Treatment of Group 2 Pulmonary Hypertension
The primary treatment for Group 2 pulmonary hypertension is optimization of the underlying left heart disease—PAH-specific therapies (prostanoids, endothelin receptor antagonists, and PDE-5 inhibitors) are NOT recommended and may be harmful. 1, 2
Core Treatment Principles
The fundamental approach requires addressing the root cause before considering any pulmonary-specific interventions. 2 Group 2 PH develops from passive backward transmission of elevated left-sided filling pressures, and in some patients, additional pulmonary vasoconstriction and vascular remodeling occur. 2 However, this pathophysiology does not respond to PAH therapies the way Group 1 PAH does.
Specific Treatment Algorithm
For Valvular Heart Disease
- Perform surgical repair when indicated 2, 3
- Timing of intervention should follow standard valvular disease guidelines, with PH presence often supporting earlier intervention 1
For Heart Failure with Reduced Ejection Fraction (HFrEF)
- Aggressive neurohormonal antagonist therapy: 2, 3
- Careful diuresis to reduce pulmonary congestion without causing hypoperfusion 1, 2
- Consider left ventricular assist device (LVAD) in appropriate candidates, which lowers pulmonary pressures through LV unloading without increasing post-implantation RV failure risk 1, 2
For Heart Failure with Preserved Ejection Fraction (HFpEF)
- Optimize volume status with diuretics 1, 3
- Control cardiovascular risk factors and metabolic syndrome features (hypertension, diabetes, obesity) 1, 2, 3
- Evidence for specific HFpEF therapies remains limited 1
Concomitant Conditions
Why PAH Therapies Are Contraindicated
The evidence against PAH-specific drugs in Group 2 PH is definitive. 1, 2, 3 While acute or short-term studies with prostanoids, ERAs, and PDE-5 inhibitors showed hemodynamic improvements, these studies had significant methodological limitations (small sample size, single center, unclear randomization). 1
Key Negative Trial Data
- Riociguat trial: A multicentre, placebo-controlled study of 201 patients with PH due to systolic heart failure showed no effect on mean pulmonary artery pressure at any dose (0.5,1, or 2 mg three times daily) compared to placebo over 16 weeks 1, 2
- Risk of severe pulmonary edema: Vasodilators, particularly intravenous epoprostenol, can cause life-threatening drug-induced pulmonary edema in this population 2
- Sildenafil is FDA-approved only for WHO Group 1 PAH, not Group 2 4
Monitoring Strategy
Regular Assessment Should Include:
- Echocardiographic monitoring of right ventricular function 2
- BNP/NT-proBNP plasma levels to assess disease progression 2
- Right heart catheterization may be necessary to reassess hemodynamics in patients with worsening symptoms despite optimal left heart disease treatment 2
When to Refer to PH Expert Center
Refer patients when: 3
- PH severity appears disproportionate to the underlying left heart disease 3
- Diagnosis remains unclear or complex 3
- Lung or heart transplantation is being considered 3
- Right ventricular dysfunction persists despite optimal treatment of the underlying condition 3
Critical Pitfalls to Avoid
- Do not use PAH therapies empirically—they provide no benefit and carry significant risk of harm 1, 2
- Do not perform vasoreactivity testing—it is specifically contraindicated in Group 2 PH and provides no clinically useful information 1, 5
- Do not under-diurese—adequate volume management is essential, though invasive monitoring may be required in severe cases 1
- Do not overlook combined pre- and post-capillary PH (CpcPH)—this subset has worse outcomes but still should not receive PAH therapies outside clinical trials 1, 6
Future Directions
Ongoing trials with sildenafil (SilHF trial) and macitentan (Melody-1 trial) are investigating whether specific hemodynamic phenotypes might benefit from targeted therapies, but current evidence does not support their use. 1 Patients with combined pre- and post-capillary PH should be enrolled in clinical trials when available. 1