Overview
Chronic thromboembolic pulmonary hypertension, or CTEPH, is a serious form of pulmonary hypertension caused by chronic blood clots that obstruct the pulmonary arteries and raise pressure in the lungs. One important treatment option is balloon pulmonary angioplasty, commonly called BPA, a catheter-based procedure that opens narrowed or blocked pulmonary arteries using small inflatable balloons.
In many patients, doctors use pulmonary hypertension-targeted medical therapy before BPA to reduce strain on the right side of the heart and improve hemodynamics. This study from the Dutch BPA registry examined whether pretreatment with dual targeted therapy offers better safety and clinical benefit than monotherapy.
Why this study matters
BPA can improve symptoms, exercise capacity, and pulmonary pressures in patients with CTEPH, but the procedure is not risk-free. Complications such as lung injury, vascular damage, bleeding, or thoracic complications can occur, especially in patients with more severe disease.
Targeted drug therapy for pulmonary hypertension may help stabilize patients before BPA. However, it has not been fully clear whether using two PH-targeted medications before BPA is better than using one. This study addressed that question by comparing outcomes in patients pretreated with monotherapy versus dual therapy.
Study design
The investigators included all consecutive patients with CTEPH in the Netherlands who underwent BPA after pretreatment with either mono or dual PH-targeted medical therapy. They assessed complications around the procedure, treatment approach, and changes in clinical and hemodynamic measures at diagnosis, before the first BPA session, and at six-month follow-up.
The study population included 169 patients. Slightly more than half were women. The average age was 66 years, and most patients were in World Health Organization functional class III or IV, meaning they had marked limitation of physical activity. At diagnosis, the group had substantial hemodynamic burden, with a mean pulmonary artery pressure of 44 mmHg and a pulmonary vascular resistance of 7.7 Wood units.
Key findings
Of the 169 patients, 93 received monotherapy pretreatment and 76 received dual PH-targeted therapy.
The main safety finding was striking: on a per BPA session basis, patients who had received dual therapy experienced fewer thoracic complications related to BPA than those pretreated with monotherapy, 8.4% versus 19.6%. This difference was statistically significant.
After adjusting for important factors such as treatment center, age, pulmonary vascular resistance, and multiple BPA sessions per patient, the study found that higher levels of N-terminal prohormone brain natriuretic peptide, or NT-proBNP, higher right atrial pressure, and monotherapy pretreatment were independent predictors of thoracic BPA complications. In other words, patients with more advanced heart strain and those who received only one PH-targeted drug were more likely to have complications.
Clinical outcomes at follow-up
The investigators also looked at changes between baseline and six months after treatment. Patients pretreated with dual therapy showed greater improvement in several important measures:
– 6-minute walking distance, a simple test of exercise capacity
– Cardiac index, which reflects how well the heart pumps blood relative to body size
– Pulmonary vascular resistance, which measures how difficult it is for blood to flow through the lung circulation
These improvements suggest that dual pretreatment may not only make BPA safer, but may also help patients recover more effectively and achieve better functional gains after the procedure.
How to interpret the results
This study suggests that dual PH-targeted pretreatment may better prepare patients with CTEPH for BPA than monotherapy. The likely explanation is that combination therapy reduces pulmonary pressure and right-heart strain more effectively, creating a safer procedural environment and possibly improving the response to BPA.
That said, this was not a randomized trial. Treatment decisions were made in real-world practice, so patients in the dual-therapy group may have differed in important ways from those who received monotherapy. The authors attempted to adjust for confounding factors, but residual bias can never be completely excluded in registry-based research.
Even with that limitation, the findings are clinically meaningful because they come from a national registry with consecutive patients and reflect everyday practice rather than a highly selected trial population.
What this means for patients and clinicians
For patients with CTEPH who are being considered for BPA, the study supports a treatment strategy that uses more than one PH-targeted medication when appropriate before the procedure. In practice, this may help reduce complications and improve short-term outcomes.
For clinicians, the study highlights the importance of pre-procedure risk assessment. Elevated NT-proBNP and right atrial pressure may identify patients at higher risk of thoracic complications during BPA. These patients may benefit from closer monitoring, more careful procedural planning, and consideration of more intensive pretreatment.
Background on PH-targeted medical therapy
PH-targeted medications include agents that act on pathways involved in pulmonary vascular constriction and remodeling. Depending on the clinical setting, these may include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclin-pathway agents. Dual therapy usually means combining two of these classes to achieve a stronger effect than monotherapy.
In CTEPH, targeted therapy does not remove the chronic clot burden, but it can improve hemodynamics and symptoms and may make subsequent interventions such as BPA safer. The best approach often depends on clot distribution, severity of disease, operability, and local expertise.
Study limitations
As with any observational registry study, several limitations should be kept in mind. Treatment choice was not randomized, and the study may reflect differences in patient selection, disease severity, or center-specific practice. Also, the abstract does not provide detailed information on the exact medications used, treatment duration, or long-term survival outcomes.
In addition, BPA complications can vary depending on operator experience and the number of sessions required. Although the analysis adjusted for several factors, not all procedural variables can be fully standardized in a multicenter real-world registry.
Bottom line
Among patients with CTEPH undergoing balloon pulmonary angioplasty, pretreatment with dual PH-targeted medical therapy was associated with fewer thoracic BPA complications and better short-term clinical improvement than monotherapy. These findings support the use of combination pretreatment in appropriately selected patients, while also emphasizing the need for individualized risk assessment and expert care.
Reference
Staal DP, Lely RY, Breuning A, et al. Pretreatment with mono or dual PH-targeted medical therapy in patients undergoing balloon pulmonary angioplasty: effect on complications and clinical outcomes. Chest. 2026; PMID: 42128277.