Treatment of Moderate Pulmonary Hypertension with Tricuspid Regurgitation and Grade 2 Diastolic Dysfunction
Critical First Step: Determine the Etiology of Pulmonary Hypertension
The optimal drug therapy depends entirely on whether this patient has WHO Group 1 (pulmonary arterial hypertension) versus WHO Group 2 (pulmonary hypertension due to left heart disease), as the treatment paradigms are fundamentally different and using PAH-specific therapies in PH-LHD can cause harm. 1
If This is PH Due to Left Heart Disease (Group 2) - Most Likely Given Diastolic Dysfunction Grade 2:
Do NOT use PAH-specific therapies (PDE5 inhibitors, endothelin receptor antagonists, or prostanoids) as first-line treatment. The presence of grade 2 diastolic dysfunction strongly suggests this is WHO Group 2 PH-LHD, where PAH therapies have failed to show benefit and may cause harm. 1
Optimize management of the underlying left heart disease first: This includes aggressive heart failure therapy, volume optimization with diuretics for the tricuspid regurgitation, and consideration of valve repair if the TR is severe and contributing to symptoms. 1
Riociguat was specifically studied in PH-LHD and showed no benefit on mean pulmonary artery pressure at any dose (0.5,1, or 2 mg three times daily) in a 201-patient randomized trial. 1
There is no evidence-based recommendation for PAH-specific drugs in PH-LHD. Multiple acute studies with prostanoids, ERAs, and PDE5 inhibitors showed hemodynamic improvements but lacked adequate methodology and did not translate to clinical benefit. 1
Sildenafil in the RELAX trial showed no improvement in right ventricular function, exercise capacity, or ventilatory efficiency in HFpEF patients with RV dysfunction and impaired RV-PA coupling, and actually decreased TAPSE at 24 weeks. 2
If This is Pulmonary Arterial Hypertension (Group 1) - Less Likely But Possible:
For WHO Functional Class II-III PAH, initiate oral monotherapy with either a phosphodiesterase-5 inhibitor (sildenafil or tadalafil) or an endothelin receptor antagonist (ambrisentan or macitentan preferred over bosentan). 1
PDE5 Inhibitor Options:
- Sildenafil 20 mg three times daily improves 6-minute walk distance by 45-50 meters, reduces mean pulmonary artery pressure, and improves WHO functional class. 1, 3
- Tadalafil 40 mg once daily offers the advantage of once-daily dosing with similar efficacy to sildenafil. 1, 4
- Avoid PDE5 inhibitors if systolic blood pressure <100 mmHg or if patient is on nitrates (absolute contraindication). 1
Endothelin Receptor Antagonist Options:
- Ambrisentan (5-10 mg daily) or macitentan (10 mg daily) are preferred over bosentan due to once-daily dosing and less frequent liver monitoring requirements. 1
- All ERAs require monthly pregnancy testing in women of childbearing age (teratogenic). 1
- Macitentan requires liver function tests every 3 months; bosentan requires monthly monitoring. 1
- Monitor for anemia and fluid retention every 1-3 months. 1
Risk Stratification Guides Initial Choice:
- Low-risk features (6-minute walk distance >380 meters, no RV failure, WHO FC II-III, normal or near-normal BNP): Start with oral monotherapy as above. 1
- High-risk features (6-minute walk distance <200 meters, RV failure, WHO FC IV, RAP >20 mmHg, cardiac index <2.0 L/min/m²): Consider parenteral prostanoid therapy (IV epoprostenol) as it is the only therapy proven to improve survival. 1
Common Pitfalls to Avoid:
- Do not assume all pulmonary hypertension is PAH. Right heart catheterization with PAWP measurement (and potentially fluid challenge) is essential to distinguish Group 1 from Group 2 PH. 1
- Do not combine riociguat with any PDE5 inhibitor due to severe hypotension risk. 4
- Do not use calcium channel blockers unless the patient has documented acute vasoreactivity on testing (rare, <10% of patients). 1
- In the setting of moderate TR and diastolic dysfunction, aggressive diuresis is critical for symptomatic management regardless of PH etiology. 1