Comorbidities and Technique Drive International Differences in BPA Outcomes

Optimizing Hemodynamic Targets in Chronic Thromboembolic Pulmonary Hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) remains a complex clinical challenge characterized by persistent vascular obstruction and progressive right heart failure [1, 2]. For patients with inoperable disease, balloon pulmonary angioplasty has become a standard intervention that significantly improves exercise capacity and reduces pulmonary vascular resistance [3, 4]. While this percutaneous approach offers substantial hemodynamic benefits, achieving complete normalization of pulmonary pressures is inconsistent across global centers [5, 6]. Current guidelines emphasize multidisciplinary evaluation to navigate procedural risks and maximize functional recovery [7, 8]. A recent multicenter study provides a detailed analysis of the patient factors and procedural variations that may explain these disparate long-term hemodynamic outcomes.

Comparing Patient Profiles Across Continents

A consistent clinical observation has been that mean pulmonary arterial pressures (mPAP) following balloon pulmonary angioplasty (BPA) are lower in Japanese patients compared to non-Japanese cohorts. To investigate this disparity, researchers conducted a retrospective study screening 200 consecutive patients with CTEPH who underwent BPA at two centers in the Netherlands and two in Japan. After excluding individuals with prior pulmonary endarterectomy (the surgical removal of organized thrombi from pulmonary arteries) or those without follow-up hemodynamic data, 138 patients were included in the final analysis. The study revealed distinct baseline clinical profiles, with the Dutch cohort presenting a higher burden of cardiovascular risk factors. Specifically, the proportion of males was 55% in the Netherlands versus 24% in Japan, and the mean body mass index was 26 ± 4 kg/m2 versus 23 ± 5 kg/m2, respectively. Furthermore, the smoking rate was 43% in the Netherlands compared to 23% in Japan, and the prevalence of atrial fibrillation was 9% versus 0%. Despite these significant differences in patient characteristics, the anatomical burden of disease was similar, as the proximal lesion distribution and severity on computed tomography imaging were comparable between the two countries. This key finding suggests that higher residual pressures in Western patients are likely driven by factors other than the location or complexity of vascular obstructions.

Hemodynamic Disparities and Procedural Success

The study's primary hemodynamic outcomes confirmed a significant difference in pressure reduction between the two groups. The Japanese cohort demonstrated a greater mPAP reduction of -16 mmHg (a 40% decrease), compared to a reduction of -10 mmHg (a 28% decrease) in the Netherlands (p_interaction = 0.03). This resulted in markedly different post-procedural hemodynamics, with a follow-up mPAP that was significantly lower in Japan at 22 ± 1 mmHg compared to 30 ± 1 mmHg in the Netherlands (p < 0.01). To isolate the factors driving these outcomes, the researchers performed a multivariable regression analysis, a statistical method that identifies which variables have the strongest independent association with an outcome. This analysis pointed toward underlying cardiopulmonary function as a key determinant. Independent factors associated with higher follow-up mPAP included a lower diffusing capacity of the lung for carbon monoxide (DLCO), which measures the efficiency of gas transfer in the lungs, as well as higher right atrial pressure and higher pulmonary arterial wedge pressure at follow-up. Procedural choices also emerged as significant, with a greater number of BPA sessions and less frequent use of intermediate-sized balloons being associated with higher residual mPAP. These results indicate that the international variation in outcomes is not simply a matter of nationality or lesion anatomy but is instead linked to underlying patient physiology and specific procedural techniques.

Identifying Drivers of Residual Pulmonary Hypertension

The multivariable analysis pinpointed specific physiological markers that independently predicted higher mPAP after BPA. Impaired gas exchange, reflected by a diffusing capacity of the lung for carbon monoxide (DLCO) that was lower in the Netherlands (69 ± 15%) than in Japan (79 ± 19%), was a primary driver. A reduced DLCO suggests underlying parenchymal lung disease or ventilation-perfusion mismatch that is not corrected by angioplasty. Furthermore, hemodynamic markers of cardiac dysfunction were critical. The findings that higher right atrial pressure and higher pulmonary arterial wedge pressure at follow-up were independent predictors of higher mPAP underscore the role of both right and left heart function. An elevated wedge pressure, an indirect measure of left atrial pressure, points to a post-capillary component of pulmonary hypertension that limits the hemodynamic benefit of opening obstructed pulmonary arteries. Procedural factors also played a role, as a greater number of BPA sessions was associated with worse outcomes. This likely indicates that patients requiring more procedures had more complex or fibrotic lesions to begin with, making this an indicator of disease severity rather than a consequence of the intervention itself. Ultimately, the researchers concluded that higher mPAP following BPA was associated with impaired lung and left heart function and procedural parameters, rather than nationality or lesion distribution. This suggests that optimizing outcomes requires careful assessment of occult cardiopulmonary comorbidities and may benefit from standardizing procedural techniques, such as balloon sizing.

References

1. Khan I, Ishaque G, Khan AA, et al. Balloon Pulmonary Angioplasty Versus Riociguat in Inoperable Chronic Thromboembolic Pulmonary Hypertension: Systematic Review and Meta-Analysis of Randomized Controlled Trials.. Cardiology in review. 2025. doi:10.1097/CRD.0000000000001049

2. Crowley AV, Banfield M, Gupta A, Raj R, Gorantla VR. Role of Surgical and Medical Management of Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review.. Cureus. 2024. doi:10.7759/cureus.53336

3. Kalra R, Duval S, Thenappan T, et al. Comparison of Balloon Pulmonary Angioplasty and Pulmonary Vasodilators for Inoperable Chronic Thromboembolic Pulmonary Hypertension: A Systematic Review and Meta-Analysis. Scientific Reports. 2020. doi:10.1038/s41598-020-65697-4

4. Guo Q, Lu L, Jia B, Liu Y. A Meta-analysis Assessing the Efficacy of Balloon Pulmonary Angioplasty in Resolving Chronic Thromboembolic Pulmonary Hypertension.. Alternative therapies in health and medicine. 2023.

5. Phan K, Jo HE, Xu J, Lau EM. Medical Therapy Versus Balloon Angioplasty for CTEPH: A Systematic Review and Meta-Analysis.. Heart, lung & circulation. 2018. doi:10.1016/j.hlc.2017.01.016

6. Zoppellaro G, Badawy MR, Squizzato A, Denas G, Tarantini G, Pengo V. Balloon Pulmonary Angioplasty in Patients With Chronic Thromboembolic Pulmonary Hypertension　- A Systematic Review and Meta-Analysis.. Circulation journal : official journal of the Japanese Circulation Society. 2019. doi:10.1253/circj.CJ-19-0161

7. Galiè N, Humbert M, Vachiéry J, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal. 2015. doi:10.1093/eurheartj/ehv317

8. [Consensus on the procedure of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension].. Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases. 2024. doi:10.3760/cma.j.cn112147-20231231-00403