N=4,146) published in The Lancet showed that adding CCTA to standard care reduced the rate of fatal and nonfatal MI by 41% at 5 years [21].

GI evaluation. If cardiac and pulmonary causes are excluded, upper endoscopy, esophageal pH monitoring, or an empiric PPI trial may clarify a gastrointestinal origin.

Psychiatric screening. The PHQ-4 or GAD-7 can identify anxiety or depression contributing to chest pain. These screening tools take less than 2 minutes and are validated across multiple languages and populations.

Treatment: Matching Therapy to the Cause

Treatment depends entirely on the underlying diagnosis. There is no generic "chest pain treatment."

ACS. Dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor), anticoagulation, and urgent or emergent percutaneous coronary intervention (PCI) for STEMI. NSTEMI patients with high-risk features proceed to angiography within 24 hours per ACC/AHA guidelines [9].

GERD-related chest pain. PPI therapy (omeprazole 20-40 mg daily or equivalent) for 8 weeks. Lifestyle modifications include elevating the head of the bed, avoiding meals within 3 hours of lying down, and reducing caffeine, alcohol, and fatty foods.

Musculoskeletal pain. NSAIDs (ibuprofen 400-600 mg three times daily or naproxen 500 mg twice daily) for 1-2 weeks. Topical diclofenac or lidocaine patches for localized chest wall tenderness. Physical therapy referral if pain persists beyond 4-6 weeks.

Pulmonary embolism. Anticoagulation with a direct oral anticoagulant (rivaroxaban 15 mg twice daily for 21 days, then 20 mg daily; or apixaban 10 mg twice daily for 7 days, then 5 mg twice daily). Duration is typically 3-6 months for provoked PE and indefinite for unprovoked or recurrent PE [22].

Panic disorder. CBT (8-12 weekly sessions) as first-line therapy. SSRI initiation if symptoms persist. Benzodiazepines should be reserved for acute rescue only due to dependence risk. Reassurance alone, without structured follow-up, does not reduce recurrent ED visits.

Patients discharged from the ED with a diagnosis of "non-cardiac chest pain" should receive a clear follow-up plan with their primary care physician within 1-2 weeks. A 2014 study in Heart found that structured follow-up reduced repeat ED visits by 40% compared to discharge without arranged outpatient care [23].