What is the diagnosis and management for a 16-year-old patient with right heart failure, portal hypertension, and elevated N-terminal pro b-type natriuretic peptide (NT-proBNP) with a normal ejection fraction?

Diagnosis: Portopulmonary Hypertension (PoPH)

This 16-year-old patient most likely has portopulmonary hypertension—a form of pulmonary arterial hypertension occurring in the setting of portal hypertension with preserved left ventricular ejection fraction. 1

Clinical Reasoning

The combination of right heart failure, portal hypertension, elevated NT-proBNP, and normal ejection fraction is pathognomonic for portopulmonary hypertension rather than primary left heart disease. 1, 2

Key Diagnostic Features Supporting PoPH:

• Right-sided heart failure with preserved LVEF: This pattern indicates pulmonary vascular disease rather than left ventricular dysfunction 1
• Portal hypertension: The underlying driver of portopulmonary hypertension, creating a pre-capillary pulmonary hypertension phenotype 1
• Elevated NT-proBNP with normal EF: NT-proBNP elevation reflects right ventricular wall stress and correlates with pulmonary artery pressures in the absence of left ventricular dysfunction 2, 3

Essential Diagnostic Workup

Immediate Investigations Required:

• Transthoracic echocardiography within 48 hours to assess right ventricular function, estimate pulmonary artery systolic pressure via tricuspid regurgitant velocity (TRV), evaluate for structural heart disease, and confirm preserved left ventricular ejection fraction 1
• Right heart catheterization is mandatory to confirm the diagnosis, differentiate pre-capillary from post-capillary pulmonary hypertension, measure mean pulmonary artery pressure (mPAP ≥25 mmHg diagnostic), assess pulmonary vascular resistance, and measure pulmonary capillary wedge pressure (PCWP <15 mmHg in PoPH) 1
• Comprehensive laboratory panel: liver function tests, renal function, complete blood count, thyroid function, and repeat NT-proBNP for trending 1

Critical Echocardiographic Findings to Document:

• TRV ≥2.5 m/second indicates increased mortality risk and significant pulmonary hypertension 1
• Right ventricular systolic pressure ≥35 mmHg suggests elevated pulmonary pressures 1
• Right ventricular size and function: look for RV dilation, reduced RV systolic function, and interventricular septal flattening 1
• Exclude left-sided structural disease: assess for valvular disease, left atrial enlargement, and diastolic dysfunction parameters (E/e' ratio, left atrial volume index) 1

Management Algorithm

Pre-Catheterization Stabilization:

• Diuretics for volume management: IV loop diuretics (bolus or continuous infusion) to treat pulmonary and peripheral congestion while avoiding excessive preload reduction that could compromise right ventricular output 1
• Avoid aggressive diuresis: the right ventricle in PoPH is preload-dependent; excessive volume depletion can precipitate hemodynamic collapse 1
• Oxygen supplementation if hypoxemic to reduce pulmonary vasoconstriction 1

Post-Catheterization Treatment Based on Hemodynamics:

If RHC confirms pre-capillary PoPH (mPAP ≥25 mmHg, PCWP <15 mmHg, elevated PVR):

• Refer urgently to pulmonary hypertension specialist center for consideration of pulmonary arterial hypertension-specific therapy 1
• Consider prostacyclin agonist or endothelin receptor antagonist in select patients with elevated pulmonary vascular resistance and normal PCWP (weak recommendation) 1
• Avoid phosphodiesterase-5 inhibitors in sickle cell disease-associated pulmonary hypertension (strong recommendation against), though this may not apply to all PoPH etiologies 1

If mixed pre- and post-capillary features or elevated PCWP:

• Optimize volume status with careful diuretic titration 1
• Do NOT initiate PAH-specific therapy if PCWP is elevated and PVR is low (strong recommendation against) 1

Addressing the Underlying Portal Hypertension:

• Hepatology consultation to determine etiology of portal hypertension (cirrhosis, portal vein thrombosis, congenital portosystemic shunts) 1
• Assess for liver transplantation candidacy: severe PoPH (mPAP >50 mmHg) is a contraindication to liver transplantation; moderate PoPH may improve post-transplant 1
• Cardiac assessment before TIPSS: if TIPSS is being considered for portal hypertension management, NT-proBNP <125 pg/mL identifies patients not at risk of cardiac decompensation; this patient's elevated NT-proBNP indicates high risk 1

Monitoring Strategy

• Serial NT-proBNP measurements: a reduction >30% indicates good treatment response; persistent elevation suggests inadequate therapy 4, 5
• Daily monitoring of electrolytes, renal function, and weight during diuretic therapy 1
• Repeat echocardiography to assess treatment response and right ventricular function 1
• Follow-up right heart catheterization at 3-6 months if PAH-specific therapy is initiated to assess hemodynamic response 1

Critical Pitfalls to Avoid

• Do not attribute elevated NT-proBNP solely to liver disease: while cirrhosis can elevate NT-proBNP independent of cardiac dysfunction, levels correlate strongly with pulmonary artery pressures and cardiac dysfunction in this population 2, 3
• Do not delay right heart catheterization: echocardiography alone cannot definitively diagnose or exclude portopulmonary hypertension; invasive hemodynamics are mandatory 1
• Do not initiate PAH-specific therapy empirically: treatment must be guided by invasive hemodynamics, as inappropriate therapy in post-capillary or mixed PH can worsen outcomes 1
• Do not overlook age-specific considerations: while most PoPH literature focuses on adults, adolescents require pediatric cardiology and hepatology co-management 1
• Recognize confounders of NT-proBNP interpretation: renal dysfunction elevates NT-proBNP independent of cardiac function; assess eGFR 1, 5, 6

Prognostic Considerations

• NT-proBNP >2000 pg/mL is associated with significantly worse outcomes including increased mortality and heart failure readmissions 4, 5
• TRV ≥2.5 m/second is an independent mortality risk factor 1
• Portopulmonary hypertension carries high mortality if untreated, but targeted therapy can improve hemodynamics and potentially enable liver transplantation in select cases 1