How to manage a patient with shortness of breath, including differential diagnosis?

Management of Shortness of Breath with Differential Diagnosis

Initial Assessment Strategy

Begin by obtaining BNP or NT-proBNP levels in all patients presenting with acute dyspnea, as this single test has the highest diagnostic utility for distinguishing cardiac from non-cardiac causes. 1, 2, 3

Critical History Elements

Ask specifically about:

• Orthopnea and paroxysmal nocturnal dyspnea - these strongly suggest cardiac causes, particularly heart failure 2, 3
• Onset, duration, and timing - acute onset (<hours) suggests pulmonary embolism, pneumothorax, or acute heart failure; chronic (>4-8 weeks) suggests COPD, interstitial lung disease, or chronic heart failure 3
• Exertional component - dyspnea worsening with activity suggests cardiac causes (HFpEF, HFrEF, valvular disease) or pulmonary disease 2
• Associated symptoms - fever suggests pneumonia or COVID-19; chest pain suggests cardiac ischemia or pulmonary embolism; cough with sputum suggests COPD or pneumonia 1, 3
• Risk factors - hypertension, diabetes, and atrial fibrillation increase likelihood of heart failure; smoking history suggests COPD or interstitial lung disease 2, 3

Essential Physical Examination

Systematically assess for cardiac congestion, pulmonary pathology, and alternative causes of dyspnea: 2, 3

Cardiovascular examination:

• Jugular venous distention (suggests volume overload) 2
• S3 gallop (indicates heart failure) 2
• Cardiac murmurs (suggests valvular disease, particularly aortic stenosis) 1, 2
• Pedal edema distribution (bilateral suggests cardiac or renal; unilateral suggests venous insufficiency) 2

Pulmonary examination:

• Bibasilar crackles/rales (suggests heart failure or pneumonia) 2, 3
• End-expiratory wheezes (suggests COPD or asthma) 1, 4
• Percussion dullness (suggests pleural effusion) 2
• Decreased breath sounds (suggests pneumothorax, effusion, or severe COPD) 3

Differential Diagnosis Framework

Primary Cardiac Causes

• Heart failure with preserved ejection fraction (HFpEF) - most common in elderly with hypertension, presents with exertional dyspnea and pedal edema 2
• Heart failure with reduced ejection fraction (HFrEF) - presents with orthopnea, paroxysmal nocturnal dyspnea, S3 gallop 2
• Valvular heart disease - particularly aortic stenosis presenting with exertional dyspnea, angina, or syncope 1, 2
• Acute coronary syndrome - consider in patients with chest pain and cardiac risk factors 3

Primary Pulmonary Causes

• COPD exacerbation - presents with increased dyspnea, cough, sputum production, and wheezing in patients with smoking history 1, 3, 5
• Pneumonia - presents with fever, cough, and infiltrates on chest X-ray 1, 4
• Asthma exacerbation - presents with wheezing, chest tightness, and response to bronchodilators 1, 3
• Pulmonary embolism - acute onset dyspnea with pleuritic chest pain 3, 4
• Interstitial lung disease - chronic progressive dyspnea with bibasilar crackles 3
• COVID-19 pneumonia - fever, dry cough, dyspnea with bilateral infiltrates 1

Other Causes

• Chronic kidney disease - presents with volume overload and edema 2
• Chronic venous insufficiency - unilateral or bilateral leg edema without orthopnea 2
• Foreign body aspiration - persistent symptoms despite treatment for presumed COPD or pneumonia 4

Diagnostic Algorithm

Step 1: Obtain BNP/NT-proBNP

• BNP >100 pg/mL or NT-proBNP >300 pg/mL - proceed to echocardiography for cardiac evaluation 1, 2, 3
• BNP <100 pg/mL - cardiac cause unlikely (sensitivity 0.96-0.99, specificity 0.61-0.76); focus on pulmonary causes 1

Important caveat: BNP levels increase with age and chronic kidney disease; use age-adjusted cutoffs (NT-proBNP <125 pg/mL for age <75, <450 pg/mL for age ≥75) 1

Step 2: Obtain Chest Radiography

Chest X-ray is the first-line imaging modality for all patients with dyspnea: 3

• Cardiomegaly with pulmonary vascular congestion - suggests heart failure 1, 3
• Infiltrates - suggests pneumonia 3
• Pleural effusion - suggests heart failure, pneumonia, or malignancy 3
• Hyperinflation with flattened diaphragms - suggests COPD 3
• Normal chest X-ray - consider pulmonary embolism, early interstitial disease, or cardiac causes 3

Step 3: Obtain Transthoracic Echocardiography

Echocardiography is the gold standard for assessing cardiac function and should be obtained in all patients with elevated BNP or suspected cardiac dyspnea: 2, 3

• Assesses left ventricular ejection fraction (distinguishes HFrEF from HFpEF) 2
• Evaluates diastolic function 2
• Identifies valvular abnormalities (particularly aortic stenosis with valve area <1.0 cm²) 1, 2
• Assesses right ventricular function and estimates pulmonary artery pressure 2

Management Based on Diagnosis

Heart Failure (BNP elevated, echocardiography confirms diagnosis)

• Increase diuretic therapy (e.g., furosemide) for volume overload 3
• Optimize afterload reduction with ACE inhibitors or ARBs 3
• Admit patients with severe symptoms, hypoxia, or hemodynamic instability 1

COPD/Asthma Exacerbation

• Bronchodilators: albuterol nebulization (2.5-5 mg every 4-6 hours) 6, 7
• Systemic corticosteroids: prednisone 40-60 mg daily for 5-7 days 3, 7
• Supplemental oxygen to maintain SpO2 >90% 3
• Antibiotics if evidence of bacterial infection 4

Critical warning: Albuterol should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency and cardiac arrhythmias 6

Pneumonia

• Broad-spectrum antibiotics based on suspected pathogen and severity 4
• Supplemental oxygen 3
• Consider COVID-19 testing if fever, dry cough, and bilateral infiltrates 1

Indications for Specialist Referral

Refer to Cardiology:

• Cardiac symptoms or risk factors with elevated BNP 3
• Suspected HFpEF (normal ejection fraction with diastolic dysfunction) 3
• Elevated tricuspid regurgitation velocity on echocardiography 3
• Severe valvular disease requiring surgical evaluation 1

Refer to Pulmonology:

• Chronic dyspnea of unclear etiology despite initial workup 3
• Suspected interstitial lung disease 3
• Post-COVID complications with persistent dyspnea 3
• Symptoms not responding to standard COPD/asthma therapy (consider foreign body aspiration) 4

Common Pitfalls to Avoid

• Do not rely solely on clinical judgment - emergency physician clinical assessment has sensitivity of only 0.49 for heart failure diagnosis; BNP measurement significantly improves diagnostic accuracy (AUC 0.90 vs 0.86 for clinical judgment alone) 1
• Do not assume COPD/pneumonia without considering alternative diagnoses - foreign body aspiration can mimic COPD exacerbation with persistent wheezing despite appropriate therapy 4
• Do not use valve area alone for aortic stenosis diagnosis - must consider in combination with flow rate, pressure gradient, and ventricular function 1
• Do not dismiss low BNP in patients with symptoms <4 hours - BNP may be falsely low in early acute heart failure 1