Balloon Pulmonary Angioplasty: Tackling the Unmet Need

Chronic thromboembolic pulmonary hypertension (CTEPH), a long-term sequela of recurrent or unresolved pulmonary thrombi, represents a formidable clinical challenge with associated high morbidity and mortality.¹ It is estimated to complicate 2% to 4% of acute pulmonary emboli and is characterized by nonresolving thromboemboli, which lead to intraluminal obstruction and remodeling of the pulmonary vasculature (fibrotic transformation).^2,3 When clinically feasible, surgical pulmonary endarterectomy (PEA) is the gold standard of treatment⁴; however, 37% to 80% of patients are deemed inoperable due to frailty, anatomical limitations (eg, distal lesions), right ventricular dysfunction, severe pulmonary hypertension (PH), and other comorbidities.^1,2,4 Furthermore, PEA is limited to large metropolitan areas with expert CTEPH teams.

Balloon pulmonary angioplasty (BPA) is an attractive and less invasive approach for treating inoperable, high-risk CTEPH cases. It is also an adjunctive therapy option for patients with residual PH after PEA.^1,5 BPA aims to reestablish flow within the pulmonary vasculature using low-pressure, semicompliant balloons. Appropriate patient selection for BPA is critical and requires a thorough assessment by the multidisciplinary team (those with expertise in PH, pulmonary imaging, PEA, and BPA).¹

BPA was first reported in a small patient series in 2001⁶; however, the high rate of complications associated with initial cases limited the widespread adoption of BPA. Subsequently, a 2012 paper by Mizoguchi et al⁷ demonstrated significant hemodynamic improvements after BPA, with a more acceptable rate of complications, reigniting interest in BPA globally. BPA has since proven to be more effective than riociguat in reducing mean pulmonary artery pressure and pulmonary vascular resistance in 2 randomized control trials.^8,9 The results of the RACE trial (BPA vs riociguat for the treatment of inoperable CTEPH) also support the initiation of riociguat in advance of BPA to mitigate complications⁸; however, BPA remains underutilized, and significant variations exist in access to BPA across the world.

Based on the increasing evidence that BPA is effective in reducing mean pulmonary artery pressure, pulmonary vascular resistance, and improving quality of life, the European Society of Cardiology/European Respiratory Society guidelines now recommend BPA as a Class I treatment for inoperable CTEPH and residual chronic thromboemboli causing PH.⁴ Furthermore, the American Heart Association recently published a consensus document to address the gap in the current clinical practice of BPA and provide a consensus opinion on the role of BPA in the overall care of patients with CTEPH with and without PH.¹

For BPA, standard coronary intervention equipment is generally used. The dedicated B-pahm wire (Japan Lifeline) is not available in Europe or the United States. Typically, a nonhydrophilic, soft-tip 0.014-inch coronary wire is used as the first choice.¹ Extreme caution is needed with hydrophilic and heavy tip load wires, especially distal wire tip management, to avoid vessel perforation. Further steps to mitigate procedural complications include the use of adjunctive imaging to accurately size balloons and staging treatment over multiple sessions with sequential dilatation of lesions with larger balloons.⁴

In this issue of JSCAI, Perkins et al¹⁰ demonstrate a proof-of-concept study focused on mechanistic considerations for the development of an ideal catheter-based strategy for BPA that minimizes the risk of pulmonary artery perforation. Through analysis of 26 histopathological samples procured during the PEA of 9 patients, the authors aimed to identify the differential force required to penetrate a CTEPH lesion vs the pulmonary arterial wall. The authors determined that although the pulmonary arterial wall of these samples is friable, a significantly higher force is needed to perforate the arterial wall vs cross CTEPH lesions. Furthermore, the inadequacy of standard 0.014-inch workhorse wires to penetrate the CTEPH lesions was demonstrated. The authors conclude that specific guide wires and devices should be able to function within a discrete therapeutic safety window to allow for lesion crossing with minimal risk.

The authors should be congratulated for their line of investigation that attempts to answer a clinically relevant question from bench to bedside. Translational research is equal parts onerous and necessary. Practicing cardiologists and surgeons who understand firsthand the limitations and safety considerations of current devices should feel empowered to lead research like this for continued innovation and improvement in quality of care.

Overall, BPA offers a potential alternative management option for inoperable and residual PH in CTEPH patients, although further refinement of techniques, with the development of dedicated interventional tools, will go a long way toward improving safety and efficacy. It should only be offered initially at dedicated centers of excellence after careful selection of patients by a multidisciplinary team approach. Furthermore, randomized controlled trials of BPA with long-term clinical follow-up are required to address the present knowledge gaps.