Currently, our group is utilizing advanced CT imaging [23▪] in addition to angiography as part of a pre-BPA strategy assessment process that includes analyzing lesion location, type, and vessel sizing for efficient treatment in each patient. Current advancements in imaging will change our understanding of CTEPH lesions and enable sophisticated BPA treatment. New imaging techniques, including advanced CT, magnetic resonance angiography, and positron emission tomography may be useful for pre-BPA assessment including anatomical assessment, risk and benefits in lesion types, distal run-off, and collateral information. New intravascular modalities such as optical coherence tomography  may also be useful during the procedure to evaluate vessel size and lesion anatomy. Further investigations for distal CTEPH lesion are mandatory.
Effect of balloon pulmonary angioplasty
All recent BPA studies show consistently favourable haemodynamic effects. Pulmonary vascular resistance decreased by 33–65% [10,12,13,14▪,16]. This haemodynamic improvement is achieved on average by 2–5 staged sessions. Haemodynamic improvement is considered to some extent in proportion to the number of treated vessels. The more the pulmonary artery is opened, the better the haemodynamic improvement for the patient. Interestingly, haemodynamic improvement is not often observed immediately after each BPA . It may take some hours for haemodynamic improvement whose process and mechanisms are not still clear. WHO functional class and 6-minute walking distance clearly improved in most of the recent studies. Exercise capacity and ventilatory efficiency as measured by cardiopulmonary exercise tests also improved [13,25]. Our results showed that exercise capacity and ventilatory inefficiency improved early after the final BPA procedure . BPA is often performed in a stage-by-stage manner. Interestingly, exercise capacity improvement is associated more with the number of procedures than is haemodynamic change. It may be speculated that exercise capacity improves stepwise along with haemodynamics, amelioration of heart failure symptoms, increased activity, and subsequent peripheral adaptation acquired during the interval between sessions.
Right heart function is one of the most important factors for predicting the prognosis of pulmonary hypertension. Right ventricular (RV) reverse remodelling with BPA as assessed by cardiac MRI [14▪] and three-dimensional/speckle-tracking echocardiography  are observed along with haemodynamic improvement. BPA improved RV volumes, RV systolic function, interventricular septal bowing, and RV dyssynchrony [14▪,26]. Improved RV function will support the usefulness of BPA for CTEPH. The evaluation of RV function by noninvasive modalities in BPA could provide significant information in terms of efficacy, treatment goals, and outcomes.
Complications and prognosis with balloon pulmonary angioplasty
Complications remain one of the current important problems with BPA. Reperfusion oedema could lead to critical conditions. Over-blood flow, high pressure, sheer stress, and possibly cytokines after dilatation of target vessel could lead to acute over-reperfusion insults. Reperfusion oedema is still a relatively common complication after BPA, with a reported incidence of 53–60% [11,12]. Severe reperfusion oedema was recognized in 0–7% of cases in recent studies, although it is sometimes difficult to distinguish between reperfusion oedema and haemorrhage without haemoptysis. High pulmonary artery pressure , first BPA session, and severe haemodynamics (low cardiac output and high brain natriuretic peptide levels)  are reported to be the risk factors for pulmonary oedema.
Prevention and management of complications are important for well tolerated BPA procedures. Inami et al. proposed the PEPSI  (predicting score: Blood flow × haemodynamics) score as a predictor for pulmonary oedema. They also reported that a combined approach using pressure wire guidance and the PEPSI score might reduce reperfusion oedema . Further evaluation of this approach to forecast and prevent reperfusion oedema is necessary. Nasal continuous positive airway pressure or nasal high-flow  are used to treat mild-to-moderate low oxygenation in reperfusion oedema instead of artificial respirators. Preventive effect of nasal continuous airway pressure for reperfusion oedema is not clear. What is the key to avoid serious reperfusion? A stepwise approach is suggested to reduce the chance to have reperfusion oedema. Although there are no solid data for the benefit of a stepwise BPA approach, it sounds reasonable, considering first BPA session, high blood flow, and severe haemodynamics may contribute to the reperfusion oedema [9,11]. Limiting blood flow improvement by under vessel size pulmonary artery dilatation will reduce the re-perfused vascular insults at initial sessions with severe haemodynamic status. And we then dilate the vessels with proper size balloon at subsequent sessions when haemodynamics is not severe. There are no solid data on pre-BPA medical treatments, such as steroids, to prevent reperfusion oedema. We previously reported that continuous intravenous prostacyclin therapy before PEA might be beneficial . Benefits of medical treatment before BPA could be an issue to be studied. Further investigation is needed to determine the mechanisms and prevention for reperfusion oedema.
