What diagnostic investigations are indicated for a 38‑year‑old married patient presenting with pallor and exertional dyspnoea, a regular cardiac rhythm and clear lung sounds?

Diagnostic Workup for Pallor and Exertional Dyspnea

Order a complete blood count (CBC) immediately to evaluate for anemia, followed by an electrocardiogram (ECG) and B-type natriuretic peptide (BNP) level to assess for cardiac causes. 1

Initial Laboratory Testing

• CBC with differential is the first-line test because pallor combined with exertional dyspnea strongly suggests anemia as the underlying cause, which is readily diagnosed and often reversible 2
• The combination of pallor (suggesting anemia) and dyspnea on exertion with clear lung fields and regular heart rhythm makes hematologic causes most likely before pursuing more complex cardiac or pulmonary workup 2

Cardiac Evaluation

• Obtain a 12-lead ECG to screen for arrhythmias, ischemic changes, or structural abnormalities that could explain exertional symptoms, as this is recommended for all patients presenting with cardiac symptoms including exertional dyspnea 3
• Measure BNP or NT-proBNP (target BNP ≥100 pg/mL as threshold) because this is the single most important test when initial evaluation is unrevealing, with BNP <100 pg/mL having 96-99% sensitivity for ruling out heart failure 1
• If BNP is elevated (≥100 pg/mL), proceed to transthoracic echocardiography to assess for heart failure with preserved ejection fraction (HFpEF), valvular disease, diastolic dysfunction, or pulmonary hypertension 1

Pulmonary Assessment

• Chest radiograph is appropriate (ACR appropriateness score 9) for initial evaluation to detect cardiomegaly, pulmonary congestion, or pleural effusions, though it provides limited diagnostic specificity 4
• Pulmonary function tests (PFTs) including spirometry and diffusing capacity (DLCO) should be obtained if the chest radiograph is abnormal or if pulmonary disease is suspected based on history 5

Sequential Diagnostic Algorithm

If CBC shows anemia:

• Proceed with iron studies, vitamin B12, folate, reticulocyte count, and peripheral smear to determine etiology 2

If CBC is normal and BNP is elevated:

• Perform echocardiography to evaluate left ventricular ejection fraction, diastolic parameters, valve function, and right ventricular systolic pressure 1
• Consider referral to cardiology if echocardiography reveals HFpEF, valvular disease, or pulmonary hypertension 1

If CBC and BNP are both normal:

• Consider cardiopulmonary exercise testing (CPET) to distinguish between cardiac limitation, pulmonary limitation, deconditioning, or exercise-induced bronchoconstriction 5, 1
• CPET can categorize abnormalities as typical of oxygen delivery (cardiovascular), oxygen utilization (peripheral muscle), or ventilatory disorders, guiding appropriate follow-up testing 5

Common Pitfalls to Avoid

• Do not assume a negative stress test excludes all cardiac causes—it primarily rules out obstructive coronary disease but not HFpEF, valvular disease, or pulmonary hypertension 1
• Do not overlook anemia as a cause simply because the patient is young; pallor is a specific physical finding that warrants immediate hematologic evaluation 2
• Do not delay BNP testing when initial cardiac and pulmonary workup is unrevealing, as clinical evaluation alone has low sensitivity (59%) for cardiac causes despite high specificity 1
• Exercise-induced bronchoconstriction may not be detected on resting pulmonary function tests and requires exercise challenge or bronchoprovocation testing if suspected 1

Additional Considerations

• Evaluate for thyroid dysfunction, metabolic acidosis, or other systemic causes if initial workup is unrevealing 1
• Consider CT chest if interstitial lung disease or pulmonary vascular abnormalities are suspected based on PFTs or clinical presentation 1
• Deconditioning is a common cause of exertional dyspnea in patients with normal resting cardiac and pulmonary function and can be confirmed with CPET 1