What is the differential diagnosis and appropriate workup for a patient presenting with chest tightness, shortness of breath (SOB) without lower limb edema, orthopnea, and elevated jugular venous pressure (JVP)?

Differential Diagnosis and Workup for Chest Tightness, SOB, Orthopnea, and Elevated JVP Without Lower Limb Edema

Primary Diagnosis to Consider

This clinical presentation—chest tightness, shortness of breath, orthopnea, and elevated JVP without peripheral edema—most strongly suggests acute decompensated heart failure with predominantly right-sided or biventricular congestion, though the absence of lower limb edema should prompt consideration of alternative diagnoses including pulmonary embolism, cardiac tamponade, and pulmonary hypertension. 1

Key Differential Diagnoses

1. Acute Heart Failure (Most Likely)

• Elevated JVP and orthopnea are the only two clinical findings from history and physical examination that reliably correlate with elevated pulmonary capillary wedge pressure (PCWP ≥18-22 mmHg) 1, 2
• In the ESCAPE trial, elevated JVP (≥12 mmHg) had an odds ratio of 4.6 for predicting PCWP ≥30 mmHg, and orthopnea ≥2 pillows had an odds ratio of 3.6 2
• The absence of peripheral edema does not exclude heart failure—in one study, 42% of patients with PCWP ≥22 mmHg had no peripheral edema 1
• JVP measurement has 81% sensitivity, 80% specificity, and 81% predictive accuracy for detecting elevated PCWP when performed carefully 1

2. Pulmonary Embolism (Critical to Exclude)

• PE presents with acute chest pain, shortness of breath, tachycardia, and hypoxemia 3
• Can cause elevated JVP due to acute right ventricular strain without time for peripheral edema to develop 3
• Affects approximately 370,000 patients per year in the US with 60,000-100,000 deaths annually 3
• The sudden onset of symptoms makes PE a must-rule-out diagnosis 4, 3

3. Cardiac Tamponade (Life-Threatening)

• Classic triad: elevated JVP, muffled heart sounds, and pulsus paradoxus 5, 6
• Presents with dyspnea, orthopnea, and chest discomfort 5, 6
• Kussmaul's sign (paradoxical rise in JVP with inspiration) is highly suggestive 6
• Peripheral edema may be absent in acute presentations 5, 6

4. Pulmonary Hypertension

• Presents with exertional dyspnea, fatigue, and chest discomfort 1
• Physical findings include elevated JVP, accentuated P2, right ventricular heave 1
• Peripheral edema occurs only in advanced disease with RV failure 1
• Orthopnea is less prominent than in left heart failure 1

5. Constrictive Pericarditis

• Elevated JVP with prominent x and y descents 7
• Kussmaul's sign present 6
• Dyspnea and orthopnea common 7
• Peripheral edema may be minimal early in disease course 7

Essential Workup Tests (In Order of Priority)

Immediate Bedside Assessment

• Measure JVP properly: patient at 30-45 degrees elevation, add vertical distance from sternal angle to highest pulsation point plus 5 cm 7, 8
• Assess for pulsus paradoxus (>10 mmHg drop in systolic BP with inspiration suggests tamponade) 6
• Check for Kussmaul's sign (JVP rise with inspiration suggests tamponade or constriction) 6
• Evaluate for third heart sound (S3 gallop suggests heart failure) 1
• Assess for laterally displaced apical impulse (suggests ventricular dysfunction) 1

First-Line Investigations

1. Electrocardiogram (ECG) 1

• Assess for acute ischemia, right ventricular strain pattern (suggests PE), low voltage (suggests tamponade or pericardial disease) 1
• Look for right axis deviation, RV hypertrophy, or RV strain (suggests pulmonary hypertension or PE) 1
• Atrial arrhythmias common in advanced heart failure 1

2. Chest Radiograph 1

• Evaluate for cardiomegaly, pulmonary vascular congestion, pleural effusions (heart failure) 1
• Assess for enlarged cardiac silhouette (tamponade) or clear lung fields with enlarged pulmonary arteries (PE or pulmonary hypertension) 1
• Normal chest X-ray does not exclude any of these diagnoses 1

3. Transthoracic Echocardiography (URGENT) 1, 5

• This is the single most important test—provides immediate information on chamber size, ventricular function, valve function, pericardial effusion, and RV function 1
• Assess left ventricular ejection fraction and diastolic function 1
• Evaluate for pericardial effusion with RV diastolic collapse (tamponade) 5, 6
• Measure RV size and function, tricuspid regurgitation velocity (estimates pulmonary artery pressure) 1
• Look for McConnell's sign (RV free wall hypokinesis with apical sparing suggests PE) 3