One of the most critical complications in BPA is pulmonary artery perforation, which may lead to severe lung haemorrhage and death. Pulmonary perforation is recognized in 0–7% of cases [11–13,14▪]. One patient (1.5%) was reported to have died from perforation . Proper wire positioning and knuckle wire techniques may be helpful to reduce pulmonary perforation. Disproportionate balloon size to the vessel could be the risk of pulmonary artery rupture. I summarized some points to avoid reperfusion oedema and pulmonary artery perforation/rupture (Table 3). Periprocedural mortality was reported to be 0–10% [11–13,14▪,15▪,16] in recent studies. As a catheter-based procedure, BPA largely relies on operator techniques and proficiency. Therefore, BPA may have a steep learning curve. In my opinion, an operator must perform at least 50 cases to perform stable procedures. Therefore, it may be suitable to centralize BPA procedures to high-volume CTEPH centres to reduce procedure-related complications. Improved devices and innovative techniques for safer BPA may prevent procedural complications.
At present, no obvious re-stenosis or recurrence after BPA has been reported. Stent implantation to prevent re-stenosis in BPA for CTEPH will not be necessary, assuming at least short-term good patency. Retrospective study data showed that the BPA group had better survival compared with the group receiving medical treatment, and the prognosis for BPA patients was comparable with that for PEA patients [15▪,16]. However, it is too soon to advocate that BPA is superior to medical treatment and similar to PEA. Long-term patency and prognosis are mandatory for this new procedure. Further evaluation of BPA is necessary to determine its role in CTEPH treatment [31▪▪]. In the future, standardization of the BPA procedure, new devices, and better strategies to maximize effects and minimize complications need continuous investigation. Treatment goal, combination with medical therapy, hybrid therapy with PEA, micro-vessel pulmonary arteriopathy involvement, poor-responder, residual pulmonary hypertension after BPA, late haemodynamic improvement mechanism, BPA education, radiation exposure, and cost-effectiveness [31▪▪] are also issues remaining to be clarified.
CTEPH is a life-threatening disease, especially for patients with severe, inoperable disease. Balloon pulmonary angioplasty, a new alternative treatment option for selected patients with inoperable CTEPH, has been promising in terms of clinical effectiveness in recent studies, although it still holds potential life-threatening complications. However, it is too soon to advocate rapid widespread application to CTEPH patients because there are still a number of concerns and unanswered questions related to this procedure. Multidisciplinary CTEPH teams should be involved in the process of investigating and establishing BPA's position in CTEPH treatment. Further investigations of BPA, including long-term data, are mandatory before the role of BPA can be determined in the new CTEPH treatment era [15▪,31▪▪].
I would like to thank Dr Jin Ueda, Dr Sigefumi Fukui, Dr Akihiro Tsuji, Dr Yoshiaki Morita, Dr Yoshihiro Sanda, Dr Tetsuya Fukuda, and Dr Norifumi Nakanishi for their contribution to BPA.
Financial support and sponsorship
This work was supported by the Division of Pulmonary Circulation, Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Centre, Japan.
Conflicts of interest
T.O. has received lecture fees from GlaxoSmithKline K.K., Actelion Pharmaceuticals Japan Ltd., Nippon Shinyaku Co., Pfizer Japan Inc., and Bayer Yakuhin Ltd., and research grant from Pfizer Japan Inc., Mochida pharmaceutical Co., Lts., Fujimoto pharmaceutical Co.
REFERENCES AND RECOMMENDED READING
Papers of particular interest, published within the annual period of review, have been highlighted as:
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Keywords:Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
balloon pulmonary angioplasty; catheter intervention; chronic thromboembolic pulmonary hypertension