In a patient admitted with chest tightness (spasm) and a normal B-type natriuretic peptide level, what other diagnoses should be considered?

Differential Diagnosis for Chest Spasm with Normal BNP

In a patient with chest tightness and normal BNP, acute coronary syndrome (ACS) remains the most critical diagnosis to exclude immediately, followed by non-cardiac causes including esophageal spasm, musculoskeletal pain, pulmonary embolism, and anxiety disorders. 1

Immediate Diagnostic Priorities

1. Rule Out Acute Coronary Syndrome

• Serial ECGs at 15-30 minute intervals are mandatory if the initial ECG is non-diagnostic but clinical suspicion remains high, as ST-segment changes may evolve over time 1
• Cardiac troponin measurement is the preferred biomarker and must be obtained in all patients with chest discomfort consistent with ACS 1
• Repeat troponin at 8-12 hours after symptom onset if the initial value is negative within 6 hours, accounting for the release kinetics of cardiac markers 1
• Normal BNP does not exclude ACS; BNP elevation in acute coronary syndromes occurs but is not required for diagnosis (median BNP in MI ≈203 pg/mL) 2, 3

2. Consider Early Marker Strategy

• Myoglobin plus troponin measured at baseline and 90 minutes may detect early MI in patients presenting within 6 hours of symptom onset 1
• 2-hour delta troponin can improve early detection when measured serially 1

Non-Cardiac Differential Diagnoses to Evaluate

Esophageal Disorders

• Esophageal spasm presents with chest tightness that mimics angina, often relieved by nitroglycerin (confounding diagnosis)
• Gastroesophageal reflux disease (GERD) causes burning chest discomfort, typically postprandial
• Consider trial of proton pump inhibitor if cardiac workup is negative

Musculoskeletal Causes

• Costochondritis produces chest wall tenderness reproducible on palpation
• Intercostal muscle strain causes pain with movement or deep breathing
• Physical examination revealing point tenderness suggests musculoskeletal origin

Pulmonary Causes

• Pulmonary embolism can elevate BNP (>500 pg/mL in high-risk PE) but may present with normal BNP in smaller emboli 4, 3
• Pneumothorax causes sudden-onset pleuritic chest pain
• Pleuritis produces sharp, positional chest pain
• Obtain chest X-ray and consider D-dimer if PE risk factors present 1

Anxiety and Panic Disorders

• Panic attacks cause chest tightness, dyspnea, and palpitations
• Diagnosis of exclusion after cardiac and pulmonary causes ruled out
• Associated symptoms: hyperventilation, paresthesias, sense of impending doom

Critical Pitfalls to Avoid

Do not assume normal BNP excludes all cardiac pathology—BNP primarily reflects ventricular wall stress from volume/pressure overload, not acute ischemia 5. Unstable angina with preserved ventricular function typically shows normal or minimally elevated BNP 6.

Do not stop at a single negative troponin—troponin rises 3-6 hours after myocardial injury begins, requiring serial measurement to exclude evolving MI 1.

Do not overlook atypical presentations—older adults and women frequently present with dyspnea, nausea, or fatigue rather than classic chest pain 1.

Recommended Diagnostic Algorithm

1. Obtain serial ECGs (every 15-30 min if symptomatic) and baseline troponin immediately 1
2. Repeat troponin at 8-12 hours from symptom onset if initial negative 1
3. Chest X-ray to evaluate for pneumothorax, pneumonia, or pulmonary congestion 1
4. Consider stress testing or coronary CT angiography if troponins negative but intermediate ACS risk 1
5. Evaluate for non-coronary causes including esophageal disorders, musculoskeletal pain, and pulmonary embolism based on clinical features 1

Prognostic Considerations

Even with normal BNP, patients with chest pain and positive troponins face significantly elevated mortality risk—each 100 pg/mL BNP increase correlates with 35% higher relative risk of death, but troponin elevation independently predicts adverse outcomes 2, 3.