Diagnostic Approach to Dyspnea on Exertion

Initial Evaluation

The American College of Radiology recommends chest radiography to identify cardiomegaly, pulmonary congestion, pleural effusion, pneumonia, or masses 1, 2
The American College of Cardiology suggests electrocardiography to detect ischemic changes, arrhythmias, or chamber enlargement 1, 3, 2
Transthoracic echocardiography is recommended to assess left ventricular systolic and diastolic function, valvular disease, right ventricular strain, and pericardial effusion 1, 3
Measurement of B-type natriuretic peptide (BNP) or NT-proBNP is suggested, with BNP <100 pg/mL or NT-proBNP <125 pg/mL effectively excluding heart failure 4, 3, 2

The American College of Cardiology states that coronary artery disease is the most common cardiac cause of dyspnea when myocardial oxygen supply does not meet demand 3, 2
Heart Failure with Preserved Ejection Fraction (HFpEF) is a potential diagnosis in persons with dyspnea and exertional intolerance, with diagnostic criteria requiring EF ≥50%, elevated natriuretic peptides, and objective evidence of structural/functional cardiac abnormality 4
Valvular heart disease, such as aortic stenosis or mitral valve disease, may cause elevated left atrial pressures and pulmonary congestion 3, 2

Chronic Obstructive Pulmonary Disease (COPD) should be considered in patients with smoking history presenting with increased dyspnea 2
Asthma may present with "chest tightness" specifically related to bronchoconstriction 2
Interstitial Lung Disease presents with progressive dyspnea, dry cough, and bibasilar crackles, with patients describing "air hunger" due to restrictive mechanics 2

History and physical examination alone have high specificity (96%) but low sensitivity (59%) for cardiac causes, and should not be relied upon alone 1, 3, 2
Normal chest radiography does not exclude cardiac disease, particularly early heart failure or diastolic dysfunction 3, 2
"Chest tightness" is relatively specific for bronchoconstriction, while "air hunger" suggests restrictive mechanics 2
Absence of edema does not exclude heart failure, as many patients with HFpEF or early heart failure present without peripheral edema 4

Cardiology referral is warranted to exclude alternative diagnoses, optimize guideline-directed medical therapy, and identify clinical trial eligibility 4
Pulmonology referral is suggested if interstitial lung disease, pulmonary hypertension, or unexplained hypoxemia is suspected 2
Specialty referral to a multidisciplinary dyspnea clinic may be necessary when diagnosis remains elusive after initial workup 2

The American College of Radiology recommends obtaining a chest radiograph (PA and lateral) to identify cardiomegaly, pulmonary congestion, pleural effusion, interstitial lung disease, or masses 5

If BNP <100 pg/mL, consider pulmonary function testing with spirometry to evaluate for COPD or asthma, and if chest radiograph shows bibasilar reticular abnormalities, consider interstitial lung disease and obtain high-resolution CT chest, as recommended by the European Respiratory Review and American Journal of Respiratory and Critical Care Medicine 6, 7, 5
Perform cardiopulmonary exercise testing (CPET) when resting tests are normal but diagnosis remains elusive, as this definitively distinguishes cardiac, pulmonary, vascular, and deconditioning causes, according to Circulation and European Heart Journal 8, 9, 10

The American Journal of Respiratory and Critical Care Medicine suggests that if HRCT shows UIP pattern, do not perform surgical lung biopsy, but if HRCT shows probable UIP, indeterminate for UIP, or alternative diagnosis pattern, consider surgical lung biopsy in appropriate surgical candidates after multidisciplinary discussion 7
Exclude other causes including drug toxicity, environmental exposures, and connective tissue disease, as recommended by the European Respiratory Review and American Journal of Respiratory and Critical Care Medicine 6, 7

Evaluate VE/VCO2 slope, VE/MVV ratio, O2 pulse trajectory, and SpO2 during exercise, as recommended by Circulation and European Heart Journal, to assess for ventilatory inefficiency, pulmonary mechanical limitation, myocardial ischemia, and disease severity 8, 9, 10