What is the management approach for a patient presenting with parasternal lift, diastolic murmur, dry crackles, clubbing, and suspected pulmonary hypertension or heart failure?

Management of Parasternal Lift, Diastolic Murmur, Dry Crackles, and Clubbing

This clinical constellation—parasternal lift (RV enlargement), diastolic murmur, dry crackles, and clubbing—strongly suggests pulmonary arterial hypertension (PAH) with possible underlying congenital heart disease or pulmonary veno-occlusive disease, requiring immediate diagnostic confirmation via right heart catheterization and comprehensive imaging to guide definitive therapy. 1

Immediate Diagnostic Workup

Clinical Examination Findings

• Parasternal lift indicates right ventricular hypertrophy and volume overload, commonly seen in atrial septal defect (ASD) with large shunts or severe PAH 1
• Diastolic murmur at the left sternal border suggests either:
  • Pulmonary regurgitation from severe PAH (Graham Steell murmur) 1
  • Tricuspid stenosis or diastolic flow rumble across the tricuspid valve from large left-to-right shunt 1
• Clubbing when present with these findings points toward: pulmonary veno-occlusive disease (PVOD), cyanotic congenital heart disease, or Eisenmenger syndrome 1
• Dry crackles are atypical for isolated PAH and should raise suspicion for PVOD or interstitial lung disease 1

Mandatory Initial Testing

• Transthoracic echocardiography with bubble study to assess:

  • Right ventricular size, function, and systolic pressure 1
  • Presence of intracardiac shunts (ASD, VSD, patent ductus arteriosus) 1
  • Tricuspid regurgitation velocity to estimate pulmonary artery systolic pressure 1
  • Left ventricular diastolic function and filling pressures (E/e' ratio) 1
  • Atrial septal anatomy from multiple views (parasternal, apical, subcostal) 1

• Electrocardiogram looking for:

  • Right axis deviation, right atrial enlargement, RV hypertrophy 1
  • RV strain pattern (more sensitive than RV hypertrophy alone) 1
  • Superior left axis deviation suggests primum ASD 1

• Chest radiograph to identify:

  • RV and right atrial enlargement 1
  • Prominent pulmonary artery segment with peripheral pruning 1
  • Pulmonary vascular congestion patterns 1

• Ventilation-perfusion (V/Q) scan to exclude chronic thromboembolic pulmonary hypertension (CTEPH), as a normal scan effectively rules out CTEPH 1

• High-resolution CT chest to evaluate for:

  • Interstitial lung disease (given dry crackles) 1
  • PVOD findings (septal thickening, ground-glass opacities, lymphadenopathy) 1
  • Pulmonary artery dilation 1

• Laboratory testing including:

  • NT-proBNP or BNP (elevated in PAH and heart failure) 1
  • Connective tissue disease screening (ANA, anti-Scl-70, anti-centromere) 1
  • HIV testing 1
  • Hepatitis serologies 1
  • Thyroid function tests 1

Definitive Diagnostic Procedure

Right heart catheterization is mandatory to:

• Confirm presence and severity of pulmonary hypertension (mean PAP ≥25 mmHg at rest) 1
• Measure pulmonary vascular resistance and cardiac output 1
• Assess pulmonary artery wedge pressure to distinguish pre-capillary from post-capillary PAH 1
• Perform vasoreactivity testing with short-acting agents (IV epoprostenol, adenosine, or inhaled nitric oxide) in appropriate candidates 1
• Calculate Qp:Qs ratio if shunt is suspected 1
• Exclude left heart disease as primary cause 1

Cardiac catheterization should include coronary angiography in patients at risk for coronary artery disease based on age or other risk factors 1

Critical Diagnostic Considerations

Atrial Septal Defect with PAH

If ASD is confirmed, assess for:

• Predictors of PAH development: defect size >2 cm, Qp:Qs ≥3, PASP >40 mmHg, older age at presentation, female sex 1
• Eisenmenger physiology: right-to-left shunting with systemic desaturation and cyanosis 1
• Operability: closure contraindicated if pulmonary vascular resistance is severely elevated (>5 Wood units or irreversible PAH) 1

Pulmonary Veno-Occlusive Disease

PVOD must be excluded given the presence of dry crackles and clubbing:

• PVOD presents with signs of pulmonary edema despite normal wedge pressure 2
• Pulmonary vasodilators can significantly worsen cardiovascular status in PVOD 2
• If pulmonary edema develops with PAH therapy, strongly consider PVOD 2

Treatment Algorithm Based on Diagnosis

If Eisenmenger Syndrome Confirmed

Bosentan is the first-line therapy for symptomatic patients with Eisenmenger syndrome and ASD or VSD 1

PDE-5 inhibitors (sildenafil or tadalafil) are reasonable alternatives for symptomatic patients with ASD, VSD, or great artery shunt 1, 2

Combination therapy with bosentan plus PDE-5 inhibitor is reasonable if symptomatic improvement does not occur with either medication alone 1

If PAH Without Eisenmenger Syndrome

• Vasoreactivity testing should be performed by experienced physicians 1
• Calcium channel blockers only for patients demonstrating favorable acute vasodilator response (fall in mean PAP ≥10 mmHg to ≤40 mmHg with increased or unchanged cardiac output) 1
• Targeted PAH therapy (endothelin receptor antagonists, PDE-5 inhibitors, prostacyclins) based on functional class and hemodynamic severity 1

If ASD Without Severe PAH

Closure of ASD (surgical or percutaneous) is indicated if:

• Qp:Qs >1.5 with evidence of RV volume overload 1
• Pulmonary vascular resistance <5 Wood units 1
• No evidence of irreversible PAH 1

Transesophageal echocardiography may be necessary for exact localization, sizing, and measurement of septal rims to determine suitability for percutaneous closure 1

Critical Pitfalls and Caveats

Do not empirically treat with calcium channel blockers without documented vasoreactivity, as this can worsen outcomes in non-responders 1

Avoid pulmonary vasodilators if PVOD is suspected until diagnosis is clarified, as they can precipitate life-threatening pulmonary edema 2

Do not rely solely on echocardiography for pulmonary artery pressure estimation, as it may be imprecise compared to invasive evaluation 1

Exercise testing is contraindicated in patients with severe PAH (PASP >60-80 mmHg) 1

Clubbing in the setting of PAH should prompt aggressive evaluation for PVOD, cyanotic congenital heart disease, or interstitial lung disease rather than idiopathic PAH 1

Monitor for epistaxis in patients with PAH secondary to connective tissue disease (13% incidence), especially with concomitant vitamin K antagonist use 2

Sildenafil carries increased mortality risk in pediatric PAH and chronic use is not recommended in children 2

Monitoring and Follow-Up

• Serial functional class assessment and 6-minute walk testing provide benchmarks for disease severity and response to therapy 1
• Repeat right heart catheterization if clinical deterioration occurs or to assess response to therapy 1
• Regular echocardiographic surveillance for RV function, estimated PA pressures, and development of complications 1
• Monitor for atrial arrhythmias (flutter/fibrillation), which occur in 25% of PAH patients after 5 years and invariably lead to clinical deterioration 1