What are the differential diagnoses for a patient on chronic long‑term oxygen therapy (4 L/min) with severe tricuspid regurgitation and pulmonary hypertension who now presents with new bilateral infiltrates on chest X‑ray, systolic blood pressure in the 120 mm Hg range, tachycardia (150 bpm), fever (38.5 °C), and oxygen saturation 88 % on 4 L/min improving to 96 % with a non‑rebreather mask?

Differential Diagnoses for Acute Decompensation in a Patient with Severe Tricuspid Regurgitation and Pulmonary Hypertension

The most likely diagnosis is acute decompensated right heart failure precipitated by pneumonia or pulmonary infection, given the fever, tachycardia, bilateral infiltrates, and hypoxemia in a patient with pre-existing severe TR and pulmonary hypertension. 1

Primary Differential Diagnoses

1. Pneumonia (Bacterial or Atypical)

• Fever (38.5°C), tachycardia (HR 150s), and bilateral infiltrates on CXR strongly suggest infectious pneumonia as the precipitating event. 1
• The acute hypoxemia (SpO2 88% on baseline 4L oxygen) with improvement to 96% on non-rebreather mask indicates acute parenchymal lung disease superimposed on chronic respiratory compromise. 1
• In patients with severe pulmonary hypertension and TR, even modest increases in pulmonary vascular resistance from infection can trigger acute right ventricular decompensation. 2
• The preserved blood pressure (120s systolic) suggests adequate preload despite right heart strain, distinguishing this from cardiogenic shock. 2

2. Acute Pulmonary Embolism

• PE must be excluded in any patient with severe pulmonary hypertension presenting with acute decompensation, as it is potentially life-threatening and treatable. 2
• The combination of tachycardia (150 bpm), hypoxemia, and bilateral infiltrates can occur with PE, though fever is less typical unless complicated by infarction. 2
• Echocardiographic signs of acute RV pressure overload (McConnell sign, 60/60 sign, or right-heart thrombi) would support PE diagnosis in a hemodynamically compromised patient. 2
• Critical pitfall: Chronic severe TR and pulmonary hypertension can mask or mimic acute PE findings on echocardiography; definitive diagnosis requires CT pulmonary angiography or V/Q scanning. 2

3. Acute Decompensated Right Heart Failure (Non-Infectious)

• Severe TR with pulmonary hypertension predisposes to right ventricular failure, which can decompensate with minimal physiologic stress. 2, 3
• Elevated jugular venous pressure with prominent V waves, hepatomegaly with pulsatile liver, and peripheral edema would be expected on examination. 1
• However, fever and bilateral infiltrates are not explained by isolated right heart failure and point toward an infectious or inflammatory trigger. 1
• Severe TR is strongly predictive of mortality in pulmonary hypertension (adjusted HR 1.83,95% CI 1.38-2.41) and correlates with greater right atrial pressure, lower cardiac index, and worse functional capacity. 3

4. Pulmonary Edema (Cardiogenic)

• Bilateral infiltrates with hypoxemia can represent pulmonary edema, though this is less likely given the preserved blood pressure and absence of left-sided heart disease history. 4
• In patients with severe TR and pulmonary hypertension, left ventricular diastolic dysfunction may be masked; right heart catheterization may be required to exclude elevated pulmonary wedge pressure. 2
• The rapid improvement in oxygenation with non-rebreather mask (88% → 96%) is more consistent with pneumonia or atelectasis than with cardiogenic pulmonary edema, which typically requires diuresis and vasodilators. 4

5. Acute Exacerbation of Chronic Lung Disease

• Patients on long-term oxygen therapy (4L baseline) likely have underlying chronic lung disease (COPD, interstitial lung disease) that can acutely worsen. 1
• Fever, infiltrates, and increased oxygen requirement suggest infectious exacerbation rather than pure bronchospasm. 1
• Key distinction: Wheeze or crackles on lung examination would support underlying parenchymal disease; their absence in isolated pulmonary hypertension is typical. 1

6. Pulmonary Veno-Occlusive Disease (PVOD) Exacerbation

• PVOD should be suspected when pulmonary artery dilation is disproportionate to hemodynamic severity and DLCO is severely reduced (<45% predicted). 5
• High-resolution CT findings of diffuse central ground-glass opacification, interlobular septal thickening, mediastinal lymphadenopathy, and pleural effusions strongly support PVOD. 5
• Critical warning: Misdiagnosing PVOD as idiopathic PAH can be fatal because pulmonary vasodilator therapy may precipitate life-threatening pulmonary edema. 5
• Digital clubbing, if present, would raise suspicion for PVOD, cyanotic congenital heart disease, interstitial lung disease, or hepatic disease. 5, 1

7. Infective Endocarditis (Tricuspid Valve)

• Fever with new or worsening TR should prompt consideration of tricuspid valve endocarditis, especially in patients with indwelling catheters, pacemakers, or intravenous drug use. 2
• Blood cultures and transesophageal echocardiography are required to exclude vegetations. 2
• Pacemaker-induced severe TR is rare but may require intervention. 2

