What is the next step in workup for a patient with normal 2D echocardiogram (2D echo) results, normal ejection fraction (EF), normal N-terminal pro b-type natriuretic peptide (NT Pro BNP), normal troponin (trop-i), and normal liver function tests (LFTs) and renal function tests (RFTs)?

Further Workup for Patient with Normal Cardiac Testing

Given the completely normal initial cardiac workup (normal 2D echo with EF 56%, normal NT-proBNP, normal troponin, normal liver and renal function), the next step depends entirely on the patient's presenting symptoms and clinical context, which are not specified in your question.

Critical Missing Information

Without knowing the patient's presenting complaint, further workup cannot be appropriately directed. The tests you've listed effectively rule out:

• Acute coronary syndrome (normal troponin) 1
• Systolic heart failure (normal EF and NT-proBNP) 1
• Significant diastolic dysfunction (normal NT-proBNP makes HFpEF unlikely) 1
• Acute cardiac injury or decompensation 1

Symptom-Directed Next Steps

If Patient Has Dyspnea or Exercise Intolerance

Review the 2D echo report for diastolic function parameters that may have been missed: 1

• Left atrial volume index (LAVI >34 mL/m²) 1
• E/e' ratio (≥13 suggests elevated filling pressures) 1
• Mean e' velocity (<9 cm/s indicates diastolic dysfunction) 1
• Tricuspid regurgitation velocity 1

If diastolic parameters are borderline or the echo was limited, consider: 1

• Diastolic stress echocardiography with semi-supine bicycle exercise to assess E/e' and pulmonary artery pressures during exertion 1
• Cardiopulmonary exercise testing (CPET) to objectively measure peak oxygen consumption, ventilatory equivalent for CO2, and end-tidal CO2 pressure 1

If Patient Has Hypertension

The 2024 ESC Hypertension Guidelines recommend assessing for hypertension-mediated organ damage (HMOD): 1

• 12-lead ECG to evaluate for left ventricular hypertrophy and atrial fibrillation 1
• Urine albumin-to-creatinine ratio (ACR) to detect early renal damage 1
• Consider coronary artery calcium (CAC) scoring by cardiac CT if it would change management decisions 1
• Consider carotid-femoral pulse wave velocity (PWV) to assess arterial stiffness 1
• Fundoscopy if hypertensive emergency is suspected 1

If Patient Has Chest Pain or Suspected Coronary Disease

Despite normal troponin, if there are symptoms suggesting ischemia: 2

• Coronary angiography is the gold standard for identifying revascularizable coronary disease, particularly if the patient would be a candidate for revascularization 2
• The American College of Cardiology gives a Class IIa recommendation for coronary angiography in patients with chest pain that may or may not be cardiac in origin 2
• Non-invasive stress imaging may be considered first to assess for myocardial ischemia and viability 2

If Patient Has Suspected Pulmonary Embolism History

For patients 3-6 months post-PE with persistent dyspnea: 1

• Ventilation/perfusion (V/Q) scan to evaluate for chronic thromboembolic disease 1
• If mismatched perfusion defects are found, referral to a pulmonary hypertension or CTEPH expert center is indicated 1
• Cardiopulmonary exercise testing if appropriate expertise is available 1

Common Pitfalls to Avoid

Do not assume normal NT-proBNP completely excludes heart failure with preserved ejection fraction (HFpEF): 1

• While a normal NT-proBNP (<125 pg/mL) makes HFpEF unlikely, it does not definitively exclude it, especially in early or mild disease 1
• Structural and functional cardiac abnormalities can exist despite normal biomarkers 1

Do not overlook the impact of renal function on NT-proBNP interpretation: 3, 4

• Although your patient has normal creatinine, mild renal dysfunction can elevate NT-proBNP without cardiac disease 3, 4
• Conversely, normal NT-proBNP in the setting of preserved renal function is highly reassuring 5

Do not order additional testing without a clear clinical indication: 1

• The guidelines emphasize that additional tests should only be performed if results are likely to change patient management 1
• Avoid "shotgun" approaches to testing in asymptomatic patients with normal initial workup 1

Bottom Line

Return to the patient's history and physical examination to identify specific symptoms, risk factors, or clinical findings that would direct further investigation. 1 The normal tests you've obtained have effectively ruled out acute cardiac pathology, but the next diagnostic step must be guided by the clinical presentation you're trying to explain or the condition you're trying to exclude.