4. Natriuretic Peptides (BNP or NT-proBNP) 1

• Elevated levels support heart failure diagnosis 1
• However, levels can be elevated in PE and pulmonary hypertension as well 3
• Normal levels make heart failure less likely but do not exclude it 1

5. D-dimer (If PE Suspected) 3

• In patients with low-to-intermediate clinical probability, D-dimer <500 ng/mL excludes PE with post-test probability <1.85% 3
• In high-probability patients (>40% likelihood), proceed directly to CT pulmonary angiography without D-dimer testing 4, 3
• Age-adjusted D-dimer threshold: age × 10 ng/mL for patients ≥50 years 3

6. CT Pulmonary Angiography (CTPA) 4, 3

• Most appropriate test for high clinical suspicion of PE 4
• Rated "usually appropriate" (7/9) by American College of Radiology 4
• High sensitivity and specificity for PE diagnosis 4, 3
• Consider early if patient has tachycardia, hypoxemia, or sudden symptom onset 4, 3

Additional Laboratory Tests

• Complete blood count, renal function, liver function tests, troponin 1
• Arterial blood gas if hypoxemia suspected 3
• Thyroid function tests (thyroid disease can precipitate heart failure) 1

Advanced Testing (If Diagnosis Remains Unclear)

7. Right Heart Catheterization 1

• Gold standard for measuring right atrial pressure and PCWP 1
• Reserved for cases where non-invasive testing is inconclusive 1
• Essential for definitive diagnosis of pulmonary hypertension 1

8. Cardiac MRI

• Useful for evaluating pericardial thickness (constrictive pericarditis) 7
• Can assess myocardial infiltration or cardiomyopathy 1

Clinical Algorithm for Workup

Step 1: Immediate Risk Stratification

• If hemodynamically unstable (hypotension, shock): Perform immediate bedside echocardiogram to assess for tamponade or massive PE 5, 6
• If pulsus paradoxus or Kussmaul's sign present: Urgent echocardiogram for tamponade 6

Step 2: Assess PE Probability

• Recent surgery, immobilization, cancer, unilateral leg swelling, tachycardia, hypoxemia = HIGH probability 4, 3
• High probability (>40%): Proceed directly to CTPA 4, 3
• Low-to-intermediate probability: Check D-dimer first 3

Step 3: Evaluate for Heart Failure

• ECG + chest X-ray + echocardiogram + BNP/NT-proBNP 1
• Echocardiogram distinguishes HF with reduced ejection fraction (HF-REF) from HF with preserved ejection fraction (HF-PEF) 1
• Both elevated JVP and orthopnea together strongly predict elevated PCWP 1, 2

Step 4: Consider Alternative Diagnoses

• If echocardiogram shows pericardial effusion: Assess for tamponade physiology 5, 6
• If RV dysfunction without PE: Consider pulmonary hypertension (requires right heart catheterization for confirmation) 1
• If constrictive physiology suspected: Cardiac MRI or CT for pericardial thickness 7

Critical Pitfalls to Avoid

Common Diagnostic Errors

• Do not assume absence of peripheral edema excludes heart failure—42% of patients with elevated PCWP have no edema 1
• Do not rely on physical examination alone—sensitivity of clinical signs for elevated PCWP is only 58% 1
• Do not skip echocardiography—it is essential for distinguishing between diagnoses 1
• Do not delay CTPA in high-probability PE patients to wait for D-dimer results 4, 3

Measurement Pitfalls

• JVP measurement is unreliable in obesity, respiratory disease, or when performed by inexperienced clinicians 7, 8
• Ensure proper patient positioning (30-45 degrees) for accurate JVP assessment 7, 8
• Hepatojugular reflux can improve sensitivity when JVP is difficult to visualize 1, 7

Treatment Considerations

• If PE is strongly suspected, consider starting therapeutic anticoagulation while awaiting imaging 4, 3
• In tamponade, urgent pericardiocentesis is life-saving—do not delay for additional testing 5, 6
• For heart failure, diuretic therapy should target JVP normalization (≤8 cm H₂O) 7

Special Populations

Elderly Patients

• Symptoms and signs may be atypical or difficult to interpret 1
• Higher threshold for advanced imaging given increased risk of PE and heart failure 3

Obese Patients

• JVP measurement particularly challenging 7, 8
• Lower threshold for echocardiography 1
• Consider CT imaging earlier in diagnostic algorithm 4