Immediate Diagnostic Approach

Clinical Examination Priorities

• Assess for elevated jugular venous pressure with prominent V waves, hepatomegaly with pulsatile liver, peripheral edema, and ascites to confirm right heart failure. 1
• Auscultate for a loud P2 (accentuated pulmonary component of S2), pansystolic murmur of TR, and absence of wheeze/crackles (typical in isolated PAH). 1
• Check for signs of infection: consolidation on lung exam, productive cough, pleuritic chest pain. 1
• Examine for digital clubbing (atypical for idiopathic PAH; suggests PVOD, cyanotic heart disease, or interstitial lung disease). 5, 1

Laboratory and Imaging Studies

• Chest X-ray: Bilateral infiltrates require differentiation between pneumonia, pulmonary edema, and PVOD; look for interlobular septal thickening and pleural effusions. 5
• Blood cultures: Obtain before antibiotics if endocarditis is suspected. 2
• Complete blood count, inflammatory markers (CRP, procalcitonin): Elevated white count and procalcitonin support bacterial pneumonia. 1
• BNP or NT-proBNP: Elevated levels correlate with right heart failure severity; severe TR patients have higher BNP (mean 695 pg/dL vs 328 pg/dL in mild TR). 3
• Arterial blood gas: Assess for hypoxemia, hypercapnia, and acid-base status. 1
• Echocardiography: Evaluate for new RV dysfunction, right-heart thrombi, vegetations, and estimate pulmonary artery systolic pressure (though Doppler estimation may be inaccurate in severe TR). 2
• CT pulmonary angiography: If PE is suspected, CT is required; V/Q scanning is more sensitive for chronic thromboembolic pulmonary hypertension (CTEPH) but less useful in acute PE. 2, 5
• High-resolution chest CT: If PVOD is suspected, look for ground-glass opacification, septal thickening, lymphadenopathy, and effusions. 5

Immediate Management Priorities

Oxygen and Respiratory Support

• Maintain SpO2 >90% with supplemental oxygen; non-rebreather mask is appropriate given the improvement from 88% to 96%. 4
• Monitor for signs of respiratory failure requiring non-invasive ventilation or intubation. 4

Empiric Antibiotic Therapy

• Initiate broad-spectrum antibiotics covering community-acquired pneumonia (e.g., ceftriaxone plus azithromycin or respiratory fluoroquinolone) given fever, infiltrates, and hypoxemia. 1
• Adjust antibiotics based on sputum culture, blood culture results, and clinical response. 1

Diuresis for Volume Overload

• Administer intravenous loop diuretic (furosemide 40-80 mg IV bolus, doubling the usual oral dose if on chronic diuretics) to reduce right heart preload and hepatic congestion. 4
• Aim for urine output >100-150 mL/h initially; reassess spot urine sodium after 2 hours and increase diuretic dose if sodium <50-70 mmol/L. 4
• Modest rises in serum creatinine (≈0.3 mg/dL) during aggressive diuresis reflect hemoconcentration rather than true renal injury; venous congestion, not low cardiac output, drives renal dysfunction in this setting. 4

Hemodynamic Monitoring

• Continuous cardiac telemetry for arrhythmia detection (atrial fibrillation is common in severe TR and can worsen cardiac output). 2, 4
• Hourly vital signs until hemodynamic stability is achieved. 4
• Strict intake-output charting and daily weights to gauge net fluid loss. 4

Anticoagulation Consideration

• If PE is suspected and patient is hemodynamically stable, initiate therapeutic anticoagulation (unfractionated heparin or low-molecular-weight heparin) pending CT angiography. 2
• If PE is confirmed and patient is hemodynamically unstable, consider thrombolysis or catheter-directed therapy. 2

Critical Pitfalls to Avoid

• Assuming bilateral infiltrates equal pulmonary edema: Fever and tachycardia strongly favor infection; treat empirically with antibiotics while awaiting cultures. 1
• Omitting V/Q scan in chronic dyspnea: CTEPH is potentially curable with pulmonary endarterectomy or balloon angioplasty; V/Q scanning is more sensitive than CT for detecting CTEPH. 5
• Misdiagnosing PVOD as idiopathic PAH: Pulmonary vasodilator therapy can precipitate fatal pulmonary edema in PVOD; high-resolution CT and markedly reduced DLCO (<45% predicted) are key discriminators. 5
• Underestimating severity of TR: Severe TR is an independent predictor of mortality in pulmonary hypertension (5-year adjusted HR 1.83); aggressive management of precipitating factors is essential. 3
• Delaying specialist referral: Exertional syncope, rapidly worsening symptoms, signs of right heart failure, or suspected mechanical complications (hoarseness, angina, hemoptysis) mandate urgent referral to a pulmonary hypertension center. 5, 1