What tests should be ordered for a patient presenting with dyspnea (shortness of breath) on exertion, stable vital signs, and gastrointestinal symptoms that improved with Zofran (ondansetron)?

Diagnostic Testing for Dyspnea on Exertion with Gastrointestinal Symptoms

Begin with chest radiography, electrocardiogram, complete blood count, basic metabolic panel, and spirometry as your initial diagnostic workup, followed by BNP or NT-proBNP measurement to differentiate cardiac from non-cardiac causes. 1, 2

Initial Laboratory and Imaging Studies

First-line testing should include:

• Chest radiography to identify cardiomegaly, pulmonary congestion, pleural effusion, pneumonia, or masses 3, 1, 2
• Electrocardiogram to detect ischemic changes, arrhythmias, chamber enlargement, or conduction abnormalities 1, 4, 2
• Complete blood count to evaluate for anemia (which can cause both dyspnea and decreased appetite) 1, 5
• Basic metabolic panel to assess for electrolyte disturbances, renal dysfunction, or metabolic disorders that may contribute to dyspnea 1, 5
• Spirometry to identify obstructive or restrictive pulmonary patterns 1, 6

Cardiac Biomarker Testing

BNP or NT-proBNP measurement is critical for risk stratification:

• BNP <100 pg/mL or NT-proBNP <125 pg/mL effectively excludes heart failure with 96-99% sensitivity 4, 2
• This single test is the most important initial diagnostic tool when cardiac causes are suspected 4
• Elevated levels warrant echocardiography for definitive cardiac evaluation 4, 2

Pulse Oximetry Assessment

Oxygen saturation monitoring should be performed:

• Resting pulse oximetry to assess for hypoxemia 3, 1
• Exercise oximetry if initial workup is non-diagnostic, as SpO2 dropping below 90% during exertion indicates pulmonary limitation 3
• This helps differentiate cardiac causes (SpO2 ≥90% throughout exercise) from pulmonary causes (SpO2 may drop <90%) 3

Secondary Diagnostic Testing Based on Initial Results

If initial testing is non-diagnostic, proceed with:

• Transthoracic echocardiography to assess left ventricular systolic and diastolic function, valvular disease, right ventricular strain, and pericardial effusion 2
• Point-of-care ultrasound (POCUS) can be added when diagnostic uncertainty persists, as it increases correct diagnoses for congestive heart failure (79-100% sensitivity), pleural effusion (89-100% sensitivity), and pneumonia (92% sensitivity) 3

Cardiopulmonary Exercise Testing for Unexplained Dyspnea

When standard evaluation remains non-diagnostic:

• Cardiopulmonary exercise testing (CPX) differentiates cardiac from pulmonary causes through specific parameters 3
• Cardiac limitation shows: reduced peak VO2, normal pre-exercise pulmonary function tests, SpO2 ≥90% throughout exercise, and no post-exercise FEV1 decline 3
• Pulmonary limitation shows: reduced peak VO2, abnormal baseline pulmonary function tests, SpO2 potentially dropping <90%, and ≥15% decrease in FEV1 or peak expiratory flow post-exercise (indicating exercise-induced bronchospasm) 3

Clinical Context Considerations

Important caveats for this presentation:

• The gastrointestinal symptoms that improved with ondansetron suggest a possible non-cardiac etiology, but do not exclude cardiac disease 2
• History and physical examination alone have only 59% sensitivity for cardiac causes despite 96% specificity, so objective testing is mandatory 2
• Decreased appetite and substernal discomfort could represent atypical anginal equivalents, particularly in women, elderly, or diabetic patients 2
• Normal vital signs do not exclude significant pathology, as many patients with heart failure with preserved ejection fraction or early cardiac disease present without hemodynamic instability 2

Algorithmic Approach

Follow this sequence:

1. Order chest X-ray, ECG, CBC, BMP, spirometry, and BNP/NT-proBNP simultaneously 1, 2
2. If BNP elevated or ECG/chest X-ray abnormal → proceed to echocardiography 4, 2
3. If spirometry shows obstruction/restriction → consider pulmonary function testing and pulmonology referral 1
4. If all initial tests normal → consider cardiopulmonary exercise testing to differentiate cardiac vs. pulmonary vs. deconditioning 3, 6
5. If diagnosis remains elusive → refer to multidisciplinary dyspnea clinic or specialty care 1, 2